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Biomedical subjects

A Mathur

Publications and source records attributed to A Mathur.

At least 73 records · Page 4Linked to original sources
PubMed1999

Repair of total anomalous pulmonary venous connection in infancy: experience from a developing country.

BACKGROUND: Corrective surgery for total anomalous pulmonary venous connection in infancy still carries high morbidity and mortality rates in developing countries. The present study evaluates the factors responsible for it. METHODS: Seventy-three infants were operated on for total anomalous pulmonary venous connection from January 1987 through October 1997. Age ranged from 5 days to 12 months (mean, 3.9+/-0.24 months), with 10 (13.7%) patients younger than 1 month old. Patient weight varied from 2.0 to 5.2 kg (mean, 3.7+/-0.27 kg). Most (90.5%) patients were small for their ages (< 50th percentile). Anomalous connection was supracardiac in 42 (57.5%), cardiac in 18 (24.7%), infracardiac in 4 (5.5%), and mixed in 9 (12.3%) patients. Thirty-five patients had obstructed drainage. Preoperatively, 30 patients received antibiotic therapy for respiratory tract infection, 3 patients had balloon atrial septostomy, and 4 patients required mechanical ventilation. Fifteen patients (20.5%) were operated on as an emergency procedure. For supracardiac and infracardiac connections, a posterior approach was used for anastomosis. In cardiac type, coronary sinus was unroofed and the resultant defect along with atrial septal defect was closed with a single patch. RESULTS: The operative mortality rate was 23.3% (17 of 73). Pulmonary hypertensive crisis was the cause of death in 10 patients. Emergency operation and weight less than the 25th percentile were the important risk factors for operative mortality. Young age (< 1 month) and type of drainage did not affect the mortality. Follow-up ranged from 1 to 108 months (mean, 56.4+/-26.0 months). There were two late deaths. The actuarial survival (Kaplan Meier) at 9 years was 72.87%+/-5.39%. CONCLUSION: Failure of early recognition, and thus delayed referral, accounted for onset of cardiac cachexia, respiratory tract infection, and severe pulmonary hypertension, which had a major effect on unfavorable outcome.

Body Weight↗
PubMed1999

Pulmonary autograft: should it be used in young patients with rheumatic disease?

BACKGROUND: Although pulmonary autograft is being increasingly used to replace the diseased aortic valve with excellent long-term results, its use in the population with rheumatic disease still needs careful evaluation. PATIENTS AND METHODS: From October 1993 through March 1998, 102 patients underwent aortic valve replacement with a pulmonary autograft (Ross procedure). The mean age was 27.9 +/- 4.2 years (range, 0.8-56 years). The cause was rheumatic disease in 75 patients (73%), bicuspid aortic valve in 26 patients (26%), and myxomatous aortoarteritis in 1 patient (1%). The root replacement technique was used in all. In addition, 31 patients had 33 associated procedures: mitral valve repair (n = 15 patients), open mitral commissurotomy (n = 15 patients), tricuspid repair (n = 2 patients), and homograft mitral valve replacement (n = 1 patient). RESULTS: Operative mortality was 6.9% (7 patients). Late mortality was 7.8% (8 patients). Follow-up ranged from 1 to 60 months (mean, 25.3 +/- 15.4 months) and was 98% complete. Two patients required reoperation for failed mitral valve repair, and 2 other patients underwent reoperation for failure of both the autograft and mitral valve repair. Echocardiographic assessment showed moderate to severe aortic regurgitation in 13 patients, along with thickening of the autograft. All of these patients had rheumatic disease and were young (<30 years). Ten of these patients had undergone associated mitral valve procedure. Morphologic and histopathologic examination of explanted autografts showed features compatible with rheumatic valvulitis. CONCLUSION: Pulmonary autograft is susceptible to rheumatic involvement. Young age (<30 years) and associated mitral valve disease are significant risk factors for autograft failure in patients with rheumatic disease. Use of pulmonary autograft in this subgroup of patients requires a cautious approach.

