PubMed Health⌕ Search

Biomedical subjects

J C Hogan

Publications and source records attributed to J C Hogan.

At least 19 recordsLinked to original sources
PubMed1997

A production limitation in syllable number: a longitudinal study of one child's early vocabulary.

The present paper reports on the phonological form of one child's productive vocabulary from age 0;10 to 1;8 with primary focus on his production of multisyllabic targets. A large percentage of his multisyllabic vocabulary was produced as one syllable until the age of 1;6. This limitation was not due to a tendency to extract only single syllables from the speech stream, but rather due primarily to a limitation on production. While some portion of his one-syllable productions could be interpreted as the result of single syllable extraction, a sizeable portion affirmed that he extracted the target size correctly by his inclusion of first and final target phonemes in his productions (e.g. [po] for piano and [kiz] for candies). The resolution of this limitation coincides with his move toward two-word speech. We conclude that there is a developmental and perhaps maturational limitation in the capacity to carry out the processes underlying word and sentence production.

Child Language↗
PubMed1996

Directed combinatorial chemistry.

Combinatorial chemistry has given chemists access to vast numbers of molecules, but selecting the right one has proved more difficult. As chemists have gained experience in the technique, however, it has become possible to use solid- or solution-phase syntheses with different chemistries and scaffolds to produce libraries tailor-made for finding or optimizing a lead directed at almost any class of target.

Chemistry, Pharmaceutical↗
PubMed1996

A new class of HIV-1 protease inhibitor: the crystallographic structure, inhibition and chemical synthesis of an aminimide peptide isostere.

The essential role of HIV-1 protease (HIV-1 PR) in the viral life cycle makes it an attractive target for the development of substrate-based inhibitors that may find efficacy as anti-AIDS drugs. However, resistance has arisen to potent peptidomimetic drugs necessitating the further development of novel chemical backbones for diversity based chemistry focused on probing the active site for inhibitor interactions and binding modes that evade protease resistance. AQ148 is a potent inhibitor of HIV-1 PR and represents a new class of transition state analogues incorporating an aminimide peptide isostere. A 3-D crystallographic structure of AQ148, a tetrapeptide isostere, has been determined in complex with its target HIV-1 PR to a resolution of 2.5 A and used to evaluate the specific structural determinants of AQ148 potency and to correlate structure-activity relationships within the class of related compounds. AQ148 is a competitive inhibitor of HIV-1 PR with a Ki value of 137 nM. Twenty-nine derivatives have been synthesized and chemical modifications have been made at the P1, P2, P1', and P2' sites. The atomic resolution structure of AQ148 bound to HIV-1 PR reveals both an inhibitor binding mode that closely resembles that of other peptidomimetic inhibitors and specific protein/inhibitor interactions that correlate with structure-activity relationships. The structure provides the basis for the design, synthesis and evaluation of the next generation of hydroxyethyl aminimide inhibitors. The aminimide peptide isostere is a scaffold with favorable biological properties well suited to both the combinatorial methods of peptidomimesis and the rational design of potent and specific substrate-based analogues.

Carbamates↗
PubMed1995

Interaction of a peptidomimetic aminimide inhibitor with elastase.

The crystal structure of an aminimide analog of a dipeptide inhibitor of porcine pancreatic elastase bound to its target serine protease has been solved. The peptidomimetic molecule binds in the same fashion as the class of dipeptides from which it was derived, making similar interactions with the subsites on the elastase surface. Because aminimides are readily synthesized from a wide variety of starting materials, they form the basis for a combinatorial chemistry approach to rational drug design.

Amino Acid Sequence↗
PubMed1994

Screening for lead poisoning in an urban pediatric clinic using samples obtained by fingerstick.

OBJECTIVE: To assess the false positive rate of blood lead (BPb) determinations on samples obtained by fingerstick from children screened in an urban clinic. METHOD: From a single fingerstick (N = 1573), blood was collected in a capillary tube for determining lead concentration (CPb) by graphite furnace and an additional sample was absorbed onto a filter paper for determining lead concentration (FPb) by atomic absorption spectrophotometry with Delves cup. Zinc protoporphyrin (ZPP) was measured immediately and a confirmatory venous lead (VPb) specimen was obtained at the same visit if the ZPP was > or = 35 micrograms/dL (0.6 mumol/L); children with either a CPb or FPb > or = 15 micrograms/dL (0.7 mumol/L) were later recalled for determining VPb. RESULTS: For the 172 children who had a VPb on the same day as the screening tests, the false positive rates (95% confidence intervals) at a lead threshold of 15 micrograms/dL (0.7 mumol/L) were: CPb, 13.5% (6.7-20.3); FPb, 19.1% (11.8-26.4). Analyses using all 679 screens with a paired venous specimen (mean delay between screen and venous testing = 30 days) yielded much higher false positive rates (CPb, 31.3%; FPb, 46.0%). CONCLUSIONS: Screening for lead poisoning is feasible within an urban pediatric clinic by direct measurement of lead concentration in blood samples obtained by fingerstick. The false positive rate that can be obtained is acceptable given the precision of measuring BPb concentration. Practitioners using a staged screening protocol may incorrectly attribute a higher false positive rate to the screening tests, when much of the error may be due to the temporal variability of BPb resulting from both biologic variability in BPb concentration and intermittent exposures.

