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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 127 records · Page 7Linked to original sources
PubMed2001

Leukocyte-reduced red blood cell transfusions in patients with anemia and human immunodeficiency virus infection: the Viral Activation Transfusion Study: a randomized controlled trial.

CONTEXT: Allogeneic blood transfusions have immunomodulatory effects and have been associated with activation of human immunodeficiency virus (HIV) and cytomegalovirus (CMV) in vitro and of HIV in small pilot studies. Retrospective studies suggest that transfusions adversely affect the clinical course of HIV. Data in selected non-HIV-infected patients requiring blood transfusion have suggested clinical benefit with leukocyte-reduced red blood cells (RBCs). OBJECTIVE: To compare the effects of leukoreduced and unmodified RBC transfusions on survival, complications of acquired immunodeficiency syndrome, and relevant laboratory markers in HIV-infected patients. DESIGN AND SETTING: Double-blind randomized controlled trial conducted in 11 US academic medical centers from July 1995 through June 1999, with a median follow-up of 12 months (24 months in survivors). PATIENTS: A total of 531 persons infected with HIV and CMV, aged 14 years or older, who required transfusions for anemia; 259 received leukoreduced transfusions and 262 received unmodified transfusions (10 did not receive the planned transfusion). MAIN OUTCOME MEASURES: Survival and change in plasma HIV RNA level 7 days after transfusion, compared by type of transfusion. RESULTS: At entry, the groups were similar in demographic, clinical, and relevant laboratory characteristics. A total of 3864 RBC units were transfused. Two hundred eighty-nine deaths occurred (151 with leukoreduced transfusion; 138 with unmodified transfusion); median survival was 13.0 and 20.5 months, respectively (relative hazard [RH], 1.20; 95% confidence interval [CI], 0.95-1.51; log-rank P =.12). Analyses adjusted for prognostic factors suggested possible worse survival with leukoreduction (RH, 1.35; 95% CI, 1.06-1.72). There was no difference in time to new opportunistic event/death or frequency of transfusion reactions. No changes in plasma HIV RNA level were seen in either group at days 7, 14, 21, or 28, even in patients not taking antiretroviral drugs. There were no differences in trends between groups in CMV DNA, CD4 cell counts, activated (CD38% or human leukocyte antigen-DR) CD8 cell counts, or plasma cytokine levels. CONCLUSIONS: We found no evidence of HIV, CMV, or cytokine activation following blood transfusion in patients with advanced HIV infection. Leukoreduction provided no clinical benefit in these patients. These data demonstrate the importance of conducting controlled studies of effects of leukoreduction in different patient populations, since smaller studies in other patient populations have suggested leukoreduction may be beneficial.

AIDS-Related Opportunistic Infections↗
PubMed2001

Soluble E-selectin induces monocyte chemotaxis through Src family tyrosine kinases.

Cellular adhesion molecules such as E-selectin function to recruit leukocytes into the inflammatory lesions of diseases such as rheumatoid arthritis (RA) and atherosclerosis. Monocytes are the key components of the cellular infiltrates present in these disorders. We hypothesized that soluble E-selectin (sE-selectin) might mediate the chemotaxis of monocytes. In this report, we show that sE-selectin induced normal human peripheral blood monocyte migration in the nanomolar range in a concentration-dependent manner. Neutralization studies using RA human joint synovial fluids and anti-E-selectin antibody showed a mean 31% reduction in RA synovial fluid-mediated monocyte chemotaxis (p < 0.05), indicating that sE-selectin is a major monocyte recruiter in RA. Next, we investigated the role of tyrosine phosphorylation pathways in sE-selectin-induced monocyte chemotaxis. Human peripheral blood monocytes stimulated with sE-selectin showed a time-dependent increase in the tyrosine phosphorylation of a broad range of cellular proteins, predominantly in the molecular size range of Src family kinases (50-60 kDa) and mitogen-activated protein kinases (MAPKs). Western blot analysis of Src family kinases showed a time-dependent increase in Src, Hck, and Lyn phosphorylation. The pretreatment of monocytes with the Src inhibitor AG1879: 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2) prior to stimulation with sE-selectin markedly inhibited Hck and Lyn phosphorylation, whereas the phosphorylation of Src was partially inhibited. In addition, the sE-selectin stimulation of monocytes resulted in the increased phosphorylation of extracellular signal-related kinase (ERK1/2) and p38 MAPK. The pretreatment of monocytes with PP2 showed 89 and 83% inhibition of ERK1/2 and p38 MAPK phosphorylation, respectively. sE-selectin also showed a time-dependent activation of Ras kinase. Furthermore, the pretreatment of monocytes with PP2 completely inhibited sE-selectin-mediated monocyte chemotaxis. Taken together, our data demonstrate a novel function for sE-selectin as a monocyte chemotactic agent and suggest that sE-selectin might be mediating its biological functions through the Src-MAPK pathway.

