Resolution of acyclovir-associated neurotoxicity with the aid of improved clearance estimates using a Bayesian approach: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Neurotoxicity is a side effect of acyclovir. We report the first case, to our knowledge, whereby Bayesian-informed clearance estimates supported a therapeutic intervention for acyclovir-associated neurotoxicity. CASE SUMMARY: A 62-year-old male with the diagnosis of disseminated zoster was being treated with intravenous (IV) acyclovir when he developed symptoms of acute neurotoxicity. Acyclovir had been dose-adjusted for renal dysfunction according to traditional creatinine clearance estimates; however, as the patient was also on vancomycin, Bayesian estimates of vancomycin clearances were performed, which revealed a 2-fold lower creatinine clearance. In response to the Bayesian estimates, acyclovir was discontinued, and improvements in mentation were noted within 24 hours. WHAT IS NEW AND CONCLUSION: Alternate approaches to estimate renal function beyond Cockcroft-Gault, such as a Bayesian approach used in our patient, should be considered when population estimates are likely to be inaccurate and potentially dangerous to the patient.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: July 2004. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Twenty-three randomised trials involving 3115 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% versus 58%) than six month therapy (Odds ratio (OR) 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR 0.75, 95% CI 0.39 to 1.43). Twelve trials examined the effect of Block-Replace versus Titration regimen. The relapse rates were similar in both groups at 51% in the Block-Replace group and 54% in the Titration group (Peto OR 0.86, 95% CI 0.68 to 1.08). Participants reporting rashes (10% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine with continued low dose antithyroid therapy after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio 0.58, 95% CI 0.05 to 6.21). Four studies considered the addition of thyroxine alone after initial therapy with antithyroid drugs. There was no significant difference in the relapse rates between the groups after 12 months follow-up with relapse rates being 31% (88/282) with thyroxine and 29% (82/284) with placebo (Peto OR 1.15, 95% CI 0.79 to 1.67). AUTHORS' CONCLUSIONS: The evidence (based on four studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 12 trials) of equal duration. Continued thyroxine treatment following initial antithyroid therapy does not appear to provide any benefit in terms of recurrence of hyperthyroidism. The incidence of hypothyroidism was not reported and there were no deaths reported in the study populations.

Effects of aluminum and magnesium antacids and ranitidine on the absorption of ciprofloxacin.

The effect of an antacid (Maalox) and ranitidine administration on the absorption of ciprofloxacin was evaluated in healthy male volunteers who were enrolled in three separate studies. Each study was designed at a three- or four-period crossover and included the administration of 750 mg ciprofloxacin alone as a control treatment. Treatments that were evaluated included the administration of ciprofloxacin 5 to 10 minutes, 2 hours, 4 hours, and 6 hours after a single 30 ml dose of antacid; the administration of antacid 2 hours after ciprofloxacin was given; and the administration of ciprofloxacin 2 hours after a 200 mg ranitidine tablet. Administration of antacid within 4 hours before ciprofloxacin dose resulted in a significant decrease in ciprofloxacin absorption (p less than 0.05). Percentages of relative bioavailability compared with control values were 15.1%, 23.2%, and 70% for the 5 to 10 minute, 2 hour, and 4 hour antacid pretreatments, respectively. Administration of antacid 6 hours before or 2 hours after the ciprofloxacin dose did not affect absorption. Ranitidine did not alter ciprofloxacin absorption. Antacids that contain magnesium and aluminum salts may reduce the absorption of ciprofloxacin. The extent of this interaction appears to increase as the time between administration of the two drugs decreases. Ranitidine is suggested as an alternative to antacids for patients receiving treatment with ciprofloxacin.

Cimetidine kinetics during resuscitation from burn shock.