Child↗
PubMed1992

Guillain-Barré syndrome following cardiopulmonary bypass.

Two cases of Guillain-Barré syndrome occurring after otherwise uneventful cardiac surgery using cardiopulmonary bypass are presented. Although Guillain-Barré syndrome has been reported after surgical procedures, it has never been reported after cardiopulmonary bypass. Recent literature supports an immune mediated process for Guillain-Barré. Cardiopulmonary bypass may act as the trigger for this immune mediated response.

Blood Transfusion↗
PubMed1991

Diastolic disease in left ventricular hypertrophy: comparison of M mode and Doppler echocardiography for the assessment of rapid ventricular filling.

OBJECTIVE: To investigate possible discrepancies between M mode and Doppler echocardiography in assessing early diastolic filling. DESIGN: Forty seven patients with left ventricular hypertrophy due to aortic stenosis and 26 healthy controls with a similar age range were studied by M mode, Doppler, apexcardiography, and phonocardiography. The patients also underwent cardiac catheterisation. M mode echograms were digitised by a computer. Early diastolic filling in both groups as assessed by the two techniques was compared. SETTING: A tertiary cardiac referral centre with facilities for non-invasive and invasive investigations. SUBJECTS: Patients referred for assessment of aortic stenosis who had left ventricular hypertrophy. MAIN OUTCOME MEASURES: Filling velocities on Doppler and rates of wall thinning and dimension increase on M mode. RESULTS: Digitised M mode indices of diastolic filling (peak wall thinning rate 6.4 (3.0) v 10.0 (3.0) cm/s and peak rate of dimension increase 9.3 (3.3) v 16 (4.5) cm/s) in the patients and controls were consistently different. In contrast, the Doppler A/E ratio and peak E wave velocity were not; they varied widely among patients with left ventricular hypertrophy. In part, this variability was because the Doppler A/E ratio, but not the digitised M mode indices, was very sensitive to the abnormalities of isovolumic relaxation frequently present in left ventricular hypertrophy. The Doppler A/E ratio varied similarly with age in both normal and hypertrophied hearts; in the patients with ventricular hypertrophy the peak rate of dimension increase depended on age only, whereas the thinning rate was independent of age in both the patients and controls. Neither the A/E ratio nor the M mode indices could be related to the left ventricular end diastolic pressure or the peak aortic pressure difference. CONCLUSIONS: When Doppler and M mode techniques are used to assess rapid filling in patients with left ventricular hypertrophy the M mode indices are more consistently abnormal. The two methods measure different aspects of left ventricular diastolic function and should be regarded as complementary rather than interchangeable.

Adolescent↗
PubMed1990

Chronic administration of N-acetylcysteine fails to prevent nitrate tolerance in patients with stable angina pectoris.

1. Reduced availability of sulphydryl groups in vascular smooth muscle cells may contribute to the development of tolerance to the action of the organic nitrovasodilators. 2. Eight patients with stable angina were treated with 10 mg of transdermal glyceryl trinitrate per 24 h, together with 400 mg N-acetylcysteine, a sulphydryl group donor, or matching placebo three times daily in a double-blind randomised crossover manner for two periods of 4 days with intervening washout period of 3 days off these drugs. Other therapy remained unaltered during the study. 3. Blood pressure, heart rate and symptom-limited treadmill walking time were measured in the pre-treatment control state and 4 h after starting treatment on day 1 and day 4 of each glyceryl trinitrate treatment period. 4. The changes seen on day 1 were attenuated by day 4 to an equal extent in N-acetylcysteine and placebo treatment periods. 5. These results suggest that chronic oral administration of N-acetylcysteine fails to prevent the development of tolerance to the anti-anginal or haemodynamic effects of glyceryl trinitrate.

Acetylcysteine↗
PubMed1989

Atrial natriuretic peptide inhibits the release of endothelium-derived relaxing factor from blood vessels of the rabbit.

We investigated the effects of atrial natriuretic peptide (ANP) on release of endothelium-derived relaxing factor (EDRF) from rabbit aorta and central ear artery using inhibition of platelet aggregation and vascular smooth muscle relaxation respectively as measures of EDRF activity. ANP at concentrations greater than 10(-9) M inhibited carbachol-induced EDRF release from rabbit aorta and acetylcholine-induced EDRF release from the central ear artery. These findings are consistent with previous observations that 8-bromo cyclic GMP inhibits EDRF release from rabbit aorta and ANP inhibits release of EDRF from cultured endothelial cells.

