Lidocaine block of LQT-3 mutant human Na+ channels

In transiently transfected mammalian cells we have identified pharmacological consequences of a naturally occurring deletion mutation, delta KPQ, of the human heart Na+ channel alpha subunit that previously has been linked to one form of the long QT syndrome, an inherited heart disease. Our results show that the Class IB antiarrhythmic agent lidocaine blocks maintained inward current through and slows recovery from inactivation of delta KPQ-encoded Na+ channels. Block is greater for maintained than for peak current. Because incomplete inactivation of mutant Na+ channels is now thought to underlie the prolonged ventricular action potential, which is the phenotype of this disease, and we find that the delta KPQ mutation speeds the recovery from inactivation of drug-free mutant channels, our results provide evidence, for the first time, that clinically relevant dysfunctional properties of an ion channel can be selectively targeted on the basis of the molecular properties conferred on the channel by an inherited genetic disorder.     

Cytology of cervical chordoma in cerebrospinal fluid from a child. A case report

The cytologic findings on cerebrospinal fluid examination of cervical chordoma in a 2-year-old girl are presented. The major cell type was a small, isolated, hyperchromatic cell with sharply defined nuclear membrane and granular cytoplasm. However, the characteristic cell of this neoplasm, the so-called physaliferous cell with typical bubbly cytoplasm, was also noted. Cytologic findings were compared to biopsy findings, with a good correlation of tumor morphology. Clinical follow-up revealed unusually aggressive tumor behavior, and the patient died a year later despite intensive chemotherapy. The differential diagnosis of the condition is also discussed.     

Comparison of NucliSens and Amplicor monitor assays for quantification of human immunodeficiency virus type 1 (HIV-1) RNA in plasma of persons with HIV-1 subtype A infection in Abidjan, C?te d'Ivoire

We compared the sensitivity and accuracy of the NucliSens assay and those of both the standard and modified (addition of a new primer set, primer mix 1, supplied by Roche) Amplicor HIV Monitor assays to quantify human immunodeficiency virus type 1 (HIV-1) RNA in persons infected with HIV-1 subtype A in Abidjan, C?te d'Ivoire. Seventy-one plasma samples from HIV-1-seropositive persons at different stages of HIV infection and 15 samples from HIV antibody-negative persons were analyzed. The HIV-1 genetic subtype was determined either by DNA sequencing or by a restriction fragment length polymorphism assay. Of the 71 samples, 70 (98%) were subtype A and 1 was subtype G. Of the 70 subtype A samples, the proportion of RNA-positive plasma samples and mean HIV-1 RNA levels were significantly higher by the modified HIV Monitor assay (n = 67 [96%]; mean RNA levels, 5.2 log10 HIV-1 RNA copies/ml) than the NucliSens assay (n = 56 [80%]; 4.3 log10 HIV-1 RNA copies/ml) or the standard HIV Monitor assay (n = 44 [63%]; mean RNA levels, 3.8 log10 HIV-1 RNA copies/ml) (all P values were <0.05). The HIV-1 RNA levels by the modified HIV Monitor assay correlated significantly with those by the NucliSens assay (r = 0.76; P < 0.001) and the standard HIV Monitor assay (r = 0.57; P < 0.001), as did the RNA levels by the NucliSens and the standard HIV Monitor assays (r = 0.60; P < 0. 001). Lower CD4 cell counts were significantly correlated with higher HIV-1 RNA levels by all three assays (r = -0.47 for the NucliSens assay, -0.45 for the standard HIV Monitor assay, and -0.62 for the modified HIV Monitor assay). These results indicate that the modified HIV Monitor assay has the highest sensitivity and efficiency at quantifying the levels of RNA in persons infected with HIV-1 subtype A and thus constitutes a valuable tool for the monitoring of RNA levels in areas of Africa were HIV-1 subtype A is predominant.     

Spectrum of disease among HIV-infected adults hospitalised in a respiratory medicine unit in Abidjan, C?te d'Ivoire

SETTING: Respiratory medicine wards of the University Teaching Hospital, Abidjan, C?te d'Ivoire. OBJECTIVES: To describe the spectrum of opportunistic infection among human immunodeficiency virus (HIV) infected adults hospitalised in the respiratory medicine unit in Abidjan, and the level of immunosuppression at which these diseases occur. DESIGN: Cross-sectional study. RESULTS: Overall, 75% of patients were HIV-positive: among these patients, the most frequent diagnosis was tuberculosis, in 61%, followed by bacterial pneumonia (15%), Gram-negative septicaemia (particularly non-typhoid Salmonella) (9%) and empyema (5%). Atypical pneumonias appeared to be rare. Most HIV-positive patients had CD4 counts indicative of advanced immunosuppression: 36% had CD4 counts below 100 x 10(6)/l, 19% between 100 and 199 x 10(6)/l, 29% between 200 and 499 x 10(6)/l, and 16% above 500 x 10(6)/l. Overall in-hospital mortality was 27% for HIV-positive patients and 22% for HIV-negative patients (P = 0.5). In a multivariate analysis, the strongest independent risk factors for death were cachexia (odds ratio [OR] 7.4, 95% confidence interval [CI] 2.1-26.3), male sex (OR 4.5, 95% CI 1.2-17.4) and age over 40 (OR 4.1, 95% CI 1.0-17.2). CONCLUSIONS: Tuberculosis and bacterial infections are the major causes of respiratory morbidity in immunosuppressed HIV-infected adults in this population. Efforts to improve the management of HIV-related disease need to focus on prevention and treatment of these infections.     

