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Biomedical subjects

R L Smith

Publications and source records attributed to R L Smith.

At least 343 records · Page 19Linked to original sources
PubMed1988

Correlation of bronchoalveolar lavage cell populations with clinical severity of Pneumocystis carinii pneumonia.

We correlated bronchoalveolar lavage (BAL) cell populations with clinical course and outcome in 19 patients with Pneumocystis carinii pneumonia and acquired immunodeficiency syndrome. Twelve patients demonstrated an elevated (greater than or equal to 5 percent) BAL combined neutrophil and eosinophil count, which correlated with the magnitude of the alveolar-arterial PO2 gradient. Patients with elevated BAL granulocytes also had significantly higher serum lactate dehydrogenase levels. Three of the four patients who died had the highest percentage of neutrophil counts observed in lavage fluid. Although no patient was thought to have a concurrent bacterial infection, potential pathogens were cultured from the sputum of patients with the most elevated neutrophil counts. Whether BAL granulocytes reflect an inflammatory process analogous to the adult respiratory distress syndrome or signify concomitant bacterial infection remains to be determined. We conclude that BAL granulocytes are associated with more severe respiratory compromise in patients with Pneumocystis carinii pneumonia.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Histoplasmosis in patients at risk for the acquired immunodeficiency syndrome in a nonendemic setting.

We reviewed 18 cases of histoplasmosis in patients at risk for the acquired immunodeficiency syndrome seen at two New York City hospitals in the past 3 1/2 years. Seventeen patients were Hispanic, including 13 born in Puerto Rico and three in South America. Clinical presentation was subacute, with high fever, weight loss, and mild respiratory symptoms with well-maintained gas exchange. Five patients had normal chest roentgenograms. The most common chest roentgenographic abnormality was diffuse small nodules. A rapid diagnosis was established histologically in 72 percent of patients, most commonly by transbronchial lung biopsy; cultures were positive in 94 percent of patients while serology was positive in five of six patients. Mycobacterium tuberculosis was a concurrent, often unrecognized, pathogen in six cases. Most patients responded to amphotericin therapy. Histoplasmosis may represent an early sign of altered host immunity in the acquired immunodeficiency syndrome.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Elevated lactate dehydrogenase values in patients with Pneumocystis carinii pneumonia.

We investigated the source of elevated serum lactate dehydrogenase (LDH) levels in seven patients with Pneumocystis carinii pneumonia (PCP) by analyzing blood and bronchoalveolar lavage (BAL) albumin (ALB) and LDH, with isoenzyme fractionation. Four patients with non-PCP lung disease served as control subjects. In PCP patients, BAL LDH was sixfold higher, and BAL ALB, fourfold higher than in the non-PCP patients. The increased LDH/ALB in BAL as compared to serum, in addition to a BAL isoenzyme pattern characteristic of lung, suggest that BAL LDH arises from a pulmonary source. We postulate that the high correlation observed between BAL and serum LDH (r = 0.93, p less than 0.001) reflects backflow of pulmonary-derived LDH into the blood through an alveolocapillary membrane (ACM) compromised by PCP. Furthermore, a comparison of BAL LDH/ALB for each isoenzyme with the same serum ratio showed less backflow for the cationic isoenzymes. The ACM appears to sieve proteins on an electrical basis which may account for the LDH isomorphic pattern observed in the serum of PCP patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Bronchogenic cyst causing a unilateral ventilation-perfusion defect on lung scan.

A 37-year-old woman had pleuritic chest pain, dyspnea, and normal findings on chest roentgenogram. Lung scan showed markedly diminished perfusion to the right lung with a matched ventilatory defect. Further evaluation revealed a bronchogenic cyst. After resection, the lung scan was normal. To our knowledge, this is the first report of a bronchogenic cyst causing a reversible, unilateral ventilation-perfusion defect on lung scan.

Adult↗
PubMed1988

Hospital pharmacy employment considerations for the chemically dependent health-care professional.

Experiences and decisions of a pharmacy services management team involving two chemically dependent individuals, one an existing pharmacist employee and the other a pharmacist applicant, are described. Because our standing on chemical dependency was to rehabilitate rather than terminate, we chose to develop a systematic approach to dealing with this problem in our employees. In the case of the existing pharmacist employee, we decided to initiate rehabilitation by intervention, a process that involved direct confrontation of the individual by his spouse and mother, immediate supervisor, a certified alcohol and drug abuse counselor, and a representative from the hospital's employee assistance program. The employee was treated by psychological/behavioral therapy on an inpatient basis. After discharge, the employee returned to work under specific terms outlined in a return-to-work contract covering the first 24 months; support structures at the workplace to guard against relapse were also instituted. Factors that might precipitate relapse were identified, and a policy for dealing with relapsing employees was developed. The pharmacist applicant was assessed like any other applicant, but a few other factors relevant to her recovering status, such as the length of continuous abstinence she had attained, were considered. An employment contract resembling the return-to-work contract also was developed. Experience with the chemically dependent employee led to the creation of a model for dealing effectively and fairly with employees afflicted with the disease of chemical dependency. We continue to support our institutional decision to rehabilitate and not terminate such employees.

