Liver Injury in People With HIV on Antituberculosis and/or Antiretroviral Therapy-Assessing Causality Using the Updated Roussel Uclaf Causality Assessment Method.

PURPOSE: We compared performance of the Roussel Uclaf Causality Assessment Method (RUCAM) with multidisciplinary expert panel review in identifying a drug-induced liver injury (DILI) due to antituberculosis therapy (ATT) and/or antiretroviral therapy (ART). METHODS: Cases were drawn from a prospective registry of hospitalised adults with suspected DILI due to ATT and/or ART in Cape Town, South Africa. Participants had to fulfil American Thoracic Society criteria for ATT interruption (alanine transaminase [ALT] ≥5 times upper limit of normal [ULN]/ALT ≥3 times [ULN] and symptomatic). Causality assessment by expert panel review served as reference standard. The panel ranked potentially implicated drugs as certain, probable, possible or unlikely causes guided by World Health Organization Uppsala Monitoring Centre criteria. The RUCAM was performed for each potentially implicated drug. We calculated sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause for liver injury. RESULTS: We included 48 participants. All were people with HIV (PWH). Twenty-seven were on concomitant ART and ATT, with a median of six potentially hepatotoxic drugs per case. Sensitivity and specificity of the RUCAM in identifying a probable/certain drug cause of liver injury compared with expert panel review was 7% and 100% respectively. Implicated drugs (times ranked probable/certain by panel) were isoniazid (18/0), pyrazinamide (17/0), rifampicin (15/1), efavirenz (6/4) and lopinavir/ritonavir (1/0). CONCLUSIONS: PWH with liver injury received multiple potentially implicated drugs, which may increase liver injury risk and complicate causality assessment. Compared with expert panel review, the RUCAM had low sensitivity in detecting probable or certain drug causes of liver injury.

Optimization of thermodynamic and surface properties of ternary Ti-Al-Si alloy and its sub-binary alloys in molten state.

Thermodynamic and surface properties of the ternary system were studied at different higher temperatures (1973 K, 2073 K, 2173 K and 2273 K). The thermodynamic properties were studied using the Chou, Kohler and Toop models. Meanwhile, the surface properties were investigated using the same models plus the Butler model. The thermodynamic and surface properties of the ternary alloys computed from different models were compared with one another. The surface concentration of the components of the ternary Ti-Al-Si alloy was computed using Butler's equation.

Study of surface tension and viscosity of Cu-Fe-Si ternary alloy using a thermodynamic approach.

The surface tension and viscosity of Cu-Fe-Si ternary alloys were computed at different temperatures using thermodynamic approaches. The thermodynamic data of the alloy were optimized in the framework of the Redlich-Kister (R-K) polynomials and exponential temperature dependent coefficients of the R-K polynomial were obtained. These coefficients were used to compute the excess Gibbs free energy of mixing of the alloy and the partial excess free energy of the components. The partial excess free energy so obtained was used to compute the surface tension of the ternary Cu-Fe-Si alloy system and its binary sub-systems. The enthalpy of mixing was also optimized and it was used to compute the viscosity of the sub-binary and ternary alloys.

Assessing the value of Western Cape Provincial Government health administrative data and electronic pharmacy records in ascertaining medicine use during pregnancy.

