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Biomedical subjects

L D Hudson

Publications and source records attributed to L D Hudson.

At least 109 records · Page 6Linked to original sources

Absence of tachyphylaxis to inhaled atropine in patients with chronic obstructive pulmonary disease.

A multicenter, 14-wk, double-blind, randomized, parallel group study of 60 patients with obstructive lung disease was performed to assess tachyphylaxis with inhaled atropine sulfate versus placebo. Forty patients completed the study; twenty-one were treated with placebo and nineteen were treated with atropine sulfate. Atropine and placebo groups were compared before and after inhaled atropine by spirometry at Weeks zero, 6, and 14. Medication side effects, other medication usage, and symptoms were recorded daily. Comparison of FEV1 response to atropine sulfate from baseline at Weeks zero, 6, and 14 did not show a statistically significant decrease. Inhaled atropine sulfate continued to be an effective bronchodilator in both placebo groups and atropine sulfate groups. There was no evidence of significant tachyphylaxis with atropine. Significant side effects in the atropine group when compared with placebo included dry mouth, dry skin, rapid heart rate, and nausea.

Administration, Inhalation↗

Pelizaeus-Merzbacher disease: an X-linked neurologic disorder of myelin metabolism with a novel mutation in the gene encoding proteolipid protein.

The nosology of the inborn errors of myelin metabolism has been stymied by the lack of molecular genetic analysis. Historically, Pelizaeus-Merzbacher disease has encompassed a host of neurologic disorders that present with a deficit of myelin, the membrane elaborated by glial cells that encircles and successively enwraps axons. We describe here a Pelizaeus-Merzbacher pedigree of the classical type, with X-linked inheritance, a typical clinical progression, and a pathologic loss of myelinating cells and myelin in the central nervous system. To discriminate variants of Pelizaeus-Merzbacher disease, a set of oligonucleotide primers was constructed to polymerase-chain-reaction (PCR) amplify and sequence the gene encoding proteolipid protein (PLP), a structural protein that comprises half of the protein of the myelin sheath. The PLP gene in one of two affected males and the carrier mother of this family exhibited a single base difference in the more than 2 kb of the PLP gene sequenced, a C----T transition that would create a serine substitution for proline at the carboxy end of the protein. Our results delineate the clinical features of Pelizaeus-Merzbacher disease, define the possible molecular pathology of this dysmyelinating disorder, and address the molecular classification of inborn errors of myelin metabolism. Patients with the classical form (type I) and the more severely affected, connatal variant of Pelizaeus-Merzbacher disease (type II) would be predicted to display mutation at the PLP locus. The other variants (types III-VI), which have sometimes been categorized as Pelizaeus-Merzbacher disease, may represent mutations in genes encoding other structural myelin proteins or proteins critical to myelination.

Amino Acid Sequence↗

The cost and efficacy of home care for patients with chronic lung disease.

A randomized controlled trial was conducted to assess efficacy and cost of sustained home nursing care for patients with chronic lung disease. Three hundred one patients were randomly assigned to a respiratory home care group (RHC) that received care from respiratory home care nurses, a standard home care group (SHC) that received care from regular home care nurses, or an office care group (OC) that received whatever care they needed except for home care. Patients were followed for 1 year. At the end of the study year, there was no difference in survival, pulmonary function, or everyday functioning among the three groups. Average annual cost of care for all study patients was $7,647 (1981-82 dollars). The average annual health care costs for patients in the RHC group was $9,768; for those in the SHC group, $8,058; and for those in the OC group, $5,051 (F = 6.45, df = 2/298, P = 0.02). These results suggest that the current policy of limited coverage of home nursing services by Medicare and other third-party payers may be appropriate.

Activities of Daily Living↗

The relation among pulmonary function, chest roentgenographic abnormalities, and smoking status in an asbestos-exposed cohort.

