Comparison of cuffed and uncuffed endotracheal tubes in young children during general anesthesia . BACKGROUND Uncuffed endotracheal tubes are routinely used in young children . This study tests a formula for selecting appropriately sized cuffed endotracheal tubes and compares the use of cuffed versus uncuffed endotracheal tubes for patients whose lungs are mechanically ventilated during anesthesia . METHODS Full-term newborns and children ( n = 488 ) through 8 yr of age who required general anesthesia and tracheal intubation were assigned randomly to receive either a cuffed tube sized by a new formula [ size ( mm internal diameter ) = ( age/4 ) + 3 ] , or an uncuffed tube sized by the modified Cole 's formula [ size ( mm internal diameter ) = ( age/4 ) + 4 ] . The number of intubations required to achieve an appropriately sized tube , the need to use more than 21.min-1 fresh gas flow , the concentration of nitrous oxide in the operating room , and the incidence of croup were compared . RESULTS Cuffed tubes selected by our formula were appropriate for 99 % of patients . Uncuffed tubes selected by Cole 's formula were appropriate for 77 % of patients ( P < 0.001 ) . The lungs of patients with cuffed tubes were adequately ventilated with 2 1.min-1 fresh gas flow , whereas 11 % of those with uncuffed tubes needed greater fresh gas flow ( P < 0.001 ) . Ambient nitrous oxide concentration exceeded 25 parts per million in 37 % of cases with uncuffed tubes and in 0 % of cases with cuffed tubes ( P < 0.001 ) . Three patients in each group were treated for croup symptoms ( 1.2 % cuffed ; 1.3 % uncuffed ) . CONCLUSIONS Our formula for cuffed tube selection is appropriate for young children . Advantages of cuffed endotracheal tubes include avoidance of repeated laryngoscopy , use of low fresh gas flow , and reduction of the concentration of anesthetics detectable in the operating room . We conclude that cuffed endotracheal tubes may be used routinely during controlled ventilation in full-term newborns and children during anesthesia .

cuffed and uncuffed endotracheal tubes

Uncuffed endotracheal tubes

cuffed tube sized by a new formula

Cuffed tubes

Uncuffed tubes

cuffed endotracheal tubes

cuffed endotracheal tubes

incidence of croup

lungs

adequately ventilated

Ambient nitrous oxide concentration

croup symptoms

Advantages

avoidance of repeated laryngoscopy

use of low fresh gas flow

young children

anesthesia .

young children

Full-term newborns and children

young children

full-term newborns and children

anesthesia


Comparison of arbutamine and exercise echocardiography in diagnosing myocardial ischemia . Arbutamine is a new catecholamine designed for use as a pharmacologic stress agent . This study compared the sensitivity of arbutamine with symptom-limited exercise to induce echocardiographic signs of ischemia . Arbutamine was administered by a computerized closed-loop delivery system that controls the infusion rate of arbutamine toward a predefined rate of heart rate increase and maximum heart rate limit . Beta blockers were stopped > or = 48 hours before both tests . Stress was stopped for intolerable symptoms , or clinical , electrocardiographic or echocardiographic signs of ischemia ( new or worsening wall motion abnormality ) , target heart rate ( > or = 85 % age predicted maximum heart rate ) , or plateau of heart rate response . Thirty-seven patients were entered into the study ( 35 arbutamine and exercise , 1 arbutamine only , 1 exercise only ) , of which 30 had angiographic evidence of coronary artery disease ( > or = 50 % lumen diameter narrowing ) . Rate-pressure product increased significantly in response to both stress modalities ( p < 0.001 ) and was significantly greater with exercise ( 11,308 +/- 2,443 ) than with arbutamine ( 9,486 +/- 2,479 , p < 0.001 ) . The time to maximum heart rate was longer during arbutamine stress echocardiography than during exercise testing ( 17.3 +/- 9.4 versus 9.3 +/- 4.2 minutes , respectively , p < 0.001 ) . There were more patients with interpretable echo data for arbutamine ( 82 % ) than for exercise ( 67 % ) . Sensitivity for recognition of myocardial ischemia was 94 % ( 95 % confidence interval 70 % to 100 % ) and 88 % ( 95 % confidence interval 62 % to 98 % ) , respectively . The most frequent adverse events during arbutamine ( n = 36 ) were dyspnea ( 5.6 % ) and tremor ( 5.6 % ) . Two arbutamine stress tests were discontinued due to arrhythmias : 1 patient had premature atrial and ventricular beats , and the other had premature atrial contractions and atrial fibrillation . Arrhythmias were well tolerated and resolved without sequelae . In conclusion , the sensitivity of arbutamine to induce echocardiographic signs of ischemia was similar to that of exercise despite a lower rate-pressure product . Arbutamine was well tolerated and provides a reliable alternative to exercise echocardiography .

arbutamine

exercise echocardiography

Arbutamine

arbutamine

symptom-limited exercise

Arbutamine

arbutamine

arbutamine

exercise

exercise

arbutamine

exercise

arbutamine

exercise

arbutamine

arbutamine

arbutamine

exercise

Arbutamine

exercise echocardiography

echocardiographic signs of ischemia .

Rate-pressure product

time to maximum heart rate

adverse events

dyspnea

tremor

arrhythmias :

premature atrial and ventricular beats

echocardiographic signs of ischemia

rate-pressure product .

diagnosing myocardial ischemia .


Effect of desonide ointment , 0.05 % , on the hypothalamic-pituitary-adrenal axis of children with atopic dermatitis . Desonide ointment has demonstrated a good safety and efficacy profile during the many years it has been used in treating dermatoses . However , there have been no controlled clinical trials to evaluate its systemic safety when used in treating children . Suppression of the hypothalamic-pituitary-adrenal ( HPA ) axis can occur after repeated application of topical corticosteroids . In general , the degree of suppression of the HPA axis function is related to the daily dosage of steroid given , the duration of its administration , the extent of body surface covered , and the potency of the corticosteroid . This study sought to determine the comparative effects of 0.05 percent desonide and 2.5 percent hydrocortisone ointments on the HPA axis of children with atopic dermatitis . There was no suppression of early morning cortisol in either treatment group . The ACTH-stimulated mean cortisol values after four weeks of treatment were not significantly different from the baseline values for either treatment group . We conclude that neither 0.05 percent desonide ointment nor 2.5 percent hydrocortisone ointment compromised the HPA axis of children with atopic dermatitis treated topically for four weeks .

desonide ointment , 0.05 %

Desonide ointment

desonide

hydrocortisone ointments

0.05 percent desonide ointment

2.5 percent hydrocortisone ointment

suppression of early morning cortisol

ACTH-stimulated mean cortisol values

children

atopic dermatitis

children

children

atopic dermatitis

children

atopic dermatitis


Vitrectomy with silicone oil or long-acting gas in eyes with severe proliferative vitreoretinopathy : results of additional and long-term follow-up . Silicone Study report 11 . BACKGROUND The Silicone Study evaluated the outcomes of vitreoretinal surgery for retinal detachment with proliferative vitreoretinopathy ( PVR ) . OBJECTIVE To evaluate short-term ( up to 36 months ) outcomes in eyes randomized to silicone oil or perfluoropropane gas and long-term ( up to 72 months ) outcomes in eyes with attached maculas at 36 months . DESIGN Prospective , randomized , multicentered surgical trial . SETTING Community- and university-based vitreoretinal practices . PATIENTS Two-hundred sixty-five eyes with PVR randomized to perfluoropropane gas and silicone oil with follow-up through 3 years ( cohort 1 ) and 249 eyes with attached maculas at 36 months ( 121 eyes randomized to long-acting gas [ either sulfur hexafluoride or perfluoropropane ] and 128 eyes randomized to silicone oil ) with follow-up up to 6 years ( cohort 2 ) . Both cohorts consisted of eyes that had and had not undergone vitrectomy for PVR ( groups 1 and 2 , respectively ) before randomization . Of the 265 eyes in cohort 1 , 24-month follow-up data were available for 218 eyes ( 82 % ) and 36-month follow-up data were available for 196 eyes ( 74 % ) . Of 208 eyes in cohort 2 , 48-month follow-up data were available for 146 eyes ( 70 % ) , 60-month follow-up data for 119 eyes ( 57 % ) , and 72-month follow-up data for 73 eyes ( 35 % ) . INTERVENTIONS Vitrectomy surgery for PVR with a long-acting gas or silicone oil as the intraocular tamponade . MAIN OUTCOME MEASURES Changes in visual acuity , recurrent retinal detachment , and incidence of complications . RESULTS In group 1 of cohort 1 , compared with oil-treated eyes , gas-treated eyes had a higher rate of complete retinal reattachment from 18 to 36 months ( P < .05 ) . No other differences were found . In group 2 of cohort 1 , no notable differences were found between treatment arms . In cohort 2 , during 6 years of follow-up , attachment of the macula was maintained for all eyes . No notable differences in the rates of complete retinal attachment , visual acuity of 5/200 or better , or glaucoma were found between treatment groups . In contrast , gas-treated eyes had more hypotony ( P < .001 ) . Silicone oil-treated eyes that underwent subsequent surgery were more likely to have the oil retained ( P = .02 ) . Compared with oil-retained eyes , oil-removed eyes had higher rates of complete posterior attachment ( P = .01 ) and of a visual acuity of 5/200 or better ( P < .001 ) and less keratopathy ( P < .05 ) . Compared with oil-removed eyes , gas-treated eyes had a worse visual acuity outcome ( P < .05 ) and more hypotony ( P < .01 ) . CONCLUSION The Silicone Study showed that silicone oil and perfluoropropane gas were equal in most respects for the management of retinal detachments with PVR . Success in the first surgery for PVR is paramount for obtaining better visual results . Overall , surgery for PVR had a high likelihood of retinal reattachment , and if anatomically and visually successful at 3 years , there is an excellent chance that the results will be maintained over the long-term .

silicone oil

long-acting gas

silicone oil

perfluoropropane gas

perfluoropropane gas

silicone oil

long-acting gas

silicone oil

Silicone oil-treated

Changes in visual acuity

recurrent retinal detachment

incidence of complications

complete retinal reattachment

attachment of the macula

rates of complete retinal attachment

visual acuity of 5/200 or better

glaucoma

hypotony

subsequent surgery

rates of complete posterior attachment

visual acuity of 5/200 or better

keratopathy

visual acuity outcome

hypotony


Long-term follow-up of cytostatic intravesical instillation in patients with superficial bladder carcinoma . Is short-term , intensive instillation better than maintenance therapy ? OBJECTIVES Comparisons of two 3-year protocols , one 20-week protocol of mitomycin C instillation and one 3-year protocol of doxorubicin instillation for the prevention of recurrent tumors and progression in patients whose superficial bladder tumors had been removed by transurethral resection . METHODS A prospective , randomized parallel group multicenter trial was conducted . 419 patients were evaluated after a median follow-up of 57 months . Cox proportional hazards analysis was performed . RESULTS An overall recurrence rate of 22.7 % and an overall progression rate of 9.8 % was found . For time to progression a significant overall treatment effect was detected dependent on the recurrence status before entry into the study ( p = 0.0059 ) . Pairwise comparisons showed the mitomycin protocol with short-term intensive ( weekly ) combined with long-term maintenance instillation to have a highly beneficial effect compared to long-term maintenance instillation only especially for patients entering the study with recurrent tumors ( RR = 0.06 , 95 % CI : [ 0.008 , 0.506 ] . CONCLUSION These results show that intensive therapeutic instillation may have an advantage over less intensive , prophylactic regimens .

