Absence of HIV antigens in renal tissue from patients with HIV-associated nephropathy

HIV-associated nephropathy (HIV-N) is considered a distinctive disease, the pathogenesis of which is still undefined. Direct virus-induced renal cell damage has been postulated. The numerous cytolytic ultrastructural changes and a few studies by immunoperoxidase support this hypothesis, but there has been no demonstration of virus by electron-microscopy (EM) or by tissue culture. In seven out of 12 cases with histological characteristics of HIV nephropathy, with proteinuria (five cases) or with nephrotic syndrome (two cases), we tested renal tissue for HIV antigens: core p18 and p25; envelope gp45 and gp110, by means of immunoperoxidase avidin-biotin complex monoclonal antibodies (MoAbs). Light-microscopy (LM) showed in five patients a focal and segmental glomerular sclerosis, and in two a mesangial hyperplasia with vacuolisation of visceral epithelium and protein inclusions. Electron-microscopy, performed in five of seven patients, showed several protein inclusions in podocyte cytoplasm, tubuloreticular inclusions in endothelial cell cytoplasm in all cases, nuclear degranulation of tubular cells in four cases and nuclear bodies in two. HIV antigens by MoAbs on renal tissue were negative in all cases, in both glomeruli and tubules. These results do not confirm the presence of HIV proteins in renal tissue of patients with HIV nephropathy. A possible explanation, apart from no direct HIV in the disease, may be the low viral load in tissues, because of the early phases of renal damage in most cases.     

Long-term follow-up of patients with adolescent idiopathic scoliosis treated conservatively: an analysis of the clinical value of progression

In a retrospective study, 217 patients with conservatively treated adolescent idiopathic scoliosis (AIS) were investigated. Forty-nine cases were operated and 168 were treated only conservatively and had been out of the brace for at least 4 years at the time of the investigation. The progression between cessation of brace treatment and follow-up (a mean of 6.9 years later) was 5.1 degrees. Almost all progression (4.5 degrees) occurred within 2 years of the end of weaning, however. The incidence of failure with regard to the length of follow-up was also studied. A follow-up of 2 years was sufficient to predict with great accuracy (97%) all incidences of failure.     

Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1

Human cytochrome P-450IIE1 has been implicated in the oxidation of a number of substrates, including protoxins and -carcinogens. To date, no drugs have been identified that are exclusive substrates for the protein and are applicable for use as noninvasive probes of the in vivo function of the enzyme in humans. Chlorzoxazone was found to be oxidized only to 6-hydroxychlorzoxazone in human liver microsomes. Results of steady-state kinetics are consistent with the view that only a single enzyme catalyzes the reaction. The microsomal reaction was strongly inhibited by rabbit anti-P-450IIE1 and, in a competitive manner, by known P-450IIE1 substrates. Rates of chlorzoxazone 6-hydroxylation in different human liver microsomal preparations were well correlated with levels of immunochemically measured P-450IIE1 and rates of (CH3)2NNO oxidation. Chlorzoxazone 6-hydroxylation was also found to be catalyzed by purified human liver P-450IIE1. These results provide strong evidence that P-450IIE1 is the primary catalyst of chlorzoxazone 6-hydroxylation in human liver. Rates of chlorzoxazone 6-hydroxylation vary considerably among human liver samples, and chlorzoxazone 6-hydroxylation may have potential use as a noninvasive probe in estimating the in vivo expression of human P-450IIE1 and its significance as a risk factor in the toxicity and carcinogenicity of a number of solvents, nitrosamines, and drugs.     

Some central effects of brofaromine given repeatedly are phase-dependent

Effects of the MAO-A-inhibitor brofaromine (BRO), 10 mg/kg po after repeated (twice daily for 14 days) administration on the spontaneous behavior (exploratory and basal locomotor activities) and the exploratory activity modified by methoxamine, clonidine and d-amphetamine in male Wistar rats were studied in both light and dark phases of a diurnal cycle (L: 0700-1900 h). After single administration BRO in the light phase had no effects. In the dark phase BRO decreased the exploration (62% of control, p less than 0.01), increased the clonidine-evoked hypoactivity and amphetamine-evoked hyperactivity. The L-D differences occurred also after repeated administration. BRO in the light phase did not influence the exploration, decreased basal locomotor activity, did not change methoxamine and clonidine action and potentiated the action of amphetamine. In the dark phase, however, it did not influence the exploration and basal locomotor activity, intensified the methoxamine effect, and did not change the clonidine and amphetamine actions. The results demonstrate that the effects of BRO on behavior in rats: 1) differ from the effects caused by other antidepressants which are not MAO inhibitors; 2) are phase-dependent after both single and repeated administration.     

New stand magnifiers do not meet rated levels of performance

A new range of stand magnifiers has been released by the COIL company in the United Kingdom. Examination of these magnifiers reveals that they fail to deliver the rated magnifications labelled prominently on the appliances, as a result of the manufacturer's conformance with the requirements of the German DIN standard and the use of back vertex power (F'_v) rather than equivalent dioptric power (F_m) of the magnifier. In this study we provide information on the optometric parameters of these new stand magnifiers that will assist the more accurate specification of improvements in vision expected from their use.     

