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Biomedical subjects

A Sharma

Publications and source records attributed to A Sharma.

At least 343 records · Page 19Linked to original sources

Modeling of jaw biomechanics in the reconstructed mandibulectomy patient.

STATEMENT OF PROBLEM: Biomechanics of occlusal force and indirect calculation of temporomandibular joint loading in patients after surgery for head and neck cancer is poorly understood. PURPOSE: This study compared occlusal force values of 6 mandibulectomy subjects with reconstructed mandibles to 6 noncancer subjects with intact mandibles and reports occlusal force predictions from a developed computer model simulation of both a mandibulectomy subject with a reconstructed mandible and noncancer subject with an intact mandible. MATERIAL AND METHODS: Maximum occlusal force was recorded at the first molar and incisal edge in 6 mandibulectomy subjects who had bony reconstruction of the mandible and 6 noncancer subjects with an intact mandible. Clinical data were then qualitatively compared with occlusal force values generated from an existing computer model simulating an average adult, and a developed model simulating an average mandibulectomy subject who had bony reconstruction of the mandible. The biomechanical parameters modeled also included an estimation of joint force magnitude and direction when biting with maximal force on the first molar. RESULTS: Clinical data revealed no significant differences in occlusal force between the 6 mandibulectomy subjects with bony reconstruction of the mandible and 6 noncancer subjects with an intact mandible; however, average molar and incisal occlusal force values were 22% and 32% less in mandibulectomy subjects with bony reconstruction. Computer simulations of a reconstructed mandibulectomy subject predicted that reconstructed subjects would have 45% less molar occlusal force, 50% less incisal occlusal force, and a higher joint/tooth force ratio compared with a simulated noncancer patient with an intact mandible. CONCLUSIONS: There were no significant differences in first molar or incisal occlusal force between reconstructed mandibulectomy subjects and noncancer subjects with intact mandibles. Trends calculated from computer simulations were consistent with clinical findings.

Adult↗

Rapid cycling affective disorder: a descriptive study from North India.

A series of 33 (4.29%) cases of rapid cycling affective disorder (RCAD ICD-10-DCR) out of a pool of 770 consecutive cases of ICD-10 affective disorder (AD) was collected over a period of 5 years. All cases of RCAD belonged to bipolar affective disorder. RCAD when compared with non-rapid cycling bipolar affective disorder (BPAD) revealed a significantly longer mean duration of illness, greater number of total episodes, greater number of hospitalizations and stronger family loading of bipolar affective disorder. These findings implicate RCAD as a severe form of bipolar affective disorder.

Adult↗

Systematic screening of chromosome 18 for loss of heterozygosity in esophageal squamous cell carcinoma.

Esophageal cancer ranks among the 10 most common cancers in the world, and is almost uniformly fatal. The genetic events leading to the development of esophageal carcinoma are not well established. To identify genomic regions involved in esophageal carcinogenesis, we performed a systematic screening for loss of heterozygosity (LOH) in 24 samples of squamous cell carcinomas, initially focusing the analysis on chromosome 18. Thirteen short tandem repeat markers spanning 18p and 18q were used. We found a broad peak of LOH spanning 18p11.2 and 18q21.1 with the most frequent LOH (72%) at D18S978 on 18q12.2, which coincides with a known fragile site FRA18A. This region is 4 cM proximal to known tumor suppressor genes and therefore suggests the possible existence of a yet undiscovered tumor suppressor gene.

Alleles↗

Placement of endosseous implants in children and adolescents with hereditary ectodermal dysplasia.

OBJECTIVE: The purposes of this investigation were to study the feasibility of placing endosseous implants in children and adolescents with ectodermal dysplasia and to assess the position and stability of such implants during growth. This article reports on 6 subjects with long-term follow-up. Study design. A prospective study was commenced in 1991. Patients with hereditary ectodermal dysplasia who were over the age of 5 years and who presented to the University of California San Francisco Ectodermal Dysplasia Clinic for dental treatment were included and maintained in the study. In each case, clinical and radiographic records were obtained before treatment, immediately after implant placement, at delivery of the prosthesis, and subsequently at yearly intervals. Six subjects are reported, 4 as members of the prospective study group and 2 who had been treated before the study began. RESULTS: A total of 41 implants (19 maxillary, 22 mandibular) were placed. The average follow-up after implant placement was 7.8 years (range, 6-11 years), and the average time since restoration was 6 years (range, 5-10 years). Forty implants successfully integrated and have been restored. There was no evidence that implant placement or prosthetic rehabilitation resulted in restriction of transverse or sagittal growth. One mandibular implant, placed in a partially dentate 5-year-old, became submerged because of adjacent alveolar development and required placement of a longer abutment. Four maxillary implants placed in a partially dentate 7-year-old also became submerged and required prosthetic revision and the placement of longer abutments. CONCLUSIONS: This preliminary report suggests that endosseous implants can be successfully placed and can provide support for prosthetic restoration in patients with hereditary ectodermal dysplasia. However, vertical dentoalveolar growth results in submergence of the implant relative to the adjacent natural dentition when implants are placed adjacent to erupting permanent teeth.

