Altered peripheral vasodilator profile of nitroglycerin during long-term infusion of N-acetylcysteine . OBJECTIVES The aim of this study was to compare the short- and long-term effects of intravenous nitroglycerin plus placebo and nitroglycerin plus N-acetylcysteine on peripheral arteries , veins and microcirculation in humans . BACKGROUND The thiol donor N-acetylcysteine may potentiate the hemodynamic response to nitrates in nitrate-tolerant and nontolerant patients . The vascular changes responsible for this effect are not clear . METHODS Eight male volunteers were treated with nitroglycerin ( 0.1 microgram/kg per min ) combined with N-acetylcysteine ( 2 g intravenously , followed by 5 mg/kg per h ) or placebo for 23 h in a double-blind , randomized , crossover study . Venous volume , the diameter of the radial and temporal arteries , calf blood flow and subcutaneous blood flow were measured at baseline and repeated after 1 and 23 h of infusion . RESULTS Prolonged coadministration of N-acetylcysteine and nitroglycerin potentiated the acute venodilator effect of nitroglycerin as estimated by changes in venous volume ( nitroglycerin plus N-acetylcysteine , 4.45 +/- 0.36 ml/100 g ; nitroglycerin plus placebo , 3.65 +/- 0.46 ml/100 g , mean +/- SEM , p < 0.05 ) and prevented development of tolerance as seen after 23 h of treatment with nitroglycerin plus placebo ( 4.35 +/- 0.25 vs. 3.47 +/- 0.41 ml/100 g , p < 0.05 ) . N-acetylcysteine had no effect on nitroglycerin-induced changes in arterial diameters ( p > 0.05 ) but significantly increased microcirculatory subcutaneous blood flow after 1 h ( nitroglycerin plus N-acetylcysteine : 6.3 +/- 1.3 ml/100 g per min vs. nitroglycerin plus placebo : 3.5 +/- 0.3 ml/100 g per min , p < 0.05 ) and after 23 h ( 4.4 +/- 0.6 vs. 3.1 +/- 0.5 ml/100 g per min , p < 0.05 ) . CONCLUSIONS The results suggest that coadministration of nitroglycerin and N-acetylcysteine in humans 1 ) potentiates and preserves nitroglycerin-induced venodilation and 2 ) augments the effect of nitroglycerin on small resistance vessels ( regulating subcutaneous blood flow ) without affecting the response to nitroglycerin in middle-sized arteries . Both the development of nitrate tolerance and the administration of N-acetylcysteine significantly change the normal vasodilator profile of nitroglycerin in humans .

intravenous nitroglycerin plus placebo

nitroglycerin plus N-acetylcysteine

N-acetylcysteine

N-acetylcysteine

placebo

N-acetylcysteine and nitroglycerin

nitroglycerin plus N-acetylcysteine

nitroglycerin plus placebo

N-acetylcysteine

nitroglycerin-induced

nitroglycerin plus N-acetylcysteine

nitroglycerin plus placebo

nitroglycerin and N-acetylcysteine

nitroglycerin-induced

N-acetylcysteine

nitroglycerin

peripheral vasodilator profile

short- and long-term effects

Venous volume

subcutaneous blood flow

acute venodilator effect

changes in venous volume

development of tolerance

nitroglycerin-induced venodilation

regulating subcutaneous blood flow

nitrate tolerance

vasodilator profile

Eight

male


A workplace intervention for increasing outdoor workers ' use of solar protection . OBJECTIVES Outdoor workers are at high risk of developing skin cancer . Primary prevention in this group can potentially reduce the incidence of skin cancer , and also potentiates the spontaneous remission of existing solar keratoses . A randomized controlled trial was conducted to evaluate a solar protection intervention targeting outdoor workers . METHODS Outdoor workers were randomly allocated to an intervention ( n = 65 ) or control group ( n = 77 ) . The intervention group received individual skin screening by a dermatologist and participated in an education session . Pre- and posttest outcome measures included solar protection behavior ( assessed using a validated diary ) , knowledge , and attitudes . RESULTS There was a significant increase ( 16 % ) in the percentage of outdoor workers who were using a high level of solar protection at posttest compared to pretest in the intervention group , but there was no change in the control group . Although both groups improved in their knowledge score , the intervention group showed a significantly greater improvement at posttest . No changes in attitudes were detected . CONCLUSIONS The findings suggest that changes in solar protection are achievable with outdoor workers .

workplace intervention

solar protection intervention

intervention

control group

solar protection behavior

knowledge

attitudes

significant increase

high level of solar protection

no change

improved

knowledge score

No changes in attitudes

solar protection


Omeprazole ameliorates aspirin-induced gastroduodenal injury . Aspirin and nonsteroidal antiinflammatory drugs ( NSAIDs ) damage the gastroduodenal epithelium by two mechanisms : direct toxic effects and effects related to the depletion of endogenous prostaglandins . The prostaglandin-depleted mucosa has increased susceptibility to luminal aggressive factors , yet the role of acid in the pathogenesis of the NSAID ulcer is controversial . In humans , standard doses of H2-receptor antagonists prevent only duodenal injury and provide no protection for the gastric mucosa . It is not known whether more potent suppression of acid can prevent NSAID damage . Twenty healthy volunteers were randomized to a double-blind , placebo-controlled , crossover study to determine if omeprazole , 40 mg/day prevents gastroduodenal injury due to two weeks of aspirin administration ( 650 mg four times a day ) . The severity of mucosal injury was quantitated by endoscopy and stratified by a scale from 0 ( normal ) to 4 ( ulcer ) . Fourteen of the 20 subjects had less gastric injury during cotherapy with omeprazole . All six with no difference received aspirin plus omeprazole in the first treatment period . Omeprazole significantly decreased aspirin-induced gastric mucosal injury ( P < 0.001 , Wilcoxon signed-rank test ) . Omeprazole protected 85 % of subjects from extensive gastric erosions ( often associated with evidence of intraluminal bleeding ) or ulceration , whereas 70 % of the subjects developed aspirin-induced grades 3 and 4 gastric injury on placebo ( P < 0.01 by chi 2 ) . No subject taking omeprazole developed duodenal injury of any grade , while 50 % taking placebo developed erosions and 15 % had ulcer ( P < 0.001 ) . Medication side effects were mild in the majority of subjects . ( ABSTRACT TRUNCATED AT 250 WORDS )

Omeprazole

NSAID

omeprazole , 40 mg/day

aspirin administration

omeprazole .

omeprazole

aspirin-induced

Omeprazole

aspirin-induced

omeprazole

placebo

severity of mucosal injury

gastric injury

aspirin-induced gastric mucosal injury

extensive gastric erosions

ulceration

duodenal injury of any grade

erosions

ulcer

gastroduodenal injury .


Naltrexone in autistic children : behavioral symptoms and attentional learning . OBJECTIVE To assess critically the short-term efficacy and safety of naltrexone in autistic children and its effects on discrimination learning in the laboratory . METHOD A parallel group design was employed . After a 2-week placebo baseline period , children were randomly assigned either to naltrexone or to placebo for a period of 3 weeks followed by a one-week posttreatment placebo period . Multiple raters and rating scales were employed in a variety of conditions . Forty-one children , all inpatients , ages 2.9 to 7.8 years , completed the study . Naltrexone reduced hyperactivity and had no effect on discrimination learning in the laboratory . There was a suggestion that it had a beneficial effect on decreasing self-injurious behavior . Untoward effects were mild and transient . CONCLUSION In the present study , naltrexone significantly reduced only hyperactivity , and no serious untoward effects were observed . The effectiveness of naltrexone in the treatment of autism and self-injurious behavior requires additional assessment in a sample of children with moderate to severe self-injurious behavior .

Naltrexone

naltrexone

naltrexone

placebo

Naltrexone

naltrexone

efficacy and safety

hyperactivity

discrimination learning

self-injurious behavior

Untoward effects

hyperactivity

serious untoward effects

autistic

children

autistic

children

Forty-one

children

inpatients

2.9 to 7.8 years

hyperactivity


The incidence of first-dose hypotension with quinapril in patients with mild to moderate hypertension . A total of 2242 patients with mild to moderate hypertension ( diastolic pressure 95-120 mmHg ) were randomised on a double-blind basis to receive a single dose of placebo , 5 mg quinapril or 10 mg quinapril . Patients were identified who : ( a ) met the blood pressure ( BP ) criteria for first-dose hypotension ( sitting or standing systolic BP < 100 mmHg , or a fall in systolic BP > or = 20 mmHg on standing ) ; ( b ) had symptoms suggestive of hypotension ; and ( c ) met the BP criteria and had symptoms . In all three classifications there were no statistically significant differences between the incidences in placebo and combined active treatment groups , or between those in the two quinapril groups . No associated serious adverse events were reported . In the low-risk population studied , it would appear that the incidence of first-dose hypotension with quinapril is similar to placebo and is not dose-related .

quinapril

placebo

quinapril

quinapril

blood pressure

associated serious adverse events

mild to moderate hypertension

mild to moderate hypertension

symptoms suggestive of hypotension

low-risk population


[ Hemostatic balance during treatment with the newest contraceptives ] . Thirty-four healthy young women were allocated to 12 consecutive cycles of treatment with monophasic combinations of : 20 micrograms ethinyl estradiol and 150 micrograms desogestrel ( n = 15 ) or 30 micrograms ethinyl estradiol and 75 micrograms gestodene ( n = 19 ) . In both groups plasma levels of fibrinogen and factor VII increased while the capacity of coagulation inhibition was affected by increased protein C and decreased protein S levels . Increased fibrinolytic capacity was indicated by elevated activity and reduced antigen levels of tissue plasminogen activator and reduced activity and concentration of tissue plasminogen activator inhibitor . The ratio between thrombin-antithrombin-III-complexes and fibrin degradation products were unchanged signifying no effect of hormonal intake on the balance between thrombin formation and fibrin resolution . In conclusion , the dynamic balance between generation and resolution of fibrin was undisturbed during treatment with both hormonal compounds and our findings do not provide evidence for increased risk of thrombosis in normal women .

150 micrograms desogestrel

30 micrograms ethinyl estradiol

75 micrograms gestodene

fibrinolytic capacity

Thirty-four

healthy

young women

normal

women


Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) allows acceleration and dose intensity increase of CEF chemotherapy : a randomised study in patients with advanced breast cancer . A randomised study was conducted in 62 patients with advanced breast cancer to assess whether granulocyte-macrophage colony-stimulating factor ( GM-CSF ) would yield an increase in the dose intensity of a standard-dose CEF regimen through an acceleration of chemotherapy administration . Patients received CEF ( cyclophosphamide 600 mg m-2 , epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m-2 ) i.v . on day 1 or the same chemotherapy , plus GM-CSF 10 micrograms kg-1 s.c. starting from day 4 , repeated as soon as haematopoietic recovery from nadir occurred . Patients in the CEF + GM-CSF group received chemotherapy at a median interval of 16 days compared with 20 days in the control group . This led to a significant increase ( P = 0.02 ) in the dose intensity actually administered in the third , fourth and sixth cycles : +28 % , +25 % , +20 % respectively . Non-haematological toxicity was mild . GM-CSF had to be reduced or suspended in 50 % of patients because of toxicity . Haematological toxicity , mainly cumulative anaemia and thrombocytopenia , was manageable . An increase in response rate for patients with measurable disease , of borderline statistical significance ( P = 0.088 , P for trend = 0.018 ) , from 42 % in the CEF group to 69 % in the CEF + GM-CSF group , was observed . This randomised trial indicates that GM-CSF is useful for chemotherapy acceleration . Accelerated CEF + GM-CSF is a moderately dose-intensive regimen that can be administered in an outpatient clinic and is associated with a high objective response .