Reduction of embryonic intracellular pH: a potential mechanism of acetazolamide-induced limb malformations

The effects of acetazolamide on the developing rodent limb bud were postulated to result from a reduction of intracellular pH (pHi). Embryonic intracellular pH was calculated from transplacental distribution of the weak acid, 5,5'-dimethyloxazolidine-2,4-dione, in teratogenically sensitive (C57BL/6) and resistant (SWV) inbred mice. pHi was reduced by acetazolamide treatment in C57 embryos and limb buds but not in SWV samples. Acetazolamide teratogenesis can be exacerbated by coadministration of amiloride, presumably through inhibition of Na+/H+ exchange attributable to the latter agent. pHi reduction after such treatment was more profound than after acetazolamide alone, providing further support for the central hypothesis. pH was also reduced in other embryonic (embryo plasma) and extraembryonic compartments (exocoelomic fluid, amniotic fluid). pH changes in these compartments could also lead or contribute to abnormal development.     

Conjugation pathways in liver disease.

1. The activities of microsomal glucuronyltransferase and thiomethyltransferase, and those of cytosolic sulphotransferase, acetyltransferase, glutathione transferase and thiomethyltransferase were measured in abnormal (cirrhosis and chronic hepatitis) and normal livers. 2. Glucuronyltransferase and sulphotransferase were investigated with 2-naphthol and ethinyloestradiol as substrates. p-Aminobenzoic acid, benzo(a)pyrene-4,5-epoxide and 2-mercaptoethanol were the substrates of acetyltransferase, glutathione transferase and thiomethyltransferase, respectively. 3. Enzyme activities are expressed as nmol min-1 incubation mg-1 protein and the averages (+/- s.d.) are given. With 2-naphthol as substrate, the glucuronyltransferase activity was 6.55 +/- 4.10 (abnormal liver, n = 33) and 7.81 +/- 4.02 (normal liver, n = 26) (NS); whereas sulphotransferase activity was 0.28 +/- 0.18 (abnormal liver, n = 35) and 0.68 +/- 0.43 (normal liver, n = 26) (P less than 0.01). Glucuronyltransferase activity towards ethinyloestradiol was 102.5 +/- 56.9 (abnormal liver, n = 30) and 107 +/- 59.9 (normal liver, n = 26) (NS), whereas sulphotransferase activity was 57.2 +/- 36.0 (abnormal liver, n = 35) and 122 +/- 67.6 (normal liver, n = 28) (P less than 0.01). Acetyltransferase activity was 0.84 +/- 0.83 (abnormal liver, n = 35) and 3.84 +/- 1.65 (normal liver, n = 26) (P less than 0.01). Glutathione transferase activity was 0.83 +/- 0.68 (abnormal liver, n = 35) and 2.90 +/- 1.59 (normal liver, n = 25) (P less than 0.01) and thiomethyltransferase activity was 1.00 +/- 0.69 (abnormal liver, n = 34) and 3.99 +/- 1.49 (normal liver, n = 25) (P less than 0.01). 4. Liver disease lowers the activities towards the substrates studied of sulphotransferase, acetyltransferase, glutathionetransferase and thiomethyltransferase but not that of glucuronyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of rat liver preservation with Eurocollins and a modified University of Wisconsin solution: transplantation and isolation of hepatocytes for culture

The efficiency of Eurocollins or modified University of Wisconsin (UW) solution (MUW) in preserving rat livers was compared. After cold storage with one of the solutions, the livers were transplanted or perfused by collagenase for isolation of hepatocytes. Five of the 6 rats receiving a graft preserved with MUW versus none of the 6 rat receiving a graft preserved with Eurocollins solution survived 24 h or more. A significantly greater number of hepatocytes were isolated from livers preserved with MUW than from livers preserved with Eurocollins solution. This suggests a better reperfusion of MUW-preserved livers by collagenase resulting from less endothelial injury. LDH release by cultured hepatocytes, ketone body production and stimulation by glucagon were not significantly different between the two groups. These results confirm the superiority of MUW solution over Eurocollins in preserving liver grafts. They suggest that the advantage of MUW solution results from better protection of vascular endothelium rather than of hepatocytes.     

Cup containment and orientation in cemented total hip arthroplasties

We reviewed the radiographs of 864 Charnley and STH (Zimmer) cemented total hip arthroplasties with a mean follow-up of seven years (maximum 16 years). Survivorship analysis was used to assess the correlation between radiographic performance and the bony containment or the coronal orientation of the acetabular cup. The cup orientation and containment were interrelated; all vertically oriented cups were completely contained, whereas 25% of more horizontal cups were only partially contained. Completely contained cups had significantly lower incidences of complete cement-bone radiolucency (p = 0.02) and of wear (p = 0.09). Vertically oriented cups had a lower incidence of continuous radiolucency than neutrally oriented cups, but this was not statistically significant (p = 0.25). Our results confirm the importance of complete bony containment, and also indicate that it is better to accept vertical orientation and obtain full bony coverage than to have a more horizontal orientation with partial containment.