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Biomedical subjects

W C Miller

Publications and source records attributed to W C Miller.

At least 19 recordsLinked to original sources

Pulmonary toxicity of inhaled polypropylene fibers in rats.

This study was initiated to assess the pulmonary toxicity of a polyolefin fiber composed of polypropylene in male Fischer 344 rats after 90 days of inhalation exposure. To increase fiber respirability in the rodent, polypropylene fibers were size-selected before aerosolization to have a geometric mean diameter of 1.6 microns (46% < 1 micron) and a geometric mean length of 30.3 microns. Three groups of animals were exposed in nose-only inhalation chambers, 6 hr/day, 5 days/week, for 90 days to 15, 30, or 60 mg/m3 of polypropylene, or filtered air (negative control). Microscopic examination of the polypropylene fiber-exposed lungs revealed that, at all time points examined in the study, there was a dose-dependent increase in pulmonary macrophages. These minimal or mild increases in cellularity appeared to be reversible, especially at the lower doses 30 days post exposure. No fibrosis was observed in any of the groups. A strong correlation was found between the external exposure concentration, the time of exposure, and the lung fiber burden. The number of partially degraded (segmented) fibers within the lung increased with the exposure concentration and period of exposure, as well as with the period of recovery after termination of exposure at 90 days. Fibers were recovered from exposed lungs using a hypochlorite digestion technique.

Administration, Inhalation

Relapsing native-valve enterococcal endocarditis: a unique cure with oral ciprofloxacin combination drug therapy.

Enterococcal endocarditis is the third most common presentation in native valves, and it is the most refractory. Unique among the streptococci, enterococci are relatively resistant to beta-lactam antibiotics requiring a combination aminoglycoside regimen for cure. Relapse is common even after apparently adequate therapy and may be seen in up to 25% of cases that involve streptomycin-resistant strains. This problem is magnified by the recent appearance of beta-lactamase-producing strains of S. faecalis resistant to both ampicillin and gentamicin. Ciprofloxacin is being investigated with a number of antimicrobials in the attempt to identify superior protocols against troublesome pathogens. However, little published data is available concerning the clinical efficacy of this drug in enterococcal endocarditis. In vitro studies and preliminary trials with animal models have generally been disappointing with broth macrodilution time-kill or agar dilution proving the most reliable in vitro methods for predicting in vivo outcomes. The urgent need to identify new combination drug regimens is underscored not only by the development of new resistance patterns, but by the well-documented toxicities of conventional therapies. The authors present a case of relapsing enterococcal endocarditis caused by a non-beta-lactamase-producing strain of S. faecalis, which demonstrated high-level resistance to streptomycin but not to gentamicin. Relapses occurred despite favorable laboratory data and aggressive beta-lactam-gentamicin therapies. Cure was achieved using oral ciprofloxacin in a combination drug regimen, which is reported here for the first time.

Adult

Autobullectomy.

Explore the source record for details and available documents.

Aged

Introduction: obesity: diet composition, energy expenditure, and treatment of the obese patient.

The association of obesity with increased risks for developing hypertension, diabetes, cardiovascular disease, and cancer has made it a complex health problem. Exacerbating the problem is the realization that there are multiple factors, both physiological and psychological, that interact to induce obesity, as well as a myriad of components that may be useful in the curtailment of obesity. The aim of this symposium is to provide a wider understanding of the elements behind the development and reduction of obesity.

Adipose Tissue

Diet composition, energy intake, and nutritional status in relation to obesity in men and women.

There are dietary factors besides the total energy value of food that can affect adiposity by disrupting the balance between energy intake and expenditure. The purpose of this paper was to examine how perturbation of these dietary factors that control energy balance affects adiposity. There is a substantial amount of evidence suggesting that obesity is not associated with overeating, but with a high dietary fat-to-carbohydrate intake ratio. Physiological adaptations to energy-reduced dieting facilitate both weight regain and make it more difficult to lose weight during subsequent dieting attempts. Since obesity may be better characterized by diet composition than by energy intake, successful weight-loss programs should include diet compositional changes in their regimes.

Adipose Tissue

Diet composition, energy intake, and exercise in relation to body fat in men and women.

This study examined the relationships among body fat, diet composition, energy intake, and exercise in adults. Male (n = 107) and female (n = 109) adults aged 18-71 y (36.6 +/- 1.0 y, means +/- SEM) were hydrostatically weighed to determine body fat (5.7-49.0% of total weight). Diet and exercise behaviors were determined by use of a questionnaire. As body fat increased, percent of energy intake derived from fat increased (p less than 0.001) whereas the percent from carbohydrate decreased (p less than 0.001). There was no relationship between energy intake and adiposity although leanness and exercise were related (p less than 0.001). When subgroups of lean and obese subjects were compared, the lean subjects derived approximately 29% of their energy from fat and 53% from carbohydrate vs 35% and 46%, respectively, for the obese subjects. No differences were found between groups for energy intake but the lean individuals exercised more often than did the obese individuals. These data suggest that diet composition may play as important a role in fat deposition as do energy intake and lack of exercise.

