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Biomedical subjects

A Mathew

Publications and source records attributed to A Mathew.

At least 37 records · Page 2Linked to original sources
PubMed1999

Impaired T cell proliferation in acute dengue infection.

Decreased proliferative responses to mitogens and recall Ags have been observed in PBMC obtained during several acute human viral infections. To determine whether cell-mediated responses are altered during acute dengue infection, we examined the proliferative responses of PBMC from children enrolled in a prospective study of dengue infections in Thailand. All responses of PBMC during acute illness were compared with the same patients' PBMC obtained at least 6 mo after their infection. Proliferative responses to PHA, anti-CD3, tetanus toxoid, and dengue Ags were decreased significantly in PBMC obtained during the acute infection. The proliferative responses to PHA were restored by the addition of gamma-irradiated autologous convalescent or allogeneic PBMC. Cell contact with the irradiated PBMC was necessary to restore proliferation. Non-T cells from the acute PBMC of dengue patients did not support proliferation of T cells from control donors in response to PHA, but T cells from the PBMC of patients with acute dengue proliferated if accessory cells from a control donor were present. Addition of anti-CD28 Abs restored anti-CD3-induced proliferation of the PBMC of some patients. The percentage of monocytes was reduced in the acute sample of PBMC of the dengue patients. Addition of IL-2 or IL-7, but not IL-4 or IL-12, also restored proliferation of acute PBMC stimulated with anti-CD3. The results demonstrate that both quantitative and qualitative defects in the accessory cell population during acute dengue illness result in a depression of in vitro T cell proliferation.

Acute Disease↗
PubMed1999

A multivariate analysis of prognostic indicators in complete hydatidiform moles (CHM).

OBJECTIVE: To analyse prognostic factors in complete hydatidiform moles using multiple logistic regression analysis. METHODS: Evaluation of host and tumour related parameters including (a) gestational age, patient age, parity, molar phenotype, grade of proliferation of the tumour and cytological atypia, (b) expression of beta-HCG, EGF, EGFR, TGF-alpha, TGF-beta, IL1-alpha, IL1-beta by immunohistochemistry, (c) serial monitoring of serum beta-HCG levels by ELISA, and (d) lectin binding using jack fruit lectin histochemistry as indices for persisting trophoblastic disease (PTD). RESULTS: Serum beta-HCG levels at 4 weeks, cellular atypia, lectin binding, expression of TGF-alpha and IL1-beta showed highly significant correlation with persistence of the tumour (P<0.001). The sensitivity and specificity at 4 weeks in combination with cytological atypia to identify spontaneously regressing lesions was 100% and those requiring chemotherapeutic intervention was 80%. CONCLUSION: The concentration of serum beta-HCG 4 weeks post evacuation(<300 mIU/ml) combined with cytological abnormalities could identify nearly 100% of the spontaneously regressing lesions (low risk) and 80% of those needing chemotherapeutic intervention (high risk), thereby suggesting that patients who have a serum beta-HCG at 4 weeks of evacuation <300 mIU/ml with no cytological atypia of the trophoblasts need only be followed up at long intervals, while those having a serum beta-HCG at 4 weeks of evacuation >300 mIU/ml accompanied with cytological atypia of the trophoblasts should be closely followed up.

Chorionic Gonadotropin, beta Subunit, Human↗
PubMed1999

Cancer vaccines: a step towards prevention and treatment of cancer.

Breakthroughs in basic science and applied biology over the last quarter of a century have had a great deal of influence on our understanding of disease processes. The structure, function and importance of various lipid and protein molecules within cells is now well known and is central in future developments of diagnostic and therapeutic modalities. Since the discovery of the double helix DNA structure by Watson and Crick, molecular biology has come a long way enabling inroads to be made in manipulating DNA and evolving into the discipline of molecular oncology. For tumours having a viral carcinogenesis, preventive vaccines directed against viruses reduce the chance of tumour formation. Therapeutic vaccination, on the other hand, is less successful. To overcome the latter, various methods involving the use of tumour-specific antibodies, anti-idiotypic antibodies, peptides, proteins and carbohydrate products of human tumours, etc. have been tried. However, as the majority of human tumours are antigenic and not immunogenic, the problem remains. Recently, inoculation with DNA plasmids, encoding a variety of proteins, has been able to generate T-cell specific responses in vivo. This novel concept may help scientist to overcome the immunological tolerance and anti-tumour ineffectiveness induced by many human cancer cells and may lead to generation of tumour-specific vaccines.

Antibodies, Neoplasm↗
PubMed1999

Malignancy load on general surgeons: the need to change the general surgical training curriculum.

