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Biomedical subjects

M P Desai

Publications and source records attributed to M P Desai.

At least 19 recordsLinked to original sources

Hyperthyroidism in children.

This study was done to characterize the clinical features, laboratory parameters and response to therapy and outcome of childhood hyperthyroidism. The evaluation included history, examination, laboratory investigations: serum T3, T4, TSH, free T3, free T4 by RIA or immunochemiluminescence (IC), antithyroid antibodies by standard techniques, bone age (BA) by Greulich and Pyle's method, clinical and laboratory response to treatment, and follow-up of 15 children with hyperthyroidism seen in past eight years. Age of onset, presentation, nature and duration of symptoms, family history, anthropometry and signs of hyperthyroidism were recorded. There were 10 girls and 5 boys (2:1). Three families had a history of thyroid disorders. Mean ages of onset and presentation were 8.25 +/- 3.4 and 9.27 +/- 3.2 years respectively. Clinical features included weight loss, heat intolerance and sweating, diarrhoea, behavioral problems, ophthalmopathy and tachycardia. BA was advanced. Serum T3 (mean = 4.29 +/- 1.77 ng/mL), T4 (18.75 +/- 5.64 micrograms/dL), FT3 (7.11 +/- 4.58 pg/mL) and FT4 (2.93 +/- 0.29 ng/mL) were markedly elevated. TSH was suppressed. Anti-microsomal antibodies (AMA) and anti-thyroglobulin antibodies (ATG) were positive in five. They were started on standard treatment with carbimazole 0.5-0.7 mg kg-1. Clinical and biochemical euthyroidism was achieved within 2.5 to 6 months in all, after which the drug was tapered, however, they required treatment for 2 years to 7.5 years. Four children were retreated for relapse and are now euthyroid and off treatment. Childhood hyperthyroidism requires long term treatment and careful monitoring. This study shows a remission rate of 67%.

Adolescent↗

Autoimmune thyroid disease in childhood: a study of children and their families.

OBJECTIVE: To study the clinical and laboratory profile of children with autoimmune thyroid disease (AITD) and its familial prevalence. DESIGN: Clinical and investigative evaluation of 96 children and adolescents 5 to 16 years old suspected of having AITD based on clinical and family data and similar assessment of parents and siblings of 30 confirmed cases of AITD. SETTING AND SUBJECTS: Of these 96 cases, 66 were from a private clinic and 30 were institution based thyroid antibody positive with confirmed AITD. On initial testing 36 (55%) of 66 clinic cases were thyroid antibodies (ab) positive and 30 were (ab) negative. In 12 of 30 ab -ve cases retesting for antibodies by newer technique or FNAC confirmed AITD. Clinical and laboratory evaluation of 90 of a total of 106 parents and siblings of the 30 institution based cases. METHODS: Clinical evaluation with goiter grading by WHO criteria was done in all. Family history of thyroid disease was inquired for in all. Clinical examination and thyroid antibody status was assessed in 90 family members as stated above. Thyroid antimicrosomal (AMA) and antithyroglobulin (ATG) antibodies were tested by standard hemogglutination kits. Titers of > 1:100 considered +ve for children and >1:400 for adults. Thyroid (ab) could be tested in ten of the ab-ve cases by ECI technique on follow up. Bone age was assessed. Ultrasonographic or TCM 99 scanning of thyroid gland and FNAC were done as indicated. RESULTS: Of the 96 children suspected to have AITD, thyroid antibodies were positive in high titers in 66 (36+30) cases (69%) on initial testing but with more sensitive ECI technique significant antibody titres were detected in 10 more cases (79%) and FNAC confirmed AITD in 2 more subjects (total 78 - initial 66 + 12). F:M ratio was 2.9:1. Sixty one per cent of children were between 6 to 12 years of age; mean age 10.12+/-2.9 years. Seventy seven per cent had hypothyroidism, 10% had thyrotoxicosis and only 13% were euthyroid. Family history of thyroid disease was elicited in 33% of the series. Survey of 90 parents and siblings of the institution based group revealed, euthyroid goiters in 17%, subclinical hypothyroidism in 10% and significant AMA titers in 43% (65% of mothers, 30% siblings and 43% fathers). CONCLUSION: Juvenile AITD is a common cause of acquired thyroid disease in children above 5 years of age with a 3-fold higher prevalence in girls. The manifestations are heterogeneous. Hypothyroidism was most common (77%), euthyroid goiters (13%) and thyrotoxicosis (10%) were less frequent. Familial aggregation was noted in adult family members (33%) with positive thyroid antibodies in 65% of mothers. Sibling affection was less frequent. The familial and genetic implications of AITD are important; diagnosis of AITD in children may also help detect subclinical disease in adult family members.

