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Biomedical subjects

R Pathmanathan

Publications and source records attributed to R Pathmanathan.

At least 19 recordsLinked to original sources

Hepatotoxicity of amiodarone.

Amiodarone, a commonly used antiarrhythmic agent, has numerous adverse effects. The purpose of this case report is to highlight its hepatotoxicity, an unusual complication of long term amiodarone therapy. Our patient is a 76-year-old man with underlying ischaemic heart disease and recurrent ventricular tachycardia. Eleven months after commencing amiodarone, he developed asymptomatic raised aminotransferases which resolved following drug withdrawal. Amiodarone was then reintroduced and four years later, the patient developed hepatomegaly, worsening liver biochemistry and histopathological changes consistent with early cirrhosis. His symptoms improved following discontinuation of amiodarone. However, hepatomegaly and a low serum albumin still persist four years later.

Aged

Pulmonary pathology in rabbits infected with the Baling and Koyan strains of Schistosoma malayensis.

Two distinct strains of Schistosoma malayensis exist in Malaysia (designated the Baling and Koyan strains). Both these strains show intraspecific variations in pathology (Greer et al, 1988). To evaluate the differences in the pulmonary pathology resulting from infections of the two different strains of Malaysian schistosome, a total of 20 experimental rabbits were infected, 10 each with cercariae of the Koyan strains. Pathological changes were studied over a period of 28 weeks. Granulomas in the lung occurring as a result of infection with the Baling strain were compared with those caused by infection with the Koyan strain. Although both strains produced parenchymatous and alveolar lesions, granulomas caused by the Baling strain of Malaysian schistosome were more numerous and larger (when comparing mean diameter as well as area of granuloma, p < 0.05). In addition, pulmonary vascular hypertensive changes were present in Baling strain infected rabbits. These comprised of pulmonary arteriolar endothelial swelling and damage, intimal elastosis and medial hypertrophy. Angiitis and pulmonary periphlebitis were also noted occasionally. In contrast, Koyan strain infection resulted in fewer and smaller granulomas. Pulmonary vascular changes were minimal.

Animals

Three cases of human Sarcocystis infection with a review of human muscular sarcocystosis in Malaysia.

Three cases of muscular sarcocystosis from West Malaysia are reported. The morphological features of the parasites from these three cases are similar to the eight cases previously reported from this country. A review of this total of eleven cases of muscular sarcocystosis showed that they were all incidental findings, where man acted as intermediate hosts of as yet unknown Sarcocystis spp. These cases of muscular sarcocystosis were probably zoonotic in origin and associated with close contact with definitive hosts (both domestic and wild animals) thus permitting the contamination of food and drink with sporocysts shed by these definitive hosts. These infections were probably acquired locally as most of the subjects were born in Malaysia and none had ever left the country to stay elsewhere. Eight of the eleven cases reported were associated with malignancies, especially of the tongue and nasopharynx.

Adult

Induction of intestinal lesions in rabbits with Koyan and Baling strains of Schistosoma malayensis Sp N.

Schistosoma malayensis Sp N is a putative new species of schistosome discovered in Peninsular Malaysia in 1973. This paper comprises the first report on the detailed gastrointestinal pathology present in rabbits infected with strains of the parasite. Two different strains of schistosome--the Baling and Koyan strains--from two different ecosystems were used to infect inbred rabbits and the resulting pathophysiology was studied. Our results showed that the Baling strain of S. malayensis was more virulent than the Koyan strain and produced nodular, segmental circumferential lesions and large bilharziomas measuring 1-7 cm in diameter in the distal jejunum, ileum and the ileo-caecal junction. The findings indicate that the Baling strain of S. malayensis was more pathogenic for rabbits as compared with the Koyan strain--in relation to the gross pathology of the gut and the tissue egg load. Earlier reports have shown that rabbits infected with S. japonicum induces significant intestinal lesions in rabbits (Cheever et al, 1980 a,b) but these animals are refractory to infection with S. mekongi (Byram and Lichtenberg, 1980). Our studies show that the two strains of S. malayensis adapted well in rabbits. It is also established that in rabbits, the virulence of the Baling strain of S. malayensis is greater than that of S. mekongi and approximates that of S. japonicum.

Animals

POEMS syndrome, osteosclerotic myeloma and Castleman's disease: a case report.

Peripheral neuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes are often the presenting features of the POEMS syndrome. Approximately 50% of these are associated with osteosclerotic myeloma, a rare variant of multiple myeloma and some with Castleman's disease, an unusual lympho-proliferative disorder. The underlying pathogenetic mechanisms have not been elucidated but amelioration of symptoms with the disappearance of the M-component suggests possible etiopathogenic mechanisms. We present a 40-year-old woman with manifestations of all three disorders.

Adult

Primary cardiac amyloidosis.

