Neuroleptic malignant syndrome in a patient with head injury

Neuroleptic malignant syndrome is an idiosyncratic reaction associated with the use of neuroleptic drugs. We report a case of this rare syndrome in a head injury patient associated with some unusual features: rhabdomyolysis with a high level of creatine kinase, the development of acute renal failure, the early use of continuous venovenous haemofiltration in treatment and rigidity that was refractory to conventional treatment with dantrolene and bromocriptine. The diagnosis in patients with multiple injuries must be based on a high index of suspicion.     

Delayed and pseudodelayed visual evoked potentials in optic neuritis compared with long time echo-short tau inversion recovery magnetic resonance imaging of optic nerve

Twenty patients affected by optic neuritis (ON) underwent serial visual evoked potential (VEP) recordings, performed with multiple electrode arrays, and with stimuli of 1 and 3 cycles per degree (cpd) for 1 year. VEP findings were correlated with long time echo-short tau inversion recovery (LTE-STIR) magnetic resonance imaging (MRI) of optic nerves and with visual field tests. MRI showed lesions in 95.2% of acute ON and in 66.6% of the 1 year follow-up. VEPs were classified into really 'delayed' VEPs and 'pseudodelayed' VEPs, based on their scalp distribution. Furthermore, VEPs to 1 or 3 cpd could be 'delayed' or 'pseudodelayed' in the same patient. Real delays could be recorded at onset or shortly after ON, and indicated the possibility of recovery of visual functions and good functional prognosis. Pseudodelays, to 3 cpd, corresponded to prominent central scotomata and indicated poor prognosis for the recovery of visual function, unless a breakthrough of normal or delayed components appeared in the first 4 months following acute ON. Pseudodelayed VEPs clustered in patients with longer demyelinating lesions, as shown by LTE-STIR MRI. There was no correlation between latency of VEPs and length of plaques. Our study addresses some reconsiderations of the pathophysiology of conduction delay in acute optic neuritis.     

Isolation and 2D NMR Studies of Alkaloids from Comptonella sessilifoliola1

Six known furanoquinoline alkaloids have been isolated from the wood and trunk bark of COMPTONELLA SESSILIFOLIOLA (Guillaumin) Hartley (Rutaceae). 2D NMR experiments gave the assignment of all the signals for both (1)H- and (13)C-NMR spectra. Pteleine and kokusaginine were used as models. The two-dimensional carbon-proton correlation experiments, performed for the first time on furanoquinoline alkaloids, led us to correct (13)C-NMR assignments previously described in the literature.     

GABA-like and glycine-like immunoreactivities of the cochlear root nucleus in rat

Summary The cochlear root nucleus is part of the cochlear nuclear complex in small rodents. Its cells, the large root neurons, have a superficial resemblance to the globular neurons of the ventral cochlear nucleus. It has been a matter of debate, therefore, whether the root neurons and globular neurons represent the same or different types of cell. In the present study the two cell types with adjacent neuropil structures were compared by light microscopic, postembedding immunocytochemistry. Pairs of 0.5 m sections of resin-embedded, glutaraldehyde-fixed material were treated with purified antisera raised against GABA- and glycine-glutaraldehyde-protein conjugates, respectively. Both types of cell were found to be immunonegative. Striking differences, however, occurred in what was interpreted as afferent nerve terminals. The globular cells appeared to receive numerous afferents with GABA- or glycine-like immunoreactivity on their somata. Immunoreactive terminals on the root neurons, on the contrary, were mostly GABA-positive and located on the dendrites. Although of unknown origin, the immunoreactive afferents were clearly different from the primary fibres as demonstrated both by the immunonegativity of the latter and by the different size and distribution of the terminals labelled anterogradely after horseradish peroxidase injections into the spiral ganglion.     

Identification of intracellular receptor proteins for activated protein kinase C.