Adolescent↗
PubMed1999

Use of reverse geometry rigid gas permeable contact lenses in the management of the postradial keratotomy patient: review and case report.

Radial keratotomy (RK) is a well-known procedure for reducing myopia. However, the complications associated with the procedure and the development of newer technologies, such as photorefractive keratectomy and laser-assisted in situ keratomileusis, has resulted in the technique of RK falling out of favor. A number of patients who received RK during the 1980s are now experiencing a shift in their prescription and are presenting to primary care practitioners for contact lens fitting. These patients pose a significant challenge to the contact lens practitioner, and novel methods frequently are required to fit corneas that exhibit such abnormal topography. This article reviews the potential problems associated with fitting patients who have received RK and describes a case in which a novel lens design was used to achieve a successful lens fit.

Journal Article↗
PubMed1999

Degradation of Japanese encephalitis virus by neutrophils.

The ability of neutrophils to degrade the phagocytosed Japanese encephalitis (JE) virion, via triggering of the respiratory burst and generation of toxic radicals has been investigated. JEV or JEV-induced macrophage derived factor (MDF) induces increase in intracellular oxidative signals with generation of superoxide anion (O2-), via activation of cytosolic NADPH and subsequent formation of hydrogen peroxide, with maximum activity on day 7 post infection. The response was sensitive to anti-MDF antibody treatment. Further, the study revealed rapid degradation of phagocytosed JE viral protein and nucleic acid. The viral protein degradation was partially dependent on the generation of toxic oxygen species as it could be abrogated by pretreatment of the cells with staurosporine.

Animals↗
PubMed1999

Endogenous mediators and thrombophilia.

Platelets are one of the most important components of primary haemostasis. Since they lack a nucleus, their functional characteristics are determined at the time of production. The role of platelets in thrombosis is further modified by the interaction with vascular mediators that are endogenously produced in response to a variety of stimuli. This chapter discusses the factors that influence platelet production, the interaction with endogenous mediators, and the potential therapeutic benefits achieved by modifying this interaction in the clinical setting.

Animals↗
PubMed1999

Extracranial vertebral artery stent placement: in-hospital and follow-up results.

OBJECT: The authors summarize their experience with stent deployment in the treatment of vertebrobasilar artery (VBA) insufficiency. This is an underdiagnosed condition, and the incidence of significant vertebral artery (VA) stenosis has been underappreciated. Medical therapy has been the mainstay of treatment because of the high rate of morbidity associated with surgical correction of VA stenosis. Recently, some authors have reported acceptable results with the use of percutaneous transluminal angioplasty, but this technique has significant weaknesses such as elastic recoil and problems in achieving safe treatment of dissections. METHODS: The authors investigated the feasibility, safety, and outcome of VA stent placement in 50 patients in whom 55 vessels were treated using stents. Technical success was achieved in 54 (98%) of 55 vessels, with no procedure-related complications. However, one patient (2%) died of nonneurological causes, and one (2%) suffered a stroke that occurred within the 30-day postprocedural period and was related to a complicated coronary intervention. Clinical follow-up review performed at a mean of 25 +/- 10 months revealed two patients (4%) with recurrence of VBA symptoms. Six-month angiographic follow up was completed in 90% of eligible patients, with a 10% incidence of restenosis as defined by greater than 50% luminal narrowing. CONCLUSIONS: Vertebral artery stent placement is feasible in patients who have significant VA stenosis, with predictably good angiographically demonstrated and clinical results. The 6-month angiographically confirmed restenosis rate appears to be low, as does the clinical recurrence rate. This technique solves the problems of elastic recoil and the treatment of angioplasty-induced dissections. Further prospective comparison with medical preventive strategies is warranted.

Adult↗
PubMed1999

Radiation dosimetry of a 99mTc-labeled IgM murine antibody to CD15 antigens on human granulocytes.