Severely burned patients suffer from rapidly changing metabolic and hemodynamic abnormalities that could alter drug kinetics. The kinetics of cimetidine, commonly used in the prophylaxis of acute stress erosions, were studied during fluid resuscitation of 11 patients with mean burn sizes of 45% total body surface area. Six patients were studied after the completion of fluid resuscitation. Total clearance, steady-state volume of distribution, and cimetidine t1/2 did not change between the early period after burn and after fluid resuscitation, but before the completion of fluid resuscitation patients had lower renal and greater nonrenal cimetidine clearance than after resuscitation. The increase in nonrenal cimetidine clearance resulted in decreased urinary recovery of unchanged drug, 50.7 +/- 14% during fluid resuscitation and 81.0% +/- 6% after resuscitation.

Kidney function during naproxen therapy in patients at risk for renal insufficiency.

The effects of naproxen on renal function in 34 patients with minimally elevated serum creatinine (Scr) or subnormal creatinine clearance (Ccr) were evaluated in a parallel-design study. All patients received open-label naproxen 375 mg twice daily for 2 weeks (phase I); patients were then randomly assigned to receive naproxen 750 mg twice daily (n = 26) or to continue naproxen 375 mg twice daily (n = 8) double-blind for an additional 2 weeks (phase II). Renal function was assessed by Scr, Ccr, and BUN measurements at baseline and at the end of each treatment phase. Neither treatment group had a clinically meaningful change in median laboratory values between baseline and the end of phase I, or between baseline and the end of phase II. During the first 2 weeks of treatment with naproxen 375 mg twice daily, there was no change in Scr. At the time of the first Scr measurement following the increase in naproxen dose to 750 mg twice daily, 13 of 26 patients had Scr levels of 1.1 mg/dL or higher, but four days later, only three patients had Scr levels of 1.1 mg/dL or higher, suggesting that a transient increase in Scr may accompany dosage increase. Chronic administration of naproxen 375 mg twice daily in patients at risk for renal insufficiency based on laboratory evidence of renal impairment was not associated with further deterioration in renal function. An increase in dosage to 750 mg twice daily in such patients appeared to be associated with only small, transient changes in laboratory measures of renal function.

Albumin standards and the measurement of serum albumin with bromcresol green. 1971.

A rapid and reliable method for measuring serum albumin employing bromcresol green is described. The addition of albumin to a solution of bromcresol green in a 0.075 M succinate buffer pH 4.20 results in an increase in absorbance at 628 nm. The absorbance-concentration relationship is linear for samples containing up to 6 g/dl albumin. Bilirubin, moderate lipemia, and salicylate do not interfere with the analysis. The use of nonionic surfactant (Brij-35) reduces the absorbance of the blank, prevents turbidity and provides linearity. The results by this method agree very well with those obtained by electrophoresis and salt fractionation. The method is simple, it has excellent precision and the reagents are stable. A protein standard is introduced which can be employed for both the total serum proteins and albumin determinations.

A longitudinal analysis of factors associated with morbidity in cocaine abusers with psychiatric illness.

We conducted a study to characterize a population of cocaine users who were referred to a state psychiatric institution, identify treatment problems including reasons for relapse, and develop strategies to improve treatment outcome. Using a data base system from a tertiary-care hospital emergency department, we identified a sample of 80 patients with a cocaine-related presentation who came to the emergency department and were referred to the psychiatric facility. Forty-six percent had consumed crack cocaine, and 65% reported ingesting cocaine with other drugs, half of them with alcohol. Suicidal ideation or attempt was the most common reason for referral. A retrospective review of 58 of the 80 referrals to the psychiatric facility showed that over half of the patients were given a concurrent psychiatric diagnosis and required hospitalization on an acute-care psychiatric unit. Sixty-two percent of those admitted had prior hospitalizations at the psychiatric facility, yet only five patients had received treatment for substance abuse. Seventy-four percent were readmitted to the psychiatric facility within 1 year of their index episode, with a higher rate of relapse among persons with dual diagnoses compared to cocaine users without dual diagnoses (p less than 0.05). Possible reasons for relapse included lack of referral for substance abuse treatment, nonintegrated treatment of psychiatric illness and substance abuse, lack of psychosocial support, and unresolved financial or job-related stressors. The data support increased funding to facilities that treat persons with dual diagnoses, and suggest the need to develop comprehensive treatment approaches involving a multidisciplinary team to address issues of mental illness and substance abuse concomitantly, and to identify and resolve stressors leading to relapse.