Adolescent↗

A novel fed-batch digestion system for biomethanation of plant biomasses.

Plant biomasses, which in the absence of adequate pretreatment pose serious operational problems in biogas production using conventional domestic flow-through digesters, can be successfully digested in a novel fedbatch digestion system that produces a steady rate of biogas. Basically, the system is a batch digestion operated with a regular input of a calculated amount of feed based on first order decay kinetics in order to maintain a regular biogas production rate. For nearly three years the system was tested in a laboratory-scale fed-batch digester (10 l) using dried water hyacinth as feed providing the desired biogas production rate. A field-scale domestic digester of masonry construction with a working volume of 10 m3 was designed and tested for about 9 months by feeding a mixture of dried water hyacinth or banana stem along with sugarcane press mud, yielding an average biogas production of 90-100% of the expected rate calculated on the basis of the feed rate.

Journal Article↗

Anti-angiogenic activity of selected receptor tyrosine kinase inhibitors, PD166285 and PD173074: implications for combination treatment with photodynamic therapy.

Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR1TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR-beta-, EGFR-, and FGFR1TKs and c-src TK by 50% (IC50) at concentrations between 7-85 nM. PD173074 displayed selective inhibitory activity towards FGFR1TK at 26 nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10 nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1-25 mg/kg) or PD173074 (25-100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5-10 mg/kg) or PD173074 (30-60 mg/kg) following PDT compared with PDT alone (p<0.001). Many long-term survivors were also noted in combination treatment groups. PD166285 and PD173074 displayed potent anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response to PDT. Interference in membrane signal transduction by inhibitors of specific RTKs (e.g. FGFR1TK) should result in new chemotherapeutic agents having the ability to limit tumor angiogenesis and regrowth following cytoreductive treatments such as PDT.

Angiogenesis Inhibitors↗

Comparison of clastogenic effects of inorganic selenium salts in mice in vivo as related to concentrations and duration of exposure.

Inorganic selenium compounds in the diet have been known to protect against cancer in laboratory animals, but were harmful in high concentrations. In the present work, the relative effects of two salts, sodium selenite and sodium selenate, administered to mice in vivo, in different concentrations and durations of exposure, were compared. Aqueous solutions of each salt (7, 14, 21 and 28 mg Kg-1 bw) were fed by gavaging to mice matched in age and sex. The animals were sacrificed at intervals of 6, 12, 18 and 24 h and chromosome preparations were made following the usual schedule of colchicine-hypotonic-fixative-airdrying-Giemsa staining. The endpoints screened were chromosomal aberrations (CA) and damaged cells (DC). Both salts affected chromosome structure and spindle formation, sodium selenite being more cytotoxic than sodium selenate. The frequencies of aberrations induced were directly proportional to the concentrations used and duration of exposure.

Analysis of Variance↗

Modeling interactions between adrenal suppression and T-helper lymphocyte trafficking during multiple dosing of methylprednisolone.

A physiologic pharmacodynamic model was developed to jointly characterize the effects of corticosteroid treatment on adrenal suppression and T-helper cell trafficking during single and multiple dosing in asthmatic patients. Methylprednisolone (MP), cortisol, and T-helper cell concentrations obtained from a previously published study during single day and 6 days of multiple dosing MP treatment were examined. The formation and disposition kinetics of MP were described with a compartmental model. The biorhythmic profile of basal cortisol secretion rate was analyzed using a recent Fourier approach based on circadian harmonics. A three-compartment loop model was proposed to represent three major T-helper cell pools: blood, extravascular site, and lymph nodes. T-helper cell synthesis and degradation rate constants were obtained from the literature. The suppressive effects of cortisol and MP on T-helper cell concentrations were described with a joint additive inhibition function altering the cell migration rate from lymph nodes to blood. The model adequately described both plasma cortisol profiles and T-helper cells in blood after single and multiple doses of MP. The potency of MP for suppression of cortisol secretion was estimated as IC50 = 0.8 ng/ml. The biorhythmic nature of the basal T-helper cells in blood was well described as under the influence of basal circadian cortisol concentrations with IC50 = 79 ng/ml. The model fitted potency of MP for suppression of T-helper cells was IC50 = 4.6 ng/ml. The observed rebound of T-helper cells in blood can also be described by the proposed model. The rhythm and suppression of plasma cortisol and T-helper cells before and during single and multiple dose MP treatment were adequately described by these extended indirect response models.

Adrenal Glands↗

Retinoic acid in association with tin-metalloporphyrins influences heme metabolism in vivo in rats.