UNLABELLED: 99mTc-labeled anti-stage specific embryonic antigen-1 (anti-SSEA-1) is an injectable IgM antibody derived from mice. It binds to CD15 antigens on some granulocytic subpopulations of human white blood cells in vivo after systemic administration. The purpose of this study was to measure biodistribution of 99mTc-labeled anti-SSEA-1 and perform radiation dosimetry in 10 healthy human volunteers. METHODS: Transmission scans and whole-body images were acquired sequentially on a dual-head camera for 32 h after the intravenous administration of about 370 MBq (10.0 mCi) of the radiopharmaceutical. Renal excretion fractions were measured from 10 to 14 discrete urine specimens voided over 27.9 +/- 2.0 h. Multiexponential functions were fit iteratively to the time-activity curves for 17 regions of interest using a nonlinear least squares regression algorithm. The curves were integrated numerically to yield source organ residence times. Gender-specific radiation doses were then estimated individually for each subject, using the MIRD technique, before any results were averaged. RESULTS: Quantification showed that the kidneys excreted 39.5% +/- 6.5% of the administered dose during the first 24 h after administration. Image analysis showed that 10%-14% of the radioactivity went to the spleen, while more than 40% went to the liver. Residence times were longest in the liver (3.37 h), followed by the bone marrow (1.09 h), kidneys (0.84 h) and the spleen (0.65 h). The dose-limiting organ in both men and women was the spleen, which received an average of 0.062 mGy/MBq (0.23 rad/mCi, range 0.08-0.30 rad/mCi), followed by the kidneys (0.051 mGy/MBq), liver (0.048 mGy/MBq) and urinary bladder (0.032 mGy/MBq). The effective dose equivalent was 0.018 mSv/MBq (0.068 rem/mCi). CONCLUSION: The findings suggest that the radiation dosimetry profile for this new infection imaging agent is highly favorable.

Adult↗
PubMed1999

Design and characterization of orally active Arg-Gly-Asp peptidomimetic vitronectin receptor antagonist SB 265123 for prevention of bone loss in osteoporosis.

The Arg-Gly-Asp (RGD)-binding integrin alpha(V)beta(3) is highly expressed on osteoclasts and has been proposed to mediate cell-matrix adhesion required for osteoclast-mediated bone resorption. Antagonism of this receptor should prevent stable osteoclast adhesion and thereby inhibit bone resorption. We have generated an orally bioavailable, nonpeptide RGD mimetic alpha(v)beta(3) antagonist, SB 265123, which prevents bone loss in vivo when dosed by oral administration. SB 265123 binds alpha(v)beta(3) and the closely related integrin alpha(v)beta(5) with high affinity (K(i) = 3.5 and 1.3 nM, respectively), but binds only weakly to the related RGD-binding integrins alpha(IIb)beta(3) (K(i) >1 microM) and alpha(5)beta(1) (K(i) >1 microM). The compound inhibits alpha(v)beta(3)-mediated cell adhesion with an IC(50) = 60 nM and more importantly, inhibits human osteoclast-mediated bone resorption in vitro with an IC(50) = 48 nM. In vivo, SB 265123 completely blocks bone resorption in a thyroparathyroidectomized rat model of acute bone resorption when dosed at 2.5 mg/kg/h by continuous i.v. infusion. When dosed orally with 3 to 30 mg/kg b.i.d. , in the ovariectomy-induced rat model of osteoporosis, SB 265123 prevents bone resorption in a dose-dependent fashion. This is the first report of an orally active alpha(v)beta(3) antagonist that is effective at inhibiting bone resorption when dosed in a pharmaceutically acceptable fashion. Such a molecule may provide a novel therapeutic agent for the treatment of postmenopausal osteoporosis.

Acetates↗
PubMed1999

Effects of age on dopamine transporters in healthy humans.

