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Biomedical subjects

R Shetty

Publications and source records attributed to R Shetty.

At least 19 recordsLinked to original sources

Laparoscopic distal pancreatectomy: results of a prospective non-randomized study from a tertiary center.

BACKGROUND: Though laparoscopic distal pancreatectomy for benign conditions was first described in the early 1990s, it has not become as popular as other laparoscopic surgeries. Published literature on this topic consists of several case reports and a handful of small series. We present our experience, which, to the best of our knowledge, is the largest series reported to date. METHODS: Since 1998, 22 patients have undergone distal pancreatectomy at our institute. The technique of distal pancreatosplenectomy, as well as spleen-preserving distal pancreatectomy, is described. RESULTS: Four males and 18 females in the age range of 12-69 years underwent operation. Splenic preservation was possible in 7 patients. The tumor diameter ranged from 2.1 cm to 7.4 cm. The mean operating time was 215 min. The mean length of incision required for specimen retrieval was 3.4 cm. All patients were started on a liquid diet on the first postoperative day. The median hospital stay was 4 days. One patient developed a pancreatic fistula that was managed conservatively. At the end of an average follow-up of 4.6 years, no recurrence has been reported. CONCLUSIONS: Laparoscopic distal pancreatectomy is a safe procedure, with minimal morbidity, rapid recovery, and short hospital stay. In appropriate cases, splenic preservation is feasible.

Adolescent↗

Distribution of SPARC during neovascularisation of degenerative aortic stenosis.

OBJECTIVE: To examine the hypothesis that degenerative aortic stenosis (AS) is associated with the development of blood vessels and the expression of the secreted protein, acidic and rich in cysteine/osteonectin (SPARC), a matricellular protein that is involved in ossification, the modulation of angiogenesis and the production of metalloproteinases. METHODS: 30 surgically excised AS valves and 20 normal aortic valves were studied. RESULTS: Blood vessels were detected in the aortic valves from patients with degenerative AS, whereas normal valves were avascular structures. Blood vessels in AS valves expressed endothelial nitric oxide synthase, CD34 and von Willebrand factor (vWF). Blood vessels were located in three distinct regions: near calcified nodules, under the leaflet border and in rich cellular areas forming cell islands. Blood vessels were predominantly present in early and intermediate grades of calcification. Cell islands were densely populated by CD45-positive cells where endothelial cells (CD34+, vWF+) forming cord-like structures were present. Immunoblotting detected SPARC only in AS valves and immunohistological analysis located SPARC in mature blood vessels. The proportion of blood vessels positive for SPARC was higher in valves with a lower grade of calcification. In cell islands, SPARC was distributed to mature blood vessels and to macrophages, where it co-located with matrix metalloproteinase-9, whereas no expression was detected in endothelial cells forming cord-like structures. CONCLUSION: The localisation of SPARC to mature blood vessels and its predominant expression in AS valves with a lower calcification grade suggest that the spatial and temporal distribution of this matricellular protein is tightly controlled to participate in the neovascularisation of AS valves.

Aged↗

Expression of bone-regulatory proteins in human valve allografts.

OBJECTIVE: To test the hypothesis that valve allograft (VA) calcification results from an ossification process in which bone-regulatory proteins are expressed. METHODS: 15 VA that were explanted at the time of surgery for dysfunction were studied. VA were analysed and compared with normal aortic valves (n = 20). RESULTS: All the VA (5 aortic, 10 pulmonary) exhibited heavy calcification and important fibrosis. Immunohistochemistry studies showed that the bone-specific transcription factor Cbfa-1 was expressed by stromal cells. Bone alkaline phosphatase was expressed in calcified regions. Immunostaining for alpha smooth muscle (alpha-SM) actin was increased in VA compared with normal valves and in 6 of the 15 valves formed cellular clusters close to the calcified nodules. In VA osteopontin and osteonectin were expressed by stromal cells, whereas osteocalcin was closely associated with the calcified regions. Furthermore, analysis of the bone-regulatory proteins that control bone resorption showed that receptor activator of nuclear factor kappaB ligand (RANKL), receptor activator of nuclear factor kappaB (RANK) and osteoprotegerin (OPG) were differentially expressed in calcified VA and normal valves. Normal valve leaflets expressed OPG, whereas OPG expression was absent or faint in calcified VA. RANKL and RANK were not detected in normal valves, whereas calcified VA expressed RANKL and RANK. CONCLUSION: These data suggest that calcification of VA results from an ossification process, which relies on tight control of bone-regulatory protein expression. The expression pattern of the RANKL/RANK/OPG system suggests that it may have a regulatory role not only in osteoclastogenesis but also in the calcification of human VA.

