Results of a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor in very low birthweight neonates : significant induction of circulatory neutrophils , monocytes , platelets , and bone marrow neutrophils . Neonates , especially those of very low birthweight ( VLBW ) , have an increased risk of nosocomial infections secondary to deficiencies in development . We previously demonstrated that granulocyte-macrophage colony-stimulating factor ( GM-CSF ) production and mRNA expression from stimulated neonatal mononuclear cells are significantly less than that from adult cells . Recombinant murine GM-CSF administration to neonatal rats has resulted in neutrophilia , increased neutrophil production , and increased survival of pups during experimental Staphylococcus aureus sepsis . In the present study , we sought to determine the safety and biologic response of recombinant human ( rhu ) GM-CSF in VLBW neonates . Twenty VLBW neonates ( 500 to 1,500 g ) , aged < 72 hours , were randomized to receive either placebo ( n = 5 ) or rhuGM-CSF at 5.0 micrograms/kg once per day ( n = 5 ) , 5.0 micrograms/kg twice per day ( n = 5 ) , or 10 micrograms/kg once per day ( n = 5 ) given via 2-hour intravenous infusion for 7 days . Complete blood counts , differential , and platelet counts were obtained , and tibial bone marrow aspirate was performed on day 8 . Neutrophil C3bi receptor expression was measured at 0 and 24 hours . GM-CSF levels were measured by a sandwich enzyme-linked immunosorbent assay at 2 , 4 , 6 , 12 , and 24 hours after the first dose of rhuGM-CSF . At all doses , rhuGM-CSF was well tolerated , and there was no evidence of grade III or IV toxicity . Within 48 hours of administration , there was a significant increase in the circulating absolute neutrophil count ( ANC ) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day , which continued for at least 24 hours after discontinuation of rhuGM-CSF . When the ANC was normalized for each patient 's first ANC , there was a significant increase in the ANC on days 6 and 7 at each dose level . By day 7 , all tested doses of rhuGM-CSF resulted in an increase in the absolute monocyte count ( AMC ) compared with placebo-treated neonates . In those receiving rhuGM-CSF 5.0 micrograms/kg twice per day , there was additionally a significant increase in the day 7 and 8 platelet count . Tibial bone marrow aspirates demonstrated a significant increase in the bone marrow neutrophil storage pool ( BM NSP ) at 5.0 micrograms/kg twice per day and 10.0 micrograms/kg once per day . Neutrophil C3bi receptor expression was significantly increased 24 hours after the first dose of rhuGM-CSF at 5.0 micrograms/kg once per day . The elimination half-life ( T1/2 ) of rhuGM-CSF was 1.4 +/- 0.8 to 3.9 +/- 2.8 hours . ( ABSTRACT TRUNCATED AT 400 WORDS )

recombinant human ( rhu ) GM-CSF

placebo

rhuGM-CSF

rhuGM-CSF

rhuGM-CSF

rhuGM-CSF .

rhuGM-CSF

rhuGM-CSF

rhuGM-CSF

GM-CSF levels

grade III or IV toxicity

ANC

absolute monocyte count ( AMC )

day 7 and 8 platelet count

Neutrophil C3bi receptor expression


Efficacy of Contractubex gel in the treatment of fresh scars after thoracic surgery in children and adolescents . Scar development was investigated in 45 young patients who had undergone thoracic surgery . Patients were randomly assigned either to a group which was treated topically with Contractubex gel ( Merz + Co. , D-Frankfurt/Main ) , containing 10 % onion extract , 50/U of sodium heparin per one g of gel and 1 % allantoin , or to a group receiving no treatment . The treatment began on average 26 days after the operation and was continued for one year . The scars of all treated and untreated patients were evaluated at monthly intervals . The appearance of the scar , including scar type and scar size as well as scar colour , was assessed by the physician . A reduction of the increase of scar width was seen in the Contractubex-treated group as compared with the untreated group . Further , physiological scars and skin-coloured scars were more frequent in the treated group than in the untreated group . Hypertrophic or keloidal scars were less frequent in the treated group . No differences in scar length and scar height were seen . At the end of the observation period , the clinical course of scar development was rated as " very good " or " good " in more than 90 % of the treated patients , " good " in less than 40 % and " moderate " or " bad " in more than 60 % of the untreated cases . The tolerability of the drug was " good " or " very good " in all cases . In conclusion , Contractubex gel is useful in scar treatment after thoracic surgery .

Hypertrophic or keloidal scars

scar length

scar height

scar development


Cyproheptadine augmentation of haloperidol in chronic schizophrenic patients : a double-blind placebo-controlled study . A 6 week double-blind placebo-controlled trial of cyproheptadine augmentation of ongoing haloperidol treatment was conducted in 40 chronic schizophrenic in-patients . Cyproheptadine augmentation , compared to administration of haloperidol with placebo , did not produce a statistically significant improvement in psychotic symptoms . Cyproheptadine augmentation caused significant reduction in the extrapyramidal symptoms , which supports the atypical profile of antipsychotics . As to the neuroendocrinological effect , cyproheptadine augmentation did not reduce the plasma prolactin level but did induce a decrease in the plasma cortisol level . Although long-term follow-up studies are needed to confirm the results , this study suggests that cyproheptadine augmentation may be effective in treating chronic schizophrenic patients who are intolerant of extrapyramidal side effects of conventional antipsychotics .

haloperidol

placebo-controlled

cyproheptadine augmentation

haloperidol

haloperidol

placebo

psychotic symptoms

extrapyramidal symptoms

neuroendocrinological effect

plasma prolactin level

plasma cortisol level

chronic schizophrenic patients

extrapyramidal side effects

chronic schizophrenic


Cyclosporin A increases somatomedin C insulin-like growth factor I levels in chronic rheumatic diseases . OBJECTIVE To determine whether anabolic hormones that affect the musculoskeletal system and active on the immune cells changed during cyclosporin A ( CysA ) therapy . METHODS We carried out a randomized study of patients with rheumatic disease attending the outpatient clinic for rheumatic diseases . Twenty-four patients with chronic arthritis [ 20 with rheumatoid arthritis ( RA ) and 4 with psoriatic arthritis ( PsA ) ] were divided into 2 groups ( 10 RA , 2 PsA ) and randomly given CysA 5 mg/kg daily or hydroxychloroquine ( OH-Chlor ) 6 mg/kg daily in divided doses . RESULTS A significant increase of insulin-like growth factor I ( IGF-I ) ( somatomedin C ) levels and of bone Gla protein was shown after 2 months in the CysA treated group , but not in the OH-Chlor group . A statistically significant correlation was observed between changes of IGF-I levels and of dehydroepiandrosterone sulphate ( DHEAS ) . This finding was confirmed in a further series of 39 patients . No changes were seen in 25 OH-D , 1-25 ( OH ) 2-D3 or parathyroid hormone after CysA . CONCLUSION The effects of CysA on IGF-I may explain some of the clinical , immunologic , and metabolic results during CysA treatment of rheumatic diseases .

Cyclosporin A

cyclosporin A ( CysA ) therapy .

CysA 5

insulin-like growth factor I

bone Gla protein

rheumatic disease

rheumatic diseases

Twenty-four

chronic arthritis

rheumatoid arthritis ( RA )

psoriatic arthritis ( PsA )


Comparison of eltanolone and thiopental in anaesthesia for termination of pregnancy . Eltanolone , a new steroid hypnotic , was compared to thiopental in short anaesthesia . Sixty unpremedicated , Asa 1-2 women were randomized to receive eltanolone 0.6 ( group E1 ) or 0.8 mg.kg-1 ( group E2 ) or thiopental 4 mg.kg-1 ( group T ) for induction of anaesthesia . One minute before induction glycopyrrolate 0.2 mg and alfentanil 15 micrograms.kg-1 i.v . were administered . If induction failed , additional boluses of the test drug were given . Anaesthesia was maintained with 67 % nitrous oxide in oxygen , and additional bolus doses of the test drug were given in a standardized fashion , if needed . Recovery was assessed by a research nurse blinded to the agent used . Mean +/- s.d . induction doss were 0.7 +/- 0.1 mg.kg-1 ( group E1 ) , 0.8 +/- 0.1 mg.kg-1 ( group E2 ) and 4.0 +/- 0.0 mg.kg-1 ( group T ) . Induction time was prolonged in the group E1 compared to the other two groups ( P < 0.05 ) . Side effects were few in all groups , but involuntary muscle movements or hypertonus occurred in 23 % of the patients in the eltanolone and in 3 % in the thiopental groups ( n.s ) . Early recovery ( eye opening , orientation and sitting ) was slower in both eltanolone groups compared to the thiopental group ( P < 0.01 ) . No differences between the groups were found in toleration of oral fluids , walking , voiding , postoperative analgesic requirements or postoperative nausea and vomiting . ( ABSTRACT TRUNCATED AT 250 WORDS )

eltanolone

thiopental

Eltanolone

eltanolone 0.6

thiopental

glycopyrrolate

alfentanil

nitrous oxide in oxygen

anaesthesia

Recovery

Mean +/- s.d . induction doss

Induction time

Side effects

termination

pregnancy .

Sixty


Angiotensin-converting enzyme inhibition does not suppress plasma angiotensin II increase during exercise in humans . Physical effort stimulates the reninangiotensin system ( RAS ) . We studied the effect of an angiotensin-converting enzyme inhibitor ( ACE inhibitor ) in a double-blind placebo-controlled study , on eight volunteers undergoing physical stress on an ergometric bicycle . The effects of captopril ( C ) ( 50 mg , three times daily for 3 days ) on arterial pressure ( AP ) , O2 consumption ( VO2 ) , variations in auricular natriuretic factor ( ANF ) , renin , angiotensin II ( AII ) plasma levels , as well as glomerular filtration rate ( GFR ) and microalbuminuria ( MA ) were evaluated . The different parameters were compared by analysis of variance ( ANOVA ) . The pressure profile and VO2 were not modified by ACE inhibitor . Exercise stimulates release of renin ; this action was greater with captopril administration ( treatment effect : p < 10 ( -4 ) , indicating blockade of the RAS . This inhibition was incomplete because AII levels increased markedly when captopril was given ( no treatment effect : p < 0.37 ) . Finally , ACE inhibitor resulted in decreased GFR ( p = 115 +/- 5.8 ml/mn-1 , C = 91.1 +/- 4 , p < 0.05 ) with exercise without modification of MA . ACE inhibitor administration does not modify the physical performance of nonathletic subjects ; AII is significantly increased with exercise despite captopril treatment ; ACE inhibitor decreases GFR significantly but does not influence MA with prolonged physical effort .

captopril

ACE inhibitor .

