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Biomedical subjects

P Mathew

Publications and source records attributed to P Mathew.

At least 55 records · Page 3Linked to original sources
PubMed1997

Use of an anti-ALK antibody in the characterization of anaplastic large-cell lymphoma of childhood.

BACKGROUND: Anaplastic lymphoma kinase (ALK) is a tyrosine kinase inappropriately expressed in lymphoid tissue involved by CD30+ anaplastic large-cell lymphoma (ALCL) with the translocation t(2;5)(p23;q35)(, which juxtaposes the nucleophosmin gene (NPM) with that encoding ALK, resulting in a hybrid (NPM-ALK) message. PATIENTS AND METHODS: A polyclonal antibody against residues of the kinase portion of NPM-ALK (designated anti-ALK 11) was tested for clinical utility in paraffin sections of 44 cases of pediatric large-cell lymphoma (LCL) and 17 additional lymphoma cases, by streptavidin-biotin-alkaline phosphatase method. RESULTS: Nineteen of 20 CD30+ cases (the majority exhibiting anaplastic morphology) labeled with anti-ALK 11, and 5/28 CD30- cases were also ALK+ (3 T cells, 1 null cell, and 1 B cell). Sixteen of 17 B-cell pediatric LCLs were negative, as were 6/6 cases of Hodgkin's disease and 7/7 cases of adult B-cell lymphoma. In pediatric LCLs with adequate follow-up (24/44 ALK+), there was no significant association between ALK expression and two-year event-free survival, similar to the finding reported previously for CD30 expression in these cases. CONCLUSION: We conclude that the majority of pediatric CD30+ ALCLs show ALK overexpression, consistent with the presence of the t(2;5)-encoded NPM-ALK fusion, but that the clinical significance of this entity remains unproven.

Adult↗
PubMed1997

Dengue haemorrhagic fever outbreak in October-November 1996 in Ludhiana, Punjab, India.

An epidemic of haemorrhagic fever broke out in Ludhiana in October and November 1996. Persons of all age groups were affected with preponderance of young adults. Haemorrhagic manifestations like rashes, epistaxis, bleeding from the gums and haematemesis were observed. The cause of fever was investigated. Serum samples collected at random from 71 patients were tested by ELISA for dengue types 1-4 IgM antibodies. These were positive in 96.7 per cent of cases. Immunoblot testing for IgM and IgG for all serotypes of dengue virus were positive in 90.2 and 73.2 per cent of the serum samples respectively. The haemorrhagic fever was serologically proven to be due to dengue virus.

Adult↗
PubMed1996

DNA index of glial tumors in children. Correlation with tumor grade and prognosis.

BACKGROUND: Although DNA index (DI) has prognostic significance in a variety of pediatric malignancies, there are few data regarding its utility in central nervous system (CNS) tumors. We have previously shown that patients with hyperdiploid medulloblastoma have a significantly better survival than those whose tumors are diploid. Here, we examine the effect of DI and tumor grade on the progression free survival (PFS) of 57 patients with a variety of glial neoplasms. METHODS: DI was determined by flow cytometry on freshly obtained tumor tissue from the initial diagnostic specimens; a DI = 1.0 was defined as diploid (DIP), 1.0 < DI < 1.1 as near diploid (NDIP), and DI > 1.1 as hyperdiploid (HYP). Tumors were histologically graded according to the World Health Organization classification. RESULTS: There were 21 Grade I tumors, 20 Grade II, 8 Grade III, and 8 Grade IV. Among the 41 low grade tumors (Grade I-II), 39 were DIP or NDIP, and 2 were HYP. Among the 16 high grade tumors (Grade III-IV), 9 were DIP, 2 NDIP, and 5 HYP. The 4-year PFS of low grade tumors was 70% (standard deviation [SD] 12%) versus 8% (SD 7%) for high grade tumors. There was a significant correlation between low grade tumor histology and a DIP/NDIP DI (P = 0.015), and univariate analysis suggested improved PFS was associated with DIP/NDIP tumors (P = 0.05). However, DI did not remain a significant prognostic factor after being stratified by tumor grade (P = 0.87). CONCLUSIONS: Unlike medulloblastoma, DI is not an independent prognostic factor in pediatric glial tumors.

Adolescent↗
PubMed1996

Der(16)t(1;16)(q21;q13) in Wilms' tumor: friend or foe.

