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Biomedical subjects

P Kumar

Publications and source records attributed to P Kumar.

At least 55 records · Page 3Linked to original sources
PubMed1998

Eating and weight changes following chemoradiation therapy for advanced head and neck cancer.

OBJECTIVE: To describe the functional outcomes of weight loss and eating following a targeted chemoradiation protocol consisting of a selective supradose of intra-arterial cisplatin (150 mg/m2 per week for 4 weeks) with parenteral sodium thiosulfate and external-beam irradiation (1.8-2.0 Gy per fraction per day for 35 days). SUBJECTS AND DESIGN: Forty-seven patients with advanced head and neck cancer treated with a targeted chemoradiation protocol were monitored for weight and eating status before treatment and as long as 18 months after treatment. RESULTS: A statistically significant weight loss (P<.001) occurred during the targeted chemoradiation protocol, with a mean weight ratio of 90% of the starting weight. The ability to eat also declined, with an increase in reported swallowing difficulties and a need for percutaneous endoscopic gastrostomy tubes from 4 (9%) to 12 (26%). There were no significant changes in weight after the initial weight loss. Tumor stage and nodal involvement had no effect on weight loss. At the start of treatment, 18 patients (38%) reported normal eating and 4 (8%) required a feeding tube. By 18 months after treatment, 41 (87%) were eating normally, 34 (72%) reported normal eating, and 6 (13%) required a percutaneous endoscopic gastrostomy tube. CONCLUSIONS: Patients undergoing a targeted chemoradiation protocol for head and neck cancer lost about 10% of their pretreatment weight and had a decline in eating ability. Difficulty swallowing during the treatment may be due to adverse effects such as mucositis and nausea. By 18 months after therapy, most were able to eat normally and maintain their weight.

Adult↗
PubMed1998

Autopsies in children: are they still useful?

BACKGROUND: Autopsy has traditionally been the criterion for determining cause of death and has played a major role in medical education and quality control. With increasing use of bedside technology, however, autopsy rates have steadily declined. OBJECTIVE: To identify (1) trends in pediatric autopsy rates during the past decade, (2) concordance between antemortem and postmortem diagnoses, and (3) patient characteristics influencing autopsy rates or diagnostic yield. METHODS: All pediatric deaths between January 1, 1984, and December 31, 1993, were retrospectively reviewed. Data collection included demographics for all patients, and length of stay, diagnostic imaging studies, antemortem diagnoses, and autopsy findings for patients with autopsies. Autopsy diagnoses were compared with antemortem findings and classified according to their concordance. RESULTS: Of 297 pediatric deaths, autopsies were performed on 107 patients (36%). Autopsy rates did not change significantly during the study period. Autopsies were not associated with patient gender, race, or insurance status, but increased significantly with age. Autopsies were performed in 26% of infants 12 months or younger, 60% of children between 13 to 60 months of age, and 100% of children 61 months or older (chi2; P <.001). In 34% of cases, new diagnoses were made at autopsy, including 7 cases where new findings, if known before death, would likely have resulted in a change in treatment or improved survival. There was no relationship between new findings at autopsy and age, length of hospital stay, or antemortem imaging studies. CONCLUSIONS: Autopsy can provide additional information in more than one third of pediatric deaths. Pediatric autopsy continues to provide clinically significant data and remains a valuable tool in modern pediatric practice.

Adolescent↗
PubMed1998

Inducible nitric oxide production and expression of transforming growth factor-beta1 in serum and CSF after cerebral ischaemic stroke in man.

