Biomedical subjects
Publications and source records attributed to R Sharma.
We report a rare case of a laryngeal pseudotumour in a child presenting with stridor, which was treated by endoscopic laryngeal resection, without the need for a tracheostomy. A short review of the literature is also presented. Although rare, laryngeal pseudotumour should be considered as part of the differential diagnosis of stridor and upper airway obstruction in children.
BACKGROUND: The insulin-like growth factor (IGF) system is implicated in the pathogenesis of diabetes and cardiovascular disease. OBJECTIVE: We report the effects of total energy intake on the IGF system in two populations with markedly different dietary macronutrient intake and cardiovascular event rate. DESIGN, SUBJECTS AND SETTING: Dietary macronutrient intake was measured in a specific Gujarati migrant community in Sandwell, UK (n=205) compared with people still resident in the same villages of origin in India (n=246). Fasting IGF-I, IGF-binding protein (IGFBP)-1 and IGFBP-3, insulin and glucose (0 and 2-hour) were measured. RESULTS: Total energy and total fat intake were higher in UK migrants, as were IGFBP-3 and IGF-I (mean (95% confidence interval): 145.9 (138.1-153.6) vs. 100.9 (94.6-107.3) ng ml(-1); F=76.6, P<0.001). IGFBP-1 was lower in UK migrants (29.5 (25.9-33.0) vs. 56.5 (50.6-62.5) microg l(-1); F=48.4, P<0.001). At both sites, IGF-I correlated positively with total energy (Spearman's rho=0.45, P<0.001) and total fat (rho=0.44, P<0.001) as did IGFBP-3 with total energy (rho=0.21, P<0.05) and fat (rho=0.26, P<0.001). Conversely, in Indian Gujaratis, IGFBP-1 fell with increasing total energy (rho=-0.27, P<0.001) and fat intake (rho=-0.26, P<0.01) but not in UK Gujaratis. Multiple linear regression modelling showed that increasing quartiles of fat intake were associated with higher IGF-I (beta=0.42, P=0.007) independent of age, body mass index, plasma insulin, fatty acids and 2-hour glucose. CONCLUSION: In these genetically similar groups, migration to the UK and adoption of a different diet is associated with marked changes in the IGF system, suggesting that environmental factors profoundly modulate serum concentrations and actions of IGFs.
OBJECTIVE: To compare the efficacy of 5% NaHCO3, 3% H2O2, Sofradex (dexamethasone sodium metasulphobenzoate 0.05%, framycetin sulphate 0.5%, gramicidin 0.005%), 0.33% acetic acid and 0.9% NaCl eardrops in clearing grommets blocked with harvested thick middle ear effusion fluid. STUDY DESIGN: A blinded in-vitro study. SETTING: District general hospital. PARTICIPANTS: A total of 473 grommets were blocked with freshly harvested unpooled thick middle ear effusion fluid obtained from 68 patients. MAIN OUTCOME MEASURES: Patency of the grommets before and 7 days after intervention was ascertained by tympanometry and close visual inspection. RESULTS: Instillation of eardrops leads to a statistically significant increase in the clearance of grommets as compared with not using any drops (chi2 = 14.3, d.f. = 5, P = 0.006). The numbers needed to treat were 2.8 for NaHCO3, 3.2 for 0.9% NaCl, 3.9 for 0.33% acetic Acid, 4.4 for Sofradex and 9.5 for H2O2 eardrops. Pair-wise comparison was only significant for comparison between 5% NaHCO3 and 3% H2O2 eardrops (Bonferroni corrected P = 0.01, odds ratio = 4.3, CI = 1.9-9.9). CONCLUSIONS: Use of eardrops leads to a clinically and statistically significant increase in the clearance of blocked grommets. Of the five drops used, 5% NaHCO3 was the most efficacious and 3% H2O2 the least efficacious. Limitations of this in-vitro study are recognized and a prospective in-vivo double blind randomized controlled trial is planned.
