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Biomedical subjects

P Rao

Publications and source records attributed to P Rao.

At least 19 recordsLinked to original sources

Iatrogenic duodenal perforations caused by endoscopic biliary stenting and stent migration: an update.

Endoscopic biliary stenting is the preferred method of decompression in obstructive jaundice. Duodenal perforations caused during stenting and stent migration are rare but life-threatening complications, and require judicious management. With the increasing use of therapeutic endoscopy, an awareness of these complications is becoming important in our surgical practice. Advances in interventional radiology, endoscopy, and laparoscopy have enhanced the scope and reduced the morbidity of both conservative and surgical treatments of these perforations. This article presents an update on the current state of our knowledge on the science and the management of this complication.

Biliary Tract↗

Protective effect of a radical scavenger, MCI-186 on islet cell damages induced by oxidative stress.

Oxidative stress generated during islet isolation and transplantation causes islet cell damage. These oxidative injuries are mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS). MCI-186 is an antioxidant used for clinical treatment of cerebral infarction in Japan. We examined a possible protective effect of MCI-186 on islet cells against oxidative stress. Islets isolated from Sprague-Dawley rats by collagenase P digestion were purified by density gradient centrifugation with Ficoll. Islets were treated with hydrogen peroxide (H(2)O(2); 5 to 250 micromol) in the presence or absence of MCI-186. Cell death was measured by an LDH release assay. Maximum islet cell death was observed at 250 micromol of H(2)O(2). MCI-186 inhibited islet cell death in a dose-dependent manner with significant reduction above 30 micromol. From the results observed we suggest that the antioxidant effects of MCI-186 may prove beneficial to improve the preservation of islet cells.

Animals↗

Does the endoscopic technique of ureterocele incision matter?

PURPOSE: Endoscopic ureterocele decompression is a well established procedure in children. However, an accurate endoscopic incision may be challenging in large ectopic ureteroceles. We describe a percutaneously assisted technique to facilitate the ease of ureterocele incision and review other described methods. MATERIALS AND METHODS: We reviewed the medical records of 12 children with ectopic ureteroceles subtending a double collecting system who underwent endoscopic, percutaneously assisted incision. Six ureteroceles were on the left side, 5 were on the right side and 1 child had bilateral ureteroceles. Decompression results were evaluated by ultrasound and Tc-mercaptoacetyltriglycine imaging during a mean of 2.8 years of followup. RESULTS: There were 7 girls and 5 boys. Mean age at presentation was 11.6 months (range 1 week to 6 years). The decompression success rate was 84% (11 of 13 renal units), and improved renal function and drainage was noted in 5 of 12 patients (41.6%). Seven of 12 patients had vesicoureteral reflux, of whom 2 were asymptomatic at followup and, hence, were treated conservatively. Five children underwent surgery because of recurrent urinary tract infections. CONCLUSIONS: Although our results are similar to those of other methods, percutaneously assisted cystoscopic incision of ureterocele enables easier and more accurate decompression. However, when comparing the various techniques described, it seems that postoperative results mostly reflect the anatomical and functional characteristics of the urinary system rather than the technique used.

Child↗

Fluorescent charge-neutral analogue of xanthosine: synthesis of a 2'-deoxyribonucleoside bearing a 5-aza-7-deazaxanthine base.

A concise route is described to prepare the 5-aza-7-deazapurine 2'-deoxyriboside (4), which presents the puADA hydrogen-bonding pattern, analogous to the hydrogen-bonding pattern presented by 2'-deoxyxanthosine (2). The route begins with the commercially available 1-alpha-chloro-2-deoxy-3-5-bistoluoyloxyribofuranose (10), which proves to be a versatile point of entry to beta-2'-deoxyribofuranosides. In the first step, 2-nitroimidazole (8) is coupled with 10 to yield intermediate 11. Reduction of the nitro group to an amino group yields 12, which is treated with phenyl isocyanatoformate to complete the nucleobase to yield 13. Removal of the toluoyloxy protecting groups of 13 yields the target nucleoside 4 in 40% overall yield in four steps. In an alternative strategy, convergent coupling of 14 with 10 under basic conditions was attempted but found to yield the heterocycle glycosylated at the undesired position. Compound 13 displays potentially useful fluorescence properties. After excitation at 250 nm, a solution of 13 in MeCN shows a fluorescence emission with a maximum at 410 nm. Furthermore, 13 is neutral at physiological pH, a property that it shares with natural nucleobases but not xanthosine itself, which is an acid with a pK(a) of ca. 5.6. Furthermore, as part of the design, 4 is made capable of presenting an unshared pair of electrons to the DNA minor groove.

