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Biomedical subjects

B Nair

Publications and source records attributed to B Nair.

At least 19 recordsLinked to original sources

Expression of epidermal growth factor receptor in gestational trophoblastic diseases.

Gestational trophoblastic disease is an abnormal condition of the placenta, the incidence of which is very high in the State of Kerala, India. The biology of this disease is vague and methods to determine the malignant potential are limited. Placentae of normal (50) and molar pregnancies (95), including 32 showing persistent disease, were used for the study. Epidermal growth factor (EGFR), expression was evaluated by immunohistochemistry using monoclonal antibody, and quantified using the 125I-EGF-binding assay. EGFR was expressed more strongly in molar placentae than in normal placentae of similar gestational age, and was strong in the molar placentae of all gestational ages, whereas expression was mainly restricted to the first and second trimesters in normal placentae. Moles with early presenting symptoms (before 16 weeks) were at a higher risk of developing persistent disease. To conclude, the immunohistochemical study shows high expression of EGFR in early normal placentae and in moles, linking its role to the proliferative and differentiating activity of trophoblasts. Tumours with a histological diagnosis of invasive moles and choriocarcinoma showed very strong binding of EGFR. The present observations also suggest the possibility of mutated EGF receptors being present in persistent trophoblastic disease.

Adult↗

Gender differences and other determinants of the rise in plasma homocysteine after L-methionine loading.

The methionine load test is widely used to identify subjects with mild homocysteinemia. We studied factors influencing the rise in plasma homocysteine (tHcy) levels following oral methionine loading, after taking into account determinants of the basal level. The study population comprised 522 persons (mean age 53, range 17 to 95; 63% male; 60% with coronary disease). tHcy was measured fasting and 4 h after administration of L-methionine (dose 4 g/m2). The percentage rise in tHcy was greater in females, at younger ages, and with lower serum creatinine. Basal tHcy was lower in those with high levels of serum folate, red cell folate and serum B12; they also showed a greater percentage rise with loading. After adjustment for age, creatinine and serum vitamins the percent rise was greater in females (mean 230%, S.D. 92) than in males (mean 172%, S.D. 71, P < 0.0001). About 1/4 of this effect was explained by the methionine dose, but important independent gender effects remained. When the results of the loading test were compared with an overall reference range, females were systematically labelled as 'high' but comparison with age and gender-specific reference ranges normalised the sex distribution. Our data show that a single L-methionine loading protocol for both sexes is not appropriate. Gender-specific reference ranges should be used to define post-load homocysteinemia and previous studies which have identified a high proportion of females with this trait probably reflect the need for gender specific reference ranges.

Adolescent↗

Fasting and post-methionine homocyst(e)ine levels in a healthy Australian population.

BACKGROUND: Plasma homocyst(e)ine (H[e]) is frequently measured in patients with occlusive vascular disease, but levels vary between populations and between laboratories. AIMS: We sought to derive reference values for an Australian population over a wide age range. METHODS: We measured plasma H(e) in the fasting state and after methionine loading in 116 volunteers selected at random from the Hunter districts of the New South Wales electoral roll and in 49 apparently healthy, active subjects recruited from the region's lawn bowling clubs. Reference ranges were derived for both sexes, in three age strata. We collaborated with two international laboratories in standardising our results. RESULTS: Mean fasting H(e) levels were approximately 2.7 mumol/L higher in men than women, at all ages (95% CI for the difference, 1.2 to 4.1 mumol/L). Levels increased with age (approximately 1.0 mumol/L/decade, 95% CI 0.5 to 1.5) and were correlated with serum creatine (r = 0.48), serum folate (r = -0.30), red cell folate (r = -0.25) and serum B12 (r = -0.31) (all p < 0.001). These results are similar to those reported in other populations. CONCLUSIONS: We have defined reference ranges for a typical Australian population, following careful laboratory standardisation. H(e) levels must be interpreted with regard to age, sex, renal function and vitamin B12 and folate status.

Adult↗

Use of patient restraints in four Australian teaching hospitals.

To examine the patterns of use of patient restraints in Australian hospitals and the level of adherence to accepted guidelines, we undertook a point-prevalence study in four teaching hospitals in three different States. This involved ward inspections and review of case notes. Overall, 51 (12.5%) of the 408 people audited were being restrained with a variety of physical and chemical agents. The rate of restraint use varied from 8.5% to 18.5% between hospitals. Although the overall prevalence of restraint use increased with age, the hospital with the oldest patients used restraints least. At all hospitals, there was scant documentation in the case notes concerning the use of restraints. The prevalence of restraint use varies widely in different hospitals. As this is not explained by the patient profile, it probably reflects different philosophies of care. Documentation of the use of restraints needs to be improved in all the centres studied.

Adolescent↗

Cardiovascular findings in self-reported healthy elderly. The Elite Seniors Study.