captopril

captopril

ACE inhibitor

ACE inhibitor

administration

ACE inhibitor

GFR

GFR

exercise

eight

volunteers

physical stress


[ Late cardiac toxicity in Hodgkin 's disease . A study with pulsed Doppler echocardiography ] . 49 patients ( 22 women , 27 men , mean age 43.7 [ 21-65 ] years ) with Hodgkin 's disease were examined by Doppler echocardiography a median of 5.37 ( 2-10 ) years after the end of chemotherapy ( given according to the COPP/ABVD scheme , with or without mediastinal irradiation ) for possible chronic changes in myocardium , pericardium or cardiac valves , as well as for any haemodynamic sequelae . Maximal and integrated early ( E , Ei ) and late ( A , Ai ) diastolic flow velocities and their ratio ( E/A , Ei/Ai ) were measured by pulsed Doppler over the mitral and tricuspid valves . Although on two-dimensional echo 21 patients ( 42.9 % ) were found to have valvar thickening , 19 ( 38.8 % ) pericardial thickening and 9 ( 18.4 % ) a reduced fibre shortening fraction , the Doppler indices were statistically not significantly different from those in 25 controls with normal hearts . These echocardiographic data of functional and morphological parameters indicate that there was no effect on various measurements of diastolic function after chemotherapy with or without mediastinal radiation . In successfully treated patients with Hodgkin 's disease the described changes are of minor significance .

pulsed Doppler echocardiography

Doppler echocardiography

mediastinal irradiation

pulsed Doppler

cardiac toxicity

haemodynamic sequelae

Maximal and integrated early

( E , Ei )

( E/A , Ei/Ai )

valvar thickening

pericardial thickening

reduced fibre shortening fraction , the

Doppler indices

functional and morphological parameters

measurements of diastolic function

women

men

Hodgkin 's disease

Hodgkin 's disease


Early educational intervention for very low birth weight infants : results from the Infant Health and Development Program . OBJECTIVE To examine the effect of early educational intervention after discharge from the hospital on the health and developmental status of very low birth weight ( < or = 1500 gm ) infants . DESIGN Randomized , controlled trial , with post hoc analysis . SETTING Eight sites , heterogeneous for sociodemographic and health care use . PARTICIPANTS Infants ( N = 280 ) born weighing < or = 1500 gm and selected for the Infant Health and Development Program . Eligibility was limited primarily by geographic distance from the day care center . One third were randomly assigned to the intervention ( INT ) group and two thirds to follow-up only . INTERVENTIONS All children received intensive pediatric and developmental surveillance . The INT group received home visits and center-based educational interventions until 36 months of age ( corrected for gestational age when final assessments were completed ) . OUTCOMES Cognitive development ( Stanford-Binet Intelligence Scale ) , behavioral competence ( Achebach Child Behavior Checklist ) , and health status ( indexes summarizing reported morbidity , the Functional Status II ( R ) Scale , and General Health Ratings Index ) . RESULTS Cognitive development scores were 7.2 points higher ( p = 0.002 ) in the INT group , after adjustment for baseline differences in site , sociodemographic characteristics , and neonatal morbidity , and were 9.4 points higher ( p < 0.0003 ) when the 29 children with significant cerebral palsy were removed . No differences in behavior , serious morbidity , functional status , or health rating were found overall . The infants in the INT group who weighted < or = 1000 gm at birth had significantly lower behavior problem scores but no differences on other outcomes . All children in the INT group had slightly higher rates of less serious morbidity . CONCLUSION The advantage conferred by being in the INT group , as previously reported for heavier infants , extends to very low birth weight children , supporting the use of early intervention in this group .

Early educational intervention

Infant Health and Development Program .

early educational intervention

follow-up only

Cognitive development scores

neonatal morbidity

lower behavior problem scores

rates of less serious morbidity .

very low birth weight infants :


Randomized controlled study of chemoprophylaxis in transurethral prostatectomy . We studied 599 evaluable patients with benign prostatic hypertrophy at 7 urological units . Before transurethral prostatectomy the patients were randomized into 3 groups : group 1 -- 197 patients given single-dose ceftriaxone ( 2 gm . ) , group 2 -- 203 patients given 160/800 mg. trimethoprimsulfamethoxazole and group 3 -- 199 controls given no antimicrobial prophylaxis . Patients with a preoperative indwelling catheter , positive urine culture , signs of active infection or preoperative antibiotic treatment were excluded . Postoperative infectious complications were demonstrated in 15 of 197 ( 7.6 % ) , 25 of 203 ( 12.3 % ) and 43 of 199 ( 21.6 % ) patients in the study groups , respectively . The difference in infectious complications between groups 1 and 3 was statistically highly significant ( p < 0.01 ) and between groups 2 and 3 it was significant ( p < 0.05 ) . Single-dose antibiotic prophylaxis proved to be useful in the prevention of serious infectious complications after transurethral prostatectomy .

single-dose ceftriaxone

trimethoprimsulfamethoxazole

controls

Postoperative infectious complications

infectious complications

serious infectious complications

transurethral prostatectomy .

benign prostatic hypertrophy


A comparison of 1- and 3-minute lockout periods during patient-controlled sedation with midazolam . PURPOSE The maximum effect of midazolam injected intravenously occurs in about 3 minutes . Patient-controlled sedation carried out with 1-mg increments of midazolam at 3-minute intervals provides comparable conditions to that of doctor-controlled sedation carried out with 1-mg increments at 1-minute intervals , except for the longer duration taken for the patients to achieve satisfactory sedation prior to surgery . The purpose of this study was to find out how safe it would be to shorten the interval of increments of midazolam to 1 minute in patient-controlled sedation . PATIENTS AND METHODS In a randomized crossover study , 26 patients undergoing bilateral lower third molar surgery at two visits had patient-controlled sedation with 1 mg midazolam increments at 1-minute or 3-minute intervals at one visit and the alternative at the other visit . RESULTS The time taken for patients to achieve a degree of sedation that they thought was sufficient to tolerate the surgery was significantly longer when the increment interval was 3 minutes ( t = -4.8 ; P < .05 ) . Both techniques provided good operating conditions , stable vital signs , mild to moderate sedation , without loss of verbal contact . CONCLUSION A significant majority preferred the sedation technique with 1-minute increment intervals ( chi 2 = 4.6 ; P < .05 ) .

midazolam .

midazolam

midazolam

midazolam

patient-controlled sedation

midazolam

degree of sedation

operating conditions

vital signs

loss of verbal contact .

bilateral lower third molar surgery


The effect of metformin and insulin on sympathetic nerve activity , norepinephrine spillover and blood pressure in obese , insulin resistant , normoglycemic , hypertensive men . To evaluate the effect of metformin on insulin sensitivity and to further examine the relationship between insulin resistance , sympathetic nerve activity and blood pressure , 6 obese insulin resistant , normoglycemic hypertensive men were investigated ( age 49 +/- 2 years , BMI 27.6 +/- 1.2 , mean +/- SEM ) . The study had a placebo controlled , double blind , cross over design with 6 weeks ' metformin treatment ( 850 mg b.i.d ) vs placebo . Blood pressure was measured weekly . At the end of each treatment period , glucose infusion rate ( GIR ) , muscle sympathetic nerve activity ( MSA ) and renal and total body norepinephrine ( NE ) kinetics ( radioisotope dilution ) were examined during euglycemic hyperinsulinemic clamp . Fasting insulin was 13 +/- 3 and 10 +/- 2 mU/l and fasting glucose 5.3 +/- 0.2 and 5.1 +/- 0.1 mmol/l after placebo and metformin treatment , respectively ( ns ) . GIR during the last hour of the insulin clamp was 3.7 +/- 0.6 vs 3.6 +/- 0.6 mg/kg x min ( ns ) . Resting MSA , total body and right renal NE spillover did not differ significantly after placebo and metformin treatment . Systolic and diastolic blood pressures were 151 +/- 10/95 +/- 5 mmHg after placebo and 146 +/- 5/94 +/- 5 mmHg after metformin treatment ( ns ) . Thus metformin treatment did not have any significant effect on insulin sensitivity , blood pressure or sympathetic activity in this small group of patients . Renal plasma flow and MSA increased significantly during the insulin clamp , whereas renal NE and total body NE spillover remained unchanged , suggesting nonuniform regional sympathetic nerve responses to acute hyperinsulinemia .

metformin

insulin

metformin

placebo

metformin

placebo

metformin

metformin

Blood pressure

glucose infusion rate ( GIR )

Fasting insulin

Resting MSA

total body and right renal NE spillover

Systolic and diastolic blood pressures

blood pressure

sympathetic activity

obese

insulin resistant

normoglycemic

hypertensive

obese insulin resistant

normoglycemic hypertensive

men

49 +/- 2


Expectant management of functional ovarian cysts : an alternative to hormonal therapy . OBJECTIVE We studied whether the administration of oral contraceptives facilitates the disappearance of spontaneously formed functional ovarian cysts . METHODS Eighty patients in whom ultrasonography revealed unilateral , mobile , unilocular , thin-walled ovarian cysts without internal echoes and greater than 30 mm but not exceeding 60 mm in diameter were enrolled into the study . Patients were randomized by stratification to receive a low-dose monophasic pill , a high-dose monophasic pill , a multiphasic pill or no therapy . Patients were re-evaluated after 5 weeks of therapy and at the end of therapy ( 10 weeks ) . RESULTS The mean ages and the mean cyst diameters of the patients for each group were not significantly different . We did not find a significant effect of oral contraceptive administration on the disappearance rate of functional ovarian cysts over that of expectant management . CONCLUSION We conclude that oral contraceptive therapy even with multiphasic pills is very effective in the management of functional ovarian cysts but expectant management achieves similar success rates and may be a good alternative to oral contraceptive therapy .

Expectant management

hormonal therapy

oral contraceptives

low-dose monophasic pill

high-dose monophasic pill

multiphasic pill

no therapy

oral contraceptive

oral contraceptive therapy

mean ages and the mean cyst diameters

functional ovarian cysts

ovarian cysts

ovarian cysts

Eighty

functional ovarian cysts

ovarian cysts


The effect of patient position on the reproducibility of cardiac output measurements . OBJECTIVE To determine the effect of patient position on the reproducibility of cardiac output measurements . DESIGN Prospective , two-group quasi-experimental design . Convenience sample . SETTING The study involved two intensive care units in two adult acute care hospitals . PATIENTS Thirty patients admitted to the intensive care unit who had a thermodilution pulmonary artery catheter in place . Ages ranged from 39 to 80 years ( mean of 66.4 +/- 11.3 years ) . OUTCOME MEASURES Thermodilution cardiac output measurements . INTERVENTION The subjects were placed in one of two groups , initially by flipping a coin then into alternate groups . Group A subjects were placed supine , and after 5 minutes had cardiac output measurements performed . They were then placed in the 45-degree upright position , and after an additional 5 minutes had cardiac output measurements performed . Group B subjects were first placed in the 45-degree upright position , and after 5 minutes had cardiac output measurements performed . They were then placed in the supine flat position , and after an additional 5 minutes had cardiac output measurements performed . RESULTS Seventy percent ( n = 30 ) of the sample population displayed a lower cardiac output in the 45-degree upright position than that obtained in the supine position , with the decrease ranging from 1 % to 32 % ( mean decrease 11 % ) . Forty percent ( n = 30 ) of cardiac output measurements obtained in the 45-degree upright were greater than or equal to 10 % less than those obtained in the supine flat position . The differences in cardiac output were analyzed with the paired t test . which produced a 95 % confidence interval from -0.539 to -0.083 . The two-group Wilcoxon test was used to analyze the mean cardiac output with the patient in the supine , flat position and in the 45-degree upright position . The mean cardiac output at 0 degrees was found to be statistically significant higher ( p = 0.0083 ) than the mean cardiac output at 45 degrees . The effect of coexisting variables was analyzed with the Kruskal-Wallis . The use of vasoconstrictors was the only variable that had a statistically significant change in cardiac output associated with a change in position . CONCLUSIONS These results indicate that cardiac output measurements are affected by alterations in patient position . To ensure accurate comparisons between consecutive cardiac output measurements , the researchers recommend that the position in which the cardiac output measurements are performed be documented and the cardiac output measurements be conducted in a uniform position .