The safety of halobetasol 0.05% ointment in the treatment of psoriasis.

The effects on the hypothalamic-pituitary-adrenal axis of the ultra-high potency corticosteroid halobetasol in the treatment of psoriasis were evaluated in seven patients with extensive, long-standing plaque psoriasis. Each patient applied 3.5 g halobetasol 0.05% ointment in the morning and evening for 7 days. Morning plasma cortisol levels and 24-hour urinary excretion of 17-hydroxycorticosteroid were determined before and on the last 2 days of treatment; plasma cortisol levels were also determined 4 and 5 days after completion of therapy. Morning plasma cortisol concentrations did not decrease significantly during treatment, and no values were below the normal range. Mean 24-hour urinary 17-hydroxycorticosteroid excretion fell from 6.6 +/- 1.4 mg to 5.1 +/- 1.4 mg. Two patients had mild, localized pruritus and stinging with the initial ointment application. No other adverse cutaneous effects were observed. Halobetasol was also clinically efficacious over the 7 days of treatment, based on evaluation of pruritus, erythema, scaling, and plaque elevation. These results demonstrate no adverse effects of the drug on the hypothalamic-pituitary-adrenal axis at doses that are clinically effective in the management of plaque psoriasis.

The effect of sucralfate pretreatment on the pharmacokinetics of ciprofloxacin.

Based on the results of our study of norfloxacin-sucralfate coadministration, we suspected that sucralfate would interact also with ciprofloxacin if the drugs were administered concurrently. Therefore, we decided to give a 1-g dose of sucralfate at 6 and 2 hours before a single 750-mg dose of ciprofloxacin and evaluate its effect on the bioavailability of ciprofloxacin. Twelve healthy, male volunteers received ciprofloxacin alone and with sucralfate pretreatment in a randomized, balanced, crossover design. Blood and urine samples were collected over 24 hours after ciprofloxacin administration, and drug concentrations were assayed by high-performance liquid chromatography. When sucralfate was given at 6 and 2 hours before ciprofloxacin, an average 30% decrease in ciprofloxacin's bioavailability was noted (p less than 0.05). Four of the 12 subjects, however, had decreases in the agent's area under the curve of more than 50% with sucralfate pretreatment. The results of this study suggest that ciprofloxacin and sucralfate should not be administered concurrently until a dosing interval is found that will avoid this potential interaction.

Phenotypic and genotypic characterization of monoclonal anti-digoxin antibodies.

Eleven hybridoma cell lines secreting monoclonal anti-digoxin antibody have been produced. They are primarily gamma heavy chain and kappa light chain molecules. Affinity constants for digoxin range from 2 X 10(6) to 3.5 X 10(8) liters/mole. Fine specificity analysis using a series of digoxin congeners demonstrates that an unsaturated lactone ring attached to the aglycone at the C-17 position is necessary for hapten recognition. The impact of other changes in digoxin's structure on antibody binding were also studied. DNA hybridization analysis demonstrates that there are at least three different variable region gene arrangements used to produce the heavy chains of the different hybridoma antibodies. Correlations between antigen binding characteristics and antibody V-gene arrangements are demonstrable.

Presenting clinical features and C-reactive protein in the prediction of a positive stool culture in patients with diarrhoea.

