Serological diagnosis of bullous pemphigoid (BP): comparison of the sensitivity of indirect immunofluorescence on salt-split to immunoblotting

Specialized immunological assays are required for the accurate diagnosis of bullous dermatoses such as bullous pemphigoid (BP), epidermolysis bullosa acquisita and bullous lupus erythematosus. The aim of this study was to analyse and compare the sensitivity of indirect immunofluorescence (IF) on salt-split skin and immunoblotting for the detection of circulating autoantibodies in BP. Of the BP patients selected for the study, 74/79 (94%) had circulating autoantibodies detected by at least one of the two methods. Both methods had comparable sensitivity and detected BP-specific autoantibodies in 82-85% of the patients. Because 20% of the patients were found to be positive by only one of the methods, both methods should be used in the diagnosis of BP. Indirect IF on salt-split skin is easier to perform and is preferable in routine analysis, but Western blotting may be used as a complementary assay with sera showing no reactivity on salt-split skin.     

OFLOXACIN VERSUS CEPHALEXIN FOR TREATING SKIN AND SOFT TISSUE INFECTIONS

Patients with acute localized skin or soft tissue infections were randomized to receive either ofloxacin (300 mg orally, b.i.d.) or cephalexin (500 mg orally, b.i.d.). Among 401 enrolled patients, 382 were evaluable for safety and 148 for microbiologic response. Microbiologic cure occurred in 93.4% of ofloxacin-treated patients and in 94.0% of those treated with cephalexin. Clinical cure or improvement, respectively, was found in 85.2% and 11.1% of patients treated with ofloxacin, and 83.6% and 14.9% of patients receiving cephalexin. Adverse effects (primarily associated with the gastrointestinal tract and central nervous system) were considered to be drug-related in 7.9% of those receiving ofloxacin and 4.8% of those receiving cephalexin. Thus, ofloxacin is as effective and well tolerated as cephalexin and a good alternate antibiotic for treating skin and skin structure infections caused by a variety of pathogens.     

Ventricular Fibrillation with Prominent Early Repolarization Associated with a Rare Variant of KCNJ8/KATP Channel

Background: Early repolarization in the inferolateral leads has been recently recognized as a frequent syndrome associated with idiopathic ventricular fibrillation (VF). We report the case of a patient presenting dramatic changes in the ECG in association with recurrent VF in whom a novel genetic variant has been identified.
Case Report: This young female (14 years) was resuscitated in 2001 following an episode of sudden death due to VF. All examinations including coronary angiogram with ergonovine injection, MRI, and flecainide or isoproterenol infusion were normal. The patient had multiple (>100) recurrences of VF unresponsive to beta-blockers, lidocaine/mexiletine, verapamil, and amiodarone. Recurrences of VF were associated with massive accentuation of the early repolarization pattern at times mimicking acute myocardial ischemia. Coronary angiography during an episode with 1.2 mV J/ST elevation was normal. Isoproterenol infusion acutely suppressed electrical storms, while quinidine eliminated all recurrences of VF and restored a normal ECG over a follow-up of 65 months. Genomic DNA sequencing of K_ATP channel genes showed missense variant in exon 3 (NC_000012) of the KCNJ8 gene, a subunit of the K_ATP channel, conferring predisposition to dramatic repolarization changes and ventricular vulnerability.     

Catheter Ablation of Atrial Tachycardia Following Atrial Fibrillation Ablation

Atrial tachycardias represent the second front of atrial fibrillation (AF) ablation. They are frequently encountered during the index ablation for patients with persistent AF and are common following ablation of persistent AF, occurring in half of all patients who have had AF successfully terminated. An atrial tachycardia is rightly seen as a failure of AF ablation, as these tachycardias are poorly tolerated by patients. This article describes a simple, practical approach to diagnosis and ablation of these atrial tachycardias.     

A case of ovarian fibromatosis with disseminated intra-abdominal fibromatosis

A case of bilateral ovarian fibromatosis and massive oedema with subsequent intra-abdominal fibromatosis which underwent an aggressive and fatal course is described. This is the first report of co-existence of these two conditions and the possible relationship between them is discussed.     

Management and treatment efficacy of drug and alcohol problems: what do doctors believe?

