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Biomedical subjects

J Barlow

Publications and source records attributed to J Barlow.

At least 91 records · Page 5Linked to original sources
PubMed1992

Discovery of a peptide-based renin inhibitor with oral bioavailability and efficacy.

Peptidic renin inhibitors have been poorly absorbed across the intestine or rapidly eliminated by the liver and have been reported to have oral bioavailabilities of less than 2%. A peptide-based renin inhibitor, A-72517 (molecular mass of 706 daltons), was devised that has oral bioavailabilities of 8, 24, 32, and 53% in the monkey, rat, ferret, and dog, respectively. Dose-related reductions in blood pressure, plasma renin activity, and plasma angiotensin II in parallel with increased plasma drug concentrations were observed after oral administration of A-72517 to conscious, salt-depleted dogs. Thus, peptide-based molecules of sizable molecular mass can be absorbed intact into the systemic circulation of animals. These findings support the potential of peptide-based drugs for oral administration.

Administration, Oral↗
PubMed1992

Discovery of a well-absorbed, efficacious renin inhibitor, A-74273.

The development of orally active renin inhibitors has been plagued by limited bioavailability in animals and humans. A-74273 is a novel, potent nonpeptide inhibitor of human renin (IC50 = 3.1 nM). This compound was absorbed into the portal and systemic circulations of anesthetized rats, ferrets, monkeys, and dogs after intraduodenal dosing. This favorable pattern also was observed after oral dosing in conscious animals, except in monkeys. Hepatic extraction of A-74273 was more efficient in rats and monkeys than in dogs or ferrets. A-74273 modestly inhibits dog renin, and when given orally as the base (0, 0.3, 1, 3, 10, and 30 mg/kg; n = 8 per dose) to conscious, salt-depleted dogs it induced dose-related reductions in mean arterial pressure and plasma renin activity. Peak falls in mean arterial pressure from normotensive baselines were -14 +/- 1, -26 +/- 3, and -44 +/- 3 mm Hg for the 3, 10, and 30 mg/kg groups, respectively (p < 0.05). Baseline plasma renin activity values (10.9 +/- 1.1-12.7 +/- 1.1 ng angiotensin I/ml/hr) were maximally inhibited, ranging from 43 +/- 8% at 0.3 mg/kg to 98 +/- 1% at 30 mg/kg. Bioavailability in this model was estimated to be 54 +/- 13% when plasma drug levels were determined by a renin inhibitory activity assay, but bioavailability was lower when compared with high-performance liquid chromatographic analysis of A-74273. This discrepancy was accounted for by the identification of structurally similar metabolites that are as active as the parent drug against human renin but much less potent against dog renin.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorption↗
PubMed1992

Double-blind comparison of patient recovery after induction with propofol or thiopentone for day-case relaxant general anaesthesia.

Postoperative recovery after induction with either propofol or thiopentone has been compared in forty ASA I unpremedicated day surgery patients undergoing surgical extraction of third molar teeth under relaxant general anaesthesia. Mean recovery times in the propofol group, required for patients to sit out of bed (44.8 minutes; SD 18.6) and meet discharge criteria (113.1 minutes; SD 34.5) were significantly (P less than 0.05) shorter than those in the thiopentone group (59.7 minutes; SD 21.4 and 133.5 minutes; SD 34.5). Fewer patients in the propofol group were treated in the recovery room for nausea and vomiting and the incidence of mild nausea not requiring treatment was less in the propofol group, but these differences were not statistically significant. Postoperative mental performance, measured by the FAST index, a new test of mental speed, was reduced on average by 1.7% of preoperative levels, during the recovery period tested, with no significant difference between the groups.

Adult↗
PubMed1991

Monozygotic twins with seizures. Shared characteristics.

Eleven sets of monozygotic twins with idiopathic seizure disorders seen at Children's Hospital, Boston, Mass, were reviewed Nine twin pairs were concordant for seizures. A marked correlation in the precise timing of onset of seizures was found; three sets of twins had their first clinical seizures within a 24-hour period of one another. The clinical features of the seizures and the electroencephalographic patterns, including the location of focal discharges, were strikingly similar in the twin pairs. The significance of these findings in suggesting aberrant processes that may contribute to epileptic syndromes is discussed.