patient position

supine

45-degree upright position

45-degree upright position

supine flat position

lower cardiac output

cardiac output measurements

differences in cardiac output

mean cardiac output

mean cardiac output

cardiac output

Thirty

39 to 80


Teaching children with autism to seek information : acquisition of novel information and generalization of responding . A time delay procedure was used to teach 3 children with autism to ask the question " What 's that ? " when novel stimuli were presented during an instructional task . Once the ability to ask the question was acquired , the children 's ability to learn novel information by asking the question was assessed . The children were then taught to ask the question within a less structured context . All three studies used a multiple baseline across participants . Generalization was assessed in a different room , to a new person , and to novel stimuli . All of the children learned to ask the question within the instructional context , while on a walk in the school building , and to request information about three-dimensional objects . The acquisition of novel information was consistent for receptive and expressive tests for 2 of the children , with varied results for the 3rd . These studies indicate that children with autism can be taught to ask questions that lead to the acquisition of new information .

acquisition of novel information

children with autism

3 children with autism


Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission . BACKGROUND Prophylactic cranial irradiation in patients with small-cell lung cancer decreases the overall rate of brain metastases without an effect on overall survival . It has been suggested that this treatment may increase neuropsychological syndromes and brain abnormalities indicated by computed tomography scans . However , other retrospective data suggested a beneficial effect on overall survival for patients in complete remission . PURPOSE Our purpose was to evaluate the effects of prophylactic cranial irradiation on brain metastasis , overall survival , and late-occurring toxic effects in patients with small-cell lung cancer in complete remission . METHODS We conducted a prospective study of 300 patients who had small-cell lung cancer that was in complete remission . The patients were randomly assigned to receive either prophylactic cranial irradiation delivering 24 Gy in eight fractions during 12 days ( treatment group ) or no prophylactic cranial irradiation ( control group ) . A neuropsychological examination and a computed tomography scan of the brain were performed at the time of random assignment and repeatedly assessed at 6 , 18 , 30 , and 48 months . Patterns of failure were analyzed according to total event rates and also according to an isolated first site of relapse , using a competing-risk approach . RESULTS Two hundred ninety-four patients who did not have brain metastases at the time of random assignment were analyzed . The 2-year cumulative rate of brain metastasis as an isolated first site of relapse was 45 % in the control group and 19 % in the treatment group ( P < 10 ( -6 ) ) . The total 2-year rate of brain metastasis was 67 % and 40 % , respectively ( relative risk = 0.35 ; P < 10 ( -13 ) ) . The 2-year overall survival rate was 21.5 % in the control group and 29 % in the treatment group ( relative risk = 0.83 ; P = .14 ) . There were no significant differences between the two groups in terms of neuropsychological function or abnormalities indicated by computed tomography brain scans . CONCLUSIONS Prophylactic cranial irradiation given to patients with small-cell lung cancer in complete remission decreases the risk of brain metastasis threefold without a significant increase in complications . A possible beneficial effect on overall survival should be tested with a higher statistical power . IMPLICATIONS The results of the trial favor , at present , the indication of prophylactic cranial irradiation for patients who are in complete remission . A longer follow-up and confirmatory trials are needed to fully assess late-occurring toxic effects . The possible effect on overall survival needs to be evaluated with a larger number of patients in complete remission , and a meta-analysis of similar trials is recommended .

Prophylactic cranial irradiation

prophylactic cranial irradiation

prophylactic cranial irradiation

Prophylactic cranial irradiation

overall survival .

brain metastasis , overall survival

late-occurring toxic effects

relapse

total 2-year rate of brain metastasis

2-year overall survival rate

overall survival

patients with small-cell lung cancer

patients in complete remission

Two hundred ninety-four patients

patients who are in complete remission

patients in complete remission


The influence of breast size on late radiation effects and association with radiotherapy dose inhomogeneity . A prospective assessment of late changes in breast appearance in 559 patients after tumour excision and radiotherapy for early breast cancer noted a strong association with breast size . Only 3/48 ( 6 % ) patients with small breasts developed moderate or severe late changes compared with 94/423 ( 22 % ) with medium sized breasts and 34/88 ( 39 % ) patients with large breasts ( p < 0.001 ) . One possibility is that greater radiation changes are related to greater dose inhomogeneity in women with large breasts . To explore this hypothesis , radiation dose distributions were assessed in a separate group of 37 women in whom three-level transverse computer tomographic images of the breast in the treatment position were available . A significant correlation was found between breast size and dose inhomogeneity which may account for the marked changes in breast appearance reported in women with large breasts .

tumour excision

and radiotherapy

after tumour excision and radiotherapy

early breast cancer


Effects of ursodeoxycholic acid on serum liver enzymes in patients with hepatitis C virus-related chronic liver disease . OBJECTIVE To study the effect of ursodeoxycholic acid ( UDCA ) on serum liver enzyme levels [ alanine aminotransferase ( ALT ) and gamma-glutamyl transferase ( GGT ) ] in 101 patients with hepatitis C virus-related chronic liver disease . METHODS Forty-nine patients were assigned to receive UDCA ( 450 mg/day ) over a period of 6 months and 52 to receive no treatment . RESULTS In the UDCA group , serum ALT and GGT levels significantly improved . ALT values decreased from pre-treatment levels of 157.0 +/- 62.6 IU/l to 82.5 +/- 46.4 IU/l ( P < 0.05 ) , and GGT fell from 141.3 +/- 86.2 IU/l to 66.0 +/- 49.5 IU/l ( P < 0.001 ) . No significant change occurred in the mean ALT and GGT levels in the control group . CONCLUSION Although our encouraging preliminary results must be validated by double-blind histological trials , UDCA may be an alternative treatment for patients who fail to respond to interferon therapy .

ursodeoxycholic acid

ursodeoxycholic acid ( UDCA )

UDCA

no treatment

UDCA

UDCA

interferon therapy

serum liver enzymes

serum ALT and GGT levels

ALT values

mean ALT and GGT levels


Effects of the cholinomimetic SDZ ENS-163 on scopolamine-induced cognitive impairment in humans . Scopolamine-induced cognitive impairment was used in healthy men to evaluate the central nervous system activity of the new cholinomimetic SDZ ENS-163 . Eighteen subjects were treated in a crossover design with oral placebo/intravenous saline , 50 mg of oral SDZ ENS-163/intravenous saline , oral placebo/0.4 mg of intravenous scopolamine , and 50 mg of oral SDZ ENS-163/0.4 mg of intravenous scopolamine . The administration of placebo with scopolamine caused significant cognitive impairment , as assessed by the Computerized Neuropsychological Test Battery ( CNTB ) , and also decreased salivation and heart rate . In contrast , SDZ ENS-163 with saline had no effect on CNTB scores , increased salivation , and increased heart rate . Despite the observed cholinomimetic effects of SDZ ENS-163 when administered with saline , the changes in CNTB scores , heart rate , and salivation were indistinguishable between placebo/scopolamine and SDZ ENS-163/scopolamine . Thus , 50 mg of oral SDZ ENS-163 has cholinomimetic activity in normal men , but this dose is insufficient to reverse the muscarinic effects of 0.4 mg of intravenous scopolamine .

cholinomimetic SDZ ENS-163

new cholinomimetic SDZ ENS-163

oral placebo/intravenous saline

cognitive impairment

significant cognitive impairment

decreased salivation and heart rate

CNTB scores

increased salivation

increased heart rate

cholinomimetic effects

changes in CNTB scores

heart rate

salivation

cholinomimetic activity

muscarinic effects


The antiemetic efficacy of prophylactic granisetron in gynecologic surgery . Postoperative nausea and vomiting are common after recovery from anesthesia . We examined the prophylactic effect of granisetron on postoperative nausea and vomiting in 120 female patients ( ASA physical status I ) undergoing gynecologic surgery . They were randomly allocated to one of three groups ( n = 40 for each ) : saline ( as a control ) , granisetron 20 micrograms/kg , and granisetron 40 micrograms/kg . Saline or granisetron was given intravenously ( IV ) over 5 min approximately 30 min before the end of anesthesia . Nausea , vomiting , and safety assessments were performed during the 24-h recovery period . For the 24-h period after surgery , the number of emesis-free patients was significantly larger in the granisetron groups than in the control group ( 83 % , 78 % , and 20 % of patients receiving granisetron 20 micrograms/kg and 40 micrograms/kg , and saline , respectively ) . Granisetron at both doses also was superior to the control for the prevention of nausea over the 24-h study period ( nausea visual analog scales at 24-h postsurgery : 49 mm , 17 mm , and 18 mm in the control , granisetron 20 micrograms/kg , and granisetron 40 micrograms/kg groups , respectively ) . Fewer patients received " rescue " antiemetics in the granisetron groups than in the control group ( 10 % , 10 % , and 43 % of patients in granisetron 20 micrograms/kg and 40 micrograms/kg , and the control groups , respectively ) . The adverse events in the granisetron groups were similar to those in the control group . The administration of granisetron had no significant effect on vital signs or clinical laboratory test profiles . Granisetron given at 20 or 40 micrograms/kg i.v . during anesthesia appears to be a simple , effective , and safe method for preventing postoperative nausea and vomiting .

prophylactic granisetron

granisetron

saline

granisetron

granisetron

Saline

granisetron

Granisetron

granisetron

granisetron

granisetron

Granisetron

antiemetic efficacy

Postoperative nausea and vomiting

postoperative nausea and vomiting

Nausea , vomiting

safety assessments

number of emesis-free patients

nausea

nausea visual analog scales

" rescue " antiemetics

adverse events

vital signs

or

clinical laboratory test profiles

simple , effective , and safe method

postoperative nausea and vomiting

gynecologic surgery .

recovery from anesthesia .