Actins↗

Laparoscopic lateral pancreaticojejunostomy: a new remedy for an old ailment.

BACKGROUND: Lateral pancreaticojejunostomy is considered as the standard surgery for chronic pancreatitis. Yet there are very few reports of this procedure being done laparoscopically. We present our experience with laparoscopic lateral pancreaticojejunostomy till date and describe our technique. MATERIAL AND METHOD: Since 1997, we have done 12 laparoscopic lateral pancreatojejunostomies. There were 9 females and 3 males and the average age was 29.3 years. The indication for surgery in all patients was intractable abdominal pain and significant weight loss. Additionally, two patients were also suffering from pancreatic ascites. RESULTS: The average diameter of the pancreatic duct was 14.7 mm. We used a four-port technique. All surgeries were completed without any conversion to open surgery. Post-operatively, there were no major morbidity and nil mortality. The average operating time was 172 minutes. Post-operative stay was short (average 5 days) and on median follow-up of 4.4 years, 83.3% patients had complete pain relief while 16.7% had partial relief. All patients had significant weight gain. CONCLUSIONS: Laparoscopic lateral pancreaticojejunostomy is safe, effective and feasible in experience hands. Mastery of intracorporeal knotting and suturing techniques is mandatory before embarking on this surgery.

Adolescent↗

Nasopalatine duct cyst.

Nasopalatine duct cyst is an intraossseous developmental cyst of the midline of the anterior palate. Management of a case of nasopalatine duct cyst in a 10 yr old male child is reported.

Child↗

Efficacy and morbidity of therapeutic renal embolization in the spectrum of urologic disease.

PURPOSE: We report the largest series of renal embolizations performed for a variety of indications. PATIENTS AND METHODS: A retrospective analysis was performed on embolizations performed in our institution from 1997 to 2002 encompassing 36 patients who underwent 44 procedures. RESULTS: Embolization was successful on the first attempt in 87% of the patients. A second embolization was performed in four of the five unsuccessful cases, three successfully, increasing the success rate to 95%. The mean postoperative narcotic use was 27.2 mg of morphine equivalent, and 10 mg or less was required by 45% of the patients. In the 14 patients who had not also undergone a surgical procedure, the mean narcotic use was 21 mg, and 64% required 10 mg or less. Only 15% of the patients developed fever, which resolved within 2 days in all cases. Leukocytosis was seen in 47%. Follow-up creatinine and hypertension information was available in 16 and 18 patients, respectively. After a mean follow-up of 269 days, only one patient had a clinically significant rise in the creatinine concentration. After a mean follow-up of 496 days, two patients had new-onset hypertension. There was no statistically significant difference in the success rate, narcotic use, complications, creatinine concentrations, or the likelihood of fever, leukocytosis, or hypertension according to the indication for embolization or the agent used. Use of a microcatheter was associated with less parenchymal loss, and decreased parenchymal loss was associated with a significant reduction of narcotic use. CONCLUSIONS: Renal embolization is a highly effective and well-tolerated procedure in a variety of urologic conditions. The indications and material used did not have a significant effect on the outcome. Reducing parenchymal loss can significantly reduce morbidity.

Analgesics↗

Congenital cervical bronchogenic cyst.

A bronchogenic cyst is a rare developmental aberration that occurs in the paediatric age group. Over 50 cases of bronchogenic cysts have been reported in the literature. There is still a possibility of clinically misdiagnosing this condition as a more common congenital neck cyst like a branchial cyst. We report here the case of a 12-year-old female presenting with a neck swelling since birth who was diagnosed to have a bronchogenic cyst based on characteristic clinical and histopathological findings.

