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Biomedical subjects

D Fletcher

Publications and source records attributed to D Fletcher.

At least 37 records · Page 2Linked to original sources

Abnormal chest x-rays in intravenous drug users: implications for tuberculosis screening programs.

OBJECTIVES: The purpose of the study was to (1) determine the prevalence of significant abnormalities in routine chest x-rays used to screen for pulmonary tuberculosis in intravenous drug users and (2) evaluate the ability of the purified protein derivative skin test to identify persons with such abnormalities. METHODS: We conducted a cross-sectional screening study on 1314 persons admitted to an opiate detoxification unit in an urban jail. Purified protein derivative tuberculin reactivity and the prevalence of abnormalities consistent with tuberculosis on screening chest x-rays were evaluated. The chest x-ray was obtained independent of the skin test. RESULTS: The chest x-rays of 73 of the inmates (5.6%) showed abnormalities consistent with tuberculosis. Tuberculin skin testing missed 17 of 26 chest x-rays (65%) with significant infiltrates. CONCLUSIONS: Purified protein derivative screening is insensitive to chest x-ray abnormalities that require additional diagnostic evaluation for tuberculosis. Routine chest studies should be performed on all intravenous drug users admitted to congregate housing settings.

Adult

[The clinical reality of preventive analgesia].

Preemptive analgesia is based on neurophysiological studies suggesting that a nociceptive input may induce a prolonged hyperexcitability of the central nervous system. This plasticity of the nervous system seems to be more easily prevented than treated. The clinical application of preemptive analgesia is not yet possible. Further clinical and fundamental studies using a good methodology are necessary. This article reviews available clinical data with a special interest for anti-inflammatory drugs that the author has personally evaluated.

Humans

Intracellular neutralization of virus by immunoglobulin A antibodies.

IgA is thought to neutralize viruses at the epithelial surface of mucous membranes by preventing their attachment. Since IgA, a polymeric immunoglobulin, is transported through the lining of epithelial cells by the polymeric-immunoglobulin receptor and since viruses are obligate intracellular parasites, we hypothesized that IgA antibodies may also interfere with viral replication by binding to newly synthesized viral proteins within infected cells. Polarized monolayers of Madin-Darby canine kidney epithelial cells expressing the polymeric-immunoglobulin receptor were infected on the apical surface with Sendai virus. Anti-Sendai virus IgA monoclonal antibody delivered from the basolateral surface colocalized with viral protein within the cell, as documented by immunofluorescence. More importantly, anti-viral IgA reduced virus titers greater than 1000-fold (P less than 0.0001) in apical supernatants and greater than 10-fold (P less than 0.0001) in cell lysates from monolayers treated with anti-viral IgA compared with those treated with either anti-viral IgG or an irrelevant IgA monoclonal antibody. We believe that the differences in viral titers between cell layers treated with specific IgA, which enters the epithelial cell by binding to the polymeric-immunoglobulin receptor, and those treated with specific IgG, which does not enter the cells, or irrelevant IgA indicate that specific intracellular IgA antibodies can inhibit viral replication. Thus, in addition to the classical role of humoral antibodies in extracellular defense, IgA antibody may be able to neutralize microbial pathogens intracellularly, giving IgA a role in host defense that has traditionally been reserved for cell-mediated immunity.

Animals

Induction of emphysema and bronchial mucus cell hyperplasia by intratracheal instillation of lipopolysaccharide in the hamster.

The aim of this study was to determine whether lipopolysaccharide-induced elastase release from recruited neutrophils in the hamster lung would induce emphysema, measured by mean linear intercept (Lm) and bronchial mucus cell hyperplasia (BMCH), scored in tissue sections stained with periodic acid-Schiff. Lipopolysaccharide (LPS) was instilled transorally twice a week for up to 5 weeks in hamsters. At 4 weeks after seven LPS instillations, Lm amounted to 87.6 +/- 1.2 microns, while it was 68.3 +/- 1.5 microns after seven saline instillations (P less than 0.01). At 6 months after the sixth LPS instillation, the Lm of these lungs was 83.3 +/- 1.6 microns, indicating irreversible tissue destruction. LPS-treated hamsters showed marked to severe BMCH, which was most evident in large intrapulmonary airways. Instillations of highly selective inhibitor of hamster PMN elastase resulted in 50 per cent inhibition of LPS-induced emphysema. The development of BMCH was inhibited by approximately 35 per cent by this agent. To study the response in time of cellular infiltration after a single LPS instillation, the lungs of groups of four hamsters were lavaged at different time points. PMN recruitment showed peak values at 4 and 48 h after LPS instillation and returned to baseline values at 96 h. Simultaneous intratracheal instillation of LPS and anti-TNF alpha antiserum resulted in a considerable reduction of neutrophil influx into bronchoalveolar spaces in the first 6 h after instillation.

