Serum levels were determined in urban Chinese, Malays and Indians and in the forest-residing Orang Asli of age group 11 to 50. There was no difference in the IgM levels in the Chinese, Indians and Malays, but the serum IgG was elevated (p less than 0.05) in the Malays and the serum IgA level (p less than 0.01) in the Indians, when compared to the other two races. In contrast to the three other races there was a significant elevation of all three immunoglobulins in the Orang Asli. The mean immunoglobulin levels of the urban Malaysians are comparable to those reported for Caucasians residing in temperate countries. However, in the Orang Asli, the immunoglobulin levels were higher than observed for populations of the temperate regions but are comparable to the levels reported for several other populations of the tropical regions. Females had higher IgM levels than males in the Chinese, Indian and Malays but in the Orang Asli there was no sex difference in the immunoglobulin levels.
Serum IgG levels and complement C3 levels were assayed on Day 0, 1, 3-4, 7 and 56-70 post-treatment with diethylcarbamizine citrate (DEC) in a series to 26 patients with Brugia malayi infection and 6 volunteers without infection. On treatment, the microfilariae were cleared from the blood within 24 hours. The eosinophils decreased dramatically on Day 1 post-treatment but increased rapidly by Day 4 to 7 and then dropped to normal levels in 45 days. The serum IgG mean levels decreased briefly following treatment with DEC but then returned to original levels. However, the complement C3 levels gradually increased over the 2 months period of study reaching statistical significance levels (p less than 0.01) in patients with initial high blood microfilariae. The observation suggests that Brugia malayi infection probably induces a high rate of synthesis of complement C3 and this process continued in the post-treatment phase. Since, DEC treatment did not cause a decrease in complement C3 with the elimination of blood microfilariae, it would appear that the complement C3 is consumed following antibody attachment to the microfilariae as they enter the blood circulation.
Serum tumor necrosis factor alpha (TNF) concentration was assayed in 105 patients with nasopharyngeal carcinoma using a sensitive ELISA technique with detection level of 10 pg/ml. The TNF levels were detectable in 45 of 63 (71.4%) patients newly diagnosed for the malignancy and 29 of 42 (69%) patients in remission following treatment with radiotherapy. In 25 normal controls the TNF were less than 10 pg/ml. While TNF may be present in the majority of the patients with the malignant disease, the TNF concentration appeared to have no clinical significance in diagnosis or prognosis of the patients.
The antibody titres to P. falciparum and Epstein-Barr Virus-associated antigens were assayed in 22 patients with NPC and 43 controls. All, but one patient had antimalarial titres; 14 had titres greater than 80 and 4 patients greater than 640. Compared to controls the mean anti-malarial titre for most age groups were higher in the patients. Those patients with high anti-malarial titres also had high IgA anti-VCA titre, an antibody which has been demonstrated to be diagnostic for NPC. The peak anti-VCA (IgG) and anti-EA (IgG) antibody titres were associated with anti-falciparum titres of 320-640 and 80-160, respectively. The results are discussed in relation to the possible association between malarial infection and etiology of NPC.
The prevalence of antibody to human herpesvirus type 6 (HHV-6) and Epstein-Barr virus (EBV) viral capsid antigens (VCA) were analysed in sera from Kadazans of Sabah, North Borneo. At a serum dilution of 10, about 34% were positive for HHV-6 antibody but in contrast all 95 individuals studied were positive for EBV VCA antibody. The study shows that HHV-6 and EBV infection occur independently. The low frequency of seropositive individuals in this community suggests that other than socioeconomic factors are responsible for the spread of the virus.
Serum immunoglobulin G, A, M, D and E levels were determined in the forest-dwelling Orang Asli of age group 8 to 64 years. The levels are higher than observed for urban Malaysians and comparable to levels reported for populations residing in the tropics. There was no significant difference in serum levels of all the immunoglobulins studied in both sexes. The elevated serum immunoglobulins levels are discussed in terms of the nature of the immune defence developed in the Orang Asli to contend with the many parasites prevalent in their environment.
