Biomedical subjects
Publications and source records attributed to S K Teo.
We report a fulminant case of Neuroleptic Malignant Syndrome in a 31-year-old male schizophrenic on haloperidol, thioridazine, benzhexol and flurazepam who presented with rigidity, fever, stupor and autonomic instability. He succumbed rapidly over 6 days to rhabdomyolysis, acute renal failure, status epilepticus and disseminated intravascular coagulopathy despite treatment with dantrolene and bromocriptine at the outset.
The direct acting mutagen 2-cyanoethylene oxide (CEO), formed in the liver by oxidation of acrylonitrile (ACN), is thought to mediate the extrahepatic carcinogenic effects of ACN in rats. This study determined the tissue distribution of CEO (3 mg/kg p.o.) in F-344 rats and B6C3F1 mice. Radioactivity from [2,3-14C]CEO was widely distributed in the major organs of rodents by 2 h and decreased by 71% to 90% within 24 h, demonstrating that there was no preferential tissue uptake or retention of CEO. CEO was detected in rodent blood and brain 5-10 min after an oral dose of ACN (10 mg/kg), demonstrating that this mutagenic epoxide metabolite circulates to extrahepatic target organs following ACN administration.
Information on lung disease due to nontuberculous mycobacteria (NTM) is lacking in Singapore. A review of the records at the Central Tuberculosis Laboratory up to the end of 1988 showed that 23 patients seen between 1976 to 1988 inclusive had cultures which were repeatedly positive for NTM. Of the 23 cases analyzed, 15 were found to have lung disease which could be attributed to NTM. There were 9 males and 6 females with a male to female ratio of 1.5:1. The patients were either middle aged or elderly. The 2 main infective agents were M avium-intracellulare and M kansasii. Ten (67%) patients had moderately advanced and 5 (33%) had far advanced disease. Concurrent disease of the lung was present in 10 patients (67%). Seven (47%) patients had bronchiectasis, 1 (7%) had both bronchiectasis and chronic obstructive pulmonary disease (COPD) and 2 (13%) had COPD. A past history of pulmonary tuberculosis was present in 10 patients (67%). Lung disease due to NTM is uncommon in Singapore. Treatment failure was attributed to poor compliance, a possibility which could not be excluded in those patients who had adverse reactions.
A study of 120 cases of tuberculosis in patients aged 65 years and above revealed that there were more males than females with the disease compared with the younger age group of 15 to 45 years old. The elderly group also had significantly more severe and more had bacteriologically positive disease. The majority of them were born outside Singapore and immigrated more than 30 years ago. Risk factors such as diabetes mellitus, past history of tuberculosis, malignancy and gastrectomy were more common in the elderly group. Standard 6-month regimens were well tolerated and adverse side effects to the drugs were negligible.
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Endobronchial tuberculosis is not as well-known to internists as tuberculosis involving the lung parenchyma. Five cases with this condition are reported to illustrate the varied clinical manifestations. The presenting features of the 5 cases were lobar or lung collapse, unresolved pneumonia, dyspnoea and stridor. Bronchostenosis developed in 2 patients many years following chemotherapy, while stenosis of the trachea developed in one patient during chemotherapy. In another patient, the tuberculous granulation tissue simulated a lung cancer at bronchoscopy. Diagnosis can be difficult as endobronchial tuberculosis can occur in the absence of chest X-ray abnormality and sputum smear may also be negative for acid fast bacilli (AFB). Therefore, bronchoscopy should be done when the condition is suspected in a patient who has unexplained cough, wheezing, dyspnoea or haemoptysis. The modalities of treatment for fibrostenosis of a large airway include surgical resection followed by anastomosis, balloon dilatation, laser photoresection or a combination of both procedures.
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The bioavailability of isoniazid, rifampin, and pyrazinamide in 2 combined formulations of the 3 drugs (Rifater) for use primarily in the short-course chemotherapy of tuberculosis has been studied in Chinese patients in Singapore and Hong Kong. One formulation, containing 50 mg isoniazid, 120 mg rifampin, and 300 mg pyrazinamide per tablet is suitable for daily use, whereas the other, containing higher proportions of isoniazid and pyrazinamide, is designed for intermittent treatment, each tablet containing 125 mg isoniazid, 100 mg rifampin, and 375 mg pyrazinamide. Appropriate dosages for the Chinese patients, whose average weight was approximately 50 kg, were 5 and 6 tablets, respectively. Plasma concentrations of the 3 drugs after giving such dosages of the 2 combined formulations were compared in 16 patients, 8 in Singapore and 8 in Hong Kong, by means of a crossover study, with the concentrations obtained when identical doses of the 3 drugs were given using standard separate drug formulations. The concomitant urinary excretions of the drugs and their major metabolites were also estimated. Very similar results were obtained whether the drugs were given as the combined preparations or in their standard separate formulations, demonstrating the excellent bioavailability of all 3 drugs in each of the 2 combined formulations.
An unusual case of intravascular bronchioloalveolar tumour in a 40-year-old Chinese woman is reported. The woman has survived 20 years after radiological abnormalities were first noted in her lungs. This slowly progressing endothelial lung tumour has only recently been recognized as a distinct pathological entity.
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The last 25 years have seen many important developments in tuberculosis chemotherapy in Singapore. Beginning in the 1950s, chemotherapy consisting of streptomycin (S), isoniazid (H) and p-aminosalicylic acid (PAS) was introduced at first with 2-drug and later 3-drug combinations (i.e., SPH/PH for a total of 18 to 24 months). In the 1960s, 2 early studies showed that thiacetazone (T) could not be substituted for PAS in standard chemotherapy as it was a more toxic and less potent drug. Routine tuberculosis treatment achieved good results for patients followed up for 5 years after completing treatment. A fully supervised regimen of streptomycin and isoniazid (S2H2) given twice weekly proved to be as effective as a largely self administered regimen of PAS/INH. Ethambutol (EMB) was shown to be effective in the initial treatment of pulmonary tuberculosis when combined with isoniazid. In the 1970s, rifampicin (R) was first investigated starting with an intermittent regimen of isoniazid and rifampicin given once or twice weekly. The success of this regimen led to 2 short course studies of 6-month regimens. Rifampicin was given daily for the full duration of 6 months (2SHRZ/HR; 2SHRZ/HRZ; Z = pyrazinamide) or intermittently 3 times a week in the continuation phase (2SHRZ/H3R3; 2HRZ/H3R3; 1SHRZ/H3R3). All the 6 months regimens were highly effective.
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