Spontaneous perforation of Meckel's diverticulum in a neonate.
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Humans↗
Biomedical subjects
P Kumar
Publications and source records attributed to P Kumar.
Gastroesophageal reflux and pulmonary complication in a neonate.
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Antiemetics↗
A randomized comparison of classical mode of administration of amphotericin B with its newer modes of administration in kala-azar.
UNLABELLED: One hundred thirty parasitologically confirmed cases of kala-azar were randomly divided in two equal treatment groups. Patients in group A were treated by infusion with amphotericin B deoxycholate (ABD), 1 mg/kg day on days 1-20 and the infusion was given in two hours. Patients in group B were treated by an escalating dose of ABD 0.05 mg/kg, 0.1 mg/kg, 0.25 mg/kg, 0.5 mg/kg, 1 mg/kg on days 1-5, respectively and then in the same dosage on alternate days. The infusion was completed in 6 hours. Total dose of 20 mg/kg remaining the same in both the groups, the treatment was completed in 20 days in group A and 43 days in group B. Clinical cure (subsidence of fever, improvement in general well being and regression in the size of the spleen) and parasitological cure (absence of parasites in splenic aspirates at the end of treatment) occurred in all patients in both the groups. Sixty four (99%) patients in each group had not relapsed clinically and parasitologically within 6 months of follow up and were ultimately cured. The two relapsed patients, one in each group were treated with a 20-day course of ABD and were cured. Leukocyte count, haemoglobin, serum albumin increased (P < 0.05) and ESR, spleen and liver size decreased (P < 0.05) at the end of treatment and follow up. Adverse events were similar in both the groups. The minimum cost of treatment estimated was Rs. 14,500 in group B and Rs. 10,000 in Group A. Thus the newer mode of administration was more cost effective. CONCLUSION: It was concluded that newer mode of administration of amphotericin B was as effective and tolerable as the classical mode of administration and was no more toxic. The newer mode of administration of amphotericin B is more cost effective and puts lesser burden on hospital staff and is recommended for use in kala-azar.
Adolescent↗
Role of early postnatal dexamethasone in respiratory distress syndrome.
OBJECTIVE: To study the effect of early postnatal dexamethasone therapy on severity of hyaline membrane disease. DESIGN: Prospective, randomized, controlled, unblinded study. SETTING: Neonatal Intensive Care Unit. METHODS: 19 babies who had hyaline membrane disease were included in this study. The inclusion criteria were clinical and radiographic diagnosis of RDS, requiring mechanical ventilation and FiO2 > 0.3. Ten babies received injection dexamethasone 0.5 mg/kg/dose 12 hourly for 3 days starting within 6 hours of birth. The control group did not receive any drug. Babies with active infection, bleeding tendency and congenital malformation were excluded. None of the babies received surfactant. The duration of ventilation and AaDO2 and FiO2 requirements from day one to five were calculated. RESULTS: The initial AaDO2 were similar in both the groups but on day 3, 4, 5 AaDO2 were low in study group (201, 85, 70) compared to control group (236, 209, 162). The initial FiO2 were 0.66 and 0.63 in dexamethasone and control groups, respectively and remained high till day 2 and came down in study group on days 3, 4 and 5 (0.41, 0.27, 0.27) compared to control group (0.53, 0.34, 0.42). The mean duration of ventilation was shorter in dexamethasone group (87 hours) vs control group (120 hours). CONCLUSION: Early use of postnatal dexamethasone reduces the disease severity and oxygen requirement in RDS and hence would be useful in the Indian context.
Anti-Inflammatory Agents↗
Pulmonary functions in Indian sportsmen playing different sports.