Chemotaxis, Leukocyte↗
PubMed2001

Structure of a serine protease proteinase K from Tritirachium album limber at 0.98 A resolution.

X-ray diffraction data at atomic resolution to 0.98 A with 136 380 observed unique reflections were collected using a high quality proteinase K crystals grown under microgravity conditions and cryocooled. The structure has been refined anisotropically with REFMAC and SHELX-97 with R-factors of 11.4 and 12.8%, and R(free)-factors of 12.4 and 13.5%, respectively. The refined model coordinates have an overall rms shifts of 0.23 A relative to the same structure determined at room temperature at 1.5 A resolution. Several regions of the main chain and the side chains, which were not observed earlier have been seen more clearly. For example, amino acid 207, which was reported earlier as Ser has been clearly identified as Asp. Furthermore, side-chain disorders of 8 of 279 residues in the polypeptide have been identified. Hydrogen atoms appear as significant peaks in the F(o) - F(c) difference electron density map accounting for an estimated 46% of all hydrogen atoms at 2sigma level. Furthermore, the carbon, nitrogen, and oxygen atoms can be differentiated clearly in the electron density maps. Hydrogen bonds are clearly identified in the serine protease catalytic triad (Ser-His-Asp). Furthermore, electron density is observed for an unusual, short hydrogen bond between aspartic acid and histidine in the catalytic triad. The short hydrogen bond, designated "catalytic hydrogen bond", occurs as part of an elaborate hydrogen bond network, involving Asp of the catalytic triad. Though unusual, these features seem to be conserved in other serine proteases. Finally there are clear electron density peaks for the hydrogen atoms associated with the Ogamma of Ser 224 and Ndelta1 of His 69.

Ascomycota↗
PubMed2001

IL-4 adenoviral gene therapy reduces inflammation, proinflammatory cytokines, vascularization, and bony destruction in rat adjuvant-induced arthritis.

IL-4 is a cytokine with anti-inflammatory properties on activated macrophages. Rheumatoid arthritis, an autoimmune inflammatory disease, is characterized by a paucity of IL-4 and an abundance of synovial macrophage-derived mediators. Herein, the effect of a single injection of adenovirus-producing rat IL-4 (AxCAIL-4) or a control virus with no inserted gene was compared with the effect of PBS injection into rat ankles. Ankles were injected before arthritis onset or at maximal inflammation. Preventatively, AxCAIL-4 reduced adjuvant-induced arthritis (AIA)- and/or AIA/adenoviral-induced ankle inflammation, decreasing articular index scores, ankle circumferences, paw volumes, radiographic scores, mean levels of monocyte chemoattractant protein-1, the number of inflammatory cells, and the number of synovial blood vessels. Therapeutically, AxCAIL-4 also decreased ankle circumferences and paw volumes in comparison with a control virus with no inserted gene and PBS groups. After arthritis onset, mean levels of TNF-alpha, IL-1beta, macrophage inflammatory protein-2, and RANTES were decreased in AxCAIL-4 rat ankle homogenates compared with PBS-treated homogenates. Thus, increased expression of IL-4 via gene therapy administered in a preventative and/or therapeutic manner reduced joint inflammation, synovial cellularity, levels of proinflammatory cytokines, vascularization, and bony destruction in rat AIA, suggesting that a similar treatment in humans may be beneficial.

Adenoviruses, Human↗
PubMed2001

Bone or cartilage invasion by advanced head and neck cancer: intra-arterial supradose cisplatin chemotherapy and concomitant radiotherapy for organ preservation.