AIMS: With the advent of newer diagnostic modalities more and more cancer patients are being diagnosed each year. The rising detection rate and greater public awareness have immensely increased the load on already overburdened and increasingly fewer surgical oncology units. As a result a large number of these cases are being dealt with by general surgeons. METHODS: We have used a retrospective case count from a single surgical unit, based at the University Hospital, Varanasi, and data from the Hospital Based Cancer Registry (HBCR), Regional Cancer Centre (RCC), Trivandrum, from 1990 to 1994, to define the malignancy load on general surgical units and to define the number and sites of malignancies commonly encountered by general surgeons. RESULTS: A total of 28,136 patients were registered at the RCC, the commonest malignancy being oral cavity (16.35%), followed by lung (12.7%) and breast (23.8%) among men and women, respectively. On the other hand, in the 2123 patients with malignancy who were treated at the Medical College (MCH) in Trivandrum, the commonest sites encountered were stomach (11.68%), thyroid (10.31%) and colorectal (9.5%). This was quite similar to the frequencies observed at Varanasi, where colorectal cancer constituted 10.26% and stomach 6.98%. Only 13.6% of the patients reporting to RCC were treated by surgery alone or in combination, while this figure was 48. 1% for MCH. Similarly 2056 (7.3%) patients presenting to RCC had completed treatment prior to being referred to RCC; almost all of these patients were treated by surgery at referral institutions by general surgeons. CONCLUSIONS: The results clearly indicate an increased demand on the surgical oncology units, or alternatively an urgent need to redefine the postgraduate curriculum for the better training of general surgeons in understanding malignant disease, especially in the developing countries. We recommend a minimum of 6 months training in surgical oncology for each general surgery postgraduate.

Cancer Care Facilities↗
PubMed1999

Survival analysis: caveats and pitfalls.

BACKGROUND: Survival analysis in clinical studies is important to assess the effectiveness of a given treatment and to understand the effect of various disease characteristics. A number of methods exist to estimate the survival rate and its standard error. However, one cannot be certain that these methods have been handled appropriately. The widespread use of computers has made it possible to carry out survival analysis without expert guidance, but using inappropriate methods can give rise to erroneous conclusions. The majority of the biomedical journals now recommend that a statistical review of each manuscript should be carried out by an experienced bio-statistician, in addition to obtaining expert referees' comments on the article. The problem is compounded in papers from third-world countries where bio-statisticians may not be available in all institutions to guide clinicians as to the selection of proper techniques. METHODS: The present paper deals with the various techniques of survival analysis and their interpretation, using a modal data set of malignant upper-aerodigestive tract melanoma patients treated in the Regional Cancer Centre, Trivandrum since 1982. RESULTS: The Kaplan-Meier method was found to be the most suitable for survival analysis. The median survival time is a better method of summarizing data than the mean. Rothman's method of estimation of the confidence limit is better than Peto's method as the confidence limit for survival probability tends to go beyond the range of 0-1.0 when calculated by Peto's method, especially when the sample size is small. CONCLUSION: The results from the present study suggest that survival analysis should be carried out by the Kaplan-Meier method. The median survival time should be provided wherever possible, rather than relying on mean survival. Confidence limits should be calculated as a measure of variability. A suitable rank test should be used to compare two or more survival curves, rather than a Z-test. Stratified analysis and Cox's model, when stratified analysis fails, can be used to define the impact of prognostic factors on survival.

Confidence Intervals↗
PubMed1999

Acute pancreatitis with cholestatic hepatitis: an unusual manifestation of hepatitis A.

Acute hepatitis A infection is an uncommon cause of pancreatitis in children. To date, only four cases have been reported in the paediatric literature. We report a 7-year-old girl with acute pancreatitis associated with hepatitis A infection who made a satisfactory recovery. The report highlights the CT findings including focal necrosis not previously reported. Because of the extreme rarity of the complication, the four previous reports have also been single case reports. This paper reviews all these cases with a view to elucidating the aetiopathogenesis of the pancreatitis.

Acute Disease↗
PubMed1999

Global perspective of tobacco habits and lung cancer: a lesson for third world countries.