Regular exercise has proved to be beneficial for the human body and the lungs are no exception. The present study was undertaken to assess the relation between the quality of exercise performed and the quantitative effect of these exercises on the lungs. Pulmonary function tests of sportsmen engaged in various sports were compared with each other and with that of the controls. Players playing football (n=18), hockey (n=19), volleyball (n=20), swimming (n=20) and basketball (n=18) were chosen for this study. Medical students (n=20) were chosen as controls. The parameters taken into account in this study were forced vital capacity (FVC), forced expiratory volume (FEV-1), and peak expiratory flow rate (PEFR). The results indicate that all the sportspersons had a higher values of lung functions compared to the controls. Among the various groups of players chosen for this study, the swimmers showed the maximum increase in their lung functions.
Adult↗
Vancomycin resistant enterococcus in a hospital-based dialysis unit.
OBJECTIVE: The emergence of vancomycin resistant enterococcus (VRE) poses a serious threat to the health care community. Reservoirs of VRE are thought to exist in certain high-risk patient groups who reintroduce the organism into the hospital environment. The frequent use of vancomycin in dialysis patients may place this population at higher risk of developing VRE. This article describes the development of VRE and a point prevalence study conducted in a hospital-based dialysis unit. SETTING/SAMPLE: A dialysis unit of a tertiary care center in the eastern United States was selected as the study site. Patients who agreed to participate in the study after giving informed consent were included. Of the 85 members of this target population 33 (38.8%) agreed to participate in the study. The duration of the study was 30 days. DESIGN: After the literature was reviewed, a point prevalence study was completed at the study site. Stool samples or rectal swabs were collected from the study participants and analyzed for the presence of VRE. A chart review of patient demographic and prior treatment information was completed in order to help identify factors that correlate to the presence of VRE. METHODS: Stool or rectal swab samples were cultured on selective media and sensitivity to vancomycin was measured. RESULTS: A 9.1% prevalence of VRE was detected within the study group. The number of VRE positive subjects (3) did not allow statistically significant correlation with the demographic and prior treatment data collected. CONCLUSION: Although VRE remains a serious threat to the health care community, the prevalence of VRE within the study group does not vary markedly from rates previously reported.
Adult↗
Infantile and childhood types of atopic dermatitis--a clinical comparison.
Atopic Dermatitis also known as infantile eczema in infants, is a chronic endogenous eczema which manifests with different characteristic distribution in infants, children and adults. Absence of any reliable laboratory investigation to confirm the diagnosis makes it very difficult to differentiate it from other eczemas especially in infantile and childhood types. This study compares a small group to patients belonging to infantile and childhood types of atopic dermatitis and documents the changes observed in these category of patients.
Age Distribution↗
Knowledge, attitude and practices related to dengue in rural and slum areas of Delhi after the dengue epidemic of 1996.
To assess the knowledge and attitudes about dengue and practice of prevention followed by the residents of a rural area and an urban resettlement colony of East Delhi, an interview based cross sectional KAP study was undertaken in Jan 97 to Feb 97, a few months after the dengue epidemic in rural area and urban areas of East Delhi. A pre-structured and pre-tested format containing the relevant questions was administered to the subjects. A total of 687 subjects (334 rural and 353 urban) were interviewed. Nearly four fifth (82.3%) of these were aware of Dengue. Audiovisual media was the most common source of information in both the areas. Knowledge about the disease was fair to good. Fever was the commonest symptom of the disease known to 92% urban and 83% rural respondents followed by symptoms of bleeding and headache. Mosquito was known to spread the disease to 71% rural and 89% urban respondents. More than two third respondents in urban and two fifth in rural areas had used some method of mosquito control or personal protection during the epidemic.
Cross-Sectional Studies↗
Microwave-assisted rapid deprotection of oligodeoxyribonucleotides.
