Predicting death from HIV/AIDS: a case-control study from Florida public HIV/AIDS clinics

BACKGROUND: After markedly decreasing for 3 years, HIV/AIDS mortality declined only slightly in 1999. METHODS: The authors conducted a case-control study in four Florida urban public health HIV clinics to evaluate modifiable factors associated with HIV/AIDS mortality in a non-research setting. Structured chart review was conducted for 120 case-patients who died in 1999 and for 240 randomly selected control-patients. Risk factors associated with death in univariate analysis were entered into three conceptually related, matched logistic regression models. RESULTS: In the final multivariate model, homelessness (adjusted odds ratio [AOR], 9.98; 95% confidence interval [CI], 2.34-42.5), Medicaid insurance (AOR, 3.10; 95% CI, 1.43-6.74), having a documented adherence problem (AOR, 3.50; 95% CI, 1.64-7.47), injection drug use (AOR, 2.46; 95% CI, 1.11-5.43), non-specific liver failure (AOR, 76.9; 95% CI, 6.79-870.9), interrupted highly active antiretroviral therapy (HAART) secondary to side effects (AOR, 4.00; 95% CI, 1.46-10.9), and not receiving HAART (AOR, 2.62; 95% CI, 1.03-6.68) were independent predictors of mortality. CONCLUSIONS: In addition to medical and clinical indicators, several sociobehavioral-demographic factors remained important throughout the multivariate analysis. Improvement in care should include a focus on social circumstances of infected people. Special attention to the homeless, those with adherence problems, and those with liver disease is clearly indicated.     

Lamin expression in human adipose cells in relation to anatomical site and differentiation state

Familial partial lipodystrophy-Dunnigan variety (FPLD) is an autosomal dominant form of lipodystrophy resulting in a loss of sc fat from the trunk and limbs with retention of fat in the visceral depots, face, and neck. Specific point mutations in the gene encoding the nuclear lamina proteins, lamins A and C, have been established to cause this syndrome. We undertook studies to determine which members of the lamin family were expressed in human fat cells, to examine the effect of differentiation state on lamin A and C expression in human preadipocytes, and to test the hypothesis that regional variation in lamin A/C expression might underlie the stereotyped anatomical pattern of FPLD. Lamins A, C, and B1, but not B2, were expressed in sc mature human adipocytes. Subcutaneous preadipocytes expressed all four lamins, with lamin A and C expression increasing with ex vivo differentiation. Consistent with previously reported resistance to ex vivo differentiation, omental preadipocytes did not show an increase in lamin A or C mRNA under these conditions. Lamin A/C mRNA levels were similar in isolated mature adipocytes and preadipocytes from omental, sc, and neck sites. However, lamin C was consistently lower, and the ratio of lamin A/C mRNA was higher in sc mature adipocytes compared with omental mature adipocytes. We conclude that the depot-specific pattern of lamin A/C expression does not provide clues to the mechanism of FPLD. Nonetheless, these studies provide new information regarding the expression of lamin isoforms in normal human adipose cells, which will inform future studies of the molecular pathogenesis of FPLD.     

Effect of phacoemulsification on corneal thickness

PURPOSE: To determine the immediate effect on corneal thickness of cataract extraction using phacoemulsification. DESIGN: Prospective consecutive nonrandomized humans undergoing standard small-incision phacoemulsification and intraocular lens insertion. METHODS: Corneal thickness was measured immediately preoperative and postoperatively in 58 consecutive patients undergoing phacoemulsification in the absence of other ocular abnormalities. Corneal thickness was determined centrally and in the midperiphery of four quadrants. The last 17 eyes were also evaluated for the effect of pressure from a Honan balloon on corneal thickness. SETTING: Faculty practice in medical school and university hospital.The cornea thinned in all five of the measured locations, with statistical significance being reached only in the four midperipheral quadrants. Pressure from the Honan balloon resulted in a negligible increase in corneal thickness preoperatively. CONCLUSIONS: Corneas were found to have thinned statistically significantly immediately after phacoemulsification; however, the degree of thinning has doubtful clinical significance and does not represent a significant dehydration of the cornea during the surgical procedure.     