BACKGROUND: In African settings, where there is a high disease burden, there is a need to improve the science of documenting and analysing accurate information regarding medicine exposures in women immediately before and during pregnancy to assess the extent of use and safety in pregnant women and their unborn children. OBJECTIVES: To compare evidence of medicine use during pregnancy, as documented in paper-based clinical records (maternity case records (MCRs)) against electronic health information resources (Provincial Health Data Centre (PHDC)) and assess the level of concordance between the two as part of baseline investigations before piloting a provincial pregnancy exposure registry and birth defect surveillance system. The PHDC consolidates electronic clinical and pharmacy data. METHODS: A folder review of completed pregnancies between November 2013 and January 2016 was conducted on randomly selected MCRs from midwife-run obstetric units and a secondary maternity hospital in Cape Town, South Africa. Medication exposures in the MCR were captured and compared with a customised PHDC data extract. The type and timing of drug exposures were compared. Total exposures were compiled from all data sources. RESULTS: Two hundred and six MCRs from three facilities were sampled: 83 women had documented antiretroviral therapy (ART) exposure; all but 1 (1%) had been recorded in the PHDC extract. There was no evidence of ART use in the MCRs of 4 (5%) cases, despite evidence in the PHDC. There were imprecise drug names in the MCRs of 14 (17%) ART patients, discordant dates of onset between the MCRs and PHDC extracts in 10/83 (12%) and inaccurate medicine names and incorrect dates in 1 (1%) case each. Nine of 10 (90%) women who were administered antituberculosis medication were recorded in the PHDC extract. Ten of 21 (48%) isoniazid preventive therapy treatments appeared in the MCRs and PHDC; 9 (42%) in the PHDC only and 2 (10%) in the MCRs only. Half (n=18/36) of all antibiotic use was reflected only in the MCRs, while 13/36 (36%) appeared only in the PHDC extract. In the former cases, antibiotics used for treatment of sexually transmitted infections and urinary tract infections were dispensed from ward stock and not captured electronically. Antibiotics reflected only in the PHDC were either dispensed at a referral facility or before the first recorded antenatal clinic visit. Folic acid and iron were mostly documented in the MCR only (n=79/99 (80%) and n=107/128 (84%), respectively). However, analgesics and antihistamines more often appeared in the PHDC extract only (n=11/16 (73%) and n=5/5 (100%), respectively). CONCLUSIONS: The PHDC extract provided a better and more complete reflection of chronic drug exposures compared with the MCRs, especially when women sought care at facilities other than the antenatal care unit where they first attended, or when exposures occurred before the initial antenatal visit. The exception was antibiotics dispensed from ward stock to treat sexually transmitted and urinary tract infections.

Isolation, purification and characterization of low molecular weight 110mAg-binding proteins from the rat and goat testis.

Low molecular weight 110mAg-binding proteins have been purified from the goat and rat testis using a combination of acetone fractionation, gel filtration and ion-exchange chromatography. Both the rat and goat 110mAg-binding proteins existed in three isoforms, although the goat isoforms carried higher net negative charge than the corresponding isoforms of the rat. The average molecular weight of the goat isoforms was 8000 daltons, whereas that of the rat isoforms was 6300. The goat 110mAg-binding protein (a mixture of all the isoforms) was stable when heated at 85 degrees C for 15 min. The isoform II of the rat 110mAg-binding protein showed little absorbance at 280 nm, although the corresponding isoform of the goat protein did show significant absorbance at the same wavelength.

Extracorporeal membrane oxygenation for cardiac support in pediatric patients.

Extracorporeal membrane oxygenation (ECMO) has been used for pediatric cardiac support in settings of expected mortality due to severe myocardial dysfunction. We reviewed the records of 34 children (<18 years) placed on ECMO between March 1995 and May 1999. Demographic, cardiac, noncardiac, and outcome variables were recorded. Data were subjected to univariate analysis to define predictors of outcome. Eighteen patients were placed on ECMO after cardiac surgery (Group A); seven of 18 were weaned off ECMO, and four survived to discharge (22%). Thirteen patients were placed on ECMO as a bridge to cardiac transplantation (Group B), six of 13 received a heart transplant, one recovered spontaneously, and six survived to discharge (46%). Three patients were placed on ECMO for failed cardiac transplantation while awaiting a second transplant (Group C); one recovered graft function, two received a second heart transplant, and two of three survived (66%). The primary cause of death was multiorgan system failure (68%). Group A patients supported on ECMO for more than 6 days did not survive. Mediastinal bleeding complications and renal failure requiring dialysis were associated with nonsurvival. We conclude that ECMO as a bridge to cardiac transplant was more successful than ECMO support after cardiotomy. Mediastinal bleeding and renal failure were associated with poor outcome. Recovery of cardiac function occurred within the first week of ECMO support if at all. Longer support did not result in survival without transplantation.

Trace element changes in hair during pregnancy: preliminary study.

Using neutrons activation analysis, the changes in concentrations of Cu, Zn and Mn in hair during pregnancy are studied. Scalp and pubic hair samples from both non-pregnant and pregnant female subjects were analysed. The results of this preliminary study are presented. Cu, Zn and Mn levels in scalp hair obtained from pregnant subjects were not significantly different from those of non-pregnant subjects. However, pubic hair samples obtained from subjects in the ninth month of pregnancy showed significantly lower Zn levels whereas Cu and Mn levels remained normal. Studies on two subjects in the last trimester showed a steady fall in Cu and Zn levels in pubic hair with advancement of pregnancy; Mn level did not, however, show any change. The reliability of analysis was checked using standard reference materials, such as Bovine Liver and Orchard Leaves (U.S. NBS).

