Search PubMed⌕ Search

Biomedical subjects

H Patel

Publications and source records attributed to H Patel.

At least 91 records · Page 5Linked to original sources

Activin, inhibin, and follistatin in zebrafish ovary: expression and role in oocyte maturation.

Activins, inhibins, and follistatins are important regulators of mammalian reproduction. However, their roles in lower vertebrates are poorly understood. In this study, we examined the expression of activin A, inhibin A, and follistatins in the zebrafish ovary and determined their role in final oocyte maturation. Using reverse transcription-polymerase chain reaction with primers specific for activin/inhibin beta(A) subunit and for follistatins, we detected DNA fragments of the expected size, which, upon sequencing, conformed to activin/inhibin beta(A) and follistatin. Western blot analysis using an antibody against activin/inhibin beta(A) subunit revealed two bands with sizes similar to those of activin A and inhibin A. The expression of follistatins was also confirmed by Western blot analysis. These results suggest that activin A, an inhibin A-like molecule, and follistatins are expressed in the zebrafish ovary. In cultured zebrafish follicles, activin A and inhibin A both induced final oocyte maturation in a dose-dependent manner. The effects of activin A and inhibin A were blocked by their binding protein, follistatin-288. Interestingly, follistatin-288 also inhibited final oocyte maturation induced by gonadotropin and by maturation-inducing hormone (MIH), suggesting that activin A and/or inhibin A may be local regulators mediating gonadotropin- and MIH-induced final oocyte maturation. Taken together, these findings suggest that activin A and inhibin A are paracrine regulators of ovarian functions in fish.

Activins↗

Effect of carbon coating on the properties of gamma irradiated ultra-high-molecular-weight polyethylene specimens.

We reported the effect of carbon coating on the changes in properties of the ultra-high-molecular-weight polyethylene standard material (Hospital for Special Surgery) alter gamma irradiation in air and storage for 2 years. The coating showed a slight improvement in crystallinity (X-ray) and tensile properties (under cyclic loading) over the uncoated and irradiated control group. The oxidation level as measured by Fourier- transform infrared spectroscopy was unaffected by coating.

Air↗

Mechanical strain-induced human vascular matrix synthesis: the role of angiotensin II.

INTRODUCTION: Reduced vascular compliance in patients with hypertension results from an increase in extra-cellular matrix (ECM) protein deposition in blood vessels. At least two key factors, namely mechanical strain and neurohumoral mediators, for example Angiotensin II (Ang II), promote fibrogenesis within vessel walls; however potential interactions between these have not been clearly defined. This work examined the direct effect of mechanical strain on matrix mRNA expression and protein synthesis by human vascular smooth muscle (VSM) cells and identified the importance of renin-angiotensin system (RAS) activation in stretch-induced matrix production. METHODS: Human VSM cells were exposed either to a cyclical mechanical strain regimen or to Ang II in the presence or absence of the Ang II receptor (AT(1) R) antagonist losartan or its more potent metabolite EXP3174. Analysis of matrix mRNA expression (Northerns) and protein synthesis (ELISA) and cellular AT(1)-receptor protein expression (Westerns) were determined. RESULTS: Ang II increased both collagen alpha1 (92%, SEM +/- 20%) mRNA expression and fibronectin (21% +/- 6%) protein synthesis in static VSM cells compared with unstimulated controls. The effect of Ang II was attenuated by antagonism of the AT(1)-receptor (AT(1) R). Similarly, mechanical strain induced an increase in both collagen alpha1 (102% +/- 30%) mRNA expression and fibronectin (50% +/-21%) protein synthesis. Surprisingly, in the absence of exogenous Ang II, AT(1)-receptor blockade attenuated this stretch-induced increase in matrix synthesis. Mechanical strain also induced an increase in total cellular AT(1)-receptor protein (30.7% +/- 3.5%) compared with static cells. CONCLUSION: Both mechanical strain and Ang II increased matrix gene expression and protein synthesis by human VSM cells. The effect of strain was attenuated by AT(1)-receptor antagonism. Our results further suggest that mechanical strain may sensitise human VSM cells to the fibrogenic actions of Ang II, perhaps via upregulation of the AT(1)-receptor.

Angiotensin II↗

Percutaneous needle bladder neck suspension for the treatment of stress urinary incontinence in women: long-term results.

