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Biomedical subjects

S J Rice

Publications and source records attributed to S J Rice.

18 recordsLinked to original sources

A placebo-controlled phase I/II study of adefovir dipivoxil in patients with chronic hepatitis B virus infection.

Adefovir dipivoxil (bis-POM PMEA) is an adenine nucleotide analogue with activity against retroviruses and herpesviruses, and in vitro activity against hepatitis B virus (HBV). This study was conducted to evaluate its safety and antiviral activity in patients with chronic HBV infection. Twenty patients (13 co-infected with human immunodeficiency virus, HIV) were randomized in a phase I/II, double-blind, placebo-controlled study. Patients who had been hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg) positive for > or = 6 months, with elevated hepatic transaminases and serum HBV DNA > or = 50 pg ml-1, were randomized to adefovir dipivoxil 125 mg (n = 15) or placebo (n = 5) as a single, daily, oral dose for 28 days. Antiviral activity was assessed by changes in serum HBV DNA (using the Digene Hybrid Capture assay) and HBeAg/hepatitis B e antibody (HBeAb) status. HBV DNA levels fell rapidly by > 1 log10 in all active drug recipients (median fall 1.8 log10 pg ml-1) but increased by 0.01 log10 pg ml-1 in controls (P = 0.002). Reductions were sustained during treatment. HBV DNA returned to baseline over 1-6 weeks following discontinuation of active drug. HBeAg became transiently undetectable in one patient on treatment and, in another, sustained seroconversion to HBeAb occurred 12 weeks after treatment ended. Liver transaminase elevations > 300 U l-1 were observed in three patients during therapy (leading to protocol-specified treatment discontinuation or dose reduction) and in four patients during follow-up. On-treatment transaminase elevations were associated with HIV status, occurring in three of six HIV-uninfected patients compared with none of nine who were HIV infected. In addition, a slower return to baseline of serum HBV DNA levels was observed in the non-HIV-infected patients. Treatment for chronic hepatitis B as a once-daily oral dose was well tolerated and associated with significant and sustained reductions in serum HBV DNA levels during treatment. Transaminase elevations, which may be related to the therapeutic effect, were observed during and after treatment. Further studies are warranted to investigate the safety, and optimum dose and duration, of adefovir dipivoxil treatment for chronic hepatitis B.

Adenine↗

Pathfinders: a self-care and health education program for older widows and widowers.

Recent studies suggest that the loss of a spouse can be disruptive to the survivor's self-care and health promotion practices, especially for those who lack the knowledge and skills to successfully engage in these behaviors. Pathfinders is a theoretically and research-based self-care and health education program for recently widowed persons aged 50 and older. This article describes the program's structure, content, and recruitment methods. Preliminary evaluation data suggest that the program is achieving many of the intended outcomes. Issues pertaining to replication as well as limitations are discussed.

Aged↗

Ion, water and neutral solute transport in Xenopus oocytes expressing frog lens MIP.

We have expressed frog (Rana pipiens) lens major intrinsic protein (MIP) in Xenopus oocytes and observed its effect on ion conductance, water permeability and neutral solute transport. SDS-PAGE and immunoblotting demonstrated oocytes injected with MIP mRNA expressed the protein at high levels. Immunolocalization indicated the expressed MIP migrated to the plasma membrane. MIP had no effect on the slope of oocyte I-V relations in the range -50 to +10 mV, although the averaged I-V curve was shifted 10 mV positive to control. MIP increased oocyte water permeability by a factor of 1.9 +/- 0.2, whereas the permeability to sucrose, 2-deoxyglucose, inositol, sorbitol, reduced glutathione or urea was unchanged. Glycerol permeability was enhanced in oocytes expressing MIP. In contrast to control oocytes, 3H-glycerol radioactivity accumulation did not follow first order kinetics. Radioactivity continued to accumulate even after 19 h of uptake and went beyond equilibrium with the bath. The time course of MIP-mediated glycerol uptake was modeled assuming metabolic trapping with good results. Based on this model, MIP increased oocyte glycerol permeability by a factor of 2.7.

Animals↗

The cDNA sequence encoding the major intrinsic protein of frog lens.

A cDNA clone encoding the frog lens major intrinsic protein (MIP) has been isolated and sequenced. The predicted protein of 28 kDa has high sequence identity and similarity to mammalian and avian lens MIP sequences. Frog lens MIP is encoded by a transcript of 4.4 kb.

Amino Acid Sequence↗

Thoracoscopic carbon dioxide laser treatment of bullous emphysema.