Selenium supplementation and diet induced hypercholesterolemia in the rat: changes in lipid levels, malonyldialdehyde production and the nitric oxide synthase activity.

Male Sprague Dawley rats were divided into three groups, viz (I) Controls, (II) High fat diet (HFD) fed, (III) HFD fed+selenium supplemented. After three months of treatment, there were significant increases in serum cholesterol and triglycerides in HFD fed group as compared to control. However, in Se supplemented group, the levels of serum cholesterol and triglycerides were significantly less as compared to group II. Selenium-dependent glutathione peroxidase (GSH-Px) activity in the liver and the aorta increased significantly in HFD fed animals and also showed additional significant increase on selenium supplementation. Malonyldialdehyde (MDA) concentrations in serum, liver and aorta and the activity of nitric oxide synthase (NOS; evident from reactive nitrogen intermediates and citrulline levels) in plasma showed significant increases in HFD fed group. However, supplementation of selenium led to a significant reduction in the levels of these parameters vis-a-vis HFD fed animals except in MDA levels in the serum and the liver where this decrease was non-significant. The important finding of this study is that selenium supplementation modulates the sequences favoring pathogenesis of atherosclerosis.

Studies of apoptosis and bcl-2 in experimental atherosclerosis in rabbit and influence of selenium supplementation.

Apoptosis is a ubiquitous physiological mechanism of cell death regulating tissue mass and architecture. An attempt was made in the present study to see the occurrence of apoptotic cell death in three different treatment groups of rabbits viz. Control, HFD fed and HFD + Selenium fed. Apoptotic activity as checked by in situ DNA end labelling (TUNEL Assay) revealed excessive staining, mostly concentrated in plaque region both in fibrous as well as atheromatous plaque in HFD fed animals. However, in selenium (Se) supplemented animals, very little TUNEL staining could be seen, and even that confined to endothelial cells only. The control group on the other hand was totally devoid of any staining. Transmission Electron Microscopic (TEM) study also depicted the occurrence of apoptosis in aortic cells of HFD fed animals and very little in Se supplemented animals. Apoptotic activity has been discussed in relation to oxidative stress in HFD fed group. bcl-2, though an antiapoptotic oncoprotein, was found to be expressed more in atherogenic group as compared to control/HFD + Se treatment. On the whole, the study highlighted the occurrence of apoptotic process in atherosclerosis and the role of Se, a potent antioxidant, in inhibition of apoptotic process in HFD fed animals.

Hyperlipidemia and type I 5'-monodeiodinase activity: regulation by selenium supplementation in rabbits.

Male New Zealand White rabbits were divided into three groups: (I) control, (II) high-fat-diet (HFD) fed, and (III) HFD fed + selenium supplemented. After 3 mo of treatment, there was a significant increase in serum cholesterol and triglycerides in the HFD-fed group as compared to the control. However in the selenium (Se)-supplemented group, the levels of serum cholesterol and triglycerides were significantly less as compared to group II. HFD feeding resulted in decreased serum Se levels, but supplementation of dietary Se along with HFD, as in group III, showed an apparent increase in its levels. The Se-dependent glutathione peroxidase (GSH-Px) activity in the liver and the aorta increased significantly in HFD-fed animals and also showed an additional significant increase on Se supplementation. Both serum T3 and T4 levels showed a significant decrease on HFD feeding. However, supplementation of Se led to a significant increase in the levels of these parameters viz-à-viz HFD-fed animals. HFD feeding significantly decreased the activity of type I iodothyronine 5'-deiodinase (5'-DI) in the liver from group II rats. On supplementation of Se along with HFD, the activity increased in the liver. However, there was no significant change in its activity in the aorta. The 5'-DI activity in the thyroid showed an opposite trend in comparison with peripheral tissues (i.e., liver). The important finding of this study is that in the hyperlipidemic state, deiodinase in the thyroid behaves in a different manner as compared to its activity in extrathyroidal tissues.

Microcornea with corectopia and macular hypoplasia in a family.

Three cases of true microcornea are presented, involving two successive generations. The possible embryological significances of the rare associated anomaly of corectopia (in two of the cases), and the so far unreported association of macular hypoplasia (in the two sibs) are discussed.

Effect of diet induced hypercholesterolemia and selenium supplementation on nitric oxide synthase activity.