CEF chemotherapy

GM-CSF

standard-dose CEF regimen

chemotherapy

CEF

cyclophosphamide 600 mg m-2

epidoxorubicin 60 mg m-2

fluorouracil 600 mg m-2

chemotherapy

GM-CSF

CEF + GM-CSF

GM-CSF

CEF

CEF + GM-CSF

GM-CSF

CEF + GM-CSF

Non-haematological toxicity

toxicity

Haematological toxicity

cumulative anaemia and thrombocytopenia

response rate

patients with advanced breast cancer .

patients with advanced breast cancer


MR imaging of pituitary region lesions with gadodiamide injection . Twelve patients with known or suspected pituitary lesions underwent MR imaging with gadodiamide injection at a dose of 0.1 ( n = 5 ) or 0.3 ( n = 7 ) mM/kg . Six of the patients were also studied with 0.1 mM/kg gadopentetate dimeglumine . Consistent with previous reports gadodiamide injection was found to be a safe and effective contrast medium for MR imaging of the pituitary region . No additional diagnostic information was obtained using 0.3 mM/kg gadodiamide injection compared to 0.1 mM/kg gadopentate dimeglumine in the same patients . The high dose ( 0.3 mM/kg ) gadodiamide injection in 7 patients did not shorten the T2 value sufficiently to overwhelm the T1 shortening and leave pathologic lesions hypointense compared to precontrast studies . With the comparable relaxivities of gadodiamide injection and gadopentetate dimeglumine , similarities in results have to be expected when using these media for MR image enhancement .

gadodiamide

MR imaging

gadodiamide injection

0.1 mM/kg gadopentetate dimeglumine

gadodiamide

gadodiamide

gadodiamide

gadodiamide

gadopentetate dimeglumine

safe and effective

shorten the T2 value sufficiently

T1 shortening

and

leave pathologic lesions hypointense


Does wavelength matter when photocoagulating eyes with macular degeneration or diabetic retinopathy ?


Continuous chemotherapy in responsive metastatic breast cancer : a role for tumour markers ? A biochemical response index comprising ESR , CEA and CA 15.3 was evaluated in 67 patients with systemic breast cancer treated by chemotherapy ; 55 were assessable by UICC criteria and the response index ( 96 % of all UICC assessable patients ) . Marker changes at 2 and 4 months showed a highly significant correlation with the UICC assessed response at 3 and 6 months ( P < 0.001 ) ; sensitivity 100 % , specificity 87 % ; positive predictive value 85 % ; negative predictive value 100 % . This index was then used to select out truly responsive patients and to prospectively direct their chemotherapy . Twenty-six responding ( biochemical/clinical ) patients were randomised to discontinue cytotoxics after 6 months and move to maintenance hormones ( n = 13 ) or continue chemotherapy whilst the biochemical markers kept falling or remained within the normal range . Biochemical progression prompted a change of chemotherapy . Continuous chemotherapy in biochemically defined responders was associated with a significant lengthening of remission duration and an improved quality of life and survival . We are now using the index to routinely direct chemotherapy and select out true responders for maintenance chemotherapy .

Continuous chemotherapy

chemotherapy

continue chemotherapy

Continuous chemotherapy

lengthening of remission duration

improved quality of life

survival

metastatic breast cancer

assessable by UICC criteria


A program of screening and prompting improves short-term physician counseling of dependent and nondependent harmful drinkers . BACKGROUND Physicians in the general medical setting commonly encounter but rarely counsel patients with dependent or harmful drinking behaviors . We tested whether providing physicians with their patients ' results on the alcohol module of the Diagnostic Interview Schedule and counseling directives would prompt them to counsel these patients . METHODS We randomly assigned 83 first- , second- , and third-year medical residents to receive or not to receive diagnostic information and counseling directives on 214 patients who reported at least one symptom of alcohol impairment as defined in the Diagnostic and Statistical Manual of Mental Disorders , Third Edition . Using binary logistic regression , we examined the effect of specific covariables on rates of physician counseling . These variables included physician information status , patient gender , and drinking disorder severity and recency . We also examined the effect of physician prompting on counseling of female patients , patients with inactive disorders , and nondependent but harmful drinkers . We determined counseling by post-visit patient interviews . RESULTS Physician prompting , dependent drinking , and recent disorder activity were significant correlates of physician counseling ( P < .05 ) , while male gender was a marginally significant correlate ( P = .08 ) . Informed physicians counseled female patients , harmful but nondependent drinkers , and patients with inactive disorders more often than their uninformed colleagues , although only the last variable achieved statistical significance . CONCLUSIONS Providing physicians with the results of the Diagnostic Interview Schedule and counseling directives resulted in short-term improvement in their rates of counseling patients with a history of dependent or nondependent but harmful drinking . Further research is necessary to determine long-term gains in rates of physician counseling and improvements in the course of these patients .

binary logistic regression

physician counseling and improvements

Physician prompting

dependent drinking

recent disorder activity


Low-dose aspirin and incidence of colorectal tumors in a randomized trial . BACKGROUND Laboratory , clinical , and epidemiologic studies have recently suggested that regular use of aspirin can reduce colorectal cancer incidence or mortality . However , observational epidemiologic analyses have had limited opportunity to control for confounding bias or to specify aspirin doses used . PURPOSE Our purpose was to examine the relationship between regular use of low-dose aspirin and incidence of invasive and noninvasive colorectal tumors by utilizing data from the Physicians ' Health Study , a randomized , double-blinded , placebo-controlled trial of aspirin and beta carotene . We also attempted to determine whether invasive cancers among aspirin users were associated with rectal bleeding and early stage at diagnosis . METHODS The Physicians ' Health Study includes 22071 U.S. male physicians . The aspirin arm was terminated in 1988 after a mean follow-up of 5 years . Stage at diagnosis and signs and/or symptoms during presentation were abstracted from medical records . Cox proportional hazards models were used to estimate relative risk ( RR ) , 95 % confidence intervals ( CIs ) , and the association between aspirin and bleeding . Differences between aspirin and placebo groups in tumor risk over time were visualized with Kaplan-Meier curves . We assessed the association between aspirin and stage at diagnosis with a Mann-Whitney rank sum statistic for non-parametric comparison of two ordinal distributions . RESULTS The RR of developing colorectal cancer for aspirin compared with placebo was 1.15 ( 95 % CI = 0.80-1.65 ) . For in situ cancers and polyps , the RR was 0.86 ( 95 % CI = 0.68-1.10 ) . There was no significant trend for decreasing RR by year of follow-up for invasive cancers ( P = .09 ) or noninvasive tumors ( P = .96 ) . Aspirin and placebo groups did not differ in stage or prevalence of rectal bleeding at diagnosis . CONCLUSIONS Regular aspirin use , at a dose adequate for preventing myocardial infarction , was not associated with a substantial reduction in the incidence of colorectal cancer during 5 years of randomized treatment and follow-up . A small decrease in polyps in the aspirin group could not be reliably distinguished from a chance association . Our results suggest that among low-dose aspirin users , ( a ) colorectal cancer mortality is not likely to be reduced by earlier detection and ( b ) incidence is not likely to be increased due to aspirin-induced gastrointestinal bleeding . IMPLICATIONS The potential for a benefit from higher doses of aspirin or longer duration of use should be addressed by more detailed observational epidemiologic studies and prevention trials with longer follow-up of randomized participants .

Low-dose aspirin

aspirin

aspirin

low-dose aspirin

placebo-controlled

aspirin

beta carotene

aspirin

aspirin

placebo

aspirin

aspirin

relative risk

confidence intervals

RR

rectal bleeding

colorectal cancer

male


A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias . Electrophysiologic Study versus Electrocardiographic Monitoring Investigators . BACKGROUND The relative efficacies of various antiarrhythmic drugs in the treatment of ventricular tachyarrhythmias are not well known . This study examined the effectiveness of imipramine , mexiletine , pirmenol , procainamide , propafenone , quinidine , and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial . METHODS Patients were randomly assigned to undergo serial testing of the efficacy of the seven antiarrhythmic drugs by one of two strategies : electrophysiologic study or Holter monitoring together with exercise testing . The seven drugs were then tested for efficacy in random order in patients who were eligible to receive them . The frequencies of predictions of drug efficacy and of adverse drug effects during the initial drug titration were tabulated for all 486 randomized subjects . Patients received long-term treatment with the first antiarrhythmic drug that was predicted to be effective on the basis of drug testing . Recurrences of arrhythmia , deaths , and adverse drug effects during long-term follow-up were recorded for the 296 patients in whom an antiarrhythmic drug was predicted to be effective . RESULTS In the electrophysiologic-study group , the percentage of patients who had predictions of drug efficacy was higher with sotalol ( 35 percent ) than with the other drugs ( 16 percent , P < 0.001 ) . There was no significant difference among the drugs in the Holter-monitoring group . The percentage of patients with adverse drug effects was lowest among those receiving sotalol . The actuarial probability of a recurrence of arrhythmia after a prediction of drug efficacy by either strategy was significantly lower for patients treated with sotalol than for patients treated with the other drugs ( risk ratio , 0.43 ; 95 percent confidence interval , 0.29 to 0.62 ; P < 0.001 ) . With sotalol , as compared with the other drugs combined , there were lower risks of death from any cause ( risk ratio , 0.50 ; 95 percent confidence interval , 0.30 to 0.80 ; P = 0.004 ) , death from cardiac causes , ( 0.50 ; P = 0.02 ) , and death from arrhythmia ( 0.50 ; P = 0.04 ) . The cumulative percentage of patients in whom a drug was predicted to be effective and in whom it remained effective and tolerated was higher for sotalol than for the other drugs ( P < 0.001 ) . CONCLUSIONS Sotalol was more effective than the other six antiarrhythmic drugs in preventing death and recurrences of arrhythmia . In patients similar to those in this study , if antiarrhythmic-drug therapy is to be used to prevent recurrences of ventricular tachyarrhythmias , treatment with sotalol and assessment of its potential efficacy by Holter monitoring are a reasonable initial strategy .