cytostatic intravesical instillation

mitomycin C instillation

doxorubicin instillation

recurrent tumors

progression

overall

recurrence rate

overall progression rate

overall treatment effect

beneficial effect

intensive therapeutic instillation

419 patients


Randomised trial of effect of amiodarone on mortality in patients with left-ventricular dysfunction after recent myocardial infarction : EMIAT . European Myocardial Infarct Amiodarone Trial Investigators . BACKGROUND Ventricular arrhythmias are a major cause of death after myocardial infarction , especially in patients with poor left-ventricular function . Previous attempts to identify and suppress arrhythmias with various antiarrhythmic drugs failed to reduce or actually increase mortality . Amiodarone is a powerful antiarrhythmic drug with several potentially beneficial actions , and has shown benefit in several small-scale studies . We postulated that this drug might reduce mortality in patients at high risk of death after myocardial infarction because of impaired ventricular function , irrespective of whether they had ventricular arrhythmias . METHODS The European Myocardial Infarct Amiodarone Trial ( EMIAT ) was a randomised double-blind placebo-controlled trial to assess whether amiodarone reduced all-cause mortality ( primary endpoint ) and cardiac mortality and arrhythmic death ( secondary endpoints ) in survivors of myocardial infarction with a left-ventricular ejection fraction ( LVEF ) of 40 % or less . Intention-to-treat and on-treatment analyses were done . FINDINGS EMIAT enrolled 1486 patients ( 743 in the amiodarone group , 743 in the placebo group ) . Median follow-up was 21 months . All-cause mortality ( 103 deaths in the amiodarone group , 102 in the placebo group ) and cardiac mortality did not differ between the two groups . However , in the amiodarone group , there was a 35 % risk reduction ( 95 % CI 0-58 , p = 0.05 ) in arrhythmic deaths . INTERPRETATION Our findings do not support the systematic prophylactic use of amiodarone in all patients with depressed left-ventricular function after myocardial infarction . However , the lack of proarrhythmia and the reduction in arrhythmic death support the use of amiodarone in patients for whom antiarrhythmic therapy is indicated .

amiodarone

Amiodarone

placebo-controlled

amiodarone

amiodarone

placebo

amiodarone

amiodarone

amiodarone

mortality

all-cause mortality

cardiac mortality and arrhythmic death

All-cause mortality

cardiac mortality

risk reduction

arrhythmic deaths

arrhythmic death


Doxymycine-cyanoacrylate treatment of recurrent aphthous ulcers . OBJECTIVE This study addressed the efficacy of singularly applied topical doxymycine in the pain relief treatment of recurrent aphthous stomatitis . STUDY DESIGN Thirty-one patients with recurrent aphthous lesions were examined and divided randomly in two groups . Experimental group ( n = 15 ) received a topical application of doxymycine and controls ( n = 16 ) received calcii gluconase in the same manner . Medications were covered by isobutyl cyanoacrylate ( Iso-Dent ) . Application was made only once during the recurrent aphthous ulcer episode . RESULTS Patients recorded their pain level on a visual analog scale for 10 days during healing . Pain decreased more rapidly in the experimental group , and a statistically significant difference ( p < 0.05 ) in the pain intensity was found from the second to the seventh day after application of doxymycine . CONCLUSIONS In recurrent aphthous ulcers , singular treatment of topical doxymycine-cyanoacrylate relieves the pain intensity remarkably for 6 days after a 1 day latency period . Topical doxymycine treatment further exerts potential to directly prevent tissue destruction and to indirectly suppress host inflammatory reaction .

Doxymycine-cyanoacrylate

doxymycine

topical application of doxymycine

controls

isobutyl cyanoacrylate

doxymycine

doxymycine-cyanoacrylate

doxymycine

pain relief

pain level

Pain

pain intensity

pain intensity

Thirty-one

aphthous lesions


Effects of frusemide and hypoxia on the pulmonary vascular bed in man . AIMS Diuretic therapy is conventionally used to treat oedema in patients with hypoxic cor pulmonale . This condition is associated with activation of the renin angiotensin system ( RAS ) with elevated levels of angiotensin II ( ANG II ) , a potent pulmonary pressor agent . We explored the hypothesis that RAS activation by diuretic therapy might therefore worsen hypoxic pulmonary vasoconstriction via the effects of ANG II on the pulmonary vascular bed . METHODS Eight normal volunteers were studied on 2 separate days . They either received 40 mg frusemide daily or placebo for 4 days and were then rendered hypoxaemic , by breathing an N2/O2 mixture for 20 min to achieve an SaO2 of 85-90 % adjusted for a further 20 min to achieve an SaO2 of 75-80 % . Pulsed wave doppler echocardiography was used to measure mean pulmonary artery pressure , cardiac output and hence pulmonary vascular resistance ( PVR ) . RESULTS Plasma renin activity ( PRA ) was significantly ( P < 0.01 ) increased after prior treatment with frusemide compared with placebo at all time points . Prior treatment with frusemide significantly ( P < 0.05 ) increased PVR compared with placebo at baseline : 185 +/- 17 vs 132 +/- 10 dyn s cm-5 at an SaO2 of 85-90 % : 291 +/- 18 vs 229 +/- 16 dyn s cm-5 and at SaO2 of 75-80 % : 356 +/- 12 vs 296 +/- 17 dyn s cm-5 respectively . However , the delta-PVR response to hypoxaemia was not significantly altered by frusemide compared with placebo . In contrast to its effect on the pulmonary vasculature prior treatment with frusemide did not significantly alter systemic haemodynamic parameters either at baseline or during hypoxia . CONCLUSIONS Thus , prior treatment with frusemide increased baseline pulmonary vascular resistance and significantly augmented the hypoxaemic pulmonary vascular response in additive fashion . It is hypothesised that this effect of frusemide may be due to RAS activation with ANG II mediated pulmonary vasoconstriction .

frusemide

Diuretic

40 mg frusemide daily or placebo

frusemide

placebo

frusemide

placebo

frusemide

placebo

frusemide

frusemide

frusemide

pulmonary vascular resistance ( PVR ) .

Plasma renin activity ( PRA )

PVR

delta-PVR response to hypoxaemia

systemic haemodynamic parameters

pulmonary vascular resistance

hypoxaemic pulmonary vascular response

pulmonary vascular bed

man

oedema

hypoxic cor pulmonale

Eight


Studies on section 2D1 monoclonal antibodies . Monoclonal antibodies in " Other Blood Groups " were tested with random blood samples collected from the various ethnic groups in KwaZulu-Natal , South Africa , and with samples of selected red cell phenotypes . Standard red cell serological techniques were used .

random blood samples

section 2D1 monoclonal antibodies


Partial-area method in bioequivalence assessment : naproxen . Regulatory authorities require demonstration of bioequivalence through comparisons of different pharmacokinetic parameters , the area under the plasma concentration-time curve ( AUC ) , the maximum plasma concentration ( Cmax ) , and the time to reach peak concentration ( Tmax ) . The applicability and validity of regulatory requirements have been widely criticized on statistical and clinical relevance grounds . For most noncomplicated absorption models , the AUC correlates well with the extent of absorption . However , in nonlinear models of absorption , in mechanisms involving recycling of drugs , and for drugs with long half-life , the use of total AUC ( from zero to infinity ) can give erroneous and clinically irrelevant results since the area is mostly determined by elimination phase or by recycling . The calculation of total AUC also involves prolonged sampling , adding to the cost and risks associated with bioequivalence studies . The use of Cmax or Tmax as a measure of rate of absorption , to correlate with clinical relevance , is widely criticized on logical , technical , and statistical grounds . For drugs used on a multiple-dose basis , Cmax and Tmax evaluations become redundant since the average plateau concentration is not affected by these parameters . To resolve the drawbacks in the traditional methodology of bioequivalence evaluation , the use of partial areas in lieu of total AUC , Tmax , and Cmax is suggested . This study investigates the logic and robustness of the partial-area method in establishing bioequivalence . We conclude that the 5h AUC is a more relevant parameter to establish naproxen bioequivalence than AUCinf . We recommend against using symmetrical confidence intervals and report excellent agreement among several methods of calculating confidence intervals , probability values , and nonparametric tests . We suggest that a single-point short-term AUC is a better indicator of the bioequivalence of generic products than the total AUC , Cmax , and Tmax as required currently by the regulatory authorities .

naproxen

naproxen

the time to reach peak concentration

( Tmax )

AUC

AUC

AUC

Cmax

Tmax

Cmax

Tmax

plateau concentration

AUC

Tmax

Cmax

5h AUC

AUCinf

single-point short-term AUC

AUC

Cmax

Tmax

Partial-area method in bioequivalence

bioequivalence


A limited sampling method for the estimation of flunarizine area under the curve ( AUC ) and maximum plasma concentration ( Cmax ) . A limited sampling model has been developed for flunarizine following a 30 mg oral dose in epileptic patients who were receiving phenytoin or carbamazepine or both , to estimate the area under the curve ( AUC ) and maximum plasma concentration ( Cmax ) . The model was developed using training data sets from 30 , 20 , 15 , or 10 patients at one or two time points . The equations describing the models for AUC using two time points ( 3 and 24h ) and Cmax for the training data set of 30 subjects were AUCpredicted = 11.1 C3h + 121.4 C24h - 157 ( r = 0.80 ) Cmax ( predicted ) = 0.036 AUC + 42.9 ( r = 0.74 ) The model was validated on 64 patients who received flunarizine orally . The model provided reasonably good estimates for both AUC and Cmax . The mean predicted AUC of flunarizine was 1230 +/- 717 ng h mL-1 , whereas the observed AUC was 1203 +/- 900 ng h mL-1 . The bias of the prediction was 2 % and precision was 28 % . The mean predicted Cmax of flunarizine was 86 +/- 32 ng mL-1 as compared to an observed mean Cmax of 90 +/- 42 ng mL-1 . The bias and precision of the prediction were 4 % and 24 % , respectively . The method described here may be used to estimate AUC and Cmax for flunarizine without detailed pharmacokinetic studies .

phenytoin

carbamazepine

maximum plasma concentration ( Cmax )

estimates for both AUC

Cmax

mean predicted AUC of flunarizine

observed AUC

bias of the prediction

predicted Cmax of flunarizine

observed mean Cmax

bias and precision of the prediction

epileptic patients


[ Restorative proctectomy , reconstruction of continuity with or without colon J pouch ] . Of 63 patients undergoing deep anterior resection of the rectum , 39 patients received a straight colo-anal anastomosis ( CAA ) , 24 additionally had a colon-j-pouch ( CPA ) constructed . Local septic complications occurred in 12.5 % of patients after pouch-anal anastomosis compared to 20.5 % after colo-anal anastomosis : stool frequency , after pouch-anal anastomosis was 3.3 per 24 h compared to 5.2 per 24 h after straight anastomosis within the first year after ileostomy closure ( p = 0.053 ) ; continence was slightly better in the pouch group ( n.s . ) ; and anal manometry showed a significant postoperative decrease only in resting pressure after straight colo-anal anastomosis ( p < 0.001 ) . Pouch construction should be considered after deep rectal resection , as it seems to improve functional outcome and has fewer local septic complications than straight anastomosis .

straight colo-anal anastomosis ( CAA )

colon-j-pouch ( CPA ) constructed

Local septic complications

continence

manometry

functional outcome

local septic complications

deep anterior resection of the rectum


[ Laparoscopic or conventional inguinal hernia repair with or without implant . A prospective randomized study ] .

with or without implant

inguinal hernia repair

inguinal hernia repair


Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid . The Tokyo Joshi-Idai Asthma Research Group . To test whether the leukotriene antagonist ONO-1078 ( pranlukast ) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid , we conducted a randomized , double-blind , placebo-controlled study in 79 asthma patients requiring high doses ( 1,500 microg/d or more ) of inhaled beclomethasone dipropionate ( BDI ) for clinical control ( duration of asthma , 11.0 +/- 3.1 yr ; duration of BDI treatment , 0.5 +/- 0.3 yr ; FEV1 percentage of predicted , 80.7 +/- 2.0 % ) . After a 2-wk run-in period , the doses of BDI were halved , while the patients were assigned to receive orally ONO-1078 , 450 mg twice daily , or placebo . In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk ( p < 0.001 ) . Likewise , morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min , respectively . By contrast these variables were sustained above baseline in the ONO-1078 group . The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group , whereas they remained unchanged in the ONO-1078 group . In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased ( p = 0.007 and p = 0.025 , respectively ) , compared with no change in the ONO-1078 group . Therefore , the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half .