The relative efficacy and incidence of hypernatremia of a rice starch based low sodium (sodium of 60 mmol/L) oral electrolyte solution was compared to the standard WHO oral rehydration solution (ORS; sodium 90 mmol/L) in 60 infants with non choleragenic acute diarrhoea. Both solutions were found to be equally effective in correcting dehydration as determined by the respective post hydration weight gain which was 150 +/- 175 gms in the rice starch low sodium ORS group and 164 +/- 125 gms in the standard WHO ORS group. However, the mean frequency of stools was greater and the duration of stay longer in the WHO ORS group compared to the rice starch low sodium group. There were 5 cases of hypernatremia in the WHO ORS group as opposed to only one in the rice starch low sodium ORS group. The present study shows that a rice starch low sodium ORS was as effective as the standard WHO ORS and had a lower incidence of hypernatremia in the fluid and electrolyte management of infants with non choleragenic diarrhoea.
The present study was undertaken to evaluate the prevalence of HPV in formalin-fixed, paraffin-embedded cervical carcinoma tissues using PCR followed by non-radioactive Southern hybridization with type-specific oligonucleotides for HPV 16 and 18. In addition, the tissue sections were immunohistochemically screened with two monoclonal antibodies, for expression of HPV 16 L1 and HPV 18 E6 proteins. A total of 57 of 60 cervical carcinomas (95.0%) were found with HPV using both techniques. HPV 16 and HPV 18 were present in equal proportions. Results of both DNA hybridization and immunohistochemistry were in agreement for the majority of the cases. HPV 16 and 18 DNA and virus-encoded antigens, L1 and E6 were found highly prevalent in these cervical carcinomas. Due to the high prevalence of HPV with cervical carcinoma in Malaysia, the implementation of routine diagnosis for the virus in cervical biopsies would be clinically useful.
Specific human papillomavirus (HPV) types have been implicated in the development of cervical carcinoma worldwide. Novel molecular techniques have facilitated the detection and typing of HPV in cervical lesions. DNA preparations from a series of 23 histopathologically confirmed cervical carcinoma patients were analyzed by polymerase chain reaction (PCR) using degenerate primers for the presence of HPV DNA sequences. A total of 22 of 23 cases studied (95.7%) were found positive for HPV DNA sequences. Further studies by DNA hybridization with viral specific probe and restriction enzyme analysis demonstrated the presence of HPV 16 in 73.9% (17/23) and HPV 18 in 65.2% (15/23) of the cases examined. Interestingly, the uncommon HPV 31 and 33 were also found but with a lower percentage (16.9%). It was noted that HPV 16 frequency in the carcinoma increased with age but HPV 18 was evenly present at all ages investigated. We found that HPV was frequently associated with the majority of the cervical carcinomas, and in all but one case, oncogenic high risk HPV genotypes were present. We conclude that HPV infection of the genital tract has an important role in the development of the disease in Malaysia.
The effect of cow's milk protein (CMP) challenge on the levels of alkaline phosphatase (ALP) in the upper jejunal mucosa and the serum were studied in 25 infants clinically suspected to have cow's milk allergy. Following CMP provocation 3 groups were identified. Group 1 consisted of 10 infants who had clinical and histological reaction to CMP challenge. All 10 infants had significant depletion in the levels of tissue and serum ALP. Group 2 consisted of 5 infants who had histological reaction but no clinical reaction. Tissue ALP was depressed in 3 but not in 2 following CMP challenge. Serum ALP were essentially unaltered in all 5. Group 3 consisted of 10 infants who clinically and histologically tolerated CMP challenge. Tissue and serum ALP were not depressed in any. Estimation of sucrase levels in the mucosa and xylose absorption before and after CMP challenge were also performed for comparison with changes of tissue and serum ALP levels. The clinical significance of the changes in serum ALP level is discussed.