Over the past 50 years, a dominant role of tobacco smoking in lung cancer causation has been demonstrated. Almost three-quarters of the lung cancer cases can be attributed to tobacco smoking. The global variation in lung cancer incidence is thought to be directly proportional to the smoking habits prevalent in that part of the world. Lung cancer shows a greater upward trend in incidence in the USA, in central and Eastern Europe than ever before, especially in females. Japan too has recorded a 10-fold increase in incidence in both sexes since 1975. In India the problem is further compounded by absence of authentic data on time trend. The recent trend of available data suggests a more or less linear trend. At present lung cancer ranks among the top three killers in men in almost every metropolis in India. The highest incidence rate has been recorded in Bombay (14.6/ 100,000) and the lowest in Barshi (2.0/100,000). How much of these can be attributed to smoking cannot be commented on as no case-control or cohort studies have ever been undertaken in India. The situation is more alarming in other developing countries, where there is no authentic data on tobacco use or lung cancer incidences. The relationship between tobacco and cancer is both simple and complex. The majority of the cancer patients are smokers, while the cancer incidence is not proportional among smokers. To explain this, various factors such as type of smoke, duration of smoke, amount of carcinogens, presence of activation and metabolism pathways, and lately genetic environment interaction, have been put forward. It appears that the relationship is more complex than at first thought. In developing countries, it is further compounded by lack of data on usage and dependence of the economies of these countries on tobacco. The situation is alarming, with ever-increasing incidence among women and non-smokers exposed to smoke (passive smokers). Tobacco use has already become an epidemic.

Carcinogens↗
PubMed1999

Primary malignant melanoma of the upper aero-digestive tract.

Malignant mucosal melanoma represents 0.3 to 10% of all melanomas. The majority of these lesions arise in the oral cavity or paranasal sinuses. Very few authors report reliable treatment results, however all suggest a uniformly poor outcome. A retrospective analysis of all cases of upper aero-digestive tract melanoma (UADT) treated since 1982 at our centre are presented. During the 15-year period, nine cases of UADT melanoma were identified. Three patients had a lesion in the palate, two in the maxillary alveolus, two in the oropharynx, while one each had a lesion in paranasal sinus and lower alveolus. Mean age was 43.25 years (28-62 years), with a male to female ratio of 1.6:1. Cervical lymphadenopathy was the commonest presenting symptom in seven patients. Radical surgery was carried out in three patients, wide excision in three and radical neck dissection in six, while no surgical intervention was undertaken in two patients. Median follow-up time was eleven months. In four patients, local recurrence occurred, while three developed pulmonary metastasis. One patient was lost to follow-up. We suggest that data from various centres be pooled together in order to carry out a meta-analysis to address the question of optimal treatment for malignant melanoma of the upper aero-digestive tract.

Adult↗
PubMed1999

Survival analysis: caveats and pitfalls.

BACKGROUND: Survival analysis in clinical studies is important to assess the effectiveness of a given treatment and to understand the effect of various disease characteristics. A number of methods exist to estimate the survival rate and its standard error. However, one cannot be certain that these methods have been handled appropriately. The widespread use of computers has made it possible to carry out survival analysis without expert guidance, but using inappropriate methods can give rise to erroneous conclusions. The majority of the biomedical journals now recommend that a statistical review of each manuscript should be carried out by an experienced bio-statistician, in addition to obtaining expert referees' comments on the article. The problem is compounded in papers from third-world countries where bio-statisticians may not be available in all institutions to guide clinicians as to the selection of proper techniques. METHODS: The present paper deals with the various techniques of survival analysis and their interpretation, using a modal data set of malignant upper-aerodigestive tract melanoma patients treated in the Regional Cancer Centre, Trivandrum since 1982. RESULTS: The Kaplan-Meier method was found to be the most suitable for survival analysis. The median survival time is a better method of summarizing data than the mean. Rothman's method of estimation of the confidence limit is better than Peto's method as the confidence limit for survival probability tends to go beyond the range of 0-1.0 when calculated by Peto's method, especially when the sample size is small. CONCLUSION: The results from the present study suggest that survival analysis should be carried out by the Kaplan-Meier method. The median survival time should be provided wherever possible, rather than relying on mean survival. Confidence limits should be calculated as a measure of variability. A suitable rank test should be used to compare two or more survival curves, rather than a Z-test. Stratified analysis and Cox's model, when stratified analysis fails, can be used to define the impact of prognostic factors on survival.

Digestive System Neoplasms↗
PubMed1998

Anencephaly-associated aganglionosis.

Autopsies of 12 consecutively born infants with anencephaly showed varying degrees of aganglionosis and lateralization defects in four of them. This seemingly regular occurrence of these three defects together suggests that they are caused by an aberration of blastogenesis that results in a polytopic field defect.

Anencephaly↗
PubMed1998

Immune mediated and inherited defences against flaviviruses.