Leukotriene antagonist

corticosteroid

orally ONO-1078 , 450 mg twice daily

placebo

placebo

placebo

leukotriene antagonist ONO-1078

morning and evening PEF

use of beta2-agonist

asthma

asthma

asthma patients

inhaled beclomethasone dipropionate

asthma


The effect of inhaled leukotriene D4 and methacholine on sputum cell differentials in asthma . The cysteinyl leukotriene LTE4 has been shown to induce airway eosinophilia in asthmatics in vivo . This phenomenon has not yet been reported for LTD4 . Hence , we examined the effect of inhaled LTD4 and a control bronchoconstrictor agent , methacholine , on cell differentials in hypertonic saline-induced whole sputum samples of 12 nonsmoking atopic asthmatic subjects ( three women , nine men ; 21 to 29 yr of age ; FEV1 , 74 to 120 % pred ; PC20FEV1 methacholine < 9.6 mg/ml ) . The study had a cross-over , placebo-controlled design consisting of 4 d separated by > or = 1 wk . On each randomized study day , the subjects inhaled five serial doses of either LTD4 ( mean cumulative concentration : 95.7 microM ) or methacholine ( mean cumulative concentration : 542 mM ) or five doses of their respective diluents ( PBS/ethanol or PBS ) . The airway response was measured by FEV1 , followed by sputum induction with 4.5 % NaCl , 4 h postchallenge . Inflammatory cells ( > or = 250 ) were counted twice on coded cytospins and expressed as percentages of nonsquamous cells . There was no significant difference in the maximal percent fall in FEV1 from baseline between LTD4 ( mean +/- SEM , 49.5 +/- 4.4 % fall ) and methacholine ( mean +/- SEM , 55.9 +/- 3.4 % fall ) ( p = 0.11 ) . LTD4 induced a significant increase in the percentage of sputum eosinophils as compared with its diluent ( mean +/- SD , 26.6 +/- 21.3 % and 10.2 +/- 8.8 % , respectively ; p = 0.025 ) , whereas a similar trend for methacholine failed to reach significance ( mean +/- SD , 19.1 +/- 22.9 % and 7.8 +/- 5.8 % , respectively ; p = 0.11 ) . There was no significant difference in the changes in the percentage of sputum eosinophils between LTD4 and methacholine ( mean difference +/- SD , 7.5 +/- 12.5 % eosinophils ; p = 0.09 ) . We conclude that LTD4 induces eosinophilia in sputum of asthmatic subjects 4 h after inhalation . Our data suggest that LTD4 recruits eosinophils into the airways of asthmatics in vivo , possibly by virtue of direct or indirect chemotactic properties , whereas an additional effect of vigourous airway narrowing per se can not be excluded .

leukotriene D4

methacholine

cysteinyl leukotriene LTE4

methacholine

( PBS/ethanol

sputum cell differentials

airway eosinophilia

cell differentials

airway response

percentage of sputum eosinophils

percentage of sputum eosinophils

eosinophilia in sputum

eosinophils

vigourous airway narrowing

asthma .


Comparative efficacy and safety of twice daily fluticasone propionate powder versus placebo in the treatment of moderate asthma . BACKGROUND Fluticasone propionate , an inhaled corticosteroid with negligible systemic bioavailability via the oral route , is efficacious in the treatment of asthma when administered via metered-dose inhaler . OBJECTIVE To evaluate the efficacy and safety of inhaled fluticasone propionate powder in patients with moderate asthma previously treated with an inhaled corticosteroid . METHODS This was a randomized , double-blind , placebo-controlled , parallel-group , multicenter study of 342 adolescent and adult patients with moderate asthma [ forced expiratory volume in 1 second ( FEV1 ) between 50 % and 80 % of predicted ] treated previously by beclomethasone dipropionate or triamcinolone acetonide . Patients received fluticasone propionate powder 50 micrograms , 100 micrograms , 250 micrograms , or placebo via a breath-actuated inhalation device , the Diskhaler , twice daily for 12 weeks . RESULTS Patients in the fluticasone propionate groups experienced a mean increase from baseline to endpoint in FEV1 ranging from 0.43 L to 0.47 L. Patients in the placebo group experienced a mean decrease from baseline of 0.22 L ( P < .001 ) . The probability of patients remaining in the study over time without developing signs of exacerbating asthma was significantly greater in the fluticasone propionate groups than in the placebo group ( P = .001 ) . Asthma symptom scores , supplemental rescue albuterol use , and number of nighttime awakenings due to asthma requiring treatment also improved significantly with all fluticasone propionate treatment regimens compared with placebo ( P < .001 ) . There were no statistically significant differences at endpoint among the three fluticasone propionate groups . No serious drug-related adverse events occurred . CONCLUSIONS Fluticasone propionate powder ( 50 , 100 , and 250 micrograms ) was well-tolerated and significantly improved lung function in patients with moderate asthma .

fluticasone propionate powder

placebo

Fluticasone propionate

inhaled fluticasone propionate powder

beclomethasone dipropionate

triamcinolone acetonide

fluticasone propionate powder

placebo

efficacy and safety

efficacy and safety

remaining in the study over time

exacerbating asthma

serious drug-related adverse events

well-tolerated and significantly

improved lung function

moderate asthma

asthma

adolescent and adult

moderate asthma

moderate asthma


Confounding by indication ?


Effects of age at introduction of complementary foods to breast-fed infants on duration of lactational amenorrhea in Honduran women . Lactational amenorrhea ( LA ) is associated with postpartum infertility and is known to be related to breast-feeding frequency and duration , but the exact role of complementary feeding of the infant has not been clearly defined . Data on LA were collected during and after a 2-mo intervention trial in which low-income Honduran women who had breast-fed fully for 4 mo were randomly assigned to one of three groups : continued full breast-feeding until 6 mo ( FBF , n = 50 ) , introduction of complementary foods at 4 mo with ad libitum breast-feeding from 4 to 6 mo ( SF , n = 47 ) , or introduction of complementary foods at 4 mo with maintenance of baseline breast-feeding frequency from 4 to 6 mo ( SF-M , n = 44 ) . Women were followed up until the infant was 12 mo of age , or later if menses had not occurred by then . All but six of the women continued to breast-feed for > or = 12 mo . With the exclusion of those whose menses returned before 18 wk postpartum ( which could not have been due to the intervention ) , the proportion of women who were amenorrheic at 6 mo was 64.5 % in the SF group , 80.0 % in the FBF group , and 85.7 % in the SF-M group ( chi-square test = 4.13 , P = 0.02 ; one-tailed test with the latter two groups combined ) . The total duration of LA did not differ significantly among groups . The most significant determinant of LA was time spent breast-feeding ( min/d ) , which was in turn negatively associated ( P = 0.06 ) with the infant 's energy intake from complementary foods in regression analyses . These results indicate that there is a significant effect of introducing foods at 4 mo on the likelihood of amenorrhea at 6 mo postpartum , but not thereafter , and that this effect is not seen in mothers who maintain breast-feeding frequency .

complementary foods

complementary feeding

breast-feeding

complementary foods

Lactational amenorrhea

total duration of LA

time spent breast-feeding ( min/d )

infant 's energy intake


A randomised trial evaluating pain and bleeding after a first trimester miscarriage treated surgically or medically . Miscarriage treated surgically and medically were compared in a randomised controlled trial evaluating pain and bleeding . Surgery is associated with less pain ( P < 0.03 ) and vaginal bleeding ( duration and severity , P = 0.001 ) than medical treatment , fewer daily hospital attendances ( 2.5 compared with three , P = 0.04 ) but a greater drop in haemoglobin concentration ( difference , 1 g/dl ; CI95 % = 0.3-1.6 ) .

surgically

medically

first trimester miscarriage


Clinical effects of buspirone in social phobia : a double-blind placebo-controlled study . BACKGROUND The results of open pilot studies suggest that the serotonin-1A ( 5-HT1A ) receptor agonist buspirone might be effective in social phobia . METHOD In the present study , the efficacy of buspirone was investigated in patients with social phobia using a 12-week double-blind placebo-controlled design . Thirty social phobic patients ( DSM-IV ) were treated with either buspirone 30 mg daily or placebo . Efficacy of treatment was measured using the Social Phobia Scale ( subscores anxiety and avoidance ) and the Hamilton Rating Scale for Anxiety . RESULTS Taking a reduction of 50 % or more on the Social Phobia Scale as a criterion for clinically relevant improvement , only 1 patient on buspirone and 1 on placebo were classified as responder to treatment . A subjective and clinically relevant improvement was reported by 4 patients ( 27 % ) on buspirone and 2 patients ( 13 % ) on placebo . There were no statistically significant differences between buspirone and placebo on any of the outcome measures . Generally speaking , buspirone was well tolerated . CONCLUSION The results of the study do not support the results of open studies , in which a reduction of social anxiety and social avoidance was reported in patients with social phobia treated with buspirone .

buspirone

buspirone

placebo-controlled

buspirone

placebo

placebo

buspirone

placebo

buspirone

efficacy

Hamilton Rating Scale for Anxiety

reduction

Social Phobia Scale

relevant improvement

well tolerated

social anxiety and social avoidance

social phobia

Thirty

social phobic patients ( DSM-IV )

social phobia


[ A randomized comparative study of surgical adjuvant chemotherapy using 5-fluorouracil and dl-leucovorin with CDDP 5-FU and dl-leucovorin for colorectal cancer ] . A randomized comparative study of surgical adjuvant chemotherapy using dl-leucovorin ( dl-LV ) and 5-fluorouracil ( 5-FU ) ( FL-therapy ) with CDDP , 5-FU , and dl-LV ( PFL-therapy ) was conducted . The following were the administration schedules : Arm A was 13 mg/m2 of CDDP , 300 mg/m2 of 5-FU , and 30 mg/body of dl-LV for 5 consecutive days and arm B was 300 mg/m2 of 5-FU and 30 mg/body of dl-LV for 5 consecutive days . Both regimens were followed by biweekly administration of the same dose of dl-LV and 5-FU in outpatients . Arm A was started at the 26th postoperative day and arm B at the 21st day on average . Some 26 cases composed of 11 cases of arm A and 15 cases of arm B completed the administration schedules . Only one case in arm A was complicated by local recurrence around 35 months after operation . Major toxicities were anorexia and neutropenia . Both toxicities were seen more in arm A than in arm B , showing complete recovery in all cases . These data suggest that PFL-therapy and FL-therapy seem to be possible and promising surgical adjuvant therapies for advanced colorectal carcinoma .

surgical adjuvant chemotherapy

surgical adjuvant chemotherapy

CDDP

dl-LV

dl-LV

dl-LV

local recurrence

toxicities

anorexia and neutropenia .

toxicities

advanced colorectal carcinoma .

colorectal cancer

advanced colorectal carcinoma .