Aza Compounds↗

Simian homologues of Epstein-Barr virus.

Gamma-herpesviruses closely related to the Epstein-Barr virus (EBV) are known to naturally infect Old World non-human primates and are classified in the same lymphocryptovirus (LCV) genera. LCV infecting humans and Old World primates share similar biology, and recent studies have demonstrated that these viruses share a similar repertoire of viral genes. Surprisingly, the latent infection genes associated with cell growth transformation demonstrate the most striking sequence divergence, but the functional mechanisms for these genes are generally well conserved. The recent discovery of LCVs naturally infecting New World primates has rewritten the old paradigm of LCV host range restriction to humans and Old World non-human primates, so that these viruses are more widespread than previously believed. However, the New World LCV genome has significant and interesting differences from EBV and other Old World LCVs despite similar biological properties. Thus, the simian homologues of EBV can provide an important animal model for studying LCV pathogenesis, and the similarities and differences that have evolved among these related viruses can provide a unique perspective towards a better understanding of EBV.

Animals↗

The active sites of the influenza cap-dependent endonuclease are on different polymerase subunits.

The cap-dependent endonuclease of the influenza viral RNA polymerase, which produces the capped RNA primers that initiate viral mRNA synthesis, is comprised of two active sites, one for cap binding and one for endonuclease cleavage. We identify the amino acid sequences that constitute these two active sites and demonstrate that they are located on different polymerase subunits. Binding of the 5' terminal sequence of virion RNA (vRNA) to the polymerase activates a tryptophan-rich, cap-binding sequence on the PB2 subunit. At least one of the tryptophans functions in cap binding, indicating that this active site is probably similar to that of other known cap-binding proteins. Endonuclease cleavage, which is activated by the subsequent binding of the 3' terminal sequence of vRNA, resides in a PB1 sequence that contains three essential acidic amino acids, similar to the active sites of other enzymes that cut polynucleotides to produce 3'-OH ends. These results, coupled with those of our previous study, provide a molecular map of the five known essential active sites of the influenza viral polymerase.

Amino Acids, Dicarboxylic↗

Inhibitors of p38 MAP kinase increase the survival of transplanted dopamine neurons.

Fetal cell transplantation therapies are being developed for the treatment of a number of neurodegenerative disorders including Parkinson's disease [10-12,21,22,24,36,43]. Massive apoptotic cell death is a major limiting factor for the success of neurotransplantation. We have explored a novel protein kinase pathway for its role in apoptosis of dopamine neurons. We have discovered that inhibitors of p38 MAP kinase (the pyridinyl imidazole compounds: PD169316, SB203580, and SB202190) improve survival of rat dopamine neurons in vitro and after transplantation into hemiparkinsonian rats. In embryonic rat ventral mesencephalic cultures, serum withdrawal led to 80% loss of dopamine neurons due to increased apoptosis. Incubation of the cultures with p38 MAP kinase inhibitors at the time of serum withdrawal prevented dopaminergic cell death by inhibiting apoptosis. In the hemiparkinsonian rat, preincubation of ventral mesencephalic tissue with PD169316 prior to transplantation accelerated behavioral recovery and doubled the survival of transplanted dopamine neurons. We conclude that inhibitors of stress-activated protein kinases improve the outcome of cell transplantation by preventing apoptosis of neurons after grafting.

Animals↗

Painless destruction of the shoulder joint: a case report.

A case of painless destruction of the shoulder joint is reported for its rarity and unusual presentation as a neuroarthropathic joint with no evidence of neurological disease. A differential diagntosis of Gorham-Stout syndrome and avascular necrosis was discussed.

Adult↗

Muscle autografts in nerve gaps. Pattern of regeneration and myelination in various lengths of graft: an experimental study in guinea pigs.