PURPOSE: We evaluated the long-term results of percutaneous needle suspension using bone anchor devices for treating stress urinary incontinence in women. MATERIALS AND METHODS: We retrospectively evaluated the long-term results of percutaneous bladder neck needle suspension performed at our institution. None of the women had undergone any anti-incontinence surgery before percutaneous needle suspension. A telephone survey was done for all available patients. Subjective cure was defined as no evidence of incontinence, significant improvement as 0 to 1 protective pad soaked daily and patient satisfaction with incontinence level, and failure as more than 1 pad used daily, lack of patient satisfaction or a secondary procedure required to treat stress urinary incontinence. In cases considered failures a detailed video urodynamic study was performed when possible before any secondary procedure. RESULTS: In 1996 and 1997, 49 patients underwent percutaneous needle bladder neck suspension with bone anchors, of whom 42 (86%) were available for telephone interview. Mean patient age was 57 years (range 31 to 77) and mean followup was 29 months (range 16 to 52). As defined, subjective outcome in the 42 women was cure in 2 (5%), significant improvement in 5 (12%) and failure in 35 (83%). Of the 35 patients with treatment failure who did not undergo a secondary procedure 25 were asked to present for video urodynamics and 18 were evaluated. Urodynamics revealed demonstrable urinary incontinence, urethral hypermobility in 16 (88%), intrinsic sphincter deficiency in 1 (6%) and detrusor instability in 1 (6%). In 2 cases x-ray revealed that a bone anchor had dislodged and migrated into the pelvis. Serious osteomyelitis at the bone anchor site in 1 case required surgical débridement and 6 weeks of intravenous antibiotics. CONCLUSIONS: Percutaneous needle suspension is associated with poor long-term results in women with stress urinary incontinence. Other procedures should be considered.

Adult↗

Palliative balloon pulmonary valvuloplasty in tetralogy of fallot: echocardiographic predictors of successful outcome.

Although balloon pulmonary valvuloplasty (BPV) has been advocated as a means of palliating patients with tetralogy of Fallot (TOF), the results of this procedure were not uniformly good in this patient population. The purpose of this study was to review our institutionOs experience with BPV in patients with TOF, and to determine whether echocardiographic criteria exist that may be used to identify patients likely to derive prolonged benefit from this procedure. Between 1991 and 1999, nine patients with TOF, ages 0. 4Eth 26.1 weeks (mean, 7.4 +/- 7.6 weeks) underwent BPV due to cyanosis and other associated medical conditions (e.g., coronary artery anomalies, small size) that rendered immediate surgical intervention undesirable. Data from the catheterization and pre-BPV echocardiograms were analyzed. All patients had at least transient improvement in oxygen saturation. However, 4 patients (Group 1) required intervention (1 open-heart repair, 3 palliative shunts) within 5 weeks of BPV due to recurrent desaturation. In the remaining 5 patients (Group 2), open-heart repair was delayed 8Eth 36 weeks (mean, 23 +/- 13 weeks). Groups 1 and 2 did not differ regarding pulmonary valve annulus, main pulmonary artery or branch pulmonary artery diameter. However, the diastolic diameter of the right ventricular outflow tract (RVOT) was significantly smaller in Group 1 (18.3 +/- 3.5 mm/m2 versus 24.4 +/- 4.1 mm/m2 in Group 2; p < 0.05). Four out of five patients with a RVOT diameter < 23 mm/m2 were in Group 1, and all patients with RVOT diameter greater than 25 mm/m2 were in Group 2. We conclude that BPV can effectively palliate patients with TOF whose RVOT diastolic diameter is > 25 mm/m2. However, patients with a diastolic RVOT diameter < 23 mm/m2 are unlikely to have sustained improvement following BPV.

Cardiac Catheterization↗

P53 mutations in primary and metastatic tumors and circulating tumor cells from colorectal carcinoma patients.

Circulating tumor cells could provide a relatively noninvasive and repeatable source of information about tumor cell genotype that might influence treatment and estimation of prognosis. We developed a technique for identifying p53 mutations in tumor cells isolated from the peripheral venous blood of colorectal cancer patients and compared the prevalence and position of these mutations with multiple solid tumor samples from the same patient. We used immunomagnetic beads to isolate tumor cells, reverse transcriptase-nested polymerase chain amplification of the coding region between exons 4 and 9 within the p53 gene, and automated gene sequencing. Nineteen p53 mutations were detected in solid tumor samples from 19 of 41 colorectal carcinoma patients. An identical p53 mutation was invariably present in all samples from primary and metastatic colorectal tumor biopsies within the same patient. p53 mutations were detected in peripheral blood from 8 of these 19 patients with p53-mutated solid tumors. Where identified, the pattern of mutation in peripheral blood samples was invariably the same as in matching solid tumor samples. A single colorectal carcinoma biopsy provided reliable p53 gene mutational information in colorectal carcinoma. Detection of this p53 mutation in tumor cells from peripheral blood was achieved with an approach based on cell selection for epithelial characteristics, reverse transcription-PCR, and gene sequencing.

Biopsy↗

Acute treatment of atrial fibrillation: spontaneous conversion rates and cost of care.

