Pharmacokinetics of Nisoldipine Coat--Core Formulation in Subjects with Liver Cirrhosis

The pharmacokinetics of a controlled-release formulation (coat--core) of the calcium channel blocker nisoldipine was investigated in eight subjects with biopsy-proved liver cirrhosis and eight healthy subjects. In Stage I, subjects received a single 10-mg dose to determine if this dose would be safely tolerated in the subjects with cirrhosis. Because all subjects in both groups tolerated the dose without difficulty, all were continued to Stage II. In Stage II, subjects received a once-daily dose of 10-mg coat-core tablets for 7 days. Serial plasma samples were assayed for nisoldipine in both stages. The C(max) and AUC of nisoldipine were approximately fourfold to fivefold higher (p < 0.01) in subjects with cirrhosis as compared to healthy subjects; however, there was overlap in the range of pharmacokinetic parameters between the two groups. The accumulation factor following multiple dosing was similar in both groups. Results suggest that nisoldipine dose should be optimized by monitoring of a pharmacodynamic end point, such as effect on blood pressure. It is likely that dose requirements for patients with liver disease will be lower.     

Ehlers-Danlos syndrome

A case of Ehlers-Danlos Syndrome in a 19 years old male involving cutaneous and skeletal systems is reported. A clinical scoring system to diagnose such cases is highlighted.     

Senile systemic amyloidosis--a case report

An 85 years old female presented with acute pain and weakness in left lower extremity and doppler evidence of femoropopliteal block was made which subsequently proved fatal. Necropsy revealed extensive amyloid deposition in the heart and amyloid angiopathy in rest of the organs.     

The Bournewood judgment: a way forward?

In this article we provide a commentary on the various reasonings behind the Law Lords' unanimous judgements in their recent decision (25 June 1998) in Regina v. Bournewood Community and Mental Health NHS Trust, Ex parte L. After summarizing the judgment and commenting on its important implications, we suggest a way forward. The 1995 Law Commission incapacity proposals, on which the 1997 consultation paper Who Decides? was based, do afford a mechanism which could resolve much of the practical difficulty which practitioners feared from the Appeal Court decision, whilst at the same time affording the sorts of rights which the House of Lords decision denies.     

Oesophagogastrectomy in the elderly high risk patients: role of effective regional analgesia and early mobilisation

BACKGROUND: Oesophagogastrectomy is the best available treatment for patients with carcinoma of the oesophagus or cardia. However, surgical resection may lead to increased mortality, morbidity and longer hospital stays in elderly (aged over 70 years) high risk patients. METHODS: To assess the impact of balanced pre-emptive and postoperative analgesia combined with early mobilisation in elderly patients undergoing oesophagogastrectomy we consecutively studied 52 patients (30 male, 22 female) of 75+/-4.2 years of age (mean+/-SD). Pre-emptive analgesia was by pre-incisional percutaneous paravertebral block combined with an opiate and a nonsteroidal anti-inflammatory drug (NSAID) premedication. Postoperative maintenance analgesia was by NSAID and continuous extrapleural intercostal nerve block. Following surgery all but three patients were returned to the ward. RESULTS: The hospital mortality rate was 7.6%. Morbidity caused by cardiovascular (27%), respiratory (23%) and cerebrovascular (19%) complications occurred in 19 patients, with two patients requiring ventilatory support. The mean hospital stay for the survivors was 10 days (range 8 to 30 days). All the survivors had their swallowing restored to normal and returned to their accustomed environment. CONCLUSIONS: These data suggests that surgical treatment can be achieved in the elderly high risk patients with acceptable mortality and morbidity. This is achieved by early mobilisation enabled by balanced pre-emptive and postoperative analgesia.     

Cyclosporine A neurotoxicity among bone marrow transplant recipients

Cyclosporine A (CsA) neurotoxicity is an iatrogenic disease with significant morbidity and occasional mortality. We retrospectively reviewed the cases of CsA neurotoxicity among bone marrow transplant recipients at our institution, and summarized the current literature on the subject. The neurologic presentation is varied and the neurologic manifestations are reversible, even after prolonged toxicity, in most instances. Serum CsA level is useful in evaluation, as the level is high in most instances. However, in a case of suspected neurotoxicity, withdrawal of the drug is the only way of determining presence or absence of such toxicity. The electrophysiologic studies, especially electroencephalogram (EEG), is very sensitive in identifying the problem, but lacks specificity. On the other hand, the neuroimaging studies are helpful in making a diagnosis if they show characteristic findings of hyperintense lesions affecting posterior cerebral regions on T2 weighted magnetic resonance images (MRI) or white matter hypodensities on computed tomographic (CT) scan. These lesions are probably due to breakdown of blood-brain barrier resulting in leakage of fluid in interstitial space. The breakdown could be serious enough to cause microhemorrhages that may coalesce to produce macrohemorrhages.     

The expression of alpha-, beta-, and gamma-synucleins in olfactory mucosa from patients with and without neurodegenerative diseases

A family of homologous proteins known as alpha-, beta-, and gamma-synuclein are abundantly expressed in brain, especially in the presynaptic terminal of neurons. Although the precise function of these proteins remains unknown, alpha-synuclein has been implicated in synaptic plasticity associated with avian song learning as well as in the pathogenesis of Parkinson's disease (PD), dementia with LBs (DLB), some forms of Alzheimer's disease (AD), and multiple system atrophy (MSA). Since olfactory dysfunction is a common feature of these disorders and the olfactory receptor neurons (ORNs) of the olfactory epithelium (OE) regenerate throughout the lifespan, we used antibodies specific for alpha-, beta-, and gamma-synucleins to examine the olfactory mucosa of patients with PD, DLB, AD, MSA, and controls without a neurological disorder. Although antibodies to alpha- and beta-synucleins detected abnormal dystrophic neurites in the OE of patients with neurodegenerative disorders, similar pathology was also seen in the OE of controls. More significantly, we show here for the first time that alpha-, beta-, and gamma-synucleins are differentially expressed in cells of the OE and respiratory epithelium and that alpha-synuclein is the most abundant synuclein in the olfactory mucosa, where it is prominently expressed in ORNs. Moreover, alpha- and gamma-synucleins also were prominent in the OE basal cells, which include the progenitor cells of the ORNs in the OE. Thus, our data on synuclein expression within the OE may signify that synuclein plays a role in the regeneration and plasticity of ORNs in the adult human OE.