The der(16)t(1;16)(q21;q13) chromosomal abnormality has been reported rarely in Wilms' tumor. This abnormality has also been found in several other pediatric and adult neoplasms, and may imply a poor prognosis in at least some of these solid tumors. To investigate its clinical significance in Wilms' tumor, we examined the records of 65 consecutive children with Wilms' tumor whose tumor cells were successfully karyotyped. The t(1;16) was present in seven patients (10%) whose ages ranged from 2.5 to 4.7 years (median 3.5 years) at diagnosis. Six of the seven patients were female. All four stages of Wilms' tumor were represented (two patients had stage IV disease). No patient had bilateral disease. All tumors were of "favorable histology." All seven patients are alive and off therapy with a median follow-up of 3.2 years (range, 2 to 8.5 years). One patient with this abnormality developed brain metastases within 4 months of completion of therapy. Comparison of these patients with the remaining 58 Wilms' tumor patients revealed no significant differences with regard to disease stage, histology, survival, or relapse-free survival. Cytogenetic evidence of der(16)t(1;16)(q21;q13) in Wilms' tumor does not appear to portend an adverse clinical outcome, although only a larger study that includes molecular detection methods can provide more conclusive evidence.

Child↗
PubMed1996

Incidence and features of galactosaemia in Saudi Arabs.

Over a 12-year period (1983 to 1994), 11 cases of classical galactosaemia were identified in the Saudi Aramco Medical Services Organization (SAMSO). This yields an incidence of 12 cases per 100,000 live births in the Easter Province of Saudi Arabia. A higher proportion of infants presented with infections compared to reports in the literature. Screening for galactosaemia is highly recommended in this high-risk population.

Follow-Up Studies↗
PubMed1996

Changes in local microvascular permeability and in the effect of intervention with 21-aminosteroid (Tirilazad) in a new experimental model of focal cortical injury in the rat.

In a new, reproducible model of rodent focal cortical injury, we have shown that in the absence of early traumatic disruption of the microvasculature and subsequent hemorrhage, delayed perivascular protein leakage and polymorphonuclear leukocyte infiltration of the injured cortex occur. In this study we employed a sensitive quantitative autoradiographic technique (using alpha-aminoisobutyric acid as a tracer) to investigate the focal changes in microvascular permeability with time and to determine the effects of administration of a 21-aminosteroid (Tirilazad) initiated 5 min after induction of the cortical injury. At all time points studied, there was a significant increase in perilesional blood-brain barrier permeability in lesioned animals treated with vehicle, compared to shamoperated animals, with the most marked increase in blood-brain barrier permeability at 4 h postinjury (mean Ki +/- SE = 19.2 +/- 2.4/1000 min with cortical injury, 1.5 +/- 0.3/1000 min in shams) (mean volume +/- SE = 15.48 +/- 0.7 mm3). In animals with cortical injury treated with Tirilazad (10 mg/kg), there was a significant reduction in microvascular permeability at the site of injury (Ki = 3.1 +/- 0.5, p < 0.001) and a significant reduction in volume of increased permeability (4.86 +/- 0.7 mm3, p < 0.01) at 4 h postinjury. In this model of cortical injury, a delayed increase in microvascular permeability occurs, which is significantly attenuated by postinjury treatment with Tirilazad.

Analysis of Variance↗
PubMed1996

Complications and effectiveness of gastrostomy feedings in pediatric cancer patients.

PURPOSE: The objective of this study was to assess the complications and efficacy of gastrostomy (GT) feedings in pediatric cancer patients. PATIENTS AND METHODS: We reviewed the medical records of 33 pediatric cancer patients who received enteral nutrition via a GT. RESULTS: Median age was 9.4 years (range, 1-19.8 years), and 28 of the 33 patients had solid tumors. Seventeen patients had a significant weight loss (median, 8.5%) and therapy-related weight loss was anticipated in 16 patients. The GT device was placed an average of 5.5 months after diagnosis. Twenty-five patients were fed via a tube and eight via a button device. The tube was placed surgically in 21 cases (including all eight button types) and endoscopically in 12. Nutritional support lasted a median of 9.5 months. One or more complications occurred in 30 patients and were categorized as (a) insertion site reactions (inflammation, 23; infection/colonization, 14; exuberant granulation tissue, 6); (b) mechanical problems (leaking, 3; obstruction, 2; breakage, 1; accidental dislodgement, 2); (c) insertion site bleeding, 8; and (d) feeding intolerance, 12. Only one insertion site cellulitis progressed to a systemic infection. All eight patients with a button GT experienced insertion site complications, with local infection occurring significantly more often in patients with the button than in those with the tube GT. There were no significant associations between insertion technique and type of complication. Twenty-seven patients (82%) achieved or maintained ideal body weight with this intervention. CONCLUSIONS: GT feeding was associated with minor complications, but permitted effective nutritional support for pediatric cancer patients.