BACKGROUND: Flavivirus infection elicits an abundant immune response in the host which is directed against a number of the viral proteins. Resistance to flavivirus-induced disease can also be controlled via a non-immune mechanism involving the product of a naturally occurring murine gene, Flv. OBJECTIVES: To review studies that have reported the mapping of epitopes on flavivirus proteins that elicit T- or B-cell immune responses in mice or humans and to discuss a possible mechanism for flavivirus-specific genetic resistance. STUDY DESIGN: Purified viral proteins and synthetic peptides were used to map B-cell epitopes. Purified proteins, vaccinia-expressed viral protein fragments and synthetic peptides were used to map T-cell epitopes. Congenic-resistant, C3H/RV and congenic susceptible, C3H/He mice and cell cultures were used to study the mechanism of genetic resistance to flavivirus infection. RESULTS: T- and B-cell epitopes have been mapped to the E, NS1 and NS3 proteins of several flaviviruses. Immune responses to the C, PreM, NS2a, NS4a, and NS5 proteins have also been documented. Data suggest that the Flv gene product acts intracellularly to suppress the synthesis of viral genomic RNA. CONCLUSIONS: Although flavivirus infection elicits an abundant immune response, this response is not always rapid enough to protect the host from developing encephalitis. During secondary infections both the humoral and cellular flavivirus-specific responses can confer protection. Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) appear to be caused by an overly vigorous immune response. In genetically resistant animals reduced production of virus results in a slower spread of the infection, which in turn allows time for the immune response to develop and to clear the infection before disease symptoms appear.

Animals↗
PubMed1998

Biliary reconstruction with or without an internal biliary stent in orthotopic liver transplantation: a prospective randomised trial.

Choledochocholedochostomy (CCD) with a 7 fr/8 fr Cotton Leung internal biliary stent removed at endoscopic retrograde cholangiography (ERC) 3 months following orthotopic liver transplantation (OLT) was the technique used on our unit for biliary reconstruction. From June 1995 to July 1996, we randomised 37 OLT patients with CCDs to receive either an internal stent (group I, nd = 18) or no stent (group II, n = 19). Patients in group I had an ERC at 3 months for stent removal whereas patients in group II had an ERC if indicated. The mean follow up was 19 (13-26) months. Biliary complications occurred in 9 out of 18 patients in group 1 compared to 1 out of 19 patients in group II (P = 0.007). In group I, ERC was required for complications in 8 patients and early surgery in 2, compared to 1 ERC for abnormal liver function tests in group II. Five of the early complications in group I were stent related. Late biliary stenosis occurred in 1 patient at 9 months. There was one stent-related death. The use of stents contributes to biliary complications and CCD without stenting is safe after OLT.

Adolescent↗
PubMed1998

Loss of glucose transport in developing avian red cells.

Although red cells are generally associated with significant glucose transport and dependence on glycolysis, the mature red cells of some species (e.g. pig) show very low glucose transport. The generally low level of glucose transport in mature mammalian red cells is the result of maturational development, since it has been shown that even in red cells which have negligible glucose transport (e.g. pig red cells) the corresponding reticulocytes have significant glucose transport activity. The reticulocytes of the chicken, however, show minimal glucose transport activity. But this also is the result of maturational development, since chicken bone marrow red cells do transport glucose which diminishes upon cell maturation in vitro. The erythroblast chicken cell line, HD3, has high glucose transport activity which is lost upon induction to the red cell phenotype. Growing HD3 cells have much higher levels of transport than native chicken bone marrow cells and this is associated in part with elevation of glucose transporter (GLUT) mRNAs as a consequence of the expression of the v-erbA and v-erbB oncogenes. Both native bone marrow red cells and HD3 cells, when incubated in vitro under conditions where maturation occurs, show substantial losses of GLUT mRNA and GLUT proteins. To assess whether the inducers of maturation (hemin and butyrate) affect only the normally expressed GLUTs, chicken GLUT3 expressed from a different promoter was introduced into the HD3 cell by retroviral infection. Both the endogenous and exogenous transporters were lost upon cell differentiation and maturation, leaving a cell with low glucose transport activity. Conversely, in growing cells, butyrate had a pronounced effect on the elevation of the GLUT3 mRNA, especially on the exogenous GLUT3 mRNA, and elevated glucose transport prior to differentiation. These results are consistent with the conclusion that chicken red cell development involves a requirement to reduce glucose transport activity. The near absence of glucose transport in the embryonic chicken red cell is thus due to a loss of this transporter during early development which occurs at an earlier developmental stage in the chicken red cell than in the mammalian red cell.

Animals↗
PubMed1998

Tuberculosis infection and anergy in hemodialysis patients.