Adenosine Diphosphate↗
PubMed1989

Glyceryl trinitrate and platelet aggregation: effects of N-acetyl-cysteine.

The concentration range of GTN causing inhibition of platelet aggregation in vitro is much higher than the plasma concentrations achieved clinically. This action is potentiated by the sulphydryl donor N-acetylcysteine. We have investigated the effects of GTN given with and without N-acetylcysteine on ex vivo platelet aggregation in man. In a double-blind randomised crossover trial eight healthy volunteers were treated with 20 mg of transdermal GTN/24 h, together with N-acetylcysteine 200 mg three times daily or matching placebo. Platelet aggregation, measured ex vivo by whole blood impedance aggregometry in response to adenosine diphosphate, was not significantly altered by GTN acutely or after 4 days' treatment with or without N-acetylcysteine. Platelet cyclic guanosine monophosphate levels were not significantly altered by GTN either in the absence or presence of N-acetylcysteine. This result implies that previously reported beneficial effects of GTN in myocardial infarction or unstable angina are unlikely to be attributable to direct pharmacological inhibition of platelet aggregation.

Acetylcysteine↗
PubMed1989

N-acetylcysteine fails to attenuate haemodynamic tolerance to glyceryl trinitrate in healthy volunteers.

1. The effects of chronic dosing with N-acetylcysteine (NAC), on nitrate-induced haemodynamic changes during the acute and chronic treatment of healthy volunteers with glyceryl trinitrate (GTN) patches (Transiderm nitro) has been investigated. 2. Seven volunteers were treated in a double-blind randomised crossover manner for two periods of 4 days with 20 mg of transdermal GTN/24 h together with NAC (200 mg three times daily) or matching placebo. There was a washout period of greater than 3 days between treatment periods. 3. Haemodynamic measurements (blood pressure (BP); heart rate (HR] at rest and following maximal treadmill exercise were performed before treatment and 4 h after starting treatment on days 1 and 4. 4. Significant haemodynamic changes as evidenced by a fall in BP and rise in HR, were seen on day 1 in both the NAC and placebo phases. By day 4 the haemodynamic changes had returned towards the pre-treatment values during both the NAC and placebo phases suggesting the development of tolerance in both treatment groups. 5. These findings suggest that concurrent administration of NAC fails to prevent the development of tolerance to GTN.

Acetylcysteine↗
PubMed1988

Haemodynamic effects of DPI 201-106, following single intravenous dose administration to patients with moderate cardiac failure.

DPI 201-106 is a novel compound unrelated to other cardioactive agents and has been shown to have an inotropic effect in animal preparations. The drug was given by intravenous infusion (20 mg over 10 min) to 10 patients with moderate cardiac failure and the haemodynamic effects measured at intervals up to 1 h following infusion. Maximal effects were seen immediately following the infusion of DPI 201-106. Cardiac index showed an increase from baseline 2.72 (0.16) 1 min-1 m-2 to 3.18 (0.21) 1 min-1 m-2 at the end of infusion (P less than 0.001). Subsequent values were not significantly raised. Pulmonary capillary wedge pressure and pulmonary artery pressure fell from 27.6 (3.2) and 36.9 (4.4) to 15.3 (3.6) and 24.2 (4.9) mmHg, respectively (P less than 0.001 in both cases). A statistically significant effect on cardiac index was not seen at 1 h. However, pulmonary pressures remained reduced at this point. Radionuclide ejection fraction showed a significant increase from 15.4 (1.5) to 21.9 (2.2)% (P less than 0.005) at the end of infusion, and maintained a significant increase at 1 h. Having demonstrated beneficial, acute haemodynamic effects in this study, further work should be undertaken with DPI 201-106 to investigate the effect of chronic treatment in patients with cardiac failure.

Adult↗
PubMed1988

In vivo EDRF activity influences platelet function.

The administration of carbachol to rabbits to stimulate the release of endothelium derived relaxing factor (EDRF) results in inhibition of platelet aggregation and elevation of platelet cyclic GMP content. These effects are reversed by simultaneous administration of the EDRF inhibitors methylene blue or haemoglobin. The data provide the first direct biochemical evidence of in vivo EDRF activity.

Animals↗
PubMed1981

Developing job-related preplacement medical examinations.

Federal regulations prohibiting discrimination in hiring require that employment selection procedures to evaluate applicants be based on job-related criteria. The preplacement physical examination used in employment, particularly in the placement of handicapped persons, must also be conducted in a job-related manner. This paper discusses the development and use of the physical examination in selecting and placing applicants for jobs in the workplace with special reference to handicapped persons and disabled veterans. It presents and justifies a method of performing these examinations in a manner consistent with humanistic and business goals as well as the goals of federal regulatory agencies prohibiting employment discrimination.

Diagnostic Tests, Routine↗