antiarrhythmic drugs

imipramine

mexiletine

pirmenol

procainamide

propafenone

quinidine

sotalol

drug efficacy

higher

no significant difference

patients with adverse drug effects

lowest

significantly lower

lower risks of death

death from arrhythmia

ventricular tachyarrhythmias

ventricular tachyarrhythmias


Fusidic acid prophylaxis before cataract surgery : patient self-administration . In a placebo-controlled , randomised , double-blind clinical trial , the authors evaluated the efficacy of patient-administered 1 % fusidic acid viscous eye drops in clearing the commonest organisms causing pseudophakic endophthalmitis ( Staphylococcus epidermidis and aureus ) from the lids and conjunctivae of 79 patients before cataract surgery . The treatment group self-administered fusidic acid viscous eye drops four times daily for seven days before surgery ; the placebo group received inert ophthalmic drops . Fellow eyes of both groups remained untreated as a natural control . Lower fornix and lid margin cultures were taken from both eyes before and after treatment . Before treatment , there was no statistical difference in organism counts between the groups . After treatment , eyes receiving fusidic acid were more likely to be free of clinically relevant Staphylococcus spp . than all pre-treatment eyes ( for lids , P < 0.001 ; conjunctivae , P = 0.02 ) . A highly significant ( P < 0.001 ) number of lid margins were rendered 'clinically clean ' ( i.e. , 0-49 organisms/swab ) by fusidic acid when compared with untreated eyes . Treatment also effectively ( P < 0.05 ) reduced the numbers of bacteria isolated from conjunctivae . This study indicates that there is a highly significant reduction of Staphylococcus spp . ( P < 0.001 ) , non-Staphylococcus spp . ( P < 0.001 ) and attainment of sterile eyes ( P < 0.001 ) at operation gained by patient self-administration of 1 % fusidic acid four times daily for seven days before surgery .

fusidic acid viscous eye drops

fusidic acid

inert ophthalmic drops .

fusidic acid

organism counts

number of lid margins

79 patients


A randomised prospective study comparing the new vacuum extractor policy with forceps delivery . OBJECTIVE To compare assisted vaginal delivery by forceps with delivery by vacuum extractor , where a new vacuum extractor policy was employed which dictated the cup to be used in specific situations . DESIGN Multicentre randomised controlled trial . SETTING Four district general hospitals in the West Midlands . SUBJECTS Six hundred-seven women requiring assisted vaginal delivery , of whom 296 were allocated to vacuum extractor delivery and 311 to forceps . MAIN OUTCOME MEASURES Delivery success rate , maternal perineal and vaginal injuries , maternal anaesthetic requirements , neonatal scalp and facial injuries . RESULTS Of the vacuum extractor group , 85 % were delivered by the allocated instrument compared to 90 % in the forceps group ( odds ratio ( OR ) 0.64 ; 95 % confidence intervals ( CI ) 0.4-1.04 ) . However , more women in the vacuum extractor group were delivered vaginally ( 98 % ) than in the forceps group ( 96 % ) . There were significantly fewer women with anal sphincter damage or upper vaginal extensions in the vacuum extractor group ( 11 % vs 17 % , OR 0.6 ; 95 % CI , 0.38-0.97 ) . There were significantly fewer women in the vacuum extractor group requiring epidural or spinal anaesthetics ( 25.4 % vs 32.7 % , OR 0.69 ; 95 % CI 0.49-0.99 ) or general anaesthetics ( 1 % vs 4 % , OR 0.17 ; 95 % CI 0.04-0.76 ) . Although there were significantly more babies in the vacuum extractor group with cephalhaematomata ( 9 % vs 3 % , OR 3.3 ; 95 % CI 1.4-7.4 ) there were fewer babies in the vacuum extractor group with other facial injuries . There were three babies in the forceps group with unexplained neonatal convulsions . CONCLUSIONS Assisted vaginal delivery using the new vacuum extractor policy is associated with significantly less maternal trauma than with forceps . Further studies are required to assess neonatal morbidity adequately .

epidural or spinal anaesthetics

general anaesthetics

cephalhaematomata

facial injuries

unexplained neonatal convulsions

maternal trauma

Six hundred-seven

assisted vaginal delivery


A comparison of the effectiveness and patient tolerance of oral sodium phosphate , castor oil , and standard electrolyte lavage for colonoscopy or sigmoidoscopy preparation . One hundred thirteen patients were randomized to receive either oral sodium phosphate ( Fleet Phospho-Soda ) , lemon-flavored castor oil ( Purge ) , or standard polyethylene glycol-based lavage solution ( GoLYTELY ) before elective colonoscopy . The study purpose was to confirm the efficacy of oral sodium phosphate and extend observations to include castor oil . Overall , patients reported that sodium phosphate and castor oil were easier to complete ( p < 0.05 ) . Scores for cleansing the entire colon as determined by endoscopists who were blinded to the cathartic agent were highest in patients receiving sodium phosphate ( p < 0.02 ) . Scores of left-colon cleansing for flexible sigmoidoscopy were equally high for the three methods . Scores for taste and symptom side effects were similar for each preparation . There were no recognized signs or symptoms of hypocalcemia in the sodium phosphate group . Because of the low cost of oral sodium phosphate combined with the lowest repeat endoscopy rate for inadequate cleansing , patient savings were projected to be $ 5000 per 100 patients at this center . Oral sodium phosphate is a cost-effective colonoscopy preparation that is better tolerated and more effective than the polyethylene glycol-electrolyte lavage solution or castor oil .

lemon-flavored castor oil ( Purge )

sodium phosphate

castor oil

sodium phosphate

castor oil

sodium phosphate

sodium phosphate

sodium phosphate

castor oil

Scores for cleansing the entire colon

Scores for taste

and symptom side effects

signs or symptoms of hypocalcemia

patient savings


Prevention of regimen-related toxicities after bone marrow transplantation by pentoxifylline : a prospective , randomized trial . Elevated levels of tumor necrosis factor alpha ( TNF-alpha ) have been reported to correlate with the development of transplant-related complications after bone marrow transplantation ( BMT ) . In a recent phase I-II trial , oral administration of pentoxifylline ( PTX ) , a xanthine derivative capable of downregulating TNF-alpha production in vitro , was reported to reduce morbidity and mortality in patients undergoing BMT . We conducted a prospective randomized trial of PTX therapy among 140 patients undergoing either allogeneic ( n = 51 ) or autologous BMT ( n = 89 ) . Patients were randomized to receive ( n = 70 ) or not receive ( n = 70 ) oral PTX , 1,600 mg/d in four divided doses from day -8 until day + 100 post-BMT . The incidence of mucositis requiring morphine sulfate ( MSO4 ) was similar in both groups ( 42.9 % ) , with the mean number of days with MSO4 being 7.8 ( SD = 3.4 ) in the PTX group versus 8.2 ( SD = 3.4 ) in the control group ( NS ) . The incidence of renal insufficiency was not affected by PTX administration ( 15.7 % in the PTX group v 21.4 % in the control group [ NS ] ) and the highest serum creatinine value during the first 100 days post-BMT was 119 mumol/L ( SD = 82.4 ) in the PTX group versus 103.9 mumol/L ( SD = 57 ) in the control group ( NS ) . The incidence of grade > or = 2 graft-versus-host disease was similar in each group ( 11/25 [ 44 % ] in the PTX group v 12/26 [ 46 % ] in the control group ) . No significant difference was observed in hematologic toxicity , transfusion requirements , duration of fever , and hepatic toxicity between the treatment groups . In conclusion , our study failed to show a prophylactic effect of PTX in transplant-related toxicities after BMT . On the basis of these findings , we can not recommend that PTX be part of early mortality and morbidity prevention programs after BMT .

pentoxifylline

pentoxifylline ( PTX )

PTX

PTX

PTX

PTX

PTX

incidence of renal insufficiency

serum creatinine value

hematologic toxicity

transfusion requirements

duration of fever

hepatic toxicity

bone marrow transplantation ( BMT ) .

BMT

BMT

BMT


A multicenter study on the use of pulsed low-intensity direct current for healing chronic stage II and stage III decubitus ulcers . BACKGROUND AND DESIGN Pulsed low-intensity direct current ( 300 to 600 microA ) has been used in a double-blind placebo multicenter study in the treatment of stage II and stage III chronic decubitus ulcers . RESULTS Seventy-four ulcers were treated in four centers . Forty-three patients were selected for the experimental group , and 31 control subjects used the sham instrument ( placebo group ) . In the treated group , 25 ulcers ( 58 % ) healed in 8 weeks , whereas in the placebo group , only one ulcer ( 3 % ) healed and most ulcers increased in size . Statistical analysis , based on surface area and ulcer depth before and after treatment , showed that low-intensity direct current had a significant influence on the healing rates for these ulcers ( P < .0001 ) . Experiments with guinea pigs ( n = 10 ) showed that pulsed low-intensity direct current caused a rapid calcium flux in the epidermis . CONCLUSIONS Pulsed low-intensity direct current represents a useful approach for the treatment of stage II and stage III chronic decubitus ulcers by increasing the healing rate . The growth of fibroblasts and keratinocytes may be enhanced by pulsed low-intensity direct current due to changes in calcium homeostasis .

pulsed low-intensity direct current

sham instrument ( placebo group ) .

low-intensity direct current

pulsed low-intensity direct current

Pulsed low-intensity direct current

pulsed low-intensity direct current

ulcers

ulcer

healing rates

rapid calcium flux

calcium homeostasis

chronic stage II

stage III decubitus ulcers

stage II

stage III chronic decubitus ulcers

Seventy-four

ulcers

Forty-three


Use of activated charcoal in a simulated poisoning with acetaminophen : a new loading dose for N-acetylcysteine ? STUDY OBJECTIVES To investigate the ability of a supranormal dose of N-acetylcysteine to overcome the effects of activated charcoal on N-acetylcysteine bioavailability and to determine the effects of activated charcoal on serum acetaminophen levels . DESIGN , SETTING , AND PARTICIPANTS Ten healthy adult volunteers participated in a controlled cross-over experiment . During phase I ( control ) , subjects ingested 3 g acetaminophen , followed one hour later by the normal loading dose of N-acetylcysteine ( 140 mg/kg ) . During phase II ( charcoal ) , subjects ingested 3 g acetaminophen , followed one hour later by 60 g activated charcoal and a supranormal loading dose of N-acetylcysteine ( 235 mg/kg ) . MAIN OUTCOME MEASURES Serum levels of N-acetylcysteine were measured every 30 minutes for six hours . A serum acetaminophen level was measured at four hours . RESULTS The area under the curve for N-acetylcysteine was significantly higher for phase II than phase I ( P < .05 , two-tailed paired t-test ) . Peak N-acetylcysteine and time to peak were not significantly different . The four-hour serum acetaminophen level was significantly lower for phase II than phase I ( P < .05 , two-tailed paired t-test ) . Diarrhea occurred during both phases , but N-acetylcysteine was otherwise well tolerated . CONCLUSION These results suggest that activated charcoal can be used safely for victims of acetaminophen overdose . A beneficial effect in preventing acetaminophen absorption can be expected if it is given within one hour after ingestion . If N-acetylcysteine is needed because of a toxic serum acetaminophen level , bioavailability can be ensured by increasing the N-acetylcysteine loading dose from 140 mg/kg to 235 mg/kg .