Adolescent↗
PubMed1996

A new experimental model of contusion in the rat. Histopathological analysis and temporal patterns of cerebral blood flow disturbances.

The authors have devised a simple reproducible rodent model of focal cortical injury that uses a mechanical suction force applied through intact dura. The time course and pattern of changes in neurons, glia, and microvasculature were investigated using this model. Early traumatic disruption of the blood-brain barrier and hemorrhage do not occur in this model; however, many of the features of human contusion seen with light and electron microscopy are closely reproduced. At the site of injury, early swelling and lucency of neural dendritic processes have been shown to precede an astrocyte response. In the absence of perivascular hemorrhage, delayed perivascular protein leakage and polymorphonuclear infiltration of the damaged cortex occurs, which is suggestive of an acute inflammatory response. Cerebral blood flow (CBF) has been measured using 14C-iodoantipyrine autoradiography at 30 minutes, 4 hours, and 24 hours after induction of negative-pressure injury in rats anesthetized with halothane and in time-matched sham-operated controls. A significant reduction in blood flow in the sensorimotor cortex at the site of the injury was present at 30 minutes, 4 hours, and 24 hours after induction of the lesion, compared to the contralateral cortex (superficial lamina, ipsilateral 50 +/- 7 ml/100 g/minute, contralateral 112 +/- 26 ml/100 g/minute). The CBF was significantly reduced at the ipsilateral entorhinal cortex at 30 minutes postinjury but no significant reduction was demonstrated at later time points. Although marked alterations in CBF occurred in this cortical injury model, the magnitude and duration of the reduction in CBF are not consistent with those necessary for production of ischemic cell damage. These data indicate that this model of cortical injury can be used to examine biomechanical aspects of contusion without domination by ischemic pathophysiology.

Animals↗
PubMed1996

New generations of implantable pacemaker defibrillators for ventricular and atrial tachyarrhythmias.

Implantable defibrillation devices have now been extensively applied to patients requiring cardioversion and defibrillation of sustained ventricular tachyarrhythmias. The focus of new developments is in improving technology, achieving physiologic operation in the atrium and ventricle, seeking new indications and identifying patient populations amenable to this therapy. Ventricular application technology is focusing on simplifying and improving robustness of lead systems yet seeking lower defibrillation thresholds. Dual chamber pacing, sensing and defibrillation are being developed. New populations for ventricular application include non-sustained ventricular tachycardia patients with coronary artery disease, dilated cardiomyopathy at risk for sudden death, long QT syndrome, pediatric patients with risk of sudden death and high risk postoperative coronary bypass patients. New applications include atrial defibrillation combined with atrial pacing in future devices. These devices are planned to have capabilities of ventricular defibrillation as a backup to address proarrhythmia concerns. It can be anticipated that implantable cardioverter defibrillator devices will be used for arrhythmia reversion in an expanding group of patients in the future.

Arrhythmias, Cardiac↗
PubMed1996

Antioxidants in hereditary pancreatitis.

OBJECTIVE: The cause of hereditary pancreatitis (HP) remains unknown. This study evaluated the hypothesis that patients with HP have genetically determined low concentrations of antioxidants that may predispose them to repetitive pancreatic injury. METHODS: This cross-sectional analysis compared antioxidant levels in four groups of patients. Group 1 included 14 related people with chronic pancreatitis. Group 2 (11 individuals) belonged to the same kindred but did not have pancreatitis. Group 3 was a group of 65 unrelated control subjects, and Group 4 consisted of seven unrelated children with chronic pancreatitis from other causes. The antioxidant levels analyzed included glutathione peroxidase, superoxide dismutase, glutathione reductase, glutathione transferase, selenium, and vitamin E. Amylase levels were measured in all patients in groups 1, 2, and 4. RESULTS: People with chronic pancreatitis or relatives of people with hereditary pancreatitis (groups 1, 2, and 4) had significantly lower mean glutathione peroxidase values than controls (group 3, p < 0.001). Group 1 also had significantly lower selenium levels than groups 2 and 3 (p < 0.001) but greater levels than group 4 (p = 0.029). Vitamin E levels were lower in group 1 than in groups 2 and 4. The superoxide dismutase levels were significantly different between each group (p < 0.001), and group 1 had the highest level. The glutathione reductase, glutathione transferase, and amylase levels did not differ significantly between groups. However, group 1 had a significantly higher glutathione transferase level than group 4. CONCLUSION: We identified antioxidant deficiencies in a group of patients with hereditary pancreatitis. Higher selenium and vitamin E levels may have prevented their relatives in group 2 from having pancreatitis secondary to oxidant injury, despite low glutathione peroxidase levels. Supplementation with selenium or vitamin E or both may be a beneficial therapeutic option in these patients to decrease the frequency of pancreatitis.