Animals

Enhanced physical therapy improves recovery of arm function after stroke. A randomised controlled trial.

Previous research on stroke rehabilitation has not established whether increase in physical therapy lead to better intrinsic recovery from hemiplegia. A detailed study was carried out of recovery of arm function after acute stroke, and compares orthodox physiotherapy with an enhanced therapy regime which increased the amount of treatment as well as using behavioural methods to encourage motor learning. In a single-blind randomised trial, 132 consecutive stroke patients were assigned to orthodox or enhanced therapy groups. At six months after stroke the enhanced therapy group showed a small but statistically significant advantage in recovery of strength, range and speed of movement. This effect seemed concentrated amongst those who had a milder initial impairment. More work is needed to discover the reasons for this improved recovery, and whether further development of this therapeutic approach might offer clinically significant gains for some patients.

Activities of Daily Living

The link between sexually transmitted disease clinics and HIV counseling and testing centers: who is not getting referred?

A total of 236 clients attending human immunodeficiency virus (HIV) counseling and testing (C&T) centers and sexually transmitted disease (STD) clinics were interviewed to evaluate who is being reached by C&T services and if STD clients are being referred to HIV C&T centers. Respondents receiving HIV C&T reported significantly more sexual risk based on characteristics of their partners, whereas STD clinics respondents more frequently reported previous STD diagnoses and sex with prostitutes. Over 50% of the high-risk individuals attending STD clinics were not referred to HIV C&T centers. The differences in perceived risk of current and future infection between STD and HIV C&T centers and the low referral rates of high-risk individuals for HIV C&T indicate a need for increased education efforts, more effective risk-assessment policies in STD clinics, and a tightening of the link between STD clinics and HIV C&T centers.

Adolescent

Evaluation of the journals of the American Association on Mental Retardation.

Perceptions of members of the American Association on Mental Retardation (AAMR) regarding the extent to which the organization's journals, the American Journal on Mental Retardation (AJMR) and Mental Retardation (MR) assist its members in adding to their knowledge and in carrying out their professional responsibilities were obtained. The 3-page survey was mailed with AAMR membership dues renewal notices for 1988. Surveys were returned by 1,619 members, 24.8% of the paid membership as of May 1988. Survey data were analyzed on the basis of division membership and occupational category for both journals.

Attitude of Health Personnel

Cardiac asthma presenting as status asthmaticus: deleterious effect of epinephrine therapy.

Epinephrine is a potent bronchodilator currently used to treat severe asthma, although there is no proven advantage of this drug over beta 2 adrenergic agonists. By contrast, as demonstrated here, the use of such a potent vasoconstrictor can worsen hemodynamic status when left ventricular dysfunction is associated with asthma or is the cause for dyspnea. We describe the case of a 60-year-old man with an history of chronic asthmatic bronchitis admitted for status asthmaticus. Bronchodilator therapy, including high dosages of intravenous epinephrine, failed to improve the patient and he was intubated and mechanically ventilated. Several hours later, a right heart catheterization revealed severe unexpected left heart dysfunction with a capillary wedge pressure of 45 mmHg and a cardiac index of 1.7 l/min/m2. Epinephrine was gradually stopped which resulted in a decrease in mean arterial blood pressure and an improvement of hemodynamic status. He was discharged on home mechanical ventilation. In this patient, ischemic left heart failure was revealed by a clinical picture mimicking status asthmaticus. Epinephrine, given as bronchodilator therapy on an empiric basis precipitated the patient into cardiogenic shock. Therefore this drug should not be recommended in face of the possibility of cardiac asthma or associated cardiac dysfunction.

Diagnosis, Differential

A computerized approach to injury description.