N-acetylcysteine

N-acetylcysteine

acetaminophen

N-acetylcysteine

3 g acetaminophen

N-acetylcysteine

N-acetylcysteine

N-acetylcysteine

N-acetylcysteine

N-acetylcysteine

Serum levels of N-acetylcysteine

serum acetaminophen level

Peak N-acetylcysteine

time to peak

four-hour serum acetaminophen level

Diarrhea

tolerated

poisoning with acetaminophen

Ten

adult volunteers

acetaminophen overdose


Early versus late replacement of autotransfused blood in elective spinal surgery . A prospective randomized study . The use of autologous blood is a well established and extremely popular technique to decrease the necessity for homologous transfusions and the attendant risks of hepatitis , HIV , and HTLV -- I/II infections . The most beneficial timing for autologous reinfusion of predonated blood remains unknown . The present study was undertaken to determine the optimal timing of autologous blood reinfusion in elective spinal surgery . Fifty-seven patients were prospectively individually randomly allocated into early versus delayed reinfusion groups prior to undergoing elective spinal surgery by a single surgeon . Three surgical subgroups were entered into the study : anterior/posterior ( A/P ) spinal fusion patients , posterior thoracolumbar scoliosis fusion patients ( PSF ) , and degenerative posterior lumbar fusion patients ( LF ) . Randomization was successful in that three was no significant difference in male to female ratio , age , preoperative hemoglobin , or number of units predonated between the early and delayed reinfusion groups . Likewise , there was no significant difference in the details of the operative procedure when compared as a group for the early versus delayed reinfusion groups . A significant increase in the postoperative day # 1 , 2 and 3 hemoglobin was seen in the early reinfusion group , while there was no significant difference seen in the postoperative day # 7 hemoglobin between the early versus delayed reinfusion group . There was no effect of surgical grouping on these significant comparisons . Earlier patient mobilization was also seen in the early reinfusion groups for the A/P and PSF groups . There was no difference in patients ' subjective evaluation of satisfaction and discomfort between the early or delayed reinfusion groups as determined by blinded interview on days 1 , 3 , 5 , and 7 postoperatively . ( ABSTRACT TRUNCATED AT 250 WORDS )

Early

late replacement

autotransfused blood

spinal surgery

autologous blood

autologous

autologous blood reinfusion

spinal surgery

early

delayed reinfusion groups

elective spinal surgery

early

delayed reinfusion

early reinfusion group

early

delayed reinfusion

early reinfusion

day # 1 , 2 and 3 hemoglobin

patient mobilization

elective spinal surgery .

undergoing elective spinal surgery


Torasemide versus furosemide in cirrhosis : a long-term , double-blind , randomized clinical study . The effects of long-term therapy ( 70 days ) with torasemide ( 20 mg/day ) , a new loop diuretic , were compared with those of furosemide ( 50 mg/day ) in a randomized double-blind trial . Both drugs were administered in association with spironolactone ( 200 mg/day ) in 28 nonazotemic cirrhotic patients with controlled ascites . The treatments did not modify creatinine clearance and exhibited a similar effect on body weight , urinary volume , and fractional excretion of uric acid , sodium , and chloride . The effect of torasemide on fractional potassium excretion was lower than that of furosemide . Torasemide showed higher sparing effect than furosemide on calcium , inorganic phosphate , and magnesium excretion and stronger action on free water clearance . No changes in serum parameters were induced by either treatment . Two episodes of hepatic encephalopathy occurred in the torasemide group . In view of its effects on sodium and water excretion and on other urinary parameters , torasemide can represent an alternative tool for the long-term treatment of ascites .

Torasemide

furosemide

torasemide

furosemide

spironolactone

torasemide

furosemide

Torasemide

furosemide

torasemide

torasemide

creatinine clearance

body weight , urinary volume

fractional potassium excretion

free water clearance

serum parameters

hepatic encephalopathy

effects on sodium and water excretion

on other urinary parameters


A prospective randomised comparison of the dynamic hip screw and the gamma locking nail . We made a randomised prospective comparison of the Dynamic Hip Screw and the Gamma locking nail for the internal fixation of 200 petrochanteric femoral fractures in elderly patients . There was less intraoperative blood loss and a lower rate of wound complications in the patients treated by the Gamma nail . They had , however , a high incidence of femoral shaft fracture which we relate in part to implant design . We do not recommend the use of the Gamma nail for these fractures .

dynamic hip screw

gamma locking nail

Dynamic Hip Screw

the

Gamma locking nail

Gamma nail

Gamma nail

femoral shaft fracture

dynamic hip screw

gamma locking nail

petrochanteric femoral fractures

elderly


Coping with distress and self harm : the impact of a primary prevention program among adolescents . The effectiveness of a school-based primary prevention psychological program is assessed in the present study . The program was designed to ( a ) improve students ' distress-coping , ( b ) prepare them as " gatekeepers " with regard to self-destructive behavior of peers and ( c ) assess the program 's face validity and social validity . The program was primarily based on cognitive-behavioral modification principles , procedures and techniques . Two hundred and thirty-seven students , drawn from six homeroom grade eight classes were randomly assigned to experimental and control ( no intervention ) conditions . The program consisted of seven units passed during twelve weekly one-hour sessions . Overall , the program had a positive effect on attitudes , emotions , knowledge and awareness of distress coping skills . In addition , it had some degree of face validity and social validity from the students ' vantage point . These results lend support to the feasibility of a cognitive-behavioral , school-based prevention program for students ' distress-coping enhancement .

primary prevention program

distress-coping

face validity

social validity

face validity and social validity

adolescents

Two hundred and thirty-seven


Video rating analysis of effect of maprotiline in patients with dementia and depression . In patients with dementia and mild depression ( DSM-III-R 290.21 ) , the effect of low doses of the antidepressant maprotiline ( up to 75 mg/d ) was examined . The main parameter was a video rating of global impression . The Mini-Mental State Examination ( MMS ) and the Geriatric Depression Scale ( GDS ) were applied to evaluate the effect of maprotiline on cognitive and depressive symptoms . The double-blind , placebo-controlled trial was of eight weeks ' duration and included 127 patients , randomized in two groups . The antidepressant effect of maprotiline was reflected in the GDS . There was , however , no indication of an effect of maprotiline on cognitive performance . The global impression , evaluated by video rating , gave no indication as to a beneficial effect of the treatment . - The video analysis showed a significant interrater reliability . The discrepancy between the results of the video rating and the GDS is discussed . - The results confirm similar findings of other authors ; i.e. , that a sedating antidepressant with some anticholinergic effects can not be expected to improve cognitive functions despite its antidepressant effect . The main interest of this study , however , lies in its methodology ( video analysis ) .

maprotiline

Mini-Mental State Examination ( MMS )

Geriatric Depression Scale ( GDS )

placebo-controlled

maprotiline

Mini-Mental State Examination

Geriatric Depression Scale

cognitive performance

reliability

cognitive functions

patients with dementia and depression .


Sodium-potassium pump activity in white blood cells from children with an increased risk of developing hypertension -- The Odense Schoolchild Study . We have measured the capacity of the sodium-potassium pump , as assessed by 86rubidium uptake and the number of [ 3H ] -ouabain binding sites on white blood cells , in children aged 9-11 years , partly cross-sectionally and partly longitudinally after a physical training programme . Children from a hypertensive subgroup comprising the upper 5 % of the blood pressure distribution and children from a randomly selected normotensive subgroup were eligible for the study . In the cross-sectional study 40 children from the hypertensive subgroup and 40 children from the normotensive subgroup were evaluated . A significant increase in 86rubidium uptake was present in boys as compared to girls . After adjustment for differences in sexual maturation the observed significant difference disappeared . Important correlates of pump activity were height , plasma glucose , and physical fitness . In the training study 10 boys from the hypertensive subgroup and 10 boys from the normotensive subgroup were also evaluated after eight months of physical training . A significant fall in 86rubidium uptake was observed . No control group was examined and probably the changes reflect some effects of sexual maturation on cation handling of cells . These results indicate a significant effect of sexual maturation in capacity of sodium-potassium pump in children .

Sodium-potassium pump activity

sodium-potassium pump

physical training programme .

pump activity

sodium-potassium pump

86rubidium uptake

86rubidium uptake

children

hypertension

children

Children

hypertensive

children

children

hypertensive

boys

hypertensive

boys

children


Radiation-induced brachial plexopathy : neurological follow-up in 161 recurrence-free breast cancer patients . PURPOSE The purpose was to assess the incidence and clinical manifestations of radiation-induced brachial plexopathy in breast cancer patients , treated according to the Danish Breast Cancer Cooperative Group protocols . METHODS AND MATERIALS One hundred and sixty-one recurrence-free breast cancer patients were examined for radiation-induced brachial plexopathy after a median follow-up period of 50 months ( 13-99 months ) . After total mastectomy and axillary node sampling , high-risk patients were randomized to adjuvant therapy . One hundred twenty-eight patients were treated with postoperative radiotherapy with 50 Gy in 25 daily fractions over 5 weeks . In addition , 82 of these patients received cytotoxic therapy ( cyclophosphamide , methotrexate , and 5-fluorouracil ) and 46 received tamoxifen . RESULTS Five percent and 9 % of the patients receiving radiotherapy had disabling and mild radiation-induced brachial plexopathy , respectively . Radiation-induced brachial plexopathy was more frequent in patients receiving cytotoxic therapy ( p = 0.04 ) and in younger patients ( p = 0.04 ) . The clinical manifestations were paraesthesia ( 100 % ) , hypaesthesia ( 74 % ) , weakness ( 58 % ) , decreased muscle stretch reflexes ( 47 % ) , and pain ( 47 % ) . CONCLUSION The brachial plexus is more vulnerable to large fraction size . Fractions of 2 Gy or less are advisable . Cytotoxic therapy adds to the damaging effect of radiotherapy . Peripheral nerves in younger patients seems more vulnerable . Radiation-induced brachial plexopathy occurs mainly as diffuse damage to the brachial plexus .

