Persistently normal alanine aminotransferase levels in HIV/HCV-coinfected patients: the role of steatosis

Objective

The frequency and significance of, and liver biopsy findings associated with, a persistently normal alanine aminotransferase (ALT) level in HIV/hepatitis C virus (HCV)‐coinfected patients are poorly characterized. We analysed factors associated with persistently normal ALT levels, defined as at least three consecutive normal ALT values over a 6‐month period, in a group of 381 HIV/HCV‐coinfected patients.

Methods

Patients were categorized into two groups according to ALT values: group 1, patients with persistently normal ALT levels; and group 2, patients with elevated ALT values. Possible interactions with host factors, HIV and HCV viral factors, antiretroviral treatment and histological features were examined.

Results

Thirty‐six patients (9.4%) had persistently normal ALT levels. None of the 36 patients had cirrhosis. Seven patients (19.4%) had a METAVIR fibrosis score of F3. In multivariate analysis, a lower mean METAVIR inflammation score [odds ratio (OR) 0.50, 95% confidence interval (CI) 0.28–0.89; P=0.017], the absence of steatosis (OR 0.43, 95% CI 0.20–0.90; P=0.026) and HCV genotype 4 infection (OR 2.81, 95% CI 1.15–6.68; P=0.023) were associated with persistently normal ALT levels.

Conclusion

The slower progression of chronic hepatitis in patients with persistently normal ALT levels could be related, in part, to a lower frequency of steatosis

     

Urethral injury associated with minimally invasive mid-urethral sling procedures for the treatment of stress urinary incontinence: a case series and systematic literature search

The introduction of the TVT™ has brought about dramatic changes in our practice as regards surgery for stress urinary incontinence, although the risk of bladder injury has caused concern. The subsequent development of tapes introduced through the obturator foramina may limit the rate of bladder injury, and some have suggested that cystoscopy is no longer required during stress incontinence surgery. Several cases of urethral injury referred to our unit have caused us concern about this approach. We present here brief details of these cases along with a systematic search of the literature on urethral injury following mid-urethral tape procedures.     

CONCURRENT MYELITIS AND GUILLAIN-BARRÉ SYNDROME AFTER VARICELLA INFECTION

Myelitis and Guillain-Barré syndrome occurring concurrently after varicella infection is very rare. A 34-year-old man presented with progressive flaccid tetraparesis, facial palsy, respiratory failure, sensory loss and urinary incontinence one week after varicella infection. Clinical, imaging and electrodiagnostic studies supported the diagnosis of myelitis and Guillain-Barré syndrome. He improved with intravenous acyclovir and gammaglobulin.     

One-stage Fowler-Stephens orchidopexy for impalpable undescended testis

Background The Fowler-Stephens orchidopexy (FSO) is a well-described treatment for high maldescended testes where the limiting factor for successful placement in the scrotum is short testicular vessels. The operation involves division of these vessels. The testicular blood supply is then dependent on collaterals from the vasal artery. Aims To assess the long-term outcome of patients who underwent this procedure in our institution. Methods The medical records of 20 patients who underwent 22 FSO from 1978 to 1999 by one urologist (HB) were reviewed. Outcome was assessed in terms of testicular position and size. Results Age at operation ranged from 2 to 14 years (mean 5.8 years). All patients had a one-stage FSO and in two of them the procedure was bilateral. In five patients, FSO was preceded by a diagnostic laparoscopy. Mean follow up was 22 months (range 0–121 months). Overall, results were considered good in 18 of 22 testes (82%). Conclusion Our results for the one-stage FSO are comparable with other procedures for the management of high maldescended testis.     

Hemolysis and thrombocytopenia following oxaliplatin administration

Oxaliplatin is a platinum derivative with an overall excellent safety profile that has a major role in the treatment of colorectal cancer. With a proven role now in the adjuvant setting, rare but potentially life‐threatening toxicities become a more significant issue. We report here a case of significant postinfusion hemolysis and thrombocytopenia in a patient undergoing adjuvant chemotherapy for stage III colon cancer, and review the literature. Six cases of hemolysis following oxaliplatin treatment have previously been reported, all in the setting of advanced colorectal cancer, with one case resulting in death. In three of the seven reports (including the present case), warning signs of low grade hemolysis were apparent during preceding cycles, with fever and/or back pain during the infusion being the most common feature. Our case appears to be the first reported with a direct antiglobulin test‐negative hemolysis with thrombocytopenia, with each of the previous reports postulating an autoimmune basis. Hemolysis and/or thrombocytopenia are potentially life‐threatening complications of oxaliplatin chemotherapy. With the increasing use of oxaliplatin in the adjuvant setting, clinicians need to be aware of this entity and the possible clinical warning signs that may be evident in preceding cycles.     

