Vitamin A deficiency and the acute phase response among HIV-1-infected and -uninfected women in Kenya

Among HIV-1-infected individuals, vitamin A deficiency has been associated with faster disease progression and greater infectivity in observational studies, but randomized clinical trials have shown no effect of vitamin A supplementation. We conducted a cross-sectional study of 400 HIV-1-infected and 200 HIV-1-uninfected women in Mombasa, Kenya to examine the relations between vitamin A deficiency (serum retinol <30 microg/dL) and HIV-1 status, HIV-1 disease stage, and the acute phase response (serum C-reactive protein >or=10 mg/L and/or alpha1-acid glycoprotein >or=1.2 g/L). Among the HIV-1-infected women, the effect of vitamin A supplementation was examined in a randomized trial. Vitamin A deficiency was independently associated with HIV-1 infection (OR = 2.7, 95% CI: 1.9-4.0) and the acute phase response (OR = 2.8, 95% CI: 1.9-4.1). Among HIV-1-infected women, vitamin A deficiency and the acute phase response were associated with each other and were both independently associated with higher HIV-1 plasma viral load and lower CD4 count. HIV-1-infected women having an acute phase response had no increase in serum vitamin A levels after supplementation. Serum levels increased significantly among women without an acute phase response, although not to normal levels among women who were deficient at baseline. Among HIV-1-infected individuals, it is likely that low serum vitamin A concentrations reflect more active infection and the acute phase response. These results provide possible explanations for the disparity between observational studies and randomized trials of vitamin A for HIV-1 infection.     

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C

Background: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. Methods: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. Results: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of ⩾3, ⩾4, or ⩾5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. Conclusions: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

Ventricular septal rupture with "normal" coronary arteries

A 73-year-old woman was admitted to St. Margaret's Hospital with a history of an acute anteroseptal infarction, a loud cardiac murmur, and low cardiac output. Cardiac catheterization revealed a large, high ventricular septal defect and normal coronary arteries. Despite successful closure of the ventricular septal rupture, death occurred in the operating room due to severe right ventricular dysfunction. Although this patient had normal major coronary arteries, a ventricular septal rupture developed, which was probably caused by spasm or isolated atherosclerotic disease of a large septal perforator.     

Generalized lymphadenopathy with morphologic features of Castleman's disease in an HIV-positive man

In recent years the literature has described a highly lethal "multicentric" variant of classic Castleman's disease (CD) with similar hyperplastic angio-follicular morphologic features. A 44-year-old man who was not known to be part of any established high-risk group for the acquired immune deficiency syndrome (AIDS) presented with clinical and laboratory features similar to "multicentric" CD. Serologic testing revealed antibody to the human immunodeficiency virus (HIV) by Western blot analysis. It is suggested that "multicentric" CD may be part of the clinicopathologic spectrum of HIV infection, and there should be a high index of suspicion for HIV in patients presenting with generalized lymphadenopathy and histopathologic features of CD.     

Alternate therapy for traumatic pneumothorax in "pocket shooters"

Traumatic pneumothorax is a common complication of the IV drug abusers in Detroit who utilize the "pocket shot" (the central approach to the internal jugular vein). Fourteen patients who sustained a total of 16 pneumothoraces (two with bilateral collapse) and who underwent catheter aspiration of a simple pneumothorax (CASP) were studied prospectively. The sizes ranged from less than 10% to 100%. In addition, there was one tension pneumothorax and one pneumomediastinum. The 16 CASP procedures produced 13 successful lung expansions (82%). The remaining three were treated with tube thoracostomy and admission. Twelve of the 13 patients in whom the procedure was successful returned for followup, and all of these had 100% continued full expansion. CASP appears to be a safe, efficacious, and cost-effective treatment for the drug abuser with simple traumatic pneumothorax. With the current pressures of cost containment, this less-invasive approach with outpatient management should be studied as initial potential treatment for any simple pneumothorax.     

Respiratory effects in two-dimensional Fourier transform MR imaging

Respiratory and other regular motions during two-dimensional Fourier transform magnetic resonance imaging produce image artifacts consisting of local blurring and more or less regularly spaced "ghost" images propagating along the direction of the phase-encoding magnetic field gradient. The patterns of these ghost artifacts can be understood in terms of the technique of image production and basic properties of the discrete Fourier transform. This understanding permits, without respiratory gating, production of images of improved quality in body regions in which there is significant respiratory motion. In particular, the ghosts can be maximally separated from the primary image by choosing intervals between phase-encoding gradient pulse increments that are equal to one-half the respiratory period; they can be minimally separated by choosing an interval equal to the respiratory period. Increasing the number of signal averages between each phase-encoding increment decreases the intensity of the ghosts.     

Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis

Experiments have demonstrated interlobe differences in the incidenceof diethylnitrosamine (DEN)-induced hepatocellular carcinoma(HCCA), with a 100% incidence in the left and right median lobesand a 30% incidence in the right anterior lobe 20 weeks afterexposure began. These tumor data provide a model to test thehypothesis that chemically induced neoplasia can be qualitativelyand quantitatively related to promutagenic DNA damage and concurrentcell replication. Experiments were performed to measure O⁴-ethyldeoxythymidine(O⁴-EtdT) (a major pro-mutagenic lesion in hepatic DNA of ratsexposed to DEN), N7-ethylguanine, cell replication and hepatocyteinitiation using the induction of growthselected -glutamyl transferase-positive(GGT+) foci in the left and right median and right anteriorhepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration.Results demonstrated that O⁴-EtdT concentrations were consistentlyhigher in the left and right median versus the right anteriorhepatic lobes, while cell replication was transiently higherin the right median and right anterior lobes. Likewise, highnumbers of GGT+ foci were observed in the left and right medianlobes in DEN-exposed rats subjected to a Cayama-Farber growthselection protocol. Following administration of [¹⁴C]DEN, thedistribution of radioactivity showed a marked left lobe preferencein 4-week-old rats that had no prior exposure to DEN and in8-week-old rats exposed to DEN for 4 weeks. This study suggeststhat interlobe differences in hepatocyte initiation and theincidence of HCCA may be due in part to differences in cellreplication and in DNA alkylation resulting from differentialDEN distribution and/or metabolism.