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Biomedical subjects

G Warner

Publications and source records attributed to G Warner.

At least 37 records · Page 2Linked to original sources
PubMed1997

Open randomised trial of prescribing strategies in managing sore throat.

OBJECTIVE: To assess three prescribing strategies for sore throat. DESIGN: Randomised follow up study. SETTING: 11 general practices in the South and West region. SUBJECTS: 716 patients aged 4 years and over with sore throat and an abnormal physical sign in the throat; 84% had tonsillitis or pharyngitis. Patients were randomised to three groups: prescription for antibiotics for 10 days (group 1,246 patients); no prescription (group 2,230 patients); or prescription for antibiotics if symptoms were not starting to settle after three days (group 3; 238 patients). MAIN OUTCOME MEASURES: Duration of symptoms; satisfaction and compliance with and perceived efficacy of antibiotics; time off school or work. Outcomes were documented in 582 subjects (81%). RESULTS: Median duration of antibiotic use differed significantly in the three groups (10 v 0 v 0 days, P < 0.001); 69% of patients in group 3 did not use their prescription. The proportion of patients better by day 3 did not differ significantly (37% v 35% v 30%, P = 0.28), nor did the duration of illness (median 4 v 5 v 5 days, P = 0.39), days off work or school (median 2 v 2 v 1, P = 0.13), or proportion of patients satisfied (96% v 90% v 93%, P = 0.09), although group 1 had fewer days of fever (median 1 v 2 v 2 days, P = 0.04). More patients in group 1 thought the antibiotics were effective (87% v 55% v 60%, P < 0.001) and intended coming to the doctor in future attacks (79% v 54% v 57%, P < 0.001). "Legitimation" of illness-to explain to work or school (60%) or family or friends (37%)-was an important reason for consultation. Patients who were more satisfied got better more quickly, and satisfaction related strongly to how well the doctor dealt with patient's concerns. CONCLUSION: Prescribing antibiotics for sore throat only marginally affects the resolution of symptoms but enhances belief in antibiotics and intention to consult in future when compared with the acceptable strategies of no prescription or delayed prescription. Psychosocial factors are important in the decision to see a general practitioner and in predicting the duration of illness.

Adolescent↗
PubMed1997

Assessment of dose proportionality, absolute bioavailability, and immunogenicity response of CTLA4Ig (BMS-188667), a novel immunosuppressive agent, following subcutaneous and intravenous administration to rats.

PURPOSE: The objectives of this study were: to delineate the pharmacokinetics of CTLA4Ig in rats after single and multiple intravenous (IV) and subcutaneous (SC) doses; to assess the relationship of the pharmacokinetic parameters of CTLA4Ig vs dose; to calculate the SC absolute bioavailability; and to assess the antibody response of CTLA4Ig. METHODS: A total of 48 (24 male and 24 female) Sprague Dawley rats were divided into eight treatments with 3 rats per gender in each group: a single dose of 10, 80, or 200 mg/kg of CTLA4Ig given either IV or SC and a repeated dose of 10 mg/kg (once every other day for 7 doses over 13 days) given either SC or IV. Serial blood samples were collected up to 43 days after single dose administration and up to 50 days following the administration of the last multiple dose on day 13. The serum concentration of CTLA4Ig and anti-CTLA4Ig antibodies were measured using ELISA assays. RESULTS: After single IV doses, Cmax and AUCinf increased in a dose proportional manner; CL appeared to be dose independent, while both Vss and T1/2 increased as the administered dose increased. Following single SC doses, Cmax and AUCinf increased in a linear manner but not proportionally; mean Tmax values were prolonged but similar among the three dose levels, while T1/2 increased as the administered dose increased. The absolute SC bioavailability of CTLA4Ig decreased as the dose increased from 10 (62.5%), 80 (55.7%), and 200 mg/kg (41.1%). Comparison of the AUCtau values between the first and last doses suggested an accumulation (3.1-4.7) of CTLA4Ig. However, regardless of the route of dosing, AUCtau after the last dose were comparable to AUCinf values following the single dose. Anti-CTLA4Ig antibodies were detected at the 10 mg/kg dose level after single or multiple doses for both routes of administration. However, regardless of single or multiple doses, antibody titers were relatively greater for the SC compared to the IV administration. CONCLUSIONS: The key findings of this study were: (i) the elimination characteristics of CTLA4Ig were comparable between the SC and IV routes; (ii) the repeated dosing did not alter the pharmacokinetics of CTLA4Ig; (iii) the SC absolute bioavailability tended to decrease as the administered dose increased; and (iv) a greater formation of anti-CTLA4Ig antibodies was observed after SC compared to IV at a single 10 mg/kg dose level; however, after multiple dosing, the formation of antibodies from either of the two routes was relatively slower, and (v) during the study period, no antibodies were observed at either the 80 or 200 mg/kg dose levels regardless of the route of administration.

