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Biomedical subjects

P Joshi

Publications and source records attributed to P Joshi.

At least 37 records · Page 2Linked to original sources
PubMed1998

A comparison of IL-2 levels in nasopharyngeal and endotracheal aspirates of babies with respiratory syncytial viral bronchiolitis.

BACKGROUND: Cytokines such as IL-2 are thought to be important in the pathogenesis of respiratory tract inflammation. Cytokine levels in nasopharyngeal aspirates (NPAs) have been used as a measure of respiratory inflammation in children with viral infections, but it is unclear whether they reflect levels in the lower respiratory tract. OBJECTIVE: We sought to assess the correlation between IL-2 levels in the nasopharyngeal and endotracheal secretions of children intubated with respiratory syncytial virus (RSV)-positive bronchiolitis. METHODS: NPA and endotracheal aspirates were collected concurrently from intubated infants with RSV-positive bronchiolitis. IL-2 levels were assayed by ELISA, and the results were compared according to collection site. RESULTS: Nine paired specimens were collected. IL-2 levels ranged from 31 pg/mL to 8040 pg/mL. No significant difference was found in the geometric mean IL-2 values from the 2 collection sites. The intraclass correlation coefficient between NPA IL-2 levels and endotracheal aspirate IL-2 levels was 0.83. CONCLUSION: IL-2 levels in NPAs are comparable with those in the lower respiratory tracts of infants with RSV-positive bronchiolitis. NPA cytokine levels provide a simple and useful means of assessing respiratory tract inflammation.

Bronchiolitis, Viral↗
PubMed1998

Ethnomedical information and in vitro screening for angiotensin-converting enzyme inhibition of plants utilized as traditional medicines in Gujarat, Rajasthan and Kerala (India).

Plants utilized as traditional medicines in India have been investigated for their ability to inhibit the angiotensin converting enzyme (ACE). In total, 75 species belonging to 42 families have been investigated and new ethnomedical information has been obtained for 41 species. Four species were found to possess a high ACE inhibiting ability and were low in their tannin content.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

The use of lumbar puncture and laboratory tests for sepsis by Australian neonatologists.

OBJECTIVE: To ascertain the current use of lumbar puncture (LP) and laboratory tests for possible or suspected sepsis by Australian neonatologists. METHODS: A self administered anonymous response questionnaire. RESULTS: Sixty-nine (73%) of 94 neonatologists responded. None performed LP routinely in preterm infants with respiratory distress syndrome (RDS) or asymptomatic term infants with maternal Group B streptococcus (GBS) colonisation. One (1.6%) performed LP in term infants with respiratory distress, and only 35 (51%) performed LP in preterm infants with suspected late-onset sepsis (LOS). Twenty-one percent did not perform LP on all preterm infants with RDS and septicaemia and 24% did not perform LP on all preterm infants with late-onset septicaemia. Sixty-six percent and 85% did not perform LP for laboratory evidence suggestive of sepsis in preterm infants with RDS and preterm infants with LOS, respectively. Forty-nine percent investigated asymptomatic term infants with maternal GBS colonisation. CONCLUSIONS: Lumbar puncture and laboratory tests for possible or suspected sepsis are not used uniformly by Australian neonatologists. The presently available information in the scientific literature is ambiguous and systematic review and further scientific study are required to determine best practice guidelines.

Australia↗
PubMed1998

Mechanism of suppression of natural killer cell activity in trauma patients.

Trauma patients develop a severe immunosuppression that includes suppression of natural killer (NK) cell activity although numbers of NK cells are not reduced. The mechanism of suppression of NK cell activity after major trauma is not known. The aim of the present study was to investigate the in vitro effect of plasma samples from trauma patients (TP) on the cytotoxic activity of normal NK cells. Buffycoat mononuclear cells (5x10(5)/well) were preincubated with either TP or plasma samples from age and sex matched healthy controls (CP) for 0, 16 or 40 h. These effector cells were then cultured with 51Cr labeled K-562 cells (2x10(4)/well) for 4 h at 37 degrees C and % lysis was calculated. No significant differences in % lysis between CP and TP were found with 0 or 16 h preincubation, however 40 h preincubation with TP severely suppressed NK cell function (p=0.003) as compared to preincubation with CP for the same period. Addition of neutralizing anti-IL-4, anti-TGF-beta1, or anti-IL-10 antibodies did not reverse the NK cell suppression. There was a partial reversal of NK cell suppression by catalase but not by SOD or L-NMMA. Removal of monocytes from buffycoat mononuclear cells also significantly reversed the NK cell suppression. These data suggest that suppression of NK cell activity in trauma patients may be an accessory cell dependent phenomenon and may partially depend on production of reactive oxygen metabolites (ROM).