A novel method for the deprotection of oligodeoxyribonucleotides under microwave irradiation has been developed. The oligodeoxynucleotides having base labile, phenoxyacetyl (pac), protection for exocyclic amino functions were fully deprotected in 0. 2 M sodium hydroxide (methanol:water : : 1:1, v/v) = A and 1 M sodium hydroxide (methanol:water : : 1:1, v/v) = B using microwaves in 4 and 2 min, respectively. The deprotection of oligodeoxyribonucleotides carrying conventional protecting groups, dAbz, dCbzand dGpac, for exocyclic amino functions was achieved in 4 min in B without any side product formation. The deprotected oligonucleotides were compared with the oligomers deprotected using standard deprotection conditions (29% aq. ammonia, 16 h, 55 degrees C) with respect to their retention time on HPLC and biological activity.
Kinetics↗
Regulation of superoxide anion radical-superoxide dismutase system in the avian thyroid by TSH with reference to thyroid hormonogenesis.
This study shows that superoxide dismutase is present in the thyroid gland of pigeons as a constitutive enzyme serving as an antioxidant against oxygen toxicity. Exogenous administration of thyrotropin induced thyroidal superoxide dismutase with a simultaneous burst in superoxide anion radical levels during the initial phase of hormone treatment. The superoxide radical generated was completely scavenged by SOD during the late phase of TSH-treatment, presumably as an adaptive measure to check the oxygen burst. TSH failed to augment serum T3 levels, although the thyroxine level in the serum was elevated. The peak level of SOD activity profile in the thyroid gland correlated very well with the peak level of thyroxine concentrations in the serum of pigeon. It is reasonable to postulate that the thyroidal SOD in homeotherms serves a dual role, firstly as a strategic antioxidant enzyme to protect the thyroid gland against the degenerative influence of toxic oxyradicals and secondly to provide H2O2 for thyroid hormone biosynthesis. Our results confirm the previous observations that TSH is mainly thyrotropic in birds and that it has no influence on the peripheral activation of thyroxine to triiodothyronine by stimulating the extra thyroidal 5'-deiodinase activity.
Animals↗
A more cultured approach to peripheral chemotransduction.
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Animals↗
Development of carotid chemoreceptor dynamic and steady-state sensitivity to CO2 in the newborn lamb.
1. The maturation of carotid chemoreceptor steady-state and dynamic responses to CO2 in newborn lambs was measured. In total, sixteen fibres (13 lambs) were studied at 3-4 days, nineteen fibres (13 lambs) at 5-9 days and twenty-one fibres (17 lambs) at 10-24 days after birth. 2. Steady-state CO2 sensitivity was measured over a range of arterial CO2 pressures (Pa,CO2) at four levels of arterial O2 pressure (Pa,O2): hyperoxia (Hyp), 115-150 mmHg; normoxia (Nx), 90-105 mmHg; moderate hypoxia (ModHx), 40-60 mmHg; and severe hypoxia (SvHx), 20-35 mmHg. 3. Steady-state CO2 sensitivity was present at all ages, and a significant effect of age (P < 0.001) and Pa,O2 (P < 0.025) (ANOVA) was observed. Older lambs were unable to sustain an increase in chemoreceptor discharge during SvHx as CO2 was increased. 4. Dynamic CO2 sensitivity was measured by producing alternations in end-tidal CO2 levels (etCO2) (alternation amplitude, 1.23 +/- 0.07% (mean +/- S.E.M.); etCO2, 7.56 +/- 0.15%) over 2-8 s at two Pa,O2 levels only: 80-100 (Nx) and 40-60 mmHg (ModHx). Peak and trough values of the oscillation in chemoreceptor discharge were plotted against maximum and minimum etCO2 for the control and CO2-loaded breaths. Dynamic CO2 sensitivity was calculated as the slope between these points. 5. Dynamic CO2 sensitivity was greater than steady-state sensitivity in Nx (P < 0.05) and ModHx (P < 0.01, Student's paired t test). Unlike steady-state CO2 sensitivity, there was no significant effect of age or Pa,O2 on dynamic sensitivity (P > 0.39 and P > 0.68, respectively, ANOVA). 6. Our results show that the neonatal lamb possesses a carotid body steady-state CO2 sensitivity within a few days of birth, an age when hypoxia sensitivity is low. This CO2 sensitivity increases with age, perhaps due to the increasing interaction between CO2 and O2. Dynamic sensitivity of the carotid body to CO2 is mature at birth and does not increase with age, as predicted if the response of the carotid body to rapid changes in CO2 is independent of the sensitivity to the partial pressure of O2 (PO2).