[ Initial nuclear magnetic resonance tomography results of the treatment course of avascular femur head necrosis after femoral core decompression ] . The vascular femoral head necrosis is a serious illness , especially when appearing in patients aged 30 to 50 years . Many etiologic factors cause a femoral head necrosis such as , for example , high-dose steroids , abuse of alcohol , defect of bone marrow and trauma of the hip . Often the X-ray photograph leads to the diagnosis in the second stage ( ARCO 1992 ) or in the third stage , when the femoral head has begun to collapse . The stage IIc and III shows an evident enhancement in contrast media in MRI . Contrast enhancement is demonstrated by STIR , FATSAT , T1-weighted and dynamic screening sequence . The characteristics of the contrast media enhancement argue for an active concomitant process of destruction and regeneration . This stage has the best chances for a drug or a surgical therapy . The evaluation of the signal intensity by the dynamic screening sequence is considered as an objective contribution for the staging of the femoral head necrosis . This enables one to differentiate between the curable stage IIc and the stage III , showing the beginning of breakdown of the femoral head .

nuclear magnetic resonance tomography

MRI

dynamic screening sequence

staging of the femoral head necrosis

curable stage IIc

stage III

breakdown of the femoral head

avascular femur head necrosis

femoral core decompression

vascular femoral head necrosis

30 to 50 years

defect of bone marrow

trauma of the hip

breakdown of the femoral head


Effect of inhaled heparin on adenosine-induced bronchial hyperreactivity . Glycosaminoglycan heparin possesses multiple noncoagulant properties including antiinflammatory actions . We have previously shown that heparin attenuates the methacholine-induced bronchoconstriction in humans . In contrast to methacholine , a stimulus that induces airway constriction mainly by " direct " stimulation of airway smooth muscle cells , adenosine airway responsiveness reflects " indirectly " induced airway narrowing via inflammatory mediators or neural reflex mechanisms . Whether heparin modulates bronchial hyperreactivity induced by adenosine , is not well known . We investigated the effect of inhaled heparin on adenosine-induced bronchoconstriction and compared the inhibitory role of heparin on the adenosine challenge test with that on the methacholine challenge test . Fifteen subjects ( 7 males , 8 females ) with mild asthma were included in the study . Bronchial provocation tests were performed in a single-blind , crossover , randomized order , and repeated 45 minutes after placebo or aerosolized heparin inhalation ( 1,000 U/kg ) . The heparin increased the geometric mean log methacholine PD20 value from 0.47 +/- 0.16 ( 2.95 mg/ml ) to 0.96 +/- 0.10 ( 8.91 mg/ml ) , ( P < 0.0009 ) in 15 patients and the geometric mean log adenosine PD20 values from 1.59 +/- 0.23 ( 38.9 mg/ml ) to 1.98 +/- 0.14 ( 97.7 mg/ml ) ( NS ) in 7 patients whose baseline adenosine PD20 levels were less than 200 mg/ml . The degree of protection by heparin against adenosine-induced bronchoconstriction was not correlated with that against methacholine-induced bronchoconstriction ( r = 0.60 , NS ) . The data suggest that inhaled heparin may have an inhibitory effect on the methacholine bronchial challenge , and thus , most likely directs its effect against smooth muscle . Heparin caused less attenuation of a challenge with adenosine and probably does not affect mast cell degranulation .

heparin

Glycosaminoglycan heparin

heparin

heparin

inhaled heparin

heparin

placebo

aerosolized heparin inhalation

heparin

heparin

heparin

Heparin

degree of protection

humans

Fifteen

males

females

mild asthma


Field trials of a vaccine against bovine mastitis . 1 . Evaluation in heifers . A vaccine was developed against bovine mastitis based on inactivated , highly encapsulated Staphylococcus aureus cells ; a crude extract of Staph . aureus exopolysaccharides ; and inactivated , unencapsulated Staph , aureus and Streptococcus spp . cells . This vaccine was tested on 30 heifers during a 7-mo period . The 30 heifers were randomly assigned to three groups of 10 heifers each . The prepartum group received two injections of the vaccine at 8 and 4 wk before calving , and the postpartum group received two injections at 1 and 5 wk after calving . The control group received two injections of a placebo at 8 and 4 wk before calving . The vaccine or the placebo was administered subcutaneously in the brachiocephalicus muscle of the neck . The frequencies of intramammary infections caused by Staph . aureus were reduced from 18.8 % for heifers in the control group to 6.7 and 6.0 % for heifers in the prepartum and postpartum groups , respectively . This protective effect was maintained for at least 6 mo . The relative risk of mastitis caused by Staph . aureus was 0.31 and 0.28 for heifers in the prepartum and postpartum groups , respectively , compared with that for heifers in the control group . The results of the trial indicated the effectiveness of the vaccine in decreasing the incidence of intrammammary infections caused by Staph . aureus . A slight but nonsignificant increase occurred in fat production in the milk of vaccinated cows . The vaccine had no observable effect on somatic cell count or streptococcal infections .

vaccine

vaccine

vaccine

vaccine

vaccine

placebo

aureus

protective effect

aureus

fat production

heifers

heifers

heifers


Randomised controlled trial of graded exercise in patients with the chronic fatigue syndrome . OBJECTIVE To test the efficacy of a graded aerobic exercise programme in the chronic fatigue syndrome . DESIGN Randomised controlled trial with control treatment crossover after the first follow up examination . SETTING Chronic fatigue clinic in a general hospital department of psychiatry . SUBJECTS 66 patients with the chronic fatigue syndrome who had neither a psychiatric disorder nor appreciable sleep disturbance . INTERVENTIONS Random allocation to 12 weeks of either graded aerobic exercise or flexibility exercises and relaxation therapy . Patients who completed the flexibility programme were invited to cross over to the exercise programme afterwards . MAIN OUTCOME MEASURE The self rated clinical global impression change score , " very much better " or " much better " being considered as clinically important . RESULTS Four patients receiving exercise and three receiving flexibility treatment dropped out before completion . 15 of 29 patients rated themselves as better after completing exercise treatment compared with eight of 30 patients who completed flexibility treatment . Analysis by intention to treat gave similar results ( 17/33 v 9/33 patients better ) . Fatigue , functional capacity , and fitness were significantly better after exercise than after flexibility treatment . 12 of 22 patients who crossed over to exercise after flexibility treatment rated themselves as better after completing exercise treatment 32 of 47 patients rated themselves as better three months after completing supervised exercise treatment 35 of 47 patients rated themselves as better one year after completing supervised exercise treatment . CONCLUSION These findings support the use of appropriately prescribed graded aerobic exercise in the management of patients with the chronic fatigue syndrome .

graded exercise

graded aerobic exercise programme

graded aerobic exercise

flexibility exercises

relaxation therapy

flexibility programme

exercise programme

exercise

flexibility treatment

exercise treatment

flexibility treatment

exercise

flexibility treatment

exercise

exercise treatment

supervised exercise treatment

graded aerobic exercise

chronic fatigue syndrome

chronic fatigue syndrome

Fatigue

functional capacity

fitness

better

chronic fatigue syndrome

chronic fatigue syndrome

chronic fatigue syndrome

psychiatric disorder

appreciable sleep disturbance

chronic fatigue syndrome


Clinical evaluation of the speed and effectiveness of subgingival calculus removal on single-rooted teeth with diamond-coated ultrasonic tips . Several studies have found incomplete calculus removal during periodontal treatment with traditional hand curets , sonic , and ultrasonic instruments . This study evaluated the speed and effectiveness of subgingival calculus removal with new diamond-coated ultrasonic tips on single-rooted teeth . Single session subgingival scaling and root planing was performed on 80 teeth with 5 to 12 mm probing depths in 15 patients . Each patient provided groups of 4 teeth that were randomly treated with either hand curets ( HAND ) ; standard smooth ultrasonic tip ( US ) ; or fine grit ( FINDIAM ) or medium grit ( MEDDIAM ) diamond-coated ultrasonic tips . The time taken to reach the therapeutic endpoint of a clean , smooth root surface in a defined region on each tooth with each instrument by the 3 therapists with differing experience levels was recorded . The teeth were then atraumatically extracted , stored in a surfactant , photographed at 10X , and the percent of calculus present in the area of the pocket or on a comparable control surface calculated by histometric point counting . ANOVA and paired t tests showed that mean percent remaining calculus on treated versus control surfaces was HAND 4.6 +/- 5.3 versus 57.5 +/- 28.2 , US 4.7 +/- 6.4 versus 54.4 +/- 25.9 , FINDIAM 4.3 +/- 5.2 versus 37.5 +/- 22.1 , and MEDDIAM 3.4 +/- 4.2 versus 50.7 +/- 20.1 , respectively ( all P < 0.01 ) . The mean time in seconds to reach the clinical endpoint ranged from HAND 289 +/- 193 , US 194 +/- 67 , FINDIAM 167 +/- 71 , to MEDDIAM 147 +/- 92 . All powered instruments were significantly faster than HAND ( P < 0.05 ) , but did not differ from each other . On a 0 = " smooth " to 3 = " rough " scale , most often HAND resulted in " smooth " surfaces ( 10/20 ) , the powered tips of all types " slight " surface roughness ( 10/20 each ) , and US the most " moderate " roughness ( 7/20 ) . There were no differences in percent calculus remaining , surface roughness , or time spent among the 3 treating clinicians despite their varying experience levels . The results of this study showed that percent calculus remaining was < 5 % with all the instruments given time ad libitum on a given root surface . Root roughness was generally slightly greater with all 3 powered tips . All of the powered instruments took significantly less time than the HAND . Both DIAM tips took less time than US . Diamond-coated ultrasonic tips appeared to be much more efficient than HAND or US in removing calculus in moderate-deep probing depths on single-rooted teeth in vivo .

diamond-coated ultrasonic tips

subgingival calculus removal

new diamond-coated ultrasonic tips

hand curets ( HAND )

standard smooth ultrasonic tip ( US )

fine grit ( FINDIAM )

US

Diamond-coated ultrasonic tips

calculus removal

mean percent remaining calculus

" smooth " surfaces

" slight " surface roughness

" moderate " roughness

percent calculus remaining

Root roughness

time

time


The low-dose monoethylglycinexylidide test : assessment of liver function with fewer side effects . The hepatic metabolism of lidocaine ( 1 mg/kg intravenously ) to its metabolite monoethylglycinexylidide ( MEG-X ) is the basis of the standard MEG-X test . To reduce the lidocaine-induced side effects , we evaluated the MEG-X formation after 0.5 and 1 mg/kg lidocaine intravenously in subjects with normal ( n = 5 ) and severely impaired liver function ( n = 7 ) ( study I ) . From this study , a low-dose test ( MEG-X concentration 30 minutes after 50 mg lidocaine intravenously [ MEG-X30min ] normalized to standard MEG-X test results ) was developed . Sensory side effects from this low dose and from the standard MEG-X test were compared in a double-blind , randomized , cross-over study ( study II ) comprising 15 individuals with normal liver function and 45 patients with cirrhosis ( 15 Child A , 15 Child B , and 15 Child C ) . In study I , MEG-X formation rate was dose-independent in patients with severely impaired liver function . In study II , normalized MEG-X test results ( ranging from < or = 4 to 120 microg/L ) were virtually identical to the standard test results ( mean difference : -1.9 microg/L ; 95 % confidence interval [ CI ] : -5.3 ; 1.5 microg/L ) . Fewer individuals experienced side effects ( 30 % vs. 53 % ) with the low-dose test ( P = .0013 ) . In a multivariate analysis , the Child-Pugh score was inversely related to the occurrence of side effects . The low-dose MEG-X test gives almost identical results to the standard MEG-X test and is associated with fewer side effects , which occur less often in individuals with more severely compromised liver function .