Catalase↗
PubMed1997

Randomised trial of oral morphine for painful episodes of sickle-cell disease in children.

BACKGROUND: Oral controlled-release morphine can provide effective analgesia through a non-invasive route and may facilitate outpatient management of severe episodes of sickle-cell pain. We compared the clinical efficacy and safety of oral morphine with continuous intravenous morphine in children with severe episodes of sickle-cell pain, by a double-blind, randomised, parallel-group design. METHODS: 56 children aged 5-17 years received loading doses of intravenous morphine of up to 0.15 mg/kg, followed by randomly assigned oral morphine 1.9 mg/kg every 12 h plus intravenous placebo (saline), or intravenous morphine 0.04 mg kg-1 h-1, plus placebo tablet. Breakthrough pain was treated with oral, immediate-release morphine 0.4 mg/kg every 2-3 h as required. Pain was assessed daily at 0900 h, 1300 h, 1700 h, and 2100 h with a picture face scale, a pictorial scale (Oucher), a behavioural-observational scale (CHEOPS), and by an investigator. FINDINGS: 50 children completed the study (28 boys, 22 girls; mean age 11.2 years [SD 3.5]; mean oral morphine dose 2.99 mg/kg daily [0.75]; mean intravenous morphine dose, 0.81 mg/kg daily [0.30]). Mean overall pain scores were similar for oral and intravenous morphine (CHEOPS, 6.3 [1.5] vs 6.4 [1.4], p = 0.8; Oucher, 31.5 [25.4] vs 39.2 [21.7], p = 0.3; Faces, 2.2 [1.4] vs 2.4 [1.3], p = 0.6; clinical rating, 1.7 [0.7] vs 1.9 [0.5], p = 0.3). Opioid analgesia was required for a mean of 4.2 days (1.7) and 5.4 days (2.6), respectively (p = 0.0591). Pain scores from all scales correlated significantly (r = 0.5865-0.8980, p = 0.0001). Frequency of rescue analgesia did not differ significantly between the oral and intravenous morphine groups (0.7 [0.8] vs 0.9 [0.7] doses daily, p = 0.2). Frequency and severity of adverse events did not differ significantly. INTERPRETATION: Oral, controlled-release morphine is a reliable, non-invasive alternative to continuous intravenous morphine for the management of painful episodes of sickle-cell disease in children.

Administration, Oral↗
PubMed1997

Suppression of natural killer cell activity in patients with fracture/soft tissue injury.

BACKGROUND: Natural killer cells (NKCs) participate in "innate" cell-mediated immunity. Fracture/soft tissue injuries are cytokine rich and may influence cell-mediated immunity. OBJECTIVE: To study the effects of fracture cytokines on NKC function. DESIGN: A case-control study. SETTING: A level I trauma center and laboratory in a university medical center. PARTICIPANTS: Patients requiring open fracture fixation and healthy volunteers. INTERVENTIONS: Fracture supernatants and peripheral plasma were collected during open fracture fixation. Volunteer mononuclear cells were used as effector (NKC) sources. Mononuclear cells were preincubated with fracture supernatants, paired peripheral plasma, or normal plasma under various conditions. MAIN OUTCOME MEASURES: Natural killer cell lysis of K562 target cells was assessed by chromium 51 release. RESULTS: Fracture supernatants suppressed NKC function more rapidly than peripheral plasma. Fracture supernatants from 1 to 4 days after injury were most suppressive. Inactivation of complement and reactive oxygen species failed to restore lysis. Neutralizing antibodies to interleukin 4 and interleukin 10 further suppressed lysis. Antibodies to transforming growth factor beta1 failed to restore lysis. The addition of interferon gamma did not restore lysis but the addition of interleukin 12 did. CONCLUSIONS: Fracture supernatants and peripheral plasma from patients with fractures suppress NKCs. The responsible mediators may be concentrated in fracture/soft tissue injuries. Responses to manipulation of the cytokine environment suggest that fracture cytokines may impair cooperation between NKCs and accessory cells.