Acute treatment of atrial fibrillation is costly although spontaneous conversion rates are high. We reviewed 114 patients admitted to our inpatient service via the emergency department with a principal diagnosis of atrial fibrillation and found the spontaneous conversion rate was 50% in 48 hours, the average length of stay was 3.9 +/- 5.2 days, and the average cost was $6,692 +/- $4,928.

Aged↗

Activation of Vav and Ras through the nerve growth factor and B cell receptors by different kinases.

Engagement of the B-cell antigen receptor (BCR) or the nerve growth factor receptor (NGFR/TrkA) induces activation of multiple tyrosine kinases, resulting in phosphorylation of numerous intracellular substrates. We show that addition of NGF or anti-IgM antibody leads to the early tyrosine phosphorylation of p95(vav), which is expressed exclusively in hematopoietic cells; NGF, similar to crosslinking the BCR, also results in the rapid activation of Ras. The phosphorylation of Vav and activation of Ras triggered by NGF is mediated through Trk tyrosine kinase, whereas signaling through the BCR uses a different tyrosine kinase. We also show that NGF induces tyrosine phosphorylation of Shc and its association with Grb2. Vav and Ras with the adaptor proteins Shc and Grb2 appear to serve as a link between different receptor-mediated signaling pathways and, in human B cells, may play an important regulatory role in neuroimmune interactions.

Adaptor Proteins, Signal Transducing↗

Cleavage of double-stranded copy RNA by RNase 1 and RNase T1 provides a robust means to detect p53 gene mutations in clinical specimens.

Detecting somatic mutations in patient specimens is challenging because of the wide variation in quality and quantity of genomic DNA in clinically derived material. In cancer specimens, the challenge of detecting mutations is usually compounded by the presence of large numbers of nonmutated normal cells that dampen the relative signal that can be obtained from employing any mutation detection strategy. In the case of somatic mutations in the gene encoding the tumor suppressor, p53, a clinically useful mutation detection assay must be able to detect a wide variety of types of mutations scattered over five coding exons and their flanking intron sequences. This study examined the ability of a mutation detection strategy, termed NIRCA, to identify single-base mutations in the clinically relevant domain of the p53 gene. This strategy relies on RNase digestion-mediated cleavage of double-stranded copy RNA transcribed in vitro from polymerase chain reaction (PCR)-amplified genomic templates to detect mismatched base pairs resulting from hybridization of complimenting mutant and wild-type copy RNA strands. This assay system was found to robustly detect all twelve possible mismatches and the plus one and minus one frame shifts. Furthermore, the assay could detect mutations in clinical specimens when the mutant alleles composed as few as 4% of the total population of alleles isolated in bulk specimen genomic DNA. This mutation detection strategy worked efficiently in bladder, breast, colon and lung tumors as well as sediments from bladder cytology specimens.

Humans↗

The development of hypertrophic pyloric stenosis in a patient with prostaglandin-induced foveolar hyperplasia.

BACKGROUND: Hypertrophic pyloric stenosis (HPS) has been described in association with several obstructive antropyloric lesions including idiopathic foveolar hyperplasia (gastric mucosal hypertrophy), feeding tubes, eosinophilic gastroenteritis, and hypertrophic antral polyps. Non obstructive antral webs have also been described with HPS. PATIENT AND METHODS: We present a case of gastric-outlet obstruction in association with HPS, namely, prostaglandin-induced foveolar hyperplasia. This entity has been previously described, but rarely in association with HPS. We report a female infant requiring prostaglandin therapy for pulmonary atresia who developed dose-related prostaglandin-induced foveolar hyperplasia and symptoms of progressive non-bilious vomiting. RESULTS: Initially, ultrasonography demonstrated evidence of antral mucosal hypertrophy as the cause for gastric-outlet obstruction. The patient subsequently developed progressive thickening of the antropyloric muscle, resulting in sonographic appearances of hypertrophic pyloric stenosis. Pyloromyotomy was eventually required for treatment of HPS. CONCLUSION: A common denominator of most of the above-described entities is thickening and/or hypertrophy of the antral mucosa. We suggest that the antropyloric musculature may hypertrophy in an effort to overcome the gastric-outlet obstruction caused by the adjacent thickened antral mucosa. In other words, these entities may represent examples of "secondary" hypertrophic pyloric stenosis.

Female↗

Cremasteric muscle hypertrophy accompanies inguinal hernias in children.

