Role of IS6110 uniplex PCR in the diagnosis of tuberculous meningitis: experience at a tertiary neurocentre.

SETTING: Tuberculous meningitis (TBM) is the commonest form of neurotuberculosis in the Indian subcontinent. Rapid laboratory confirmation of TBM is important for the institution of early treatment and to avoid associated morbidity and mortality. The polymerase chain reaction (PCR) is the most widely applied alternative rapid diagnostic technique for TBM. OBJECTIVE: To evaluate the efficacy of an in-house developed IS6110 uniplex PCR (uPCR) in the diagnosis of TBM. DESIGN: A prospective, blinded study was conducted in a large sample base of 677 cerebrospinal fluid samples from 677 patients with clinically suspected TBM. RESULTS: All culture-positive samples (n = 136) were positive (100%) by the PCR assay. The assay was found to be positive in 70% (n = 541) of the samples with a clinical diagnosis of TBM. The assay had an observed sensitivity of 76.37% (negative predictive value 59.90%) and a specificity of 89.18% (positive predictive value 94.69%). A diagnostic accuracy of 80% (kappa 0.57) was seen in patients with a clinical diagnosis of TBM. Statistical significance was observed, as patients with a clinical diagnosis of TBM were found to be 9.38 times more likely to be PCR-positive (OR 9.38, chi2 = 149.94, P < 0.001). CONCLUSION: The performance of the in-house IS6110 uPCR assay merits its use as a sensitive and specific tool for the rapid diagnosis of TBM.     

Vesicular pityriasis rosea: response to erythromycin treatment

Pityriasis rosea (PR) is a relatively common disease although its aetiology has not yet been identified. It occurs worldwide and there is no racial susceptibility factor. It usually affects teenagers and young adults between 10 and 35 years of age. Typical PR is much easier to diagnose than the rare atypical forms. We report a rare case of vesicular PR in a black woman who had vesicular lesions limited to her palms and soles in addition to regular typical lesions. We devised an efficient oral erythromycin treatment for this patient.     

Unannounced simulated patients' observations of physician STD/HIV prevention practices.

Studies describing sexually transmitted disease (STD) and human immunodeficiency virus (HIV) prevention practices of primary care physicians have relied on physician or patient reports. This study describes physician STD/HIV prevention practices as observed by unannounced simulated patient evaluators (SPEs). SPEs visited sixty-five primary care physicians. Each SPE portrayed a sexually active female, new to the area, requesting a consultation on STD prevention. One-third of the physicians in the study asked no risk questions, and over 80% failed to ask the SPE specifically about her sexual practices. Most physicians discussed the risks of STDs and HIV and covered basic recommendations (use condoms and know partners better); however, few physicians provided any individualized information or advice about safer sexual practices and the specifics of condom use, such as how to use them or what kind to use. These observations support the low rates of STD/HIV prevention indicated in physicians' self-report and further identify specific deficiencies in the thoroughness of their risk assessment and preventive counseling practices.     

Constitutional heteromorphism of 9q13→q21 in a patient with chronic myelogenous leukemia

An apparently balanced de novo reciprocal translocation t(5;21) (q13;q22) was demonstrated in a girl with acrobrachycephaly, ventriculomegaly, pulmonary stenosis and anal malformation. The possible relationships between her karyotype and malformations are discussed.     

环孢菌素A阻断人HL－60抗药性细胞于G_1期而诱导敏感细胞凋亡

进一步研究了抗三尖杉酯碱的ＨＬ－６０细胞（ＨＲ２０）抗细胞凋亡的机制及该抗性和抗药性的关系。结果表明，环孢菌素Ａ（ＣｓＡ）２０，１０μｇ·ｍｌ￣（－１）诱导ＨＬ－６０细胞发生凋亡，而阻断ＨＲ２０细胞于Ｇ＿１期，就不能诱导细胞发生凋亡。低浓度的ＣｓＡ明显增加柔红霉素在ＨＲ２０细胞内的积聚，其逆转抗药性作用与阻断细胞周期运行无关。ＣｓＡ１０μｇ·ｍｌ￣（－１）处理ＨＲ２０细胞，可引起５０ｋＤａ的蛋白质高度磷酸化。结果提示：环孢菌素Ａ阻断抗三尖杉酯碱的ＨＬ－６０细胞于Ｇ＿１期，而诱导敏感的ＨＬ－６０细胞发生凋亡，其阻断作用与抗药性无关     

Mutation analysis of feline Niemann-Pick C1 disease

Niemann-Pick C (NPC) disease is an autosomal recessive neurovisceral lysosomal storage disorder that results in defective intracellular transport of cholesterol. The major form of human NPC (NPC1) has been mapped to chromosome 18, the NPC1 gene (NPC1) has been sequenced and several mutations have been identified in NPC1 patients. A feline model of NPC has been characterized and is phenotypically, morphologically, and biochemically similar to human NPC1. Complementation studies using cultured fibroblasts from NPC affected cats and NPC1 affected humans support that the gene responsible for the NPC phenotype in this colony of cats is orthologous to human NPC1. Using human-based PCR primers, initial fragments of the feline NPC cDNA were amplified and sequenced. From these sequences, feline-specific PCR primers were generated and designed to amplify six overlapping bands that span the entire feline NPC1 open reading frame. A single base substitution (2864G-C) was identified in NPC1 affected cats. Obligate carriers are heterozygous at the same allele and a PCR-based assay was developed to identify the geneotype of all cats in the colony. The mutation results in an amino acid change from cysteine to serine (C955S). Several of the mutations identified in people occur in the same region. Marked similarity exists between the human and feline NPC1 cDNA sequences, and is greater than that between the human and murine NPC1 sequences. The human cDNA sequence predicts a 1278aa protein with a lysosomal targeting sequence, several trans-membrane domains and extensive homology with other known mediators of cholesterol homeostasis.     

HLA–DRw4 in Pemphigus Vulgaris Patients in Israel

Pemphigus vulgaris (PV) is relatively common in Jews. Three HLA antigens were significantly more frequent in 39 Israeli Jewish PV patients than in controls: A26 – 59% vs 20%; Bw38 – 61% vs 20%; and DRw4 – 90% vs 38%. The joint occurrence of A26–Bw38–DRw4 was observed in 46% of PV patients and in 10% of controls. Similar results were recently reported for Jews in the Los Angeles area. Yet, when our patient sample was grouped into Ashkenazi and non-Ashkenazi Jews, it was evident that each of the three antigens had a higher frequency both in Ashkenazi patients and controls as compared to non-Ashkenazim. The relative risk for DRw4 in Ashkenazim was 33.8 as compared to 14.4 in the total sample of Israeli PV patients. The phenotype A26–Bw38–DRw4 was present in 57% of Ashkenazi patients and in 13% of controls. Ashkenazi Jews have the highest prevalence of PV, and HLA associations were strongest with Ashkenazi PV patients. These associations were with three antigens, all of high frequency in that group.