Histopathological responses of newly hatched larvae of whitefish (Coregonus lavaretus s.l.) to UV-B induced toxicity of retene

Positively phototactic fish larvae may be exposed to increased ultraviolet-B (UV-B) radiation alone or, potentially and in addition, to polycyclic aromatic hydrocarbons (PAHs) such as retene (7-isopropyl-1-methylphenanthrene) at the egg or larval stages. Suspended and sedimental particulate material near pulp and paper mills may act as sources of retene in chemically contaminated lake areas. In laboratory conditions whitefish larvae were pre-exposed to retene (10, 32 and 100 microg/l), with relevant controls, and irradiated in semi-static tests for 3 h once a day (2 consecutive days) with two UV-B doses (CIE-weighted 2.8 or 5.4 kJ per m(2) per day) or with visible light only. These UV-B doses correspond with slightly subambient and 80% increases relative to the natural maximum daily doses of the solar UV-B in Finland in early May. The UV-B radiation alone increased mortality only slightly (2.7 and 4.0%, respectively). Similarly, no mortality was observed due to retene alone. On the contrary, simultaneous UV-B and retene exposure caused very high mortality to whitefish and all larvae died in the highest retene concentration. The photoinduced acute LC(50) for retene was 13.3 microg/l. Retene treated fish exhibited signs of behavioral irritation and hypoxia during and after the exposure to UV light. Severe skin damages were detected in larvae exposed simultaneously to retene and UV-B. The structural signs of sunburn could also be seen in UV-B and solvent controls (DMSO) with UV-B. Even at the lowest retene concentration, the number of mucous cells increased significantly in simultaneous chemical and UV-B treatment. We consider the tissue reaction as protective response against UV induced retene toxicity. Further, regarding liver parenchyma, fish exposed to retene with UV-B had lesions, revealing hepatotoxicity. We suggest that synergism of the UV-B radiation and the photoactivating pollutants such as retene is a potential risk factor to be taken into consideration in lake areas chemically contaminated by the pulp and paper industry.     

Evidence for an altered balance between matrix metalloproteinase-9 and its inhibitors in calcific aortic stenosis

BACKGROUND: Recently, aortic valve stenosis has been demonstrated to exhibit increased expression of certain matrix metalloproteinases (MMPs), and this has relevantly raised the question about possible interdependency between these and their tissue inhibitors. We sought to assess the expression of elastolytic MMPs and their inhibitors (TIMPs) in nonrheumatic aortic stenosis. METHODS: The study comprised 30 stenotic and six noncalcified human aortic valves. To measure the expression levels and the amount and molecular forms of gelatinases (MMP-2, MMP-9) and TIMPs (1, 2), in situ hybridization, gelatin zymography, and reverse zymography were carried out. Antielastin staining by a monoclonal BA-4 antibody was performed to investigate the changes of one of the main substrates of these MMPs, and to substantiate the nature of the putative MMP- synthesizing cell. The cases were also immunostained with an antibody to alpha-smooth muscle actin. Inflammatory cell characterization was managed by monoclonal mouse antibodies (UCHL-1, L26, and PGM-1). RESULTS: Compared with the controls, the calcific valves showed increased mRNA expression and activation of MMP-9, and this was associated with typical characteristics of valve disease. MMP-2 mRNA production was rare, but proMMP-2 protein was detected in all valves. In agreement with the interdependency between MMP-9 and its inhibitors, a suggestive imbalance came out in diseased valves. CONCLUSIONS: The disproportion between MMP-9 and its tissue inhibitors may favor a persistent MMP activation state within the calcific valve and likely contribute to the valvular remodeling process in the setting of developing aortic stenosis.     