lidocaine

monoethylglycinexylidide ( MEG-X )

MEG-X

lidocaine-induced

MEG-X

MEG-X

lidocaine

MEG-X

MEG-X

assessment

MEG-X formation rate

Child-Pugh score

side effects .

fewer side effects


Low intensity physical training in older subjects . BACKGROUND This study was designed to evaluate the effects of a low intensity general training program ( < 50 % of heart rate reserve ) on physical fitness of healthy older subjects , by comparing maximal and submaximal indices of training response . METHODS Twenty-two volunteers over 60 years of age participated in the present study . The sample was randomly divided in an experimental group of 13 older subjects ( 3 men and 10 women , mean age 63.5 +/- 3 years ) while the remaining 9 subjects ( 3 men and 6 women , mean age 64.2 +/- 4 years ) served as inactive control group . After medical screening all participants were evaluated before and after 12 weeks in which the experimental subjects underwent a low intensity training . Each subjects-either inactive or active-performed two treadmill tests at two-days interval , to measure maximal and submaximal responses to exercise , respectively . Heart rate ( HR ) , oxygen uptake ( VO2 ) and pulmonary ventilation ( VE ) were measured using a telemetric apparatus . RESULTS The major finding of the study was the significant improvement in submaximal response to exercise of experimental subjects , expressed by the reduction in HR , VO2 VE while VO2 max did not change . CONCLUSIONS Thus , it appears that a low intensity general training similar to that followed in the present study may represent a good means to improve physical fitness in healthy elderly people . Similarly , this study supports the effectiveness of evaluation tests based on submaximal responses to exercise in this population .

Low intensity physical training

low intensity general training program

inactive control group

low intensity training

two treadmill tests

oxygen uptake ( VO2 )

pulmonary ventilation ( VE )

HR

physical fitness

submaximal responses

older subjects .


Dose-response relationship of complementary radiotherapy following four cycles of combination chemotherapy in intermediate-stage Hodgkin 's disease . PURPOSE To determine the appropriate irradiation dose after four cycles of modern combination chemotherapy in nonbulky involved field ( IF/BF ) and noninvolved extended-field ( EF/IF ) sites in patients with intermediate-stage Hodgkin 's disease ( HD ) . MATERIALS AND METHODS HD patients in stage I to IIIA with a large mediastinal mass , E stage , or massive spleen involvement were treated with two double cycles of alternating cyclophosphamide , vincristine , procarbazine , and prednisone ( COPP ) plus doxorubicin , bleomycin , vinblastine , and dacarbazine ( ABVD ) followed by EF irradiation in two successive trials ( HD1 and HD5 ) . In the HD1 trial ( 1983 to 1988 ) , 146 patients who responded to chemotherapy were randomized to receive 20 Gy ( 70 patients ) or 40 Gy ( 76 patients ) of EF irradiation in all fields outside bulky disease sites . A cohort of 111 patients who fulfilled the same inclusion criteria in the subsequent trial HD5 ( 1988 to 1993 ) were treated with 30 Gy . Bulky disease always received 40 Gy . RESULTS Freedom-from-treatment-failure ( FFTF ) and survival ( SV ) curves showed no differences between the 20- , 30- , and 40-Gy groups . However , acute toxicities were more frequent in the 40-Gy arm . Analysis of relapse patterns showed that 18 of 26 relapsing patients either failed to respond in initial bulky sites ( n = 5 ) or had an extranodal relapse ( n = 9 ) or both ( n = 4 ) . After 5 years , the cumulative risk for relapse in bulky sites is 10 % , despite 40 Gy of radiation . CONCLUSION Our results strongly suggest that there is no relevant radiotherapy dose effect in the range between 20 Gy and 40 Gy in IF/BF and EF/IF after 4 months of modern polychemotherapy in patients with intermediate-stage HD . Relapse patterns indicate that patients destined to relapse need more systemic , rather than local , treatment . Based on our data , we conclude that 20 Gy is sufficient in EF/IF of intermediate-stage HD following four cycles of modern polychemotherapy .

radiotherapy

chemotherapy

modern combination chemotherapy

cyclophosphamide

vincristine

procarbazine

prednisone ( COPP ) plus doxorubicin

bleomycin

vinblastine

dacarbazine ( ABVD )

EF irradiation

radiation

radiotherapy

polychemotherapy

polychemotherapy

Freedom-from-treatment-failure ( FFTF )

survival ( SV ) curves

acute toxicities

Analysis of relapse patterns

risk for relapse

radiotherapy dose effect

Hodgkin 's disease

chemotherapy

Hodgkin 's disease

HD

HD

stage I to IIIA

large mediastinal mass

E stage

massive spleen involvement

chemotherapy

polychemotherapy

intermediate-stage HD


Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus ( HIV ) immunoglobulin administered to HIV-infected pregnant women and their newborns . Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group . The pharmacokinetics and safety of hyperimmune anti-human immunodeficiency virus ( HIV ) intravenous immunoglobulin ( HIVIG ) were evaluated in the first 28 maternal-infant pairs enrolled in a randomized , intravenous immunoglobulin ( IVIG ) -controlled trial of HIVIG maternal-infant HIV transmission prophylaxis . Using 200 mg/kg , mean half-life and volume of distribution ( Vd ) in women were 15 days and 72 mL/kg , respectively , after one and 32 days and 154 mL/kg after three monthly infusions , with stable 4 mL/kg/day clearance . Transplacental passage occurred . Newborn single-dose half-life , Vd , and clearance were 30 days , 143 mL/kg , and 4 mL/kg/day , respectively . HIVIG rapidly cleared maternal serum immune complex-dissociated p24 antigen , and plasma HIV-1 RNA levels were stable . Mild to moderate adverse clinical effects occurred in 2 of 103 maternal and 2 of 25 infant infusions . No adverse hematologic , blood chemistry , or immunologic effects were seen . HIVIG is well-tolerated in HIV-infected pregnant women and their newborns , clears antigenemia , crosses the placenta , and exhibits pharmacokinetics similar to those of other immunoglobulin preparations .

HIVIG

HIVIG

Safety

pharmacokinetics

pharmacokinetics

safety

adverse clinical effects

well-tolerated

pharmacokinetics

HIV-infected

women

maternal-infant pairs

intravenous immunoglobulin

HIV

pregnant women

their newborns


Comparison of the efficacy and safety of ebrotidine in the treatment of duodenal ulcer . A multicentre , double-blind , placebo-controlled phase II study . Ebrotidine ( N- [ ( E ) - [ [ 2- [ [ [ 2- [ ( diaminomethylene ) amino ] -4 -thiazoly ] methyl ] thio ] ethyl ] amino ] methylene ] -4-bromo-benzenesulfon amide , CAS 100981-43-9 , FI-3542 ) is a new H2-receptor antagonist characterized by its high receptor affinity and gastroprotective effect . This Phase II study has been undertaken to establish the efficacy and safety of ebrotidine , administered in four dosages as a single evening dose versus placebo in the treatment of duodenal ulcer . A total of 110 duodenal ulcer patients were studied in a randomized , double-blind , placebo-controlled , multicentre clinical trial . The patients were assigned to 5 groups : placebo , 200 mg , 400 mg , 600 mg and 800 mg of ebrotidine once daily . Controls were performed at baseline and every two weeks at four follow-up visits unless ulcer healed before . Endoscopic examination was the main parameter for the assessment of treatment efficacy and ulcer healing rate . Vital signs and blood/ urine analysis were used to establish safety . The three groups treated with higher dosages ( 400 to 800 mg of ebrotidine daily ) showed an endoscopic ulcer healing rate of 90-95 % , significantly higher than 55 % achieved with placebo ( p < 0.05 ) , whilst the differences between these three dosages of ebrotidine were not statistically significant . Healing rate in the group treated with 200 mg of ebrotidine daily was not significantly different from that in the placebo group . The development of symptoms , number of episodes of ulcer-related pain , total ulcerated surface area or subjective ratings by the patients and investigators also differed significantly between ebrotidine ( 400 , 600 and 800 mg daily ) and placebo , and again , no marked differences were found between these three doses of ebrotidine . As far as tolerance is concerned , no clinically or statistically significant changes were observed in vital signs and analytical parameters . The incidence of side effects was less than that presented by the placebo group , possibly due to a greater consumption of antacids in this group . Results showed that a daily dose of 400 mg ebrotidine is effective and safe in the treatment of duodenal ulcers .

ebrotidine

placebo

placebo

efficacy and safety

efficacy and safety

treatment efficacy

ulcer healing rate

Vital signs

blood/ urine analysis

endoscopic ulcer healing rate

Healing rate

development of symptoms

total ulcerated surface area

tolerance

side effects

110 duodenal ulcer patients


Efficacy of ebrotidine and ranitidine combined with amoxicillin and metronidazole in the eradication of Helicobacter pylori in patients with duodenal ulcer . This double-blind , randomized , phase III clinical trial was carried out in two parallel groups to assess the efficacy of ebrotidine ( N- [ ( E ) - [ [ 2- [ [ [ 2- [ ( diaminomethylene ) amino ] -4-thiazolyl ] methyl ] thio ] ethyl ] amino ] methylene ] -4-bromo-benzenesulfonamide , CAS 100981-43-9 , FI-3542 ) 400 mg and ranitidine 300 mg given in single evening dose , combined with amoxicillin 750 mg and metronidazole 500 mg three times daily for 14 days , in the eradication of Helicobacter pylori in patients with duodenal ulcer . Thirty patients were included , divided into two groups of 15 , to whom one of the study therapies was administered based on a randomization code . Clinical and endoscopic controls were performed 4 , 6 and 8 weeks after the onset of the treatment . No differences were seen between the two treatment groups with regard to demographic parameters and clinical histories . They were both perfectly homogeneous . There were no differences between the eradication of both therapies in both the antrum and gastric body samples ( over 80 % eradication ) , allowing the results to be classified as satisfactory . Moreover , perfect control was achieved through the study of clinical symptoms , which even disappeared in some cases . There were no differences in the healing rate of the duodenal ulcer after four weeks , 86.7 % being achieved for both groups .