UNLABELLED: 99mTc-TRODAT-1 is a new radiopharmaceutical that selectively binds the dopamine transporters. This study characterized the effects of aging on its regional cerebral distribution in healthy human volunteers. METHODS: The sample consisted of 27 men and 28 women with a mean age of 41.1 +/- 17.1 y (age range 18.7-73.8 y). Dynamic SPECT scans of the brain were obtained with a standardized acquisition and processing protocol on a triple-head camera. Mean counts per pixel were measured in multiple regions of interest within each basal ganglia. Regression analyses were used to relate the specific uptake values at 3-4 h after administration to age. Both linear and nonlinear models of aging were tested. RESULTS: The relative concentration of radioactivity in most subregions of the basal ganglia decreased significantly with age (all P values < 0.0001). Nonlinear models of aging fit the data significantly better than a straight line. The rate of decline was significantly faster in young adults than in older volunteers (P < 0.001). The break-point age at which the rate of change slowed down and became more stable was 36 y old for the whole striatum and ranged from 32 to 44 y old depending on subregion. CONCLUSION: The effects of aging on central nervous system dopamine transporters do not appear to be linear. Most effects seem to occur during young adulthood before people reach their 40s. The distribution then appears to remain relatively stable until late in life. The findings suggest that the adult life cycle is better characterized as a series of phases than as a continuum.

Adult↗
PubMed1999

Effects of a 99mTc-labeled murine immunoglobulin M antibody to CD15 antigens on human granulocyte membranes in healthy volunteers.

UNLABELLED: An injectible, 99mTc-labeled, murine immunoglobulin M antibody to stage-specific embryonic antigen-1 has been developed that can localize infections by binding to CD15 glycoproteins expressed on the cell membranes of human granulocytes in vivo after systemic administration. The purpose of this study was to measure its clinical effects on healthy people. METHODS: Multiple blood samples were aspirated before and after the intravenous administration of about 125 microg antibody labeled with approximately 370 MBq (10.0 mCi) 99mTc in 10 healthy human volunteers. Complete blood cell counts were performed at each time point. Whole-body scans were acquired contemporaneously with a dual-head gamma camera. The fraction of the administered dose at each time point was quantified in 18 regions of interest. Statistical analyses included paired t tests. RESULTS: Administration was associated with a transient decrease in the concentration of red and white blood cells in the whole blood. The effect always began within 3 min of administration. Its nadir was always reached 15-20 min after administration. There was full recovery with mild overcompensation in about an hour. The hematocrit dropped by a mean of 3.8% (P<0.002), whereas the total white blood cell count fell 44.0%+/-3.1% (P<0.001). The effect was most pronounced on the number of circulating granulocytes, which fell from 5.7+/-2.1 to 3.2+/-1.3x10(3)/microL blood. The drop paralleled a decrease in the percentage of whole blood radioactivity bound to the white blood cell membranes, which peaked at 50.4%+/-7.6% at 3 min after injection and then fell to 26.1%+/-9.3% over the next 30+/-13.4 min before recovering to 40.7%+/-8.2% at 2 h. Image analysis showed that the effect was temporally associated with an increase in the amount of radioactivity within the liver and the spleen. Recovery was associated with a decrease in hepatosplenic radioactivity. No evidence of cell destruction or agglutination could be detected. CONCLUSION: This study confirmed that administration of this radiolabeled antibody is associated with a transient decrease in the number of circulating granulocytes. However, there also seems to be a secondary hemodilutionlike effect on all blood components that has not been reported previously. The effect appears to be clinically silent and very short-lived.

Adult↗
PubMed1999

A clinical study of the patients with dengue hemorrhagic fever during the epidemic of 1996 at Lucknow, India.