Abatacept↗
PubMed1997

Epidemic and sporadic hepatitis E virus transmission in West Kalimantan (Borneo), Indonesia.

A cross-sectional survey was conducted in West Kalimantan (Borneo), Indonesia to geographically profile hepatitis E virus (HEV) prevalence in the riverine areas recognized as the foci of epidemic HEV transmission in 1987. Additionally, a contiguous, although distinct, population with no identifiable historical exposure to epidemic HEV was surveyed downstream for comparative purposes. Eight hundred eighty-five sera were assayed by enzyme immunoabsorbent assay for anti-HEV IgG and anti-hepatitis A virus (HAV) IgG markers. A very high percent (90%) of both the outbreak and comparison populations was anti-HAV IgG positive by the age of nine years. In contrast, the prevalence of anti-HEV IgG in the outbreak area (50%) was significantly higher than in the comparison area (23%) (P < 0.0001). In both the outbreak and comparison areas, anti-HEV IgG prevalence increased with age ( < 0.0001), except for the group > or = 50 years of age. The prevalence (53%) of antibody to HEV in the population > or = seven years of age from the outbreak area (alive during the actual 1987 outbreak) was significantly (P < 0.0001) greater than among the children < seven years of age (born after the outbreak) (15%). However, anti-HEV IgG prevalence among the population from the comparison area did not differ significantly between the > or = seven- (23%) and < seven- (20%) year-old age groups. The percentage of anti-HEV IgG-positive individuals among males (47%) from the outbreak area was lower (P < 0.05) compared with females (55%). While overall usage of river water for drinking purposes was not universal, dependence on river water as a primary source was significantly higher (P < 0.001) in households from the outbreak area (60%) compared with the comparison area (30%). This study indicates persistence of an anti-HEV IgG response in a large percentage of the population seven years after an epidemic of HEV infections. Also, the relatively high prevalence (15%) of anti-HEV in children < seven years of age from the outbreak area reflects continuing, sporadic infections.

Adolescent↗
PubMed1997

Functional magnetic resonance imaging studies of emotional processing in normal and depressed patients: effects of venlafaxine.

BACKGROUND: Functional magnetic resonance imaging (fMRI) techniques were used to identify the neural circuitry underlying emotional processing in control and depressed subjects. Depressed subjects were studied before and after treatment with venlafaxine. This new technique provides a method to noninvasively image regional brain function with unprecedented spatial and temporal resolution. METHOD: Echo-planar imaging was used to acquire whole brain images while subjects viewed positively and negatively valenced visual stimuli. Two control subjects and two depressed subjects who met DSM-IV criteria for major depression were scanned at baseline and 2 weeks later. Depressed subjects were treated with venlafaxine after the baseline scan. RESULTS: Preliminary results from this ongoing study revealed three interesting trends in the data. Both depressed patients demonstrated considerable symptomatic improvement at the time of the second scan. Across control and depressed subjects, the negative compared with the positive pictures elicited greater global activation. In both groups, activation induced by the negative pictures decreased from the baseline scan to the 2-week scan. This decrease in activation was also present in the control subjects when they were exposed to the positive pictures. In contrast, when the depressed subjects were presented with the positive pictures they showed no activation at baseline, whereas after 2 weeks of treatment an area of activation emerged in right secondary visual cortex. CONCLUSION: While preliminary, these results demonstrate the power of using fMRI to study emotional processes in normal and depressed subjects and to examine mechanisms of action of antidepressant drugs.