Adolescent↗
PubMed1995

Clinical efficacy and safety of atrial defibrillation using biphasic shocks and current nonthoracotomy endocardial lead configurations.

We undertook a prospective randomized clinical trial evaluating efficacy and safety of internal atrial defibrillation in patients with drug-refractory atrial fibrillation (AF). Consecutive patients with paroxysmal or chronic AF were randomly tested with 3 internal atrial defibrillation lead configurations and biphasic shocks. Patients with implanted cardiac pacemakers were tested with the right atrium (RA) and left pulmonary artery or coronary sinus (CS) configuration. Shocks were initially delivered without anesthesia to assess patient tolerance. The need for backup ventricular defibrillation and pacing support was evaluated. Eighteen patients with (n = 15) or without (n = 3) structural heart disease, mean left ventricular ejection fraction 36 +/- 14%, and mean left atrial diameter 4.5 +/- 0.6 cm were studied. The mean defibrillation threshold in the best randomized lead configuration was 9.9 +/- 7.7 J. Mean defibrillation threshold for the right ventricle (RV) and superior vena cava configuration was 13.3 +/- 5 J, which was significantly lower than the RA and axilla configuration (20.1 +/- 7.4 J, p < 0.04) but not the RV to RA configuration (16.5 +/- 11 J, p > 0.2). The mean defibrillation threshold using the RA-left pulmonary artery/CS configuration was 8.9 +/- 9 J (p > 0.2 vs RV-superior vena cava). There was a bimodal distribution of defibrillation thresholds. Low atrial defibrillation thresholds correlated with absence of heart disease, higher ejection fraction, and smaller left ventricular end-diastolic diameter. Shocks were hemodynamically well tolerated, but 2 of 18 patients (11%) had nonsustained ventricular tachycardia after shock delivery. Six of 18 patients (33%) had postshock bradyarrhythmias. Fourteen of 16 patients perceived shocks > or = 3 J as intolerable.(ABSTRACT TRUNCATED AT 250 WORDS) [corrected]

Adult↗
PubMed1995

Efficacy and safety of radiofrequency catheter ablation of left-sided accessory pathways through the coronary sinus.

Radiofrequency catheter ablation of left-sided accessory pathways (APs) with the use of an endocardial technique carries all potential risks of left heart catheterization. We analyzed the determinants of success, efficacy, and safety of radiofrequency catheter ablation from the coronary sinus (CS), as a potential alternative to the endocardial technique in these patients. Thirteen patients (mean age 40 +/- 20 years) with 15 left-sided APs and a history of symptomatic supraventricular tachycardia were included in the study. Nine APs were localized in the left posteroseptal region, and the remaining 6 in the left free wall. Ablation from CS was attempted in 12 patients with 14 APs. In 1 patient ablation within the CS was not deemed safe because of a small venous lumen. All 14 APs were successfully ablated using either CS ablation alone or combined with the endocardial technique. Efficacy of the CS ablation as a primary technique was 56% (5 of 9 APs). In 5 additional APs, ablation in the CS eliminated pathway conduction after failed endocardial attempts. CS ablation either as a primary or a secondary technique eliminated conduction in 10 of 14 APs (71.4%) (group 1). In the remaining 4 APs (group 2), the primary CS attempt was unsuccessful and APs were ablated with a subsequent endocardial approach. Determinants of success for the CS method were local AP to atrial and/or ventricular electrogram amplitude ratios > or = 1 (p < 0.05). The success rate of CS ablation was 83% in the left posteroseptal APs adjoining the branching point of the middle cardiac vein or a CS anomaly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Pharmacokinetics and pharmacodynamics of 21-day continuous oral etoposide in pediatric patients with solid tumors.