Denatured muscle autograft contains large inner basement membrane tubes, which are anatomically and chemically similar to peripheral nerve basement membrane tubes. These autografts can be used for bridging nerve gaps. In 30 Duncan-Hartley guinea pig sciatic nerves, experimentally induced gaps of 5 mm, 10 mm, and 15 mm were bridged with freeze-thawed gluteus maximus muscle autografts. The results were studied for up to 12 weeks. Functional and histological criteria, morphometry, and electron microscopy were used for the evaluation of regeneration and myelination. Functional recovery was seen by 12 weeks in 5-mm grafts. Morphometric study of 1-microm semithin sections was carried out, and the number of axons in each representative field was studied, as the percentage of myelinated and unmyelinated fibers; the thickness of myelin was also measured. The percentage of myelinated and unmyelinated fibers was estimated by transmission electron microscopy (TEM). Axonal repopulation in the distal segment was seen by the third week in the 5-mm graft, and myelination was more extensive in this group in comparison to the others. On morphometric analysis, the mean fiber diameter in the distal part of the graft was 3.81 microm in the 5-mm graft and 2.9 microm in the 15-mm graft at 12 weeks. The results of this experiment prove that the length of the graft is an important consideration for muscle autografts when they are used for mixed peripheral nerve repair.

Animals↗

The relation between nutrition indices and age in patients on continuous ambulatory peritoneal dialysis receiving similar small solute clearances.

OBJECTIVE: To analyze the effect of age on nutrition indices in subjects on the same continuous ambulatory peritoneal dialysis (CAPD) schedule. METHODS: We analyzed 613 sets of clearance values and nutrition indices in 302 CAPD patients. Small solute clearances included urea clearance (Kt/Vurea) and creatinine clearance (Ccr). Nutrition indices included body mass index (BMI), serum albumin, urea and creatinine, 24-h urea nitrogen and creatinine excretion in urine plus dialysate, protein nitrogen appearance (PNA), PNA normalized by standard weight (nPNA), lean body mass (LBM) computed by creatinine kinetics, and LBM/Weight. CAPD subjects were classified in 4 age quartiles (Q): Group Q1, age 33.7 +/- 7.6 years, N = 149; group Q2, age 49.5 +/- 3.8 years, N = 158; group Q3, age 61.5 +/- 2.6 years, N = 154; and group Q4, age 72.1 +/- 5.4 years, N = 152. Group comparison was done by one-way ANOVA or chi-square. Predictors of low nutritional parameters were identified by logistic regression. Selected variables were compared by linear regression. RESULTS: Mean Kt/Vurea and Ccr were above the current adequacy standards and did not differ between the age quartiles. In contrast, older quartiles had, in general, lower nutrition indices than younger quartiles. However, the youngest quartile had the lowest BMI. By logistic regression, young age was a predictor of low BMI, while advanced age was a predictor of low creatinine and urea nitrogen excretion, low nPNA, and low LBM/Weight. The regressions of nPNA on Kt/Vurea differed between the age quartiles. By these regressions, the youngest quartile had higher nPNA values for the same Kt/Vurea than the oldest quartile in the clinically relevant range of Kt/Vurea and nPNA values. CONCLUSIONS: Nutrition indices are worse in older than in younger CAPD patients with the same small solute clearances. Nutrition of CAPD patients is adversely affected by age and requires special attention in the older age group.

Adult↗

The use of palivizumab monoclonal antibody to control an outbreak of respiratory syncytial virus infection in a special care baby unit.

An outbreak of respiratory syncytial virus (RSV) infection affected seven premature infants in a special care baby unit during November and December 1999. Conventional infection control measures (cohorting infected babies, strict reinforcement of the use of gloves and aprons, emphasis on hand disinfection) failed to prevent spread. Palivizumab, a respiratory syncytial virus monoclonal antibody, was given to eight high-risk preterm infants. There were no further cases of RSV in the unit and none of the babies given palivizumab developed RSV. One baby who acquired RSV during the outbreak (and who was not given palivizumab) was subsequently admitted to hospital with another episode of RSV bronchiolitis. The role of palivizumab in the control of hospital outbreaks of RSV infection merits further investigation.

Antibodies, Monoclonal↗

Familial presacral masses: Screening pitfalls.