A new technique of thoracoscopic laser ablation of pulmonary bullae suitable for patients with multiple bullae and diffuse emphysema was developed and assessed in 22 patients. 20 of 22 patients survived. Pre-operative and postoperative functional evaluation is available for the 11 patients followed up for more than a month; at 1 to 3 months postoperatively there were increases in FVC (mean 2.0 litres pre-operatively to 2.7 litres postoperatively, p less than 0.001), in FEV1 (0.74 to 1.06 litres, p = 0.01), and in maximum exercise treadmill times (5.4 min to 8.0 min, p less than 0.01). Postoperative air leaks lasted a mean of 13 days and usually resolved spontaneously. Other complications were bleeding (1 patient) and unilateral acute lung injury (1 patient). These results suggest that selected patients with diffuse emphysema and pulmonary bullae may benefit from thoracoscopic carbon dioxide laser ablation.

Cysts↗

Late-onset hemorrhagic cystitis associated with urinary excretion of polyomaviruses after bone marrow transplantation.

Hemorrhagic cystitis is a well known complication of allogeneic bone marrow transplantation (BMT) and is normally attributed to the use of high-dose cyclophosphamide in the preparative regimen. Hemorrhagic cystitis occurring late after BMT is unlikely to be due to the effects of this conditioning, and probably has an infective etiology. Three patients undergoing BMT for chronic granulocytic leukemia (CGL) developed terminal dysuria and hematuria at 38, 56, and 149 days post-BMT. Electron microscopy (EM) of urine voided at these times revealed large numbers of papovavirions, which were subsequently identified as BK virus. Urine samples inoculated onto human embryonic lung fibroblasts induced infection of the cells and replication of the virus as detected by EM of tissue culture fluid. Urine from one of these patients was examined by standard cytological techniques, and EM of urothelial cells showed nuclear inclusions consisting of nonencapsulated virus particles of diameter 40 nm, consistent with papovavirus. Five further patients were found to be excreting BK virus without symptoms of cystitis, although one of these patients did experience abnormalities of liver function that were otherwise unexplained. BK virus has already been implicated in hepatic dysfunction posttransplant, and in cystitis in nonimmunosuppressed children. We postulate that it may also be involved in the etiology of late hemorrhagic cystitis after BMT.

Adult↗

HIV infection due to a platelet transfusion after allogeneic bone marrow transplantation.

A 30-yr-old man with chronic granulocytic leukaemia received a bone marrow transplant from his histocompatible sister in December 1982. His post-transplant course was complicated by Grade III graft-versus-host disease and multiple infectious episodes until his death from pneumonia on d + 190. He was later found to be seropositive for anti-HIV at the time of his death. Retrospective analysis of stored sera showed a transient period of seropositivity from d + 11 to d + 20 thought to reflect passive transfer of antibody from a blood product transfused prior to d + 11 when he was also exposed to infectious virus. He remained seronegative until d + 78 when anti-HIV was again found. Seropositivity persisted until his death and was attributed to endogenous antibody response. Although it is unclear whether his clinical course was due to AIDS, exposure of an immunosuppressed patient to HIV may be associated with more rapid development of clinical disease.

Acquired Immunodeficiency Syndrome↗

Microvillous surface area in secondary disaccharidase deficiency.

Electron microscopy was used to measure microvillous surface area in seven small intestinal biopsies showing secondary disaccharidase deficiency and in five biopsies having normal disaccharidase levels. There were significant reductions in microvillous surface area in the enzyme deficient group, although the microvilli were not severely damaged. Histological abnormality was not always present with disaccharidase deficiency. There was no significant difference in intraepithelial lymphocyte counts between the two groups.

Adolescent↗

Small intestinal intraepithelial lymphocyte levels in cow's milk protein intolerance.

The mean small intestinal intraepithelial lymphocyte count in seven children with untreated cow's milk protein intolerance (CMPI) on a milk-containing diet was significantly higher than 22 control children also having a milk-containing diet. Ten milk-intolerant children on a milk-free diet had a mean intraepithelial lymphocyte count which was significantly lower than the level in the 22 control children on a milk-containing diet. When these 10 children were challenged with cow's milk they relapsed clinically, and in every case the intraepithelial lymphocyte count rose, although it remained within normal limits. Nineteen children on milk-free diets who had recovered from CMPI had a mean lymphocyte count which was also significantly lower than controls on normal diets, suggesting that when milk is remo-ed from the diet the lymphocyte count is low regardless of whether the child is milk sensitive or not. The reaction of intraepithelial lymphocytes to milk in CMPI is markedly different from their response to gluten in coeliac disease.

Animals↗