PubMed Health⌕ Search

Biomedical subjects

S Raja

Publications and source records attributed to S Raja.

At least 37 records · Page 2Linked to original sources
PubMed2000

Laparoscopic repair of giant paraesophageal hernia: 100 consecutive cases.

OBJECTIVE: To summarize the authors' laparoscopic experience for paraesophageal hernia (PEH). SUMMARY BACKGROUND DATA: Laparoscopic antireflux surgery and repair of small hiatal hernias are now routinely performed. Repair of a giant PEH is more complex and requires conventional surgery in most centers. Giant PEH accounts for approximately 5% of all hiatal hernias. Medical management may be associated with a 50% progression of symptoms and a significant death rate. Conventional open surgery has a low death rate, but complications are significant and return to routine activities is delayed in this frequently elderly population. Recently, short-term outcome studies have reported that minimally invasive approaches to PEH may be associated with a lower complication rate, a shorter hospital stay, and faster recovery. METHODS: From July 1995 to February 2000, 100 patients (median age 68) underwent laparoscopic repair of a giant PEH. Follow-up included heartburn scores and quality of life measurements using the SF-12 physical component and mental component summary scores. RESULTS: There were 8 type II hernias, 85 type III, and 7 type IV. Sac removal, crural repair, and antireflux procedures were performed (72 Nissen, 27 Collis-Nissen). The 30-day death rate was zero; there was one surgery-related death at 5 months from a perioperative stroke. Intraoperative complications included pneumothorax, esophageal perforation, and gastric perforation. There were three conversions to open surgery. Major postoperative complications included stroke, myocardial infarction, pulmonary emboli, adult respiratory distress syndrome, and repeat operations (two for abscess and one each for hematoma, repair leak, and recurrent hernia). Median length of stay was 2 days. Median follow-up at 12 months revealed resumption of proton pump inhibitors in 10 patients and one repeat operation for recurrence. The mean heartburn score was 2.3 (0, best; 45, worst); the satisfaction score was 91%; physical and mental component summary scores were 49 and 54, respectively (normal, 50). CONCLUSION: This report represents the largest series to date of laparoscopic repair of giant PEH. In the authors' center with extensive experience in minimally invasive surgery, laparoscopic repair of giant PEH was successfully performed in 97% of patients, with a minimal complication rate, a 2-day length of stay, and good intermediate results.

Aged↗
PubMed2000

Role of Tc-99m MIBI in the evaluation of single pulmonary nodules: a preliminary report.

BACKGROUND: Survival in bronchial carcinoma is closely related to the stage of the disease at the time of diagnosis and a single pulmonary nodule represents a potentially curable stage. This study was conducted to assess the feasibility of using Tc-99m labelled 2-methoxy isobutyl isonitrile (MIBI) to differentiate benign from malignant single pulmonary nodules. METHODS: A prospective study was conducted in the outpatient pulmonary clinic at the Cleveland Clinic Foundation. Twenty five patients with single pulmonary nodules considered indeterminate by their physicians and undergoing a procedure for tissue diagnosis were evaluated by Tc-99m MIBI SPECT scanning prior to definitive testing. Assessment of MIBI uptake was done qualitatively (subjectively) and quantitatively and correlated with the histopathology and nodule size. RESULTS: Of the 21 patients with malignant lesions, 18 had increased uptake of MIBI corresponding to the location of the nodule and were considered positive. The predominant tumour types were large cell (n = 5) and adenocarcinoma (n = 10). All four patients with benign lesions had negative MIBI scans. For malignancy the overall specificity was 100%, sensitivity was 85.7%, positive predictive value was 100%, and negative predictive value was 57%. Quantitative uptake of MIBI correlated with the diameter of the nodule with a correlation coefficient of 0.61 by Spearman's rank sum test. This relationship was statistically significant (p = 0.02). CONCLUSION: This preliminary study suggests that Tc-99m MIBI has a very high specificity and positive predictive value for malignant single pulmonary nodules and might be a useful non-invasive diagnostic modality in their management.

Aged↗
PubMed1999

Scintigraphic detection of post-pneumonectomy bronchopleural fistulae.

