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Biomedical subjects

R Desai

Publications and source records attributed to R Desai.

At least 19 recordsLinked to original sources

Xerophthalmia clinics in rural eye camps.

Even though the primary prevention of many eye diseases can be effectively incorporated into the existing pattern of rural eye camps, efforts in this direction are restrained and insubstantial. We describe our technique and experience in the prevention of xerophthalmia by organising a distinct entity called a xerophthalmia clinic in our eye camps. The clinic consists of an Ophthalmologist or an Ophthalmic assistant who will exclusively examine children who come to the eye camp. This is perhaps, the first report on rural xerophthalmia clinics, in ophthalmic literature. Over a seven year period from 1984 to 1990 we have conducted 71 xerophthalmia clinics amongst the ninty eye camps organised. A total of 11,370 children were examined in the xerophthalmia clinic out of which 18.9% were afflicted with the disease. Therapeutic doses of Vitamin A were administered on the spot to the afflicted and prophylactic doses were administered to the rest. Intensive health education efforts are made through clinics to effectuate change in dietry habits towards consumption of locally grown DGLV (Dark Green Leafy Vegetables) like Anthenum, chenopodium and Amaranthus. A bipronged offensive consisting of mega-dosing and health education is, for the present and the foreseeable future, the best strategy to combat xerophthalmia in this desert region. A year by year breakdown of prevalence rates in the present study shows that in years of severe drought the prevalence of xerophthalmia increases three fold over the non-drought or mild drought years, thereby demonstrating that drought is a substantial risk factor in developing countries leading to vitamin A deficiency and xerophthalmia.

Child

DNA sequence analysis and comparison of the variable heavy and light chain regions of two IgM, monoclonal, anti-myelin associated glycoprotein antibodies.

The complete variable heavy and light chain gene sequences of two monoclonal, IgM, anti-myelin associated glycoprotein (MAG) antibodies associated with peripheral neuropathy, are presented. Comparative analysis of the two VH regions has revealed that they are 88% homologous to one another and are both members of the VH3 gene family. They are also highly homologous to a gene which is frequently utilized in the fetal B-cell repertoire. The V kappa light chain gene of one of the antibodies is 99% homologous to a V kappa II gene and the V lambda light chain gene of the other antibody is only 72% homologous to other known V lambda genes. Further analysis of V genes utilized by anti-MAG antibodies should reveal the structural basis for their binding activity.

Amino Acid Sequence

Aqueous kinetics of sisomicin sulphate.

Sisomicin sulphate is a new-generation aminoglycoside with a broad spectrum of antimicrobial activity that includes Pseudomonas aeruginosa. It is superior to gentamicin against indole-negative Proteus and some resistant strains of Pseudomonas. The ocular pharmacokinetics of sisomicin have not been explored. We used the agar diffusion technique of microbial assay to determine the aqueous penetration and bioavailability of a subconjunctivally placed standard dose of 20 mg/0.4 ml of sisomicin sulphate in 20 human volunteers undergoing elective cataract surgery. A peak concentration of 16.4 mg/l was found in the aqueous humour 78 minutes after injection, which is 65 times the minimum inhibitory concentration for Pseudomonas. The antibiotic was bioavailable up to 1203 minutes after injection in a concentration of 0.9 mg/l, which easily covers the minimum inhibitory concentration of Staphylococcus aureus and Pseudomonas. The antibiotic disappears from the aqueous humour at the 1434 minute interval (approximately 24 hours). The elimination half-life (t1/2 of sisomicin was determined to be 5.16 hours (K = 0.134/hour) and the aqueous clearance was 2.87 microliters/min.

Aqueous Humor

Cloning and sequence analysis of the VH and VL regions of an anti-myelin/DNA antibody from a patient with peripheral neuropathy and chronic lymphocytic leukemia.

We have cloned and determined the nucleotide sequence of the Ig VH and VL region genes of an IgM kappa mAb that binds to denatured DNA and myelin from a patient (POP) with chronic lymphocytic leukemia and peripheral neuropathy. Sequence analysis indicates that the V region of the kappa L chain gene (PopVK) has 99% homology to a V kappa IIIa germ-line gene and the V region of the mu H chain gene (PopVH) has 96% homology to the VH26 germ-line gene that is a member of the VH3 gene family. It is likely the V kappa and VH genes arose from these respective germ-line genes via somatic mutation or from closely related genes. V kappa III genes have frequently been used by other IgMk mAb especially those with rheumatoid factor activity, and the VH26 gene with no somatic mutation has been used by several anti-DNA antibodies, suggesting the possibility of preferential association of these or related germ-line genes with autoantibodies. The minor differences between the sequences of POP's VH and V kappa genes and sequences used by other autoantibodies, may be responsible for this antibody's crossreactivity with myelin and, as a result, the autoimmune neuropathy.