We conducted a survey of the attitudes of postgraduate medical trainees in Australia on the management of drug and alcohol problems and examined the medical practitioner's role in managing drug and alcohol problems, factors influencing prognosis and beliefs about the efficacy of a number of treatment interventions. Of 2461 trainees enrolled in specially training programmes in internal medicine, psychiatry and general practice 1361 (55%) participated. There was a high level of acceptance of responsibility for management of alcohol and drug problems, with the strongest support observed among psychiatry trainees. However, views of the efficacy of various treatment interventions were less positive. Alcoholics Anonymous was considered to be an approach well supported by the research literature. Dynamic psychotherapy was less well supported, and there was considerable uncertainty about the evidence for brief advice and cognitive-behaviour therapies. The opinions expressed on treatment efficacy were in many cases in striking contrast to the research evidence. The implications for future training in drugs and alcohol in specialty programmes are discussed.     

A study of school children who had identified virus infections of the central nervous system during infancy

Forty-nine children who had a virus infection of the central nervous system (CNS) when under 1 year of age were studied. One child had died during the initial illness and three of the survivors were severely disabled. The other survivors, more than 5 years after the initial illness, were all attending normal schools. These 45 children, together with 45 matched controls, were examined. We confirm the findings of other studies that virus infections of the CNS in infancy may cause severe disabilities in some cases, and may depress intellectual abilities in others, even though they appear to have recovered fully. Many of the children who had a virus infection of the CNS in infancy had adverse birth and social histories and so were exceptionally vulnerable, but these factors did not account fully for the findings, and when their influence was included in the analysis, the index children still had a mean performance IQ (WISC) 6 points lower than the control children (P less than 0.05), whereas there was less than 1 point difference between the verbal IQs. Attention is drawn to the problem of virus infections in neonatal units.     

THE KINDLING HYPOTHESIS: FURTHER EVIDENCE FROM A U.S. NATIONAL STUDY OF ALCOHOLIC MEN

A sample of 6818 alcoholic men participating in a short in-patientdetoxification episode was studied to examine the kindling effectof repeated prior alcohol withdrawals on occurrence of seizuresor severe withdrawal problems observed during the hospitalization.Subjects studied were hospitalized in one of 172 U.S. Departmentof Veterans Affairs medical centers. Patients with seizuresand withdrawal problems had more prior detoxifications and otheralcohol-specific hospitalizations. They were also more likelyto be later readmitted for an alcoholism diagnosis. Patientswith withdrawal problems during the detoxification episode studiedwere more likely to have such problems again as well as seizuresduring the readmission; those with seizures during the indexdetoxification were more likely to have repeated seizures duringthe readmission. These results confirm the kindling effect ina large, multi-site patient sample and suggest that alcoholdetoxification programs may need to consider anticonvulsanttherapy in patients with many prior detoxifications or withdrawals.     

A phase II study of fixed dose rate gemcitabine in patients with relapsed müllerian tumors

Gemcitabine (2',2'-difluorodeoxycytidine) is a novel purine analog with clinical activity against ovarian cancer. Accumulation of gemcitabine triphosphate (dFdCTP) increases in a linear fashion with prolonged infusions of gemcitabine, and there is a strong relationship between intracellular accumulation of dFdCTP and DNA damage. Women with ovarian, fallopian tube, or primary peritoneal carcinoma and documented recurrent disease were eligible for the study. Patients could not have received more than four prior lines of chemotherapy and had to have measurable or evaluable disease. Gemcitabine 800 mg/m2 administered by intravenous infusion at 10 mg/m2/min (fixed dose rate [FDR]) on days 1 and 8 of a 21-day schedule. Twenty-eight patients with a median age 60 (range, 40-77) years were treated. Although 43% were Eastern Cooperative Oncology Group 0, 50% had liver metastases. Eighty-eight cycles of therapy were delivered (median 2 [range, 1-6]). Five of the first ten patients treated at 800 mg/m2 could not receive day 8 FDR-gemcitabine because of neutropenia, and the starting dose was reduced to 700 mg/m2. Even at this dose there was cumulative hematologic toxicity resulting in dose reductions. Vomiting, mucositis, diarrhea, allergy, rash, fever, and alopecia were mild. In 28 patients, there was only one partial response (4%, 95% CI 0-18%) and median time to progression was 1.7 (interquartile range, 1.2-3.9) months. FDR-gemcitabine 700 mg/m2 administered by intravenous infusion at an FDR of 10 mg/m2/min had minimal activity against heavily pretreated recurrent tumors of müllerian origin. The optimal dose and schedule of gemcitabine is yet to be defined in this population.