Bronchogenic Cyst↗

Single SPECT measures of cerebral cortical perfusion reflect time-index estimation of dementia severity in Alzheimer's disease.

UNLABELLED: To determine the relationship between cerebral cortical blood flow loss and the temporal development of the dementia in Alzheimer's disease (AD), SPECT was studied in a cross section of AD patients with a broad range of impairment. METHODS: Thirty patients with a diagnosis of probable AD had their mini-mental state examination scores transformed into time-index values to give an estimation of dementia severity relative to the developmental time course. SPECT images were obtained using 99mTc-ethyl cysteinate dimer and a 3-head camera. Cortical surface perfusion was analyzed, including modified Talairach standardization, to obtain cortical elements from the convexity (each representing about 0.25 cm2 at the surface, 6.6-mm cortical depth) referenced to the mean perfusion of the full greater cerebellar hemisphere. These element ratios were analyzed (individually and by averages of estimated Brodmann's areas and brain regions) using linear regression with the time-index value. RESULTS: For individual posterotemporal and inferoparietal Brodmann's areas (21, 22 and 39, 40, respectively) the correlation coefficients between cortical perfusion ratios and dementia severity ranged between -0.67 and -0.78 (P < 0.001). Perfusion ratios from these regions declined 2.5%-4.2% for each estimated year of progression. Prefrontal area perfusion showed less association with severity. Perfusion in primary cortical regions had no significant association with dementia severity. CONCLUSION: Cerebral cortical perfusion loss is temporally related to development of dementia. The spatial pattern of high, significant correlations between cortical perfusion and dementia severity shows a regional distribution that corresponds closely to the distribution of AD pathology described in autopsy studies.

Aged↗

The T-superfamily of conotoxins.

We report the discovery and initial characterization of the T-superfamily of conotoxins. Eight different T-superfamily peptides from five Conus species were identified; they share a consensus signal sequence, and a conserved arrangement of cysteine residues (- -CC- -CC-). T-superfamily peptides were found expressed in venom ducts of all major feeding types of Conus; the results suggest that the T-superfamily will be a large and diverse group of peptides, widely distributed in the 500 different Conus species. These peptides are likely to be functionally diverse; although the peptides are small (11-17 amino acids), their sequences are strikingly divergent, with different peptides of the superfamily exhibiting varying extents of post-translational modification. Of the three peptides tested for in vivo biological activity, only one was active on mice but all three had effects on fish. The peptides that have been extensively characterized are as follows: p5a, GCCPKQMRCCTL*; tx5a, gammaCCgammaDGW(+)CCT( section sign)AAO; and au5a, FCCPFIRYCCW (where gamma = gamma-carboxyglutamate, W(+) = bromotryptophan, O = hydroxyproline, T( section sign) = glycosylated threonine, and * = COOH-terminal amidation). We also demonstrate that the precursor of tx5a contains a functional gamma-carboxylation recognition signal in the -1 to -20 propeptide region, consistent with the presence of gamma-carboxyglutamate residues in this peptide.

Amino Acid Sequence↗

Speciation of cone snails and interspecific hyperdivergence of their venom peptides. Potential evolutionary significance of introns.

All 500 species of cone snails (Conus) are venomous predators. From a biochemical/genetic perspective, differences among Conus species may be based on the 50-200 different peptides in the venom of each species. Venom is used for prey capture as well as for interactions with predators and competitors. The venom of every species has its own distinct complement of peptides. Some of the interspecific divergence observed in venom peptides can be explained by differential expression of venom peptide superfamilies in different species and of peptide superfamily branching in various Conus lineages into pharmacologic groups with different targeting specificity. However, the striking interspecific divergence of peptide sequences is the dominant factor in the differences observed between venoms. The small venom peptides (typically 10-35 amino acids in length) are processed from larger prepropeptide precursors (ca. 100 amino acids). If interspecific comparisons are made between homologous prepropeptides, the three different regions of a Conus peptide precursor (signal sequence, pro-region, mature peptide) are found to have diverged at remarkably different rates. Analysis of synonymous and nonsynonymous substitution rates for the different segments of a prepropeptide suggests that mutation frequency varies by over an order of magnitude across the segments, with the mature toxin region undergoing the highest rate. The three sections of the prepropeptide which exhibit apparently different mutation rates are separated by introns. This striking segment-specific rate of divergence of Conus prepropeptides suggests a role for introns in evolution: exons separated by introns have the potential to evolve very different mutation rates. Plausible mechanisms that could underlie differing mutational frequency in the different exons of a gene are discussed.