The biological and biochemical effects of CP-654577, a selective erbB2 kinase inhibitor,on human breast cancer cells

Aberrant expression or activity of epidermal growth factor receptor (EGFr) or the closely related p185(erbB2) can promote cell proliferation and survival and thereby contribute to tumorigenesis. Specific antibodies and low molecular-weight tyrosine kinase inhibitors of both proteins are in clinical trials for cancer treatment. CP-654577 is a potent inhibitor selective for p185(erbB2), relative to EGFr tyrosine kinase, and selectively reduces erbB2 autophosphorylation in intact cells. Treatment of SKBr3 human breast cancer cells with CP-654577 reduces the levels of the activated form of mitogen-activated protein kinase, increases the levels of cyclin-dependent kinase inhibitor p27(kip1) and reduces expression of cyclins D and E. These biochemical changes result in a reduced level of phosphorylated retinoblastoma protein and an inhibition of cell-cycle progression at G(1). Apoptosis is triggered in both SKBr3 and another high erbB2-expressing cell line, BT474, by exposure to 1 micro M CP-654577, but this effect is not observed in MCF7 cells that express low erbB2. Levels of activated Akt, an important positive regulator of cell survival, are reduced within 2 h of exposure to 250 nM CP-654577, and this may contribute to the increased apoptosis. These biochemical effects are distinct from those produced by Tarceva, a selective EGFr inhibitor. The antitumor activity of CP-654577 was investigated in athymic mice bearing s.c. tumors from Fischer rat embryo fibroblasts transfected with erbB2. CP-654577 produced a dose-dependent reduction of p185(erbB2) autophosphorylation and inhibited the growth of these tumors. CP-654577 warrants further evaluation in tumors with high expression of p185(erbB2) and may differ from selective EGFr inhibitors or nonselective dual EGFr/erbB2 inhibitors in efficacy and therapeutic index.     

Morgagni hernia: case report

This is a case report of an elderly woman who presented with a history of epigastric pain and persistent vomiting diagnosed initially as a duodenal ulcer, later as a pyloric stenosis and at laparotomy was found to have an anterior diaphragmatic hernia with gastric volvulus. Hernia of Morgagni occurs through a congenital defect in the diaphragm but usually presents in adulthood. It could be an incidental diagnosis or can present with obstructing symptoms of the herniated viscera. Treatment is surgical with reduction of hernia and repair of the diaphragmatic defect. If misdiagnosed, this can lead to considerable morbidity and occasionally mortality due to the obstructed/strangulated hernial contents.     

Plummer Vinson syndrome: case report

Plummer Vinson syndrome is characterised by dysphagia, iron deficiency, anaemia and oesophageal web or webs. This is a case report of a 33 year old Asian female who presented with slowly progressive dysphagia and a long history of iron deficiency anaemia. The anaemia was confirmed on repeated haemograms and a barium swallow revealed an upper oesophageal web. Upper gastrointestinal endoscopy and forceful dilatation were necessary to effect relief of dysphagia.     

Radiation safety of personnel during catheter-based Ir-192 coronary brachytherapy

Catheter-based brachytherapy using Ir-192 seed sources has shown significant reduction in the rate of restenosis among patients with coronary in-stent restenosis. High-energy gamma rays from Ir-192 raise some radiation safety issues of personnel. The aim of this study was to fully analyze the radiation safety issues associated with Ir-192 brachytherapy in the cardiac cath lab environment. Measurements were made to assess the penetrating ability of Ir-192 gamma rays through tissues, concrete and lead. Radiation exposure levels were measured around a large number of patients undergoing Ir-192 brachytherapy. Personnel were carefully monitored for any additional dose received from brachytherapy for the last five years covering > 500 cases. Our results showed that with a proper radiation safety program in place, the dose to cath lab staff was negligible. It was concluded that radiation safety of personnel was easy to maintain during catheter-based coronary brachytherapy using Ir-192 seed sources.