OBJECTIVES: To devise a scoring system by which clinical features and C-reactive protein (CRP) can be used to predict a positive stool culture in patients admitted with acute diarrhoea. METHODS: One hundred and thirty-two patients admitted to the Regional Infection Unit with diarrhoea thought to be due to bacterial gastroenteritis were included. Clinical features, CRP and outcome of stool culture were recorded, together with the final diagnosis. RESULTS: Forty-one patients had bacterial gastroenteritis characterized by the isolation of a bacterial enteropath (BGE). Sixty-three patients had non-specific gastroenteritis, defined as more than three loose stools per day with no bacterial enteropath isolated (NSGE). In 28 patients another diagnosis was made (Others). More of the patients with BGE (91%) had abdominal pain as compared with those with NSGE (67%) and Others (61%) (P=0.01). The mean duration of symptoms was longer in the Others group (6.14 days) as compared with patients with BGE (3.29) and NSGE (3.25) (P=0.01). The mean CRP was significantly higher in those with BGE (113.9mg/l) and Others (116.9mg/l) as compared to the NSGE patients (38.9mg/l) (P=0.001). A scoring system was devised which incorporated the presence or absence of abdominal pain (+10 or 0), the duration of symptoms (-10, for 5 or more days, 0 for less than 5 days of symptoms) and the CRP (CRP<50=0, CRP>50=5). A score of 15 or more predicted 79% of patients with BGE, while a score of <15 predicted 87% of those with NSGE and 86% of those with another diagnosis. CONCLUSIONS: This simple scoring system may be useful in predicting the positivity of stool culture, and therefore may be helpful in targeting those small number of patients who require antimicrobial therapy after hospital admission. We would not, however, favour reliance on this scoring system alone to choose whom to treat with antimicrobials.

In vivo cytogenetic activity of sulphonylurea drugs in man.

A cytogenetic investigation of diabetic patients undergoing treatment with sulphonylurea drugs, particularly chlorpropamide, shows that significantly more chromatid aberrations and chromosome exchange aberrations are present in the lymphocytes of these patients compared with controls. This is taken as evidence of possible mutagenic activity by these drugs, although the possibility cannot be ruled out that the diabetic state itself is a contributory factor.

Emergency medicine residents' shiftwork tolerance and preference.

OBJECTIVES: To determine the shift lengths currently worked by emergency medicine (EM) residents and their shift length preferences, and to determine factors associated with EM residents' subjective tolerance of shiftwork. METHODS: A survey was sent to EM-2 through EM-4 allopathic EM residents in May 1996. This questionnaire assessed the residents' shift length worked, shift length preferences, night shift schedules, and self-reported ability to overcome drowsiness, sleep flexibility, and morningness-eveningness tendencies. When providing shift length preferences, the residents were asked to assume a constant total number of hours scheduled per month. RESULTS: Seventy-eight programs participated, and 62% of 1,554 eligible residents returned usable surveys. Current shift lengths worked were 8 hours (12%), 10 hours (13%), 12 hours (37%), combinations of 8-hour, 10-hour, or 12-hour (34%) shifts, and other combinations (4%). Seventy-three percent of the respondents indicated that they preferred to work 8-hour or 10-hour shifts, and only 21% preferred a 12-hour shift. Shiftwork tolerance was recorded as: not well at all (2%), not very well (14%), fairly well (70%), and very well (14%). The EM residents' eveningness preference, ability to overcome drowsiness, sleep flexibility, younger age, and having no children at home were all associated with greater shiftwork tolerance. CONCLUSIONS: Emergency medicine residents generally tolerate shiftwork well and prefer 8-hour or 10-hour shift lengths compared with 12-hour shift lengths. Emergency medicine residencies with 12-hour shifts should consider changing residents' shifts to shorter shifts.

Morningness-eveningness preferences of emergency medicine residents are skewed toward eveningness.