A total of 20 ventilation studies [16 with xenon-133 and four with technetium-99m diethylenetriamine pentaacetic acid (DTPA)] were performed in 11 patients with suspected post-pneumonectomy bronchopleural fistulae. The findings on the ventilation scan were correlated with bronchoscopy, taken as the gold standard for purposes of comparison. The sensitivity and specificity for 133Xe scans were 83% and 100% respectively, while the sensitivity for 99mTc-DTPA aerosol studies was poor at 0%. Special techniques for optimal visualization of the fistulae are enumerated.

Aerosols↗
PubMed1999

Secondary victimization of rape victims: insights from mental health professionals who treat survivors of violence.

Rape victims may turn to the legal, medical, and mental health systems for assistance, but there is a growing body of literature indicating that many survivors are denied help by these agencies. What help victims do receive often leaves them feeling revictimized. These negative experiences have been termed "the second rape" or "secondary victimization." If indeed secondary victimization occurs, then these issues may be raised in rape survivors' mental health treatment. In the current study, probability sampling was used to survey a representative sample of licensed mental health professionals about the extent to which they believe rape victims are "re-raped" in their interactions with social system personnel. Most therapists believed that some community professionals engage in harmful behaviors that are detrimental to rape survivors' psychological well-being. Implications for future research on secondary victimization are discussed.

Adult↗
PubMed1998

NRP/B, a novel nuclear matrix protein, associates with p110(RB) and is involved in neuronal differentiation.

The nuclear matrix is defined as the insoluble framework of the nucleus and has been implicated in the regulation of gene expression, the cell cycle, and nuclear structural integrity via linkage to intermediate filaments of the cytoskeleton. We have discovered a novel nuclear matrix protein, NRP/B (nuclear restricted protein/brain), which contains two major structural elements: a BTB domain-like structure in the predicted NH2 terminus, and a "kelch motif" in the predicted COOH-terminal domain. NRP/B mRNA (5.5 kb) is predominantly expressed in human fetal and adult brain with minor expression in kidney and pancreas. During mouse embryogenesis, NRP/B mRNA expression is upregulated in the nervous system. The NRP/B protein is expressed in rat primary hippocampal neurons, but not in primary astrocytes. NRP/B expression was upregulated during the differentiation of murine Neuro 2A and human SH-SY5Y neuroblastoma cells. Overexpression of NRP/B in these cells augmented neuronal process formation. Treatment with antisense NRP/B oligodeoxynucleotides inhibited the neurite development of rat primary hippocampal neurons as well as the neuronal process formation during neuronal differentiation of PC-12 cells. Since the hypophosphorylated form of retinoblastoma protein (p110(RB)) is found to be associated with the nuclear matrix and overexpression of p110(RB) induces neuronal differentiation, we investigated whether NRP/B is associated with p110(RB). Both in vivo and in vitro experiments demonstrate that NRP/B can be phosphorylated and can bind to the functionally active hypophosphorylated form of the p110(RB) during neuronal differentiation of SH-SY5Y neuroblastoma cells induced by retinoic acid. Our studies indicate that NRP/B is a novel nuclear matrix protein, specifically expressed in primary neurons, that interacts with p110(RB) and participates in the regulation of neuronal process formation.

Adult↗
PubMed1998

A third locus (GLC1D) for adult-onset primary open-angle glaucoma maps to the 8q23 region.