Cardiac amyloidosis is an uncommon and often unrecognised cause of cardiac failure. It is an infiltrative disease that may mimic either a restrictive or hypertrophic cardiomyopathy, constrictive pericarditis, coronary artery disease or valvular heart disease. The diagnosis should be suspected in a patient with cardiac failure who has low voltage complexes on the electrocardiogram, in association with increased myocardial mass and echogenicity on the echocardiogram. The definitive diagnosis, however, can only be made by endomyocardial biopsy or biopsy of any involved organ in systemic amyloidosis. Prognosis is poor and treatment ineffective.

Adult

Review of sarcocystosis in Malaysia.

Sarcocystis is a tissue coccidian with an obligatory two-host life cycle. The sexual generations of gametogony and sporogony occur in the lamina propria of the small intestine of definitive hosts which shed infective sporocysts in their stools and present with intestinal sarcocystosis. Asexual multiplication occurs in the skeletal and cardiac muscles of intermediate hosts which harbor Sarcocystis cysts in their muscles and present with muscular sarcocystosis. In Malaysia, Sarcocystis cysts have been reported from many domestic and wild animals, including domestic and field rats, moonrats, bandicoots, slow loris, buffalo, and monkey, and man. The known definitive hosts for some species of Sarcocystis are the domestic cat, dog and the reticulated python. Human muscular sarcocystosis in Malaysia is a zoonotic infection acquired by contamination of food or drink with sporocysts shed by definitive hosts. The cysts reported in human muscle resembled those seen in the moonrat, Echinosorex gymnurus, and the long-tailed monkey, Macaca fascicularis. While human intestinal sarcocystosis has not been reported in Malaysia so far, it can be assumed that such cases may not be infrequent in view of the occurrence of Sarcocystis cysts in meat animals, such as buffalo. The overall seroprevalence of 19.8% reported among the main racial groups in Malaysia indicates that sarcocystosis (both the intestinal and muscular forms) may be emerging as a significant food-borne zoonotic infection in the country.

Animals

Detection of Epstein-Barr virus DNA in nasopharyngeal carcinoma using a non-radioactive digoxigenin-labelled probe.

The presence of Epstein Barr virus (EBV) DNA in biopsies from the post-nasal space (PNS) of patients suspected of nasopharyngeal carcinoma (NPC) was detected by in situ cytohybridization with an EBV DNA probe labelled with the novel labelling compound digoxigenin. The digoxigenin probe was hybridised to cryostat sections of NPC biopsies and subsequently detected by an enzyme immunoassay procedure. It was found that in situ cytohybridization using the digoxigenin probe was much more rapid and sensitive (96 h compared to five weeks) than the current method of using 3H-labelled probe. Using the digoxigenin EBV probe, it was found that in all the eighteen NPC biopsies tested, EBV DNA was detected in malignant epithelial cells and infiltrating lymphocytes. EBV DNA was also detected in some normal epithelial cells in these NPC biopsies. EBV DNA was not detected in epithelial cells of non-malignant biopsies.

Cell Line

Evaluation of the possible role of glucose, carnitine, coenzyme Q10 and steroids in the treatment of Reye's syndrome using the margosa oil animal model.

Glucose and steroids have been used in the treatment of children with Reye's syndrome, while carnitine and coenzyme Q10 have been the subject of some recent studies which suggest that these agents may have a role in the treatment of Reye's syndrome and Reye-like syndrome due to margosa oil poisoning. Because of the paucity of causes of Reye's syndrome seen at any one centre, the clinical variability of the disease, and limited knowledge of definite aetiologic factors, controlled clinical trials are not easy to carry out or to interpret in human cases. These caveats were overcome by evaluation of these four treatment modalities in an established margosa-oil-induced animal model of Reye's syndrome. Effectiveness of the treatment modalities was determined from clinical response and histopathologic parameters (grading of light microscopic fatty changes and ultrastructural changes in the hepatocytes). Results show that carnitine per se produces a small improvement in survival, but statistically, more significant benefit is seen with glucose administration. Carnitine plus 10% dextrose appears to produce better results. Evaluation of coenzyme Q10 and carnitine on histopathologic parameters in the liver after a sublethal dose of margosa oil showed no obvious ameliorating effect on liver pathology. Steroids (dexamethasone/methylprednisolone) had no beneficial effects in reducing mortality, affecting glycogen storage or lipid accumulation. Changes in the mitochondria, ribosomes and endoplasmic reticulum were unaltered from the groups treated with margosa oil alone. While glucose and carnitine supplements appear to be beneficial, the other modes of therapy do not seem to hold much promise in the treatment of Reye-like syndrome in the margosa-oil-induced animal model.

Animals

Carcinoma of the vulva in pregnancy: a rare occurrence.

A rare case of squamous cell carcinoma diagnosed in early pregnancy in a 28-year-old woman is described. At the time of radical surgery, which was carried out in the puerperium, the growth had already advanced to Stage IV disease. The rapid growth of the tumor seen in this patient suggests that although treatment needs to be individualised, the definitive radical surgery should not be delayed.

