Gentamicin-induced increases in cytosolic calcium in pig kidney cells (LLC-PK1)

LLC-PK1 cells, an established epithelial cell line derived from pig kidney, were tested as a model system for assessing the role of calcium in gentamicin-induced nephrotoxicity. Cell viability was evaluated by a vital dye exclusion procedure, and intracellular free calcium [Ca2+]i was measured employing Fura-2 fluorescence. Exposing cell suspensions (10(6)/ml) to concentrations of the drug, which had no apparent effect on viability, produced a rapid and prolonged increase in intracellular [Ca2+]. The perturbation of calcium homeostasis could be blocked by the addition of mepiperphenidol, an inhibitor of the organic cation transport system. We propose that LLC-PK1 cells are an appropriate model to study drug-induced nephrotoxicity. Gentamicin disrupts calcium homeostasis and causes plasma membrane alterations. Since mepiperphenidol blocked the gentamicin-induced Ca2+ increases, the data suggest that aminoglycosides enter the cell via the organic cation transporter.     

The relationship of serotonin to depression in Parkinson's disease

We have previously reported a correlation between depression in patients with idiopathic Parkinson's disease and decreased concentrations of the cerebrospinal fluid content of the serotonin metabolite, 5-HIAA. To further examine this relationship, we repeated the study in a new cohort of patients while they remained on dopaminergic medications, conducted follow-up interviews and examinations in our original cohort, and conducted an open trial of the serotonin precursor, 5-hydroxytryptophan in a group of new patients with depression. We were again able to demonstrate a significant reduction in cerebrospinal 5-HIAA in depressed patients in comparison to controls and patients without depression. Demented patients with Parkinson's disease, particularly those with concurrent depression, had the lowest values of 5-HIAA. No new cases of depression occurred in our original cohort after 2 1/2 years of follow-up, and depression remitted following conventional or experimental treatment in four patients. Depression improved in six of the seven new patients following oral 5-hydroxytryptophan. Three of these patients allowed a repeat lumbar puncture, and the concentration of 5-HIAA increased following 5-hydroxytryptophan. These three studies support our hypothesis that depression in idiopathic Parkinson's disease is associated with a reduction in brain serotonin. However, it also suggests that other factors, biological or environmental, may be causal factors.     

Fatal esophageal-arterial fistula 17 years following tetralogy of Fallot repair.

Blalock-Taussig shunts (subclavian to pulmonary anastomoses) have remained the most effective palliation in cyanotic heart disease. Late complications are rare but can be devastating. The case of a 26-year-old female with tetralogy and an original Blalock shunt constructed at age four years is reported. Despite subsequent primary repair of the tetralogy and presumed ligation of the Blalock shunt, the patient succumbed to a fatal hemorrhage due to esophageal-arterial fistula involving the Blalock shunt. The circumstances leading to this dramatic outcome are outlined and discussed. It is important for cardiologists caring for congenital heart disease patients to be aware of the late complications of congenital heart surgery, and carry out the proper follow-up investigations.     

Identification of an insulin-like factor in astrocyte conditioned medium

Survival of dissociated 19-day fetal rat telencephalic neurons in a hormone-free defined medium required the addition of insulin at pharmacological concentrations. However, survival of astrocytes cultured from the cerebral cortex of newborn rats in the same medium did not require insulin. When fetal neurons were incubated with astrocyte conditioned medium or plated on a monolayer of astrocytes, their survival was significantly increased in the absence of insulin. This effect of astrocyte conditioned medium was visibly inhibited by affinity chromatography on an anti-insulin protein A agarose column. A 5-30 kDa ultrafiltration fraction of astrocyte conditioned medium also increased neuronal survival. In addition, the 5-30 kDa fraction stimulated [3H]leucine incorporation into the TCA insoluble material from cultured neurons and competed for [125I]insulin binding to intact neuronal cultures. These results indicate that cultured astrocytes produce a factor with biological and immunological properties similar to those of insulin. This factor may in part mediate the observed neurotrophic effects of astrocyte conditioned medium and may play a role in the normal development and differentiation of central nervous system neurons.     

Prognostic value of c-erbB-2 expression in uterine cervical carcinoma.

AIMS: To study the pattern of expression and prognostic importance of c-erbB-2 protein in cervical carcinoma. METHODS: Sixty two cases of stage IB/IIA cervical carcinoma, representing the three main tumour types, were investigated immunohistochemically for the presence of c-erbB-2 protein expression, using a monoclonal antibody (CB11) to its internal domain. Follow up of at least five years' duration was available in all cases. RESULTS: Definite membrane staining was seen in 38.7% of cases. There was a strong correlation with poor survival (p less than 0.0001) particularly. For those with adenocarcinomas, this was the case when nodal metastases were present. In contrast, for squamous carcinomas and adenosquamous carcinomas, the association with a poor prognosis was most apparent in those patients without lymph node metastases. CONCLUSIONS: These findings raise the possibility that immunostaining for c-erbB-2 protein could be used as a prognostic marker and may help identify those patients for whom early adjuvant treatment might be beneficial.     

The effect of fulminant hepatic failure on protein C antigen and activity

In eighteen patients with fulminant hepatic failure (FHF), in grade III or IV coma, both protein C antigen and activity were significantly decreased (0.35 +/- 0.03 u/ml and 0.35 +/- 0.03 u/ml respectively). There was a significant correlation between protein C antigen and activity (r = 0.61, p less than 0.01). Protein C antigen levels were inversely correlated with prothrombin time (r = -0.57, p less than 0.05) as were protein C activity levels (r = -0.57, p less than 0.05). There was also significant correlations between fibrinogen and protein C antigen (r = 0.69, p less than 0.01) and protein C activity (r = 0.61, p less than 0.01). These results demonstrate that the naturally occurring inhibitor of coagulation, protein C, is present at low levels in FHF and this is probably due to the lack of synthesis of the protein in the damaged liver. The low levels of protein C may make these patients more susceptible to the disseminated intravascular coagulation which is known to occur in FHF and this in turn will lead to a further reduction in protein C levels.     

Capillary anastomosis in vena caval thrombosis

A 29-year-old woman presented with recurrent diffuse histiocytic lymphoma. Bilateral brachial venous catheters were placed for chemotherapy, which resulted in thrombotic occlusion of the superior vena cava. A lung scan with Tc-99m MAA (flow study and static images) demonstrated extensive collateral vessels in the upper thorax and trapping of particles in the right upper abdomen, anteriorly. A simultaneous liver scan with Tc-99m sulfur colloid (flow and delayed images) illustrated a normal liver with no other abnormal sites of tracer deposition. The accumulation of a lung imaging agent in the anterior abdominal wall was secondary to capillary anastomosis between the superior and inferior epigastric veins.