PURPOSE: Two genes for adult-onset primary open-angle glaucoma have been mapped to chromosomes 2cen-q13 and 3q21-q24. We studied a family with adult-onset primary open-angle glaucoma in which the disease did not map to these two chromosomal regions. METHODS: We ascertained a four-generation family with adult-onset primary open-angle glaucoma in which the disease status of individuals was objectively assigned using defined criteria. Complete ophthalmologic examinations, visual field testing, optic nerve head photographs, and venous blood samples were obtained. Family members were genotyped using polymerase chain reaction amplification of microsatellite polymorphic markers. Linkage analysis was performed and lod scores were calculated. Haplotype transmission data were analyzed. RESULTS: A total of 20 subjects in three successive generations agreed to participate in the study. This included samples from eight affected subjects, one glaucoma suspect, one normal individual, and two spouses in generations II and III, and an additional eight individuals in generation IV. The phenotype in this family appears to be variable, with onset of visual field loss in middle age, followed by modest elevation of intraocular pressure and progression of the disease in older individuals. Linkage was established with a group of DNA markers located in the 8q23 region. A lod score value of 3.61 was obtained using marker D8S1471. Three other markers from the same region gave lod score values of over 3.0. Haplotype transmission data identified two recombination events that placed the gene in a 6.3-cM region flanked by D8S1830 and D8S592. The disease-bearing haplotype was inherited by eight affected subjects and three glaucoma suspects. CONCLUSION: We present evidence for a third adult-onset primary open-angle glaucoma locus (GLC1D) on chromosome 8q23. The genetic heterogeneity of adult-onset glaucoma is evident from the multiplicity of chromosomal loci associated with this disease.

Aged↗
PubMed1997

Tyrosine phosphorylation of the novel protein-tyrosine kinase RAFTK during an early phase of platelet activation by an integrin glycoprotein IIb-IIIa-independent mechanism.

A key regulatory event controlling platelet activation is mediated through the phosphorylation of several cellular proteins by protein-tyrosine kinases. The related adhesion focal tyrosine kinase (RAFTK) is a novel cytoplasmic tyrosine kinase and a member of the focal adhesion kinase (FAK) gene family. FAK phosphorylation in platelets is integrin-dependent, occurs in a late stage of platelet activation, and is dependent on platelet aggregation. In this study, we have investigated the involvement of RAFTK phosphorylation during different stages of platelet activation. Treatment of platelets with thrombin induced, in as early as 10 s, a rapid tyrosine phosphorylation of RAFTK in a time- and concentration-dependent manner. Treatment of platelets with thrombin in the absence of stirring or pretreatment of platelets with RGDS peptide prevented platelet aggregation, but not RAFTK phosphorylation. Furthermore, phosphorylation of RAFTK did not require integrin engagement since platelets treated with the 7E3 inhibitory antibodies that block fibrinogen binding to glycoprotein IIb-IIIa did not inhibit RAFTK phosphorylation. Similarly, platelets treated with LIBS6 antibodies, which specifically activate glycoprotein IIb-IIIa, did not induce RAFTK phosphorylation. Stimulation of platelets by several agonists such as collagen, ADP, epinephrine, and calcium ionophore A23187 induced RAFTK phosphorylation. Tyrosine phosphorylation of RAFTK in platelets is regulated by calcium and is mediated through the protein kinase C pathway. Phosphorylation of RAFTK is dependent upon the formation of actin cytoskeleton as disruption of actin polymerization by cytochalasin D significantly inhibited this phosphorylation. The RAFTK protein appears to be proteolytically cleaved by calpain in an aggregation dependent manner upon thrombin stimulation. These results demonstrate that RAFTK is tyrosine-phosphorylated during an early phase of platelet activation by an integrin- independent mechanism and is not dependent on platelet aggregation, suggesting different mechanisms of regulation for FAK and RAFTK phosphorylation during platelet activation.

Adenosine Diphosphate↗
PubMed1997

Usefulness of ictal and interictal 99mTc ethyl cysteinate dimer single photon emission computed tomography in patients with refractory partial epilepsy.

PURPOSE: Ictal perfusion single photon emission computed tomography (SPECT), using HMPAO, has been shown to localize epileptic foci in approximately 90% of studies. Unfortunately, HMPAO decomposes rapidly, precluding the performance of ictal studies. Ethyl cysteinate dimer (ECD) is a SPECT perfusion agent recently approved by the Food and Drug Administration. After preparation, this compound is stable for approximately 6 h. facilitating the performance of ictal studies. METHODS: In a prospective, open-label, uncontrolled, non randomized study, we evaluated the potential benefits of the use of 99mTc-ECD SPECT for lateralization of the epileptic focus. Ten consecutive adult epilepsy surgery candidates were studied with ictal and interictal 99mTc-ECD SPECT. RESULTS: The mean delay between seizure onset and ictal SPECT injection was 23.2 s. The mean seizure duration was 84.1 s. Ictal studies agreement between the epilepsy focus and area of hyperperfusion was evident in 8 of 10 cases. In one case, SPECT was lateralized in a patient with bilateral temporal lobe epilepsy (TLE); however, hyperperfusion was observed on the same side of that particular seizure. In another case, there was location disagreement. Interictal SPECT showed focal hypoperfusion in three cases. CONCLUSIONS: 99mTc-ECD proved to be an optimal tracer for ictal studies. Although this is a small series, the results of ictal and interictal findings using 99mTc-ECD are similar to those reported with 99mTc-HMPAO. Because 99mTc-ECD has a longer decomposition time, true ictal studies are easier to obtain. This new tracer will probably allow the use of ictal SPECT to become widely accepted in most epilepsy centers.