This paper describes the clinical findings in 206 patients with dengue fever (DF) or with dengue hemorrhagic fever (DHF) during the epidemic of 1996 at Lucknow. The age group affected most was 11 to 30 years and 21% of the patients were less than 10 years old. The male:female ratio was 1.9:1. The onset was abrupt in all the patients, severe frontal headache was observed in 97%, myalgia in 90%, skin rash in 40%, vomiting in 29% and arthralgia in knee and hip joints in 9%. Anuria was seen in two patients. Lymphadenopathy was noted in 14%, hepatomegaly in 4%, being associated with mild jaundice in one patient, and splenomegaly in 2% of the patients. Involvement of the heart and lungs was seen in one patient each and no case with encephalitis was recorded. Hemorrhages from various sites were observed in 54% patients and 17 patients had profound shock. The commonest bleeding site was gums. Profound shock was preceded by various warning signs, the commonest being sudden hypotension. Among the patients with profound shock the mortality was 47% while the overall fatality rate was 3.8%. A number of the risk factors existed for a long time in this part of the world, but what precipitated the present epidemic at this time, is not known.

Adolescent↗
PubMed1998

Biphenylsulfonamide endothelin antagonists: structure-activity relationships of a series of mono- and disubstituted analogues and pharmacology of the orally active endothelin antagonist 2'-amino-N- (3,4-dimethyl-5-isoxazolyl)-4'-(2-methylpropyl)[1, 1'-biphenyl]-2-sulfonamide (BMS-187308).

Substitution at the ortho position of N-(3,4-dimethyl-5-isoxazolyl) benzenesulfonamide led to the identification of the biphenylsulfonamides as a novel series of endothelin-A (ETA) selective antagonists. Appropriate substitutions on the pendant phenyl ring led to improved binding as well as functional activity. A hydrophobic group such as isobutyl or isopropoxyl was found to be optimal at the 4'-position. Introduction of an amino group at the 2'-position also led to improved analogues. Combination of the optimal 4'-isobutyl substituent with the 2'-amino function afforded an analogue (20, BMS-187308) with improved ETA binding affinity and functional activity. Compound 20 also has good oral activity in inhibiting the pressor effect caused by an ET-1 infusion in rats. Doses of 10 and 30 micromol/kg iv 20 attenuated the pressor responses due to the administration of exogenous ET-1 to conscious monkeys, indicating that the compound inhibits the in vivo activity of endothelin-1 in nonhuman primates.

Administration, Oral↗
PubMed1998

Elective carotid artery stenting in the presence of contralateral occlusion.

Significant carotid stenosis in the presence of an occluded contralateral artery has a poor prognosis with medical therapy alone. Carotid cross clamping during surgical endarterectomy results in critical flow reductions in patients with inadequate collateral flow, and represents a significant risk for procedural strokes. Carotid stenting is being evaluated as an alternative to endarterectomy. We describe the immediate and late outcome of a series of 26 patients treated with carotid stenting in the presence of contralateral carotid occlusion. The mean age of the patients in this group was 65 +/- 9 years, 23 (89%) were men and 10 (39%) were symptomatic from the vessel treated. The procedural success of carotid stenting in this group of patients was 96%. The mean diameter stenosis was reduced from 76 +/- 15% to 2.8 +/- 5%. There was 1 (3.8%) minor stroke in a patient who developed air embolism during baseline angiography. At late follow-up there was no neurologic event in any patient at a mean of 16 +/- 9.5 months after the procedure. Thus, carotid stenting of lesions with contralateral occlusion can be performed successfully with a low incidence of procedural neurologic complications and late stroke.

Aged↗
PubMed1998

Predictors of stroke complicating carotid artery stenting.