Quantifications of the major urinary metabolite of the E prostaglandins by mass spectrometry : evaluation of the method 's application to clinical studies . Measurement of 7alpha-hydroxy-5,11-diketotetranoprostane-1,16-dioic acid , ( PGE-M ) , the major urinary metabolite of prostaglandin E1 and E2 in man provides a useful indicator to monitor prostaglandin biosynthesis . For quantitative analysis of this prostaglandin metabolite and the stable-isotope dilution techniqe of selected ion monitoring ( SIM ) is employed using gas-liquid chromatography-mass spectrometry . The preparation of the bis ( D3-methyloxime ) , bis-methyl ester of PGE-M containing a tritium tracer in position 2 which was used as internal standard for the SIM method is described . The synthesis of this internal standard includes the biosynthetic conversion of 11-hydroxy-9,15-diketoprostanoic acid to PGE-M by the rabbit . The intra-assay coefficient of variation of this SIM method ranged between 4.0 to 6.7 percent . The recovery of authentic , underivatized PGE-M added to urine was 93 +/- 3 % ( mean +/- SEM , n=17 ) . The levels of PGE-M excreted in urine were higher ( p less than 0.001 ) in males than in females ( 15.2 +/- 1.9 mug/24 hours ( n=24 ) and 3.3 +/- 0.3 mug/24 hours ( n=17 ) , respectively . These levels were in close agreement with values published previously . No significant difference in excretion of PGE-M between the sexes was observed in the pre-pubertal age-grou ( male : 2.9 +/- 0.8 mug/24 hours , n=5 ; female : 3.1 +/- 0.9 mug/24 hours , n=5 ) or in the age-group of 45-80 years ( male : 9.3 +/- 1.1 mug/24 hours , n=21 ; female : 7.3 +/- 0.9 mug/24 hours , n=12 ) . The amount of PGE-M excreted decreased significantly after administration of indomethacin or acetyl salicylic acid in therapeutic doses . The concomitant reduction of the urinary excretion of PGE-M ( 68 to 85 % decrease ) and prostaglandin E ( 73 to 100 % decrease ) after indomethacin treatment in each case ( n=8 ) is evidence that a diminished urinary PGE-M output reflects a decrease in prostaglandin E biosynthesis .

mass spectrometry

selected ion monitoring

indomethacin

acetyl salicylic acid

indomethacin

levels of PGE-M excreted

man

males

females

pre-pubertal age-grou

age-group of 45-80 years


Dose-related difference in progression rates of cytomegalovirus retinopathy during foscarnet maintenance therapy . AIDS Clinical Trials Group Protocol 915 Team . PURPOSE A previous dose-ranging study of foscarnet maintenance therapy for cytomegalovirus retinopathy showed a positive relationship between dose and survival but could not confirm a relationship between dose and time to first progression . This retrospective analysis of data from that study was undertaken to determine whether there was a relationship between dose and progression rates , which reflects the amount of retina destroyed when progression occurs . METHODS Patients were randomly given one of two foscarnet maintenance therapy doses ( 90 mg/kg of body weight/day [ FOS-90 group ] or 120 mg/kg of body weight/day [ FOS-120 group ] after induction therapy . Using baseline and follow-up photographs and pre-established definitions and methodology in a masked analysis , posterior progression rates and foveal proximity rates for individual lesions , selected by prospectively defined criteria , were calculated in each patient . Rates were compared between groups . RESULTS The following median rates were greater for the FOS-90 group ( N = 8 ) than for the FOS-120 group ( N = 10 ) : greatest maximum rate at which lesions enlarged in a posterior direction ( 43.5 vs 12.5 microns/day ; P = .002 ) ; posterior progression rate for lesions closest to the fovea ( 42.8 vs 5.5 microns/day ; P = .010 ) ; and maximum foveal proximity rate for either eye ( 32.3 vs 3.4 microns/day ; P = .031 ) . CONCLUSION Patients receiving higher doses of foscarnet have slower rates of progression and therefore less retinal tissue damage during maintenance therapy . A foscarnet maintenance therapy dose of 120 mg/kg of body weight/day instead of 90 mg/kg of body weight/day may help to preserve vision in patients with cytomegalovirus retinopathy .

foscarnet maintenance therapy .

foscarnet maintenance therapy

two foscarnet maintenance therapy doses

foscarnet

foscarnet

lesions

posterior progression rate for lesions

cytomegalovirus retinopathy


The costs and effects of a nutritional education program following work-site cholesterol screening . OBJECTIVES The purpose of this study was to assess the costs and impact of a nutrition education program following a cholesterol screening . METHODS Forty work-sites were randomly assigned to one of two educational interventions : a " usual " intervention of 5 minutes of counseling , or a " special " intervention of 2 hours of behaviorally based education on dietary changes to lower serum cholesterol . Costs were monitored , and cholesterol levels were retested 6 and 12 months later . RESULTS The total per-person cost for screening and the educational intervention was about $ 50 . Cholesterol levels differed little between the two intervention groups 6 months after screening , but after 12 months those in the special intervention worksites showed a 6.5 % drop in cholesterol , whereas those at the usual intervention worksites showed a drop of only 3.0 % . Hence a 3.5 % cholesterol reduction was attributable to the special intervention . CONCLUSIONS A behaviorally based nutrition education program following cholesterol screening can have a meaningful impact on long-term cholesterol levels at a low cost . Nutrition education in work-sites may therefore be a useful way to lower the risk of heart disease in communities .

nutritional education program

nutrition education program

educational interventions

Nutrition education

costs

effects

costs

impact

Costs

cholesterol levels

total per-person cost

Cholesterol levels

cholesterol

cholesterol reduction


[ The value of local administration of antibiotics in treatment of bone infections ] . An open , controlled , randomized clinical investigation was carried out in 33 patients suffering from osteomyelitis . In the first group , 17 patients , a through drainage with sterile physiologic solution was applied , while in the second group , 16 patients , antibiotic was added to the sterile physiologic solution . In all patients values of C reactive protein ( CRP ) in the blood were examined , and later on every third day after the operation . A significant difference of average values of CRP between the 3rd and 21st day in both groups of patients was established , as well as the similarity in average values of CRP , which points to the fact that the mechanical effect of through drainage is dominant , speaking about rinsing focus of infection and eliminating necrotic tissues and small sequesters .

antibiotics

sterile physiologic solution

A significant difference of

average values of CRP

similarity in

average values of CRP

infection

treatment of bone infections ]


The effect of fasting on total serum bilirubin concentrations . Thirty-seven healthy volunteers , 19 of whom had consistently elevated total serum bilirubin ( TSB ) concentrations , took part in an open , randomised cross-over study to determine the effect of fasting on TSB concentrations . The study comprised of two treatments . During one treatment period volunteers ate a standard supper but fasted for 24 h thereafter . During the other treatment period volunteers ate a standard supper , snacks , breakfast and lunch . TSB concentrations were measured at regular intervals . In both the normal and high bilirubin groups , minimum TSB values were recorded 4 h after the supper . A 24 h fast more than doubled TSB concentration from baseline values in both the normal and high bilirubin groups . A clinically relevant rise in TSB took place after 12 h into the fasting period ( TSB of 17.3 mumol l-1 in the fasted group vs 14.0 mumol l-1 in the non-fasted group ) . When designing a clinical trial , selecting volunteers , or judging the tolerance of a new drug , the rise in TSB caused by fasting must therefore be taken into account , particularly in trials where volunteers or patients fast before entering the study .

fasting

fasting

ate a standard supper but

fasted for 24 h

thereafter

total serum bilirubin concentrations .

TSB concentrations

minimum TSB values

more than doubled TSB concentration

rise in TSB

TSB


Plasma norepinephrine and mortality . Plasma norepinephrine levels , which reflect sympathetic nervous system activity , are almost universally elevated in patients with left ventricular dysfunction . This elevation occurs in patients with overt , symptomatic heart failure ( HF ) and in patients with asymptomatic left ventricular dysfunction . Evidence suggests that the elevation in plasma norepinephrine levels can be at least partly attributed to an increase in sympathetic nervous system activity . It has become evident that elevated plasma norepinephrine levels are directly related to prognosis ; patients with levels > 900 pg/ml have a poor prognosis and shortened life expectancy . However , plasma norepinephrine levels bear little relationship to physiologic and clinical variables observed in HF , including ejection fraction and exercise capacity . Data from the V-HeFT II show that at 2-year follow-up , a progressive rise of plasma norepinephrine was observed in both treatment arms , suggesting that disease progresses despite treatment with either an angiotensin-converting enzyme inhibitor , enalapril , or vasodilator therapy with hydralazine/isosorbide dinitrate . It is possible that interventions aimed at the progressive neurohormonal activation that occurs in HF may improve the course of illness . Further study is needed to test this hypothesis .

enalapril

hydralazine/isosorbide dinitrate

plasma norepinephrine levels

ejection fraction

exercise capacity

rise of plasma norepinephrine


A prospective comparison of the multiplane probe with the biplane probe in structure visualization and Doppler examination during transesophageal echocardiography . To compare the imaging capability of the multiplane probe with that of the biplane probe , 317 consecutive patients were randomized to undergo transesophageal echocardiography with either probe . Images of 24 cardiac structures and nine Doppler signals were graded prospectively on a three-grade system . Both multiplane and biplane probes provided excellent visualization of cardiac structures and Doppler signals , but the multiplane probe was significantly superior to the biplane probe . There were no differences in the number of attempts at esophageal intubation , the amount of sedation used , and the examination time . The number of complications was similar , although all failed intubations occurred with the multiplane probe .

multiplane probe

biplane probe

multiplane probe

biplane probe

transesophageal echocardiography

multiplane and biplane probes

multiplane probe

multiplane probe

imaging capability

nine Doppler signals

Doppler signals

the amount of sedation used ,

the examination time

number of complications

failed intubations


[ Postoperative analgesia : peridural morphine versus sublingual buprenorphine . Comparative clinical study ] . The authors herein present their personal series on the clinical evaluation of the analgesic efficacy of 2 opiodes , peridural morphine hydrochloride ( 0.5 mg/kg ) administered to group A patients , and sublingual buprenorphine ( 0.4 mg ) administered to group B patients in the management of post-operative pain in major abdominal surgery . The study was conducted on 44 patients , both male and female , classified as ASA II and III . Statistical analysis of cardiovascular parameters ( BP and cardiac frequency ) , respiratory frequency and pain score showed an overlapping progression among the two groups . Spontaneous pain decreased significantly to zero at T6 ( p < 0.001 ) . However , the necessity to administer buprenorphine more frequently after the sixth hour and the consequent increase in side effects , lead us to believe that the method used for group A patients is more advantageous .

peridural morphine

sublingual buprenorphine .

sublingual buprenorphine ( 0.4 mg )

buprenorphine

respiratory frequency

pain score

Spontaneous pain

side effects

male

female


[ Effects of betamethasone on neuromuscular blockade induced by vecuronium in continuous infusion ] . The aim of the study was to determine a possible interaction between a corticosteroid ( betamethasone ) and vecuronium , a nondepolarizing muscle relaxant . The authors studied 20 patients , ASA I-II , aged 20-54 , both sexes , scheduled for abdominal surgery . Mechanomyographic and clinical evaluation by single twitch and TOF stimulation of the ulnar nerve at the wrist and measurement of the concomitant abductor pollicis muscle was applied . The onset time of vecuronium after a single bolus dose of 0.08 mg/kg , duration of action to 10 % single twitch recovery , duration of continuous infusion of 0.4-0.5 micrograms/kg/min of vecuronium started at 10 % single twitch recovery , and the effects of 0.1 mg/kg betamethasone administration 10 min after continuous infusion were evaluated . The recovery rate of vecuronium after stopping infusion at 10 % recovery was also evaluated . Corticosteroids may interact with non-depolarizing muscle relaxants both in prejunctional and postjunctional acetylcholine receptors by several mechanisms of action .