Adult↗

Persistent hyperinsulinemic hypoglycemia of infancy.

OBJECTIVE: To study the nature and clinical course of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) due to nesidioblastosis. DESIGN: Clinical, laboratory and therapeutic evaluation of infants with this disorder and study the outcome. SETTING: Hospital born neonates and infants referred from other hospitals. SUBJECTS: Thirteen infants from 9 families inclusive of four pairs of siblings referred within few hours of birth to 3 months of age, for seizures. Mean birth weight was 3.68 +/- 0.45 kg. Consanguinity documented in one sporadic and one familial case. METHODS: Clinical and laboratory evaluation by standard biochemical and radioimmunoassay techniques. RESULTS: The mean serum insulin level of 24.2 +/- 12.5 mIU/ml was in the normal range but inappropriately high for the corresponding hypoglycemic blood sugar (23.1 +/- 9.1 mg/dl) value, with an I/G ratio of 1.36 +/- 0.97; as in hyperinsulinemia (normal < 0.4). Investigations excluded other causes of persistent hypoglycemia. A trial of i.v./oral glucose, frequent carbohydrate rich feeds in all, oral diazoxide (10 to 20 mg/kg) in 9/13 cases along with subcutaneous octreotide (20 micrograms/kg QID) in one helped, but pancreatic resection (85 to 90%) was opted for in two (1 familial, 1 sporadic). Six infants including one with pancreatic resection succumbed to hypoglycemia (n = 1) or fulminating infection (n = 3) or brain damage. Of the seven survivors, one familial case with pancreatic resection is brain damaged, and of the six on diazoxide therapy, one is slightly subnormal while one sporadic and three familial cases have done well. One infant was lost to follow up. Diazoxide could be withdrawn in two subjects (1 familial, 1 sporadic) by 8 years of age signifying maturation of islet cell function. CONCLUSION: PHHI appropriately known as 'Islet cell dysmaturation syndrome' is a complex disorder posing problems in diagnosis and therapy. The high familial incidence (77%), with intrafamilial variation in the severity, insulin levels in the normal range but in appropriately high for the blood glucose levels, normal C-peptide levels, with normal I/G ratio (< 0.4) in 4/13 are some of the notable features of this study. Severe recurrent infections in nearly 30%, is an unusual feature in this series and needs an indepth study. The mortality (46%) and morbidity (43%) in survivors is high and calls for greater awareness, early diagnosis and genetic counselling, as this disorder may be familial.

Birth Weight↗

The mechanism of uptake of biodegradable microparticles in Caco-2 cells is size dependent.

PURPOSE: To study the uptake of biodegradable microparticles in Caco-2 cells. METHODS: Biodegradable microparticles of polylactic polyglycolic acid co-polymer (PLGA 50:50) of mean diameters 0.1 micron, 1 micron, and 10 microns containing bovine serum albumin as a model protein and 6-coumarin as a fluorescent marker were formulated by a multiple emulsion technique. The Caco-2 cell monolayers were incubated with each diameter microparticles (100 micrograms/ml) for two hours. The microparticle uptake in Caco-2 cells was studied by confocal microscopy and also by quantitating the 6-coumarin content of the microparticles taken up by the cells. The effects of microparticle concentration, and incubation time and temperature on microparticle cell uptake were also studied. RESULTS: The study demonstrated that the Caco-2 cell microparticle uptake significantly depends upon the microparticle diameter. The 0.1 micron diameter microparticles had 2.5 fold greater uptake on the weight basis than the 1 micron and 6 fold greater than the 10 microns diameter microparticles. Similarly in terms of number the uptake of 0.1 micron diameter microparticles was 2.7 x 10(3) fold greater than the 1 micron and 6.7 x 10(6) greater than the 10 microns diameter microparticles. The efficiency of uptake of 0.1 micron diameter microparticles at 100 micrograms/ml concentration was 41% compared to 15% and 6% for the 1 micron and the 10 microns diameter microparticles, respectively. The Caco-2 cell microparticle (0.1 micron) uptake increased with concentration in the range of 100 micrograms/ml to 500 micrograms/ml which then reached a plateau at higher concentration. The uptake of microparticles increased with incubation time, reaching a steady state at two hours. The uptake was greater at an incubation temperature of 37 degrees C compared to at 4 degrees C. CONCLUSIONS: The Caco-2 cell microparticle uptake was microparticle diameter, concentration, and incubation time and temperature dependent. The small diameter microparticles (0.1 micron) had significantly greater uptake compared to larger diameter microparticles. The results thus suggest that the mechanism of uptake of microparticles in Caco-2 cell is particle diameter dependent. Caco-2 cells are used as an in vitro model for gastrointestinal uptake, and therefore the results obtained in these studies could be of significant importance in optimizing the microparticle-based oral drug delivery systems.

