Treatment of severe diarrhoeal dehydration in hospital and home by oral fluids

This paper reports on 1330 infants, from birth to 24 months old, suffering from diarrhoea and moderate to severe dehydration who were hospitalized in Tehran University Hospital over a period of 11 months. Fifteen per cent of them had signs of shock and 36% had marasmus. All patients were treated orally in two phases: rehydration therapy and maintenance therapy. For rehydration, an isotonic fluid (sodium 80 mmol l-1, potassium 20 mmol l-1) was administered at a rate of 40 ml kg-1 h-1 until all signs of dehydration disappeared. Following complete hydration, the patients were discharged and maintenance therapy was performed at home, by mothers, administering Maintenance Solution (sodium 40 mmol l-1, potassium 30 mmol l-1) ad libitum. Intravenous fluids were not used, even in severe dehydration. The efficacy and safety of this regimen were confirmed by rapid and successful rehydration in 99.7% of the patients and correction of a wide variety of electrolyte abnormalities present on admission, though some relapsed. The study suggests that this protocol could be employed in varied types and severities of dehydration and electrolyte abnormalities, and could also be used in both well nourished infants and in those with severe marasmus. It also demonstrates that mothers can serve as effective health workers and can perform successful maintenance therapy. Nine per cent of treated children required readmission to hospital within 24 h of discharge and a further 8% were hospitalized elsewhere with recurrent symptoms.     

Do vascular surgery patients need a cardiology work-up? A review of pre-operative cardiac clearance guidelines in vascular surgery.

OBJECTIVES: to outline the appropriate pre-operative cardiac work-up for patients who are scheduled for major peripheral vascular surgery. DESIGN: review of the literature. MATERIALS AND METHODS: a review of the literature focusing on studies that have correlated the pre-operative cardiac work-up patients receive to the cardiac morbidity and mortality following vascular surgery. Only studies with level A evidence were included. RESULTS: peri-operative beta blockade has been shown to decrease cardiac complications after vascular surgery in all risk groups. Non-invasive cardiac testing is only necessary for patients in the intermediate/high risk group. Coronary revascularization should only be considered after a positive non-invasive cardiac test. CONCLUSIONS: patients must be risk stratified pre-operatively based on history and physical examination. Low risk patients should receive peri-operative beta blockade only with no further non-invasive testing. On the other hand, intermediate and high risk patients should undergo non-invasive cardiac testing before going to the operating room.     

'Acute on chronic' effect of depot leuprolide in patients with stage D2 cancer of prostate

During a phase III open study of depot leuprolide for stage D2 cancer of the prostate, we studied the effect of depot leuprolide on chronic leuprolide users. To determine whether there was a transient elevation of testosterone or luteinizing hormone (LH) 4-24 h and 3-5 days following the monthly injections, we monitored the changes of testosterone and LH before injection and 24 h post-injection in 10 patients who have been under depot leuprolide Rx for 24-36 weeks, and in 35 patients before injection and 3-5 days post-injection who have received depot leuprolide for 8-24 weeks prior to monitoring. Comparison of the data between pre-injection within 24 h and 3-5 days post-injection showed no significant changes of testosterone and LH values between these levels for either testosterone (P = 0.31) or LH (P = 0.45). We therefore conclude that there was no 'acute on chronic' effect of depot formulation in chronic users of depot leuprolide.     

The impact of telomere erosion on memory CD8+ T cells in patients with X-linked lymphoproliferative syndrome