Adult↗
PubMed1996

The related adhesion focal tyrosine kinase forms a complex with paxillin in hematopoietic cells.

Related adhesion focal tyrosine kinase (RAFTK), also known as proline-rich tyrosine kinase 2 and cellular adhesion kinase beta, has been recently cloned and characterized as a member of the focal adhesion kinase (FAK) subfamily. RAFTK has an overall 48% amino acid homology to p125(FAK) and contains a kinase domain but lacks a transmembrane region, myristylation sites, and Src homology region 2 and 3 domains. By Northern blot analysis, RAFTK is expressed in myeloid, lymphoid, and megakaryocytic hematopoietic cells. Like p125(FAK), we found that RAFTK interacts with the focal adhesion protein paxillin. In the lymphoid cell line BaF3 and the myeloid cell line 32Dcl3, RAFTK coprecipitates with paxillin. Using in vitro binding assays, RAFTK and paxillin were shown to bind directly, through a segment of paxillin that required amino acids 100-227 and a domain in the C terminus of RAFTK. In vitro, RAFTK could phosphorylate paxillin on tyrosine residues. These results suggest that RAFTK, as well as p125(FAK), may be important in phosphotyrosine-signaling events within the focal adhesion.

Animals↗
PubMed1996

Characterization of RAFTK, a novel focal adhesion kinase, and its integrin-dependent phosphorylation and activation in megakaryocytes.

We have recently isolated a cDNA encoding a novel human intracellular tyrosine kinase, termed RAFTK (for a related adhesion focal tyrosine kinase). The RAFTK cDNA, which encodes a polypeptide of 1,009 amino acids, shares 65% homology to the focal adhesion kinase (FAK), including several consensus motifs. In this report, we describe the biochemical characterization and functional analysis of the RAFTK protein. Coexpression of RAFTK and FAK proteins in megakaryocytic cells and blood platelets was observed. Using a specific antibody to RAFTK and the monoclonal antibody 2A7 to FAK, FAK and RAFTK could be distinguished antigenically. RAFTK had intrinsic tyrosine kinase and autokinase activities. It was phosphorylated on tyrosine in growing cultures of COS cells transfected with the pCDNAIII/flag-RAFTK expression vector containing the RAFTK cDNA ligated with the 8 amino acid flag peptide sequence. Similar to FAK, dephosphorylation of RAFTK was observed when adherent transfected COS cells were detached. Phosphorylation was regained upon replating of these cells on the fibronectincoated dishes. Analysis of tyrosine-phosphorylated RAFTK from adherent transfected COS cells showed that the Src homology 2 (SH2) domains of the Src and Fyn protein kinases as well as the Grb2 adaptor protein were able to specifically associate with RAFTK. Tyrosine phosphorylation of endogenous RAFTK was observed upon fibronectin-induced activation of human megakaryocytic cells. Furthermore, colocalization of RAFTK protein with vinculin, a focal adhesion protein, was observed by confocal microscopy in focal adhesion-like structures in adherent CMK cells and in transfected pCDNAIII/flag-RAFTK COS cells upon fibronectin activation. These data suggest that RAFTK is a novel member of the FAK family, that it localizes to focal adhesion-like structures in CMK megakaryocytic cells, that it participates in integrinmediated signaling pathways in megakaryocytes, and that it is able to associate with the tyrosine kinases Src and Fyn as well as the adaptor protein Grb2 via SH2-phosphotyrosine interactions.