Animals↗

A clinicopathologic profile of adrenocortical tumors.

OBJECTIVE: To study the clinical, biochemical, hormonal, radiological and histopathological profile of adrenocortical tumors in children; to assess the clinicopathological correlations and note the future outcome. DESIGN: Retrospective and prospective study. SETTING: Hospital based; Endocrine Service of our institution and other institution based services. SUBJECTS: 14 children (Females = 11, Males = 3) with adrenocortical tumor, aged 8 months to 13 years (mean age 5.1 +/- 3.42 years), seen over a period of 9 years. RESULTS: Females predominated (F:M = 3.7:1). Majority (64%) had a mixed picture with cushingoid features and virilization, whereas 36% presented only for virilization. Elevated serum cortisol levels with loss of diurnal variation was noted only in those with mixed clinical presentation. Adrenal androgen elevation was noted in majority of cases as virilization was common to all. CT confirmed the diagnosis of tumor, 7 on either side. Thirteen cases were operated. Histopathologic diagnosis was carcinoma in 7 and adenoma in 6 cases. Three of the seven with carcinoma died within 3 months to 2 years but two of these with small tumours (weight 60-65 g and diameter < 6 cm) were well at 2 and 5 years, while as one of the six with a large adenoma had recurrence and metastasis after three years. CONCLUSION: Female preponderance was marked (4 times), 43% of tumors had occurred by 3 years of age and 64% by 6 years. Neither the hormonal parameters nor the histopathology correlated well with the biological behavior and outcome. Prolonged and vigilant follow up is essential.

Adolescent↗

Paraferritin: a protein complex with ferrireductase activity is associated with iron absorption in rats.

Recent studies reported that iron salts were absorbed in the duodenum utilizing a pathway involving membrane-associated integrin and a cytosolic protein named mobilferrin. In addition, a large molecular weight cytoplasmic complex was labeled with radioiron during mucosal uptake of iron in the duodenum. The molecular mass of this protein was 520 000 daltons, slightly larger than ferritin. On denaturing SDS-PAGE, the purified protein complex appeared to consist of at least four polypeptides, closely associated with each other. This complex was called paraferritin because its hydrodynamic volume resembled ferritin. In the present work, antibody studies demonstrate the presence of integrin, mobilferrin, and flavin monooxygenase in the water-soluble complex. Biochemical studies demonstrate the presence of a NADPH-dependent flavin monooxygenase ferrireductase activity that reduces Fe(III) to Fe(II). Antibodies against either integrin or mobilferrin inhibit monooxygenase activity. Inhibition of monooxygenase activity decreases radioiron uptake by tissue culture intestinal cells. Thus, we postulated that paraferritin plays a role in the mucosal uptake and transport of inorganic iron in small intestinal absorptive cells and is a mechanism for both the internalization of integrin from membranes to cellular cytosol and the delivery of iron to cellular constituents in an appropriate redox state.

Animals↗

Pituitary enlargement on magnetic resonance imaging in congenital hypothyroidism.

OBJECTIVE: To assess pretreatment and posttreatment pituitary gland size by magnetic resonance imaging in children with subtle or overt signs of long-standing hypothyroidism. DESIGN: Etiologic diagnosis of hypothyroidism was confirmed by thyrotropin, triiodothyronine, and thyroxine assays; thyroid antibody tests; and radionuclide thyroid scan. Repeated magnetic resonance imaging was obtained after 6 to 12 months of therapy with levothyroxine sodium to restore a euthyroid state. SETTING: Endocrine service at a hospital for children in Bombay, India. PATIENTS: Ten children whose mean (+/-SD) chronologic age, bone age, and duration of symptoms were 11.39 +/- 1.81, 3.78 +/- 2.05, and 6.95 +/- 2.91 years, respectively. One patient was seen for acute neurologic symptoms suggesting a suprasellar lesion. RESULTS: Magnetic resonance imaging showed homogeneous diffuse enlargement of the pituitary gland in all patients. The superior margin of the gland was flat in five patients and convex in the rest, with suprasellar extension and partial or complete obliteration of the infundibulum in three and mild compression of optic chiasma in two, thus mimicking a sellar or suprasellar tumor. Pretreatment pituitary mean (+/-SD) vertical height in the coronal plane was 10.02 +/- 2.24 mm, with a posttreatment regression to 4.93 +/- 1.11 mm (P < .001, Student's t test) and restoration of clinical and hormonal euthyroid status. CONCLUSION: Awareness of pituitary enlargement and the rare occurrence of neurologic symptoms and chiasmal syndrome are important in children with longstanding congenital hypothyroidism.

