Chediak-Higashi syndrome.
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Biomedical subjects
Publications and source records attributed to R Fernando.
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The identification of activated T cells in the brains of patients with multiple sclerosis (MS) suggests that these cells are critical in the pathogenesis of this disease. Recently we have used the PCR method to analyse rearrangements of V alpha and V beta genes of the T cell receptor (TCR) in samples of MS and control brains. The results of these studies showed that TCR V gene usage in MS brains may be restricted and in particular that V beta genes may be preferentially rearranged in certain HLA haplotypes associated with susceptibility to MS. In view of the recent evidence that T lymphocytes bearing the gamma delta chains may have autoreactive potential, we have assessed whether or not such TCR-bearing lymphocytes were also present in chronic MS lesions. TCR V gamma and V delta were analysed by the PCR method using a panel of V gamma and V delta primers paired with C gamma or C delta primers in 12 MS brains, as well as in brain samples of ten normal post-mortem cases and three neurological controls. TCR V gamma-C gamma and V delta-C delta rearrangements were confirmed using Southern blotting and hybridisation of the PCR products with specific C gamma and C delta probes. Only one to four rearranged TCR V gamma and V delta transcripts were detected in each of the 23 brain samples obtained from 12 MS patients, with the majority of gamma delta T cells expressing the V gamma 2 and V delta 2 chains. In marked contrast, V gamma and V delta transcripts could only be found in one of the ten non-neurological control brains analysed. To assess the clonality of V gamma 2 and V delta 2 T cell receptor chains in the brain samples of MS patients, we have sequenced the junctional regions of the TCR V gamma-N-J gamma-C gamma and V delta-N-D delta-N-J delta-C delta segments amplified from brain tissues, CSF and spleens of two MS patients and from the spleen of two control subjects. The sequence analysis obtained so far shows no compelling evidence of an MS specific expansion of one or more clones expressing particular types of gamma delta T cell receptors. In contrast, a clonal expansion of a different population of TCR gamma delta-bearing T cells was found in the spleen of both an MS patient and one of the control individuals.(ABSTRACT TRUNCATED AT 400 WORDS)
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1. The effects of different amounts of passive stretch per day and number of days of stretch on muscle hypertrophy in the chicken patagialis (PAT) muscle were determined. 2. Stretch for 24 hr per day (h/d) resulted in a more rapid hypertrophy both on a wet and dry tissue basis (P less than 0.001) than stretch for 4 h/d. 3. Stretch increased PAT weight 43% and 25% in 24 h/d and 4 h/d treatments, respectively, after 10 days of stretch, but by day 25 of stretch there was no difference between treatments. 4. In a second experiment, the PAT muscle was hypertrophied and then the effects of intermittent stretch (4 h/d) on regression of hypertrophy (muscle atrophy) were investigated. 5. Intermittent stretch (4 h/d) for 5 and 10 d significantly (P less than 0.001) inhibited regression of hypertrophied muscle. 6. The results of the present study indicate that stretch-induced hypertrophy can be modulated by varying the amount of stretch applied per day. 7. Intermittent stretch can be used to inhibit the regression which occurs when a continuous stretch stimulus is removed. 8. Intermittent stretch is a useful model for investigating mechanisms of muscle hypertrophy and inhibition of muscle atrophy.
We have examined a local anaesthetic mixture of 0.5% bupivacaine 10 ml and 2% lignocaine 10 ml with adrenaline 1 in 200,000, to which 8.4% sodium bicarbonate 2 ml was added, for extradural Caesarean section. The alkalinized mixture of local anaesthetics produced a block of more rapid onset and density than a mixture of bupivacaine and lignocaine alone (P less than 0.001).
The importance of acute poisoning as a cause of morbidity and mortality in many developing countries has been highlighted in recent times. This study discusses the utilization of routinely collected data from hospitals for background information required in planning and implementing preventive programs. The high prevalence of poisoning and its distribution countrywide were highlighted by the routinely collected data, while the retrospective study of hospital admissions identified the wide range of toxic agents and age and sex differentials in the pattern of poisoning. Even though the overall case fatality rate was 7.6%, there was wide variation among the different toxic agents.