To clarify the clinical value of the International Labor Office (ILO) roentgenographic classification of pneumoconiosis in assessing asbestos-exposed persons, we determined the relationships among spirometric values, radiographic evidence of parenchymal pulmonary fibrosis and/or pleural thickening, and cigarette smoking history in 684 consecutively enrolled male plumbers and pipefitters participating in a larger cross-sectional prevalence study. The subjects were mainly marine pipefitters (35%), plumbers (24%), and steamfitters/welders (23%); 28% had never smoked, 39% were ex-smokers, and 33% currently smoked cigarettes. Mean values for FVC and FEV1 were 95.0 and 91.9% of predicted, respectively, with mean FEV1/FVC ratio 77.7%; by standard criteria, 7.8% had restrictive impairment, and 21.7%, obstructive defects. Chest radiographs were normal in 63% and showed pleural abnormalities only in 17%, parenchymal abnormalities only in 7%, and both pleural and parenchymal abnormalities in 12%. Both FVC and FEV1 correlated with the degree of small opacity profusion, as assessed by ILO grade. Pleural abnormalities were associated with lower FVC values, independently of ILO profusion grade for Grades less than or equal to 1/0, and were unexplained by smoking status. In addition, there was a positive association between smoking history and degree of ILO parenchymal abnormality, particularly in those with the heaviest cumulative smoking history. Our results suggest that the ILO classification of pneumoconiosis, although a useful epidemiologic tool, should be applied with caution in persons with asbestos exposure, and that pleural abnormalities may be associated with physiologic impairment in such persons.

Adult↗

Evaluation of clinical competence in pulmonary disease.

The American Board of Internal Medicine has called upon directors of pulmonary disease training programs to establish systems to evaluate, document, and substantiate those components of overall clinical competence considered essential for certification in the subspecialty. Many of these can be assessed only by repeated direct observations. In particular, proficiency is now required in endotracheal intubation, fiberoptic bronchoscopy, mechanical ventilatory support, thoracentesis and percutaneous pleural biopsy, percutaneous arterial puncture, vascular monitoring, calibration and operation of hemodynamic recording systems, and supervision of the technical aspects of pulmonary function testing. The goal of this expanded evaluation program is to ensure that the public and the profession can identify through certification, physicians with demonstrated excellence in the practice of pulmonology.

Certification↗

Single-dose efficacy and safety of zindotrine, a new oral bronchodilator.

Zindotrine, a new bronchodilator, may be an alternative to theophylline in treating reversible airflow obstruction. Efficacy and cardiovascular effects of a single 300 mg oral dose of zindotrine were compared with placebo in a two-period, double-blind, crossover trial. Twelve subjects with airflow obstruction reversible after isoproterenol and theophylline completed the trial. Improvement in pulmonary function (forced vital capacity [FVC], forced expiratory volume in one second, and forced expiratory flow rate from 25 to 75 percent of FVC) was greater after zindotrine than with placebo. Pulmonary function tests increased 15 percent or more over baseline in 30 minutes after active drug, lasting up to 6 hours. Mild decreases in heart rate and mean blood pressure occurred after both treatments, with changes equal in both treatment groups. Six subjects had mild subjective side effects after zindotrine (headache, dizziness, vertigo, flushing, and heartburn) compared with one report of lightheadedness after placebo. A single dose of zindotrine 300 mg provides effective bronchodilator action with a relatively prolonged response and tolerable side effects.

Adult↗

Total lung capacity. An insensitive measure of impairment in patients with asbestosis and chronic obstructive pulmonary disease?

The total lung capacity (TLC) is frequently used as a measure of respiratory impairment in patients with asbestosis. Because asbestosis and chronic obstructive pulmonary disease (COPD) exert opposite effects on the TLC, it may be an insensitive measure of impairment in patients with both abnormalities. To assess this, we compared asbestos-exposed patients with functional evidence of COPD and radiographic evidence of interstitial fibrosis (group 1) to those with interstitial fibrosis alone (group 2). Despite the two groups being comparable in degree of radiographic "fibrosis," no case of restrictive impairment (reduced TLC) was identified among those with both interstitial fibrosis and COPD (group 1), compared to 33 percent of those with interstitial fibrosis alone (group 2). In addition, those patients with both interstitial fibrosis and COPD, compared to those with interstitial fibrosis alone, were found to have greater impairment as measured by alveolar-arterial oxygen difference and diffusing capacity. We conclude that the TLC is an insensitive measure of impairment due to asbestosis in patients with the common setting of coexistent asbestosis and COPD.

