Gliotoxic actions of excitatory amino acids.

Cultures of neonatal Type I astrocytes of the rat were exposed to a series of excitatory amino acid analogs to identify those compounds that were gliotoxic. In addition to L-alpha-aminoadipate, a previously identified gliotoxin, L-homocysteate, L-serine-O-sulfate, L-alpha-amino-4-phosphonobutyrate and L-alpha-amino-3-phosphono-propionate were also found to induce a sequence of degenerative events that led to the lysis of the astrocytes. Cellular injury was assessed by quantifying the activity of lactate dehydrogenase present in the surviving astrocytes. Prior to lysis, the cells went through a succession of distinctive morphological changes, the most prominent of which involved nuclear alterations. The nuclei appeared swollen, contained "pale" or "watery" nucleoplasm and exhibited a very prominent nuclear membrane and obvious nucleoli. These astrocytes appeared quite similar in appearance to the Alzheimer's Type II astrocytes, principally associated with the pathology of hepatic encephalopathy. The nuclear anomalies, which are thought to be indicative of cellular damage and compromised function, were also produced by the endogenous transmitters L-glutamate and L-aspartate, although with time, the affected astrocytes appeared to recover and return to normal morphology, without lyzing. These findings suggest that excessive levels of excitatory amino acids may induce cellular damage to astrocytes, as well as neurons. Once damaged, the resulting reductions in astrocyte function may further contribute to CNS losses and the overall pathology attributed to the excitatory amino acids.

Low rates of preventive practices in patients with peripheral vascular disease.

BACKGROUND: Patients with peripheral vascular disease (PVD) have a three-fold increased risk of myocardial infarction, stroke and death. Recently, a number of therapies have been demonstrated to prevent morbidity or mortality in patients with PVD or other arterial disease. Given the scarcity of data on the preventive practice patterns of this high risk patient group, the in-hospital management of patients admitted to hospital for a peripheral vascular intervention was reviewed. PATIENTS AND METHODS: Charts of 195 patients with a diagnosis of peripheral arteriosclerotic disease (International Classification of Diseases, 9th revision, code 440.2) who were hospitalized at a tertiary care hospital in Ontario between June 1996 and June 1998 were reviewed. RESULTS: The average age of patients admitted was 70.6 years, and 39% of patients were women. The main reason for admission was peripheral artery bypass graft surgery in 88% (172 of 195). Fifty-four per cent (106 of 195) of patients had clinically apparent coronary or cerebrovascular disease, and 92% (180 of 195) of patients had at least one cardiovascular disease risk factor. Fewer than half of all patients (49%) were discharged on any antithrombotic therapy (antiplatelet agent or anticoagulant), and a small proportion of patients were treated with a beta-blocker (20%) and cholesterol-lowering medications (16%). CONCLUSIONS: The leading cause of morbidity and mortality in PVD patients is coronary and cerebrovascular disease. Despite this, the use of proven antithrombotic agents and other cardiac medications is suboptimal. Health professionals need to be aware of the high risk nature of the PVD population and to develop strategies to ensure that patient care is optimized.

Organo-phosphorus insecticide poisoning-review of 53 cases.

A review of 53 cases of organo-phosphorus insecticide poisoning admitted to the department of intensive care at the Jinnah Postgraduate Medical Centre between 15th January to 31st December, 1976 has shown that these insecticides form a majority of the causes of acute poisoning and are associated with a comparatively high mortality rate. Out of a total of 157 cases of acute poisoning admitted to the department, 34% were cases of organo-phosphorus insecticide poisoning forming 13 5% of the total admissions. These insecticides being easily accessible, are frequently used as suicidal agents specially by uneducated housewives. They are highly toxic and their management is very complicated. Of a total of 15 deaths from poisoning, 11 (73%) were due to this cause. This being such a common mode of poisoning in our country, we have presented here our experience of the clinical features and management of these cases.

Prevalence of right ventricular myocardial infarction in patients with acute inferior wall myocardial infarction.

The objective was to evaluate the prevalence of right ventricular myocardial infarction (RVMI) in patients with acute inferior wall myocardial infarction (IWMI) admitted to the National Institute of Cardiovascular Diseases, Karachi, Pakistan. Between August 2000 and May 2001, a total of 100 patients with acute IWMI were enrolled. History of all patients was taken, and thorough clinical examination was performed to asses the presence of signs of right ventricular infarction. Standard 12-lead electrocardiogram was recorded immediately on arrival of patients along with right precordial leads. All patients were considered for thrombolytic therapy in the absence of any contraindication and were managed with standard treatment strategies. Complications arising during the course of admission were recorded and compared between the two groups. There were 86 (86%) males and 14 (14%) females. Mean age was 56.3 +/- 13.13 years (range 33-83 years). The prevalence of RVMI in IWMI was 34%. Smoking and diabetes were more prevalent in RVMI group, while hypertension and family history of ischemic heart disease were more common in isolated IWMI. Ninety per cent of patients received thrombolytic therapy. In-hospital mortality (23.5%) was higher in RVMI group than isolated IWMI (18.1%). Other major complications were also higher in RVMI group than isolated IWMI. Right ventricular infarction was found in approximately one-third of IWMI. Right ventricular infarction was associated with considerable morbidity and mortality, and its presence defines a higher risk subgroup of patients with inferior wall left ventricular infarction.

Parasuicide in Pakistan: experience at a university hospital.

There have been few reports of parasuicide from Pakistan, where the act is considered to be a criminal offence and the Islamic religion strongly disapproves of it. In order to address the problem, a retrospective case report analysis of all index cases of parasuicide presenting over a period of 3.5 years to a university hospital in Karachi, Pakistan, was undertaken. Our results showed that most of the subjects were young adults, with married women representing the single largest group. Self-poisoning with medication was the most common method, and benzodiazepines the most frequently used drug. Interpersonal conflict with the opposite sex was the most common precipitating cause. In Pakistani culture, marriage appears to be a significant source of stress for women. Reports based on official police records do not reflect the true picture of the problem in Pakistan.

Radiological articular involvement in the dominant hand in rheumatoid arthritis.

Scoring the severity of joint involvement in the x-rays of hands of patients with rheumatoid arthritis showed significantly greater joint destruction in the dominant hand. The difference was seen in all the joints, and especially in the wrists, but with the exception of the metacarpophalangeal joint of the thumb. The grip strength was not, however, different in the 2 hands.

Status of rheumatic heart disease in rural Pakistan.

OBJECTIVES: To determine the community based prevalence of rheumatic heart disease (RHD) in the rural population of the district of Rahim Yaar Khan in Pakistan. SUBJECTS AND METHODS: A representative sample of the rural population of Rahim Yaar Khan district was selected. RHD was screened for by physical examination and the diagnosis was confirmed with echocardiographic Doppler studies. Sociodemographic data on each screened person were collected. RESULTS: 54 cases of RHD were found among the 9430 people screened (prevalence of 5.7 in 1000, 95% confidence interval 4.2 to 7.2). Females were significantly more likely to be affected. There was no significant relation with other factors studied (education, crowding, and socioeconomic status). Less than 20% of those found to have RHD were aware of their diagnosis before participation in this study and only three affected people (8%) were taking rheumatic prophylaxis. CONCLUSIONS: There is a high prevalence of RHD among the rural population of Pakistan. The prevalence has not declined over the past three decades. Nearly all people with RHD, including most of those who know their diagnosis, do not receive the benefit of potentially life saving secondary prevention measures.