Adult↗
PubMed1997

How tubulin subunits are lost from the shortening ends of microtubules.

Microtubules exhibit dynamic instability, switching between persistent states of growth and shortening at their ends. The switch between growth and shortening has been proposed to depend on end conformation where growing ends have "straight" tubulin protofilaments stabilized by a terminal cap of GTP-tubulin, while-shortening ends have lost their GTP-tubulin cap, allowing terminal GDP-tubulin dimers to curve inside-out and peel rapidly away from the microtubule lattice. This "conformational cap" model predicts that tubulin dissociation from shortening ends is a two-step process where the average lengths of curved GDP-tubulin protofilaments at a depolymerizing end will depend on the ratio of the rate of peeling to the rate of breakage of the longitudinal bonds between adjacent curved dimers. We have tested this model for the plus and minus ends of microtubules assembled with pure porcine tubulin off the ends of axoneme fragments in standard assembly buffer. Individual microtubule ends were imaged using video-enhanced differential interference contrast light microscopy. The rate of rapid shortening was systematically increased by isothermal dilution into assembly buffer containing various concentrations of Mg2+ or Ca2+ ions. At 1 mM Mg2+ and no Ca2+, shortening occurred at 20 (plus) and 45 (minus) microns/min. The ends appeared similar in contrast to growing ends and the core of the microtubule and the ends appeared blunt or slightly frayed by negative stain electron microscopy. Above 20 mM Mg2+ or above 5 mM Ca2+, microtubule shortening occurred at 60 (plus) and 115 (minus) microns/min or faster and "knobs" were distinctly visible at depolymerizing ends, particularly at the faster minus ends, and knob contrast remained constant during many micrometers of rapid shortening. Negative stain electron microscopy revealed that these knobs were "blossoms" of inside-out curved protofilaments, some extending for several helical turns (30 to 60 dimers in length) at constant curvature from the ends. At these high shortening velocities, the peeling of curved protofilaments was confined to within several dimers of the end of the microtubule cylinder, suggesting that dimer curling and protofilament peeling is constrained to the tip by interactions between adjacent straight protofilaments. Depolymerization is produced by conformational changes in GDP-tubulin since microtubules assembled with a slowly hydrolizable analog of GTP, GMPCPP, are stable even at 20 mM Mg2+ or 5 mM Ca2+. Monte Carlo simulations show that the ratio of the peeling to breakage rate constants can control the steady-state average length of curved GDP-tubulin protofilaments at the depolymerizing end.

Animals↗
PubMed1997

Dose comparison of remifentanil and alfentanil for loss of consciousness.

BACKGROUND: This study evaluated the efficacy and safety of remifentanil, a potent mu agonist opioid with a rapid onset and offset of effect, as a sole induction agent for loss of consciousness (LOC) and compared it with alfentanil. METHODS: Remifentanil and alfentanil were administered intravenously over 2 min in ascending doses (remifentanil 2, 3, 4, 5, 6, 8, 10, 15, 20 microg/kg; alfentanil 40, 60, 80, 100, 120, 160, 200 microg/kg) to unpremedicated healthy patients. Patients were observed for rigidity and LOC for 30 s after the end of infusion. If patients had not lost consciousness, 2 mg x kg(-1) x min(-1) thiopental was administered until LOC was achieved. Arterial blood samples, obtained at specified time intervals, were analyzed for remifentanil and alfentanil whole-blood concentration. Blood pressure and heart rate were also recorded at preset time intervals. RESULTS: Neither drug could reliably produce LOC. With both drugs, there was a dose-dependent decrease in thiopental requirements and a dose-dependent increase in the incidence and severity of rigidity (P < 0.05). The median effective dose (ED50) for LOC with remifentanil was 12 microg/kg, and for alfentanil it was 176 mcrog/kg. The median effective concentration (EC50; whole-blood concentration) of remifentanil was 53.8 ng/ml and for alfentanil it was 1,012 ng/ml. Minimal hemodynamic changes were observed after either drug was given. CONCLUSIONS: Remifentanil is 15 times more potent than alfentanil, based on the ED50 to achieve loss of response to a verbal command and 20 times more potent than alfentanil based on the EC50. Neither opioid is suitable as a sole induction agent.