Humans↗
PubMed1987

Effect of poly rI:rC treatment upon the metabolism of [14C]-paracetamol in the BALB/cJ mouse.

The effect of the immunomodulator, poly rI:rC, upon the in vivo metabolism of [14C]-paracetamol has been investigated in male BALB/cJ mice. In both poly rI:rC treated and control groups of mice the major part of the dose was excreted in the 0-24 hr urine and the major urinary metabolites were the glucuronic acid and sulphate conjugates. The urinary excretion of these two conjugates and of free paracetamol was not significantly altered following poly rI:rC treatment. Following enzymic hydrolysis of glucuronides and sulphates, the 3-cysteine, 3-mercapturate, 3-thiomethyl and 3-methylsulphoxide metabolites of paracetamol were all identified in the 0-24 hr urine together with very small amounts of 3-methoxy paracetamol. Although poly rI:rC treatment reduced the proportional urinary excretion of each of the thio adducts the individual differences were not significant. However, total thio adduct excretion, an indirect estimate of the metabolic activation of paracetamol, was significantly lower following poly rI:rC treatment. This depression in the urinary excretion of thio adducts following poly rI:rC treatment is discussed in relation to possible implications for paracetamol toxicity.

Acetaminophen↗
PubMed1987

Effect of interferon synthesis upon the metabolism of [carboxyl-14C]-aspirin in the mouse.

The effect of stimulation of interferon (IFN) synthesis with the immunomodulators, polyriboinosinic polyribocytidylic acid (poly rI:rC) and Newcastle Disease Virus (NDV) upon the in vivo metabolism of [carboxyl-14C]-aspirin was investigated in male mice of three different strains. Following poly rI:rC administration to DBA/2 mice, the metabolic conjugation of salicylic acid with glycine was significantly increased, glucuronidation was little changed and there was an approximately 10-fold reduction in the excretion of the oxidation product, gentisic acid. Prolongation of hexobarbitone-induced sleeping time confirmed the ability of this agent to depress oxidative metabolism in vivo. Poly rI:rC administration to C57BL/6By and BALB/cBy mice resulted in similar changes in aspirin metabolism in vivo. Treatment of C57BL/6By mice with NDV produced high levels of circulating IFN and produced alterations in aspirin metabolism similar to those seen after poly rI:rC treatment. Comparable studies in BALB/cBy mice, which did not produce detectable levels of IFN in response to NDV challenge, revealed no change in the fate of aspirin metabolism following treatment with this agent. These data indicate that the in vivo oxidation of salicylate, but not its conjugation, can be depressed, at least indirectly, by an interferon-associated mechanism.

Alleles↗
PubMed1987

Metabolism of estragole in rat and mouse and influence of dose size on excretion of the proximate carcinogen 1'-hydroxyestragole.

The major metabolic pathways of estragole have been established in rats and mice, and in both species the relative importance of the different pathways has been shown to be dose related. At low doses, estragole mainly undergoes detoxication reactions, notably O-demethylation and side-chain cleavage, but as the dose is increased, the extent of O-demethylation falls and other pathways, notably l'-hydroxylation, come into prominence. The disproportionate relationship between dose size and the elimination of the proximate carcinogenic metabolite l'-hydroxyestragole may influence the relationship between dose size and tumour incidence. These findings may have important implications for the safety assessment of this food flavouring, since the dose levels used in carcinogenicity studies have been very much larger than the estimated human daily intake. Moreover the percentage of an administered dose of estragole eliminated as 1-hydroxyestragole glucuronide in human urine is much lower than that found with even the lowest doses examined in rats in this study.

Allylbenzene Derivatives↗
PubMed1987

A genetic polymorphism of the N-oxidation of trimethylamine in humans.

Trimethylamine (TMA) and its N-oxide (TMAO) are normal components of human urine. They are present in the diet and also derived from the enterobacterial metabolism of precursors such as choline. Dietary TMA is almost entirely metabolized to and excreted as TMAO. However, the extent to which TMA undergoes N-oxidation appears to be polymorphic in a British white population study (n = 169). Two propositi were identified with relative TMA N-oxidation deficiency that was further confirmed by oral challenge with TMA (600 mg). The study of the families of the two propositi, as well as those of two identified subjects with trimethylaminuria, under both normal dietary conditions and after oral TMA challenge strongly indicates that the conditions of impaired N-oxidation is inherited as a recessive trait. It is proposed that the N-oxidation of TMA in humans is polymorphic and under single gene diallelic control in which individuals who are homozygous for the variant allele exhibit marked N-oxidation deficiency and trimethylaminuria.

Adolescent↗
PubMed1987

Disclosure of the metabolic retroversion of trimethylamine N-oxide in humans: a pharmacogenetic approach.