Adaptor Proteins, Signal Transducing↗
PubMed1996

Induction of spinal cord neuronal nitric oxide synthase (NOS) after formalin injection in the rat hind paw.

The nitric oxide synthase (NOS) inhibitor L-nitroarginine methyl ester has been found to exhibit antinociceptive activity in a rat model of pain [Kitto, K.F. et al., Neurosci. Lett., 148 (1992) 1-5; Lee, J.H. et al., NeuroReport, 3 (1992) 841-844; Moore, P.K. et al., Br. J. Pharmacol., 102 (1991) 198-202]. We investigated the hypothesis that hind paw injection of formalin increases the number of dorsal horn neuronal nitric oxide synthase (nNOS) containing neurons. Results showed a bilateral increase in the number of nNOS-positive neurons at the L4-5 dorsal horn area following formalin injection. The increase was always greater on the ipsilateral side compared to the contralateral side. This upregulation of nNOS following formalin stimulation of the hind paw suggested that nitric oxide (NO) may play a role in the central mechanism of hyperalgesia that follows peripheral inflammation.

Animals↗
PubMed1996

Present assessment of myocardial viability by nuclear imaging.

Prospective delineation of viable from nonviable myocardium in patients with coronary artery disease in an important factor in deciding whether a patient should be revascularized or treated medically. Two common techniques--single-photon emission computed tomography (SPECT) and positron-emission computed tomography (PET)--are used in nuclear medicine using various radiopharmaceuticals for the detection of myocardial viability in patients. Thallium-201 (201Tl) and technetium-99m (99mTc)-sestamibi are the common radiopharmaceuticals used in different protocols using SPECT, whereas fluoride-18 (18F)-fluorodeoxyglucose (FDG) and rubidium-82 (82Rb) are most widely used in PET. The SPECT protocols involve stress/redistribution, stress/redistribution/reinjection, and rest/redistribution imaging techniques. Many studies have compared the results of 201Tl and (99mTc)-sestamibi SPECT with those of FDG PET; in some studies, concordant results have been found between delayed thallium and FDG results, indicating that 201Tl, although considered a perfusion agent, shows myocardial viability. Discordant results in a number of studies have been found between sestamibi and FDG, suggesting that the efficacy of sestamibi as a viability marker has yet to be established. Radiolabeled fatty acids such as iodine-123 (123I)-para-iodophenylpentadecanoic acid and carbon-11 (11C)-palmitic acid have been used for the assessment of myocardial viability with limited success. 11C-labeled acetate is a good marker of oxidative metabolism in the heart and has been used to predict the reversibility of wall motion abnormalities. (18F)-FDG is considered the marker of choice for myocardial viability, although variable results are obtained under different physiological conditions. Detection of myocardial viability can be greatly improved by developing new equipment and radiopharmaceuticals of better quality.

Artifacts↗
PubMed1996

Epilepsy surgery in infants.

PURPOSE: We report 12 infants who had frontal (n = 3), temporal (n = 2), or temporoparieto-occipital (n = 2) resection or functional hemispherectomies (n = 5) at age 2.5-29 (mean 15.3) months for catastrophic epilepsy due to focal cortical dysplasia (n = 5), Sturge-Weber syndrome (n = 3), ganglioglioma (n = 3), or hemimegalencephaly (n = 1). Seizures began at 1 day to 14 months (mean, 4.0 months) after birth, occurred frequently (often many times per day, and were refractory to antiepileptic drugs. Patients were evaluated for surgery at 2.5-24 (mean 12.4) months of age. Seven patients had hemiparesis and eight had slowed cognitive development. Seizures were characterized by arrest or marked reduction of behavioral motor activity with nuclear level of consciousness (n = 4, with temporal or temporoparietal EEG seizures), focal clonic activity (n = 3, with perirolandic EEG seizures), generalized tonic stiffening (n = 3, with temporoparieto-occipital, parietal, or frontal EEG seizures), or infantile spasms and hypsarrhythmia (n = 2, with a frontal tumor or temporoparieto-occipital cortical dysplasia). METHODS: Magnetic resonance imaging (MRI) revealed the epileptogenic lesion in all but two patients, both with cortical dysplasia localized by interictal positron-emission tomography (PET) and other clinical or EEG features and confirmed on histopathologic examination of resected tissue. RESULTS: At follow-up 4-86 (mean 32) months after surgery, six patients were seizure free (Engel outcome class I), three had rare seizures with none in at least the previous 6 months (Engel class II), and two had worthwhile improvement (Engel class III). Except for the severely developmentally delayed infant with hemimegalencephaly, several patients had marked "catch-up" developmental progress after class I, II, or III outcome. Postoperative complications included subdural hematoma over the contralateral hemisphere (one patient) and entrapment and enlargement of the ipsilateral temporal horn (one patient) after hemispherectomy, both corrected uneventfully with a second surgical procedure. One patient died of unexplained causes several hours after frontal lobectomy. No patients had new neurologic deficits after surgery, and one patient had resolution of progressive fluctuating hemiparesis after resection of temporoparieto-occipital cortical dysplasia. CONCLUSIONS: Our results agree with previous reports that epilepsy surgery can provide relief from catastrophic epilepsy in carefully selected infants.