Aging↗
Multiplicity of the beta form of the cAMP-dependent protein kinase inhibitor protein generated by post-translational modification and alternate translational initiation.
Two distinct species of the thermostable inhibitor of the cAMP-dependent protein kinase, PKIalpha and PKIbeta, exist that are the products of separate genes. The PKIbeta form, as first isolated from rat testis, is a 70-amino acid protein, but the genomic sequence suggested that an alternate form might exist, arising as a consequence of alternate translational initiation. This species, now termed PKIbeta-78, has been synthesized by bacterial expression, demonstrated to be equipotent with PKIbeta-70, and also now demonstrated to occur in vivo. By Western blot analyses, six additional species of PKIbeta are also evident in tissues. Two of these represent the phospho forms of PKIbeta-78 and PKIbeta-70. The other four represent phospho and dephospho forms of two higher molecular mass PKIbeta species. These latter forms are currently termed PKIbeta-X and PKIbeta-Y, awaiting the full elucidation of their molecular identity. In adult rat testis and cerebellum, PKIbeta-70, PKIbeta-X, and PKIbeta-Y constitute 39, 23, and 32% and 15, 29, and 54% of the total tissue levels, respectively. In adult rat testis, 35-42% of each of these three species is present as a monophospho form, whereas no phosphorylation of them is evident in cerebellum. PKIbeta-78 is present at much lower levels in both rat testis and cerebellum (approximately 6 and 2% of the total, respectively) and almost entirely as a monophospho species. PKIbeta-78, like PKIbeta-70, is a high affinity and specific inhibitor of the cAMP-dependent protein kinase. PKIbeta-Y and PKIbeta-X, in contrast, also significantly inhibit the cGMP-dependent protein kinase.
Amino Acid Sequence↗
Specific testicular cellular localization and hormonal regulation of the PKIalpha and PKIbeta isoforms of the inhibitor protein of the cAMP-dependent protein kinase.
We have previously demonstrated that there exist two distinct genes for the thermostable inhibitor protein of the cAMP-dependent protein kinase, PKIalpha and PKIbeta (Van Patten, S. M., Howard, P., Walsh, D. A., and Maurer, R. A. (1992) Mol. Endocrinol. 6, 2114-2122). We have also shown that in the testis, at least eight forms of PKIbeta exist, differing as a result of at least post-translational modification and alternate translational initiation (Kumar, P., Van Patten, S. M., and Walsh, D. A. (1997) J. Biol. Chem. 272, 20011-20020). We now report that in the testis, there is a unique cellular distribution of protein kinase inhibitor forms, with PKIbeta being essentially (if not exclusively) a germ cell protein and PKIalpha being expressed primarily in Sertoli cells. Furthermore, there is a progressive change in the forms of PKIbeta that are present within germ cells with development that is initiated in testis tubules and continues as the germ cells migrate through the epididymis. These conclusions are derived from studies with isolated cell populations and with the at/at germ cell-deficient mouse line, by in situ hybridization, and by following the developmental expression of these proteins in both testis and epididymis. We have also shown that follicle-stimulating hormone (FSH) can increase the expression of both PKIalpha and PKIbeta. The FSH-regulated expression of PKIalpha in the Sertoli cell likely occurs via the normal route of second messenger signal transduction. In contrast, the FSH-dependent PKIbeta expression must arise by some form of Sertoli cell-germ cell intercommunication.
Adaptor Proteins, Signal Transducing↗
Developmental changes in isolated rat type I carotid body cell K+ currents and their modulation by hypoxia.