Adolescent↗

Gastrointestinal uptake of biodegradable microparticles: effect of particle size.

PURPOSE: To investigate the effect of microparticle size on gastrointestinal tissue uptake. METHODS: Biodegradable microparticles of various sizes using polylactic polyglycolic acid (50:50) co-polymer (100 nm, 500 nm, 1 micron, and 10 microns) and bovine serum albumin as a model protein were formulated by water-in-oil-in-water emulsion solvent evaporation technique. The uptake of microparticles was studied in rat in situ intestinal loop model and quantitatively analyzed for efficiency of uptake. RESULTS: In general, the efficiency of uptake of 100 nm size particles by the intestinal tissue was 15-250 fold higher compared to larger size microparticles. The efficiency of uptake was dependent on the type of tissue, such as Peyer's patch and non patch as well as on the location of the tissue collected i.e. duodenum or ileum. Depending on the size of microparticles, the Peyer's patch tissue had 2-200 fold higher uptake of particles than the non-patch tissue collected from the same region of the intestine. Histological evaluation of the tissue sections demonstrated that 100 nm particles were diffused throughout the submucosal layers while the larger size nano/microparticles were predominantly localized in the epithelial lining of the tissue. CONCLUSIONS: There is a microparticle size dependent exclusion phenomena in the gastrointestinal mucosal tissue with 100 nm size particles showing significantly greater tissue uptake. This has important implications in designing of nanoparticle-based oral drug delivery systems, such as an oral vaccine system.

Animals↗

A multicentric evaluation study of an indigenously prepared cost effective prototype pregnancy test.

A multicentric evaluation of an indigenously developed pregnancy detection kit (named Preglisa) based on urinary human chorionic gonadotropin (hCG) detection was carried out at 12 centres where the outcome of the kit was compared with the existing parameter (e.g., ultrasonography, clinical judgement, serum beta hCG levels) used by the centre for confirmation of the pregnancy. The specificity, sensitivity and accuracy of the kit were 98.05, 98.7 and 98.69 per cent (n = 382) when results of Preglisa were compared with those of non-immunological tests. When compared with commercially available kits, sensitivity was 97.9 per cent, specificity was 97.2 per cent and accuracy was 97.94 per cent (n = 155). The kit is cost effective with a sensitivity of 300 mlU/ml and is recommended for detecting pregnancy 35 days after the last menstrual period thus fulfilling the general requirement in the Indian situation.

Adult↗

Excretory profile of inhibin-like peptide (ILP) during human menstrual cycle: a probable marker for determination of fertile period.

The excretory profile of inhibin-like peptide (10.4 kDa) and its interrelationship with urinary LH, FSH, oestrone glucuronide (E1G) and pregnanediol glucuronide (PdG) during the menstrual cycle were studied. These hormones/metabolites were estimated in daily early morning urine samples obtained from 20 regularly menstruating women. The data revealed that the excretory profile of inhibin-like peptide (ILP) follows a pattern similar to that of E1G. In 17 cycles, ILP peaked 3-4 days prior to the urinary LH peak. A value of 70 ng/mg creatinine (95th centile of ILP levels obtained between 2 and 4 days prior to urinary LH peak and also 5th centile of peak ILP levels) was considered as an indicator of the start of the fertile period. A value of PdG more than 2 micrograms/mg creatinine on two consecutive days was considered as an end of the fertile period. The entire fertile period could be determined in 18 out 20 cycles when criteria based on ILP and PdG levels were applied (accuracy, 90%), whereas it could be determined in 13 out of 20 cycles when criteria based on E1G and PdG levels were applied (accuracy, 65%). Thus, ILP levels in urine may prove to be one of the signals for determining the start of fertile period.

Adult↗

Trace decomposition of selegiline. Use of worst-case kinetics for a stable drug.

A solution of selegiline hydrochloride reference standard, which contained no detectable impurities at the time of its preparation, was found by HPLC to contain a trace of a compound at the locus of methamphetamine when analyzed after 1 year. Heating selegiline solutions at pH 7 and 105 degrees C produced methamphetamine as the major product at a rate which closely followed the first-order rate equation. Using only these data and worst-case assumptions, rate constants were estimated at various temperatures; the activation energy was estimated to be about 25 kcal, and the stability-indicating validity of the assay used was reaffirmed. Selegiline undergoes degradation at a negligibly slow rate.