Adult

Disseminated histoplasmosis presenting as a non-healing tongue ulcer.

A 51-year old man presented with a persistent tongue ulcer, fever, cervical lymphadenopathy and hepatomegaly. The diagnosis was initially thought to be tuberculosis. This led to the initiation of antituberculous chemotherapy to which the patient failed to respond. The correct diagnosis of histoplasmosis was made after the detection of Histoplasma capsulatum on further review of the tongue ulcer biopsy specimen. He responded to treatment with amphotericin B.

Chronic Disease

Effect of dietary palm oils on mammary carcinogenesis in female rats induced by 7,12-dimethylbenz(a)anthracene.

Female Sprague-Dawley rats, 50 days of age, were treated with a single dose of 5 mg of 7,12-dimethylbenz(a)anthracene intragastrically. 3 days after carcinogen treatment, the rats were put on semisynthetic diets containing 20% by weight of corn oil (CO), soybean oil (SBO), crude palm oil (CPO), refined, bleached, deodorized palm oil (RBD PO) and metabisulfite-treated palm oil (MCPO) for 5 months. During the course of experiments, rats fed on different dietary fats had similar rate of growth. Rats fed 20% CO or SBO diet have higher tumor incidence than rats fed on palm oil (PO) diets; however differences of mean tumor latency periods among the groups were not statistically significant. At autopsy, rats fed on high CO or SBO diets had significantly more tumors than rats fed on the three PO diets. Our results showed that high PO diets did not promote chemically induced mammary tumorigenesis in female rats when compared to high CO or SBO diets. CO and SBO differ greatly from the palm oils in their contents of tocopherols, tocotrienols, and carotenes. But further experiments would be required to determine whether the observed differences in tumor incidence and tumor numbers were due to the differences in these minor components or due to the unique triglyceride structure of the palm oils. Analysis of the fatty acid profiles of plasma total lipids of tumor-bearing rats and of the tumor total lipids showed that, with the exception of arachidonic acid, the fatty acid profiles reflect the nature of the dietary fats. At autopsy, there were no differences in the plasma total cholesterol contents among rats fed on different dietary fats, but rats fed on palm oil diets had a significantly higher plasma triglyceride level than that of rats fed CO or SBO diets. As for the tumor lipids, there were no significant differences in the triglyceride, diglyceride, and phospholipid levels when the CO or SBO groups were compared to the palm oil groups.

9,10-Dimethyl-1,2-benzanthracene

Atrophy of left lobe of the liver associated with hepatolithiasis and cholangiocarcinoma.

A case of liver atrophy associated with hepatolithiasis and cholangiocarcinoma is presented. Intraductal calculus and left hepatic lobar atrophy were seen on both ultrasound and computerised tomography examinations. The lobar atrophy was accompanied by hypoplasia of left common hepatic artery. Cholangiocarcinoma was diagnosed on histology. There have been several reported cases of hepatolithiasis and cholangiocarcinoma. To our knowledge, there has been only one reported case of hepatolithiasis and cholangiocarcinoma with liver atrophy (Nishihara K et al 1986) but this was not angiographically demonstrated.

Adenoma, Bile Duct

Microscopically diagnosed head and neck cancers in the University Hospital, Kuala Lumpur.

A retrospective study of 1000 cases of microscopically diagnosed head and neck cancers in the University Hospital, Kuala Lumpur was done. Head and neck neoplasms comprise 7.1% of all tumours diagnosed in this Hospital and the commonest sites of involvement are the nasopharynx (29.1%), cervical lymph nodes (22.6%), oral cavity (10.2%), thyroid (8.2%) and skin (6.5%). Histologically, 87% of tumours are epithelial in nature. The results of this study show that nasopharyngeal carcinoma is commonest in Chinese males, while oral and laryngeal malignancies occur more frequently in Indians.

Asian People

Immature teratoma of the ovary.

Results of treatment of 9 cases of pure immature teratoma of the ovary seen at the University Hospital, Kuala Lumpur, are presented. Six patients were in Stage 1 and three in Stage 3. A majority of them had grade 2 or 3 tumors. Four patients in Stage 1 had the conservative surgery of salpingo-oophorectomy performed, the more radical procedure of total hysterectomy, bilateral salpingo-oophorectomy omentectomy, and tumor debulking where feasible being carried out in the others. Adjuvant chemotherapy consisted of either pulsed cyclophosphamide, VAC (vincristine, actinomycin D, and cyclophosphamide) or PVB (cis-platinum, vinblastine, bleomycin) regimes. Seven patients have survived for periods up to 9 years with no clinical evidence of disease.

Adolescent

Anorectal melanoma.

Four cases of anorectal melanoma are presented. The authors believe that this is the first report of the occurrence of this tumour in Malays. Advanced disease at initial presentation accounts for the poor prognosis observed in this series. Surgery remains the principal treatment modality, although controversy exists regarding optimal extent of resection.

Adult