ebrotidine

ranitidine

amoxicillin

metronidazole

ebrotidine

diaminomethylene

ranitidine

amoxicillin

metronidazole

eradication

eradication

demographic parameters

clinical histories

eradication

clinical symptoms

healing rate

duodenal ulcer

two groups of 15


Circulating blood B cells in multiple myeloma : analysis and relationship to circulating clonal cells and clinical parameters in a cohort of patients entered on the Eastern Cooperative Oncology Group phase III E9486 clinical trial . Recent analyses of circulating blood B cells in myeloma have generated controversy concerning the exact levels of these cells and whether they may represent circulating clonal tumor B cells . Previous reports suggested that CD19+ B cells are markedly increased in myeloma patients and that this population shares clonotypic rearrangements with the malignant plasma cell . We studied the numbers of CD19+ B cells by flow cytometry in previously untreated newly diagnosed myeloma patients in Eastern Cooperative Oncology Group ( ECOG ) phase III trial E9486 . There were 628 patients who were eligible for the clinical protocol E9486 , but of these 521 were also entered on the companion laboratory study ( E9487 ) and had CD19 data . In comparison with normal controls , the myeloma patients exhibited a marked heterogeneity in the number of circulating CD19+ B cells as detected by flow cytometry . Approximately 20 % of patients had significantly increased levels of circulating CD19+ B cells . However , the total CD19+ blood population from myeloma was not significantly different from the median of age-matched , normal controls . Analysis of CD19+ blood cells in relationship to circulating clonal cells was done in 13 myeloma patients using a clonotypic , quantitative allele-specific oligonucleotide-polymerase chain reaction ( PCR ) assay . No correlation was found between the numbers of CD19+ B cells ( range , 5 % to 51 % ) and PCR estimates of the number of clonal cells in the peripheral blood ( range , .009 % to 3.6 % ) . Low CD19+ B-cell level ( < 125 microL ) was associated with clinical stage III ( P = .033 ) . A significant relationship exists between higher levels ( > or = 125/microL ) of CD19 cells and longer overall survival ( P < .0001 ) . In addition , high CD19 levels also predicted a clinical response and longer event-free survival . There was a strong inverse association between the level of CD19 values at diagnosis and infections within the first 2 months of diagnosis . Importantly , the number of deaths related to infections was significantly greater in the low versus high CD19 group ( P < .0202 ) . Also , CD19 is an independent prognostic factor in addition to plasma cell labeling indices , beta2-microglobulin , hemoglobin , and plasmablastic morphology . Patients with infections were more likely to have low levels of CD19+ cells . In summary , higher CD19+ cell levels are a favorable prognostic sign with no apparent relationship to circulating tumor cells . In addition , this analysis strongly suggests that low peripheral blood levels of CD19+ cells are an adverse prognostic sign in myeloma . The CD19+ cell levels in myeloma patients is an important parameter in the overall assessment of these patients .

Circulating blood B cells

CD19+ B cells

flow cytometry

PCR

CD19 values

CD19+ B cells

CD19+ B cells

CD19+ B cells

levels of circulating CD19+ B cells

total CD19+ blood population

CD19+ blood cells

CD19+ B cells

CD19+ B-cell level

clinical stage III

CD19 cells

longer overall survival

CD19 levels

event-free survival

CD19 values

number of deaths related to infections

levels of CD19+ cells

CD19+ cell levels

blood levels of CD19+

CD19+ cell

myeloma patients

628 patients


Effect of age and activity on knee joint proprioception . Falls lead to significant morbidity and mortality in persons older than 65 years of age . Impaired proprioception may be a contributing factor to falls , and this may be influenced by the level of habitual physical activity . The primary purpose of this study was to investigate knee joint proprioception among young volunteers and active and sedentary elderly volunteers . Knee joint proprioception was measured through reproduction of static knee angles using a Penny and Giles electrogoniometer . The secondary purpose of this investigation was to test the reproducibility of the Penny and Giles electrogoniometer in measuring static knee angles . Sixteen young subjects ( age range , 19-27 years ) and 24 elderly subjects ( age range , 60-86 years ) participated . Subjects were given a screening history and physical examination to exclude neuromuscular or vestibular disorders or lower limb injuries . Knee joint proprioception was measured two times during one week . The elderly group was separated into active and sedentary subgroups based on their level of activity during the past year . The electrogoniometer was placed laterally across the dominant knee joint . From the prone position each subject attained one of ten randomly predetermined knee joint angles from 10 degrees to 60 degrees . The subject then returned to the starting position and reproduced the test angle . The absolute angular error ( the absolute difference between the test angle and subject perceived angle of knee flexion ) was determined . A positive correlation was found between control visits for all subjects ( r = 0.88 ) , and significant differences were observed between young ( mean , 2.01 +/- 0.46 degrees ) and active-fold ( mean , 3.12 +/- 1.12 degrees ; P < 0.001 ) , young and sedentary-old ( mean , 4.58 +/- 1.93 degrees ; P < 0.001 ) , and active-old and sedentary-old ( P < 0.03 ) . These findings demonstrate that the Penny and Giles electrogoniometer is a reproducible device for measuring knee joint angles in both young and elderly subjects . Furthermore , we found that proprioception is diminished with age and that regular activity may attenuate this decline . One strategy to reduce the incidence of poor proprioception and fall with ageing may be regular exercise .

Penny and Giles electrogoniometer

Penny and Giles electrogoniometer

knee joint proprioception .

morbidity

mortality

Knee joint proprioception

measuring static knee angles .

Knee joint proprioception

absolute angular error

proprioception

proprioception

persons older than 65 years of age .


The benefit of low-dose dopamine during vigorous diuresis for congestive heart failure associated with renal insufficiency : does it protect renal function ? BACKGROUND Low-dose dopamine , a renal vasodilator , has been used empirically to improve renal function or outcome in critically ill patients with oliguria or acute renal failure . HYPOTHESIS This study was designed to investigate the efficacy of low-dose dopamine ( 2 micrograms/kg/min ) as a renal-protective agent during vigorous diuresis for congestive heart failure ( CHF ) associated with mild or moderate renal insufficiency . METHODS Of 20 study patients ( mean age 74.3 +/- 15 years ) with severe CHF , 10 ( Group A ) were randomized to a treatment strategy of intravenous bumetanide ( 1 mg b.i.d . ) alone and another 10 ( Group B ) to low-dose dopamine and a similar diuretic regimen for a duration of 5 days or less if clinical edema remitted . RESULTS Group B patients showed a significant improvement in renal function and urinary output : serum blood urea nitrogen 48.9 +/- 10.3 to 32.1 +/- 14.4 mg/dl ( p < 0.05 ) ; serum creatinine 1.97 +/- 0.24 to 1.49 +/- 0.39 mg/dl ( p < 0.05 ) ; creatinine clearance 35.6 +/- 11.6 to 48.8 +/- 12.3 ml/min ( p < 0.05 ) ; and indexed urinary output 0.56 +/- 0.16 to 2.02 +/- 0.72 ml/kg/h ( p < 0.05 ) . Group A patients showed a significant increase in urinary output but nonsignificant renal functional deterioration . CONCLUSION The renal-protective effect of low-dose dopamine in the setting of CHF and vigorous diuresis is supported by this study .

dopamine

dopamine

dopamine

bumetanide

dopamine

dopamine

renal function and urinary output

serum blood urea nitrogen

serum creatinine

creatinine clearance

indexed urinary output

urinary output

congestive heart failure

renal insufficiency

critically ill

oliguria

acute renal failure

mean age 74.3 +/- 15 years

severe CHF ,


Clozapine versus placebo in Huntington 's disease : a double blind randomised comparative study . OBJECTIVES To establish the effect of the atypical neuroleptic clozapine on chorea , voluntary motor performance , and functional disability in patients with Huntington 's disease . METHODS Thirty three patients with Huntington 's disease participated in a double blind randomised trial . A maximum of 150 mg/day clozapine or placebo equivalent was given for a period of 31 days . Assessments were performed in the week before and at the last day of the trial . Chorea was scored using the abnormal involuntary movement scale ( AIMS ) , the chorea score of the unified Huntington 's disease rating scale ( UHDRS ) , and judgement of video recordings . Voluntary motor performance was assessed using the UHDRS motor scale . Patients and their partners completed a questionnaire regarding functional disability . Twelve patients already used other neuroleptic medication , which was kept unchanged during the trial period . Results of neuroleptic naive and neuroleptic treated patients were analysed separately . RESULTS Clozapine tended to reduce chorea in neuroleptic naive patients only ( AIMS ) ; improvement seemed more pronounced in patients receiving higher doses of clozapine . Other measures of chorea ( UHDRS chorea score , video ratings ) showed no improvement . Clozapine had no beneficial effect on chorea in patients already receiving neuroleptic medication . Voluntary motor performance did not improve with clozapine . Neuroleptic naive patients reported aggravation of functional disability , possibly reflecting the frequent occurrence of side effects . Adverse reactions forced trial termination in six patients and dose reduction in another eight , and consisted mainly of drowsiness , fatigue , anticholinergic symptoms , and walking difficulties . CONCLUSIONS Clozapine has little beneficial effect in patients with Huntington 's disease , although individual patients may tolerate doses high enough to reduce chorea . Because adverse reactions are often encountered , clozapine should be used with restraint in this patient group .

Clozapine

placebo

clozapine

clozapine

or placebo

Clozapine

Clozapine

Clozapine

clozapine

chorea

chorea

Voluntary motor performance

functional disability

Huntington 's disease

Thirty three


Treatment with buspirone in a patient with autism . This study evaluates the safety and efficacy of buspirone hydrochloride for the treatment of a patient with autism and hyperactivity disorder and determines the effect of buspirone on the number of performance tasks completed by the patient at school . A 3-week , double-blind , placebo-controlled crossover study was performed in a private physician , office-based practice . A child with autism , which was diagnosed by Diagnostic and Statistical Manual of Mental Disorders , Third Edition , Revised , criteria , was studied . The child received placebo for 3 weeks and buspirone for 3 weeks ; there was a 1-week interval between the 2 treatments . The outcome was measured by using Conners abbreviated parent and teacher questionnaires and by determining the number of daily performance tasks completed by the child at school . Statistical analysis was performed by linear models and standard F tests . Buspirone was found to be safe and efficacious , without side effects , for decreasing hyperactivity and increasing completed performance tasks . The beneficial effects of buspirone in helping this patient with autism in his natural daily settings suggest that buspirone may be an alternative to neuroleptic agents in the medical therapy of autism ; further study in other patients is needed .

buspirone

buspirone hydrochloride

buspirone

placebo-controlled

placebo for 3 weeks

buspirone

Buspirone

buspirone

safe and efficacious

without side effects

hyperactivity

completed performance tasks

patient with autism .


Brief report : autistic children 's attentiveness and responsivity improve after touch therapy .

touch therapy .

autistic

children 's


Gonadotropin-releasing hormone agonist in the treatment of premenstrual symptoms with and without ongoing dysphoria : a controlled study . Gonadotropin-releasing hormone ( GnRH ) agonists have been shown to reduce symptoms of premenstrual syndrome ( PMS ) . This randomized , placebo-controlled study examined the efficacy of the GnRH agonist , leuprolide acetate depot , in a clearly defined PMS sample versus women with premenstrual symptoms in combination with dysphoric symptoms throughout the cycle , termed the premenstrual exacerbation ( PME ) group . Evaluation included the Structured Clinical Interview for DSM-III-R , administered in the follicular phase , and the subject Penn Dally Symptoms Report ( DSR ) maintained throughout the study . Thirty-three eligible women were randomized to double-blind treatment and administered 3.75 mg of depot leuprolide or a placebo once a month for 3 months . The subjects were seen for efficacy evaluations at the end of each cycle . Outcome measures were the DSRs and the 17-item Hamilton Depression Rating Scale ( HAM-D17 ) . The PMS leuprolide subjects improved significantly compared with the PMS placebo and PME leuprolide groups . The PME leuprolide group , who had dysphoric symptoms throughout the cycle , did not improve . Depression symptoms were at clinical levels premenstrually in the PMS and PME groups ; following treatment they remitted in the PMS group but not in the PME leuprolide subjects . Efficacy did not occur until after several months of leuprolide treatment , but there was no evidence that PMS symptoms worsened with the onset of treatment . These results replicate the findings in our preliminary open-label study . Leuprolide reduced PMS symptoms to minimal levels where symptoms were limited to the luteal phase . Leuprolide was not effective for women with ongoing dysphoric symptoms , suggesting that premenstrual depression may have mechanisms different from those of other dysphoric mood disorders .