OBJECTIVE: To determine the morningness-eveningness (ME) distribution of emergency medicine (EM) residents. METHOD: A voluntary, modified ME questionnaire was administered to all EM residents in the United States at the time of the 1995 American Board of Emergency Medicine's annual In-Training Examination. RESULTS: Seventy-eight percent (2,047/2,614) of the surveys were returned. ME scores ranged from 24 to 76, with a median score of 49 (interquartile range 44, 56). The scores were distributed differently from those of the normal population (p < 0.001), being skewed toward eveningness. There was a correlation (r = 0.13, p < 0.0001) between resident age and ME score, with older residents being more morning-oriented. Males were more morning-oriented than females (p = 0.005), and respondents with children living at home also were significantly more morning-oriented (p < 0.001). Stepwise logistic regression showed that the influence of age, gender, and children was cumulative (r = 0.19) but accounted for only 4% of the observed variability. CONCLUSION: EM residents are distributed differently from the normal population in terms of their ME preferences, tending slightly toward eveningness. The importance of this distribution in EM residents in unknown. A longitudinal follow-up of this cohort may help to determine the association of ME preference with overall practice satisfaction, tolerance of shift work, and career longevity.

Validation of a rapid urine screening assay for cocaine use among pregnant emergency patients.

OBJECTIVES: To determine the accuracy of the OnTrak rapid urine latex agglutination immunoassay (AIA) for testing pregnant ED patients for the cocaine metabolite benzoylecgonine (BE), and to determine the frequency of urine BE in pregnant ED patients and the association of test results with patient demographics. METHODS: A test performance evaluation was conducted using an inception cohort of pregnant patients at an urban teaching hospital ED. Patients with positive urine chorionic gonadotropin tests who had adequate remaining urine samples were studied. Patient demographics, ED diagnoses, and assay results were recorded without patient identifiers. Urine was tested using the rapid AIA. The first 150 samples were confirmed using a second immunoassay and gas chromatography with a nitrogen phosphorus detector. All positive samples also were confirmed with thin-layer chromatography, and quantification by gas chromatography-mass spectrometry. RESULTS: Twenty of 342 (5.9%, 95% CI 3.4-8.4%) pregnant patients had urine samples positive by AIA testing for BE. Confirmation testing demonstrated no false-positive or -negative AIA result. Positive test results were not associated with specific patient diagnoses or demographics. CONCLUSIONS: ED screening for cocaine use among pregnant patients can be accurately performed using the OnTrak AIA for BE. In the ED population screened, 5.9% of the pregnant women had urine samples positive for BE.

The occupational risk of motor vehicle collisions for emergency medicine residents.

OBJECTIVE: To determine the prevalence and risk factors associated with motor vehicle collisions (MVCs) and near-crashes as reported by emergency medicine (EM) residents following various ED shifts. METHODS: A survey was sent to all allopathic EM-2-EM-4 residents in May 1996 asking whether they had ever been involved in an MVC or near-crash while driving home after an ED shift. The residents' night shift schedules, self-reported tolerance of night work, ability to overcome drowsiness, sleep flexibility, and morningness/eveningness tendencies also were collected. RESULTS: Seventy-eight programs participated and 62% of 1,554 eligible residents returned usable surveys. Seventy-six (8%, 95% CI = 6% to 10%) residents reported having 96 crashes and 553 (58%, 95% CI = 55% to 61%) residents reported being involved in 1,446 near-crashes. Nearly three fourths of the MVCs and 80% of the near-crashes followed the night shift. Stepwise logistic regression of all variables demonstrated a cumulative association (R = 0.19, p = 0.0004) that accounted for 4% of the observed variability in MVCs and near-crashes. Univariate analysis showed that MVCs and near-crashes were inversely related to residents' shiftwork tolerance (p = 0.019) and positively related to the number of night shifts worked per month (p = 0.035). CONCLUSIONS: Residents reported being involved in a higher number of MVCs and near-crashes while driving home after a night shift compared with other shifts. Driving home after a night shift appears to be a significant occupational risk for EM residents.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWERS' CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Antithyroid drug regimen for treating Graves' hyperthyroidism.