Patients on hemodialysis are at increased risk for developing active tuberculosis (TB) after primary infection. Although this increased risk is well documented, the prevalence of TB infection, as indicated by a positive tuberculin skin test (TST), is not well described. End-stage renal disease is also known to be a risk factor for skin test anergy, but the rate of anergy in hemodialysis patients is unclear. We sought to identify rates of anergy and TST positivity in patients at four hemodialysis units in St Louis, Missouri, from June 1996 through August 1996. Data obtained from patients and medical records included age, years on hemodialysis, medical history, and basic laboratory data. Patients without a history of TB or a positive TST had a TST with Tubersol, as well as candida and tetanus controls, placed by the Mantoux method. Tests were read 48 hours later. Of the patients enrolled at these units, 307 of 331 (93%) were evaluated. Patients had a mean age of 58 years (range, 19 to 91 years) and had been on hemodialysis for a mean of 3.7 years (range, 1 week to 18.7 years). Blacks made up 81% of the population. A history of a positive TST was obtained from 24 patients (8%), and an additional seven (2%) had a history of active TB. Of the 276 patients tested, 93 did not respond to either control antigen, but five of these patients had a positive TST, leaving 88 (32%) anergic. Anergy was related to age, immunosuppressive drug use, and the reagents used, but not to urea reduction ratio. Positive TSTs were found in 17 of 188 of nonanergic patients (9%) (6% of all tested patients). Overall, 48 of 307 patients (16%) had a positive TST or history of TB. TB or a positive TST was associated with liver disease and peptic ulcer disease, but not socioeconomic status. All 17 newly identified TST-positive patients received chest radiographs. No new cases of active TB were found. Only two of 17 of these patients (12%) were started on isoniazid (INH) prophylaxis. We identified high rates of TST positivity and anergy in the hemodialysis patients tested. Hemodialysis patients should receive regular TST screening, and INH prophylaxis needs to be more strongly encouraged. Studies are ongoing to define the rate of TST conversion over time.

Adult↗
PubMed1998

Primary malignant melanoma of the mucous membranes.

AIMS: To investigate malignant mucosal melanoma (MMM), a rare disease and one which has, till lately, remained unrecognized. Incidence of MMM ranges from 2 to 10% in various series. METHODS: We retrospectively reviewed the cases of malignant melanoma treated at the Regional Cancer Centre, Trivandrum, India, over a period of 15 years. RESULTS: A total of 163 cases of melanoma were identified, of which 21 had a lesion in mucosal sites. There were eight cases of upper aero-digestive tract (UADT) melanoma, seven cases of rectal melanoma, five cases with lesions in the vagina and one case with a lesion in the urethra. The mean age of the patients was 52.8 years; mean age of presentation in urogenital and anorectal lesions was similar to overall mean age, while this was lower (47.5 years) for UADT lesions. Almost half of the patients presented with ulcer or nodule with or without pigmentation. Pain was present in three-quarters and vaginal bleeding was present in all cases of vaginal lesions. Almost one-third of the patients failed locally while another third developed distant metastasis during the follow-up period. A 2-year disease-free survival rate of 13.2% (95% CI: 2.2-34.1) was observed, which dropped to 6.6% (95% CI: 0.4-25.7) after 3 years. Survival appeared a little better in UADT melanoma compared to urogenital and anorectal melanoma; however, the difference was not statistically significant. CONCLUSIONS: Malignant mucosal melanoma seems to have an aggressive biological behaviour with a high incidence of local failure and metastasis.

Adult↗
PubMed1998

Predominance of HLA-restricted cytotoxic T-lymphocyte responses to serotype-cross-reactive epitopes on nonstructural proteins following natural secondary dengue virus infection.

We examined the memory cytotoxic T-lymphocytic (CTL) responses of peripheral blood mononuclear cells (PBMC) obtained from patients in Thailand 12 months after natural symptomatic secondary dengue virus infection. In all four patients analyzed, CTLs were detected in bulk culture PBMC against nonstructural dengue virus proteins. Numerous CD4+ and CD8+ CTL lines were generated from the bulk cultures of two patients, KPP94-037 and KPP94-024, which were specific for NS1.2a (NS1 and NS2a collectively) and NS3 proteins, respectively. All CTL lines derived from both patients were cross-reactive with other serotypes of dengue virus. The CD8+ NS1.2a-specific lines from patient KPP94-037 were HLA B57 restricted, and the CD8+ NS3-specific lines from patient KPP94-024 were HLA B7 restricted. The CD4+ CTL lines from patient KPP94-037 were HLA DR7 restricted. A majority of the CD8+ CTLs isolated from patient KPP94-024 were found to recognize amino acids 221 to 232 on NS3. These results demonstrate that in Thai patients after symptomatic secondary natural dengue infections, CTLs are mainly directed against nonstructural proteins and are broadly cross-reactive.

CD4-Positive T-Lymphocytes↗