Adult↗
PubMed1997

The immune microenvironment of human fracture/soft-tissue hematomas and its relationship to systemic immunity.

The immune environment of human soft-tissue injury is unstudied. We studied fracture soft-tissue hematomas (FxSTH) in 56 patients with high-energy bony fractures. FxSTH serum and mononuclear cells (MNC) as well as fracture patient plasma and blood MNC were studied. Twenty healthy controls donated plasma and MNC. Soluble tumor necrosis factor (TNF)-alpha, interleukin (IL-1 beta, IL-2, 6, 8, 10, 12, and interferon-gamma were studied by enzyme linked immunosorbent assay. Cells were studied by flow cytometry after cell-membrane stains for CD-14, TNF-alpha (mTNF), and human leukocyte antigen-DR, or intracellular stains for TNF (icTNF) and IL-10. Thirty-six patients with Injury Severity Score < 15 were analyzed further to evaluate the effects of isolated fracture on systemic immunity. Cytokines were rarely detectable in control plasma. TNF-alpha, IL-1 beta, IL-2, and interferon-gamma were rarely found in FxSTH serum or fracture patient plasma. All FxSTH sera were rich in IL-6, peaking before 48 hours (12,538 +/- 4,153 vs. 3,494 +/- 909 pg/mL, p = 0.02, U test). In Injury Severity Score < 15, IL-6 was not detectable in most early fracture patient plasma, but rose after 48 hours (p = 0.028). FxSTH serum IL-8 peaked after 48 hours (440 +/- 289 vs. 4,542 +/- 1,219 pg/mL, p = 0.006) and circulating IL-8 appeared after 72 hours. IL-6 and IL-8 showed gradients from FxSTH serum to paired PtS (p < 0.05, Wilcoxon). IL-10 was abundant (884 +/- 229 pg/mL) in FxSTH serum < 24 hours old. FxSTH serum IL-12 peaked late (3,323 +/- 799 pg/mL, day 4-7) then fell (p < 0.001, analysis of variance). Only IL-12 was higher in fracture patient plasma (1,279 +/- 602 pg/mL) than FxSTH serum (591 +/- 327 pg/mL) during the first 48 hours (p = 0.032, U test). On flow cytometry, control monocytes expressed 201 +/- 31 mTNF sites/cell, but icTNF was absent. mTNF was up-regulated after injury more in FxSTH monocytes (3,202 +/- 870 sites/cell) than peripheral blood monocytes (584 +/- 186 sites/cell) (p < 0.05 vs. peripheral blood monocytes by Wilcoxon, p < 0.001 vs. control monocytes by U test). Intracellular IL-10 was abundant in all MNC, but varied widely after injury. Fracture and peripheral blood monocytes expressed far less human leukocyte antigen-DR than control monocytes. Fractures create an inflammatory local environment. Proximal mediators are cell-associated and relatively confined to the wound, but soluble IL-6, IL-8, and IL-10 are abundant and probably exported. Systemic MNC have complex responses to local injuries. These may reflect the combined impact of multiple soluble cytokines initially generated within the wound. FxSTH appear to be a potentially important source of immunomodulatory cytokines in trauma.

Adolescent↗
PubMed1997

A case of nondigitalis cardiac glycoside toxicity.

A case is presented of cardiac glycoside poisoning in a 1-year-old patient from the plant Nerium oleander (common oleander). The patient had bradycardia, vomiting, altered level of consciousness, and no history of ingestion. Antibody-based digoxin assays may cross-react with other cardiac glycosides nonquantitatively. Chromatographic techniques can be used in the specific diagnosis.

