Pancreatic islet transplantation future prospects

There is good evidence that the long-term complications of diabetes are caused by poor control of blood sugar, even in patients where intensive glucose monitoring is used to control insulin therapy. Pancreatic transplantation offers the potential for normalisation of glucose metabolism, but at the cost of major surgery and immunosuppression. The possibility of separating the insulin-secreting tissue from the exocrine gland has many attractions. Isolated pancreatic islets are small enough to allow transplantation as free grafts by an injection technique. Furthermore, it may be possible to modify the graft in such a way as to prevent rejection with minimal or no immunosuppression. For pancreatic islet transplantation to become useful in clinical practice it will be necessary to develop efficient techniques for harvesting viable islet tissue in adequate quantities, identify a suitable site for transplantation and prevent rejection. Over the past 20 years experimental models of islet transplantation have proven the potential of this approach, but until recently it has not been possible to translate these experiments into clinical practice. Recently, there have been significant advances in the techniques available for separation of islets from the pancreas of large mammals and man, and recent clinical trials of islet transplantation have shown evidence of short-term function. However, significant problems remain, particularly those of rejection and the maintenance of long-term function, before introduction of clinical islet transplantation as standard therapy for diabetes can be expected.     

Effectiveness of training health professionals to provide smoking cessation interventions: systematic review of randomised controlled trials.

OBJECTIVE--To assess the effectiveness of interventions that train healthcare professionals in methods for improving the quality of care delivered to patients who smoke. DESIGN--Systematic literature review. SETTING--Primary care medical and dental practices in the United States and Canada. Patients were recruited opportunistically. SUBJECTS--878 healthcare professionals and 11,228 patients who smoked and were identified in eight randomised controlled trials. In each of these trials healthcare professionals received formal training in smoking cessation, and their performance was compared with that of a control group. MAIN MEASURES--Point prevalence rates of abstinence from smoking at six or 12 months in patients who were smokers at baseline. Rates of performance of tasks of smoking cessation by healthcare professionals, including offering counselling, setting dates to stop smoking, giving follow up appointments, distributing self help materials, and recommending nicotine gum. METHODS--Trials were identified by multiple methods. Data were abstracted according to predetermined criteria by two observers. When possible, meta-analysis was performed using a fixed effects model and the results were subjected to sensitivity analysis. RESULTS--Healthcare professionals who had received training were significantly more likely to perform tasks of smoking cessation than untrained controls. There was a modest increase in the odds of stopping smoking for smokers attending health professionals who had received training compared with patients attending control practitioners (odds ratio 1.35 (95% confidence interval 1.09 to 1.68)). This result was not robust to sensitivity analysis. The effects of training were increased if prompts and reminders were used. There was no definite benefit found for more intensive forms of counselling compared with minimal contact strategies. CONCLUSIONS--Training health professionals to provide smoking cessation interventions had a measurable impact on professional performance. A modest, but non-robust, effect on patient outcome was also found, suggesting that training alone is unlikely to be an effective strategy for improving quality of care, unless organisational and other factors are also considered.     

Dose response and toxicity of doxorubicin microspheres in a rat tumor model.

The therapeutic response and toxic effects of chemotherapy using several doses of doxorubicin in conventional solution form or bound to an ion-exchange resin were compared in a rat tumor model, to assess the relationship of drug dose to therapeutic efficacy and associated toxicity. Single bolus injections of 3.0, 4.5, 6.0, 7.5 and 9.0 mg/kg were administered via the abdominal aorta to rats bearing hindlimb tumors. Tumor size was measured serially and the growth rates of treated groups were compared with a control growth curve. In addition, the effect of empty microspheres on tumor growth rate was assessed. The levels of circulating white blood cells were measured and compared to control levels to provide an indication of the severity of bone marrow toxicity experienced by each form of treatment. Finally, any difference in the distribution of doxorubicin to tumor, hindlimb and cardiac tissue following administration of doxorubicin as free drug or on microspheres was ascertained. Empty ion-exchange resin exerted a small although significant detrimental effect on tumor growth which may be explained by the embolization of microspheres in the precapillary blood vessels of the tumor resulting in a transient delay in tumor growth rate. The lowest dose of doxorubicin produced a significantly better therapeutic response when administered in the free drug form, but higher doses elicited an equivalent delay in tumor growth for both drug microsphere and free drug groups in a dose-dependent manner, with the maximum anti-tumor response occurring at the highest dose. Treatment with free doxorubicin at high doses resulted in significant reductions of circulating white blood cells suggesting the occurrence of bone marrow toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of di-(2-ethylhexyl) phthalate and five of its metabolites on rat testis in vivo and in in vitro

In an attempt to establish which compound or compounds are responsible for the testicular damage observed after administration of di-(2-ethylhexyl) phthalate (DEHP) in rats, the effects of the parent compound and five of its major metabolites (mono-(2-ethylhexyl) phthalate (MEHP), 2-ethylhexanol (2-EH), mono-(5-carboxy-2-ethylpentyl) phthalate, mono-(2-ethyl-5-oxohexyl) phthalate and mono-(2-ethyl-5-hydroxyhexyl) phthalate) were investigated in vivo and in vitro. The concentrations of MEHP and the three MEHP-derived metabolites in plasma were determined after single and multiple oral doses of DEHP. The plasma concentrations and areas under the plasma concentration-time curves (AUC's) of each of the MEHP-derived metabolites were considerably lower than those of MEHP both after single and after repeated administration of 2.7 mmol of DEHP/kg body weight. The mean elimination half-life of MEHP was significantly shorter in animals given repetitive doses than in those given a single dose, but there was no statistically significant difference between the mean AUC values. No testicular damage was observed in young rats given oral doses of 2.7 mmol of DEHP or 2-EH/kg body weight daily for five days. In animals which received corresponding doses of MEHP the number of degenerated spermatocytes and spermatids was increased, whereas no such effects were found in animals given the MEHP-derived metabolites. MEHP was also the only compound that enhanced germ cell detachment from mixed primary cultures of Sertoli and germ cells.     

Pigmentary type of orthochromatic leukodystrophy (OLD): a new case with ultrastructural and biochemical study

A 34-year-old woman with no family history of orthochromatic leukodystrophy (OLD) developed progressive intellectual deterioration, a frontal syndrome and spastic tetraparesis. She died four years after the onset of the clinical illness. Neuropathological studies included light and electron microscopy of cerebral and nerve biopsies, and a complete postmortem examination. Light microscopy demonstrated OLD with pigmented macrophages and glial cells. Electron microscopy showed electron-dense, membrane-bound intracytoplasmic lamellar inclusions with curved or straight parallel arrangement, or fingerprint pattern, in white matter macrophages, astrocytes and oligodendrocytes. Cortical cells contained lipofuscin which was normal in type and amount. This suggests that the material in white matter glial cells and macrophages is ceroid pigment, however, the distribution is not that seen in ceroid-lipofuscinosis. Similar inclusions have been found in oligodendrocytes in other forms of OLD. Biochemical study did not show evidence of demyelination. Galactolipids were normal. Polyunsaturated fatty acids were decreased. The most striking feature was an increase in plasmalogens.     

Percutaneous drainage of a tuberculous liver abscess

The authors describe the management by percutaneous drainage of a rare solitary tuberculous liver abscess in a 37-year-old woman. Open surgical drainage of such abscesses can be avoided using percutaneous drainage combined with transcatheter infusions of antituberculous agents. For the safe and successful use of this method three criteria must be met: the abscess should be unilocular, there must be a safe access route and a previously sterile compartment must not be contaminated. In addition a small (22 or 23 gauge) needle should be used for the initial puncture.