Brain↗
PubMed1991

Patient satisfaction among the residential population of a psychiatric hospital.

Patient satisfaction with the interpersonal and amenities aspects of care in a psychiatric hospital was investigated in an Australian setting. The study was carried out among the long-term residential population of a psychiatric hospital and involved 112 out of 195, or 57% of all eligible patients. Cluster analysis identified seven major groups of related items concerning the patients' views of hospital life and their perception of problems. The study largely replicated the findings of an English investigation, showing that many of the same underlying clusters of satisfaction-dissatisfaction with life in a psychiatric hospital emerge, across widely geographically separated settings. The results from the present study further indicate that improvements in autonomy for the patients and a greater say in the running of wards are more important factors contributing to satisfaction with life in a hospital than the physical surroundings themselves.

Adolescent↗
PubMed1990

Neonatal cilia: ultrastructure.

The number of inner and outer dynein arms and gross cilial abnormalities of well newborn children and adults were similar. Inability to see all nine outer dynein arms in healthy adults may be due to technique and not recent infection or congenital cilial malformation.

Adult↗
PubMed1989

Whole body and regional fuel metabolism during early postexercise recovery.

We studied whole body and regional fuel metabolism 1-4 h after cycle exercise [70% maximum O2 consumption (VO2max)], using the insulin clamp technique (40 mU.M-2.min-1) with indirect calorimetry. Substrate fluxes were determined in nonexercised (forearm) muscle tissues. Total glucose utilization was not increased by exercise, either in the preinsulin or insulin-stimulated state. Glucose oxidation tended to decrease, and lipid oxidation was increased after exercise. Forearm glucose uptake (FGU) was increased 5 times by insulin in the resting state, due largely to increased fractional extraction (P less than 0.05). After exercise, FGU was not increased by insulin. Forearm alanine and lactate release was doubled 2 h after exercise. Branched-chain amino acid (BCAA) concentrations were increasing after exercise (P less than 0.01) at a time when forearm muscle was taking up these amino acids. Insulin infusion suppressed the elevated release of gluconeogenic precursors from the forearm and suppressed the elevated concentrations of BCAAs, free fatty acids, and glycerol present after exercise. In summary, basal and insulin-stimulated glucose utilization is not augmented by prior high-intensity exercise, partly because nonexercised muscle is insulin resistant. Insulin infusion attenuates the altered metabolic milieu seen during early recovery.

Adult↗
PubMed1989

Bulimia: independence of antibulimic and antidepressant properties of desipramine.

The purpose of this study was to identify variables useful for predicting a positive response to the tricyclic antidepressant desipramine, amongst bulimic subjects. Using a randomized double-blind cross-over design, 24 normal weight bulimics completed a 15-week protocol in which they received either desipramine (150 mg/day) for six weeks, no drug for three weeks, followed by placebo for six weeks, or the reverse sequence. At weeks 0, 2, 4, 6, 9, 11, 13, and 15, each subject was assessed using the EDI, SCL-90, POMS and binge records. The DST, Diagnostic Interview Schedule (DIS), and a personal and family medical-psychiatric history questionnaire were administered at initial assessment, while plasma desipramine levels were obtained at weeks 4 and 13. Responders were defined in terms of both binge frequency reduction, and decrease in depressive symptoms. In the sample of 24 subjects, desipramine was significantly more effective than placebo in reducing the frequency of weekly binging and vomiting, as well as causing a reduction in the fatigue scale of the POMS. No significant effect of the drug was obtained on the EDI or the SCL-90. In terms of reduction in binge frequency, seven responders were identified; another seven were found to be borderline responders, while 10 were labeled as non-responders. The three groups did not differ in terms of their initial scores on the SCL-90, POMS, DST, DIS results, or psychological subscales of the EDI. However, responders were found to have lower EDI bulimia subscale scores, but a higher frequency of purging episodes than were non-responders. Eight patients were identified as borderline responders with respect to depressive symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Immunological detection of myeloperoxidase in synovial fluid from patients with rheumatoid arthritis.