BACKGROUND/PURPOSE: Anterior sacral meningocele (ASM) and presacral teratoma (PT) are related malformations. Both can have familial occurrence. Surgical treatment of occult cases is essential. Hence, it is important to screen the asymptomatic relatives. Plain radiograph of the sacrum to look for any bony abnormalities is the usual accepted screening modality. The authors report ASM and PT in siblings (with positive family history) with no sacrococcygeal bony abnormality on imaging. Both the siblings had presacral mass on imaging. METHODS: The medical records of 2 siblings with ASM and PT were reviewed for the clinical presentation, diagnostic workup, and family history. RESULTS: One sibling was symptomatic, whereas the other was completely asymptomatic. A family history of sacral bony abnormalities and anterior meningoceles was present in father, 2 paternal cousins, paternal uncle, paternal aunt, paternal grandmother, and paternal grand uncle. CONCLUSIONS: These case reports suggest that imaging for screening for ASM and PT should be directed at identifying the presacral mass rather than sacral bony defect. Hence, computed tomography or magnetic resonance imaging looking for presacral mass rather than plain radiograph should be the screening modality. J Pediatr Surg 36:1841-1844.

Adolescent↗

The use of helical computed tomography in pregnancy for the diagnosis of acute appendicitis.

OBJECTIVE: Accurate diagnosis of acute appendicitis in pregnancy by clinical evaluation is difficult. A safe, reliable test was sought to decrease a delay in diagnosis and to avoid unnecessary invasive procedures. A helical or spiral computed tomographic technique has proven to be a very accurate test in the nonobstetric population for the identification of acute appendicitis. We report its use in pregnant patients with suspected acute appendicitis. STUDY DESIGN: All pregnant patients who were undergoing helical computed tomography at our institution from April 1997 to February 1998 for the suspected clinical diagnosis of acute appendicitis were retrospectively reviewed. Helical computed tomography was performed by standard departmental protocol. A positive study was reported if an enlarged appendix, which did not fill with contrast material, was present with periappendiceal inflammatory changes. Outcomes were determined by the results of surgery and pathologic examination or clinical follow-up. RESULTS: Seven patients were identified in the study period. Two patients had positive findings on helical computed tomography, and acute appendicitis was confirmed at laparotomy and by pathologic inspection. There were no further prenatal complications and both patients delivered at term. Five patients had a normal-appearing appendix on helical computed tomography, and all of these patients had resolution of their pain and symptoms. CONCLUSION: Helical computed tomography appears to be a useful, noninvasive test to accurately diagnose acute appendicitis in pregnancy.

Adult↗

Spectral karyotyping analysis of head and neck squamous cell carcinoma.

OBJECTIVES/HYPOTHESIS: The genetic content of head and neck squamous cell carcinomas is ill defined. Spectral karyotyping (SKY) is a new technique that allows the simultaneous detection of all chromosomal translocations by labeling each individual chromosome with different fluorescent agents. In the current study we used SKY to analyze cell lines and a primary tumor derived from head and neck squamous cell carcinomas (HNSCC) to delineate recurrent translocations and breakpoints. STUDY DESIGN: Spectral karyotyping analysis of head and neck cancer. METHODS: Two cell lines (MDA886 and MSK922) and one primary tumor in short-term culture were subjected to metaphase growth arrest with colcemide in their exponential growth phase and fixed onto glass slides. Painting probes for each of the autosomes and the sex chromosomes were generated from flow-sorted human chromosomes using sequence-independent DNA amplification. The probes were labeled using a polymerase chain reaction-based reaction and hybridized to metaphase preparations for 2 days at 37 degrees C. Biotinylated probes were detected using avidin Cy5 and digoxigenin-labeled probes with an anti-mouse digoxigenin antibody followed by goat anti-mouse antibody conjugated to Cy5.5. Chromosomes were counterstained with 4,6-diamino-2-phenyliodole (DAPI), and a minimum of five metaphases were captured and analyzed for each case. Breakpoints on the SKY-painted chromosomes were determined by comparison of corresponding DAPI banding. RESULTS: Spectral karyotyping analysis revealed a complex pattern of chromosomal abnormalities. A total of 66 translocations were identified in the three cases, with one new recurrent translocation at (der(4)t(4;20)(q35;?)). Nine complex translocations, involving three or more chromosomes, were identified in these cases. Overall, 96 breakpoints were assigned to metaphase chromosomes and another 74 breakpoints could not be assigned. Breakpoints most commonly involved chromosomes in genetic rearrangements were 1, 3, 5, 8, 13, 16, and 17. CONCLUSIONS: Spectral karyotyping analysis reveals the true complexity of chromosomal aberrations in cell lines derived from head and neck squamous cell carcinomas. The use of SKY, in combination with other techniques, may allow for a more complete assessment of the genetic abnormalities of head and neck cancers and serve as a starting point for gene identification.