In this study we describe the development of peptidomimetic analogs of the potent vasoactive intestinal peptide receptor binding inhibitor, Leu(1) -Met(2) -Tyr(3) -Pro(4) -Thr(5) -Tyr(6) -Leu(7) -Lys(8) -OH 1, by incorporating furanoid sugar amino acids (SAAs) 2-4 into the molecule. The furanoid SAAs 2-4 were used as dipeptide isosteres to replace Tyr(3) -Pro(4) or Pro(4) -Thr(5) in sequence 1. The resulting analogs 5-9 were tested for their anti-cancer activities in vitro, following the standard MTT assay on a panel of human cancer cell lines. One of the potent analogs, 6a was tested in vivo for tumor regression on primary colon tumor xenografted nude mice. Our experimental results suggest that many of these analogs show either retention or enhancement of biological activity.
With increasing local regional control and survival rates, the incidence of distant metastasis is increasing. Head and neck malignancies traditionally metastasize to the lung, liver and bone. We present a case of an elderly woman who was loco-regionally controlled after radiotherapy for carcinoma of the tonsil, but later presented with breast metastasis. To our knowledge, this metastatic pattern has never been reported in published literature. We also discuss the management of breast metastasis and the need to avoid unnecessary mastectomies in such patients.
BACKGROUND: Gefitinib is an oral, selective epidermal growth factor receptor (EGFR) inhibitor that has activity in non-small cell lung cancer (NSCLC). AIM: To evaluate the tolerability, safety-profile and response of single agent gefitinib in patients with advanced stage NSCLC. METHODS: Twenty-seven patients of good performance status with stage IIIB or IV NSCLC were entered on the study at the Sydney Cancer Centre. Gefitinib was prescribed at an oral dose of 250 mg daily, as a continuous dose. Radiological evaluation of indicator lesions occurred at baseline and were repeated every 2-3 months until disease progression. Toxicity was graded using standard measures at baseline and at every month. RESULTS: The response rate was 17% in the patients eligible for evaluation. Symptom improvement was observed in 75% of patients. No patients withdrew because of adverse events. Toxicity was observed in 15 patients and consisted mainly of rash (59%), which was usually mild in severity. CONCLUSION: Gefitinib is active in NSCLC. It is well tolerated with minimal side-effects. Symptomatic improvement was found in the majority of patients treated with gefitinib. There may be a role for gefitinib in the palliation of symptoms in patients with advanced NSCLC.
The advantage of helium plasma treatment in enhancing endothelial cell growth and adhesion on polyurethane film coated on glass substrate is demonstrated with experimental data. Human coronary artery endothelial cell (HCAE) growth and attachment was studied on (1) bare glass substrate, used as control, (2) coated glass, with and without helium plasma treatment and (3) collagen-treated polyurethane-coated glass substrates. The untreated polyurethane film surface was rough (RMS = 690 nm) and highly hydrophobic (contact angle theta = 90 degrees). Cell growth on the untreated polyurethane surface was poor (cell concentration approximately 3750/cm2) compared to glass surface (cell concentration approximately 17 665/cm2). The atmospheric helium plasma treatment of the polyurethane film resulted in oxidation of the surface, a slight increase in roughness (RMS = 735 nm) and a significant drop in hydrophobicity (contact angle theta = 79 degrees). The critical surface tension (gamma c) of polyurethane film was also increased by 2 dynes/cm due to helium plasma treatment. These changes resulted in enhanced HCAE cell growth in polyurethane film (cell concentration approximately 16 230/cm2) compared to the untreated polyurethane film. The cell growth was also comparable to cell growth on a glass surface (17 665/cm2) and the collagen-treated polyurethane film surfaces (cell concentration approximately 21 645/cm2), respectively. Moreover, the strength of cell attachment on a plasma-treated surface (cell retention R = 89%) under laminar flow was significantly higher than that on a glass surface (R = 71%). While the collagen-treated polyurethane surface had the highest number of HCAE cells, the cell adhesion was found to be poor (R = 42%) compared to that of a plasma-treated surface. Thus, the overall performance of the plasma-treated polyurethane film surface on endothelial cell growth was better than other substrates studied here.
The chance finding of the vermiform appendix lying within an inguinal hernia occurs in approximately one percent of cases of inguinal hernia, and is known as an Amyand's hernia. We report a rare presentation of Amyand's hernia, where the appendix was found within the left hernial sac during surgery for an obstructed inguinal hernia in a nine-month-old male baby.