A residual blood supply to the ischaemic brain is a crucial determinant for tissue survival. Early changes in the vascular network and subsequent angiogenesis may be mediated by short-lived molecules like nitric oxide (NO) or growth factors such as transforming growth factor-beta1 (TGF-beta1). Although TGF-beta1 can inhibit NO production, this interaction has not been studied after ischaemia in humans. Serum samples were taken from patients at 24 h and 6 months and cerebrospinal fluid (CSF) samples at 24 h and 1 week later for possible correlation between the two factors. Tissue expression of TGF-beta1 and of the inducible isoform of NO synthase (NOS2) was assessed by immunohistochemistry. CSF levels of NO2-/NO3- as well as total (active + latent) TGF-beta1 were higher in stroke patients as compared to controls 24 h after the stroke. Both NO2-/NO3- and TGF-beta1 were lower 6 months after the stroke compared to 24 h. Levels of NO2-/NO3- correlated with levels of TGF-beta1 within the time points (P = 0.041, Kendall correlation coefficient). There was a strong staining for NOS2 in brain tissue sections in neurones, reactive astrocytes, infiltrating white blood cells, and endothelial cells of larger microvessels. TGF-beta1 expression was mainly limited to neurones and reactive astrocytes. These findings suggest that the interaction between TGF-beta1 and NOS2 might be important for angiogenesis after cerebral ischaemia and may indicate that TGF-beta1 is upregulated as a negative feedback response to elevated levels of NO.

Adult↗
PubMed1998

Influence of immunoadjuvants and a promiscous T-cell determinant on the immunogenicity of RESA peptide antigen of P. falciparum.

Synthetic peptide antigens representing the repeat sequences of malarial antigens showed poor immunogenicity and protection in clinical trials. In the present study, RESA, an asexual blood stage antigen, containing (EENVEHDA)2 and (DDEHVEEPTVA)2 sequences were chemically linked to a promiscous T-cell determinant (CS.T3) of the circumsporozoite protein of P. falciparum. The synthetic constructs either alone or coentrapped with immunoadjuvants (nor muramyl dipeptide/lauroyl tetrapeptide) were administered in liposomes to mice of varying genetic background and the immunogenicity of different formulations were compared under identical experimental conditions. The RESA peptide formulations containing the T-cell determinant and the adjuvants generated high titre and affinity antibodies in all the strains, as compared to peptide(s) alone. The booster immunization induced a strong anamnestic response in each group. Though the major IgG isotype is of IgG1 and IgG2b interestingly, formulations containing CS.T3 have a higher proportion of cytophilic IgG2b isotype. There was a significant fall in the levels of IgG2b isotype while IgG1 levels were maintained same in the third bleed (day 60, without booster immunization). The mixed peptide group preparation containing the adjuvant is found to be a better immunogen than that of respective peptides itself. The in vitro merozoite reinvasion inhibition assay showed 76-96% inhibition with the formulations containing RESA peptide(s)-CS.T3 and the adjuvant, while with peptides alone the inhibition was 50-56%. This study highlights the importance of an alternative approach for developing peptide based immunogen against malaria.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1998

Do the diminishing efficacy and increasing toxicity of sodium stibogluconate in the treatment of visceral leishmaniasis in Bihar, India, justify its continued use as a first-line drug? An observational study of 80 cases.

Eighty parasitologically confirmed cases of visceral leishmaniasis (kala-azar) in Bihar, India, were treated daily with 20 mg sodium stibogluconate/kg for 30 days, to assess the current efficacy and toxicity of this 30-day regimen. Clinical and parasitological cure was obtained in 48 (60%) of the patients. However, 26 (33%) patients did not respond to the first course of treatment (primary unresponsiveness), two relapsed after initial clinical and parasitological cure, and two were withdrawn from the study (one on day 6 of treatment because of cardiotoxicity in the form of supraventricular tachycardia and the other on day 24 because of severe loss of appetite). All 30 patients who were not entirely cured with sodium stibogluconate were successfully treated with amphotericin B. Electrocardiographic changes occurred in many of the patients as the result of treatment with sodium stibogluconate. Diminution in the height of the T wave was seen in 32 (40%), inversion of the T wave (Minnesota code 5-1, 5-2) in seven (9%), elevation of the ST segment (Minnesota code 4-1) in three (4%), prolonged QT interval (compared with baseline findings) in six (8%), and diminution in the height of the P, R and T waves in two (3%). Cardiac arrhythmia occurred in five patients (6%), supraventricular arrhythmia (coarse atrial fibrillation) occurred in one patient and ventricular tachycardia, ventricular fibrillation, torsade de pointes and multifocal ventricular ectopics occurred in the four patients (5%) who died of cardiotoxicity. Minor side-effects, such as pain at the site of injection (two cases), mild diminution in appetite (12 cases), metallic taste in mouth (six cases), and joint pain (two cases), were also observed. It was concluded that the efficacy of sodium stibogluconate in the study area has declined over the years and that its toxicity has increased. A more efficacious, safer and cheaper, alternative drug is required as the first line of treatment of kala-azar.