Amino Acid Sequence↗

Palatal tremor, progressive multiple cranial nerve palsies, and cerebellar ataxia: a case report and review of literature of palatal tremors in neurodegenerative disease.

We describe a patient with an unusual clinical presentation of progressive multiple cranial nerve palsies, cerebellar ataxia, and palatal tremor (PT) resulting from an unknown etiology. Magnetic resonance imaging showed evidence of hypertrophy of the inferior olivary nuclei, brain stem atrophy, and marked cerebellar atrophy. This combination of progressive multiple cranial nerve palsies, cerebellar ataxia, and PT has never been reported in the literature. We have also reviewed the literature of PT secondary to neurodegenerative causes. In a total of 23 patients, the common causes are sporadic olivopontocerebellar atrophy (OPCA; 22%), Alexander's disease (22%), unknown etiology (43.4%), and occasionally progressive supranuclear palsy (4.3%) and spinocerebellar degeneration (4.3%). Most patients present with progressive cerebellar ataxia and approximately two thirds of them have rhythmic tremors elsewhere. Ear clicks are observed in 13% and evidence of hypertrophy of the inferior olivary nucleus in 25% of the patients. The common neurodegenerative causes of PT are OPCA/multiple system atrophy, Alexander's disease, and, in most of them, the result of an unknown cause.

Adult↗

Local graft irradiation after failure of modern immunosuppression in acute cellular and vascular graft rejection.

PURPOSE: With improved chemical immunosuppressive agents, approximately 90% of rejection episodes can be reversed. However, in situations of failed immunosuppression, graft loss becomes inevitable. Our objective is to assess the efficacy of local graft irradiation (LGI) as an effort of last resort in a contemporary group of patients in whom graft failure to irreversible cellular and vascular rejection is imminent. METHODS AND MATERIALS: A total of 308 renal transplantations were performed at our institution from 1992 to 1995, and an overall 1-year graft survival rate of 90% has been seen as a result of improvement in chemical immunosuppression. However, 6 patients were referred for LGI when all other measures failed to reverse the rejection crisis. Parameters that were studied in these patients included graft function and postirradiation graft histology. RESULTS: Irradiation was associated with reversal of the rejection crisis and resulted in documented histological long-term graft survival in 1 of the 6 patients (17%). Two of the six patients (33%) had reversal of the rejection episode based on postirradiation biopsy of the renal allograft. Three of the six patients showed some level of clinical improvement of graft function for varying periods of time. One patient maintained stable allograft function without deterioration and with continued independence from hemodialysis. One recipient died from sepsis despite histologic improvement after irradiation. CONCLUSIONS: Our impression is that LGI is indicated when all other measures have failed to reverse an acute rejection episode in the transplanted renal allograft. The role of radiation in this setting should be studied further.

Graft Rejection↗

Acute IOP elevation with scleral suction: effects on retrobulbar haemodynamics.

AIMS/BACKGROUND: Mechanical and vascular factors may both contribute to glaucoma. This study investigated the relation of mechanical to vascular factors by examining how acute IOP elevation altered flow velocities in the central retinal and ophthalmic arteries. METHODS: IOP was elevated from a baseline near 14 to approximately 45 mm Hg using suction ophthalmodynamometry. During recovery from scleral suction, IOP fell to near 8 mm Hg. At each IOP, peak systolic and end diastolic velocities (PSV and EDV) were measured in the central retinal and ophthalmic arteries using colour Doppler imaging (Siemens Quantum 2000). Eleven healthy people served as subjects. RESULTS: Acute elevation in IOP had no effect upon PSV, EDV, or the derived resistance index in the ophthalmic artery: flow velocities in this vessel were identical at IOP of 8 mm Hg or 45 mm Hg. In contrast, in the central retinal artery, PSV and EDV fell, and the resistance index rose, in steady progression as IOP was acutely elevated (each p < 0.01). At IOP of 45 mm Hg, EDV was virtually absent and the resistance index was very nearly 1.0. CONCLUSION: Ophthalmic arterial haemodynamics are unrelated to acute fluctuations of the IOP over a wide range, suggesting that ocular hypertension itself cannot induce vascular dysfunction in this artery. In contrast, flow velocities in the central retinal artery were highly IOP dependent, implying that haemodynamic and mechanical factors are closely linked in this vascular bed.