Chromatography, Gas↗

A sensitive ELISA for 6 beta-hydroxycortisol in urine using enzyme penicillinase (beta-lactamase).

A sensitive and specific, enzyme labelled immunosorbent assay (ELISA) for 6 beta-hydroxycortisol in diluted urine using penicillinase was developed. 6 beta-Hydroxycortisol-21-hemisuccinate was conjugated with enzyme penicillinase. Antibody immobilized on a polyvinylchloride ELISA plate (Dynatech) was used for separation of bound from free ligand. The sensitivity of the assay was between 2.0-3.0 pg per well and recovery of 6 beta-hydroxycortisol from urine ranged between 85.0-108.0%. The assay is simple, rapid and precise.

Enzyme-Linked Immunosorbent Assay↗

Neonatal screening for congenital hypothyroidism using the filter paper thyroxine technique.

A total of 25,244 full term consecutive newborns were screened for hypothyroidism at 24 to 96 h of birth using the filter paper technique for thyroxine. The screening protocol based on our pilot study considered filter paper thyroxine (FP-T4) values of 51 to 80 ng/ml (-1 SD) as borderline and < 50 ng/ml (-2 SD) as high risk for congenital hypothyroidism. FP-T4 and/or serum T4 and TSH were reestimated in all neonates with FP-T4 < 80 ng/ml. A total of 4775 (18.9%) newborns (FP-T4, 51 to 80 ng/ml in 4435 and < 50 ng/ml in 340) needed the recall; 2237 (50.4%) with FP-T4 51 to 80 ng/ml recalled by letters and 283 (83.3%) of the 340 subjects with FP-T4 < 50 ng/ml recalled by home visit, responded by 6 wk of age. Congenital hypothyroidism was confirmed in 6 newborns. FP-T4 in one persisted at 55 ng/ml on follow up and in the remainder both initial and repeat values were < 50 ng/ml. Follow up serum T4 values were subnormal (7.8-50.2 ng/ml) and serum TSH elevated (80-1233 IU/ml). Technetium thyroid scan showed agenesis in 3, ectopia in 2 and normal gland with probable dyshormonogenesis in one. Three other newborns (FP-T4 93 to 143 ng/ml) escaped primary detection and were referred later for congenital hypothyroidism. The incidence of congenital hypothyroidism by primary screening was 1:4207 (6 of 25,244) but with these 3 missed cases, probably 1:2804. Congenital hypothyroidism was reconfirmed in all 9 infants between the ages of 2 1/2 to 4 yr.(ABSTRACT TRUNCATED AT 250 WORDS)

Congenital Hypothyroidism↗

Stability studies of the components of a prototype penicillinase (beta-lactamase)-linked ELISA kit.

Penicillinase (beta-lactamase) enzyme-linked immunosorbent assay (ELISA) for various reproductive hormones developed in the laboratory were found to have wide applicability in the fertility check clinic of the Institute. A need was thought to transform these assays into ready-to-use kit forms. Therefore, prototype ELISA kits for these hormones were developed and stability of the individual component was ascertained at various temperatures (room temperature, 37 degrees C and 2-8 degrees C). Stability studies were conducted on previously validated assay for pregnanediol-3 alpha-glucuronide (PdG). The studies showed that immunosorbents (antibody coated plates) are stable at room temperature for a period of 2 weeks, at 37 degrees C for 1 week and at 2-8 degrees C for a period of 9 months when preserved after treatment with glycerol solution. The lyophilised conjugate, standard and immunoassay buffer, colour reagent, and its substrate were stable at 37 degrees C up to 1 week and at room temperature up to 2 weeks and at 2-8 degrees C for a period of 6 months, during which the stability was studied.

Enzyme Stability↗

An indirect ELISA for urinary gonadotropins using immobilized human menopausal gonadotropin.

An indirect ELISA for the estimation of urinary gonadotropins is described. Human menopausal gonadotropin is adsorbed on a microtitre plate, where it serves as an immunosorbent. The residual antigonadotropin antibody is captured by the immunosorbent after reaction with the sample or standard and detected with enzyme-labelled antispecies antibody (antirabbit gamma-globulin-horse radish peroxidase). The assay developed here is rapid and satisfies usual validatory criteria expected from an immunoassay. Moreover, it obviates the need for extraction of samples with acetone, as shown by the close agreement between the respective lutropin or follitropin concentrations in extracted and unextracted urine samples.

Animals↗