Adolescent↗
PubMed1997

Sore throat.

Explore the source record for details and available documents.

Anti-Bacterial Agents↗
PubMed1996

Pharmacokinetics and pharmacodynamics of CTLA4lg (BMS-188667), a novel immunosuppressive agent, in monkeys following multiple doses.

The dose proportionality and multiple dose pharmacokinetics of CTLA4Ig, an immunosuppressive drug under development, were investigated in 12 cynomolgus monkeys in a parallel study. The activity of CTLA4Ig in suppressing the immunoresponses to sheep red blood cell (SRBC) was also assessed. Two monkeys per gender were randomly assigned to one of the three dose levels, 1.0, 2.9, and 8.7 mg/kg of CTLA4Ig. The monkeys in each dose level received the assigned intravenous dose of CTLA4Ig by a bolus injection into a saphenous vein on days 1, 4, 8, 11, 15, and 18. Immediately after the administration of CTLA4Ig on day 1, each monkey was challenged with SRBC. Serial blood samples were collected up to 720 h following administration of CTLA4Ig on day 18 (last dose). In addition, predose blood samples were obtained on days 1, 4, 8, 11, 15, and 18. Serum samples were analyzed for the concentrations of CTLA4Ig using a validated ELISA method. The data obtained were subjected to noncompartmental pharmacokinetic analyses. The serum concentrations of CTLA4Ig attained steady state by day 11 regardless of the dose levels. The mean AUC0-720 values of CTLA4Ig increased in a dose proportional manner. The mean values of Cmax increased in a ratio of 1:3:3:8:5 while the dose administered increased in a ratio of 1:3:9. Predose serum concentrations (Cmin) of CTLA4Ig increased in a dose proportional manner. The mean T1/2 values were not significantly different among the dose groups, suggesting that the elimination characteristics of CTLA4Ig were not altered as the dose increased. Dose-related immunosuppressive activity of CTLA4Ig (78-98% inhibition) was observed in monkeys immunized intravenously with SRBC. In conclusion, CTLA4Ig exhibits linear kinetics and demonstrates significant immunosuppressive activity over a dose range of 1.0-8.7 mg/kg in monkeys.

Abatacept↗
PubMed1996

The role of endogenous nerve growth factor in human diabetic neuropathy.

Nerve growth factor (NGF) is trophic to sensory and sympathetic fibers. In animal models, NGF is depleted in diabetic nerves and NGF deprivation produces hypoalgesia. Exogenous NGF can reverse some of the pathological changes in diabetic nerves and NGF excess leads to hyperalgesia. We have quantified sensory and autonomic function in early diabetic polyneuropathy and correlated changes with levels of NGF and neuropeptides in affected skin. We describe an early length-dependent dysfunction of sensory small-diameter fibers, prior to dysfunction of sympathetic fibers, with depletion of skin NGF and the sensory neuropeptide substance P. We describe a significant correlation between NGF depletion and decreased skin axon-reflex vasodilation, mediated by small sensory fibers partly via substance P release. Immunostaining shows depletion of NGF in keratinocytes in diabetic skin. We propose that a decrease in endogenous skin-derived NGF influences the presentation of diabetic polyneuropathy, although metabolic or vascular abnormalities may be the cause of the neuropathy. As loss of nociception and axon-reflex vasodilation contribute to diabetic foot ulceration, early and prolonged NGF treatment at an appropriate dose may provide rational prophylaxis for this condition.