BACKGROUND: Invasion of bony or cartilaginous structures by advanced upper aerodigestive tract cancer has been considered an indication for surgery on the basis of historic experience of poor responsiveness to radiation therapy. At University of Tennessee-Memphis, patients with advanced head and neck cancer have been treated on a protocol of concomitant intra-arterial (targeted) cisplatin and conventional radiation therapy. OBJECTIVE: To compare the efficacy, in terms of disease control and survival, of this protocol in patients with T4 squamous cell cancers and invasion of bony or cartilaginous structures (group 1; n = 45) vs those with T4 disease but no bone or cartilage involvement (group 2; n = 90). DESIGN: Subset analysis of protocol database and retrospective chart review. METHODS: Treatment consisted of 4 weekly intra-arterial infusions of cisplatin (150 mg/m(2) per week), with simultaneous systemic neutralization by intravenous sodium thiosulfate (9 mg/m(2)), and concurrent radiation therapy at 180 rad (1.8 Gy) or 200 rad (2 Gy) per fraction to a planned total of 6600 to 7400 rad (66-74 Gy) to the primary site or overt nodal disease. Presence of bone or cartilage invasion was established by review of tumor diagrams of clinical findings and computed tomography or magnetic resonance imaging reports. RESULTS: Of 135 patients who had T4 disease and a minimum follow-up of 9 months (median, 40 months), 45 had clinical or radiologic evidence of bone (n = 29: mandible, 12; maxilla, 9; sphenoid, 3; hyoid, 6) and/or cartilage (n = 18: thyroid, 16; cricoid, 4) invasion (some patients had involvement of more than 1 site). The rate of complete response in group 1 (66.7%) was not significantly different from that in group 2 (71.1%) (chi(2) test, P = .79). The 2-year overall actuarial survival for group 1 (46.3%; 95% confidence interval, 30.3%-62.3%) was not significantly different (generalized Wilcoxon test, P = .36) from that of group 2 (36.9%; 95% confidence interval, 25.5%-48.4%). A marked trend was noted for higher response rates in cases of cartilage invasion (81.2%) than in those with bone invasion (58.6%) (P = .15). CONCLUSION: Equivalent efficacy of treatment in the 2 groups suggests that targeted chemoradiation can be a definitive therapeutic option in patients with advanced head and neck cancer invading bony or cartilaginous structures.

Adult↗
PubMed2001

Neonatal jaundice in very low birth weight babies.

Very low birth weight (VLBW) neonates born between January 1995 to December 1998, who survived for > 2 days, were studied for the incidence, causes and interventions required for neonatal jaundice. Significant neonatal jaundice was defined as the total serum bilirubin (TSB) level beyond which baby required intervention (phototherapy and/or exchange transfusion) for neonatal jaundice. The incidence of significant neonatal jaundice (NNJ) was 76.6% and 37.3% required exchange transfusion. It was 82.9% at gestational age < or = 28 weeks reduced whereas to 56.9% at gestational age of 35-36 weeks. The incidence was 75.3%, 78.5% and 76.7% in the birth weight group of 750-799 grams, 1000-1249 grams and 1250-1499 grams respectively. Glucose 6 phosphatase dehydrogenase (G-6-PD) deficiency (12.1%) was the commonest cause of jaundice. There is a need for evaluation of prophylactic therapies that enhances liver function or decreases production of bilirubin, which would prevent the rise of TSB to dangerous levels and thus would decrease the need for exchange transfusions.

Female↗
PubMed2001

Neurocysticercosis presenting as psychiatric illness.

Neurocysticercosis is a common neuroparasitosis. Presentation with psychiatric symptoms is uncommon in neurocysticercosis. The present paper describes a patient who presented with mutism, neglect of personal care and incontinence in a psychiatric setting and investigations revealed diagnosis of neurocysticercosis. The case report highlights the possible misdiagnoses of a case of neurocysticercosis as psychiatric illness and mutism as an uncommon presentation of neurocysticercosis.

Adolescent↗
PubMed2001

Postasphyxial encephalopathy in preterm neonates.

OBJECTIVE: Perinatal asphyxia is an important determinant of infant neurological outcome. There are very few studies looking exclusively at postasphyxial encephalopathy in preterm neonates. METHODS: We studied the neurologic and sonographic abnormalities in 40 preterm babies with severe birth asphyxia during their hospital stay and till 3 months corrected age. RESULT: 87.5 % of the asphyxiated preterm babies had neonatal neurologic abnormality, compared to only 17% of the control babies (p<0.0001). Generalised hypotonia and reduced activity were the commonest abnormalities (observed in 85% of asphyxiated babies) while depressed sensorium (60%) and seizures (35%) were seen in more severe cases. White matter disease (WMD-including periventricular flare, cerebral edema and periventricular leucomalacia) was significantly more frequent in the study cases (34.5% in study cases vs 7.5% in controls, p<0.0001) as was grade 3/4 intraventricular hemorrhage(IVH) (25% in study cases vs 2.5% in controls, p<0.0001). There was 11 fold higher mortality among the asphyxiated babies (23 deaths in study cases vs 2 in controls, p<0.0001). CONCLUSION: The survivors had a significantly higher incidence of both mild and severe neurological abnormalities at corrected age of 3 months among the asphyxiated babies. There was a good correlation between the severity of the neonatal encephalopathy as well as the sonographic findings and the outcome.

Asphyxia Neonatorum↗
PubMed2001

Long-term nutritional effects of ICDS.