adjuvant therapy

postoperative radiotherapy

with 50 Gy

cytotoxic therapy

tamoxifen

Cytotoxic therapy

Radiation-induced brachial plexopathy

paraesthesia

hypaesthesia

weakness

decreased muscle stretch reflexes

pain

recurrence-free breast cancer

younger


Subcutaneous low-molecular-weight heparin compared with continuous intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis . BACKGROUND A low-molecular-weight heparin , enoxaparin sodium , has been shown to be effective and safe in preventing deep vein thrombosis both in general surgery and in high-risk orthopedic surgery . We conducted a controlled , randomized trial with enoxaparin in the treatment of established deep vein thrombosis . METHODS In a multicenter trial , we compared fixed-dose subcutaneous enoxaparin , given twice daily , with adjusted-dose intravenous unfractionated heparin ( UFH ) given by continuous intravenous infusion for the initial 10 days of treatment of patients with proximal vein thrombosis . The primary efficacy outcome was the change of the size of the thrombus assessed by repeated venograms between day 0 and day 10 . The primary analysis of safety was based on the incidence of major bleeding during 10 days of treatment . RESULTS There were 67 patients in each group . Venographic assessment of clot size evolution between day 0 and day 10 showed a statistically significant superiority ( P < .002 ) of enoxaparin over the reference treatment with UFH . Moreover , the incidence of overall recurrent thromboembolic events during 10 days of treatment was significantly higher ( P < .002 ) in the UFH group ( seven of 67 ) than in the enoxaparin group ( one of 67 ) . There were no serious bleeding complications in either group . CONCLUSIONS Enoxaparin is at least as effective and safe as UFH under the conditions of this study . Moreover , it is more comfortable for patients and less time-consuming for nurses and laboratories . Thus , our study confirmed , with the use of enoxaparin , other observations that low-molecular-weight heparin provides a real therapeutic advance in the treatment of deep vein thrombosis .

low-molecular-weight heparin

unfractionated heparin

low-molecular-weight heparin

enoxaparin sodium

enoxaparin

unfractionated heparin ( UFH )

enoxaparin

UFH

UFH

enoxaparin

Enoxaparin

UFH

enoxaparin

low-molecular-weight heparin

change of the size of the thrombus

incidence of major bleeding

clot size evolution

serious bleeding complications

proximal deep vein thrombosis

deep vein thrombosis

proximal vein thrombosis

deep vein thrombosis


Effect of extradural analgesia on stress responses to abdominal surgery in infants . We studied 40 children younger than 4 yr having elective abdominal surgery under general anaesthesia supplemented with either systemic opioids or extradural bupivacaine . Venous blood samples were obtained before tracheal intubation to measure baseline concentrations of adrenaline , noradrenaline , glucose , ACTH and cortisol . Additional samples were obtained 45 min after the start of surgery , at the end of surgery , 1 h and 24 h after the end of surgery . Plasma concentrations of bupivacaine were measured also in the extradural group at each sampling time . Both techniques provided acceptable analgesia , but the perioperative increases in adrenaline , glucose and ACTH were significantly greater in the opioid group . Noradrenaline concentrations decreased to less than baseline values in the extradural group and were significantly less than in the opioid group . The perioperative increase in cortisol was similar in the two groups , despite the differences in ACTH responses . Most responses returned to the baseline values within 24 h. Plasma bupivacaine concentrations remained within safe limits during the study , but systemic concentrations increased in some of the patients during postoperative infusion with 0.125 % bupivacaine .

extradural analgesia

general anaesthesia

bupivacaine

bupivacaine

stress responses

Venous blood samples

Plasma concentrations of bupivacaine

Noradrenaline concentrations

perioperative increase in cortisol

Plasma bupivacaine concentrations

systemic concentrations

infants .


Milk protein quantity and quality in low-birth-weight infants . IV . Effects on tyrosine and phenylalanine in plasma and urine . Well , appropriate-for-gestational age , low-birth-weight infants were divided into three gestational age groups and assigned randomly within each age group to one of five feeding regimens : pooled human milk ( BM ) ; formula 1 ( F1 ) = 1.5 gm/dl protein , 60 parts bovine whey proteins : 40 parts bovine caseins ; F2 = 3.0 gm/dl , 60:40 ; F3 = 1.5 gm/dl , 18:82 ; F4 = 3.0 gm/dl , 18:82 . Plasma and urine concentrations of tyrosine and phenylalanine were far higher in the infants fed F1 to F4 , especially F2 and F4 , than in the infants fed BM . These findings offer further evidence for the limited capacity of the low-birth-weight infant to catabolize tyrosine . Infants fed F3 had significantly higher plasma tyrosine concentrations than infants fed F1 , and those fed F4 had higher concentrations than those fed F2 . Thus , increased plasma tyrosine concentrations in low-birth-weight infants are related directly both to the quantity and to the quality of the protein in their diets .

pooled human milk

protein

bovine whey proteins

bovine caseins

tyrosine

phenylalanine

tyrosine

phenylalanine

catabolize tyrosine

plasma tyrosine concentrations

plasma tyrosine concentrations

low-birth-weight

infants

appropriate-for-gestational age

low-birth-weight

infants


The relative contributions of medication adherence and AA meeting attendance to abstinent outcome for chronic alcoholics . Our preliminary studies of the efficacy of lithium carbonate therapy for alcoholism under double-blind , placebo-controlled conditions demonstrated that alcoholics who took their assigned medication ( lithium or placebo ) for the first 6 months after discharge from an inpatient rehabilitation program were more likely to abstain from any alcohol use for 18 months following discharge than were alcoholics who took their medication erratically or not at all . Attendance at Alcoholics Anonymous ( AA ) meetings was also associated with medication adherence . We applied a structural equation model to data on the relationships between medication adherence , AA meeting attendance and abstinent outcome to clarify whether medication adherence or AA meeting attendance better explains the positive-outcome " adherence effect " we observed . Both medication adherence and AA meeting attendance evidenced direct and independent influences on abstinent outcome : medication adherence showed a small direct influence , and AA meeting attendance showed a much larger , independent influence .

lithium carbonate therapy

lithium

placebo

abstinent outcome

" adherence

alcoholics

alcoholics

alcoholics

Alcoholics


Cimetidine is not more effective than placebo in acute infectious mononucleosis .

Cimetidine

placebo

effective

acute infectious mononucleosis .


Pharmacokinetic study of RU 486 and its metabolites after oral administration of single doses to pregnant and non-pregnant women . RU 486 and three of its metabolites ( RU 42633-monodemethyl , RU 42848-didemethyl , and RU 42698-hydroxymetabolite ) were determined by HPLC in plasma from nine non-pregnant and 36 pregnant women . Each non-pregnant subject took an oral dose of RU 486 ( 25 , 100 , 400 and 600 mg consecutively ) once per menstrual cycle . Six of the nine women also received a dose of 200 mg . The 36 pregnant women were randomized into four groups which were given a single dose of 25 , 100 , 400 or 600 mg RU 486 . Blood samples were taken up to 120 h after dosing . Peak concentrations of RU 486 occurred on most occasions within 2 h. Plasma concentrations at 1 h and at 24 h increased in proportion to log dose . There was a wide variability ( up to ten-fold ) in the pharmacokinetic parameters within each dose group . Plasma concentrations of RU 42633 were similar to those of RU 486 but concentrations of RU 42848 and RU 42698 were much lower . As with RU 486 , the plasma concentrations of the metabolites were maintained at high levels for up to 48-72 h after dosing . The findings were consistent with a rapid metabolism of RU 486 to RU 42633 ; removal of the second methyl group leading to RU 42698 occurred much more slowly and to a much less extent than removal of the first . There appeared to be no significant differences between the non-pregnant and pregnant women in either the plasma concentrations or pharmacokinetic parameters of RU 486 and its metabolites .

RU 486

RU 486

RU 42698-hydroxymetabolite

RU 486

RU 486

Blood samples

Peak concentrations of RU 486

Plasma concentrations

Plasma concentrations of RU 42633

RU 486 to RU 42633

pregnant

non-pregnant

women

nine

non-pregnant

pregnant

women

pregnant

women

non-pregnant

pregnant

women


[ The effect of indobufen on aortocoronary bypass patency after 1 week and after 1 year ] . A randomized clinical study was conducted to compare the effect of " conventional " antiaggregation therapy ( ASA plus dipyridamole ) versus indobufen in patients after aortocoronary bypass ( ACB ) surgery . The patency of venous ACB using coronary DSA one week and one year after surgery was evaluated in 52 patients divided into two groups . The study included only ACB 's with intraoperative blood flow rates < or = 40 ml/min as it is just these ACB 's which are at the highest risk of early and late occlusions . While , in the ASA plus dipyridamole-treated group , occlusions were found in 11 of the 39 reconstructions ( 28.2 % ) , the proportion was nine out of 37 procedures ( 24.3 % ) in the indobufen group . One year after surgery , occlusion was found in 14 out of 32 ACB 's ( 43.7 % ) in the ASA plus dipyridamole group compared to 14 occlusions in 31 ACB 's ( 45.2 % ) in the indobufen group . The difference in the number of occlusions between the two groups was not statistically significant . Because of some benefits of indobufen compared to ASA ( shorter time of effect , superior tolerance in patients with ulceration ) , the former drug can be recommended for use in some indicated cases .

indobufen

conventional " antiaggregation therapy

ASA plus dipyridamole

indobufen

ASA plus dipyridamole-treated

indobufen

dipyridamole

indobufen

occlusions

occlusion

number of occlusions

aortocoronary bypass patency


[ Comparison of complications after intra- and extracapsular cataract extraction with lens implantation . Results of a prospective , randomized , clinical study ] . BACKGROUND The postoperative complications of ICCE with ACL implantation are compared with those of ECCE and PCL . Our clinical experience with ICCE and ACL implantation can not confirm the widespread rejection of this method . PATIENTS AND METHOD A prospective , randomized , clinical study with participation of medical statisticians was performed . A total of 190 patients with ICCE and ACL and 170 patients with ECCE and PCL were followed up for 2 years . The follow-up examinations were performed upon dismission from the hospital , after 6 , 12 and 24 months . The data were compiled in a computer program designed for this study and evaluated by the statisticians . The surgical procedures and the surgeons were defined prior to the beginning of patient recruitment . RESULTS ICCE with ACL shows much less postoperative complications as usually emphasized . There were only 2 ( 1.2 % ) of retinal detachment and no case of corneal decompensation . Cystoid macular edema 8 ( 4.7 % ) , postoperative vitreous prolaps into the anterior chamber 4 ( 2.3 % ) and spontaneous complaints of pain 16 ( 9.4 % ) occurred in a low percentage after ICCE with ACL . These complications did not occur after ECCE with PCL . The patients with ECCE and PCL showed capsular fibrosis in 48 ( 28 % ) making it the most frequent complication of the whole study . 33 % of these patients required YAG-laser capsulotomy . Since retinal detachment occurs in 2.5 % after YAG-laser capsulotomy we can not regard capsular fibrosis as a totally harmless complication . It is noteworthy that visual acuity is almost identical 1 year after surgery in both methods . CONCLUSIONS The results of this study show that the evaluation of ICCE with ACL is too negative . The elimination of postoperative complications in this method is more difficult . ECCE with PCL is burdened by frequent capsular fibrosis . Visual acuity is almost the same in both methods 1 years after the operation . ACL-implantation remains our method of choice for secondary implantation in patients with an intact iris diaphragm .

ICCE with ACL implantation

ECCE and PCL .