Animals↗
PubMed1997

Review of a home-based palliative care program for children with malignant and non-malignant diseases.

This retrospective chart review presents the patient characteristics and utilization of the home-based palliative care program at The Hospital for Sick Children in Toronto. A total of 126 children dying from a broad spectrum of diseases was admitted during the period 1986-1994, referred from neurosurgery, genetic/metabolic, neurology, neonatology, nephrology, cardiology, general pediatrics, general surgery, and pulmonology. At the time of review, 15 patients remained alive and 18 had been discharged from the program. Mean age at the time of referral was 4.8 +/- 0.51 years and mean age at death was 5.3 +/- 0.55 years. The mean number of days in hospital was 26.5 +/- 14.6 while days spent at home averaged 98.4 +/- 15.2; thus 80% of the children's remaining time was spent at home. The average number of parent-team contacts was 3.5 +/- 0.9 by pager and 24.0 +/- 2.9 by telephone. Of the 93 patients who died in the program, 53% died at home, 18% died in community hospitals, and 29% died in a tertiary care facility. Analgesic medications were administered to 54% of the patients; 56% of these then required opioid analgesia for pain and symptom management. Home-based palliative care appeared to be an effective program for many children with a variety of terminal illnesses after adequate supports for the child and family had been established.

Adolescent↗
PubMed1996

Psychiatric diagnoses in the child and adolescent members of extended families identified through adult bipolar affective disorder probands.

OBJECTIVE: To investigate the type and distribution of psychiatric disorders in the child and adolescent members of extended pedigrees identified through bipolar probands. METHOD: The child and adolescent offspring (24 male, 26 female, aged 6 to 17 years) and the adult parents (60) of 14 bipolar pedigrees ascertained for the National Institutes of Mental Health Genetics Initiative Study of Bipolar Affective Disorder were personally assessed using structured psychiatric interviews. A parent was also interviewed about each child or adolescent offspring. RESULTS: Twelve of the 50 interviewed offspring received a lifetime DSM-III-R diagnosis of an affective disorder. This included six cases of bipolar disorder, five cases of major depressive disorder, and one case of dysthymia. Eight of the offspring who received an affective disorder diagnosis also qualified for an anxiety disorder (four), a disruptive behavior disorder (two), or both (two). Offspring who had a parent with an affective disorder had a 5.1-fold higher risk for receiving an affective disorder diagnosis than did offspring with healthy parents. CONCLUSIONS: In a consecutive series of families identified through a proband with bipolar disorder, there were significant increases in the prevalence of affective disorder diagnoses in the child and adolescent offspring. The distribution of illness in offspring was compatible with the presence of important genetic factors which contribute to early-onset affective illness.

Adolescent↗
PubMed1996

Production of interleukin-10 in human fracture soft-tissue hematomas.

Clinical trauma suppresses immunity and experimental wound fluids have been shown to be immunosuppressive. To ascertain whether human wounds contain immunosuppressive cytokines, we assayed serum from fracture/soft-tissue hematomas (FSTH) of 22 patients for interleukin (IL)-10, transforming growth factor (TGF)-beta 1, and IL-4. Results were correlated to concurrent plasma cytokine concentrations in the same patients and in volunteer plasma. IL-10 was present in high concentration (1376 +/- 539 pg/mL) in all (7/7) FSTH < 24 h old. In FSTH > 24 h old, IL-10 was found intermittently and at lower levels (239 +/- 106 pg/mL, p = .011 vs. FSTH < 24 h old). IL-10 was rarely detectable in fracture patient plasma and never detectable (< 20 pg/mL) in normal plasma. No significant variations of IL-4 or total TGF-beta 1 were found in FSTH or plasma. FSTH are significant potential sources of IL-10 activity in trauma patients, which may be overlooked when only plasma is assayed. The potential for a relationship between cytokines found locally at sites of injury and clinical immune modulation in trauma requires further study.

Adult↗
PubMed1996

Increase in brain nitric oxide synthase activity in daunorubicin-treated rats.