Trimethylamine N-oxide (TMAO), which is naturally occurring in dietary marine fish, is well absorbed and excreted apparently unchanged as judged by end-product analysis. Such observations may conceal the fact that the amine N-oxide has undergone a sequence of deoxygenation and oxygenation reactions only to revert to the parental form and be excreted as such--a process that we propose to call metabolic retroversion. To evaluate this phenomenon for TMAO we have investigated the fate of the orally administered substance in healthy volunteers and in four subjects previously phenotyped as having an inherited deficiency with respect to the metabolic N-oxidation of trimethylamine (TMA). Two of these subjects were typed as homozygous affected and the other two as "carriers." If substantial reduction of orally administered TMAO occurs during the course of its postulated retroverted metabolism, it was hypothesized that this would be revealed by the extensive urinary excretion of unoxidized TMA by the four affected subjects. After oral TMAO administration in the four healthy subjects, greater than 94% of the urinary TMA was in the form of TMAO and only less than 4% as the free base. However, after oral TMAO in the two homozygous-affected subjects, unoxidized TMA accounted for 35% and 51%, respectively, of the total urinary TMA, the balance being due to TMAO. For the carrier subjects, TMA accounted for 12% and 16% of the total urinary TMA after TMAO administration. It is thus clear that the urinary excretion of unoxidized TMA is increased greatly in affected subjects with an inherited deficiency of N-oxidation after the oral administration of TMAO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1987

Effects of prone spinal extension exercise on passive lumbar extension range of motion.

The purpose of this study was to determine the effectiveness of prone spinal extension exercises for increasing passive lumbar extension range of motion in healthy young adults. Eighteen healthy female and 18 healthy male volunteers were divided randomly into control groups (women, n = 10; men, n = 8) and experimental groups (women, n = 8; men, n = 10). The experimental groups performed 20 repetitions of a prone extension exercise each day for four weeks; the control groups did not. We used spondylometry to measure lumbar extension ROM. The exercises produced a significant difference (p less than .025) in the passive lumbar extension ROM between the male experimental and control groups preventing a loss of spinal mobility in the men who exercised. Analysis of the data revealed no significant difference between the female groups. The results are discussed in light of the clinical significance of lumbar extension ROM. We suggest further studies to examine the effects of lumbar extension exercises on patients with restricted ROM and low back pain.

Exercise Therapy↗
PubMed1987

Sodium aurothiomalate toxicity and sulphoxidation capacity in rheumatoid arthritic patients.

The association between sulphoxidation capacity and sodium aurothiomalate toxicity was investigated in 65 patients undergoing treatment for rheumatoid arthritis. Of those showing side-effects, 30/37 (81%) were also poor sulphoxidizers compared with only 9/28 (32%) in the group not displaying adverse reactions. A patient with poor sulphoxidation had a nine-fold greater risk of developing toxicity. The prior measurement of sulphoxidation capacity may help to identify those patients most susceptible to the deleterious effects of this drug.

Adult↗
PubMed1987

Depression of oxidative metabolism of aspirin in mice via an interferon-associated mechanism in relation to Reye's syndrome.

Interferon synthesis was induced in inbred strains of mice with either polyriboinosinic-polyribocytidylic acid or Newcastle disease virus. The strains, BALB/cBy and C57BL/6By, respond to Newcastle disease virus by producing 'low' and 'high' levels of serum interferon, respectively. 24 h after interferon induction mice received [carboxyl-14C]-aspirin orally. The metabolic conjugation of aspirin was little changed after either treatment while the urinary excretion of gentisic acid, a minor product of metabolic oxidation, was significantly depressed after polyriboinosinic-polyribocytidylic acid in both strains and in C57BL/6By mice after Newcastle disease virus. The results suggest that such a metabolic impairment in aspirin metabolism would not significantly affect salicylate clearance and hence are unlikely to be directly related to the aetiology of Reye's syndrome which has been associated with both a prodromal viral infection and aspirin therapy.

Animals↗
PubMed1987

Conservation of adapting components in auditory-nerve responses.

The responses of single auditory-nerve fibers of Mongolian gerbil were studied using tonal stimuli. The peristimulatory adaptation of firing rate in response to tone bursts presented in quiet and during a background stimulus is described quantitatively. The total transient response which can be produced to the onset of a tone burst, whether presented in quiet or as an intensity increment, is limited and appears to demonstrate a form of conservation. Specifically, the total numbers of spikes produced by the rapidly adapting component, and the slower short-term adaptation component, are proportional at all intensities, and are limited for each fiber. Furthermore, when an incremental stimulus is presented on a background, the total transient response to the background and to the increment is limited and depends upon the final intensity, not the background intensity. When the presumed underlying synaptic drive is derived by removing the effects of refractoriness from the spike train, the same conservation of the transient response components, and proportionality between rapid and short-term components, are observed.

Animals↗