Protein kinase C (PKC) translocates from the cytosol to the particulate fraction on activation. This activation-induced translocation of PKC is thought to reflect PKC binding to the membrane lipids. However, immunological and biochemical data suggest that PKC may bind to proteins in the cytoskeletal elements in the particulate fraction and in the nuclei. Here we describe evidence for the presence of intracellular receptor proteins that bind activated PKC. Several proteins from the detergent-insoluble material of the particulate fraction bound PKC in the presence of phosphatidylserine and calcium; binding was further increased with the addition of diacylglycerol. Binding of PKC to two of these proteins was concentration-dependent, saturable, and specific, suggesting that these binding proteins are receptors for activated C-kinase, termed here "RACKs." PKC binds to RACKs via a site on PKC distinct from the substrate binding site. We suggest that binding to RACKs may play a role in activation-induced translocation of PKC.     

Phase II and pharmacokinetic study of ecteinascidin 743 in patients with progressive sarcomas of soft tissues refractory to chemotherapy.

PURPOSE: To assess the efficacy of the marine-derived alkaloid ecteinascidin 743 (ET-743) in patients with soft tissue sarcomas that progressed despite prior conventional chemotherapy and to characterize the pharmacokinetic profiles of ET-743 in this patient population. PATIENTS AND METHODS: Thirty-six previously treated soft tissue sarcoma patients from three institutions received ET-743 as a 24-hour continuous intravenous (IV) infusion at a dose of 1,500 microg/m(2) every 3 weeks. Pharmacokinetic studies were also performed. Patients were restaged every two cycles for response by objective criteria. RESULTS: Objective responses were observed in three patients, with one complete response and two partial responses, for an overall response rate of 8% (95% CI, 2% to 23%). Responses were durable for up to 20 months. Two minor responses (43% and 47% tumor reduction) were observed, for an overall clinical benefit rate of 14%. The predominant toxicities were neutropenia and self-limited transaminitis of grade 3 to 4 severity in 34% and 26% of patients, respectively. The estimated 1-year time to progression and overall survival rates were 9% (95% CI, 3% to 27%) and 53% (95% CI, 39% to 73%), respectively. The maximum observed plasma concentration and total plasma clearance of ET-743 (mean +/- standard deviation), 1.04 +/- 0.48 ng/mL and 35.6 +/- 16.2 L/h/m(2), respectively, were consistent with previously reported values from phase I studies of the drug given as a 24-hour IV infusion. CONCLUSION: ET-743 is a promising new option for the management of several histologic subtypes of sarcoma. Durable objective responses were obtained in a subset of sarcoma patients with disease progression despite prior chemotherapy. Additionally, the relatively high survival rate noted in this series of previously treated patients further justifies development of this agent.     

Impact on blood pressure control of a six-month intervention project

The aim of this study is to evaluate the impact of a six-month structured education programme on blood pressure (BP) control in patients with uncontrolled hypertension. All patients attending the Specialist Hypertension Clinic, University Hospital of the West Indies (UHWI), between January 4 and March 29, 1999, with blood pressure > 140/90 mmHg (n = 80), were randomly divided into Group 1, cases (n = 42) and Group 2, controls (n = 38). A 40-item pretested questionnaire, administered at the baseline and final visits of both groups, elicited demographic, lifestyle and knowledge data. Group 1 attended monthly structured interventions for six months. Except for diastolic blood pressure among male controls, diastolic blood pressure and systolic blood pressure were significantly reduced at the end of the intervention period (p < 0.01). Knowledge improved among the male patients (p < 0.01). Among the female patients, activity scores were significantly increased (p < 0.01), weight (p < 0.05) and BMI (p < 0.05) were significantly reduced. There were no differences in these variables among the controls. This intervention had a benefit in blood pressure control.     

Pharmaceutical expenditure in Spain: cost and control.

In recent years, the Spanish government has been battling to keep pharmaceutical expenditures under control. Its measures include control of prices, introduction of a "negative list" of drugs no longer reimbursed, increased cost-sharing, and introduction of overall budgets for pharmaceutical expenditures. Although the average prices of old pharmaceutical products declined by 39 percent over the last 15 years and consumption in value increased by only 10 percent, real pharmaceutical expenditures in Spain increased by 264 percent over that period. The main reason for the continuing rise in these expenditures and the failure of cost-containment measures is the introduction of new, more expensive drugs, which often fail to offer any real therapeutic advantages over products already on the market. This situation is exacerbated by a lack of effective demand-side measures such as budgets for doctors and lack of a generics market.