betamethasone

vecuronium

nondepolarizing muscle relaxant

abdominal surgery .

vecuronium

vecuronium

betamethasone

vecuronium

Corticosteroids

neuromuscular blockade

concomitant abductor pollicis muscle

onset time

duration of action

single twitch recovery

single twitch recovery

recovery rate of vecuronium

both sexes

abdominal surgery


Diet and vitamin D status among pregnant Pakistani women in Oslo . OBJECTIVES In the present study the diet and the nutritional status of pregnant Pakistani immigrant women have been compared with a group of Norwegian women . DESIGN A cross-sectional survey of women in the 18th week of pregnancy . SETTING Women referred to routine ultrasound examination at Aker and Ullevål Hospitals in Norway . SUBJECTS All ( 58 ) healthy women of Pakistani origin referred from October of 1991 to January of 1992 were included , of whom 38 ( 66 % ) participated . Forty-five Norwegian women were randomly included in the same period and 38 ( 84 % ) of these women participated . RESULTS The serum levels of 25-hydroxyvitamin D3 were significantly lower in the Pakistanis compared with the Norwegians ( median 19 nmol/l vs 55 nmol/l , P < 0.001 ) and 83 % of the Pakistani women had 25-hydroxyvitamin D3 levels below the reference value ( < 30 nmol/l ) . The Pakistanis had higher levels of serum parathyroid hormone ( median 2.6 vs 1.6 pmol/l , P < 0.001 ) . The Pakistanis also had a lower dietary intake of vitamin D than that of the Norwegians ( median 2.2 vs 3.3 micrograms/day , P < 0.05 ) , and a lower total intake , including supplements ( median 2.9 vs 7.0 micrograms/day , P < 0.001 ) . Among the Pakistanis a correlation was found between the dietary intake of margarine , the main source of vitamin D in the diet , and the concentration of 25-hydroxyvitamin D3 in serum , r = 0.48 ( P = 0.01 ) . In general , the Pakistanis avoided any direct sunshine exposure , and no relation between outdoor activity and serum level of 25-hydroxyvitamin D3 was found . The Pakistani women had a lower intake of calcium than the Norwegians ( median 793 vs 1134 mg/day , P < 0.001 ) . CONCLUSION This study has shown that Pakistani women living in Oslo are at great risk of developing vitamin D deficiency during pregnancy . The main reasons for this are avoidance of sun exposure , a low dietary intake of vitamin D , and no or little use of supplementation .

serum levels of 25-hydroxyvitamin D3

25-hydroxyvitamin D3 levels

serum parathyroid hormone

lower dietary intake of vitamin D

pregnant Pakistani

women

pregnant

women

Norwegian

women

women

18th week of pregnancy

Women


Randomized , controlled study of various agents for endoscopic injection sclerotherapy of bleeding canine gastric varices . The purpose of this study was to compare the relative efficacy and technical ease of use of eight different agents for endoscopic hemostasis and obliteration of bleeding gastric varices in a canine model , as no comparative data are available on gastric variceal sclerotherapy . Large bleeding gastric varices in 20 heparinized dogs were randomized to endoscopic injection treatment with one of the following agents : cyanoacrylate ; a 1:1:1 mixture of sodium tetradecyl sulfate 3 % , ethanol 98 % , and normal saline solution ; ethanolamine oleate 5 % ; sodium morrhuate 5 % ; sodium tetradecyl sulfate 1.5 % ; polidocanol 1 % ; normal saline solution with epinephrine 1:10,000 ; or normal saline solution ( control ) . The number and volume of injections and the time required to achieve complete hemostasis were evaluated ; follow-up endoscopy was performed at 1 month to assess gastric variceal obliteration . Cyanoacrylate was the best agent overall in terms of immediate efficacy , low volume requirement , time required for initial hemostasis , and reduction of gastric variceal size . Cyanoacrylate , tetradecyl sulfate , and polidocanol were the most effective agents for reducing gastric variceal size . Epinephrine was effective for controlling induced or secondary bleeding caused by puncture of the gastric varices with the sclerotherapy needle during intravariceal injections . Ongoing studies are evaluating combinations of agents with different mechanisms of action , such as epinephrine ( for vasoconstriction to minimize secondary bleeding ) plus alcohol , and/or tetradecyl sulfate ( for variceal thrombosis and sclerosis ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

cyanoacrylate

ethanolamine oleate 5 %

normal saline solution ( control )

immediate efficacy

low volume requirement

time required for initial hemostasis

reduction of gastric variceal size

Cyanoacrylate

tetradecyl sulfate

polidocanol

induced or secondary bleeding

heparinized


Cytokine levels and systemic toxicity in patients undergoing isolated limb perfusion with high-dose tumor necrosis factor , interferon gamma , and melphalan . PURPOSE Isolated limb perfusion ( ILP ) with tumor necrosis factor ( TNF ) , interferon gamma , and melphalan ( M ) has been reported to result in high response rates for extremity melanoma and sarcoma . We have evaluated the relationship of systemic TNF exposure to induction of several secondary mediators and incidence of systemic toxicity . PATIENTS AND METHODS Nineteen patients with extremity melanoma ( n = 16 ) or sarcoma ( n = 3 ) , underwent 90-minute ILP with TNF-alpha , interferon gamma ( 0.2 mg ) , and M ( 10 to 13 mg/L of limb volume ) ( TNF/IFN/M ) ( n = 12 ) , or M alone ( n = 7 ) . Continuous intraoperative monitoring ( CIM ) for systemic leak from the perfusion circuit was performed using radioactive iodine-131 albumin . Cytokine levels in the perfusate and systemic circulation during and after ILP were measured by enzyme-linked immunosorbent assay . RESULTS Systemic leaks > or = 1 % from the perfusion circuit occurred in six patients who received TNF/IFN/M and in four who received M alone . Hypotension that required vasopressor support occurred in six of six patients with evidence of a leak ( > or = 1 % ) and zero of six patients without a leak ( < 1 % ) . These six patients had significantly higher peak systemic TNF levels during and after perfusion than patients without a leak ( 2.8 and 8.2 ng/mL v 0.7 and 2.0 ng/mL , respectively ; P < .05 ) . All patients who received TNF/IFN/M had significantly greater increases in systemic interleukin-6 ( IL-6 ) levels than in patients with M alone ( 12,395 +/- 10,374 pg/mL v 79.4 +/- 7.2 pg/mL , respectively ; P < .001 ) . Intracellular adhesion molecule ( ICAM ) , IL-8 , and TNF-R levels were also increased after ILP with TNF/IFN/M . CONCLUSION ILP with TNF/IFN/M can be safely performed , as I131 albumin provides a sensitive measure of systemic leakage from the perfusion circuit . Patients with a measured leak of > or = 1 % develop mild and transient postoperative hypotension with significantly higher systemic TNF levels and lower perfusate TNF levels than in patients without leaks .

isolated limb perfusion

with high-dose tumor necrosis factor

interferon gamma

melphalan

Isolated limb perfusion ( ILP )

with tumor necrosis factor ( TNF )

interferon gamma

melphalan ( M )

ILP

with TNF-alpha

interferon gamma

M

TNF/IFN/M

M alone

iodine-131 albumin

Cytokine levels

systemic toxicity

response rates

secondary mediators

systemic toxicity

Systemic leaks

> or = 1 %

perfusion circuit

peak systemic TNF levels

systemic interleukin-6 ( IL-6 ) levels

Nineteen

extremity melanoma

sarcoma


Low power Ga-Al-As laser treatment of painful osteoarthritis of the knee . A double-blind placebo-controlled study . The aim of this double-blind study was to evaluate the effect of low power Ga-Al-As laser treatment on chronic pain related to osteoarthritis of the knee with periarticular tender points . Twenty-nine out-patients with uni- or bilateral osteoarthritis of the knee were included and randomly assigned to treatment with either laser or placebo laser . Fourteen patients received active laser treatment and all patients included completed the study . The effect variables were daily levels of pain , analgesic requirements , palpation tenderness and isokinetic quadriceps strength . Each patient participated in the study for 9 weeks and registered daily level of pain and consumption of analgesics . In weeks 4 , 5 and 6 the patients received a total of nine treatments , each of 15 min and administered to periarticular tender points . The dose per treatment was 22.5 joule . No significant differences in any of the effect variables were found between the two groups before , during or after treatment . With regard to the patients ' overall assessment there was a clearly demonstrable positive effect of treatment in both groups . This is likely to be due to a placebo effect .

Ga-Al-As laser treatment

placebo-controlled

low power Ga-Al-As laser treatment

laser

placebo laser

laser treatment

placebo

painful osteoarthritis

chronic pain

daily levels of pain ,

analgesic requirements

daily level of pain

consumption of analgesics


Health promotion and disease prevention for older adults : opportunity for change or preaching to the converted ? Health promotion and disease prevention for the elderly offer the potential for improving the quality of life for the growing population of older adults , while reducing the economic burden on the health system . Whether this potential can be realized depends , in part , on whether those older adults whose health behaviors put them at risk actually use preventive services when offered the opportunity . In 1988 the Health Care Financing Administration began a series of health promotion demonstrations to address health issues related to older adults . This article reports on program participation at one of the five demonstration sites . Over 1,900 community-dwelling Medicare beneficiaries who receive their health care through fee-for-service providers were enrolled in the demonstration . These enrollees were randomly assigned to control and experimental groups , with the latter offered health screening and promotion services . Nine hundred-seventy-three of the experimental subjects and 938 of the control subjects completed a lengthy telephone interview , which determined each person 's use of preventive services and practices . Although all 973 experimental subjects were invited by letter and follow-up telephone calls to attend these free-of-charge , Medicare-provided sessions , not everyone attended . We analyzed 17 health behaviors of those who attended the first session and those who did not . Those engaging in these preventive behaviors were neither more nor less likely to attend the screening services . Thus , we found neither " favorable " nor " unfavorable " selection bias in the use of these preventive services .

preventive services

health promotion demonstrations

control

health screening

promotion services

older adults :

the elderly

older adults

health behaviors put them at risk

older adults .

Nine hundred-seventy-three


Lipoprotein ( a ) serum levels in post-menopausal women treated with oral estrogens administered at different times . The different effects on serum lipoprotein ( a ) [ Lp ( a ) ] levels by administering estrogens at different times of the day ( 8 a.m. and 8 p.m. ) were evaluated in twenty-four post-menopausal women . Patients were assigned to one of the two treatment groups by random sampling numbers . Patients of both groups received 0.625 mg conjugated equine estrogens daily per os for 21 days . Group A patients ( n : 9 ) received the pill at 8 a.m. , and group B patients ( n : 12 ) received the pill at 8 p.m . There were no statistically significant differences between the two treatment groups as regards the anthropometric characteristics , the basal values of the Lp ( a ) , the sex steroid and pituitary hormone levels . Administration of conjugated equine estrogens resulted in decreased levels of Lp ( a ) only in group B after treatment . The different Lp ( a ) behaviour in the two groups and in the presence of the same serum hormonal levels , seems to be dependent on the existence of a circadian rhythm of the hepatic responsiveness to estrogens , whose expression is higher during evening hours .

oral estrogens

estrogens

conjugated equine estrogens

conjugated equine estrogens

effects

levels of Lp ( a )

twenty-four post-menopausal women .