The activities of malate-aspartate shuttle enzymes viz., cytosolic and mitochondrial aspartate aminotransferase (c- and m-AsAT) and malate dehydrogenase (c- and m-MDH) were measured in liver and kidney of ad libitum (AL) and dietary-restricted (DR) mice and also on triiodothyronine (T3) treatment. The results show that the activity (U/mg protein) of c-AsAT is increased significantly in liver and the activities of c-MDH and m-AsAT are increased significantly in kidney during DR. On T3 treatment, the activities of both the isoenzymes (c- and m-) of MDH and AsAT are increased significantly in the liver of AL- and DR-fed mice. In the kidney, m-MDH showed no effect by T3 treatment, however, c-MDH increased significantly in both AL- and DR-fed mice. In contrast, m-AsAT is increased significantly in the kidney in AL-fed mice, but was not affected in DR-fed animals. In vitro reconstitution of malate-aspartate shuttle showed a higher activity in the liver and kidney of DR-fed mice, as compared to AL-fed ones and also in the T3-treated mice, compared to untreated ones. These findings suggest that malate-aspartate shuttle enzymes are differentially regulated during DR in mice, in order to adapt to the metabolic need of liver and kidney. T3 potentially regulates the shuttle enzymes, albeit to a varying degree in the liver and kidney of AL- and DR-fed mice.
Recent studies have shown that expanded-simple-tandem-repeat (ESTR) DNA loci are efficient genetic markers for detecting radiation-induced germline mutations in mice. Dose responses following irradiation, however, have only been characterized in a small number of inbred mouse strains, and no studies have applied ESTRs to examine potential modifiers of radiation risk, such as adaptive response. We gamma-irradiated groups of male out-bred Swiss-Webster mice with single acute doses of 0.5 and 1.0 Gy, and compared germline mutation rates at ESTR loci to a sham-irradiated control. To test for evidence of adaptive response we treated a third group with a total dose of 1.1 Gy that was fractionated into a 0.1 Gy adapting dose, followed by a challenge dose of 1.0 Gy 24h later. Paternal mutation rates were significantly elevated above the control in the 0.5 Gy (2.8-fold) and 1.0 Gy (3.0-fold) groups, but were similar to each other despite the difference in radiation dose. The doubling dose for paternal mutation induction was 0.26 Gy (95% CI = 0.14-0.51 Gy). Males adapted with a 0.1 Gy dose prior to a 1.0 Gy challenge dose had mutation rates that were not significantly elevated above the control, and were 43% reduced compared to those receiving single doses. We conclude that pre-meiotic male germ cells in out-bred Swiss-Webster mice are sensitive to ESTR mutations induced by acute doses of ionizing radiation, but mutation induction may become saturated at a lower dose than in some strains of inbred mice. Reduced mutation rates in the adapted group provide intriguing evidence for suppression of ESTR mutations in the male germline through adaptive response. Repetitive DNA markers may be useful tools for exploration of biological factors affecting the probability of heritable mutations caused by low-dose ionizing radiation exposure. The biological significance of ESTR mutations in terms of radiation risk assessment, however, is still undetermined.
Two girls and one boy are described, with severe infantile parkinsonism-dystonia. This syndrome is usually caused by endogenous dopamine deficiency but in these patients was associated with elevated dopamine metabolites in CSF and an unusual eye movement disorder: ocular flutter together with saccade initiation failure. Pyramidal tract signs also emerged in the course of the disease in two patients. This combination of symptoms and biochemical findings suggests a unique pathogenic mechanism.
BACKGROUND: Deficiency of aromatic L-amino acid decarboxylase (AADC) is associated with severe developmental delay, oculogyric crises (OGC), and autonomic dysfunction. Treatment with dopamine agonists and MAO inhibitors is beneficial, yet long-term prognosis is unclear. OBJECTIVE: To delineate the clinical and molecular spectrum of AADC deficiency, its management, and long-term follow-up. RESULTS: The authors present six patients with AADC deficiency and review seven cases from the literature. All patients showed reduced catecholamine metabolites and elevation of 3-O-methyldopa in CSF. Residual plasma AADC activity ranged from undetectable to 8% of normal. Mutational spectrum was heterogeneous. All patients presented with hypotonia, hypokinesia, OGC, and signs of autonomic dysfunction since early life. Diurnal fluctuation or improvement of symptoms after sleep were noted in half of the patients. Treatment response was variable. Two groups of patients were detected: Group I (five males) responded to treatment and made developmental progress. Group II (one male, five females) responded poorly to treatment, and often developed drug-induced dyskinesias. CONCLUSIONS: The molecular and clinical spectrum of AADC deficiency is heterogeneous. Two groups, one with predominant male sex and favorable response to treatment, and the other with predominant female sex and poor response to treatment, can be discerned.