Adolescent↗
PubMed1998

Influence of a melatonin implant on the free radical load in avian thyroid and its relation with thyroid hormonogenesis.

The primary aim of this study was to evaluate the effect of melatonin on the oxiradical load in avian thyroid. The superoxide free radicals have been spin trapped by EPR spectroscopy in the thyroid gland of Indian rock pigeon Columbia livia following melatonin implantation for two weeks. Melatonin implantation resulted in augmentation in the levels of superoxide radical in the thyroid gland of pigeons with a concomitant decrease in the levels of the total superoxide dismutase activity. This was also associated with increased lipid peroxidation. Melatonin implantation caused a significant increase in plasma levels of glucose. Plasma levels of thyroxine (T4) and triiodothyronine (T3) were lower in the melatonin-treated pigeons. However, the T3/T4 ratio was higher following melatonin implantation. Since iodination of tyrosine is an H2O2-dependent phenomenon, the inhibition in the activity of SOD could lead to impaired thyroid hormone synthesis.

Animals↗
PubMed1998

Epidemiology of systemic candidiasis in a tertiary care neonatal unit.

143 neonates were diagnosed to have acquired systemic candidiasis out of a total 4530 admissions (3.2 per cent) to the neonatal intensive care unit (NICU) during a period of 6 1/2 years from January 1990 to June 1996. Mean age at onset was 10.4 days, mean birth weight 1454 g, and mean gestation was 31.7 weeks. Ninety-four per cent were premature, 95 per cent low birth weight (LBW), and all had undergone peripheral vein catheterization and had received broad spectrum antibiotics, except one, prior to the diagnosis. Fifty-eight per cent were ventilated and 15 per cent received parenteral nutrition. Persistent/recurrent pneumonia, apnoea, lethargy, high gastric aspirates, and abdominal distension were the common clinical manifestations. Candida tropicalis, C. albicans, and C. guillermondii were the most common isolates. Blood and urine were the predominant sites for isolation of Candida. Fluconazole was the most used antifungal agent, with 24 per cent resistance against it. Fifty per cent of babies died due to all causes. Of all the deaths, two-thirds were Candida related. Candida-attributable deaths occurred in 24 cases (17 per cent).

Age of Onset↗
PubMed1998

Design of peptides with alpha,beta-dehydro residues: synthesis, crystal structure and molecular conformation of N-Boc-L-Ile-deltaPhe-L-Trp-OCH3.

The dehydro-peptide Boc-L-Ile-deltaPhe-L-Trp-OCH3 was synthesized by the azlactone method in the solution phase. The peptide was crystallized from methanol in an orthorhombic space group P2(1)2(1)2(1)with a = 10.777(2), b = 11.224(2), c = 26.627(10) A. The structure was determined by direct methods and refined to an R value of 0.069 for 3093 observed reflections [I > or = 2delta(I)]. The peptide failed to adopt a folded conformation with backbone torsion angles: phi1 = 90.8(8)degrees, psi1 = -151.6(6)degrees, phi2 = 89.0(8)degrees, psi2 = 15.9(9)degrees, phi3 = 165.7(7)degrees, psi3T = -166.0(7)degrees . A general rule derived from earlier studies indicates that a three-peptide unit sequence with a deltaPhe at the (i + 2) position adopts a beta-turn II conformation. Because the branched beta-carbon residues such as valine and isoleucine have strong conformational preferences, they combine with the deltaPhe residue differently to generate a unique set of conformations in such peptides. The presence of beta-branched residues simultaneously at both (i + 1) and (i + 3) positions induces unfolded conformations in tetrapeptides, but a beta-branched residue substituted only at (i + 3) position can not prevent the formation of a folded beta-turn II conformation. On the other hand, the present structure shows that a beta-branched residue substituted at the (i + 1) position prevents the formation of a beta-turn II conformation. These observations indicate that a beta-branched residue at the (i + 1) position prevents a folded conformation whereas it cannot generate the same degree of effect from the (i + 3) position. This may be because of the trans disposition of the planar deltaPhe side-chain with respect to the C=O group in the residue. The molecules are packed in an anti-parallel manner to generate N2-H2...O2 (-x, y -1/2, -z + 3/2) and N3epsilon1-H3epsilon1 ...O1(-X, y -1/2, -z + 3/2) hydrogen bonds.