Nutritional status of 1243 children (636 boys and 607 girls) in the age group of 7-13 years was assessed in relation to utilisation of Integrated Child Development Services (ICDS) during their childhood. All the houses in every 10th Anganwadi selected by systematic random sampling were surveyed in the ICDS project, Nand Nagri in East Delhi. Information regarding utilisation of ICDS facilities, sociodemographic details, general awareness etc. was collected by interview technique and anthropometric and clinical examination of every child was done and Anganwadi attendance score was calculated for each child. It was found that most of the children were non-beneficiaries (59.1%). On univariate analysis Anganwadi attendance score, age, sex of the child and education status of the father showed statistically significant association (p < 0.005) with malnutrition. On Multiple logistic regression analysis higher age (OR 1.4155 for grade 1 malnutrition and 1.6913 for grade 4 malnutrition) and being female (OR 1.5214 for Grade 4 malnutrition) remained significant risk factors for development of malnutrition for all grades. Anganwadi attendance score did not show any statistically significant association for decreasing the risk of getting malnourished for any grades of malnutrition in 7-13 years age group. There is special need to take special care for girls as well as to continue the special nutrition care even at an higher age. More in depth studies are needed so as to formulate effective nutritional policies for children.

Adolescent↗
PubMed2001

Roberts-SC phocomelia syndrome.

A severely growth retarded baby was born at 38 weeks gestation. He had multiple craniofacial anomalies, microbrachycephaly, phocomelia in the upper limbs and renal cysts visible on ultrasound. He died of recurrent apneas. The autopsy showed left sided multicystic dysplastic kidney and absence of one testis. Cytogenetic studies did not reveal any abnormality. The phenotypic features match those described in the Roberts-SC phocomelia syndrome. A literature review revealed that 50% of these patients have chromosomal defects and antenatal detection is possible on ultrasound and by chromosome analysis of the amniocytes.

Abnormalities, Multiple↗
PubMed2001

Mixed anaerobic and aerobic testicular abscess in a neonate.

A premature baby developed a testicular abscess on day 28 of life. The pus aspirated from the abscess grew a mixture of beta hemolytic Streptococcus and a Bacteroides species. The source of this infection could not be identified. The baby improved on antibiotic therapy. This is the first reported case of a polymicrobial testicular infection involving an anaerobe in a neonate. The relevant literature is reviewed.

Bacteroides Infections↗
PubMed2001

Early onset mixed Morganella and Klebsiella sepsis in a neonate.

A premature baby girl was delivered vaginally to a mother who had an otherwise normal pregnancy, and spontaneous premature onset of labour. She had early onset neonatal sepsis with pneumonia. The baby's blood culture as well as the amniotic membrane culture grew Morganella and Klebsiella. She recovered on appropriate antibiotics. This is only the second reported case of early onset neonatal sepsis due to Morganella. The literature is reviewed.

Anti-Bacterial Agents↗
PubMed2001

Base excess and lactate as prognostic indicators for patients admitted to intensive care.

OBJECTIVE: To examine whether values of arterial base excess or lactate taken on admission to a general intensive care unit indicate prognosis, and whether this can be used as a screening tool for future intensive care admissions. DESIGN: Observational study. SETTING: University teaching hospital general adult intensive care unit. PATIENTS: 148 consecutive patients admitted to the intensive care unit. INTERVENTIONS: Arterial blood samples were obtained on admission to the intensive care unit and 24 h following admission. MEASUREMENTS AND RESULTS: Arterial base excess and lactate concentrations were measured from the blood samples. Both base excess and arterial lactate samples on admission have good prognostic abilities (area under the curve on receiver operator characteristic analysis of 0.73, 0.78, respectively). The value of base excess on admission with the best predictive ability was a base excess more negative than -4 mmol/l, and the corresponding value for lactate was greater than 1.5 mmol/l. The combination of these two markers on admission to the intensive care unit led to a sensitivity of 80.3 % and a specificity of 58.7 % for mortality. The achievement of this combination was associated with an increased mortality (50.6 % vs. 15 %, p < 0.0001), older age (70 vs. 61.5 years, p < 0.05), a greater requirement for inotropic support (30.9 % vs. 4.5%, p < 0.0001) and higher organ failure scores both on admission and for the subsequent 24 h. CONCLUSIONS: Both base excess and lactate, or the combination of the two, can be used to predict outcome in patients admitted to the intensive care unit. These variables could be utilized to identify patients who have a high risk for mortality and thus who should be admitted to the intensive care unit.

Acid-Base Equilibrium↗
PubMed2001

Allelic loss of cyclophilin 40, an estrogen receptor-associated immunophilin, in breast carcinomas.