[ A comparison of 2 methods of plastic cast fixation in treatment of loco classico radius fracture . A prospective , randomized study ] . The purpose of this study was to compare the functional and radiological result of two different positions of the wrist in a plaster cast following Colles ' fracture . For this prospective study , each of 50 patients with type A 2.2 , A 3.3 , C 1.2 or C 2.2 ( AO classification ) fractures of the radius was randomly assigned to one of two groups . Both groups were treated in the same way as far as anaesthesia and reduction were concerned . The only difference in treatment lay in the position of fixation in plaster . In group 1 the wrist was immobilized in neutral flexion-extension . In group 2 the wrist was dorsiflexed 20 degrees , while the carpus was pushed in a volar direction by an impression in the plaster cast . At review 2-7 years after the accidents , the two groups were compared with reference to symptoms , range of motion at the wrist , power of first closure and radiographic appearance . In group 1 there were 5 patients with significant disability , compared with only 1 in group 2 . A significant difference was found in the range of movement between the two groups for flexion and ulnar abduction ( p < 0.01 ) . The loss of power of first clenching ( difference between injured and healthy hand ) was 6.2 mmHg for group 1 and 3.8 mmHg for group 2 ( not significant ) . The radiographic examination showed significant differences both in sagittal inclination ( p < 0.001 ) and in radial shortening ( p < 0.05 ) . ( ABSTRACT TRUNCATED AT 250 WORDS )

plastic cast fixation

plaster cast

range of movement

loss of power of first clenching


The effect of cisapride on delayed colonic transit time in patients with idiopathic Parkinson 's disease . Disorders of autonomic regulation are common in patients with Parkinson 's disease ( PD ) . Patients most frequently complain of dysphagia and therapy resistant constipation , as far as the gastrointestinal tract is concerned . These symptoms have to be attributed to a neuronal degeneration . In a pilot study we therefore investigated the effect of stimulation of the myenteric plexus by cisapride . 11 women and 13 men were examined , the average age was 67.3 years , the Webster rating 17 points . In 2 out of 24 patients , colonic transit was prolonged up to the limit , both with and without therapy . The other 22 patients showed an acceleration in transit on response to cisapride . On average the colonic transit of 130 hours was reduced to 79 hours . This objective improvement was associated with a subjective improvement . Central side effects or a worsening of Parkinsonian symptoms were not found . We conclude that cisapride is effective in the treatment of constipation in idiopathic PD .

cisapride

cisapride .

cisapride .

cisapride

colonic transit time

colonic transit

acceleration in transit

colonic transit

worsening of Parkinsonian symptoms

idiopathic Parkinson 's disease

Disorders of autonomic regulation

Parkinson 's disease

PD

women

men

constipation

idiopathic PD


Physiological pacing improves symptoms and increases exercise capacity in the elderly patient . We evaluated the benefits of physiological pacing in the elderly by recruiting 13 subjects > 75 years of age , already fitted with a physiological pacing system . All had been paced for complete or Mobitz II heart block . Double blind cross over study was performed comparing exercise capacity , measuring distance walked on a 6-min walking test and time taken to climb two flights of stairs ; and symptoms , evaluated by an activity of daily living questionnaire , in atrioventricular synchronous and ventricular pacing . Mean distance walked was significantly higher in atrioventricular synchronous than in ventricular pacing ( 360 +/- 65 m vs. 327 +/- 69 m ; P < 0.01 ) . No significant difference was found in the ability to climb stairs but there was a marked improvement in the symptomatic questionnaire score , 19 +/- 5 in physiological pacing increasing to 28 +/- 10 with ventricular . Physiological pacing in the elderly produces an increase in exercise tolerance and improves symptoms ; therefore , age alone should not be a contraindication to a physiological system .

physiological pacing system .

atrioventricular synchronous

ventricular pacing

physiological pacing

Physiological pacing

exercise capacity

symptoms

activity of daily living questionnaire

Mean distance walked

No significant difference

ability to climb stairs

marked improvement

symptomatic questionnaire score

physiological pacing

Physiological pacing

increase

exercise tolerance

improves symptoms

elderly

> 75 years of age


Vigorous , aerobic exercise versus general motor training activities : effects on maladaptive and stereotypic behaviors of adults with both autism and mental retardation . Examined the effects of antecedent exercise conditions on maladaptive and stereotypic behaviors in 6 adults with both autism and moderate to profound mental retardation . The behaviors were observed in a controlled environment before and after 2 exercise and 1 non-exercise conditions . From the original group of 6 participants , 2 were selected subsequently to participate in aerobic exercise immediately before performing a community-integrated vocational task . Only antecedent aerobic exercise significantly reduced maladaptive and stereotypic behaviors in the controlled setting . Neither of the less vigorous antecedent conditions did . When aerobic exercise preceded the vocational task , similar reductions were observed . There were individual differences in response to antecedent exercise . Use of antecedent aerobic exercise to reduce maladaptive and stereotypic behaviors of adults with both autism and mental retardation is supported .

Vigorous , aerobic exercise

general motor training activities

antecedent exercise conditions

exercise

non-exercise

aerobic exercise

antecedent aerobic exercise

aerobic exercise

antecedent exercise

antecedent aerobic exercise

maladaptive and stereotypic behaviors

maladaptive and stereotypic behaviors

maladaptive and stereotypic behaviors

maladaptive and stereotypic behaviors


[ Carbohydrate substitutes : comparative study of intestinal absorption of fructose , sorbitol and xylitol ] . BACKGROUND The carbohydrate substitutes fructose , sorbitol and xylitol are gaining more and more importance in the production of dietary food . But they can provoke gastrointestinal side-effects . In a randomized double blind study the rate of malabsorption of these sugars was compared and the concomitant symptoms were recorded . SUBJECTS AND METHODS 25 healthy controls received 25 g of each sugar within 3 consecutive days . The intestinal absorption was determined by H2-exhalation tests and the clinical symptoms were recorded . RESULTS The rate of malabsorption was 84 % for sorbitol , 36 % for fructose and 12 % for xylitol ( p < 0.01 for sorbitol versus fructose and xylitol ) . 57 % of the participants with pathological H2-test after sorbitol and 56 % after fructose reported symptoms , while all of the 3 malabsorbers of xylitol were symptomatic . CONCLUSIONS There is an advantage to administering xylitol and fructose with regard to the intestinal absorption and concomitant symptoms as compared with sorbitol . H2-exhalation tests appear to be a reliable diagnostic tool to detect carbohydrate malabsorption and should find broader application in patients suffering from non-specific abdominal complaints .

fructose

sorbitol

xylitol

fructose

sorbitol

xylitol

25 g of each sugar

sorbitol

fructose

xylitol

sorbitol

fructose

xylitol

sorbitol

fructose

xylitol

xylitol

fructose

sorbitol

clinical symptoms

rate of malabsorption

intestinal absorption

carbohydrate malabsorption

intestinal absorption of fructose

healthy controls


Interferon treatment for hairy cell leukemia . An update on a cohort of 69 patients treated from 1983 to 1986 . We report follow-up information on 69 hairy cell leukemia ( HCL ) patients treated with interferon alfa-2b ( IFN ) as primary treatment from 1983 to 1986 . Follow-up through April , 1993 shows that only 14 patients have expired . Forty-seven of the 61 patients completing the intended 12 or more months of initial IFN treatment were eventually considered IFN failures . Forty-three required re-treatment ( 41 received a second course of IFN and 2 received pentostatin ) . Four patients died without further therapy for HCL . The median time to interferon failure was 31.3 months . Fourteen patients are alive and have not required further treatment after completing their initial 12 or more months of interferon . Fifteen patients underwent a third course of interferon therapy at a median time after completion of a second course of IFN of 1.0 year . Eighteen patients were eventually treated with pentostatin and ten with 2-chlorodeoxyadenosine ( 2-CdA ) . Thirteen patients developed a second malignancy ; six of these patients developed a hematologic malignancy between 44.6 months and 99.1 months after initiation of interferon therapy . We conclude that although interferon provides excellent palliation , that most patients will eventually require further treatment with interferon or chemotherapy . Future trials in HCL must be aware of the risk of second malignancies .

interferon alfa-2b ( IFN )

IFN

IFN

IFN

pentostatin )

interferon

interferon

interferon

IFN

pentostatin

2-chlorodeoxyadenosine ( 2-CdA ) .

interferon

interferon

interferon

chemotherapy

hairy cell leukemia

hairy cell leukemia ( HCL )

HCL

second malignancy ;

hematologic malignancy

interferon

chemotherapy

second malignancies

hairy cell leukemia

hairy cell leukemia ( HCL )


[ New approaches to evaluation of nonspecific inhalation provocation ( dose-response relationship ) in the comparative evaluation of bronchial hyperreactivity within the scope of clinical trials ] . For the performance of clinical drug trials in the therapy for bronchial hyperresponsiveness , unspecific inhalatory provocation tests are generally employed to judge therapeutic success . In particular , the parameter-specific provocation doses are considered to be the main target values . However , it must be considered that these provocation doses are not equally calculable for every patient in the same way and at any examination time . This leads to the fact that the number of evaluable case studies is often appreciably lower than the number of test participants and that a meaningful therapy group comparison may even not be possible under certain circumstances . An evaluation model is presented here in order to fully exploit the obtained data ; in this the percentile changes of the function parameters ( estimated by linear regression ) at a defined dose of the provocation substance are analyzed . In analogy , a survival time model and , as a supplement , a best case/worst case analysis are performed for further statistical evaluation . With the present procedure , an evaluation with inclusion of all test participants is possible . In contrast to the previously used evaluation procedures , this allows a reliable statistical confirmation of the results of clinical tests in the therapy for bronchial hyperresponsiveness .

nonspecific inhalation provocation

survival time model

bronchial hyperreactivity

bronchial hyperresponsiveness

bronchial hyperresponsiveness .