Crystallography↗
PubMed1998

Tongue papillae in goat: a scanning electron-microscopic study.

The tongue papillae of 6-9-month-old Jamunapari goats were studied by scanning electron-microscopy. The conical-shaped filiform papillae had 3-6 pointed projections and 6-8 secondary papillae at the free tip and the base of the dorsal surfaced of the tongue, respectively. The convex surfaced fungiform papillae were raised above the lingual mucosa. The vallate papilla was characterized by a papillary groove and an annular pad. The large conical papilla had a round base and a blunt tip without any projection. Two types of lenticular papillae could be distinguished. The irregular surface of all types of papillae revealed microplicae in the form of microridges and micropits. The fungiform papilla was studded with microvilli. The taste pores were oriented on the dorso-lateral surface of the vallate papilla.

Animals↗
PubMed1998

Tolerance and pharmacokinetic interactions of rifabutin and clarithromycin in human immunodeficiency virus-infected volunteers.

This study evaluated the tolerance and potential pharmacokinetic interactions between clarithromycin (500 mg every 12 h) and rifabutin (300 mg daily) in clinically stable human immunodeficiency virus-infected volunteers with CD4 counts of <200 cells/mm3. Thirty-four subjects were randomized equally to either regimen A or regimen B. On days 1 to 14, subjects assigned to regimen A received clarithromycin and subjects assigned to regimen B received rifabutin, and then both groups received both drugs on days 15 to 42. Of the 14 regimen A and the 15 regimen B subjects who started combination therapy, 1 subject in each group prematurely discontinued therapy due to toxicity, but 19 of 29 subjects reported nausea, vomiting, and/or diarrhea. Pharmacokinetic analysis included data for 11 regimen A and 14 regimen B subjects. Steady-state pharmacokinetic parameters for single-agent therapy (day 14) and combination therapy (day 42) were compared. Regimen A resulted in a mean decrease of 44% (P = 0.003) in the clarithromycin area under the plasma concentration-time curve (AUC), while there was a mean increase of 57% (P = 0.004) in the AUC of the clarithromycin metabolite 14-OH-clarithromycin. Regimen B resulted in a mean increase of 99% (P = 0.001) in the rifabutin AUC and a mean increase of 375% (P < 0.001) in the AUC of the rifabutin metabolite 25-O-desacetyl-rifabutin. The usefulness of this combination for prophylaxis of Mycobacterium avium infections is limited by frequent gastrointestinal adverse events. Coadministration of clarithromycin and rifabutin results in significant bidirectional pharmacokinetic interactions. The resulting increase in rifabutin levels may explain the increased frequency of uveitis observed with concomitant use of these drugs.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Oxygen-insensitive nitroreductases: analysis of the roles of nfsA and nfsB in development of resistance to 5-nitrofuran derivatives in Escherichia coli.

Nitroheterocyclic and nitroaromatic compounds constitute an enormous range of chemicals whose potent biological activity has significant human health and environmental implications. The biological activity of nitro-substituted compounds is derived from reductive metabolism of the nitro moiety, a process catalyzed by a variety of nitroreductase activities. Resistance of bacteria to nitro-substituted compounds is believed to result primarily from mutations in genes encoding oxygen-insensitive nitroreductases. We have characterized the nfsA and nfsB genes of a large number of nitrofuran-resistant mutants of Escherichia coli and have correlated mutation with cell extract nitroreductase activity. Our studies demonstrate that first-step resistance to furazolidone or nitrofurazone results from an nfsA mutation, while the increased resistance associated with second-step mutants is a consequence of an nfsB mutation. Inferences made from mutation about the structure-function relationships of NfsA and NfsB are discussed, especially with regard to the identification of flavin mononucleotide binding sites. We show that expression of plasmid-carried nfsA and nfsB genes in resistant mutants restores sensitivity to nitrofurans. Among the 20 first-step and 53 second-step mutants isolated in this study, 65 and 49%, respectively, contained insertion sequence elements in nfsA and nfsB. IS1 integrated in both genes, while IS30 and IS186 were found only in nfsA and IS2 and IS5 were observed only in nfsB. Insertion hot spots for IS30 and IS186 are indicated in nfsA, and a hot spot for IS5 insertion is evident in nfsB. We discuss potential regional and sequence-specific determinants for insertion sequence element integration in nfsA and nfsB.

