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Biomedical subjects

R J Costello

Publications and source records attributed to R J Costello.

14 recordsLinked to original sources
PubMed1994

On closed test procedures for dose-response analysis.

This paper concerns the testing of a dose-response effect in medical studies. We consider two situations. The first is when the drug effect on a parameter of interest is likely to increase (or decrease) with increasing doses. We propose a procedure based on the closure principle of Peritz combined with an application of a closed testing procedure of Marcus et al. to a test proposed by Turkey et al. The second situation is the analysis of a drug effect where one might observe a reversal at higher doses. For this situation, we propose simultaneous examination of contrasts among the doses at each of several stages of the testing scheme. We calculate critical values for this procedure incorporating the correlation structure among the contrasts. Both procedures strongly control the family-wise error rate at the pre-determined alpha level. They also provide information about the shape of the dose response lacking in other commonly used procedures for testing against an ordered alternative hypothesis. We illustrate the procedures on two datasets.

Algorithms↗
PubMed1993

Electrode cuff-induced changes in DNA and PDGF gene expression in the rat carotid artery.

Low current (0.25, 3 mA) stimulation through a miniature electrode cuff encased around the carotid artery of the rat was used to induce intimal hyperplasia, an important feature of the atherosclerotic plaque and a phenomenon limiting the long term success of angioplasty. Compared to contralateral unstimulated arteries, 11-14 days of daily transmural stimulation of cuffed arteries (20 min period) significantly increased the amount of extracted DNA (diphenylamine colorimetric assay). Low current (0.25 mA) was as effective as 3 mA in producing an increase in extractable DNA. The cuff alone without applied current also stimulated an increase in DNA content but to a smaller degree than in arteries receiving current. Infusion of a calcium channel antagonist, diltiazem, at a dose which achieved therapeutic drug levels, significantly reduced the amount of electrode cuff-induced DNA content but had no effect on the increase in DNA induced by the presence of the cuff without applied current. Gene expression of PDGF-A chain, PDGF-B chain and PDGF-beta receptor (beta r) (Northern analysis of extracted carotid RNA) increased within 4 h after electrical stimulation with 3 mA. Lower current (0.25 mA) and the presence of the cuff also enhanced PDGF gene expression but with a delayed onset of several days. The pattern of gene expression for PDGF ligands and beta r during the 11-14 days of stimulation differed, but each remained above contralateral control levels. It is concluded that the continued coexpression of PDGF and one of its receptors may contribute to induced hyperplastic changes.

Animals↗
PubMed1988

Membrane heterogeneity in sensory receptors of rat vibrissae: Merkel receptors differ from other nerve endings.

The cupric/ferrocyanide reaction was used to analyse cation-binding sites in rat vibrissae. The heminode of the last myelinated segment had moderate staining. No staining of any complex receptor was found except for Merkel receptors. Both the Merkel cell and associated nerve ending were stained except for their apposed cell membranes, suggesting either reciprocal membrane specialization at that site, or prevention of cupric/ferrocyanide penetration into the space between the two cells.

Animals↗
PubMed1988

Cation-binding sites in trigeminal ganglia and maxillary nerve: unusual reactivity of perikarya, stem axons and satellite cells.

We have used the cupric/ferrocyanide reaction to study cation-binding in trigeminal ganglia and maxillary nerve of adult rats. Unmyelinated axons did not react, whereas myelinated axons were stained at nodal, paranodal or cleft sites. At 'nodal' sites, metallic deposits were found in the axoplasm, along the axolemma, and at the extracellular interfaces of the paranodal myelin. At 'paranodal' sites, particles were concentrated in the paranodal axoplasm and in the intracellular spaces of the myelin loops. Most maxillary axons examined at successive sites had all nodal or all paranodal staining, but 13 of 51 had a mixture. In trigeminal ganglia there was no staining of perineurial sheath, endoneurial cells or mast cells. Satellite cells and their basal laminae were prominently stained, with those around small neurons more reactive than those of large neurons. Patches of neuronal membrane on cell bodies were stained, more often for small than large neurons. The axon hillock and proximal stem axon were not stained in some cases, but approximately half the neurons had staining of perikaryal cytoplasm at the axon hillock or a dense asymmetric band in the proximal stem axon. Strong intraaxonal staining was found at the junction between unmyelinated proximal and myelinated distal stem axon. In distal stem axons, staining was found at the first myelin segment and at each successively thicker myelin segment; staining was mostly weak and paranodal, with intensity proportional to myelin thickness. The T-junction between stem and main myelinated axon had nodal or paranodal patterns; unmyelinated T-junctions were not stained. The varied cation-binding patterns in trigeminal ganglia show unusual properties of satellite cells and important differences between stem and main axons. The results that the cell membrane of axon hillock and proximal stem regions of many sensory large and small neurons may have numerous sodium channels and could affect signal propagation.