Gonadotropin-releasing hormone

GnRH agonist

3.75 mg of depot leuprolide

placebo

leuprolide

leuprolide

leuprolide

leuprolide

Leuprolide

Leuprolide

efficacy

DSRs

dysphoric symptoms

Depression symptoms

PMS symptoms

PMS symptoms

clearly defined PMS sample

premenstrual exacerbation ( PME )

Thirty-three

women


Mortality in patients with small choroidal melanoma . COMS report no . 4 . The Collaborative Ocular Melanoma Study Group . OBJECTIVE To describe the clinical characteristics and survival experience of a prospectively followed up group of patients with small choroidal melanoma . METHODS The Collaborative Ocular Melanoma Study ( COMS ) is a set of clinical trials designed to compare the role of radiotherapy and enucleation in the treatment of medium and large-size choroidal melanoma . From December 1986 to August 1989 , patients with small choroidal melanoma , not large enough to be eligible for the COMS clinical trials , were offered participation in a nonrandomized prospective follow-up study . Small choroidal melanomas were defined as 1.0 to 3.0 mm in apical height and at least 5.0 mm in basal diameter . A total of 204 patients were enrolled in the study . Patients were followed up annually through August 1989 . Two additional assessments of treatment status and mortality were conducted in 1993-1994 and 1995-1996 . The median length of follow-up was 92 months . Eight percent of patients were treated at the time of study enrollment and an additional 33 % were treated during follow-up . RESULTS Twenty-seven patients have died ; 6 deaths were reported by the clinical center as due to metastatic melanoma . The Kaplan-Meier estimate of 5-year all-cause mortality was 6.0 % ( 95 % confidence interval , 2.7 % -9.3 % ) and 8-year all-cause mortality was 14.9 % ( 95 % confidence interval , 9.6 % -20.2 % ) . CONCLUSIONS Otherwise healthy patients , average age of 60 years , without a previous diagnosis of malignant disease who have small choroidal lesions judged to be melanoma have a low risk of dying within 5 years .

radiotherapy

enucleation

Mortality

mortality

median length

died

deaths

metastatic melanoma

mortality

mortality

choroidal lesions


Safety of nifedipine in patients with hypertension : a meta-analysis . Our objective was to compare cardiovascular event rates in patients with mild or moderate hypertension who received nifedipine with active drug controls . We performed a MEDLARS search using the MeSH heading " hypertension " and the text word " nifedipine " to identify all articles that were published between 1966 and August 1995 in English , French , German , Italian , and Spanish languages and that involved human subjects . The computerized search was supplemented by a manual search of article bibliographies . Review of 1880 citations revealed 98 randomized controlled clinical trials that met protocol criteria . Articles were extracted independently by two doctors who were blinded for author , institution , and treatment regimen , using a structured , pretested extraction form . Differences of opinion were resolved by consensus . Fourteen events occurred in 5198 exposures ( 0.27 % ) to nifedipine and 24 events in 5402 exposures ( 0.44 % ) to other active drug controls . Unadjusted odds ratios for nifedipine versus controls were 0.49 ( 95 % confidence interval [ CI ] , 0.22-1.09 ) for definitive events ( death , nonfatal myocardial infarction or stroke , revascularization procedure ) and 0.61 ( 95 % CI , 0.31-1.17 ) for all events ( definitive plus increased angina ) . The odds ratio for nifedipine monotherapy ( sustained- or extended-release in 91 % of exposures ) was nonsignificantly higher for definitive and all events ( odds ratio , 1.40 ; 95 % CI , 0.49-4.03 and odds ratio , 1.39 ; 95 % CI , 0.59-3.32 , respectively ) . The odds ratio for nifedipine in combination with another drug was significantly lower for definitive and all events ( odds ratio , 0.09 ; 95 % CI , 0.01-0.66 and odds ratio , 0.15 ; 95 % CI , 0.03-0.65 , respectively ) . Differences in odds ratio for nifedipine monotherapy and combined therapy were statistically significant ( P=.02 for definitive events and P=.001 for all events ) . Results support the safety of sustained- and extended-release nifedipine in the treatment of mild or moderate hypertension when it is used in combination with other drugs .

nifedipine

nifedipine

active drug controls

nifedipine

nifedipine

nifedipine

nifedipine

nifedipine

nifedipine

Safety

cardiovascular event rates

Unadjusted odds ratios

death

odds ratio for nifedipine monotherapy

hypertension

mild or moderate hypertension


[ Clinical diagnosis of deep venous thrombosis after hip replacement surgery ] . Hip replacement surgery is associated with a high frequency of postoperative deep vein thrombosis . This prospective study was performed in order to investigate if routine bedside questioning and examination by the visiting doctor could reveal deep vein thrombosis in the legs of patients who had received a hip replacement . 258 patients were evaluated . Thromboprophylaxis ( dextran-70 , low molecular weight heparin and graded elastic stockings ) was given during the first week after operation . Bilateral venography was performed in all patients on day seven after operation , and showed an overall deep vein thrombosis incidence of 16 % . The visiting doctors had not suspected deep vein thrombosis in any of the patients . This may have been because postoperative painful and swollen legs effectively masked any signs and symptoms of deep vein thrombosis . Our results show that deep vein thrombosis during the first week after hip replacement surgery can not be discovered by clinical diagnostics . The high subclinical frequency of deep vein thrombosis indicates the importance of improving thromboprophylaxis in order to further minimise the occurrence of deep vein thrombosis and the risk of thromboembolic complications .

graded elastic stockings

Bilateral venography

postoperative painful and

swollen legs

deep vein thrombosis

hip replacement


2-Chloroprocaine antagonism of epidural morphine analgesia . BACKGROUND 2-Chloroprocaine ( 2-CP ) used for lumbar epidural anesthesia ( LEA ) reportedly decreases the efficacy of epidural morphine ( EM ) administered for post-cesarean section ( CS ) analgesia . The amount of supplemental i.v . morphine self-administered by the patient via the patient-controlled analgesia device ( PCA ) is used to study the interaction between EM and 2-CP . METHODS Forty-two patients scheduled for elective CS were randomly divided into 3 equal groups , and received 2-CP , 2-CP + epinephrine ( Epi , 5 micrograms.ml-1 ) or 2 % lidocaine ( Lido ) with Epi for LEA . All patients received 5 mg EM and i.v . PCA morphine for postoperative pain . Cumulative amount of i.v . morphine used in the first 24 hours as well as the amount of the drug used during each 2-h period were noted . Nonparametric analysis of variance and Chi-squared analysis were used for statistical comparisons . RESULTS The mean cumulative 24-h i.v . PCA morphine requirement in the 2-CP , 2-CP+Epi and Lido+Epi groups respectively was 20.5 +/- 24 , 33.1.5 +/- 27 and 4.07 +/- ( mean +/- SD ) . The Lido + Epi group used significantly less morphine ( P = 0.01 ) compared to either of the 2-CP groups with no significant difference between the 2-CP groups . The maximum i.v . PCA morphine use occurred in the first 4 hours following surgery in all three groups . CONCLUSION Analgesic efficacy of EM is decreased when 2-CP is used for LEA compared to when Lido + Epi is used .

2-Chloroprocaine ( 2-CP )

morphine ( EM )

morphine

EM

2-CP + epinephrine

2 % lidocaine ( Lido ) with Epi

EM

PCA morphine

morphine

morphine

EM

Lido + Epi

less morphine

maximum i.v . PCA morphine use

Analgesic efficacy

post-cesarean section ( CS )


High-dose pyridoxine and magnesium administration in children with autistic disorder : an absence of salutary effects in a double-blind , placebo-controlled study . Several reports have described salutary effects such as decreased physical aggression and improved social responsiveness being associated with the administration of high doses of pyridoxine and magnesium ( HDPM ) in open-labeled and controlled studies of patients with autism . Despite this fact , this intervention remains controversial . A 10-week double-blind , placebo-controlled trial was undertaken to examine both the efficacy and safety of HDPM in autism . Twelve patients were enrolled , and 10 patients ( mean age 6 years 3 months ) were able to complete the study . HDPM at an average dose of 638.9 mg of pyridoxine and 216.3 mg of magnesium oxide was ineffective in ameliorating autistic behaviors as assessed by the Children 's Psychiatric Rating Scale ( CPRS ) , the Clinical Global Impression Scale , and the NIMH Global Obsessive Compulsive Scale . Furthermore , no clinically significant side effects were noted during HDPM administration . A trend for a transient change on the CPRS was found that was possibly due to a placebo response . This study raises doubts about the clinical effectiveness of HDPM in autistic disorder .

pyridoxine and magnesium ( HDPM )

HDPM

HDPM

pyridoxine

magnesium oxide

HDPM

HDPM

ameliorating autistic behaviors

the Clinical Global Impression Scale

NIMH Global Obsessive Compulsive Scale

children

autistic disorder

autism

Twelve

6 years 3 months


Cranberry concentrate : UTI prophylaxis .

Cranberry concentrate

UTI


Association of PML-RAR alpha fusion mRNA type with pretreatment hematologic characteristics but not treatment outcome in acute promyelocytic leukemia : an intergroup molecular study . In each case of acute promyelocytic leukemia ( APL ) one of three PML-RAR alpha mRNA types is produced , depending on the break/fusion site in the PML gene that is linked to a common RAR alpha gene segment : a short ( S ) -form type , PML exon 3 RAR alpha exon 3 ; a long ( L ) -form type , PML exon 6 RAR alpha exon 3 ; or a variable ( V ) -form type , variably deleted PML exon 6 RAR alpha exon 3 . We evaluated whether PML-RAR alpha mRNA type is associated with distinct pretreatment clinical characteristics and therapeutic outcome in previously untreated adult APL patients registered to protocol INT 0129 by the Eastern Cooperative Oncology Group , the Southwest Oncology Group , and the Cancer and Leukemia Group B . Of 279 clinically eligible cases , 230 were molecularly evaluable , and of these , 111 were randomized to receive remission induction therapy with all-trans retinoic acid ( ATRA ) and 119 with conventional chemotherapy . Nine cases not excluded by central pathology review were PML-RAR alpha negative , and notably , none of five of these cases treated with ATRA achieved complete remission ( CR ) . Among 221 PML-RAR alpha-positive cases , there were 82 S-form cases ( 37 % ) , 121 L-form cases ( 55 % ) , and 18 V-form cases ( 8 % ) . Before any antileukemic therapy , the S-form type , compared with the L-form type , was associated with higher values for the white blood cell ( WBC ) count ( median 2,500/microL v 1,600/microL ; P = .009 ) , the percentage of blood blasts plus promyelocytes ( median 29 % v 8.5 % ; P = .03 ) , and the absolute blood blasts plus promyelocytes ( 884/microL v 126/microL ; P = .019 ) . Also , an increased percentage of S-form versus L-form cases had the M3 variant phenotype , 24 % v 12 % ( P = .036 ) . There were no differences between S-form and L-form cases in either CR rate ( 79 % v 69 % ; P = .14 ) or disease free survival distribution ( multivariate analysis adjusting for the association of S-form type and higher WBC count ; P = .40 ) . We conclude that the S-form type is associated with previously-identified adverse risk WBC parameters but that the identification of the S-form or L-form type of PML-RAR alpha mRNA , per se , does not predict clinical outcome or add to the value of an increased WBC count as a negative prognostic indicator in APL patients .