Amino Acid Sequence↗
PubMed1998

Elevation of metabolic rate by pyrogen administration does not affect the gain of respiratory peripheral chemoreflexes in unanesthetized kittens.

We previously reported that reducing environmental temperature from 30 to 25 degrees C increases the gain of respiratory chemoreflexes. To investigate the role of increased metabolism in mediating the effect on the gain of the respiratory chemoreflex, we compared the respiratory responses, at ca. 26 degrees C to breath-by-breath alternations of inspired gas between air and 14% oxygen (hypoxia run) or air and 5% CO2 (CO2 run) with that to alteration of air between two inspired lines (control run) before and after the injection of a pyrogen (IL-1beta 400 ng/kg i.p.) in eight kittens at 27-35 d of postnatal age. The respiratory chemoreflex was quantified from the alternations in inspiratory and expiratory variables produced during test runs in terms of the direction and the amplitude of the alternation for each variable and compared with the results of control runs at the same temperature. Pyrogen administration produced a rise in rectal temperature and in oxygen consumption. However, there was no difference in the chemoreflex response to hypoxia or CO2 runs, in terms of either the pattern or of the amplitude of alternation, before and after the injection of the pyrogen. We conclude that the increase in the gain of chemoreflex observed during cooling in a previous study is not due to an increase in metabolism. Some change in input from thermoreceptors may bias the gain of chemoreflexes.

Animals↗
PubMed1998

A novel insulin receptor substrate protein, xIRS-u, potentiates insulin signaling: functional importance of its pleckstrin homology domain.

A novel Xenopus insulin receptor substrate cDNA was isolated by hybridization screening using the rat insulin receptor substrate-1 (IRS-1) cDNA as a probe. The xIRS-u cDNA encodes an open reading frame of 1003 amino acids including a putative amino-terminal pleckstrin homology (PH) domain and phosphotyrosine-binding (PTB) domain. The carboxy terminus of xIRS-u contains several potential Src homology 2 (SH2)-binding sites, five of which are in the context of YM/LXM (presumptive binding sites for phosphatidylinositol 3-kinase). It also contains a putative binding site for Grb2 (YINID). Pair-wise amino acid sequence comparisons with the previously identified xIRS-1 and the four members of the mammalian IRS family (1 through 4) indicated that xIRS-u has similar overall sequence homology (33-45% identity) to all mammalian IRS proteins. In contrast, the previously isolated xIRS-1 is particularly similar (67% identical) to IRS-1 and considerably less similar (31-46%) to the other IRS family members (2 through 4). xIRS-u is also distinct from xIRS-1, having an overall sequence identity of 47%. These sequence analyses suggest that xIRS-u is a novel member of the IRS family rather than a Xenopus homolog of an existing member. Microinjection of mRNA encoding a Myc-tagged xIRS-u into Xenopus oocytes resulted in the expression of a 120-kDa protein (including 5 copies of the 13-amino acid Myc tag). The injection of xIRS-u mRNA accelerated insulin-induced MAP kinase activation with a concomitant acceleration of insulin-induced oocyte maturation. An aminoterminal deletion of the PH domain (xIRS-u deltaPH) significantly reduced the ability of xIRS-u to potentiate insulin signaling. In contrast to the full-length protein, injection of xIRS-u (1-299), which encoded the PH and PTB domain, or xIRS-u (1-170), which encoded only the PH domain, blocked insulin signaling in Xenopus oocytes. Finally, xIRS-u (119-299), which had a truncated PH domain and an intact PTB domain, had no effect on insulin signaling. This is the first report that the PH domain of an IRS protein can function in a dominant negative manner to inhibit insulin signaling.

Adaptor Proteins, Signal Transducing↗