ICCE and ACL implantation

ICCE and ACL

ECCE and PCL

ICCE with ACL

ICCE with ACL

ECCE with PCL

ECCE and PCL

YAG-laser capsulotomy

YAG-laser capsulotomy

ICCE with ACL

ECCE with PCL

ACL-implantation

complications

postoperative complications

postoperative complications

retinal detachment

corneal decompensation

Cystoid macular edema

spontaneous complaints of pain

capsular fibrosis

visual acuity

frequent capsular fibrosis


Effect of ranitidine and amoxicillin plus metronidazole on the eradication of Helicobacter pylori and the recurrence of duodenal ulcer . BACKGROUND Persistent infection with Helicobacter pylori is associated with the recurrence of duodenal ulcer . Whether the efficacy of bismuth therapy in reducing the rate of recurrence of duodenal ulcer is due to its antimicrobial effects on H. pylori or to a direct protective action on the mucosa is still a matter of debate . METHODS To study the effect of the eradication of H. pylori on the recurrence of duodenal ulcer , we treated 104 patients with H. pylori infection and recurrent duodenal ulcer with either amoxicillin ( 750 mg three times daily ) plus metronidazole ( 500 mg three times daily ) or identical-appearing placebos , given orally for 12 days . All patients also received ranitidine ( 300 mg each night ) for 6 or 10 weeks . Endoscopy was performed before treatment and periodically during follow-up for up to 12 months after healing . RESULTS Among the 52 patients given antibiotics , H. pylori was eradicated in 46 , as compared with 1 of the 52 given placebo ( 89 percent vs. 2 percent , P < 0.001 ) . After six weeks , the ulcers were healed in 48 patients given antibiotics and 39 given placebo ( 92 percent vs. 75 percent , P = 0.011 ) . Side effects , mainly diarrhea , occurred in 15 percent of the patients given antibiotics . Among the patients followed up for 12 months , duodenal ulcers recurred in 4 of 50 patients given antibiotics and 42 of 49 given placebo ( 8 percent vs. 86 percent , P < 0.001 ) . Ulcers recurred in 1 of 46 patients in whom H. pylori had been eradicated , as compared with 45 of 53 in whom H. pylori persisted ( 2 percent vs. 85 percent , P < 0.001 ) . CONCLUSIONS In patients with recurrent duodenal ulcer , eradication of H. pylori by a regimen that does not have any direct action on the mucosa is followed by a marked reduction in the rate of recurrence , suggesting a causal role for H. pylori in recurrent duodenal ulcer .

ranitidine

amoxicillin

metronidazole

amoxicillin

metronidazole

identical-appearing placebos

ranitidine

antibiotics

placebo

antibiotics

placebo

antibiotics

antibiotics

placebo

eradicated

healed

diarrhea

duodenal ulcers recurred

Ulcers recurred

eradication

H. pylori infection

recurrent duodenal ulcer

recurrent duodenal ulcer


Timing of antibiotic administration in knee replacement under tourniquet . Cephamandole levels in serum and drain fluid were measured in 32 knee replacement operations to determine the benefit of an intravenous dose of antibiotic at the time of tourniquet deflation . Concentrations of cephamandole in drain fluid were directly proportional to the serum concentration at the time of tourniquet release . A 'tourniquet-release ' dose of antibiotic increased drain fluid concentration threefold .

antibiotic administration

Cephamandole

cephamandole

cephamandole in drain fluid

drain fluid concentration

knee replacement under tourniquet .

knee replacement operations


Effect of reduced alcohol consumption on blood pressure in untreated hypertensive men . Fifty-four untreated , mildly hypertensive men whose daily alcohol consumption was > or = 28 ml ethanol and who drank at least 4 times per week took part in a randomized , controlled crossover trial . The purpose of the trial was to test the effects of alcohol reduction on blood pressure . After a 2-week familiarization period , the participants were assigned to either a reduced alcohol drinking group or a usual drinking group for 3 weeks ( experimental period 1 ) . The situation was then reversed for the next 3 weeks ( experimental period 2 ) . The participants were requested to limit their daily alcohol consumption to zero or reduce it as much as possible for the reduced alcohol consumption period . The self-reported alcohol consumption was 56.1 +/- 3.6 ( SEM ) ml/day during the usual alcohol drinking period and 26.1 +/- 3.0 ml/day during the period of reduced alcohol consumption . Systolic and diastolic blood pressures in the intervention group were found by analysis of variance to be significantly lower ( 2.6-4.8 and 2.2-3.0 mm Hg , respectively ) than those in the control group during experimental period 2 for systolic blood pressure and experimental period 1 for diastolic blood pressure . Significant ( 3.6 mm Hg ) and nonsignificant ( 1.9 mm Hg ) decreases in systolic and diastolic blood pressure , respectively , were observed . The method of Hills and Armitage was used , reducing ethanol in daily alcohol consumption by 28 ml . The lowering effect of reduced alcohol consumption on blood pressure was independent of changes in salt consumption , which were estimated by 24-hour urine collection and body weight . ( ABSTRACT TRUNCATED AT 250 WORDS )

reduced alcohol drinking

usual drinking group

Effect

blood pressure

effects

blood pressure .

self-reported alcohol consumption

Systolic and diastolic blood pressures

systolic blood pressure

diastolic blood pressure .

systolic and diastolic blood pressure

hypertensive

men

Fifty-four


Effects of reducing dietary [ ( Na+ + K+ ) - ( Cl- + SO4= ) ] on the rate of calcium mobilisation by dairy cows at parturition . The effects of feeding diets with different milliequivalents ( meq ) of dietary [ ( Na+ + K+ ) - ( Cl- + SO4= ) ] to dairy cows during the last seven weeks of pregnancy on their acid-base status and calcium mobilisation rate around parturition were studied . Ten monozygotic twin pairs of pregnant cows ( five pairs of parity 1 or 2 , and five pairs of parity 3 or more ) were allocated to two diets which were formulated to provide either -4 meq ( anion diet ) or +572.5 meq ( cation diet ) of [ ( Na+ + K+ ) - ( Cl- + SO4= ) ] kg-1 dietary dry matter ( DM ) . The daily rations consisted of 4 kg grass hay and 7 kg concentrates . Changes in meq of dietary [ ( Na+ + K+ ) - ( Cl- + SO4= ) ] were achieved by adding KCl , K2SO4 and ( NH4 ) 2SO4 ( anion diet ) or K2CO3 ( cation diet ) to basal concentrates . Plasma calcium concentration and blood acid-base parameters were not affected by dietary treatment . However , urinary calcium excretion was markedly higher and urinary pH and bicarbonate excretion significantly lower in cows fed the anion diet than in cows fed the cation diet . The responses to hypocalcaemia induced by an intravenous infusion of EDTA solution were similar in the cows fed either diet .

[ ( Na+ + K+ ) - ( Cl- + SO4= ) ]

grass hay and

concentrates .

[ ( Na+ + K+ ) - ( Cl- + SO4= ) ]

anion diet

cation diet .

Plasma calcium concentration

blood acid-base parameters

urinary calcium excretion

urinary pH and bicarbonate excretion

dairy cows at parturition .


Neostigmine and edrophonium antagonism of moderate neuromuscular block induced by pancuronium or tubocurarine . Edrophonium and neostigmine are anticholinesterase drugs used commonly to antagonize competitive neuromuscular block . Although it has a faster onset of action than neostigmine , edrophonium is unreliable when used to antagonize deep neuromuscular block . We have compared the antagonist characteristics of these two drugs when used to antagonize a moderate degree of pancuronium- or tubocurarine-induced neuromuscular block . Forty ASA I or II patients undergoing surgical procedures were allocated randomly to receive either pancuronium 70 micrograms kg-1 or tubocurarine 0.5 mg kg-1 , and to receive either edrophonium 0.5 mg kg-1 or neostigmine 0.05 mg kg-1 . Antagonism was attempted when the first response to train-of-four ( TOF ) stimulation recovered spontaneously to 25 % of the control height . Neuromuscular function was monitored using the evoked integrated electromyogram of the first dorsal interosseous muscle of the hand . Adequate recovery was defined as the achievement of a TOF ratio of 0.70 or greater . Only seven of 20 patients who received edrophonium demonstrated adequate recovery 30 min after antagonism . Under the conditions described in this study , edrophonium 0.5 mg kg-1 was less effective as an antagonist than neostigmine 0.05 mg kg-1 .

Neostigmine

edrophonium

Edrophonium

neostigmine

neostigmine

edrophonium

neuromuscular block .

neuromuscular block .

Neuromuscular function

evoked integrated electromyogram

Forty

ASA

undergoing surgical procedures


Torasemide in the treatment of patients with cirrhosis and ascites . The effects of torasemide ( 20 mg/day ) and furosemide ( 50 mg/day ) , each given over 4 days , were compared in a randomized and crossover study carried out in seven patients with cirrhosis and tense ascites . Patients also received a low-sodium ( 40 mmol/day ) diet and the aldosterone antagonist , potassium canrenoate ( 100 mg b.i.d. ) . Torasemide induced a remarkably higher natriuretic ( 120 +/- 15 vs. 33 +/- 6 mmol/day , p < 0.02 ) and diuretic ( 1450 +/- 63 vs. 900 +/- 58 ml , p < 0.005 ) effect than furosemide . Body weight loss was also significantly higher ( 2.5 +/- 1.6 vs. 0.2 +/- 1.3 kg , p < 0.01 ) during the torasemide period . Kaliuresis was similar during the two treatment periods , despite the striking differences observed in natriuresis . Neither torasemide nor furosemide induced any significant change in serum electrolyte or creatinine concentrations , or in ammonia levels . The results of this study indicate that torasemide is suitable for the treatment of sodium retention in patients with cirrhosis and ascites .

Torasemide

torasemide ( 20 mg/day )

furosemide ( 50 mg/day )

low-sodium ( 40 mmol/day ) diet

aldosterone antagonist

potassium canrenoate

Torasemide

furosemide

torasemide

torasemide

furosemide

torasemide

natriuretic

diuretic

Body weight loss

Kaliuresis

cirrhosis and ascites

seven

cirrhosis and tense ascites

cirrhosis and ascites


Metronidazole in periodontitis ( IV ) . The effect of patient compliance on treatment parameters . Patient compliance with the unsupervised usage of prescription medication can be poor . In the treatment of periodontal infections with systemic antimicrobial agents , in situations where the efficacy of the antimicrobial agent is being evaluated , non-compliance could underestimate the true efficacy of the agent . Metronidazole is an agent with reported success in the treatment of anaerobic periodontal infections . Metronidazole is particularly effective in vitro against spirochetes , and this efficacy was investigated as a means of measuring patient compliance with metronidazole usage . Patients who had high proportions of spirochetes , i.e. , > 20 % , in plaques removed from diseased periodontal sites , were given metronidazole ( 500 mg bid ) under supervision . In all individuals who received the metronidazole , there was a significant and rapid decline and/or disappearance of spirochetes from the plaque during the time interval that metronidazole was detectable in the saliva . This observed decline in spirochetes was then used to determine which patients had been compliant in a double-blind clinical trial involving the unsupervised usage of metronidazole . Only 10 of 18 patients ( 56 % ) were considered compliant in their usage of metronidazole . These 10 patients experienced a significantly greater benefit from the metronidazole than did the 8 patients who were considered noncompliant , i.e. , a reduction of surgical needs of 8.3 teeth per compliant patient versus 3.6 teeth per non-compliant patient . A test for the hydrolysis of the synthetic peptide ( BANA ) was also able to identify most non-compliant patients . Clinical trials involving the unsupervised usage of systemic medication need to take into account patient non-compliance .