In the current study we report the perturbation of key enzymes of the heme metabolic pathway, i.e. delta-amino levulinic acid synthase, heme oxygenase and biliverdin reductase, in vivo by administration of retinoic acid (RA) and retinoic acid in association with tin-metalloporphyrins, viz., tin-protoporphyrin (SnPP) and tin-mesoporphyrin (SnMP) in the liver, spleen, heart and lung of rats. RA at a dosing regimen of 50,000 I.U. stimulated splenic ALA-S activity, whereas co-administration of tin-metalloporphyrins with RA antagonised the RA mediated induction of ALA-S. In the other tissues viz., liver, heart and lung our results showed a diminution of ALA-S activity on RA administration, the level of repression was further attenuated when tin-metalloporphyrins were co-administered with RA. This marked suppression of ALA-S brought forth by concurrent administration of RA and tin-metalloporphyrins is suggestive of the beneficial effect of this formulation in acute attacks of porphyria, similar to heme. Furthermore, our results emphasize that the combined dosing of RA with tin-metalloporphyrins leads to a substantial decline in bilirubin levels due to a profound inhibition of HMOX in the probed tissues. The features of the combined action of RA and tin-metalloporphyrins in vivo lead to a substantial suppression of formation of the potentially toxic metabolite bilirubin, and the enhancement of disposal of the untransformed substrate (heme) of the enzyme that is inhibited. These results define some of the characteristics of a therapeutically useful formulation and represent a new therapeutic approach for the amelioration and management of hyperbilirubinemia.

5-Aminolevulinate Synthetase↗

Mycotic keratitis in non-steroid exposed vernal keratoconjunctivitis.

PURPOSE: To report a patient with vernal keratoconjunctivitis who developed mycotic keratitis in absence of known risk factors. METHODS: A 17-year-old male suffering from vernal keratoconjunctivitis presented with infective keratitis. The patient had been treated in the past with topical antihistaminics and vasoconstrictors. The patient had not been exposed to topical steroids in 2 years of follow-up. He did not have dry eye or corneal micro or macroerosions prior to the development of infective keratitis. Corneal scrapings were obtained and subjected to KOH wet mount smear, calcofluor and Grams stain as well as bacterial culture sensitivity and fungal culture. RESULTS: Clinical diagnosis of mycotic keratitis in association with vernal conjunctivitis was supported by microbiological investigations. KOH wet mount and calcofluor staining showed presence of filamentous septate hyphae while fungal culture showed growth of aspergillus fumigatus. Antifungal therapy was initiated in the form of topical natamycin 5% suspension to which the patient responded and recovered 6/6 final visual acuity. CONCLUSION: The authors wish to conclude that patients suffering from vernal keratoconjunctivitis, even in the absence of corneal involvement, steroid exposure and trauma, may be at increased risk of developing keratomycosis.

Adolescent↗

Corneal biopsy with tissue micro-homogenisation for isolation of organisms in bacterial keratitis.

PURPOSE: To evaluate a novel two-stage technique to increase yield of bacteria isolated from infected corneal ulcers. METHODS: A new blade was designed to remove friable material from infected corneal ulcers. The new blade was used in combination with standard tissue micro-homogenisation equipment in a two-stage technique intended to distribute biopsy samples evenly between relevant agar plates. Patients with presumed-bacterial corneal ulcers underwent sequential corneal sampling using the new two-stage technique and a scalpel blade, used without micro-homogenisation (the order of sampling was varied between two groups). Bacterial isolation rates were compared using the chi-squared test. RESULTS: Twenty-four patients with presumed-bacterial corneal ulcers were studied. The overall positive bacterial isolation rate was 88%, with identical bacterial isolation rates for the new two-stage technique and the scalpel blade (71%). The new technique isolated bacteria from three ulcers that had initially been 'sterile' when sampled with a scalpel blade. Polymicrobial infections were identified in two ulcers with the new blade where only a single organism had been identified using the scalpel blade (not significantly different). CONCLUSIONS: The new two-stage technique shows promise for improving bacterial isolation rates from presumed-bacterial corneal ulcers.

Bacteria↗

D4 dopamine receptor-mediated phospholipid methylation and its implications for mental illnesses such as schizophrenia.

Previous studies have shown D2-like dopamine receptor involvement in the regulation of phospholipid methylation (PLM), while others have documented impaired methionine and folate metabolism in schizophrenia. Utilizing [14C]formate labeling in cultured neuroblastoma cell lines, we now show that D4 dopamine receptors (D4R) mediate the stimulatory effect of dopamine (DA) on PLM. The effect of DA was potently blocked by highly D4R-selective antagonists and stimulated by the D4R-selective agonist CP-226269. DA-stimulated PLM was dependent upon the activity of methionine cycle enzymes, but DA failed to increase PLM in [3H]methionine labeling studies, indicating that a methionine residue in the D4R might be involved in mediating PLM. A direct role for MET313, located on transmembrane helix No. 6 immediately adjacent to phospholipid headgroups, was further suggested from adenosylation, site-directed mutagenesis and GTP-binding results. A comparison of PLM in lymphocytes from schizophrenia patients vs control samples showed a four-fold lower activity in the schizophrenia group. These findings reveal a novel mechanism by which the D4R can regulate membrane composition. Abnormalities in D4R-mediated PLM may be important in psychiatric illnesses such as schizophrenia.