PURPOSE: The objectives of this study were to determine etoposide pharmacokinetics during continuous low-dose oral administration to children with solid tumors and to evaluate the relationships between parameters of etoposide systemic exposure and toxicity. PATIENTS AND METHODS: In this phase I study, children were administered oral etoposide (25 to 75 mg/m2/day) for 21 days as a diluted solution of the intravenous preparation, divided into three equal daily doses. Plasma pharmacokinetics were studied on day 1 of therapy in 18 children and again on day 21 in 14 of these children. Etoposide plasma concentration-time data were fitted to a first-order absorption, two-compartment model with use of bayesian estimation. Pharmacokinetic parameter estimates from day 1 were used to estimate steady-state etoposide systemic exposure in all children. Stepwise multivariate regression was used in an exploratory manner to determine patient, laboratory, or pharmacokinetic predictors of toxicity. RESULTS: Although there was substantial intrapatient variability, there was no difference in the area under the concentration-time curve [AUC(0-8hr)] measured at day 21 compared with the steady-state AUC(0-8hr) estimated from day 1 pharmacokinetic parameters (p = 0.64). Degree of neutropenia was best predicted by the estimated duration that steady-state plasma etoposide concentrations were maintained above 1 microgram/ml (t > 1 microgram/ml) rather than peak plasma concentrations, AUC(0-8hr), dosage, or other patient characteristics. Assuming a bioavailability of the oral solution of approximately 50%, the median etoposide systemic clearance was 21.4 ml/min/m2, a value similar to clearance estimates after intravenous etoposide in pediatric populations. CONCLUSION: We conclude that a parameter reflective of etoposide systemic exposure (t > 1 microgram/ml) correlates more strongly with neutropenia than does dosage or other patient characteristics.

Administration, Oral↗
PubMed1995

Clinicopathological correlates of CD56 expression in multiple myeloma: a unique entity?

Prior studies have suggested that loss of plasma cell CD56 expression in multiple myeloma defines a unique patient subset and that CD56 expression reliably discriminates between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM). We conducted a study of 68 untreated patients with MM from a single institution to define the clinicopathological correlates of CD56 expression. We find CD56 expression in 55% of MM. Lack of CD56 expression does not define a unique clinicopathological or prognostic entity in MM. Strong CD56 expression can also be found in MGUS and does not help to distinguish from MM.

Antigens, CD↗
PubMed1995

Effect of intravenous gammaglobulin (IVIG) on the platelet count in patients with Wiskott-Aldrich syndrome.

The ability of IVIG to increase platelet counts in patients with idiopathic thrombocytopenic purpura suggests its potential usefulness in other disease states characterized by low platelet counts. This possibility was evaluated in nine patients with the Wiskott-Aldrich syndrome (WAS) who received IVIG, at a dose of 400 mg/kg every 4 weeks. The mean platelet count prior to institution of IVIG was 32,000/cumm (range 2,400 to 98,000). Following administration of IVIG, the platelet count ranged between 5,000 and 85,000/cumm. There were no immediate increases in platelet counts after IVIG infusion in any patient who had serial platelet counts. During treatment, patients were not given any routine platelet transfusions for low platelet counts. However, while on IVIG, two patients showed a good response to platelet transfusion prior to surgical procedures. In conclusion, chronic IVIG therapy does not appear to affect platelet counts in patients with the Wiskott-Aldrich syndrome.

Child↗
PubMed1995

LMP-1 activates NF-kappa B by targeting the inhibitory molecule I kappa B alpha.

LMP-1, an Epstein-Barr virus membrane protein expressed during latent infection, has oncogenic properties, as judged from its ability to transform B lymphocytes and rodent fibroblasts. LMP-1 induces the expression of bcl2, an oncogene which protects cells from apoptosis, as well as of genes encoding other proteins involved in cell regulation and growth control. The mechanisms by which LMP-1 upregulates these proteins is unknown, but it is plausible that LMP-1 modifies signal transduction pathways that result in the activation of one or more transcription factors that ultimately regulate transcription of oncogenic genes. NF-kappa B, a transcription factor controlling the expression of genes involved in cell activation and growth control, has been shown to be activated by LMP-1. The mechanism(s) regulating this activation remains unknown. Our data indicate that increased NF-kappa B DNA binding and functional activity are present in B-lymphoid cells stably or transiently expressing LMP-1. I kappa B alpha is selectively modified in LMP-1-expressing B cells. A phosphorylated form of I kappa B alpha and increased protein turnover-degradation correlate with increased NF-kappa B nuclear translocation. This results in increased transcription of NF-kappa B-dependent-genes, including those encoding p105 and I kappa B alpha (MAD3). These results indicate that LMP-1 activates NF-kappa B in B-cell lines by targeting I kappa B alpha. Identification of the pathways activated by LMP-1 to result in posttranslational modifications of I kappa B alpha will aid in determining the role of this virus-host cell protein interaction in Epstein-Barr virus-mediated oncogenesis.

B-Lymphocytes↗