The study of trauma has been handicapped from its inception by the absence of a single coherent method of cataloging injuries. The AIS and ICD-9 systems have failed to fill this void because they lack the precision necessary to describe surgically treated injuries. We conceived a simple system of injury description in which injuries are rapidly encoded using a microcomputer in sufficient detail to distinguish among millions of different injuries. This system is easily searched by a microcomputer and allows for the automatic assignment of AIS, ISS, and CPT codes. In this system a patient is described by a 'paragraph' consisting of any number of identically patterned 'sentences,' each describing one of the patient's injuries. Each 'sentence' is composed of a string of six 'words' from controlled vocabularies and has the following structure: "Body region, Organ, Anatomic region, Injury, Physiology, Treatment." Defining the vocabulary allowed for each 'word' in a 'sentence' is complex because the allowed vocabulary is dependent upon the preceding 'words' in a 'sentence,' but in practice a microcomputer simply provides short lists of acceptable choices at each step of injury description, and records the user's selections. Additionally, the microcomputer assigns AIS, ISS, and CPT codes appropriate to the injury description sentence. The ease of data entry, the fineness of detail captured, the automation of code assignment, and the accuracy of database searching for specific injuries, classes of injuries, or combinations of injuries, we believe will give this approach widespread application in academic trauma centers where an accurate and accessible trauma database is important.

Humans

Pharmacological profile of the substituted beta-lactam L-659,286: a member of a new class of human PMN elastase inhibitors.

Human polymorphonuclear leukocyte elastase (PMN elastase) is inhibited by L-659,286 (7 alpha-methoxy-8-oxo-3-[[(1,2,5,6-tetrahydro-2-methyl-5,6-dioxo-1,2,4- triaz-in-3-yl)thio]methyl]-5-thia-1-aza-6R-bicyclo[4.2.O]oct-2-ene -2- pyrrolidine carboxamide-5,-dioxide) with a Ki of 0.4 microM. This inhibition is time-dependent, rapid, and only slowly reversible, with a t1/2 of greater than 3 days at 25 degrees C. L-659,286 is also highly selective for PMN elastase, as it does not inhibit thrombin, trypsin, papain, plasmin, chymotrypsin, or cathepsin G. L-659,286 administered intratracheally inhibits lung damage caused by administration via the same route of human PMN elastase into hamsters. In marmosets, L-659,286 is cleared from blood very rapidly after an intravenous injection but is recovered in bronchoalveolar lavage fluid for several hours after intratracheal administration.

Animals

Variability of peritoneal clearances for apolipoprotein and its relationship to susceptibility for atherosclerotic changes in CAPD.

Apolipoprotein Clearance and Atherogenicity in CAPD: Protein and lipoprotein loss is one of the disadvantages of CAPD. The impact of these losses on serum constituents is not fully understood. Lipoprotein disorders are observed in patients with chronic or acute renal failure or undergoing dialytic therapy with resultant increase in atherosclerotic clinical events yet these phenomenon are poorly understood, underinvestigated and underreported. Thus the impact of dietary and pharmacological steps to prevent these events are limited by lack of clinical facts. The recent emergence of effective lipid lowering agents makes a rapid analysis of parameters important. We studied the relationships between peritoneal clearance of apolipoproteins and serum atherogenicity indicators in a preliminary study of 10 CAPD patients with and without peritonitis. We measured total cholesterol (TC), HDL-Cholesterol (HDL-C), Apo A-I and Apo B and dialysate levels of Apo A-I and Apo B. Apo levels were determined immunotubidimetrically, and dialysate was concentrated by ultrafiltration. A subsequent prospective group of 10 additional patients was studied to test the relationship found in the preliminary study. In both preliminary and prospective nonperitonitis groups, the ratio of peritoneal clearance of Apo A-I to Apo B correlated strongly with the serum TC/HDL-C (r = 0.9 preliminary, r = 0.78 prospective group). There was an inverse correlation between the clearance ratio and both serum HDL-C (r = -0.71 preliminary, r = -0.77 prospective group) and serum Apo A-I/Apo B (r = -0.74 preliminary, r = -0.62 prospective group).(ABSTRACT TRUNCATED AT 250 WORDS)

Apolipoprotein A-I

Sex steroid replacement in post-menopausal women: effects on thyroid hormone status.

We have measured serum thyroxine (T4), triidothyronine (T3), thyroid-stimulating hormone (TSH) free thyroxine (FT4) and thyroxine-binding globulin (TBG) levels in a total of 5 post-menopausal women who were receiving oestrogen alone (Premarin, n = 19), progestogen alone (Primolut-N, n = 12), a combination of oestrogen and progestogen (Prempak C, n = 14) or no treatment (control group, n = 12). No differences were observed between the Premarin and Prempak C groups; both exhibited elevated T4 and TBG levels, although free thyroxin (FT4) and T4/TBG concentrations were normal relative to those in the control group. The Primolut-N subjects showed subnormal T3 and FT4 levels relative to the controls. It was concluded that it is not possible to make general statements regarding the effects of sex steroids on FT4 levels.

Estrogens, Conjugated (USP)