BACKGROUND: Antithyroid drugs are widely used in the therapy of hyperthyroidism. There are wide variations in the dose, regimen or duration of treatment used by health professionals. OBJECTIVES: To assess the effects of dose, regimen and duration of antithyroid drug therapy for Graves' hyperthyroidism. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (Central), MEDLINE, EMBASE, BIOSIS, CINAHL, HEALTHSTAR, Current Controlled Trials and reference lists. We contacted investigators and hand searched conference abstracts. Most recent search: June 2002. SELECTION CRITERIA: Randomised and quasi-randomised trials of antithyroid medication for Graves' hyperthyroidism were used. DATA COLLECTION AND ANALYSIS: Trial allocation to included, excluded and awaiting assessment categories was made by consensus. Two reviewers independently extracted data and assessed trial quality. Pooling of data for primary outcomes, and select exploratory analyses were undertaken. MAIN RESULTS: Nineteen randomised trials involving 2233 participants were included. Overall the quality of trials as reported was poor; specifically in terms of allocation concealment, assessor blinding and loss to follow-up. Four trials examined the effect of duration of therapy on relapse rates of Graves' hyperthyroidism. In one trial using the Titration regimen, longer duration therapy (18 months) had significantly fewer relapses (37% vs 58%) than six month therapy (Odds ratio (OR) = 0.42, 95% confidence interval (CI) 0.18 to 0.96). In one quasi-randomised trial using the Block-Replace regimen, there was no significant difference between the six and 12 month (relapses rates 41% versus 35%) arms of the study. Extending the duration of therapy to over 18 months was not associated with improved relapse rates (Peto OR = 0.75, 95% CI 0.39 to 1.43). Ten trials examined the effect of Block-Replace versus Titration regime. Relapse rates were similar in both groups at 54% in the Block-Replace group and 58% in the Titration group (Peto OR = 0.83, 95% CI 0.63 to 1.10). Participants reporting rashes (11% versus 5%) and withdrawing due to side effects (16% versus 9%) were significantly higher in the Block-Replace group compared to the Titration group respectively. Three studies considered the addition of thyroxine after initial therapy with antithyroid drugs. There was significant heterogeneity between the studies and the difference between the two groups were not significant (Odds ratio = 0.58, 95% CI 0.05 to 6.21). REVIEWER'S CONCLUSIONS: The evidence (based on three studies) suggests that the optimal duration of antithyroid drug therapy for the Titration regimen is 12 to 18 months. The six month Block-Replace regimen was found to be as effective as the 12 month treatment in one quasi-randomised study. The Titration (low dose) regimen had fewer adverse effects than the Block-Replace (high dose) regimen and was no less effective in trials (based on 10 trials) of equal duration. The incidence of hypothyroidism was not reported and there were no deaths in the study populations.

Nocardia species as a possible cause of ovine abortion.

An instance of ovine abortion is described in which focal placental lesions were caused by a Gram-positive branching filamentous organism. The organism was present in well oxygenated tissues and so is thought more likely to have been a Nocardia sp than an Actinomyces sp.

Influence of Temperature and Wetting Period on Inoculum Production by Monilinia fructicola in Peach Twig Cankers.

Overwintering cankers in peach twigs caused by the brown rot fungus, Monilinia fructicola, were studied to identify the relationships of wetting period and temperature on sporulation. Sporulation was observed on blighted blossoms, peduncles, abscission scars, and cankers resulting from contact with infected fruits. The frequency of sporulation on overwintered infected tissues was greater at 15 and 23°C than at 4 or 11°C. Twelve hours of wetting was sufficient at all temperatures studied (5 to 23°C) for sporulation to occur, but the number of twig cankers supporting sporulation increased with time of wetting up to 72 h. Given the additional moisture requirements for spore germination, ingress, and infection, 17 to 30 h of wetting or high humidity during bloom may be needed for blossom blight to occur unless viable conidia are already present as a result of previous wetting periods.