1. Whole-cell patch-clamp recordings were used to investigate possible age-related changes in K+ currents of type 1 carotid body cells isolated from the rat. K+ current density increased with age, as measured in cells isolated from 4-day-old, 10-day-old and adult rats (> or = 5 weeks old). 2. The proportion of current reversibly inhibited by high [Mg2+] (6 mM), low [Ca2+] (0.1 mM) solutions, indicative of the proportion of current attributable to activation of Ca(2+) -sensitive K+ (KCa) channels, was significantly smaller in cells of 4-day-old rats compared with 10-day-old rats, despite inward Ca2+ current densities being similar in these two age groups. Inhibition of K+ currents by high [Mg2+], low [Ca2+] solutions was similar in 10-day-old and adult type 1 cells. 3. Hypoxia (PO2, 16-23 mmHg) caused reversible reductions in type I cells from rats of all age groups. However, reductions seen in cells of 4-day-old rats were significantly smaller than those seen in cells of 10-day-olds and adults. The degree of hypoxic inhibition in these latter two groups was not significantly different. 4. In the presence of high [Mg2+], low [Ca2+] solutions, hypoxia (PO2, 16-23 mmHg) was without significant effect on residual K+ currents in cells from all age groups. 5. These observations indicate that K+ current density increases with postnatal age in the rat. Between days 4 and 10, there appears to be a predominant enhancement of KCa channels, and over the same age range hypoxic sensitivity of K+ currents increases. Our findings demonstrate that this latter observation arises because hypoxia selectively inhibits KCa channels in cells at all ages studied. These results suggest an important role for KCa channels in postnatal maturation of hypoxic chemoreception in the rat carotid body.
Aging↗
Efficacy of targeted supradose cisplatin and concomitant radiation therapy for advanced head and neck cancer: the Memphis experience.
PURPOSE/OBJECTIVE: To evaluate the feasibility, response rates, and toxicity of a Phase II study using targeted supradose cisplatin and concurrent radiation therapy in unresectable Stage III-IV head and neck squamous cell carcinoma. METHODS AND MATERIALS: Sixty patients presenting between 6/93-9/94 were enrolled, 44 (73%) of whom had T4 and/or N2-N3 nodal disease. All patients were treated with rapid targeted superselective intraarterial infusions of cisplatin (150 mg/m2 weekly x 4) and simultaneous sodium thiosulfate intravenously (9 g/m2) for systemic neutralization of cisplatin. Concurrent (day 1) daily radiation therapy was delivered to the primary tumor and overt nodal disease to 66-74 Gy while the uninvolved lower neck received 50 Gy, at 2.0 Gy/fraction. RESULTS: Fifty-one (85%) patients completed the full RADPLAT protocol as planned. Fifty-seven of 60 patients were evaluable for response. Histological (n = 50) or clinical (n = 7) assessment of primary site revealed a complete response (CR) in 52 patients, partial response (PR) in 4, and stable disease (SD) in 1. Of the 40 patients presenting with nodal metastases, pathological (n = 31) or clinical (n = 6) assessment revealed a CR in 25, PR in 11, and SD in 1, while 3 were unevaluable. Overall, for both primary site and nodal disease, CR was attained in 44 (75%), PR in 12 (23%), and SD in 1 (2%) of the 57 evaluable patients. Only 2 (4%) of 57 evaluable patients have recurred above the clavicle, 1 in the primary site and 1 in the regional lymph nodes. Twelve patients (23%) have failed in distant sites. Grade III/VI toxicity has included gastrointestinal in 6, hematologic in 6, mucosal in 12, vascular in 4, and neurological in 4 patients. CONCLUSION: Concurrent radiation therapy and targeted supradose cisplatin (i.e., RADPLAT) can be safely delivered with high response rates and excellent loco-regional control in advanced Stage III/IV head and neck squamous cell carcinoma.