BACKGROUND: A descriptive study of self-reported healthy elderly in Newcastle was undertaken for an adequate understanding of the normal characteristics of the elderly. AIMS: We sought to determine the frequency of abnormal clinical, laboratory and echocardiographic findings in a self-reported healthy elderly population. METHODS: Volunteers aged greater than 75 years were recruited from active members of the region's bowling clubs. Forty-five subjects with no self-reported vascular or cardiac disease underwent clinical, laboratory and echocardiography assessment. RESULTS: Minor cardiovascular abnormalities were frequently detected. Echocardiography correspondingly found a high frequency of haemodynamically insignificant degenerative valvular lesions. Doppler left ventricular filling pattern of abnormal relaxation was a universal finding. CONCLUSION: There is a high prevalence of age-related echo-Doppler abnormalities in the self-reported healthy elderly with important implications for the interpretation of echo-Doppler studies.

Aged↗

X-ray structure of gelonin at 1.8 A resolution.

Gelonin is a single chain ribosome inactivating protein (RIP) with potential application in the treatment of cancer and AIDS. Diffraction quality crystals grown using PEG3350, belong to the space group P21, with a = 49.4 A, b = 44.9 A, c = 137.4 A and beta = 98.4 degrees, and contain two molecules in the asymmetric unit. Diffraction data collected to 1.8 A resolution has a Rm value of 7.3%. Structure of gelonin has been solved by the molecular replacement method, using ricin A chain as the search model. Crystallographic refinement using X-PLOR resulted in a model for which the r.m.s deviations from ideal bond lengths and bond angles are 0.012 A and 2.7 degrees, respectively. The final R-factor is 18.4% for 39,806 reflections for which I > 1.0 sigma (I). The C alpha atoms of the two molecules in the asymmetric unit superpose to within 0.38 A for 247 atom pairs. The overall fold of gelonin is similar to that of other RIPs such as ricin A chain and alpha-momorcharin, the r.m.s.d. for C alpha superpositions being 1.3 and 1.4 A, respectively. The catalytic residues (Glu166, Arg169 and Tyr113) in the active site form a hydrogen bond scheme similar to that observed in other RIPs. The conformation of Tyr74 in the active site, however, is significantly different from that in alpha-momorcharin. Three well defined water molecules are located in the active site cavity, and one of them, X319, superposes to within 0.2 A of a corresponding water molecule in the structure of alpha-momorcharin. Any of the three could be the substrate water molecule in the hydrolysis reaction catalysed by gelonin. Difference electron density for a N-linked sugar moiety has been observed near only one of the two potential glycosylation sites in the sequence. The amino acid at position 239 has been established as Lys by calculation of omit electron density maps. The two cysteine residues in the sequence, Cys44 and Cys50, form a disulphide bond, and are therefore not available for disulphide conjugation with antibodies. Based on the structure, the region of the molecule that is involved in intradimer interactions is suggested to be suitable for introducing a Cys residue for purposes of conjugation with an antibody to produce useful immunotoxins.

Binding Sites↗

Adult Hodgkin's disease in Kerala.

BACKGROUND: Hodgkin's disease seen in the developing countries differs from that seen in developed countries. There are only a few reports from India regarding the epidemiologic and clinicopathologic features of Hodgkin's disease. METHODS: The records of 159 evaluable patients with Hodgkin's disease seen at the Regional Cancer Centre, Trivandrum, India, during the period 1983-1989 were reviewed for clinicoepidemiologic profile and survival analysis. The Kaplan-Meier product limit method was used to compute survival, and Cox proportional hazard regression analysis was used to study the factors affecting survival. RESULTS: The male-to-female ratio was 3.1:1. The mean age at presentation was 38 years in adults. Supradiaphragmatic presentation (44.7%) was more common, and mixed cellularity (50.3%) was the predominant histologic subtype. There were 9.4% patients with Stage I disease, 37.1% with Stage II, 33.4% with Stage III, and 20.1% with Stage IV disease. Of the patients, 57.9% were treated with chemotherapy, whereas 23.3% had radiation therapy alone, and 18.8% had a combination of radiation therapy and chemotherapy. Complete response was noted in 77.4% (n = 123) of patients, of whom 20.3% (n = 25) later experienced disease relapse. Second remission could be achieved in 8 of 25 patients with disease relapse. The overall 5-year survival rate was 55%. The stage-related survival rates were 89%, 69%, 53%, and 27% in Stage I-IV, respectively. On multivariate regression analysis, patient age and disease stage emerged as significant predictors of survival. CONCLUSION: Mixed cellularity was the most common histologic subtype. The inferior survival rate observed could be attributable to advanced stage of presentation, compromise on the drug and dose, and the lack of proper supportive measures. Patient age and disease stage were the important predictors of survival.

Adolescent↗

A case of dementia.

Recognition of cognitive impairment in the elderly is an important part of medical care. This will lead to the proper diagnosis and optimum treatment. Families seldom realise that the patient has dementia. Even with a high index of suspicion, the diagnosis can often be missed. The correct tool for making the diagnosis is also controversial.

Aged↗