Eighteen infants clinically suspected to be intolerant of cow's milk were placed on a milk-free formula and six to eight weeks later were orally challenged with cow's milk. Following challenge three groups were recognised. Group A: Four infants tolerated oral feeds ofcow's milk and lacked mucosal abnormality or clinical symptoms. Group B: Seven infants had mucosal deterioration but lacked clinical symptoms and tolerated cow's milk. Group C: Seven infants had mucosal abnormality, developed clinical symptoms and were intolerant of cow's milk. The intestinal transudation of IgA was increased in Group A and unchanged in Group Band C : the IgM levels in the duodenal juice was increased in Group A and B but unchanged in Group C : the IgG levels in the juice were increased in all Groups following challenge. It appears that increased transmission of IgA and IgM or IgM alone in the duodenal juice is associated with lack of development of clinical symptoms. Symptoms are present in infants in whom the IgA and IgM levels in duodenal juice remained unchanged after challenge. It is suggested that patients responding to cow's millt challenge with intestinal production of IgA and IgM (or IgM alone) are able to counter balance the deleterious mechanisms leading to clinical cow's milk intolerance whereas those who, for some unknown reason, do not mount a secretory immune response become ill.
Infants, one to 56-weeks-old, presenting with persistent diarrhoea were placed on a diet free of cow's milk protein which improved their clinical condition. Six weeks later, 67 infants were challenged with a low-lactose cow's milk formula and jejunal biopsy was taken before and 24-hours after challenge. On the basis of histological changes in the intestinal mucosa and development of clinical symptoms the infants were categorised into three groups: Group 1 (n = 16) with no clinical or mucosal abnormality, Group 2 (n = 20) with mucosal abnormality but lacking clinical symptoms, and Group 3 (n 31) with manifestation of mucosal abnormality and clinical symptoms. In addition to the total IgE the radioallergosorbent test (RAST) was performed on sera from the infants taken before and after milk provocation. The mean total serum IgE level ranged from 288 to 560 IU/ml. In Groups 2 and 3 the prechallenge serum IgE levels were significantly higher than the postchallenge levels but in Group 1 the levels remained unchanged on challenge. A positive RAST to milk proteins was observed in five infants (7.4%), that is, one in Group 2 and four in Group 3, of 67 infants studied. In a survey of 405 consecutive paediatric-age patients admitted for a variety of symptoms, 90 were positive for RAST specific for milk proteins. Interestingly the majority of the patients positive for RAST presented with gastrointestinal ailments. The measurement of specific IgE appears not to be a useful adjunct in the diagnosis of CMPSE in Malaysian children.
Enterokinase has a critical role in initiating proteolytic digestion by hydrolysing the conversion of pancreatic trypsinogen into trypsin. The enzyme is synthesised by enterocytes of the proximal small intestine and initially incorporated into the brush border from where it is released into the intestinal lumen by the action of pancreatic secretions. The aim of the study was to analyse enterokinase activity in the duodenal mucosa of infants with diarrhoeal disease including cow's milk protein-sensitive enteropathy. Our observations show that the mean depletion of enterokinase was only 17% compared to 60-80% for other brush border enzymes like disaccharidases, peptidases and alkaline phosphatases in infants with diarrhoea. This suggests that enterokinase activity in the small bowel enteropathies may be dependent not only on the degree of mucosal damage specifically but also on the extent of damage to the goblet cell population where the enzyme is synthesised. Thus the enterokinase activity was reduced in acute and chronic diarrhoea with marked mucosal damage where significant reduction of goblet cell population was evident but the enzyme was relatively little affected when the mucosa was damaged mildly.
Dengue fever (DF) which is caused by four serotypes of dengue virus may in some cases progress into a life threatening situation of dengue haemorrhage fever (DHF) and dengue shock syndrome (DSS). It has been suggested that sequential infection with different dengue virus serotypes predisposes the patient towards DHF/DSS. We report here a primary dengue infection in a 10-year-old boy progressing from DF to DSS while under clinical observation. The report provides unequivocal evidence for the development of DSS in primary dengue infection caused by virus serotype 4. The close relationship between sequential changes in the levels of tumour necrosis factor (TNF), Interleukin 1 and 6 (IL-1 and IL-6) in the serum, to the clinical progression of the disease from DF to DHF/DSS and then to full recovery implicates a pathogenetic role for the inflammatory cytokines. The child also manifested clinical features consistent with Reye's syndrome and this suggests a common pathogenetic origin for DSS and the Reye-like syndrome induced by dengue virus.