Efficacy and safety of timolol/pilocarpine combination drops in glaucoma patients . The aim of this randomized , double-blind study with two parallel groups was to examine the safety , efficacy and tolerability of two combination eye drops containing 0.5 % timolol and 2 % pilocarpine ( Fotil , Leiras , Finland , and Timpilo , MSD , USA ) in patients with glaucoma or ocular hypertension . Efficacy was determined based on daytime intraocular pressure curve and safety by examining visual fields , visual acuity , optic discs , by determining blood pressure and pulse rate , and by performing Schirmer and fluorescein tests . A total of 89 patients were enrolled , and 71 completed the 10-week treatment period . This study showed that the two combinations of 0.5 % timolol maleate and 2 % pilocarpine HCl compared in this study were equally effective in reducing intraocular pressure . The decrease in mean daily intraocular pressure from 0 to 10 weeks was 7.48 mmHg for Fotil , and 6.31 for Timpilo . The mean decrease in mean daily intraocular pressure was 29.3 % for Fotil , and 26.0 % for Timpilo . No significant differences were found between the groups . Adverse event were reported by 70 out of 89 patients by the end of 2 weeks , but were severe enough only in 11 for the treatment to be discontinued . In all others , adverse events were of transient nature and considered mild . In general , adverse events were similar in both study groups . However , burning was more common in patients on Fotil , and blurring of vision and light sensitivity were more common in patients on Timpilo . In patients with no contraindication to beta-blockers , these drugs appeared to be safe . ( ABSTRACT TRUNCATED AT 250 WORDS )

timolol/pilocarpine

timolol

pilocarpine

timolol maleate

pilocarpine HCl

intraocular pressure

mean daily intraocular pressure

mean daily intraocular pressure

Adverse event

adverse events

adverse events

burning

glaucoma patients .


Co-administration of pethidine and clonidine : a spinal anaesthetic technique for total hip replacement . Co-administration of pethidine 0.75 mg kg-1 and clonidine 75 micrograms intrathecally provided good intraoperative anaesthesia for total hip replacement , similar to that obtained using 0.5 % isobaric bupivacaine . Sensory and motor block were of shorter duration than that after 0.5 % isobaric bupivacaine and 0.5 % isobaric bupivacaine with morphine 0.5 mg ( P < 0.001 sensory block , P < 0.001 motor block ) . Postoperative morphine consumption , measured using a patient-controlled system , was similar to that in patients in the bupivacaine only group ( pethidine-clonidine : median 39 mg/24 h ; bupivacaine : median 34 mg/24 h ) but greater than that in the bupivacaine-morphine group ( median 8 mg/24 h ) ( P < 0.001 ) . Visual analogue pain scores after operation were similar to those with bupivacaine alone at all but one of the recording times but were greater than those in patients who received bupivacaine and morphine at 4 , 6 and 10 h after operation ( P < 0.001 , P < 0.04 , P < 0.02 ) . The combination did not offer any major advantage over conventional agents .

pethidine

clonidine

total hip replacement

pethidine 0.75 mg kg-1

clonidine 75 micrograms

total hip replacement

0.5 % isobaric bupivacaine

isobaric bupivacaine

isobaric bupivacaine

morphine

morphine

bupivacaine

pethidine-clonidine

bupivacaine

bupivacaine-morphine

bupivacaine alone

bupivacaine

morphine

Postoperative

morphine consumption

Visual analogue pain scores


Effect of flurbiprofen sodium on pupillary dilatation during scleral buckling surgery . Maintenance of pupillary dilatation is necessary for success of scleral buckling procedures . The efficacy of 0.03 % flurbiprofen in preventing intraoperative miosis was evaluated by a prospective randomized , double-masked controlled trial of 60 patients . Thirty patients received 0.03 % flurbiprofen 6 times at 15 minute intervals 90 minutes preoperatively in addition to the routine dilation regimen . The treated group had a mean pupillary decrease of 1.88 mm and the control group had a decrease of 1.57 mm ( p > 0.05 ) . Flurbiprofen did not affect the pupillary size at any step of the surgery . Factors such as age of the patient , lens status , number of cryo applications , duration of surgery , and the size and extent of buckle were assessed . The use of flurbiprofen did not affect the mean pupillary change for any of these groups . Preoperative use of flurbiprofen does not significantly decrease intraoperative miosis during scleral buckling procedures .

flurbiprofen sodium

0.03 % flurbiprofen

flurbiprofen

Flurbiprofen

flurbiprofen

flurbiprofen

pupillary dilatation

pupillary dilatation

mean pupillary decrease

pupillary size

age of the patient

lens status

number of cryo applications

duration of surgery

size and extent of buckle

mean pupillary change

scleral buckling surgery

scleral buckling procedures

Thirty


Scales for the assessment of neuroleptic response in schizophrenic children : specific measures derived from the CPRS . This article reports the psychometric properties of two scales for rating positive and negative schizophrenic signs and symptoms . These Positive and Negative Syndrome Scales consist of items selected from the Children 's Psychiatric Rating Scale ( CPRS ) , which contains items covering a wide range of childhood psychopathology . CPRS rating data were analyzed for 19 schizophrenic children , 16 males and 3 females , mean age 8.9 years ( range 5.5-11.7 ) , evaluated in a double-blind , placebo-controlled crossover study of haloperidol . We describe the item composition and coherence of each scale , the interrater reliabilities of clinicians using the scales , and the sensitivity of the scales for resolving treatment response . Schizophrenic children showed both positive and negative signs and symptoms , and both improved with neuroleptic treatment .

placebo-controlled

haloperidol

neuroleptic

response

Positive and Negative Syndrome Scales

neuroleptic treatment

schizophrenic

children

schizophrenic

children

males

females

mean age 8.9 years

Schizophrenic

children


Naltrexone plasma levels , clinical response and effect on weight in autistic children . This research measured naltrexone levels in plasma , to assess the relationship between behavioral response to naltrexone and plasma levels , and the effects of naltrexone on weight in hospitalized autistic children ( n = 41 ) . A double-blind , placebo-controlled , parallel groups design with fixed dose was used , with random assignment to naltrexone or placebo . Drug plasma levels were analyzed by gas chromatography/mass spectrometry , and weights were obtained weekly . Naltrexone levels measured in 17 children ranged from 0.12 to 5.60 ng/mL ( mean = 0.71 , standard error of the mean = 0.32 ) . There was no relationship between plasma levels and age , level of intellectual functioning , scores on the 14 selected Children 's Psychiatric Rating Scale ( CPRS ) items , Clinical Global Impressions , Global Clinical Consensus , and the CPRS hyperactivity factor . There was a trend ( p = .06 ) for children receiving naltrexone in the highest weight percentile ( > or = 90th ) to lose weight ( mean = -0.42 kg ) but this was not the case for those in the lower weight percentiles ( mean = +0.03 kg ) .

Naltrexone

naltrexone

naltrexone

naltrexone

placebo-controlled

placebo

gas chromatography/mass spectrometry

, and

weights were obtained weekly

Naltrexone

Drug plasma levels

autistic children .

children

14 selected


Dexamethasone for the treatment of depression : a randomized , placebo-controlled , double-blind trial . OBJECTIVE The authors ' goal was to assess dexamethasone for the treatment of depression . METHOD Thirty-seven outpatients ( 11 men and 26 women ) meeting DSM-III-R criteria for major depressive disorder were randomly assigned to receive either placebo or 4 mg/day of oral dexamethasone for 4 days . Baseline Hamilton depression scale scores were compared with scores obtained 14 days after the first dose of study medication . Data were analyzed by using two-sample t tests , chi-square methods , and Fisher 's exact test . RESULTS Seven ( 37 % ) of the 19 patients given dexamethasone but only one ( 6 % ) of the 18 patients given placebo responded positively . No adverse events or side effects were reported , and all patients who entered the study completed it . CONCLUSIONS A brief course of oral dexamethasone ( 4 days ) was significantly more effective than placebo within 14 days for the treatment of depression in a randomized , double-blind study of depressed outpatients .

Dexamethasone

dexamethasone

placebo

oral dexamethasone

dexamethasone

placebo

Hamilton depression scale scores

adverse events or side effects


The efficacy of audiotapes in promoting psychological well-being in cancer patients : a randomised , controlled trial . Open or uncontrolled studies have suggested that providing cancer patients with audiotapes of their clinical interviews can improve information recall and reduce psychological distress . We tested these hypotheses in a 'clinician-blind ' , prospective , randomised controlled trial . A total of 117 patients newly referred to a medical oncology clinic who were to be given 'bad news ' had their consultations audiotaped . Blind to the clinician , patients were randomly allocated to receive a copy of the tape to play at home or not ( control group ) . At 6 months follow-up , tape group patients reported positive attitudes to the audiotape and were shown to recall significantly more information about their illness than did controls . Overall improvement in psychological distress at 1 and 6 months follow-up , as measured with the 30-item General Health Questionnaire and the Hospital Anxiety and Depression Scale was no different in the two groups . However , a second-order interaction suggested that poor-prognosis patients were disadvantaged specifically by access to the audiotape , with less improvement in psychological distress at 6 months follow-up than non-tape controls . Patient access to audiotapes of clinical interviews promotes factual retention but does not reliably reduce psychological distress and may be actively unhelpful in some subgroups of patients .

audiotapes

audiotapes

audiotaped

audiotape

audiotapes

promoting psychological well-being

information recall

psychological distress

positive attitudes

psychological distress

psychological distress

factual retention

psychological distress

cancer

cancer


Profound luteinizing hormone suppression after stopping the gonadotropin-releasing hormone-agonist leuprolide acetate . OBJECTIVE To compare levels of serum LH during continued use of leuprolide acetate ( LA ) with levels during the first week after discontinuing LA . DESIGN Prospective controlled study . SETTING Clinical assisted conception program . PATIENTS Women undergoing controlled ovarian stimulation for assisted conception were randomized to receive LA according to " short " or " ultrashort " protocols . The alternative protocol was used then in a second cycle . Each patient was thus her own control . MAIN OUTCOME MEASURES Serum LH over time . RESULTS When LA was stopped after 5 days of administration , LH levels fell profoundly when compared with levels when LA was continued . CONCLUSION Loss of LH after stopping LA is likely to be clinically important in ovarian stimulation regimens that use pure FSH with LA in ultrashort protocols . The fall in LH lasts at least 1 week and may be explainable by persistent suppression of endogenous GnRH by LA during this time .

leuprolide acetate ( LA )

LA

LA

LA

LA

LA

Serum LH over time

LH levels

LH

LH

Women

ovarian stimulation


Acute exposure to acid fog : influence of breathing pattern on effective dose . Concern about the possible adverse health effects of acid fog has been fed by two observations : air pollution disasters earlier in this century were typically associated with fog , and current samples of fog water can be strongly acid . To study the acute effects of acid fog on the lung , the authors generated a monodisperse 10 microM MMAD aerosol of H2SO4 with a pH of 2.0 and a nominal concentration of 500 micrograms/m3 . They exposed seven healthy young men on alternate days to acid or control equiosmolar NaCl aerosol during 40 min of resting ventilation and 20 min of exercise ; the latter was sufficiently intense to induce oronasal breathing . Exposure was by means of a head dome , a head-only exposure device that permitted continuous measurement ( unfettered breathing ) of Vr , f , VE , and the onset and persistence of oronasal breathing . In this article the authors compare the relative importance of parameters contributing to the between-subject variability in estimated hydrogen ion dose to the lower airways ( H+LAW ) , based on analysis of variance . Physiologic parameters accounted for 70 % of the variability , of which 34 % was due to differences in duration of oronasal breathing ( tON ) and 36 % to differences in ventilation rate during oronasal breathing ( VE ( ON ) ) ; inhaled hydrogen ion concentration [ H+ ] , the environmental parameter , contributed only 30 % . Minute ventilation at the time of transition from nasal to oronasal breathing varied significantly among subjects even if normalized to FVC , an index of lung size .

nominal concentration

acid

control

equiosmolar NaCl aerosol

effective dose

adverse health effects

oronasal breathing

oronasal breathing

lower airways

duration of oronasal breathing ( tON )

exposure to acid fog :

seven

healthy young men


Hypericum treatment of mild depressions with somatic symptoms . In a randomized , placebo-controlled , double-blind study , 39 patients with depression with somatic symptoms were treated with hypericum extract LI 160 . The therapy lasted for 4 weeks ; the dosage was 300 mg three times daily . At the onset of the study as well as after 2 and 4 weeks , the following criteria were analyzed : HAMD , B-L , CGI , and vegetative symptoms . The results show a significant improvement in the active treatment group at the 5 % level as compared to placebo . Seventy percent of the patients treated with LI 160 were free of symptoms after 4 weeks . Typical symptoms of the depression such as lack of activity , tiredness , fatigue , and disturbed sleep , were especially responsive . In no case were any undesirable side effects observed .