Adolescent↗
PubMed1996

The placebo effect in acute headache management: ketorolac, meperidine, and saline in the emergency department.

In a prospective, double-blind, randomized study, ketorolac 60 mg, meperidine 50 mg plus promethazine 25 mg, and normal saline given by intramuscular injection were compared as treatment for acute headache crises. Thirty patients (6 men and 24 women) presenting to an urban emergency department with any type of benign headache were randomized into three groups and filled out the McGill Short-Form Pain Questionnaire with a Pain Rating Index and a Visual Analogue Pain scale. They received one of the study medications and repeated the testing after 1 hour. The objective was to test the efficacy of ketorolac in this population. Separate analyses of the McGill Short-Form (Total, Sensory, Affective, and Pain Rating Index scales) and the Visual Analogue Pain scale responses showed that the three treatments produced a significant reduction in pain (P < .0001), but that pain reduction did not differ among the treatments. This profound reduction observed after administration of a placebo prevented accurate evaluation of the effects of ketorolac. The placebo response must be considered in the design of future trials using intramuscular medications in the acute intervention of headache crises. In addition, the use of a standard analgesic is necessary to demonstrate both assay sensitivity and magnitude of response to placebo.

Acute Disease↗
PubMed1995

Kawasaki disease associated with streptococcal infection within a family.

OBJECTIVE: To describe the illness occurring in four members of a family, which had clinical and laboratory features of Kawasaki disease and streptococcal infection. METHODOLOGY: A retrospective report of three siblings and an adult male living in one household. The children had serology, blood counts, cultures and echocardiography performed and were treated with antibiotics and gammaglobulin infusions. RESULTS: The patients developed clinical, and exhibited laboratory, features suggesting streptococcal infection and 4/5 criteria suggesting the diagnosis of Kawasaki disease. All made a good clinical recovery but the youngest developed a coronary artery aneurysm. CONCLUSIONS: It may be difficult to distinguish streptococcal infection and Kawasaki disease. It is possible that some cases of Kawasaki disease are precipitated by streptococcal infection.

Adult↗
PubMed1995

Protein C deficiency and stroke in early life.

Plasma concentrations of protein C, protein S and antithrombin III were measured in 33 unselected children with a history of cryptogenic stroke (group 1), four children with previously ascertained low plasma concentrations of protein C following stroke (group 2) and 42 healthy children undergoing minor surgery (group 3). Protein S and antithrombin III were normal in all patients. Low concentrations of protein C were found in two patients in group 1 and in six healthy children in group 3. Low protein C concentrations returned to normal over many months in three of the four patients in group 2. Prophylactic antithrombotic therapy and/or termination of pregnancy had been carried out unneccessarily in two families in whom inherited protein C deficiency was not confirmed. The suggestion that heterozygous protein C deficiency contributes to the risk of arterial stroke was not supported by this study.

Adolescent↗
PubMed1991

Survival after neonatal myocardial infarction.

These are case reports of two children with structurally normal hearts and with normal coronary arteries, who survived myocardial infarction in the early neonatal period. They are only the third and fourth reported survivors of neonatal myocardial infarction and the first in which hypercholesterolemia is postulated to have played an important role. The most likely cause of the myocardial infarction was thrombosis or thromboembolism. Changes in hemostatic function associated with hypercholesterolemia may be relevant.

Coronary Angiography↗
PubMed1990

Metabolism of nicotine by hepatocytes.

