Deep venous thrombosis and pulmonary embolism. The importance of heightened awareness.

Left untreated, deep venous thrombosis and pulmonary embolism have a high rate of mortality and long-term morbidity. Physicians therefore must maintain a high index of suspicion for these conditions. Accurate diagnosis is facilitated by knowing the most common sites of thrombus formation, the likelihood of propagation, which patients are at greatest risk, signs and symptoms, and which tests to order. Prompt administration of anticoagulants and, in some cases, thrombolytic agents can minimize the consequences of these diseases. Interruption of the inferior vena cava, thrombectomy, and thromboembolectomy are other treatment options.     

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.     

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)