BACKGROUND: The evolving technique of carotid stenting is being evaluated as an alternative to endarterectomy. Identification of the factors that predispose a patient to neurological complications would facilitate further refinement of the technique and optimize patient selection. METHODS AND RESULTS: We analyzed the impact of various clinical, morphological, and procedural determinants on the development of procedural strokes in 231 patients who underwent elective (primary) stenting of 271 extracranial carotid arteries. The mean age of the patients was 68.7+/-10 years, 165 (71%) were males, and 139 (60%) had symptoms attributed to the lesion treated. This series represented a high-risk subset with 164 patients (71%) having significant coronary artery disease, 91 (39%) having bilateral disease, and 28 (12%) having contralateral carotid occlusion. Of the treated vessels, 59 (22%) had prior carotid endarterectomy, 66 (24%) had ulcerated plaques, and 87 (32%) had calcified lesions. Only 37 treated vessels (14%) would have been eligible for inclusion in the North American Symptomatic Carotid Endarterectomy Trial (NASCET). There were 17 (6.2%) minor and 2 (0.7%) major strokes during and within 30 days of the procedure. NASCET-eligible patients had a low (2.7%) risk of procedural strokes after carotid stenting. The results of multivariate analysis revealed advanced age (P=.006) and presence of long or multiple stenoses (P=.006) as independent predictors of procedural strokes. CONCLUSIONS: During this procedural developmental phase of carotid stenting, neurological complications were highly dependent on patient selection. Advanced age and long or multiple stenoses were independent predictors of procedural stroke.

Aged↗
PubMed1998

Elevated levels of IL-8 in dengue hemorrhagic fever.

Dengue virus causes dengue fever, a mild febrile illness, and at times dengue hemorrhagic fever (DHF), a severe illness the pathogenesis of which is not fully understood. Given the crucial roles played by interleukin-8 (IL-8) as a chemoattractant cytokine and in inflammatory processes, levels of circulating IL-8 in the sera and IL-8 mRNA in the peripheral blood mononuclear cells (PBMC) were measured in 99 patients of a recent dengue epidemic that occurred in India in 1996 and in 21 normal healthy controls. Twenty-six of the patients had dengue fever (DF) and the remaining 73 were diagnosed as having different grades of DHF. All the control normal sera were negative for IL-8, so were their PBMC for IL-8 mRNA. Increased levels of IL-8 in the sera and IL-8 mRNA in their PBMC were observed in patients with severe illness of DHF grades III and IV. Only two out of 26 patients of DF and one out of 10 DHF grade I patient were positive for IL-8 and all three deteriorated to DHF grade IV within 24 hr. All six patients of DHF grade IV who died had higher serum level of IL-8 above 200 pg/ml, the highest being 5,568 pg/ml in one patient; the presence of mRNA for IL-8 was very high in all patients. A striking correlation was observed between increased levels of IL-8 and severe DHF, with greater levels in patients with increased grade of the disease and death. These results suggest that IL-8 may have an important role and may be an indicator of increasing severity of the disease and death.

Adolescent↗
PubMed1998

Angioplasty of totally occluded old vein grafts with new interventional techniques: a long-term follow-up study.

The long-term patency of saphenous vein graft (SVG) lesions after intervention has been shown to be improved with new interventional techniques such as stents. Long-term outcome of patients undergoing successful angioplasty of totally occluded old SVGs with new devices is unknown. From July 1994 to June 1996, 19 patients with totally occluded old SVGs had successful angioplasty with new interventional techniques. Mean SVG age was 123 +/- 8 mo. Thrombolysis in myocardial infarction trial (TIMI) flow was 0 in all target lesions. TIMI 2 or 3 flow was restored after angioplasty in all patients. Intracoronary urokinase, transluminal extractional atherectomy, and stenting were used in 14, 12, and 6 patients, respectively. There was one in-hospital death due to ongoing myocardial infarction, no recurrent infarction, and no repeat angioplasty or bypass surgery in the hospital. At follow-up of 21 +/- 1 mo, there was one sudden death and one myocardial infarction. Five patients had repeat coronary bypass surgery, and 4 had repeat angioplasty. Thirteen patients remained asymptomatic, and 4 had angina. The long-term outcome of patients who had successful reopening of occluded old SVGs is encouraging in this small sample.

Aged↗