Amino Acid Sequence↗

Role of abdominal drains in perforated duodenal ulcer patients: a prospective controlled study.

BACKGROUND: Duodenal ulcer perforation is a common emergency in south India, with about 100-120 cases being treated at Jawaharalal Institute of Post Graduate Medical Education and Research each year. The routine to date has been to leave two tube drains: one in the Morrison's pouch and one in the pelvis after omental patch closure. This study was conducted to test the efficacy and safety of drain usage routinely after duodenal ulcer perforation closure with Roscoe Graham omental patch technique. METHODS: In this prospective controlled study, 44 patients formed the test group (without drains) and 75 patients formed the control group (with abdominal drainage). Only patients of perforated duodenal ulcer closed with Roscoe Graham omental patch technique were included in the study. The incidence of postoperative fever, wound infection, time for return of bowel function and duration of hospital stay were noted. Details of drainage noted were the mean amount of daily drainage, mean time of drain removal and occurrence of drain-related complications. Peritoneal fluid, wound discharges, drain tips and drain wounds were cultured. Abdominal ultrasound was performed in all patients in the second postoperative week or if earlier indicated to detect intra-abdominal collections. RESULTS: It was found that there was no difference in incidence or duration of postoperative pyrexia, return of bowel function or postoperative hospital stay between the two groups. Routine use of drains was not effective in preventing postoperative fluid collection nor in decreasing the incidence of intra-abdominal abscesses. The migration of bacteria from the exterior to the peritoneal cavity via the drain was also demonstrated. Drains were found to cause morbidity including intestinal obstruction. CONCLUSION: The routine use of drains was found to be neither safe nor effective in patients of perforated duodenal ulcer treated by omental patch closure.

Adult↗

Potential use of genetically modified pigs as organ donors for transplantation into humans.

1. Transplantation is currently viewed as a successful treatment for end-stage organ failure. Its more widespread use is severely limited by a shortage of human organ donors. This has stimulated the scientific and medical communities to look at the potential use of animals to solve this problem. For a number of reasons, the pig appears to be the preferred species. 2. The initial immunological problem encountered in pig-to-primate transplantation is a process of hyperacute rejection, which is mediated by the binding of antibodies to the graft endothelium followed by the activation of the complement cascade. We have sought to overcome these initial immunological challenges by focusing our attention not only on the recipient of the graft but also on the donor. Therefore, we have generated transgenic animals with specific genetic modifications designed to inhibit the activation of the complement cascade. Upon transplantation to baboons of organs derived from these transgenic pigs, we have been able to demonstrate that hyperacute rejection can be prevented. We will discuss the generation of these and other transgenic animals and their potential role in clinical xenotransplantation.

Animals↗

Moderate renal failure in association with prolonged acquired hypothyroidism in children.

We evaluated five children with prolonged primary hypothyroidism and noted a significant reduction in renal function (40%), which was reversible with hormonal replacement. This decline was higher than reported in adults and was of sufficient magnitude to warrant altering drug-dosing schedules. Furthermore, patients with moderately reduced renal function should be carefully evaluated for signs and symptoms of hypothyroidism.

Adolescent↗

Endoscopic neck surgery: expanding horizons.

There have now been several attempts at neck exploration using minimally invasive surgery. These encouraging reports paved the way for the authors to attempt endoscopic neck surgery. Having the necessary technical expertise in minimally invasive surgery with an experience of more than 6000 laparoscopic procedures, they attempted endoscopic parathyroidectomy in three patients with hyperparathyroidism. Of these, two had a hyperfunctioning adenoma and one had parathyroid hyperplasia. The hyperfunctioning tissue was accurately localized using a 99Tc-thallium subtraction scan. It was possible to localize and dissect the parathyroid tissue in two of the three patients. One patient required an open hemithyroidectomy before the adenoma could be localized and excised. The total operative time averaged 113 min. The working space was found to be adequate provided good hemostasis was maintained. The magnification proved excellent in identifying and defining important neck structures. Sufficient mobilization of the lateral thyroid lobe for access to the tracheoesophageal groove was found to be technically very difficult. No subcutaneous emphysema was observed beyond the neck region, and none lasted beyond 24 h. Cosmesis was acceptable to both the patient and the surgeon.

Adenoma↗