Short-term fasting and the reversal of the stage of promotion in rat hepatocarcinogenesis: role of cell replication, apoptosis, and gene expression

Studies of the multistage nature of hepatocarcinogenesis in the rat have led to the development of models having significant potential application to carcinogenesis in other tissues as well as other species. Whereas the initial and final stages of carcinogenesis- initiation and progression-involve genetic changes and are operationally irreversible, the intermediate stage of promotion is operationally reversible and can be modulated by a variety of environmental factors. Numerous investigations have demonstrated that chronic caloric restriction modifies neoplastic development, primarily during the stage of promotion, so that fewer lesions develop. Short- term fasting of rats, initiated with a nonnecrogenic dose of diethylnitrosamine (DEN) and promoted with 0.05% phenobarbital (PB) for 4 weeks, results in loss of virtually all of the measurable altered hepatic foci (AHF) after two 5-day periods of fasting with an intermediate 2-day period of feeding. This change was accompanied by a marked decrease in bromodeoxyuridine (BrdU) labeling of hepatocytes within AHF together with a significant increase in apoptosis of such cells measured by nick end-labeling. Similar but lesser effects were noted in surrounding, nonfocal hepatocytes. On refeeding, both the numbers and volume percentage of AHF returned within 2 weeks to values seen in nonfasted controls. Administration of PB during the fasting period did not alter these results, although AHF reappeared more rapidly in such animals on refeeding. Nuclear DNA fragmentation was evident in samples of whole liver from fasted animals. During this same period the expression of c-myc mRNA increased 3- to 9-fold, while levels of albumin and insulin-like growth factor I mRNAs decreased significantly. This study demonstrates a model system in which the reversibility of the effects of promoting agents may be rapidly determined and the effects of chemopreventive inhibitors of promotion may be rapidly evaluated.      

Metabolic activation of methyl-hydroxylated derivatives of 7,12- dimethylbenz[a]anthracene by human liver dehydroepiandrosterone-steroid sulfotransferase

Methyl-hydroxylated metabolites of the potent carcinogen, 7,12- dimethylbenz[a]anthracene (DMBA), namely, 7-hydroxymethyl-12- methylbenz[a]anthracene (7-OH-DMBA), 7-methyl-12- hydroxymethylbenz[a]anthracene (12-OH-DMBA) and 7,12- dihydroxymethylbenz[a]anthracene (7,12-diOH-DMBA), were examined as substrates for sulfotransferase bioactivation in different human tissue cytosols. Hepatic cytosols, which were able to catalyze the 3'- phosphoadenosine 5'-phosphosulfate (PAPS)-dependent DNA binding of 7-OH- DMBA, 12-OH-DMBA and 7,12-diOH-DMBA, were highly sensitive to inhibition by dehydroepiandrosterone (DHEA), a specific substrate for human DHEA-steroid sulfotransferase (IC50 = 5 microM). By comparison, 2,6-dichloro-4-nitrophenol, a potent inhibitor of the thermostable (TS)- phenol and estrogen sulfotransferases, did not have an appreciable inhibitory effect. Neither p-nitrophenol, a high affinity substrate for human TS-phenol and estrogen sulfotransferases, nor dopamine, a specific substrate for the thermolabile (TL)-phenol sulfotransferase, significantly inhibited the DNA binding of 12-OH-DMBA catalyzed by hepatic cytosols. Inter-subject variation (n = 12) of the PAPS- dependent DNA binding of 12-OH- and 7,12-diOH-DMBAs also correlated well with DHEA-sulfotransferase activity (r = 0.90; P < 0.00001 and r = 0.92; P < 0.00001, respectively). This sulfation-dependent metabolic activation was not detected in cytosols from human colon, pancreas, larynx or mammary gland. Both TS- and TL-phenol sulfotransferases were active in human liver and colon but only liver contained DHEA- sulfotransferase activity. These results indicate that the sulfotransferase-mediated activation of the methyl-hydroxylated DMBAs is predominantly catalyzed by DHEA-steroid sulfotransferase in human liver and that TS- and TL-phenol sulfotransferases and estrogen sulfotransferase are not involved in the catalysis.      

Monoclonal antibodies to mammalian heat shock proteins impair mouse embryo development in vitro

Two-cell mouse embryos (B6D2F1) were cultured in the presence or absence of 100 microg/ml monoclonal antibodies specific for the mammalian 60 kDa (HSP60), 70 kDa (HSP70) and 90 kDa (HSP90) heat shock proteins. Embryo development was evaluated after 3, 5 and 7 days in culture by determining the number of blastocysts, hatched blastocysts and outgrown trophoblasts at the successive time points. At day 3, only 29% (22/75) of the embryos cultured with anti-HSP60 antibody developed to the blastocyst stage (P < 0.0001) as compared to 67% (31/46) of the embryos cultured with anti-HSP70, 72% (43/60) cultured with anti-HSP90, and 79% (49/62) in medium plus mouse IgG1. By day 5, hatched embryos were present in 28% (13/ 46) of the cultures containing anti-HSP70 (P < 0.0001), as opposed to 57% (34/60) containing anti-HSP90 and 73% (45/62) containing IgG1. At day 7, outgrown trophoblasts were observed in 9% (4/46) of cultures containing anti-HSP70 (P < 0.0001), 45% (27/60) containing anti-HSP90 (P < 0.01) and 66% (41/62) cultured in medium plus IgG1. Antibodies to different heat shock proteins exerted a detrimental effect on mouse embryo development at unique development stages. Immune sensitization to heat shock proteins may be a cause of reproductive failure.