Metronidazole

periodontitis

Metronidazole

Metronidazole

metronidazole

metronidazole

metronidazole

metronidazole

metronidazole

metronidazole

metronidazole

reduction of surgical needs

high proportions of spirochetes , i.e.


Clinical and prognostic significance of serum magnesium concentration in patients with severe chronic congestive heart failure : the PROMISE Study . OBJECTIVES The aim of this study was to determine the prognostic significance of alterations in serum magnesium in patients with moderate to severe congestive heart failure . BACKGROUND Reductions in serum magnesium have been postulated to play a role in promoting arrhythmias and to have an adverse impact on survival in congestive heart failure , although support for this postulate is lacking . METHODS Serum magnesium levels were measured in 1,068 patients enrolled in a survival study of class III or IV heart failure at the time of double-blind randomization to milrinone , a phosphodiesterase inhibitor , or placebo . All patients received conventional therapy with digoxin , diuretic drugs and a converting enzyme inhibitor throughout the trial . The median follow-up period was 6.1 months ( range 1 day to 20 months ) . RESULTS Patients with high serum magnesium ( defined as > or = 1.9 mEq/liter , n = 242 ) were less likely to survive than were patients with a normal magnesium level ( n = 627 ) ( p < 0.05 , risk ratio = 1.41 ) . Patients with a low magnesium level ( defined as < or = 1.5 mEq/liter , n = 199 ) had no difference in survival compared with the group with a normal magnesium level ( p = NS , risk ratio = 0.89 ) . At baseline , the patients in the high magnesium group were older and had more severe functional and renal impairment . An analysis after adjustment for these variables demonstrated no difference in survival comparing the low , normal and high magnesium groups . Although the three groups had no difference in frequency of ventricular tachycardia , length of longest run or frequency of ventricular premature beats on baseline Holter monitoring , the group with hypomagnesemia had more frequent ventricular couplets . CONCLUSIONS Serum magnesium does not appear to be an independent risk factor for either sudden death or death due to all causes in patients with moderate to severe heart failure . Hypomagnesemia is associated with an increase in the frequency of certain forms of ventricular ectopic activity , but this is not associated with an increase in clinical events . The higher mortality rate among the patients with hypermagnesemia is attributable to older age , more advanced heart failure and renal insufficiency .

milrinone

phosphodiesterase inhibitor

placebo

conventional therapy with digoxin

Serum magnesium levels were measured

survive

survival

functional and renal impairment

survival

ventricular tachycardia

baseline Holter monitoring

sudden death or death

ventricular ectopic activity

severe chronic congestive heart failure

class III or IV heart failure


Sustained augmentation of parasympathetic tone with angiotensin-converting enzyme inhibition in patients with congestive heart failure . OBJECTIVES The objective of this investigation was to evaluate the changes in parasympathetic tone associated with long-term angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure . BACKGROUND Angiotensin-converting enzyme inhibitors provide hemodynamic and symptomatic benefit and are associated with improved survival in patients with congestive heart failure . Angiotensin II , whose production is ultimately inhibited by these agents , exerts significant regulatory influence on a variety of target organs including the central and peripheral nervous systems . Accordingly , it would be anticipated that angiotensin-converting enzyme inhibitors would significantly alter the autonomic imbalance characteristic of patients with congestive heart failure and that this influence over neural mechanisms of cardiovascular control may significantly contribute to the hemodynamic benefit and improved survival associated with angiotensin-converting enzyme inhibitor therapy . METHODS In the current investigation , changes in autonomic tone associated with long-term administration of an angiotensin-converting enzyme inhibitor were measured using spectral analysis of heart rate variability in 13 patients with congestive heart failure who were enrolled in a double-blind randomized placebo-controlled trial of the angiotensin-converting enzyme inhibitor zofenopril . Both placebo and treatment groups were balanced at baseline study in terms of functional class , ventricular performance and autonomic tone . RESULTS After 12 weeks of therapy with placebo , there was no change in total heart rate variability , parasympathetically governed high frequency heart rate variability or sympathetically influenced low frequency heart rate variability . In contrast , therapy with zofenopril was associated with a 50 % increase in total heart rate variability ( p = 0.09 ) and a significant ( p = 0.03 ) twofold increase in high frequency heart rate variability , indicating a significant augmentation of parasympathetic tone . CONCLUSIONS These results demonstrate that long-term treatment of patients having congestive heart failure with an angiotensin-converting enzyme inhibitor is associated with a restoration of autonomic balance , which derives in part from a sustained augmentation of parasympathetic tone . Such augmentation of vagal tone is known to be protective against malignant ventricular arrhythmias in patients with ischemic heart disease and therefore may have similar benefit in the setting of ventricular failure , thus contributing to the improved survival associated with angiotensin-converting enzyme inhibitor therapy in patients with congestive heart failure .

placebo-controlled

placebo

zofenopril

angiotensin-converting enzyme inhibitor

total heart rate variability

heart rate variability


Diode laser photocoagulation for threshold retinopathy of prematurity . A randomized study . BACKGROUND Although peripheral cryotherapy decreases the incidence of unfavorable anatomic outcomes in threshold retinopathy of prematurity ( ROP ) , apnea , bradycardia , and lid edema can occur . Argon laser indirect ophthalmoscope photocoagulation has been used as an alternative to cryotherapy , with fewer adverse effects . Retinal lesions placed with diode lasers are deeper than similar argon laser lesions , and it is not known whether this difference could influence the response to ablative therapy . METHODS Patients were enrolled under a prospective , randomized protocol . One eye of each patient with symmetric , threshold ROP was treated with an 814/815 nm diode laser , while the other eye was treated with cryotherapy . Patients with asymmetric diseases also were randomized for treatment in the threshold eye . RESULTS Nineteen infants ( 33 eyes ) were treated , ranging from 485 to 863 g birth weight ( 23 to 27 weeks gestational age ) ; 18 patients ( 32 eyes ) were followed for 3 months or longer . Four patients ( 8 eyes ) had bilateral zone 1 disease . Postconceptional age was 36 to 45 weeks at the time of treatment . The diode laser treatment was better tolerated than cryotherapy , and the treatment apparatus was more easily transported . Apneic episodes requiring intubation resulted from two cryotherapy sessions but no diode laser sessions . Five cryotherapy-treated eyes required retreatment because of persistent disease with adjacent skip areas . In the group followed for 3 to 15 months , 1 cryotherapy-treated eye and 1 diode laser-treated eye progressed to stage 5 retinal detachment . CONCLUSION Compared with cryotherapy , the diode laser was more convenient , technically easier to administer , and better tolerated by the patient . Although the number of patients was too small for meaningful statistical analysis of outcome , diode laser peripheral retinal ablation appeared to be as effective as cryotherapy for the treatment of threshold ROP .

Diode laser photocoagulation

peripheral cryotherapy

cryotherapy

diode lasers

argon laser

ablative therapy

diode laser

cryotherapy

diode laser

cryotherapy

cryotherapy

diode laser

cryotherapy-treated

cryotherapy-treated

laser-treated

cryotherapy

diode laser

diode laser peripheral retinal ablation

cryotherapy

adverse effects

response

tolerated

Apneic episodes requiring intubation

retreatment

stage 5 retinal detachment

threshold retinopathy of prematurity

retinopathy of prematurity

ROP

Nineteen infants ( 33 eyes )

18 patients ( 32 eyes )

Four patients ( 8 eyes )

36 to 45 weeks


Beta-carotene in HIV infection . beta-Carotene has been reported to have an immunostimulatory effect . Recent studies suggest that beta-carotene supplementation can increase CD4 counts in HIV-infected patients . Our double-blind , placebo-controlled clinical trial was designed to test the efficacy of beta-carotene in raising CD4 counts in HIV-infected patients . Twenty-one HIV-seropositive patients were randomized to receive either beta-carotene , 180 mg/day or placebo for 4 weeks , and then crossed over to receive the alternative treatment for the following 4 weeks . beta-Carotene resulted in a statistically significant increase in total WBC count ( p = 0.01 ) , % change in CD4 count ( p = 0.02 ) , and % change in CD4/CD8 ratios ( p = 0.02 ) compared to placebo . The absolute CD4 count , absolute CD4/CD8 ratio , and total and B-lymphocytes all increased on carotene and fell during placebo , but these differences did not reach statistical significance . No toxicity was observed on either treatment . beta-Carotene appears to have an immunostimulatory effect in HIV-infected patients . Further studies are needed to demonstrate whether beta-carotene has a role as adjunct therapy in treatment of HIV-infected patients .

Beta-carotene

beta-Carotene

beta-carotene supplementation

placebo-controlled

beta-carotene

beta-carotene , 180 mg/day

placebo

CD4 counts

total WBC count

CD4 count

CD4/CD8 ratios

CD4 count

CD4/CD8 ratio

toxicity

immunostimulatory effect

HIV-infected patients

HIV infection .

HIV-infected

HIV-infected

Twenty-one

HIV-seropositive

HIV-infected

HIV-infected


Antinuclear antibodies with enalapril .

enalapril

Antinuclear antibodies

Antinuclear antibodies


Adjuvant cyclophosphamide , doxorubicin , vincristine , and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma . Results of a prospective randomized study . BACKGROUND In a prospective randomized manner , this study evaluated the effect of adjuvant chemotherapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone ; CHOP ) in patients with Stage I non-Hodgkin lymphoma ( NHL ) who have achieved a complete response ( CR ) after radiation therapy ( RT ) . METHODS Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone ( median dose , 40 Gy ) or regional RT followed by six cycles of CHOP chemotherapy . There were no differences in clinical and pathologic characteristics between the two treatment groups . RESULTS The median follow-up was 7 years ( range , 2-10 years ) . The actuarial relapse-free survival ( RFS ) rate for the RT plus CHOP group at 7 years was 83 % compared with 47 % ( P < 0.03 ) for the RT-alone group . The overall survival ( OS ) for the two groups was 88 % and 66 % , respectively ( P = 0.2 ) . In patients with intermediate-grade NHL , the 7-year actuarial RFS for RT and CHOP was 86 % compared with 20 % for RT alone ( P = 0.004 ) . The corresponding actuarial survival rates were 92 % and 47 % , respectively ( P = 0.08 ) . In patients with low-grade histologic findings , the addition of adjuvant CHOP did not improve RFS ( P = 0.6 ) or OS . All relapses in this study were at sites remote from the initially involved areas , and in 5 of 11 patients ( 45 % ) , there were recurrences 5 years or longer after initial treatment . CONCLUSIONS This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT . The chemotherapeutic regimen favorably affected their probability of survival .

cyclophosphamide

doxorubicin

vincristine

prednisone chemotherapy

adjuvant chemotherapy

cyclophosphamide

doxorubicin

vincristine

prednisone

CHOP

CHOP

CHOP chemotherapy

median follow-up

overall survival ( OS )

7-year actuarial RFS

corresponding actuarial survival rates

RFS

probability

survival .