The profile of nicotine metabolites produced by freshly isolated hepatocytes from rats, hamsters, guinea pigs, mice and humans was investigated after a 30-min exposure to nicotine ([2-14C]pyrrolidine). Large species differences occurred in the extent of nicotine metabolism; these ranged from 95% metabolism in guinea pig hepatocytes to only 30% metabolism in human and rat hepatocytes. The spectrum of metabolites formed also varied widely in different species. In hepatocytes from obese human subjects, nicotine was metabolized most extensively in smokers, least in nonsmokers, and to an intermediate degree in exsmokers, suggesting that cigarette smoking enhances the rate of nicotine metabolism. Pretreatment of all nonhuman species studied with phenobarbital and beta-naphthoflavone and with Aroclor in rats produced distinctive inductive patterns. Phenobarbital pretreatment of nonsmokers for 2 days prior to liver biopsy doubled the extent of nicotine conversion to cotinine by their hepatocytes. Rat and hamster hepatocytes exhibited sex and stereoselectivity differences in nicotine metabolism. Collectively, these studies indicate that hepatocytes offer some advantages over in vivo systems in investigating certain aspects of nicotine metabolism.

Animals↗
PubMed1987

Effect of hypoxia-induced periodic breathing on upper airway obstruction during sleep.

We studied the effect of hypoxia-induced unstable and periodic breathing on the incidence of obstructed breaths in nine subjects who varied widely in their increase in total pulmonary resistance (RL) during non-rapid-eye-movement (NREM) sleep. During normoxic NREM sleep, all subjects showed hypoventilation, augmented diaphragmatic electromyogram (EMGdi), and increased RL. This response varied: two subjects doubled their mean RL (range 6-9 cmH2O X l-1 X s); four moderate snorers increased RL four- to eightfold (RL = 16-48 cmH2O X l-1 X s); three heavy snorers showed high RL (31-89 cmH2O X l-1 X s) plus cyclical obstructive hypopnea as their predominant breathing pattern. In seven of nine subjects, hypoxia and coincident hypocapnia initially caused an irregular cyclical breathing pattern with obstructed breaths (RL greater than 50 cmH2O X l-1 X s). The incidence of obstructed breaths induced by unstable breathing was closely correlated with the level of RL experienced in the control condition of normoxic sleep (r = 0.91). The obstructed breaths had relatively high O2 saturation (90-96%) and markedly reduced EMGdi activity and peak flow rate (less than 0.2 l/s) compared with breaths immediately after the obstructed breaths, which showed lower O2 saturation (81-93%) and markedly augmented EMGdi and flow rates. After 3-6 cycles of obstructive hypopnea, periodic breathing occurred in most subjects. During periodic breathing in six of seven subjects, the incidence of obstructed or high-resistance breaths was decreased or eliminated since each central apneic period was followed by breath clusters characterized by very high EMGdi, very low RL, and high flow rates. The remaining subject showed a high incidence of obstructed breaths during all phases of normoxic and hypoxic sleep. These data show that hypoxia-induced instability in breathing pattern can cause obstructed breaths during sleep coincident with reduced motor output to inspiratory muscles. However, this obstruction is only manifested in subjects susceptible to upper airway atonicity and narrowing (such as snorers) and can be prevented in most cases if respiratory drive is permitted to reach sufficiently high levels (as during central apnea).

Adult↗
PubMed1986

Balloon dilatation pulmonary valvuloplasty in pulmonary stenosis.

Balloon valvuloplasty was used to treat congenital pulmonary valve stenosis in 13 patients, 11 with isolated pulmonary stenosis, one associated with complex univentricular heart and tricuspid atresia, and one associated with tetralogy of Fallot. A balloon catheter was introduced through the pulmonary valve over a guidewire positioned in the distal pulmonary artery and inflated for 15 seconds on two or three occasions to 3 to 5 atmospheres and rapidly deflated. Marked improvement in pressure gradients was achieved in eight of the 11 patients with isolated pulmonary valve stenosis and symptoms disappeared in the only patient in this group who was symptomatic. The two patients with complex congenital malformations improved clinically. The procedure was without complication and satisfactory results have been maintained from two to twelve months later. The procedure offers effective treatment. We believe that pulmonary balloon valvuloplasty should be the initial treatment for isolated severe and moderate pulmonary valve stenosis.

Catheterization↗