We have used rocket immunoelectrophoresis and immunoblotting to detect myeloperoxidase in synovial fluid from patients with rheumatoid arthritis. This protein was enzymatically inactive but its identity as myeloperoxidase was confirmed by comparing its subunit structure with that of the purified enzyme. When neutrophils were stimulated to secrete myeloperoxidase in vitro, a polypeptide with an apparent molecular mass of 62 kDa was detected extracellularly by immunoblotting. Neutrophils isolated from synovial fluid showed a reduced level of this 62 kDa polypeptide but it was detected extracellularly in synovial fluid by immunoblotting. Thus, we conclude that neutrophils in synovial fluid from patients with rheumatoid arthritis have been activated in vivo to secrete myeloperoxidase and propose that the products of this enzyme system can contribute to the tissue damage associated with this disease.

Arthritis, Rheumatoid↗
PubMed1988

A focused casework approach to the treatment of child abuse: a controlled comparison.

Two contrasting therapies for the treatment of child abuse were compared in a randomised design: a focused casework approach to the whole family and a structured play therapy approach to the child. The Patterson coding system was used as an outcome measure. There was a high drop-out rate from both the therapies, but of those who completed the treatment, there was a greater improvement in the focused casework regime on some of the comparisons made.

Adolescent↗
PubMed1988

Treatment of bulimia with desipramine: a double-blind crossover study.

The purpose of this study was to evaluate the effect of desipramine, a tricyclic antidepressant with relatively specific noradrenergic effects, on bulimic behaviour, eating attitudes, and mood. Using a double-blind crossover design, 47 normal weight bulimics were randomly assigned to receive either desipramine (150 mg/day) for six weeks, no drug for three weeks, followed by placebo for six weeks, or the reverse sequence. At weeks 0, 2, 4, 6, 9, 11, 13, and 15, each subject was assessed using the EDI, SCL-90, POMS and binge records. Plasma desipramine levels were obtained at weeks 4 and 13. Twenty-four subjects completed the entire fifteen week protocol, while 23 dropped out. Desipramine was significantly more effective than placebo in reducing the frequency of weekly binding, weekly vomiting, and the fatigue scale of the POMS. No significant effect of the drug was obtained on the EDI or the SCL-90. The clinical effect was modest. Desipramine's antibulimic effects were not associated with an alleviation of depressive symptoms.

Adult↗
PubMed1987

Echocardiographic and hemodynamic correlates of diastolic closure of mitral valve and diastolic opening of aortic valve in severe aortic regurgitation.

Acute severe aortic regurgitation (AR) is characterized by a steep increase in left ventricular end-diastolic pressure, exceeding left atrial pressure and occasionally equilibrating with aortic diastolic pressure. These pressure phenomena correlate with the M-mode echocardiographic (echo) findings of diastolic closure of the mitral valve (DCMV) and diastolic opening of the aortic valve (DOAV). Six men, aged 23 to 48 years, with recent-onset, severe AR were evaluated by M-mode echo and pressures at cardiac catheterization. DCMV was seen in all 6 patients and DOAV in 4. Near-constant time intervals from the preceding R wave of the electrocardiogram to DCMV and DOAV were seen, even in 3 patients with varying RR intervals (1 with atrial fibrillation and 2 with asynchronous and demand atrial pacing). When the RR intervals were shorter than these intervals, DCMV and DOAV did not occur. Increasing the heart rate in the 2 patients by atrial pacing resulted in a marked decrease in left ventricular end-diastolic pressure. In conclusion, DCMV and DOAV have a near constant relation to the preceding R wave of the electrocardiogram, DCMV with competence of the mitral valve must be present for DOAV to occur, DOAV indicates that the diastolic blood pressure equals left ventricular end-diastolic pressure, and heart rate is an important factor influencing the hemodynamic and echocardiographic parameters in recent-onset, severe AR.

Adult↗