Patients with X-linked lymphoproliferative syndrome (XLP) experience excessive T cell proliferation after primary Epstein-Barr virus (EBV) infection, due to mutations in the signalling lymphocyte activation molecule (SLAM) associated protein (SAP) molecule. We examined the impact of dysfunctional proliferative control on the extent of CD8+ T cell differentiation in XLP patients who recovered from primary EBV infection. Although these young patients have normal numbers of lytic and latent EBV-epitope-specific CD8+ T cells, they were extremely differentiated as defined by loss of CCR7 and CD27, low telomerase activity and very short telomeres. This was not a direct effect arising from the loss of SAP, but was due to excessive T cell stimulation due to this defect. Thus, transduction of XLP CD8+ T cells with the catalytic component of telomerase (hTERT), but not SAP, prevented telomere loss and considerably extended proliferative lifespan in vitro. These results indicate that excessive proliferation in CD8+ T cells in XLP patients may lead to end-stage differentiation and loss of functional EBV-specific CD8+ T cells through replicative senescence. This may contribute to the defective immunity found in XLP patients who survive acute EBV infection who develop EBV-related B cell lymphomas before the fourth decade of life.     

Therapeutic effects of leuprorelin microspheres in prostate cancer

Leuprorelin has demonstrated effectiveness comparable to orchiectomy and oral diethylstilboestrol for the palliation of advanced prostate cancer. Unlike orchiectomy, leuprorelin's effects are reversible; also leuprorelin is not associated with the cardiovascular or thromboembolic adverse effects of oestrogens. For these reasons, leuprorelin has been widely used as an alternative to surgical castration or to oestrogens in the treatment of metastatic prostate cancer. Sustained-release leuprorelin microsphere formulations have been developed which exhibit zero order release of active drug from the injection site, such that in the United States the 7.5 mg dosage strength is recommended to be administered once a month and the 22.5 mg dosage strength once every three months. Although most patients will have suppressed release of pituitary luteinizing hormone by the third or fourth week after the first dose of depot leuprorelin, 4-5% of treated patients have been reported to have delayed responses, taking many more weeks or months to respond. A transient biochemical hormone escape has also been reported, although worsening of clinical symptoms has not accompanied the elevation of serum testosterone levels during treatment. Usually, leuprorelin is initiated as monotherapy when patients with advanced prostate cancer become symptomatic. However, newer studies of combination therapy of luteinizing hormone releasing hormone analogs with antiandrogens suggest that early initiation of therapy, at the time of diagnosis of advanced disease, may be beneficial, particularly in a subgroup of patients with small volume disease and good performance status. Leuprorelin is also undergoing evaluation as neoadjuvant therapy prior to radical prostatectomy for localized prostate cancer. Preliminary studies suggest that neoadjuvant leuprorelin in combination with an antiandrogen may be effective in downstaging prostate tumours. Leuprorelin commonly produces several adverse effects: hot flashes, decreased libido and impotence, and tumour flare.     

Isolation and characterization of the mouse homolog of the preprodynorphin (Pdyn) gene

We have isolated and sequenced the mouse preprodynorphin gene (Pdyn). The Pdyn gene can encode for six biologically active dynorphin peptides. The predicted mouse preprodynorphin has 90%, 67%, and 66% identity with the predicted rat, porcine, and human preprodynorphins, respectively. Using an RT-PCR technique, we show that the Pdyn gene starts being expressed at embryonic day 12.5, with a steep increase of expression by embryonic day 14.5; in the adult mouse it is expressed in the brain, but not in liver, heart, spleen, or kidney.     

Nodular lymphoid lesion of the liver: an immune-mediated disorder mimicking low-grade malignant lymphoma

Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in the liver were studied in the authors' surgical pathology laboratory. These lesions posed difficulty in diagnosis, and their differentiation from low-grade lymphoma was not possible on histopathologic evaluation alone. The liver masses were analyzed histologically and immunohistochemically as well as for clonal immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene rearrangements. The lesions were seen as solitary grossly distinct firm nodules in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their greatest dimensions. Two were found in livers removed because of end-stage primary biliary cirrhosis at the time of orthotopic liver transplantation, and the third was an incidental finding during laparotomy. Microscopically, these were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with varying degrees of admixed acute inflammatory cells and scattered lymphoid follicles. By immunohistochemistry and molecular studies, these were found to be reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13 years, respectively. It is concluded that these cases represent a unique type of nodular lymphoid lesion, which is probably an immune-mediated benign reactive hyperplasia. It constitutes an entity by itself and must be distinguished from low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and molecular studies are required.