Adult↗
Early-response gene signalling is induced by angiogenic oligosaccharides of hyaluronan in endothelial cells. Inhibition by non-angiogenic, high-molecular-weight hyaluronan.
The degradation products of hyaluronan are known to stimulate endothelial-cell proliferation and to promote neovascularization associated with angiogenesis, whilst native high-molecular-weight hyaluronan is inhibitory to these processes. To investigate the cellular signalling pathways coupled to hyaluronan-induced responses in angiogenesis, we have analyzed early-response gene expression in vitro, in cultured bovine aortic endothelial cells. Angiogenic oligosaccharides of hyaluronan induced rapid transient up-regulation of the immediate early genes c-fos, c-jun, jun-B, Krox-20 and Krox-24. In contrast, native hyaluronan when used alone failed to elicit a significant change in expression of any of the genes tested, and when used in combination with angiogenic oligosaccharides of hyaluronan, gave a dose-dependent inhibition of induced gene expression. However, prior addition of angiogenic hyaluronan, as little as one minute before addition of high-molecular-weight hyaluronan, abrogated this inhibition, suggesting that positive or negative responses associated with hyaluronan signalling are integrated at a very early stage following receptor binding. Conversely, prior addition of high-molecular-weight hyaluronan led to an irreversible block in gene expression and proliferative response. These data are consistent with native hyaluronan antagonizing the angiogenic response in part by blocking a signalling cascade at or immediately following ligand-receptor interaction. Finally, we demonstrated that chronic exposure to oligosaccharides of hyaluronan is essential for cell proliferation, indicating that short-term immediate early-gene signalling is insufficient to elicit the proliferation of endothelial cells.
Animals↗
Role of Fas ligand and receptor in the mechanism of T-cell depletion in acquired immunodeficiency syndrome: effect on CD4+ lymphocyte depletion and human immunodeficiency virus replication.
Direct killing of CD4+ lymphocytes by human immunodeficiency virus-1 (HIV-1) probably cannot account for the magnitude of the loss of these cells during the course of HIV-1 infection. Experimental evidence supports a pathophysiologic role of the apoptotic process in depletion of CD4 cells in acquired immunodeficiency syndrome (AIDS). The Fas-receptor/Fas-ligand (Fas-R/Fas-L) system mediates signals for apoptosis of susceptible lymphocytes and lympoblastoid cell lines. A number of investigators have recently reported increased expression of the Fas receptor in individuals with HIV infection, along with increased sensitivity of their lymphocytes to anti-Fas antibody mimicking Fas ligand. We attempted to determine the role of Fas-mediated apoptosis in disease progression and viral replication. Increased Fas-receptor (CD95) expression on CD4+ and CD8+ lymphocytes was found in a large group of HIV-1-infected patients compared with normal controls; individuals with a diagnosis of AIDS and a history of opportunistic infection had significantly more Fas receptor expression than did asymptomatic HIV-infected persons and normal blood donor controls (P < .01). Triggering of the Fas-R by agonistic anti-Fas monoclonal antibody, CH11, was preferentially associated with apoptosis in the CD4+ cells; this effect was more pronounced in lymphocytes derived from HIV+ individuals. Soluble and membrane-bound forms of Fas-L were produced in greater amounts in peripheral blood mononuclear cells (PBMC) cultures and in plasma obtained from HIV-1-infected persons than from normal controls. Furthermore, triggering of lymphocytes from HIV-infected persons by CH11 increased levels of interleukin-1beta converting enzyme (ICE), a protein associated with apoptosis. When PBMC were cultured in the presence of CH11, p24 production per number of viable cells was decreased as compared with the same PBMC without CH11 (P < .01). These findings suggest that multiple mechanisms, including increased production of Fas-L by infected PBMC, increased Fas-R expression, and induction of a protease of ICE family, may play roles in the apoptotic depletion of CD4+ cells in HIV infection.
Acquired Immunodeficiency Syndrome↗