Amino Acid Sequence

Molecular cloning of a human immunoglobulin heavy chain variable (VH) region with anti-myelin-associated glycoprotein activity.

A cDNA clone that encodes the heavy chain variable region (VH) of an IgM M-protein with anti-myelin-associated glycoprotein (MAG) activity secreted by chronic lymphocytic leukemia cells (B-C11) from a patient with peripheral neuropathy was cloned and sequenced. The JH region was identical to the germline JH4 sequence except for deletion of a thymidine residue at the site of D-JH recombination, and the D region showed greatest homology to DM2. Sequence analysis of the VH region revealed greatest homology to VH26, a member of the VH3 gene family, but homology was only 83.7% over 326 bases, suggesting that it was derived from as yet an unidentified member of the VH3 gene family.

Amino Acid Sequence

Angiotensin-converting enzyme inhibitors. 9. Novel [[N-(1-carboxy-3-phenylpropyl)amino]acyl]glycine derivatives with diuretic activity.

A series of molecules 1 having sulfonamide diuretic moieties covalently linked to non-sulfhydryl angiotensin-converting enzyme inhibitors (ACEI) were prepared and tested for both activities. IC50 values for ACEI as low as 7 nM were observed. Discernable diuretic activity was seen for several hydrochlorothiazide-based molecules. Effects of the ACEI and diuretic structures on the respective potencies are discussed.

Angiotensin-Converting Enzyme Inhibitors

Assessment of elastin maturation by radioimmunoassay of desmosine in the developing human lung.

Desmosine has been quantitated in the normally grown fetal and early infant lung by radioimmunoassay. Desmosine could first be detected at 22 weeks gestation: the concentration of desmosine expressed per milligram lung DNA increased in approximately linear form up to about 55 weeks postconceptional age. The concentration in peripheral lung was approximately half that in whole lung homogenates. Lungs of infants dying with acute HMD and lungs of growth retarded infants showed no significant differences from the normals, although there was a tendency for higher desmosine concentrations in prematurely born growth retarded infants.

Amino Acids

The effects of preterm delivery and mechanical ventilation on human lung growth.

The effects of preterm birth and mechanical ventilation on growth of the alveolar region of the lung were assessed by morphometric and/or quantitative biochemical methods in the lungs from 104 perinatal and infant autopsies. The lungs of 4 preterm infants who died at 4-16 weeks age without having received mechanical ventilation were large relative to body weight but showed normal alveolar number and alveolar surface area. Infants treated by mechanical ventilation for hyaline membrane disease (HMD) and who died at ages from 1 week up to 14 months showed impairment in alveolar development evidenced by low alveolar number and a low alveolar surface area. Lung volume and total lung DNA values were relatively normal. Dilated alveolar ducts were a feature at all ages with emphysematous changes apparent in the longest surviving infants. Biochemical features included a high concentration of hydroxyproline, reflecting collagen, and a high desmosine concentration, reflecting elastin, in infants dying at less than 60 weeks postconceptional age. Changes in the lungs of infants ventilated at low pressures for conditions other than HMD were of a similar nature but less severe than those seen in the HMD group. These findings indicate that preterm birth alone may have little adverse influence on lung development but that conditions necessitating mechanical ventilation may lead to permanent impairment in alveolar development. We postulate that the standard technique of applying positive pressure ventilation may itself lead to impaired alveolar growth, although the effect is enhanced by concomitant HMD and BPD.

Apnea

Quantitative aspects of perinatal lung growth.

Weight, DNA, protein, hydroxyproline and disaturated phosphatidylcholine (DSPC) content were investigated in lungs of 97 normally formed infants over an age range from 22 to 75 postconceptional weeks, including 25 cases of hyaline membrane disease (HMD) and 13 small-for-dates infants (SFD). Lung weight and lung DNA relative to body weight were markedly lower in infants who died at 37-41 weeks than in those who died at shorter gestations or in early infancy. Total lung DSPC and DSPC concentration had a narrow peak at 36-41 weeks. The DSPC concentration per milligram of lung DNA in the first few months of infant life was similar to that in infants at 24 weeks gestation. Lung protein concentrations increased steadily but were variable at all ages. SFD infants had significantly higher concentrations of hydroxyproline and showed a peak DSPC concentration at an earlier gestation than the normals. Lungs of HMD infants showed some increase in hydroxyproline concentration but little other quantitative evidence of difference from the normals. We suggest that the relatively small lung size in many infants who die near term may result from recurrent intrauterine stress. Lung changes in small for dates infants are compatible with an advance in lung maturation, while the increased hydroxyproline concentration in the lungs of cases of HMD implies an early proliferative response to lung injury.