The aim of the present study was to examine the activity of nitric oxide synthase (NOS, EC 1.14.23) in plasma of high fat diet (HFD, 2% cholesterol and 100 g table butter/kg diet) and HFD + selenium (Se, 1 ppm as sodium selenite) fed rabbits for three months. Significant increase in the serum cholesterol and triglyceride levels in HFD fed group was observed. The activity of NOS also increased very significantly. However in Se supplemented animals, there was a significant reduction in serum cholesterol as well as in plasma NOS activity relative to HFD fed animals. It is concluded that the protective effect of Se on HFD induced NOS activity acts probably through its antioxidant/inhibitory action.

Iron bioavailability from Spirulina platensis, whole egg and whole wheat.

Bioavailability of iron from Spirulina was assessed in comparison with whole egg, whole wheat and standard ferrous sulphate using haemoglobin depletion repletion assay. Haemoglobin regeneration efficiency of Spirulina and whole egg was similar and significantly higher than that of whole wheat. The absorption of iron from Spirulina was significantly lower than that of ferrous sulphate and whole egg but significantly greater than that from whole wheat.

Selenium supplementation protects from high fat diet-induced atherogenesis in rats: role of mitogen stimulated lymphocytes and macrophage NO production.

The present study was designed to demonstrate the involvement of immune response in experimental atherogenesis. The mitogenic stimulation of lymphocytes and NO production by macrophages in experimental atherogenesis were studied. Further, influence of selenium a potent antioxidant was also studied in the disease process. Three different treatment groups of rats undertaken for study were: group 1, control; group II, high fat diet (HFD) fed group and group III, HFD+Se supplemented group. Atherogenic conditions induced have already been explained earlier [Kang BPS et al. Gen Physiol Biophys, 17 (1998) 71]. Significant increase in 3H-thymidine incorporation was obtained in lymphocytes from HFD fed animals in both presence and absence of mitogen (Con-A). However, these values decreased in group III animals, which were supplemented with selenium. Similarly, NO levels with LPS+ and LPS- macrophages also found to be higher in HFD fed group and decreased in group III. These studies reveal the protective role of selenium in HFD-induced atherogenic process.

Effect of dietary zinc and copper on peripheral blood plasma cholesterol, testosterone and histomorphology of testes in rats.

Total plasma cholesterol (mg/dl) significantly (P less than 0.01) decreased from 70.8 to 54.01 as the dietary Cu levels increased from 2.5 to 5 ppm at 12 pm Zn concentrations in male weanling rats. A similar trend was observed in the blood peripheral testosterone concentration at 12 ppm Zn and 2.5 ppm Cu. Histological examination of testes revealed smaller seminiferous tubules with atrophy of germinal epithelium. Also a marked loss of spermatogenic cells was observed in Zn and Cu deficient rats.

Effect of anticalmodulin and antitubulin on LDL-receptor synthesis in aortic smooth muscle cells cultured in vitro.

Effect of trifluoperazine and colchicine on LDL-receptor synthesis in smooth muscle cells exposed to hypercholesterolemic medium in vitro have been studied. While trifluoperazine at 25 microM concentration caused stimulation of LDL-receptor synthesis, colchicine acted as a dose-dependent inhibitor of LDL-receptor synthesis. Thus calmodulin down regulates LDL-receptor synthesis independent of microtubular involvement.

Total alloplastic temporomandibular joint reconstruction using Biomet stock prostheses: the University of Florida experience.

The purpose of this study was to report the subjective and objective outcomes of temporomandibular joint (TMJ) replacement with Biomet stock prostheses at a single institution in Florida. In this retrospective study, patients who underwent TMJ replacement using a Biomet stock prosthesis from 2005 to 2012 were analyzed. Subjective (pain, diet) and objective (maximal incisal opening) information was obtained. In addition, a quality of life measure was obtained pre- and postoperatively. Significance was set at <0.01. Thirty-six patients (26 bilateral, 6 left, and 4 right) who underwent TMJ replacement using a Biomet stock prosthesis were eligible for the study. Maximal incisal opening improved from 26.1mm preoperatively to a mean of 34.4mm postoperatively. The pain score decreased from 7.9 preoperatively to a mean of 3.8 postoperatively. Diet restriction decreased from 6.8 preoperatively to a mean of 3.5 postoperatively. Quality of life improved from a median of 4 preoperatively to a postoperative median of 2. Four implants were removed/replaced because of heterotopic bone formation, infection, and/or loose hardware. Follow-up ranged from 6 to 83 months. Overall, TMJ reconstruction using the Biomet stock joint is effective and safe in this patient population.