Paraquat, a useful contact herbicide is now used in over 130 countries of the world, including Sri Lanka. The number of cases of accidental poisoning reported with paraquat is small, relative to instances of suicide. When a clear history is not available, accidental paraquat poisoning is sometimes difficult to diagnose. A 9-year-old boy was admitted to a peripheral hospital with a history of diarrhoea and vomiting. He later developed abdominal pain, subcutaneous emphysema and difficulty in breathing. Following transfer to a district hospital and then to a teaching hospital, poisoning with paraquat was suspected only on day 11 of the illness. On persistent questioning, on day 13 of the illness the child remembered that the day prior to the onset of illness, on his way from a shop, he felt thirsty and having found an empty bottle of Gramoxone (paraquat) on the wayside he used it to drink water from a water tank. The child died on day 17 and the histology of the lung showed typical changes of paraquat poisoning. This tragic episode emphasises the need for proper disposal of empty containers of all poisonous substances.
Hypertrophic cardiomyopathy is a familial condition with a very distinct risk of sudden death in males in certain families. The disease appears to be not uncommon in Sri Lanka. A sudden death in a 26-year-old healthy man is reported: At autopsy the heart was 500 g due mainly to left ventricular hypertrophy, and showed histological changes consistent with cardiomyopathy. Symptomless family members of the deceased were subsequently referred to a cardiologist. Cardiomyopathy was diagnosed in one of them.
Recent animal studies suggest that abnormal lipid metabolism may play a role in the pathogenesis of glomerulosclerosis. In order to define mechanisms whereby lipoproteins could contribute to glomerular injury, the effect of Low-density lipoprotein (LDL) concentration on the proliferation of rat mesangial cells was studied in vitro. Human LDL was added to culture medium that had been rendered otherwise lipid free and proliferation rate was estimated by measuring incorporation of 3H-thymidine. When compared to standard medium, LDL-enriched medium stimulated cell division when present in protein concentrations of between 10 and 100 micrograms/ml. At greater concentrations (more than 200 micrograms/ml), cell proliferation was inhibited and above 500 micrograms/ml cells sustained visible morphological injury when assessed under phase contrast microscopy. Estimation of 51Cr release from prelabelled cells confirmed that LDL was cytotoxic in these greater concentrations. A similar pattern of proliferation and toxicity has been observed in vascular smooth muscle cell cultures over a corresponding range of LDL concentrations. These results strengthen the analogy between glomerulosclerosis and atherosclerosis and provide further evidence that lipoproteins may contribute directly to glomerular scarring.
Electrocution is a rare mode of suicide. In Sri Lanka, where the suicide rate is extremely high, ingestion of liquid pesticides is the commonest method used. The case of a 34-year-old labourer of the Electricity Board, who committed suicide using 220-240 volt domestic electricity supply is described. He had been suffering from a depressive illness for some time. Suicide by electrocution has not been documented in Sri Lanka before.
The National Poisons Information Centre (NPIC) in Sri Lanka was established in January 1988. It received 353 enquiries in the first year of which 37% concerned pesticide poisoning. More than half the instances were of self-poisoning; consistent with the high suicide rate in the island. Over a quarter of poisoning episodes were among 19-25 year olds. Follow-up of enquiries showed 31 (9%) deaths. Collaboration with developed countries helped in the formation of the NPIC, fulfilling a long felt need among doctors in the island.
A retrospective hospital-based study in Sri Lanka showed that out of 4556 cases of poisoning, 2.5% were caused by plants and mushrooms. Gloriosa superba (44%), and Ricinus communis (24%) were the commonest plants responsible for poisoning; 39% of the victims were less than 15 y old. Gastric lavage and iv fluids were the most common therapeutic measures used. There were 8 deaths, all due to G superba. There is a need for public education to prevent poisoning, which is a major health concern.
To determine the accuracy of death certification by hospital doctors, all certificates of deaths issued for one month in the General Hospital, Colombo were studied. Only 97 (38%) of the 253 certificates were correctly recorded according to the internationally accepted criteria. The immediate, antecedent and contributory causes of death were not written in the correct place in 75 (30%) certificates, while unacceptable causes of death were found in 49 (19%). Abbreviations had been written in 13 (5%) instances. Death certificates had been issued without informing the coroner in 14 (6%) cases, which was irregular. The need for accurate certification of death for disease surveillance, research and planning is stressed.