The ��tumour overkill syndrome��. A potentially lethal complication of cancer chemotherapy

Two cases of acute leukaemia of Burkitt type in whom chemotherapy was associated with the ‘tumour overkill syndrome’ are described. One patient died with severe metabolic derangement which followed chemotherapy. In the other, an intensive programme of allopurinol administration, alkalinization of the urine and forced diuresis was instituted before chemotherapy, thus correcting the initial biochemical abnormalities and modifying those which occurred after chemotherapy. This approach prevented a fatal outcome, allowing the patient to survive to achieve bone marrow remission.     

Delayed-release bleomycin

Summary Experimental and clinical evidence indicates that bleomycin by continuous infusion is superior to intermittent administration. Continuous infusion is less convenient, however. It has been suggested that a suspension of bleomycin in sesame oil, given by IM injection, simulates a continous infusion.The pharmacokinetics of this formulation have been compared with those of bleomycin in saline following IM injection, in six patients.The pharmacokinetic profiles of the two formulations were similar. The only difference between the profiles was the long terminal half-life at very low concentrations between 12 and 48 h after injection of the oil suspension. This difference is of unknown, but doubtful, clinical significance.     

High-dose cytosine arabinoside: response to therapy in acute leukaemia and non-Hodgkin's lymphoma

Summary Twenty-six patients with acute leukaemia and 14 with high-grade lymphoma received cytosine arabinoside (ara-C) at a twice daily dose of 2 g/m² administered as a 3-h infusion. Thirty-four patients received 12 doses and six electively received four doses only. Complete remission was achieved in six of seven patients with acute myelogenous leukaemia (AML), one of two evaluable patients with blast crisis of chronic myeloid leukaemia and three of eight patients with acute lymphoblastic leukaemia (ALL). Three further patients with ALL had only minimal bone marrow infiltration after one cycle, toxicity precluding administration of a second. Three patients with AML who received four doses only showed no evidence of response. Four of 14 patients with lymphoma who received 12 doses, entered complete remission. Five additional patients died with minimal residual disease whilst severely neutropenic. A complete and a partial response were seen in two patients with immunoblastic and centrocytic lymphoma respectively who received four doses. These results confirm the activity of high-dose ara-C in patients with AML and suggest that it may also be a potentially useful agent in ALL and high-grade lymphoma, especially as the incidence of CNS toxicity is lower than that reported at higher doses.Presented in part at the Third International Symposium on Therapy of Acute Leukaemia, Rome, December 1982     

The pharmacokinetics of subcutaneous bolus cytosine arabinoside in an arachis oil plus aluminium distearate suspension

Summary An attempt was made to create a delayed release preparation of cytosine arabinoside (araC) which could be administered subcutaneously, and would produce plasma levels similar to steady state infusion concentrations. A thixotropic suspension of araC in arachis oil and aluminium distearate was formulated. This preparation was similar to that previously used with bleomycin oil suspension and procaine penicillin. Two hundred mg/ml of araC in arachis oil containing varying amounts of aluminium distearate were administered firstly to New Zealand White rabbits and then to patients with acute myelogenous leukaemia. This preparation was well tolerated by both rabbits and patients but did not delay the release of araC from the subcutaneous tissues.     

Epilepsy-induced decrease of L-type Ca2+ channel activity and coordinate regulation of subunit mRNA in single neurons of rat hippocampal 'zipper' slices

L-type voltage-sensitive Ca2+ channels (VSCCs) preferentially modulate several neuronal processes that are thought to be important in epileptogenesis, including the slow afterhyperpolarization (AHP), LTP, and trophic factor gene expression. However, little is yet known about the roles of L-type VSCCs in the epileptogenic process. Here, we used cell-attached patch recording techniques and single cell mRNA analyses to study L-type VSCCs in CA1 neurons from partially dissociated (zipper) hippocampal slices from entorhinally-kindled rats. L-type Ca2+-channel activity was reduced by >50% at 1.5-3 months after kindling. Following recording, the same single neurons were extracted and collected for mRNA analysis using a recently developed method that does not amputate major dendritic processes. Therefore, neurons contained essentially full complements of mRNA. For each collected neuron, mRNA contents for the L-type pore-forming alpha1D/Ca(v)1.3-subunit and for calmodulin were then analyzed by semiquantitative kinetic RT-PCR. L-type alpha1D-subunit mRNA was correlated with L-type Ca2+-channel activity across single cells, whereas calmodulin mRNA was not. Thus, these results appear to provide the first direct evidence at the single channel and gene expression levels that chronic expression of an identified Ca2+-channel type is modulated by epileptiform activity. Moreover, the present data suggest the hypothesis that down regulation of alpha1D-gene expression by kindling may contribute to the long-term maintenance of epileptiform activity, possibly through reduced Ca2+-dependent AHP and/or altered expression of other relevant genes.     