A randomized trial of radiation therapy compared to split course radiation therapy combined with mitomycin C and 5 fluorouracil as initial treatment for advanced laryngeal and hypopharyngeal squamous carcinoma . Two hundred and twelve patients with previously untreated advanced squamous carcinoma of the larynx or hypopharynx were randomized to receive initial treatment with radiotherapy , 50 Gy in 20 fractions in 28 days or split course radiotherapy and concurrent chemotherapy , 25 Gy in 10 fractions in 14 days followed by a 4 week rest and a further 25 Gy in 10 fractions in 14 days starting on day 43 ; Mitomycin C was given on day 1 and day 43 and 5FU continuous infusions on days 1 -- 4 and days 43 -- 46 . Surgery was reserved for persistent or recurrent disease . Two hundred and nine of the 212 patients randomized were included in the analyses . Outcome analyses were performed at a median follow-up interval of 4.4 years . No patients were lost to follow-up . No significant difference was found between the two arms for the end points of local relapse-free rate ( p = 0.91 ) , regional relapse-free rate ( p = 0.17 , adjusted ) or overall survival ( p = 0.86 ) . Eight-eight patients had attempted surgical resection following radiotherapy failure . The contribution of salvage surgery to overall survival was similar for both arms of the study as was the surgical complication rate . Serious late radiation toxicity was minimal ( 3 % in the RT group , 0 % in the radiation therapy plus chemotherapy group ) . The result of the trial shows no advantage in terms of local control or survival for the experimental treatment arm of split course radiotherapy and concurrent chemotherapy with Mitomycin C and 5 Fluorouracil compared to radiotherapy alone .

radiation therapy

split course radiation therapy

mitomycin C

5 fluorouracil

radiotherapy

split course radiotherapy

concurrent chemotherapy

Mitomycin C

radiotherapy

radiotherapy

concurrent chemotherapy

Mitomycin C

5 Fluorouracil

local relapse-free rate

regional relapse-free rate

overall survival

overall survival

surgical complication rate

Serious

late radiation toxicity

Two hundred and twelve


Long-term consequences of different immunosuppressive regimens for renal allografts . The long-term effects of four different immunosuppressive regimens on renal allografts have been investigated up to four years . A total of 128 recipients of first cadaveric renal allograft were randomized , after an initial induction period , to receive either triple drug therapy -- i.e. , ( low-dose ) cyclosporine , azathioprine , and methylprednisolone , or any possible combination of two drugs -- i.e. , Aza plus CsA , Aza plus MP , and CsA plus MP . The actual four-year graft survival rates for the triple therapy , Aza plus CsA , Aza plus MP , and CsA plus MP groups were 72 % , 69 % , 75 % , and 59 % , and patient survival rates were 78 % , 81 % , 81 % , and 84 % , respectively , with no significant differences . The cumulative number of chronic rejections up to 4 years was 0.09 , 0.29 , 0.25 , and 0.34 per patient per group ( P = ns ) , respectively . At 2 , 3 , and 4 years posttransplantation , the graft function was significantly worse in the Aza plus MP group compared with the triple therapy group ( P < .05 ) . Of the 98 patients who did not have type I or II diabetes at the time of transplantation , 17 developed posttransplantation diabetes mellitus or an abnormal glucose tolerance test within 2 years posttransplantation . All these patients had received steroids and none of the patients without steroids had these abnormalities . At two years the mean cholesterol level was highest in the Aza plus MP group , 6.8 mmol/L and lowest in the group receiving triple therapy , 5.8 mmol/L ( P = ns ) . The use of ( low-dose ) CsA was not associated with lipid abnormalities or with disturbances in glucose metabolism . A protocol graft biopsy was performed at two years on all functioning kidneys , and the histological changes were scored blindly . No CsA-specific changes , except isometric vacuolation in tubuli , were found . Histological alterations characteristic of chronic rejection were expressed as " chronic allograft damage index . " Chronic allograft damage index was lowest in the triple therapy group , 1.5 , compared with the other groups , 3.2-4.3 ( P = .01 ) , indicating the least histopathological change in the triple therapy group . In conclusion , this long-term study did not show any serious cyclosporine-related side-effects when used in low dose in combination with two other drugs . Some side-effects , such as posttransplant diabetes mellitus and probably some lipid abnormalities , could rather be traced to a higher dose of steroids . Moreover , the triple drug therapy was more efficacious than any double drug regimen in the prevention of chronic histological changes in renal allografts .

immunosuppressive regimens

different immunosuppressive regimens

cyclosporine

azathioprine

methylprednisolone

Aza plus CsA

Aza plus MP

CsA plus MP

Aza plus CsA

Aza plus MP

CsA plus MP

Aza plus MP

steroids

Aza plus MP

triple therapy

cyclosporine-related

steroids

triple drug therapy

Long-term consequences

long-term effects

graft survival rates

chronic rejections

graft function

posttransplantation diabetes mellitus

abnormal glucose tolerance test

cholesterol level

lipid abnormalities

disturbances in glucose metabolism

histological changes

CsA-specific changes

isometric vacuolation in tubuli

histopathological change

cyclosporine-related side-effects

posttransplant diabetes mellitus

some lipid abnormalities

renal allografts

first cadaveric renal allograft

did not have type I or II diabetes


Hypotensive effects and influence on serum lipids of SQ29,852 , a new angiotensin converting enzyme inhibitor , in patients with essential hypertension : a comparison with atenolol . The effects of SQ29,852 ( n = 24 ) , a new angiotensin converting enzyme inhibitor , and atenolol ( n = 22 ) , monotherapies were compared in 46 patients with mild to moderate essential hypertension . Both SQ29,852 ( mean dose 15.0 +/- 5.1 mg/day ) and atenolol ( mean dose 37.5 +/- 18.5 mg/day ) significantly decreased both systolic and diastolic blood pressures . There were no significant changes in serum lipids , apolipoproteins , lipoproteins or atherosclerotic indices after both SQ29,852 and atenolol . There were also no significant inter-group differences . There were no serious side effects or abnormal laboratory tests in both treatment groups . It is concluded that SQ29,852 is an effective antihypertensive drug without adverse effect on lipid metabolism .

atenolol

angiotensin converting enzyme inhibitor

atenolol

atenolol

atenolol

serum lipids

systolic and diastolic blood pressures

adverse effect

patients with essential hypertension :


Treatment of vasculogenic sexual dysfunction with pentoxifylline . OBJECTIVE To evaluate the use of pentoxifylline to treat impotence in men with mild to moderate penile vascular insufficiency . DESIGN Double-blind randomized clinical trial . SETTING Sexual Dysfunction Clinic at VA Medical Center , Sepulveda , CA . PARTICIPANTS Convenience sample of couples . INTERVENTION Twelve weeks of treatment with placebo or 400 mg tid of pentoxifylline . MEASUREMENTS ( 1 ) Report of patient verified by partner as to number of coital episodes per month ; ( 2 ) penile-brachial pressure index determinations . RESULTS Pentoxifylline therapy regularly increased the PBPI in impotent men in comparison with the placebo , frequently into the normal range . Pentoxifylline therapy was particularly useful in restoring the PBPI in men with the pelvic steal syndrome ; six of seven such subjects improved into the normal range . During the pentoxifylline treatment period , in contrast with the control period , nine men were able to reestablish coital function and three had no improvement . Six couples did not attempt intercourse despite a professed interest in sexual activity ; however five out of the six men experienced erections during episodes of fantasy or attempts at masturbation during treatment . There were no complications of therapy . CONCLUSIONS These promising preliminary results suggest a well tolerated alternative therapy for erectile dysfunction in patients with mild to moderate penile vascular disease .

pentoxifylline .

pentoxifylline

placebo

400 mg tid of pentoxifylline

Pentoxifylline therapy

PBPI

restoring the PBPI

reestablish coital function

attempt intercourse

sexual activity

complications

vasculogenic sexual dysfunction


[ Prevention of pneumonia by endotracheal micronebulization of tobramycin ] . In 69 artificially ventilated patients the clinical , bacteriological and pharmacological effects of endotracheally administered tobramycin were studied in comparison to a control group . In the therapy group , 52 % of all specimens were sterile , in the control group only 25 % . During the first 4 days these changes were significant ( p < 0.05 ) . In the therapy group the endotracheal colonisation with ps . aeruginosa was significantly lower between the 4th and 14th day ( p < 0.05 ) . The incidence of secondary pneumonia was reduced from 42 % to 17.5 % ( not significant ) . Systemic administration of antibiotics , e.g . of aminoglycosides , was significantly more often necessary in the control group . No increasing of growth of fungi in the upper respiratory tract was observed , but these was a non-significantly higher incidence mainly of staph . epidermidis . The application of 80 mg tobramycin four times a day as an aerosol was well tolerated by the patients . Under there conditions , tobramycin could not be measured in the serum . No allergic reactions , increased respiratory pressures or bronchoconstrictions were observed .

tobramycin

tobramycin

pneumonia

clinical , bacteriological

pharmacological effects

incidence of secondary pneumonia

Systemic administration of antibiotics

incidence mainly of staph . epidermidis

tolerated

allergic reactions

respiratory pressures

bronchoconstrictions

pneumonia

69 artificially ventilated


Use of granulocyte-macrophage colony-stimulating factor and erythropoietin in combination after autologous marrow transplantation . The toxicities and possible utility of the combination of recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) and recombinant human erythropoietin ( rHuEPO ) given after autologous BMT were evaluated in this pilot trial . Eighteen patients received the combination and were compared with six concurrent control and 65 historical control patients treated with rhGM-CSF alone . Patients treated with the combination tended to have more rapid recovery to an absolute neutrophil count of 500 x 10 ( 6 ) /l ( median = 12.5 vs 18 days for concurrent and 19 days for historical control patients ) . There was no apparent impact on red cell transfusion requirements , platelet recovery or duration of hospitalization . Patients treated in the current study with rhGM-CSF plus either rHuEPO or with placebo had a higher incidence of rash than seen in our historical experience using rhGM-CSF . This difference may reflect changes in the source of rhGM-CSF or in the infusion schedule . Erythropoietin can be combined safely with rhGM-CSF after autologous transplantation . Larger controlled trials will be necessary to detect possible therapeutic effects .

erythropoietin

autologous marrow transplantation

autologous BMT

rhGM-CSF

recovery

absolute neutrophil count

red cell transfusion requirements ,

platelet recovery

duration of hospitalization

incidence of rash

after autologous marrow transplantation

Eighteen

six