Aged↗

Aberrant splicing of proteolipid protein mRNA in the dysmyelinating jimpy mutant mouse.

cDNA clones encoding proteolipid protein (PLP) were isolated from a mouse brain library and sequenced. We describe two transcripts arising from the PLP locus by alternative splicing: the major one encodes the 277-amino acid PLP protein and the minor one corresponds to the DM-20 protein, a PLP-like protein of 20,000 Mr that shares both amino and carboxyl regions with PLP. These two transcripts lack approximately 70 bases in PLP mRNA from the dysmyelinating jimpy mutant. The deletion spans amino acids 208-232; however, this region is present in the jimpy PLP-encoding gene. We propose that the jimpy mutant suffers a point mutation or the deletion of a few bases in the PLP gene that alters the normal splicing pattern and generates partially deleted PLP transcripts.

Amino Acid Sequence↗

Effect of positive end-expiratory pressure on right and left ventricular function in patients with the adult respiratory distress syndrome.

The predominant mechanism of the cardiac output reduction associated with positive end-expiratory pressure (PEEP) is unclear. Reported possibilities include decreased systemic venous return, increased pulmonary vascular resistance, or change in ventricular contractility. We investigated this question by studying 9 patients with the adult respiratory distress syndrome (ARDS) during PEEP application. We used an equilibrium radionuclide angiography method modified for improved right ventricular imaging to evaluate changes in left and right ventricular volume and contractility. Thermodilution cardiac output and stroke volume progressively declined (27 and 33% mean decrease, respectively) with increasing increments of PEEP. Right and left ventricular end diastolic counts, reflecting volume, also progressively diminished as PEEP increased (38 and 27% mean decrease in RV and LV counts, respectively; p less than 0.001 for both ventricles). A slight upward trend in ejection fraction was found for both ventricles. These findings support the concept that during PEEP application the reduction in cardiac output is due to biventricular reduction in blood volume. This biventricular volume reduction is compatible with either preload reduction to both ventricles because of impeded venous return or to change in ventricular configuration caused by external compression of both ventricles.

Adult↗

Severe precocious emphysema in intravenous methylphenidate (Ritalin) abusers.

Intravenous (IV) drug abuse is known to cause pulmonary tale granulomatosis. Reports have documented a syndrome of pulmonary vascular sclerosis in long-term IV methylphenidate users. Although this would be expected to produce restrictive lung disease, we hereby report six patients who have severe obstructive lung disease. All had used IV methylphenidate for at least four years. One of these patients died of progressive respiratory insufficiency and the others are clinically disabled. Their symptoms and airflow obstruction are more severe than those of most patients with chronic obstructive pulmonary disease. In these individuals, we cannot say that precocious obstructive lung disease is not due to a combination of smoking and other factors, nor can we be certain that methylphenidate is the offending agent. However, this cluster of cases among methylphenidate abusers suggests that long-term IV exposure to this drug might lead to early severe obstructive lung disease.

Adult↗

Rationing of intensive care unit services. An everyday occurrence.

We investigated the extent to which bed availability affects decision making in an intensive care unit (ICU). For 1,151 ICU patients, we determined the number of empty ICU beds available at times of admission and discharge and the outcome for those patients. For a randomly chosen group we assessed severity of illness. Patients admitted during times of bed shortage were, on average, more severely ill than those admitted when many beds were unoccupied. Patients discharged under crowded conditions were sicker and had a shorter stay than patients discharged when more beds were available. The relative risk of discharge was inversely related to empty bed availability, illness severity, and age. Bed availability had no effect on rates of death in the ICU, death after discharge, or readmission to the ICU. We conclude that physicians can effectively ration intensive care beds on a regular basis by altering admission and discharge decision making.

Bed Occupancy↗

Cost and outcome of care for patients with chronic obstructive lung disease. Analysis by physician specialty.

We studied the effect of physician specialization and board certification on costs and outcome of health care for a group of 213 patients with chronic lung disease followed prospectively for a year. Linear, semilogarithmic, and logistic regressions were used to control for differences in pulmonary function, functional ability, and sociodemographic characteristics. The cost of health services during the year was estimated from the total charges incurred. Patient's pulmonary function, functional ability, number of medical conditions, and insurance status were significant predictors of total cost. Combinations of these variables were important determinants of institutional days, outcome health status, and survival. Physician specialization and board certification were not significant descriptors of total costs or outcomes, although large variances limited the power of these findings. We conclude that differences in characteristics of primary care physicians do not appear to affect significantly the total cost or outcome of care for patients with moderate to severe chronic lung disease.

Aged↗