Age Factors↗
PubMed1996

Epilepsy surgery in the setting of periventricular leukomalacia and focal cortical dysplasia.

We report an infant who had successful epilepsy surgery for intractable infantile spasms in the setting of bilateral periventricular leukomalacia and remote germinal matrix hemorrhage. Although MRI gave evidence of a diffuse cerebral insult and EEG showed hypsarrhythmia, focal epileptogenicity was suggested by previous partial seizures with onset over the right temporoparietal-occipital region and PET hypometabolism in that same area. Right temporoparietal and lateral occipital resection at 15 months resulted in seizure freedom and dramatic developmental progress at 1-year follow-up. Histopathologic examination of resected tissue showed cortical dysplasia, possibly due to the same insult that also resulted in the bilateral periventricular leukomalacia. From an etiologic perspective, this is one of very few reported cases strongly implicating acquired focal cortical dysplasia in response to a prenatal insult. From a clinical perspective, the case illustrates that the spectrum of potential surgical candidacy in infants may be broader than usually suspected.

Brain↗
PubMed1996

Outcome of temporal lobe epilepsy surgery predicted by statistical parametric PET imaging.

UNLABELLED: PET is useful in the presurgical evaluation of temporal lobe epilepsy. The purpose of this retrospective study is to assess the clinical use of statistical parametric imaging in predicting surgical outcome. METHODS: Interictal 18FDG-PET scans in 17 patients with surgically-treated temporal lobe epilepsy (Group A-13 seizure-free, group B = 4 not seizure-free at 6 mo) were transformed into statistical parametric imaging, with each pixel representing a z-score value by using the mean and s.d. of count distribution in each individual patient, for both visual and quantitative analysis. RESULTS: Mean z-scores were significantly more negative in anterolateral (AL) and mesial (M) regions on the operated side than the nonoperated side in group A (AL: p < 0.00005, M: p = 0.0097), but not in group B (AL: p = 0.46, M: p = 0.08). Statistical parametric imaging correctly lateralized 16 out of 17 patients. Only the AL region, however, was significant in predicting surgical outcome (F = 29.03, p < 0.00005). Using a cut-off z-score value of -1.5, statistical parametric imaging correctly classified 92% of temporal lobes from group A and 88% of those from Group B. CONCLUSION: The preliminary results indicate that statistical parametric imaging provides both clinically useful information for lateralization in temporal lobe epilepsy and a reliable predictive indicator of clinical outcome following surgical treatment.

Adult↗
PubMed1995

Tyrosine kinases in megakaryocytopoiesis.

Protein-tyrosine kinases (PTKs) are of vital importance in a variety of cell functions. Recent studies have provided considerable insight into the binding of growth factors to tyrosine kinase receptors and the consequent induction of signal pathways that lead to a biologic response. Future studies will further delineate the signals that result in a proliferative response and those that induce a differentiation response. Current studies, reviewed here, indicate an important biologic role for PTKs in the regulation of megakaryocyte development and maturation. Whether PTKs function in megakaryocytes in signaling pathways that are similar to pathways in other cells will need to be examined in future studies.

Animals↗