Adipose Tissue

Epinephrine-activation of heparin-nonreleasable lipoprotein lipase in 3 skeletal muscle fiber types of the rat.

Epinephrine was used to activate the heparin non-releasable lipoprotein lipase (LPL) in the 3 skeletal muscle fiber types of the perfused rat hindlimb. Following a 9 min washout of the capillary-bound lipoprotein lipase, the hindquarter of the rat was perfused with a buffer containing 10 nM of epinephrine. Activity of the residual LPL in soleus, red vastus lateralis, and white vastus lateralis muscles increased 75%, 96%, and 102% respectively, following epinephrine perfusion. These results suggest that skeletal muscle LPL is under hormonal control possibly through protein phosphorylation by cyclic AMP dependent protein kinase.

Animals

Role of the alkaline TG lipase in regulating intramuscular TG content.

Three TG lipases have been identified in muscle (i.e., acid, neutral, and alkaline), but as yet we do not know which enzyme is responsible for tissue TG hydrolysis. Over the past 8 yr, work in our laboratory has focused on intracellular lipoprotein lipase (LPL). The results show that this lipase is regulated by the classical cAMP cascade and that the activity of this enzyme is inversely related to endogenous TG concentration. Using these results as a foundation we plan to examine molecular mechanisms involved in the synthesis, compartmentalization, and transport of the alkaline TG lipase. Further, the evidence suggests that this enzyme may be regulated by protein phosphorylation mediated by cyclic AMP-dependent protein kinase. We plan to test this possibility.

Animals

Clinical application of measurement of angiotensin-converting enzyme level.

Assay of angiotensin-converting enzyme (ACE) in the sera of 69 patients demonstrated elevated levels in 19 of 22 (86%) of those with clinically active, biopsy-proved sarcoidosis. Patients with dormant sarcoidosis and generally those with various other disorders had normal levels. Elevated levels were also seen in six cases possibly representing sarcoid variants and in one case each of leprosy, carcinoma, tuberculosis, lymphomatoid granulomatosis, and immunoblastic sarcoma. Although ACE is sensitive to active sarcoidosis, the presence of false-positive findings limits its diagnostic usefulness to an adjunctive role; the assay should be combined with medical evaluation and tissue biopsy in selected cases.

Adult

Respiratory failure in cancer patients.

A review of 180 cancer patients requiring mechanical ventilation disclosed that 26% survived to extubation, and 13% and 7% were alive at two and six months, respectively. Mortality was related to several factors individually and the cumulative number of organ systems dysfunctioning in a given patient. Compared with general intensive care patients, those with respiratory failure and neoplastic disease demonstrated a high incidence of drug-induced pulmonary disease, hematologic abnormalities, pneumothorax, and infections with multiple and unusual organisms--all of which alter the approach to management. Although the long-term survival was poor, immediate survival was comparable with that of many groups of patients with respiratory failure.

Adolescent

Methotrexate-induced diffuse interstitial pulmonary fibrosis.

Three patients received respectively 190 mg, 175 mg, and 196 mg of methotrexate and developed bilateral pulmonary infiltrates without evidence of peripheral blood eosinophilia. Sputum in the three cases failed to reveal acid-fast bacilli, pathogenic fungi, or opportunistic organisms by cultures and appropriate stains. Despite discontinuance of the drug and/or institution of corticosteroid therapy, progressive respiratory failure led to death. In all three cases, autopsy revealed gross and microscopic features indistinguishable from those seen in the Hamman-Rich syndrome, and methotrexate hepatotoxicity was present in one. Pulmonary eosinophilia or granulomas, classically seen in previously reported cases of methotrexate pneumonitis, were not observed. It is suggested therefore that methotrexate be added to the list of agents capable of inducing diffuse interstitial pulmonary fibrosis. Conversely, diffuse interstitial pulmonary fibrosis should be considered in the differential diagnosis of patients receiving methotrexate who develop bilateral pulmonary infiltrates seen on chest roentgenograms.

Aged

Are all recently detoxified alcoholics depressed?

Reports of the prevalence of depression among alcoholics vary from 3% to 98%; the authors attribute this variation to the use of different diagnostic criteria. They used clinical diagnosis, the Hamilton Depression Rating Scale, the Zung Self-Rating Depression Scale, and the MMPI to diagnose 35 men recently withdrawn from alcohol. The percentages of depression diagnosed were 8.6%, 28%, 66%, and 43%, respectively. The authors point out that the Hamilton, Zung, and MMPI scales are not diagnostic of depression in themselves and that accurate diagnosis of depression in alcoholics will reduce inappropriate treatment of nondepressed alcoholics and ensure careful treatment of the truly depressed.

Alcoholism

Inhaled atropine in asthma.

Ten adult asthmatics inhaled atropine and isoproterenol to determine the site of action in the airways and relative effectiveness of the two drugs. The two agents were equal in their effect on lung volumes and airway resistance but isoproterenol produced significantly better flows. Atropine was shown to be an effective bronchodilator with a predominant site of action in large airways. The authors believe atropine and atropine derivatives deserve ongoing investigation, especially regarding potential side effects of retarding mucociliary clearance and the clinical significance of apparent failure to dilate small airways.

Administration, Intranasal