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A new sandwich dot-enzyme linked immunosorbent assay (sdot-ELISA) was developed using omniserum prepared against different strains of Streptococcus pneumoniae as capture antibody and also as second or revealing antibody after its conjugation with horseradish peroxidase (HRP) for detection of pneumococcal antigen in cerebrospinal fluid (CSF). A total of 103 CSF samples of different categories were screened with newly developed dot-ELISA and results were compared with commercially available latex agglutination (LA) kit. The newly developed sdot-ELISA was more sensitive than LA test and can be used as an alternative diagnostic tool in laboratory and in field conditions. An added advantage of this ELISA system was that it did not require antibodies produced in two different animal species.
OBJECTIVE: The objectives were to study the relationships of insulin resistance with generalized and abdominal obesity, and body fat patterning in urban postpubertal Asian Indian children. DESIGN: Cross-sectional, population-based epidemiological study. SUBJECTS: In all, 250 (155 males and 95 females) healthy urban postpubertal children. MEASUREMENTS: Anthropometric profile, percentage of body fat (%BF), fasting serum insulin, and lipoprotein profile. RESULTS: Fasting insulin correlated significantly with body mass index (BMI), %BF, waist circumference (WC), central and peripheral skinfold thicknesses and sum of four skinfold thicknesses (Sigma 4SF) in both sexes, and with systolic blood pressure and waist-to hip circumference ratio (W-HR) in males only. Consistent increase in fasting insulin was noted with increasing values of central skinfold thickness at each tertile of peripheral skinfold thickness, WC, and %BF. Central skinfold thickness correlated with fasting insulin even after adjusting for WC, W-HR, and %BF. The odds ratios (OR) (95% CI) of hyperinsulinemia (fasting insulin concentrations in the highest quartile) were 4.7 (2.4-9.4) in overweight subjects, 8 (4.1-15.5) with high %BF, 6.4 (3.2-12.9) with high WC, 3.7 (1.9-7.3) with high W-HR, 6.8 (3.3-13.9) with high triceps skinfold thickness, 8 (4.1-15.7) with high subscapular skinfold thickness, and 10.1 (5-20.5) with high Sigma 4SF. In step-wise multiple logistic regression analysis, %BF [OR (95% CI): 3.2 (1.4-7.8)] and Sigma 4SF [OR (95% CI): 4.5 (1.8-11.3)] were independent predictors of hyperinsulinemia, similar to insulin resistance assessed by HOMA (homeostatic model of assessment) in the study. CONCLUSION: A high prevalence of insulin resistance in postpubertal urban Asian Indian children was associated with excess body fat, abdominal adiposity, and excess truncal subcutaneous fat. Primary prevention strategies for coronary heart disease and diabetes mellitus in Asian Indians should focus on the abnormal body composition profile in childhood.
UNLABELLED: Oral feeding of male rats with plumieride (15 mg/rat/day) for the period of 60 days did not cause any significant change in the body weight of treated rats. However, the weights of testes, epididymides, seminal vesicle and ventral prostate were significantly reduced when compared to control values. The production of step-19 spermatids was reduced by 87.26% in plumieride treated rats. The population of preleptotene and pachytene spermatocytes were decreased by 64.26% and 55.13% respectively. Spermatogonia and sertoli cell population was also affected. Plumieride treatment resulted in an arrest of spermatogenesis without any systemic side effect. Sperm motility as well as sperm density was reduced significantly. The number of mature Leydig cells was decreased and complete suppression of fertility was observed. A significant fall in the protein and sialic acid contents of the testes, epididymides, seminal vesicle and ventral prostate as well as glycogen content of testes was also noticed. Fructose in seminal vesicle was lowered whereas testicular cholesterol was elevated. There was no significant change in RBC and WBC count, haemoglobin, haematocrit and sugar in the whole blood and total protein, cholesterol, phospholipid and triglycerides in the serum. CONCLUSION: Plumieride administration arrests spermatogenesis in male rats without noticeable side effects. For the clinical use more experiments should be carried out in a phased programme.
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