Acute Disease↗

Tunnel restorations using glass ionomer or glass cermet: in vitro marginal ridge fracture and microleakage.

The purpose of this in vitro study was to compare the marginal ridge fracture resistance and microleakage following restorations of partial tunnel preparations using glass ionomer and glass cermet cements. Sixty eight sound premolars were selected for this study and were divided randomly into six groups. A standardized partial tunnel preparation was done on all the teeth except specimens belonging to Group I. The partial tunnel preparations of Groups III & V were restored with glass ionomer and that of Groups IV & VI were restored with glass cermet. The teeth belonging to Groups I, II, III & IV were subjected to marginal ridge fracture resistance testing. The teeth of Groups V & VI were tested for microleakage after immersing them in 5% methylene blue solution for 4 hours. The results indicated that the teeth restored with glass cermet were marginally better than that with glass ionomer in terms of marginal ridge fracture resistance. Both the materials failed to reinforce the marginal ridge to the level of an intact tooth. The microleakage which occurred around both the materials were statistically insignificant, but on comparison glass ionomer showed better results. Hence, glass ionomer is preferred as a restorative material for partial tunnel preparations because of additional inherent advantages like superior esthetics and fluoride leachability.

Bicuspid↗

Serum copper concentration as an index of clinical lung injury.

The purpose of this ongoing study is to determine whether thoracic radiotherapy for lung cancer produces an early increase in serum copper (Cu) concentration, an increase which might predict clinical outcome. Copper and iron concentrations were measured in serum obtained from nonsmall cell lung cancer patients at 0, 1, 2, 4, and 6 weeks after the start of radiotherapy. Control groups included patients irradiated for breast cancer (low dose of radiation to the lung), for endometrial, cervical or prostatic cancer (no dose to lung), and patients with congestive heart failure, pulmonary hypertension, chronic obstructive pulmonary disease (COPD), and cutaneous burns with or without smoke inhalation (no irradiation). Serum Cu concentration increased at least 10 micrograms/dl from the pretreatment level in approximately 75% of the adenocarcinoma and squamous cell lung cancer patients, but in only 1 of 4 undifferentiated lung cancer cases. In virtually all of these responders, serum Cu increased to a maximum at 2 weeks after the start of therapy, then plateaued or decreased slightly despite continuing irradiation. Within the subset of squamous cell lung cancers, there was a direct correlation between the degree of histologic differentiation and both baseline serum Cu concentration and the probability of an early increase therein. In contrast, only 33% of breast cancer patients and 15% of endometrial, cervical and prostate cancer patients exhibited an increase in serum Cu concentration at 2 weeks after the start of radiotherapy. Serum Cu concentration was within normal limits in virtually all patients with congestive heart failure, pulmonary hypertension, and COPD. Burn patients exhibited a significant reduction in serum Cu, although concomitant smoke inhalation increased serum Cu back to low-normal levels. Serum iron concentration did not change significantly in any category of patients. These data suggest that thoracic radiotherapy for well differentiated non-small cell lung cancer is accompanied by an early increase in serum Cu concentration. This increase is partly but not wholly related to lung dose in particular rather than tissue dose in general, and specifically reflects radiation-induced lung injury rather than pneumopathy in general. In lung cancer patients, the change in serum Cu concentration during the first 2 weeks of radiotherapy exhibits a sufficiently broad range (+60 to -13 micrograms/dl) to permit testing this parameter as a predictor of tumor response and pulmonary complications.

Adenocarcinoma↗