Animals↗
PubMed1985

Air monitoring at the drum bulking process of a hazardous waste remedial action site.

Air monitoring was performed at a hazardous waste remedial action site to measure inhalation exposure at the drum bulking unit processes and ambient emissions downwind from that process. Contaminant concentrations were all well below permissible exposure limits. This study suggests that when workers remain in fixed job locations at hazardous waste sites, occupational inhalation exposure monitoring must consider contaminants generated upwind of the job location as well as contaminants generated at the specific job site. Air sampling must also consider both the particulate and vapor phases of the site contaminants.

Air↗
PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. I.

Chlorthalidone 25 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 25 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reactions.

Adult↗
PubMed1984

The efficacy of a potassium-sparing combination of chlorthalidone and triamterene in the control of mild and moderate hypertension. II.

Chlorthalidone 50 mg/triamterene 50 mg in once-daily oral doses was as effective in reducing blood pressure as chlorthalidone 50 mg alone. The decrease in serum potassium was statistically significantly less with the combination than for chlorthalidone. There were no notable differences between the treatments in any other measure of laboratory safety or adverse reaction.

Adult↗
PubMed1983

A quantitative sampling device for use at hazardous waste sites.

A device to draw air through up to 10 direct reading indicator tubes simultaneously has been developed. The qualitative results obtained can be used to obtain a rapid preliminary classification of the unknown chemical substances at spill scenes or at hazardous waste sites, and to devise protocols for laboratory sample analysis.

Equipment and Supplies↗
PubMed1982

Protecting workers who clean up hazardous waste sites.

On April 21, 1980, an explosion and fire among the 40 000 drums of unlabeled chemical wastes at the former site of Chemical Control Corporation in Elizabeth, New Jersey, attracted national attention and raised serious concern about the health and safety of workers who would be called upon to clean up the disaster site. Evaluation of workers' exposure during clean up operation and an assessment of the level of respiratory protection needed were necessary. NIOSH conducted 8 days of air monitoring. The chemicals of concern were organic vapors, metals, pesticides, polychlorinated biphenyls, cyanide compounds, and dioxins (TCDD). No excessive exposure to chemical substances by inhalation was found. However, continuous use of respiratory protective equipment and other personal protective devices was necessary because of frequent drum ruptures.

Air Pollutants↗
PubMed1982

Occupational exposure to arsine. An epidemiologic reappraisal of current standards.

In an evaluation of chronic occupational exposure to arsine (AsH3), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As2O3) vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 micron/m3. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 micron/m3) and to As2O3 (maximum (20.5%) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 micron/1 (0.67 mumol/1) or above, indicating increased arsenic absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (N = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 micron/m3 were associated with urinary arsenic concentrations in excess of 50 micron/1 (0.67 mumol/1). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to As2O3. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion. It was concluded that the current arsine exposure standard, 200 micron/m3, fails to prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine.

Air Pollutants↗
PubMed1979

Calibration testing of the jet filter as a respirable sampler.

This work was done to determine whether the jet filter can satisfactorily serve as a respirable sampler. Monodisperse polystyrene latex (PSL) spheres, crushed quartz particles, and hot-mix asphalt plant dust were used to calibrate the jet filter. The deposition characteristics for the sampler matched those specified by standards quite well for the PSL and the crushed quartz particles, i.e., those particles with optical and equivalent aerodynamic diameters near the same. The jet filter can meet its original design purpose - respirable sampling of radioactive aerosols. The sampler can also be used in gravimetric determinations by cutting the filter into two parts for weighing - the center portion with the non-respirable and the outer annulus with the respirable fraction.

Calibration↗
PubMed1978

Pharmacokinetics of netilmicin in patients with renal impairment and in patients on dialysis.

The pharmacokinetics of netilmicin were examined in 25 adult subjects, 7 normal subjects, and 18 patients with renal impairment. Five were dialysis patients who were studied on and off dialysis. Netilmicin, 2 mg/kg, was infused intravenously over 1 h. The peak serum concentration ranged from 9 to 11 mug/ml. The mean biological half-life of netilmicin for subjects with a creatinine clearance (Ccr) > 70 ml/min was 2.7 h, for those with Ccr > 25 < 70 ml/min it was 10 h, for those with Ccr > 4 < 25 ml/min it was 32 h, and for those who were anephric it was 42 h. Ccr was correlated positively with the elimination constant and the drug's serum clearance. It was negatively correlated with the drug's volume of distribution. The dialyzer clearance of netilmicin was positively correlated with plasma flow rate and was similar to values previously reported for gentamicin. Netilmicin behaves in a fashion similar to other aminoglycosides. Therapeutic guidelines are suggested.

Adult↗