conventional chemotherapy

hematologic characteristics

PML-RAR alpha negative

complete remission

white blood cell ( WBC ) count

blood blasts plus promyelocytes

M3 variant phenotype

CR rate

disease free survival distribution

acute promyelocytic leukemia :

acute promyelocytic leukemia ( APL )

adult


Active warming , not passive heat retention , maintains normothermia during combined epidural-general anesthesia for hip and knee arthroplasty . STUDY OBJECTIVE to compare passive heat retention by low-flow anesthesia , alone and with additional thermal insulation by reflective blankets , with forced-air warming preventing intraoperative hypothermia during combined epidural-general anesthesia . DESIGN Randomized , controlled study . SETTING Inpatient anesthesia at a university department of orthopedic surgery . PATIENTS 30 ASA physical status I and II patients , who were scheduled for elective hip or knee arthroplasty and were free from systemic disease . INTERVENTIONS Patients received epidural block up to T10 by alkalinized lidocaine 2 % , and then were administered standard general anesthesia by means of low-flow rebreathing system ( fresh gas flow = 1 L/min ) . All procedures started between 8 and 10 AM , and operating room ( OR ) temperature was maintained between 21 degrees and 23 degrees C , with relative humidity ranging between 40 % and 45 % . For heat retention or warming therapy , patients received either low-flow anesthesia only ( control , n = 10 ) , low-flow anesthesia with additional reflective blankets ( blanket , n = 10 ) , or low-flow anesthesia with active forced-air warming ( forced-air , n = 10 ) . Tympanic temperature was measured at OR arrival ( baseline ) ; immediately following general anesthesia induction ; 30 , 60 , 90 , and 120 minutes from general anesthesia induction ; and at the end of surgery . MEASUREMENTS AND MAIN RESULTS Duration of anesthesia , invasiveness of surgery , and baseline core temperature were similar in the three groups . Core temperature decreased in all the three groups 30 minutes after general anesthesia induction compared with baseline ( p < 0.01 ) ; afterwards , it progressively decreased in the control and blankets groups ( p = 0.004 ) , with a reduction from baseline values measured at the end of surgery of 2.0 degrees C and 1.6 degrees C , respectively . In the forced-air group , after the initial significant decrease ( p = 0.01 vs. baseline ) , core temperature progressively increased to 35.8 +/- 0.6 degrees C , which was similar to preoperative values and significantly higher than either the control or blankets groups ( p = 0.004 ) . CONCLUSIONS During combined epidural-general anesthesia for elective hip and knee arthroplasty , passive heat retention by means of low-flow anesthesia alone and in combination with reflective blankets is ineffective in maintaining intraoperative normothermia and definitely inferior to active forced-air warning .

Active warming

alkalinized lidocaine 2 %

low-flow rebreathing system

low-flow anesthesia only

normothermia

Tympanic temperature

Core temperature

reduction from baseline values

core temperature

maintaining intraoperative normothermia

arthroplasty

I

II

systemic disease .


Intravenous pretreatment of hypertonic saline can prevent systemic hypotension induced by spinal anesthesia . BACKGROUND Hypertonic saline improves organ perfusion and patient survival during hemorrhagic shock because it expands plasma volume and increases tissue oxygenation . Its beneficial results have been reported in patients suffering from hypotension during spinal anesthesia . The purpose of this study was to compare the influence between prehydration with 3 % hypertonic saline and with isotonic lactated Ringer 's solution on the hemodynamic changes and serum electrolyte concentrations in patients undergoing spinal anesthesia . METHODS Sixty ASA class I patients scheduled for herniorrhapy under spinal anesthesia were assigned randomly into two groups . Group 1 = patients were prehydrated with isotonic lactated Ringer 's solution at 7 mg/kg ( n = 30 ) ; Group 2 = patients were given prehydration with 3 % hypertonic saline at 7 ml/kg ( n = 30 ) . Following prehydration , arterial blood pressure and heart rate were recorded and serum electrolyte concentrations were measured . RESULTS The incidence of hypotension was 17/30 ( 57 % ) in the isotonic lactated Ringer 's solution group as against 7/30 ( 23 % ) in the hypertonic saline group ( p < 0.05 ) . There was no significant difference between two groups in relation to the level of anesthesia or maximal heart rate , and electrolyte imbalance did not occur in either group . CONCLUSIONS Prior to spinal anesthesia , hydration with small amount of hypertonic saline is effective to minimize hypotension associated with spinal anesthesia . If so administered it would not increase bodily sodium load and unlike isotonic crystalloid solution it dose not cause accumulation of water in the body on equipollent basis .

hypertonic saline

herniorrhapy

hypertonic saline

systemic hypotension

organ perfusion

patient survival

arterial blood pressure

heart rate

serum electrolyte concentrations

incidence of hypotension

significant difference

level of anesthesia

maximal heart rate

electrolyte imbalance

Sixty


Comparison of hand-sewn and stapled esophagogastric anastomosis after esophageal resection for cancer : a prospective randomized controlled trial . OBJECTIVE The objective of this study was to compare the hand-sewn and stapled methods in esophagogastric anastomosis . SUMMARY BACKGROUND DATA After esophageal resection for cancer , the relative merits of the hand-sewn and the stapled methods of esophagogastric anastomosis , especially regarding leakage and stricture rates , have not adequately been studied . METHODS A prospective randomized controlled trial was undertaken in 122 patients with squamous cell cancer of the thoracic esophagus who underwent a Lewis-Tanner esophagectomy . Patients were stratified according to esophageal size , based on the diameter of the divided esophagus ( < or > or = 30 mm ) and then were randomized to have either a hand-sewn or a stapled anastomosis . RESULTS The mean total operating times ( standard error of the mean ) when the hand-sewn and the stapled methods were used were 214 ( 4 ) minutes and 217 ( 3.4 ) minutes , respectively ( p = not significant [ NS ] ) . The respective in vivo proximal resection margins ( standard error of the mean ) were 8 ( 0.4 ) cm and 7.6 ( 0.4 ) cm ( p = NS ) . Leakage rates were 1.6 % and 4.9 % ( p = NS ) . Excluding hospital deaths , patients with leakage or anastomotic recurrence , and those who received radiation therapy to histologically infiltrated resection margin , anastomotic stricture was found in 5 ( 9.1 % ) of 55 patients in the hand-sewn group and 20 ( 40 % ) of 50 in the stapler group ( p = 0.0003 ) . The difference in stricture rates was significant in small as well as large esophagi . Anastomotic recurrence developed in only one patient in each group . CONCLUSIONS The authors conclude that both methods were safe , but the stapled technique resulted in more stricture formation .

hand-sewn

stapled esophagogastric anastomosis

hand-sewn

stapled

esophagogastric anastomosis .

Lewis-Tanner esophagectomy .

hand-sewn

stapled anastomosis

leakage

stricture

mean total operating times

vivo proximal resection margins

Leakage

rates

hospital deaths

leakage or anastomotic recurrence

anastomotic stricture

difference in stricture rates

Anastomotic recurrence

safe

stricture formation


Plasma dilution and the rate of infusion of Ringer 's solution . Changes in the volume of the fluid space expanded by i.v . infusion of Ringer 's acetate solution have been analysed recently using mathematical models . Data obtained by such analyses allow simulation of the dilution of the plasma volume during infusion of the solution at different rates . To obtain basic kinetic data for such simulations , the plasma dilution-time curves were measured during and after i.v . infusion of Ringer 's solution 25 ml kg-1 over 30 min in 15 healthy male volunteers ( mean age 31 yr ) and over 30 , 45 and 80 min in six females ( mean age 32 yr ) . Based on these experiments , nomograms were constructed from which the rate of infusion of Ringer 's solution and the infusion time required to obtain a defined plasma dilution in both males and females can be estimated together with the infusion rate needed to maintain the dilution at the level reached .

Ringer 's solution

Ringer 's acetate solution

i.v . infusion of Ringer 's solution

Ringer 's solution

Plasma dilution

plasma volume

plasma dilution-time curves

healthy

male

six


Dose-response and concentration-response relation of rocuronium infusion during propofol-nitrous oxide and isoflurane-nitrous oxide anaesthesia . The dose-response and concentration-response relation of rocuronium infusion was studied in 20 adult surgical patients during propofol-nitrous oxide and isoflurane ( 1 MAC ) -nitrous oxide anaesthesia . Neuromuscular block was kept constant , initially at 90 % and then at 50 % with a closed-loop feedback controller . At 90 % block the steady-state infusion of rocuronium was 0.55 +/- 0.16 mg kg-1 h-1 and the corresponding concentration 1714 +/- 281 ng mL-1 in patients receiving propofol . At 50 % block the corresponding infusion rate was 0.27 +/- 0.11 mg kg-1 h-1 and the concentration 1077 +/- 244 ng mL-1 , respectively . At 50 % block isoflurane reduced the rate of infusion by 52 % ( P < 0.005 ) and the concentration by 59 % ( P < 0.001 ) ; at 90 % block both the mean infusion rate and the concentration of rocuronium were reduced by 35 % ( P < 0.005 ) . The mean rocuronium clearance at 50 % block was unaffected by the type of anaesthesia ; it was 4.1 +/- 1.6 and 4.9 +/- 2.7 mL kg-1 min-1 in the groups receiving propofol and isoflurane anaesthesia , respectively . We conclude that isoflurane reduces the infusion requirements of rocuronium by changing the pharmacodynamic behaviour .

rocuronium infusion

propofol-nitrous oxide

isoflurane-nitrous oxide anaesthesia

rocuronium infusion

propofol-nitrous oxide

closed-loop feedback controller

steady-state infusion of rocuronium

propofol

isoflurane

rocuronium

anaesthesia

propofol

isoflurane anaesthesia

rocuronium

steady-state infusion

concentration

corresponding infusion rate

concentration

rate of infusion

concentration

mean infusion rate

concentration of rocuronium

mean rocuronium clearance

infusion requirements of rocuronium


Postoperative analgesia with preoperative oral ibuprofen or acetaminophen in children undergoing myringotomy . Previous studies have shown over 70 % of children require analgesics following bilateral myringotomy and tube placement ( BM & T ) . This double-blind , placebo-controlled study compared the postoperative analgesic effects of preoperatively administered oral acetaminophen or ibuprofen . Forty three ASA I or II children age six months or older scheduled for elective BM & T were randomized to receive acetaminophen ( paracetamol ) 15 mg.kg-1 , ibuprofen 10 mg.kg-1 , or placebo . Postoperative pain was assessed using the Children 's Hospital of Eastern Ontario Pain Scale ( CHEOPS ) upon arrival to the PACU and at 5 , 10 , 15 , 30 , 45 , and 60 min . CHEOP scores did not differ between the groups at any time . There was no difference in the number of children receiving rescue analgesia . This study showed no benefit of preoperatively administered oral ibuprofen 10 mg.kg-1 or acetaminophen 15 mg.kg-1 over placebo for the relief of postoperative pain in children undergoing BM & T .

ibuprofen

acetaminophen

analgesics

acetaminophen

ibuprofen

acetaminophen ( paracetamol

ibuprofen

placebo

ibuprofen

acetaminophen

rescue analgesia