Multiple deletions of the mitochondrial DNA in polymyalgia rheumatica

We analyzed the mitochondrial DNA of patients with polymyalgia rheumatica, a disease frequently associated with mitochondrial myopathy. In an attempt to study the deletions, we have developed a qualitative PCR method using a highly thermostable polymerase in order to amplify multiple mitochondrial DNA large fragments (up to 12 kb). PCR serves to observe both deleted and normal fractions of the mitochondrial DNA. We found multiple deletions of the mitochondrial DNA in all of the patient muscles. Although these muscles harbored many ragged red fibers, we found no point mutations of the tRNA(Leu)(UUR)) and the mutation at nucleotide position 8344 was not present.     

VIRULENCE FACTORS ASSOCIATED WITH PATHOGENICITY OF AEROMONAS ISOLATES

Aeromonas species have been associated with diarrhea, and disseminating infections. Diarrhea is either "cholera-like" or "dysentery-like". Both types of diarrhea are normally mild. However, either type can be severe enough to cause hospitalization. The sources of Aeromonas in these infections are foods and water. Two virulence factors associated with Aeromonas diarrhea are a relatively heat-stable cholera-like enterotoxin and a heat-labile cytotoxic enterotoxin. Researchers who observed either of these enterotoxins rarely saw evidence of the other. These differences are probably due to the rare occurrence of the cholera-like toxin and to differences in purification methods. Human feeding studies showed that enterotoxin production is not sufficient for causation of diarrhea. The Aeromonas must also be able to colonize the intestine or invade the intestinal lining. Virulence factors associated with colonization or invasion have not been identified.     

Neurologic manifestations of HIV infection

A wide spectrum of central and peripheral nervous system abnormalities may be associated with HIV infection. These disorders may be caused by HIV infection, result as secondary complications related to immunosuppression, or be a neurotoxic effect of therapeutic agents. The range of neurologic disorders includes dementia, focal cerebral mass lesions, myelopathy, peripheral neuropathies, and myopathy. Early diagnosis and therapy is critical, and may result in substantial improvement in patients' quality and quantity of life. This article reviews the approach to differential diagnosis of these neurologic disorders and presents theories of pathogenesis and current approaches to treatment.     

Neuroblastoma in Europe: differences in the pattern of disease in the UK. SENSE. Study group for the Evaluation of Neuroblastoma Screening in Europe

BACKGROUND: Neuroblastoma is a major contributor to childhood cancer mortality, but its prognosis varies with age and stage of disease, and some tumours regress spontaneously. Urinary screening programmes or clinical examination may detect the disease before symptoms appear, but the benefit of early diagnosis is uncertain. We examined the incidence, pattern, and presentation of neuroblastoma in four European countries. METHOD: Population-based incidence rates were derived for France, Austria, Germany, and the UK. Age, sex, and stage distribution were analysed by Mantel-Haenszel techniques and Poisson regression. The proportion of incidental diagnoses (cases without symptoms found at routine health checks or during investigation of other disorders) and mortality rates were also compared. FINDINGS: Between 1987 and 1991, 1672 cases of neuroblastoma were diagnosed in children under 15 years old (France, 624; Austria, 69; Germany, 493; UK, 486). Age-standardised annual incidence was significantly lower in the UK (10.1/million) than in France (12.5) and Germany (11.4). In the UK a deficit of low-stage disease in infants was accompanied by an excess of stage IV in older children. The UK had significantly fewer incidental diagnoses (8%) than Austria (27%) and Germany (34%). UK mortality rates were significantly higher than German or French rates. INTERPRETATION: In the UK, neuroblastoma diagnosis is delayed, possibly because of a less rigorous system of health checks for children. Although some overdiagnosis occurs in mainland Europe, our data suggest that in the UK some low-stage cases, undetected in infancy, may later present as advanced disease. This finding has implications for screening programmes and organisation of routine surveillance of infant health in the UK.     

Cocaine and metabolites in amniotic fluid may prolong fetal drug exposure

OBJECTIVE: Cocaine and metabolites can be found in the amniotic fluid after maternal use, presumably as a result of fetal urination. The fetus may be repeatedly exposed to the effects of these drugs through contact with amniotic fluid that contains these substances. The purpose of this study was to determine whether the naive fetal lamb generates detectable fetal blood levels of cocaine and metabolites when cocaine is placed directly into the amniotic fluid and, if so, whether fetal swallowing accounts for these findings. STUDY DESIGN: Six pregnant ewes with singleton fetuses of 120 to 125 days' gestation were chronically catheterized for daily sampling of cocaine and metabolite levels in maternal venous plasma, fetal venous plasma, and amniotic fluid over a 7-day period. Esophageal ligation was performed in three additional animals similarly instrumented to evaluate the role of fetal swallowing in the distribution of amniotic fluid cocaine and its metabolites. In each case, at the time of surgery, an Alzet osmotic pump delivering cocaine at 0.5 mg/kg estimated fetal weight per hour into the amniotic fluid was secured to the fetal back. Cocaine and metabolites (benzoylecgonine, ecgonine methyl ester, and norcocaine) were measured daily in material and fetal plasma, amniotic fluid, and meconium by solid-phase extraction and derivatization and quantified by high-performance gas chromatographic techniques. RESULTS: The concentrations of ecgonine methyl ester were highest in the amniotic fluid followed by cocaine and benzoylecgonine. In the normal and esophagus-ligated groups, cocaine, benzoylecgonine, and norcocaine were found in fetal plasma in concentrations of approximately 3% that of amniotic fluid. Ecgonine methyl ester was not detected in fetal plasma from either group. Meconium samples from sheep with and without esophageal ligation demonstrated high levels of norcocaine. CONCLUSION: We conclude that cocaine and metabolites in amniotic fluid enter the fetal circulation to produce detectable plasma levels through routes other than swallowing. Moreover, the results of meconium analyses in the two groups of fetuses suggest that fetal swallowing is not the primary mechanism by which cocaine and metabolites enter the intestine.     

True trisomy 15 mosaicism, detected by amniocentesis at 12 weeks of gestation and fetal echocardiography

A case of mosaicism of trisomy 15, with two-thirds of the cells trisomic, was detected at 12 weeks of gestation in amniotic fluid cell cultures obtained with the filtration technique. Ultrasound examination at 13 weeks showed a nodule protruding into the amniotic cavity which was speculated to be remnants of a co-twin, causing the trisomic cell line. At 20 weeks of gestation, a malformation scan (level III) was normal, but supplementary fetal echocardiography revealed a severe cardiac defect (mitral atresia and a ventricular septal defect). Fetal lymphocytes obtained by cordocentesis showed trisomy 15 mosaicism, but only in 5 per cent of the mitoses. After termination, the same percentage of trisomy 15 mosaicism was found in cells from skin and tendon as in the original early amniocentesis. No sign of earlier twinning was found in the placenta or membranes. We conclude that mosaicism in early amniotic fluid obtained by the filter technique in this case reflected the true karyotype accurately and that supplementary echocardiography added significantly to the interpretation of the clinical implications.