PURPOSE: The physical finding of a thickened spermatic cord as indicator of an inguinal hernia in children is well documented. This thickening has been attributed to the presence of a hernia sac. Based on our clinical observations, cremasteric fibers appeared thickened in the presence of an inguinal hernia. The authors postulated that hypertrophy of cremasteric fibers contributed to the physical finding of cord thickening. METHODS: The authors evaluated 18 patients ages 5 months to 9 years, 17 boys and one girl. Each patient was found to have a unilateral inguinal hernia with palpable thickened cord on the affected side. The contralateral side contained no detectable hernia or palpable cord thickening. Each patient underwent repair of the clinical hernia and exploration of the contralateral groin. Cremasteric fiber biopsy sections were taken from both sides for cross-sectional measurement and comparison. The biopsy specimens were evaluated by a pathologist unaware of the hypothesis. RESULTS: In 15 of 18 patients microscopic measurement of the cremasteric fibers showed hypertrophy on the side of the clinical hernia when compared with the contralateral side. The contralateral side was found to have either no hernia or a small patent or obliterated processus vaginalis. CONCLUSION: The authors conclude that the palpable thickening of the spermatic cord, the "silk glove sign," in most cases is caused not only by an empty hernia sac but also by hypertrophied cremasteric muscle fibers.

Child↗

Survival 12 years after randomization to streptokinase: the influence of thrombolysis in myocardial infarction flow at three to four weeks.

OBJECTIVES: The purpose of this study was to determine whether the mortality benefit of intravenous streptokinase administered within 4 h of the onset of acute myocardial infarction is maintained at 12 years, and whether Thrombolysis in Myocardial Infarction (TIMI) flow grades independently influence late survival. BACKGROUND: Treatment with reperfusion therapies and achievement of TIMI 3 flow are associated with increased short- and medium-term survival after infarction. Whether infarct artery flow independently influences survival more than five years after infarction is unknown. METHODS: The late survival of patients randomized to receive either streptokinase (1,500,000 IU over 30 to 60 min) or a matching placebo within 4 h of symptom onset in 1984-1986 was determined. Angiography was performed in surviving patients at three to four weeks, and TIMI flow grades were assessed blind to randomization and outcomes. The late vital status was determined in 99% of patients. RESULTS: Patients randomized to receive streptokinase (n = 107) had improved survival compared with those randomized to placebo (n = 112) at five years (84% vs. 70%; p = 0.023) and 12 years (66% vs. 51%; p = 0.022). At five years 94% of patients with TIMI grade 3 flow, 81% of those with TIMI grade 2 flow and 72% of those with TIMI grade 0-1 flow survived (p = 0.005). At 12 years 72% of patients with TIMI 3, 67% of those with TIMI 2 and 54% of those with TIMI 0-1 flow survived (p = 0.023). Multivariate analysis identified the ejection fraction (p = 0.014), exercise duration (p = 0.013) and TIMI 3 flow (p = 0.04 compared with TIMI 0-2 flow) as important factors for five-year survival. At 12 years multivariate predictors of late survival were the ejection fraction (p = 0.006), exercise duration (p = 0.003) and myocardial score (p = 0.013). The end-systolic volume index was similar to the ejection fraction as a predictor of survival at five and 12 years. CONCLUSIONS: The survival benefits of streptokinase persist for 12 years after infarction. TIMI flow at three to four weeks is an independent predictor of five-year survival.

Actuarial Analysis↗

Presurgical evaluation and surgical outcome of temporal lobe epilepsy.

The authors analyzed 22 patients younger than 18 years of age with temporal lobe epilepsy (TLE) treated surgically. Patients underwent a comprehensive presurgical evaluation, including video-electroencephalogram. Fifty-five percent had a history of febrile seizures. Eighty-two percent had auraes and most exhibited oroalimentary and gestural automatisms. Contralateral dystonic posturing was present in 36% and postictal dysphasia in 54% of patients with left-sided resections. Cranial magnetic resonance imaging (MRI) was abnormal in 59% of patients. MRI revealed changes consistent with mesial temporal sclerosis in 8 (47%) of 17 patients without lesions. Fluorodeoxyglucose-positron emission tomography (PET) scans revealed ipsilateral temporal hypometabolism (PET-TH) in 12 (85.7%) of 14 patients. The intracarotid amobarbital procedure revealed impaired memory of the epileptogenic side in 59% of patients. Seventeen patients underwent en-bloc resections and five lesionectomies and resection of the epileptogenic area. There was no surgical morbidity or mortality. Forty-three percent had hippocampal sclerosis, 28.5% gliosis, 14% low-grade tumors, 9.5% cavernous angiomas, and 5% had no pathologic findings. Follow-up (6 months to 12 years) was available for 21 patients; 76% became seizure free, 19% had rare seizures, and 5% had a worthwhile improvement. TLE can be safely treated surgically in younger patients with excellent results. The clinical manifestations were similar to adult patients. PET-TH was present even at a younger age, suggesting that the focal functional deficits appear early in patients with medically refractory TLE, which may help in the early identification of these patients.

Adolescent↗