Anthracyclines such as daunorubicin are very effective anticancer agents. These drugs are known to cause side effects including cardiotoxicity. Anthracyclines are neurotoxic to laboratory animals. Nitric oxide is a novel and very important chemical messenger in the brain. However, at higher levels, nitric oxide causes well defined neurotoxicity. Therefore, we determined nitric oxide synthase activity in rat brain after daunorubicin treatment in an effort to explain the neurotoxicity produced by anthracyclines. Male Sprague-Dawley rats were treated with different subcutaneous doses of daunorubicin (0.1-4.0 mg/kg/week for five weeks) while control animals were injected with phosphate buffered saline. There was a significant increase (80%) of nitric oxide synthase activity in daunorubicin-treated animals as compared to controls. This activity was inhibited by N-monomethyl-L-arginine (NMMA), nitroarginine, N-6-aminohexyl-5-chloro-1-napthalene sulfonamide (W-7), a calmodulin antagonist, suggesting that the nitric oxide synthase activity is calmodulin dependent. Further, our in vitro studies demonstrated that daunorubicin interacted with calmodulin as measured by N-phenyl-1-napthylamine (NPN) fluorescence. These results indicate that daunorubicin increases nitric oxide synthase activity in rat brain which may increase the levels of nitric oxide. The increased levels of nitric oxide may cause neurotoxicity. Our results further indicate that daunorubicin interacts with calmodulin and enhances nitric oxide synthase activity which is dependent on calmodulin.

Animals↗
PubMed1996

Suppression of natural killer cell activity in biliary obstruction.

Prior studies regarding immune function in bile-duct ligated rats have illustrated blunted immune function. The present study measures natural killer (NK) cell activity. Rats underwent bile duct ligation (BDL) or sham celiotomy (SC) and were sacrificed at 1, 2, and 3 weeks after surgery. Ficoll-Hypaque density centrifugation was used to obtain a purified preparation of splenocytes. NK cell activity was determined by incubating varying concentrations of splenocytes with chromium-labelled YAC-1 tumor cells for 4 hours. Chromium release was measured by a gamma counter and expressed as per cent activity (compared with 100 per cent activity obtained by complete lysis with detergent). The experiments were repeated after preincubation in tissue culture flasks to remove an adherent cell population. NK cell activity was decreased at all spleen cell:target cell ratios studies at 1 week after BDL. At 2 weeks after BDL, NK cell activity was decreased at all but the lowest two concentrations; and 3 weeks after BDL, NK cell activity was decreased only at the highest concentrations used. Separation of an adherent cell fraction restored NK cell activity. This suppression in NK cell activity one week after BDL may account, in part, for the poor response of BDL animals to bacterial and immune challenge. Restoration of activity after removal of an adherent cell fraction suggests that macrophages may be at least partly responsible for this inhibition.

Animals↗
PubMed1995

Isolation of a spermatozoa motility inhibiting factor from chicken seminal plasma with antibacterial property.

A 78-kDa spermatozoa motility inhibiting factor (SMIF) was purified from chicken (Gallus domesticus) seminal plasma by anion exchange (DE-53) followed by affinity chromatography on concanavalin A-Sepharose. The factor is thermostable and inhibited the spermatozoa motility in a dose dependent manner. In addition, SMIF inhibited the growth of gram negative bacteria, Pasteurella multocida but not gram positive Streptococcus equi. The factor lost its spermatozoa immobilizing property after treatment with trypsin, chymotrypsin or pepsin. The inhibition of SMIF by beta-mercaptoethanol suggest the involvement of disulfide bonds in its activity. Similarly, this property was lost in presence of chicken seminal plasma or incubating SMIF with anti-SMIF antibodies. Evidence is provided for the presence of a high molecular weight protein (> 100 kDa) in chicken seminal plasma that neutralizes the motility inhibiting property of SMIF. No significant decrease in spermatozoa ATP was observed in presence of SMIF suggesting that the loss of spermatozoa motility was due to factors other than depletion in cell's energy. Using anti-SMIF antibodies, a cross-reactive protein was identified in the blood, liver and reproductive tissues of chicken and the seminal plasma of cattle and buffalo. However, the cross-reactive protein failed to inhibit chicken spermatozoa motility. The significance of SMIF in chicken seminal plasma is discussed.

Animals↗