Hypericum treatment

placebo-controlled

hypericum extract LI 160

significant improvement

symptoms

lack of activity

tiredness

fatigue

disturbed sleep

undesirable side effects


Safety and efficacy of thymopentin in zidovudine ( AZT ) -treated asymptomatic HIV-infected subjects with 200-500 CD4 cells/mm3 : a double-blind placebo-controlled trial . Thymopentin , 50 mg subcutaneously ( s.c. ) 3 times per week , was evaluated in a double-blind , randomized , placebo-controlled trial of zidovudine ( AZT ) -treated asymptomatic human immunodeficiency virus ( HIV ) -infected subjects with 200-500 CD4 cells/mm3 at entry . The 352 subjects were prestratified by prior AZT use into stratum I ( 235 subjects , > 6 months AZT at entry ) and stratum II ( 117 subjects , < or = 6 months AZT at entry ) . Clinical end points , CD4 cell counts , serum p24 , serum immune complex dissociated ( ICD ) p24 , and safety variables were evaluated through 48 weeks , using an intent-to-treat analysis . The two strata were analyzed individually because they yielded different clinical outcomes , with a statistically significant treatment-by-stratum interaction . In stratum I ( mean , 16 months AZT at entry ) two AIDS or death events occurred in thymopentin and 10 in placebo recipients ( p = 0.024 ; relative risk ( RR ) estimate , 4.9 [ 95 % confidence limit ( CI ) , 1.1 to 22.2 ] ) . There were three AIDS-related complex ( ARC ) , AIDS , or death events in thymopentin and 18 in placebo recipients [ p = 0.001 ; RR estimate , 5.9 ( 95 % CI , 1.7 to 20.0 ) ] . In stratum II ( mean , 3 months AZT at entry ) , four AIDS or death events occurred in thymopentin and none in placebo recipients ( p = 0.11 ) , and four ARC , AIDS , or death events occurred in thymopentin and two in placebo recipients ( p = 0.79 ) . The treatment groups did not differ significantly with respect to changes in CD4 counts or p24 antigen levels or with respect to clinical adverse experiences or laboratory abnormalities . Thus , AZT-experienced placebo-treated subjects had relatively high progression rates to AIDS or death and to ARC , AIDS , or death , and these rates were reduced by thymopentin treatment . In contrast , placebo-treated subjects with little prior AZT experience had low progression rates ; these were not significantly changed by thymopentin treatment . There was no increase in the incidence of adverse reactions with thymopentin .

Thymopentin

placebo-controlled

placebo

Safety and efficacy of thymopentin

safety variables

AIDS or death events

AIDS or death events

ARC , AIDS , or death events

CD4 counts or p24 antigen levels

clinical adverse experiences

laboratory abnormalities .

adverse reactions


Neuroendocrine effects of sumatriptan . The neuroendocrine effects of the 5-HT receptor agonist , sumatriptan ( 6 mg subcutaneously ) , were studied in 11 healthy male subjects using a placebo-controlled , cross-over design . Compared to placebo , sumatriptan significantly lowered levels of plasma prolactin but increased those of plasma growth hormone . There was no effect on plasma cortisol concentrations . The neuroendocrine effects of sumatriptan differ from those of previously described 5-HT-receptor agonists , and may be a consequence of selective activation of 5-HT1D or 5-HT1B receptors . However , the present data can not exclude the possibility that the neuroendocrine changes reflect nonspecific stress responses or changes in pituitary blood flow .

sumatriptan

sumatriptan ( 6 mg subcutaneously )

placebo-controlled

placebo

sumatriptan

sumatriptan

Neuroendocrine effects

plasma prolactin

plasma growth hormone .

plasma cortisol concentrations .

11 healthy male subjects


The effect of eradication of Helicobacter pylori upon the duodenal ulcer recurrence -- a 24 month follow-up study . OBJECTIVES To evaluate the effect of eradication of Helicobacter pylori ( H.pylori ) in the patients with duodenal ulcer ( Du ) upon the DU recurrence . METHODS This study was performed for 190 patients with DU . Four different methods-microscopy of Gram stained mucosal smear , specific culture , biopsy urease test , histology of H & E staining-were taken for identifying colonization of H. pylori before treatment , and for finding the eradication of H. pylori 4 weeks after completion of therapy in each treatment group ( cometidine , omeprazole , colloidal bismuth subcitrate ( CBS ) , CBS and metronidazole double therapy , CBS , metronidazole and amoxicillin triple therapy ) . To detect DU recurrence , the gastroscopy was performed at 6 , 12 , 18 , and 24 months after therapy . RESULTS The eradication rate of the cimetidine group the omeprazole group , and the CBS group were 0 % , 7.7 % , 0 % , respectively , and that of the double therapy group and the triple therapy group were 44.4 % and 89.3 % , respectively . Seventy three patients who were followed up for 2 years were categorized into two groups according to the eradication of H. pylori . The recurrence rate was 3.2 % both in 1 year and 2 years later in the former group-one consisting of 31 patients with H. pylori eradicated , while the recurrence rate was 57.1 % in 1 year and 78.6 % in 2 years later , in the latter group-the other of 42 patients with H. pylori not eradicated . CONCLUSION The eradication of H. pylori in patients with DU reduces the recurrence of DU .

cimetidine

omeprazole

double therapy

duodenal ulcer recurrence

eradication

DU recurrence

Gram stained mucosal smear

specific culture

biopsy urease test

histology of H & E staining-were

DU recurrence

gastroscopy

eradication rate

eradication of H. pylori

recurrence rate

recurrence rate

recurrence of DU

duodenal ulcer ( Du )

DU

Seventy three

H. pylori

DU


Effect of omega 3 fatty acids and vitamin E supplements on lipid peroxidation measured by breath ethane and pentane output : a randomized controlled trial .

breath ethane

pentane output

lipid peroxidation


Randomized , prospective comparison of halothane , isoflurane , and enflurane on baroreflex control of heart rate in humans .

halothane

isoflurane

enflurane

control of heart rate


Vitamin C and acute illness in Navajo school children . To evaluate earlier observations , including our own , showing usefulness of vitamin C for managing the common cold , we performed a double-blind trial of vitamin C versus placebo in 868 children . There was no difference in number becoming ill ( 133 versus 129 ) , number of episodes ( 166 versus 159 ) or mean illness duration ( 5.5 versus 5.8 days ) between the groups . Children receiving vitamin C had fewer throat cultures yielding beta-hemolytic streptococcus ( six versus 13 , P less than 0.10 ) , but no difference in overall complicated illness rate ( 24 versus 25 ) . Plasma ascorbic acid levels were higher in the vitamin group 24 to 26 hours after supplementation ( 1.28 versus 1.04 mg per 100 ml , P less than 0.01 ) . Children with high plasma ascorbic acid concentrations had longer mean illness ( 6.8 versus 4.0 days , P less than 0.05 ) than those with low levels . Vitamin C does not seem to be an effective prophylactic or therapeutic agent for upper respiratory illness .

Vitamin C

vitamin C

vitamin C

placebo

Vitamin C

number becoming ill

number of episodes

mean illness duration

throat cultures

beta-hemolytic streptococcus

overall complicated illness rate

Plasma ascorbic acid levels

mean illness

Navajo school children .


Gastric ulcer treatment with intravenous human epidermal growth factor : a double-blind controlled clinical study . We introduced a double-blind controlled clinical study to compare intravenous human epidermal growth factor ( hEGF ) to cetraxate hydrochloride ( CH ) , an antiulcer drug , for their healing effect on gastric ulcers . We also prospected an oral use of EGF on the basis of our experimental evidence . In the clinical trial , the rate of ulcer healing within 8 weeks was 77.9 % ( 67/86 ) in patients receiving 6 micrograms EGF intravenously twice a week , being significantly greater than 51.7 % ( 45/87 ) in those given CH . Taking together all aspects assessed including the healing rate , pain relief , blood examination and adverse reactions , we judged the hEGF to be a useful and safe anticuler drug . In rats , 50 micrograms/kg mouse EGF ( mEGF ) and 2 % hydroxypropyl cellulose ( HPC ) or 1.0 g/kg sucralfate given by gastric intubation significantly raised the residual mEGF levels in both gastric luminal content ( HPC : x 30 ; sucralfate : x 300 as high as those in EGF alone ) and tissue ( HPC : x 60 ; sucralfate : x 100 ) . In addition , the combined treatments significantly promoted healing of rat gastric ulcers whereas each agent alone had no significant effect as compared with control ( saline ) . This indicated the beneficial effect on ulcers of oral administration of EGF with agents allowing it to remain at high levels in the stomach , whereas most reports suggested less effect of oral EGF on healing of gastroduodenal ulcers . Subsequent to the clinical study , evaluation of oral use of EGF may be expected as the next step in the treatment of ulcers . The experimental evidence above would possibly be a guide for such trial .

human epidermal growth factor

cetraxate hydrochloride ( CH )

EGF

EGF

CH

hEGF

hydroxypropyl cellulose

EGF

EGF

gastric ulcers

rate of ulcer healing

healing rate

pain relief

blood examination

adverse reactions

residual mEGF levels

healing of rat gastric ulcers

Gastric ulcer

gastric ulcers


Analysis of multiple-dose bioequivalence studies . In multiple-dose bioequivalence studies , it is possible at steady state to take repeated measurements of pharmacokinetic variables , such as area under the curve ( AUC ) and the maximum concentration ( CMAX ) of the blood concentration-time profile , within each period of a crossover design . We develop a bivariate random effects model for such a situation in a 2 x 2 crossover design using the natural log scale for AUC and CMAX that assumes no differential carryover effects and includes components for inter- and intrasubject variability with respect to both formulations . We derive the uniformly minimum variance unbiased estimators , which also happen to be restricted maximum likelihood estimators , and we provide a sample size formula .

multiple-dose bioequivalence studies

pharmacokinetic variables

area under the curve ( AUC )

maximum concentration ( CMAX )

bivariate random effects model

natural log scale for AUC and CMAX

multiple-dose bioequivalence studies