PURPOSE: Cyclophilin 40 (CyP40) is an estrogen receptor-associated protein which appears to modify receptor function. The aim of this study was to determine the extent of allelic loss at the CyP40 locus in a panel of breast carcinomas using a newly characterized microsatellite marker located upstream of the CyP40 gene and then to correlate this with losses at chromosomal sites for cancer-associated genes. METHODS: Allelic loss at CyP40 was determined from patients' matched tumor and normal breast tissue using Genescan 672 software analysis of fluorescently labeled, PAGE-separated PCR products incorporating the marker. For each patient, allelic loss at CyP40 was then assessed and compared with losses at markers for various cancer-associated genes. RESULTS: Allelic loss was detected in 30% of breast carcinomas from patients heterozygous for the CyP40 marker. All carcinomas demonstrating allelic loss were grade II or III invasive ductal carcinomas and generally showed multiple losses at other sites near known cancer-associated genes. CONCLUSIONS: The polymorphic marker which we characterized was useful in determining allelic loss at the CyP40 locus in breast cancer patients and when applied in these studies in conjunction with various cancer-associated gene markers, suggests that deletions in the region of the CyP40 gene might be a late event in breast tumor progression.

Breast↗
PubMed2001

Treatment of advanced head and neck cancer with intra-arterial cisplatin and concurrent radiation therapy: the 'RADPLAT' protocol.

The prognosis for patients presenting with advanced head and neck squamous cell carcinoma using "standard" treatment approaches, such as surgery followed by radiotherapy or radiotherapy alone, remains poor. Additionally, patients often lose their voice or swallowing ability when a primary surgical approach is used. Although systemic chemotherapy, when combined concurrently with radiotherapy, appears to be superior to radiation alone, the use of neoadjuvant or adjuvant systemic chemotherapy has not improved survival when combined with either surgery or radiotherapy. Even with the use of concurrent systemic chemotherapy and radiotherapy, the majority of the patients still succumb to their disease, usually failing locoregionally. Among the newer strategies being explored is the use of supradose intra-arterial chemotherapy (ie, cisplatin) with current radiotherapy. Acronymed "RADPLAT," this novel therapeutic approach delivers supradoses of weekly cisplatin chemotherapy with concurrent radiotherapy with acceptable toxicity, high locoregional tumor control rates, and very promising survival results. In addition, the RADPLAT approach allows for the preservation of organ function. This article reviews the evolution of the RADPLAT concept from a phase I trial to a recently completed Radiation Therapy Oncology Group trial confirming its feasibility in a multi-institutional setting.

Carcinoma, Squamous Cell↗
PubMed2001

Concomitant off-pump myocardial revascularization and pheochromocytoma resection.

Surgical management of patients with coexisting ischemic heart disease and pheochromocytoma remains challenging. We present one such case in which hybrid myocardial revascularization (angioplasty with stenting and off-pump coronary artery bypass grafting) and resection of pheochromocytoma were undertaken. Unusual features included simultaneous coronary artery surgery and tumor resection and, in particular, coronary artery surgery being performed without cardiopulmonary bypass.

Adrenal Gland Neoplasms↗
PubMed2001

Prevalence and patterns of presentation of genetic disorders in a pediatric emergency department.

OBJECTIVES: To determine the prevalence and patterns of presentation of previously diagnosed and of suspected genetic disorders among pediatric emergency department (ED) visits to a hospital that serves an inner-city population. PATIENTS AND METHODS: A retrospective review of 15,258 pediatric (<18 years old) ED visits at Lincoln Medical and Mental Health Center was undertaken for visits that occurred between October 1998 and February 1999. Suspected genetic disorders, classified into chromosomal, single gene, multifactorial, and other syndromic categories, were recorded. RESULTS: Of 15,258 visits reviewed, 2839 visits (18.6%) were by patients who had known or suspected genetic disorders. Previously diagnosed genetic disorders were documented in 80 visits (2.8%). Of these, 69 visits (86.2%) were related to single gene disorders, 3 (3.8%) to chromosomal disorders, 6 (7.5%) to multifactorial disorders, and 2 (2.5%) to disorders in the "other" category. Of these 80 visits, 59 (74%) were associated with sickle cell disease. The remaining 2759 visits (97.2%) were associated with complaints or diagnoses that suggested the possibility of an underlying genetic disorder requiring further evaluation and diagnostic work-up. CONCLUSIONS: Pediatric patients with known or suspected genetic disorders are frequently treated in EDs. Awareness of underlying genetic disorders facilitates diagnostic evaluation, treatment planning, and referral to a genetics clinic for counseling.

Adolescent↗