DNA

Fetal lung growth in congenital laryngeal atresia.

Morphometric and biochemical indexes of lung growth were measured in 2 cases of uncomplicated laryngeal atresia at 27 and 30 weeks gestation and in 1 case of cryptophthalmos syndrome with anomalies including laryngeal atresia and renal agenesis. Findings were compared with those in normally formed fetuses and newborn infants. The cases of pure laryngeal atresia showed a marked increase in surface area and lung volume for age, associated with an increase in alveolar number and apparent advance in elastin maturation, but little increase in cell population as measured by lung DNA content. Alveolar walls were thin but there was no increase in disaturated phosphatidylcholine (DSPC) content. Similar features were observed in the case of cryptophthalmos in marked contrast to the lung hypoplasia expected to result from renal agenesis. The results give further support to the importance of lung liquid retention for normal fetal lung growth. Overdistention with lung liquid appears to promote alveolar development by redistribution of cells rather than increase in cell population.

Female

Alveolar development in the human fetus and infant.

The lungs from 29 infants aged from 29 weeks of gestation to 18 weeks postnatal age were studied using morphometric analysis; total DNA was estimated in 12 of these. Alveoli could first be counted and measured at 29 weeks gestation; with increasing age they became more mature in appearance as the walls elongated and thinned, and they gradually increased in diameter. Lung volume increased 4-fold between 29 weeks and term, and further doubled in the 4 months after birth. Lung volume, alveolar surface area and DNA all increased linearly with age and weight. Alveolar number showed a curvilinear increase with age and DNA, but a linear relationship to body weight. At birth the lungs had an average of 150 million alveoli, half of the expected adult number. There was a wide normal range. The surface area was between 3 and 5 m2 at birth, one twentieth of the adult value.

Body Weight

Prolactin secretion in Sheehan's syndrome. Responses to thyrotropin-releasing hormone and metoclopramide.

The prolactin response to thyrotropin-releasing hormone (TRH) and metoclopramide was studied in 16 patients with Sheehan's syndrome and 16 matched controls in the follicular phase. Metoclopramide resulted in a greater prolactin response than TRH did in the controls. However, both stimuli failed to evoke any appreciable prolactin response in the patients with Sheehan's syndrome. Since metoclopramide is generally free of side effects and far cheaper than TRH, we recommend the prolactin response to metoclopramide as the preferred screening test in the diagnosis of Sheehan's syndrome.

Adult

Insulin secretion in healthy Indian volunteers.

The insulin response to a 100 g oral glucose load was studied in 20 non-obese, healthy Indian females and 20 matched Indian males. There were no differences between the mean glucose responses of the two groups. However, early-phase (0-60 minutes) insulin release was significantly greater in the females. While there were no significant differences between the two groups when the total areas under the insulin and glucose curves were computed, the female volunteers had a significantly higher mean insulinogenic index. It therefore appears that healthy Indian females have significantly greater early-phase insulin release than their matched male counterparts.

Adult

Intravenous glucose tolerance tests in women with twin pregnancy.

Carbohydrate metabolism was evaluated in 20 twin gestations and 20 singleton pregnancies. The groups were matched for age, parity, weight, height, and gestational age. Intravenous glucose tolerance tests were performed on all women in the third trimester of pregnancy using a glucose load of 0.5 g/kg body weight. Venous plasma glucose and insulin level were measured and statistically compared. The glucose disappearance rates (K) were not different in the two groups. No significant differences in the mean insulin or glucose responses were found between singleton and twin pregnancies. Thus, twin gestations are not at higher metabolic risk of gestational diabetes than are singleton pregnancies.

Adult

Small calvarial bone scan foci--normal variations.

In a series of 3,000 bone scans reviewed retrospectively 21 (0.7%) small calvarial foci were observed. Seventeen of these lesions were found along skull suture lines. No evidence for metastatic disease could be found. Skull radiographs were normal and follow-up bone scans demonstrated no change in the size or location of the lesion. These intense calvarial foci are thought to represent normal variations; among the possibilities are subradiographic cartilaginous rests, sutural foramina, or enlarged Pacchionian granulations.

Diagnosis, Differential