A decision-making model for health promotion advocacy: the case for advocacy of drunk driving control measures

This paper presents a decision-making model which can help public health professionals justify their decision to advocate for a particular intervention. The model is demonstrated by a case study related to advocacy of Random Breath Testing (RBT). For the purpose of this paper advocacy is a "catch-all word for the set of skills used to create a shift in public opinion and mobilise the necessary resources and forces to support an issue, policy, or constituency..." (Wallack, Dorfman, Jernigan & Themba, 1994).     

Restless legs syndrome.

PURPOSE: The signs and symptoms, epidemiology, etiology, pathophysiology, diagnosis, pharmacologic and nonpharmacologic treatments, and options and guidelines for the treatment of restless legs syndrome (RLS) are reviewed. SUMMARY: RLS was first described in the 17th century and further characterized in 1945. RLS is a common disorder, occurring in about 10% of the population. Patients with RLS often describe the urge to move, uncomfortable sensations, and pain, which begin or worsen during rest or inactivity such as lying or sitting. Symptoms of RLS make sleeping difficult for many patients, and significant daytime difficulties result from the condition. RLS can either be primary or arise from secondary causes that lead to iron deficiency. There is a familial component in primary RLS, but its underlying mechanisms remain unknown. Of individuals with conditions associated with iron-deficiency states, including pregnancy, renal failure, and anemia, 25-30% may develop RLS. The goals of RLS treatment include improving its symptoms and the patient's quality of life. There are limited data on the treatment of RLS. Pharmacologic therapies include iron replacement, dopaminergic agents (e.g., levodopa), dopamine agonists, anticonvulsants, opioids, and benzodiazepines. There have been no systematic trials of nonpharmacologic therapies for RLS, but good sleep hygiene and avoidance of alcohol, caffeine, and nicotine may improve symptoms. CONCLUSION: RLS is a common disorder thought to involve abnormal iron metabolism and dopaminergic systems. Nonpharmacologic therapy should be suggested for all patients with RLS, but pharmacologic therapy may be required, and evidence is strongest for levodopa and dopamine agonists.     

Contribution of cyclin d1 (CCND1) and E-cadherin (CDH1) polymorphisms to familial and sporadic colorectal cancer

The molecular basis for most non-HNPCC familial colorectal cancer cases is unknown, but there is increasing evidence that common genetic variants may play a role. We investigated the contribution of polymorphisms in two genes implicated in the pathogenesis of colorectal cancer, cyclin D1 (CCND1) and E-cadherin (CDH1), to familial and sporadic forms of the disease. The CCND1 870A/G polymorphism is thought to affect the expression of CCND1 through mRNA splicing and has been reported to modify the penetrance of HNPCC. Inactivation of E-cadherin is common in colorectal cancer, and truncating germline mutations have been reported to confer susceptibility to colorectal as well as diffuse gastric cancer. The -160A/C CDH1 polymorphism appears to affect expression of CDH1 and may therefore also confer an increased risk. We found a significantly higher frequency of CCND1 870A allele in 206 familial cases compared to 171 controls (P=0.03). Odds ratios in heterozygotes and homozygotes were 1.7 (95% CI: 1.0-2.66) and 1.8 (95% CI: 1.0-3.3) respectively. The difference was accounted for by an over-representation of A allele in non-HNPCC familial cases (P=0.007). Over-representation of the CCND1 A allele was also seen in sporadic colorectal cancer cases compared to controls but this did not attain statistical significance (P=0.08). No significant differences between the frequency of CDH1 -160A/C genotypes in familial, sporadic colorectal cancer cases and controls were seen, although a possible association between the low expressing A allele and right-sided tumours was detected in familial cases.