Carcinoma, Squamous Cell↗

Correlation of marrow dose estimates based on serial pretreatment radiopharmaceutical imaging and blood data with actual marrow toxicity in anti-CD20 yttrium-90 monoclonal antibody radioimmunotherapy of non-Hodgkin's B-cell lymphoma.

The purpose of this study was to investigate whether marrow radiation absorbed dose estimates predict haematotoxicity following radioimmunotherapy with an yttrium-90 labelled anti-CD20 monoclonal antibody in non-Hodgkin's B-cell lymphoma (NHL). Radiopharmaceutical data from 12 NHL radioimmunotherapy patients were analysed retrospectively using three methods of marrow radiation absorbed dose estimation based on serial pretreatment indium-111 labelled anti-CD20 monoclonal antibody activity versus time data (0-144 h): (i) lumbar spine (LS) image counts; (ii) blood clearance (BL); and (iii) whole body (WB) activity. Linear regressions were performed between the methods, and between each method and the 0-6 month post-treatment platelet and white blood cell count nadir and absolute drop in count (ADC). For the range of yttrium-90 activities (740-1547 MBq), absorbed dose estimates (mean +/- sigma) were: LS, 142+/-50 cGy (range 62-233 cGy); BL, 89+/-21 cGy (range 63-140 cGy); and WB, 54+/-10 cGy (range 36-63 cGy). The LS and BL marrow estimates differed significantly (P <0.003), with a correlation coefficient r of 0.36 (P = NS), while WB correlated significantly with both LS (r = 0.50, P < 0.05) and BL (r = 0.58, P < 0.05). The range of r with platelet nadir and ADC was -0.20 < or = r < or = 0.01, except for WB with ADC (r = 0.38) (all P = NS). Values of r for white blood cell nadir were unexpectedly positive, being 0.13 for BL and 0.29 for LS (P = NS), and 0.60 for WB (P < 0.025). Values of r for white blood cell ADC were 0.36 for BL and -0.26 for LS (P = NS), and 0.50 for WB (P < 0.05). These results indicate that different commonly employed methods of estimating marrow radiation absorbed dose may yield significantly differing results, which may not correlate with actual radiation toxicity. Therefore, caution must be exercised in relying on these results to predict haematotoxicity.

Algorithms↗

A measure for predicting audibility discrimination thresholds for spectral envelope distortions in vowel sounds.

Both in speech synthesis and in sound coding it is often beneficial to have a measure that predicts whether, and to what extent, two sounds are different. This paper addresses the problem of estimating the perceptual effects of small modifications to the spectral envelope of a harmonic sound. A recently proposed auditory model is investigated that transforms the physical spectrum into a pattern of specific loudness as a function of critical band rate. A distance measure based on the concept of partial loudness is presented, which treats detectability in terms of a partial loudness threshold. This approach is adapted to the problem of estimating discrimination thresholds related to modifications of the spectral envelope of synthetic vowels. Data obtained from subjective listening tests using a representative set of stimuli in a 3IFC adaptive procedure show that the model makes reasonably good predictions of the discrimination threshold. Systematic deviations from the predicted thresholds may be related to individual differences in auditory filter selectivity. The partial loudness measure is compared with previously proposed distance measures such as the Euclidean distance between excitation patterns and between specific loudness applied to the same experimental data. An objective test measure shows that the partial loudness measure and the Euclidean distance of the excitation patterns are equally appropriate as distance measures for predicting audibility thresholds. The Euclidean distance between specific loudness is worse in performance compared with the other two.

Auditory Threshold↗