Differential north to south gastric cancer-duodenal ulcer gradient in China. China Ulcer Study Group

There are suggestions that duodenal ulcer protects individuals from gastric cancer and that rice is ulcerogenic while wheat is gastro-protective. We aimed to examine the relationship of gastric cancer, duodenal and gastric ulcers in different geographical regions in China and identified dietary risk factors for duodenal ulcer and gastric cancer. The prevalence of peptic ulcer and gastric cancer among symptomatic patients in eight major cities, four each from the north and the south representing all the six defined regions of China were studied. Endoscopy and case records over a 10 year period were reviewed and cases of confirmed duodenal and gastric ulcer and gastric cancer, together with the total number of endoscopies performed per year, were recorded. Rates were expressed as cases/1000 endoscopies. Results were compared to another epidemiological study on diet and mortality in the same regions in China conducted at the same time. Duodenal ulcer rates were 2.4-fold higher in southern China than northern China, whereas gastric cancer rates were 1.6-fold higher in the north than in the south. Correlation studies showed for the first time an inverse linear relationship between the gastric cancer rates and the duodenal ulcer rates (r=-0.8076, P=0.015), as well as the duodenal ulcer: gastric ulcer ratios (r=-0.9133, P=0.002). Gastric ulcer rates were higher in southern China but did not correlate with the gastric cancer rates (r=0.1455, P=0.731). Duodenal ulcer rates were found to be related to daily rice intake (r=0.8554, P=0.029) and inversely related to daily wheat flour intake (r=-0.8472, P=0.033). Gastric cancer rates were not related to any dietary risk factors tested. We concluded there was an inverse relationship between gastric cancer rates and duodenal ulcer rates. Although duodenal ulceration and gastric cancer are both linked to Helicobacter pylori infection, the findings of this study indicate independent additional aetiological factors for the pathogenesis of these conditions. Dietary factors such as rice or wheat intake may play a role.     

Trichloroethylene biodegradation by phenoloxidizing cultures grown from various conditions

The rate and extent of trichloroethylene (TCE) degradation by three cultures of phenol oxidizing bacteria grown from two chemostats and one from rotating biological contactors was investigated. Batch experiments were performed to measure the disappearance of TCE both with the resting cell alone and with the formate added. Experimental data were then compared with mathematical predictions from a model describing TCE transformation. Through nonlinear regression analysis, a best fit between the measurements and predictions was achieved when residual sum of squares reached a minimum. Based on the resultant parameters of transformation capacity and reaction rate, the suspended cells with a mean cell retention time (MCRT) of 3.8 days were the most active in degrading TCE, while the attached bacteria had the least activity. Based on the results presented herein, it is recommend that using suspended-growth reactors operated at short MCRT to produce desirable cells for cometablic transformation of TCE.     

Healthy cats are commonly colonized with "Helicobacter heilmannii" that is associated with minimal gastritis

Gastric Helicobacter infection in healthy pet cats is not well characterized. We performed endoscopy with gastric biopsy on 15 healthy pet cats that were rigorously screened to exclude underlying or concurrent diseases that might affect Helicobacter colonization. Gastric mucosa biopsy specimens were examined by histology, culture, and PCR for the presence of Helicobacter infection and by histology for the presence of gastritis. Of 15 cats, all but 1 had gastric Helicobacter-like organisms (GHLOs) on examination by light microscopy, and in the one histologically negative cat, GHLOs were detected by PCR. Gastric inflammation was mild or was absent for all cats. No Helicobacter species were identified by culture. Analysis of the 16S rRNA sequence from Helicobacter strains from 10 cats showed that all bacteria were closely related to Helicobacter felis, although there was heterogeneity among the sequences. These results suggest that the gastric mucosa of healthy pet cats is commonly colonized with an uncultivated Helicobacter that is closely related to H. felis, is associated with little or no gastritis, and shows heterogeneity in its 16S rRNA sequence. The epithet "Helicobacter heilmannii" continues to be an appropriate working designation for these bacteria.     

Binding of pertussis toxin to lipid vesicles containing glycolipids

The binding of pertussis toxin and its B oligomer to lipid vesicles containing glycosphingolipids was studied. Both pertussis toxin and the B oligomer bound to lipid vesicles containing ganglioside GD1a. Binding of pertussis toxin to these vesicles decreased upon treatment of the vesicles with neuraminidase, suggesting that sialic acid residues are important for efficient binding of the toxin to GD1a.