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W C Miller

Publications and source records attributed to W C Miller.

At least 19 recordsLinked to original sources

Delayed-type hypersensitivity testing in Tanzanian adults with HIV infection.

Delayed-type hypersensitivity (DTH) testing and total lymphocyte counts as measures of cell-mediated immune function were assessed for medical patients in Dar es Salaam, Tanzania. DTH testing was performed with the Multitest CMI device which simultaneously administers seven antigens. Of 201 patients completing DTH testing, 90 were HIV seropositive. Anergy occurred more frequently among HIV-seropositive patients (39 of 90) as compared with HIV-seronegative patients (17 of 111). DTH skin test reactivity, measured by anergy, the number of positive antigens, and the combined DTH response induration, was significantly related to the clinical stage of HIV disease. Median total lymphocyte counts were significantly lower in HIV-seropositive patients than in HIV-seronegative patients (1,130 vs. 1,680 lymphocytes x 10(6)/L). Total lymphocyte counts decreased with increasing severity of HIV disease. In multivariable analysis, the number of positive antigens in DTH testing and lymphopenia significantly predicted HIV infection. The findings suggest that DTH testing and total lymphocyte counts may be useful, inexpensive tests of immune function in African patients with HIV disease.

Adult

Diagnosis and screening of HIV/AIDS using clinical criteria in Tanzanian adults.

The clinical utility of the World Health Organization (WHO) clinical case definition (CCD) of acquired immune deficiency syndrome (AIDS) in Africa, several proposed modifications of the WHO CCD, and two proposed screening algorithms for human immunodeficiency virus (HIV) infection were examined in adult medical inpatients in Dar es Salaam, Tanzania. Sensitivity, specificity, and positive and negative predictive values were determined for the CCDs and screening algorithms. Multivariable analysis identified factors with high accuracy for HIV infection. Of 223 patients enrolled in the study, 95 were seropositive for HIV infection. The WHO CCD and the modified CCDs had low sensitivities (14.7-32.6%) but high specificities (95.3-99.2%) and positive predictive values (83.8-94.7%). The screening algorithms had moderate sensitivities (66.3-77.9%) and poor specificities (46.1-79.7%). Multivariable analysis consistently identified oral candidiasis and lymphadenopathy as the best predictors of HIV infection. Although patients with asymptomatic or early HIV infection may be missed by clinical criteria, in a high prevalence population, AIDS may be diagnosed accurately clinically because of the effect of prevalence on the positive predictive values of the CCDs. Furthermore, selection of patients for HIV serologic testing may be guided by simple combinations of clinical features.

Acquired Immunodeficiency Syndrome

International health and internal medicine residency training: the Duke University experience.

OBJECTIVE: To evaluate the impact of the Duke University Medicine Residency International Health Program (IHP) on program participants and to evaluate the relationship of the IHP to the residency program. SUBJECTS AND METHODS: The Duke University Medicine Residency Program classes of 1988 to 1996 participated in a questionnaire-based survey. All program participants (n = 59), a group of nonparticipants (n = 138), and residents who had not yet had an opportunity to participate (preparticipants; n = 106). RESULTS: The overall response rate to the questionnaire was 93%. Participation exceeded expectations and had a strongly positive impact on personal and professional lives of the majority of the participants. Participants reported a significant positive impact on their training in internal medicine and their knowledge of tropical medicine. A minority of nonparticipants identified a positive effect in these areas due to conferences and interactions with their participating colleagues. Participants who changes career plans during residency tended to move toward areas of general internal medicine or public health, in contrast to nonparticipants who tended to change areas of subspecialty or chose private practice. The IHP was identified as a significant factor for selection of the Duke Medicine Residency by 42% of the preparticipant group. Nearly all of the respondents (99%) indicated that the IHP should be continued. CONCLUSION: The IHP has a measurable positive impact on the participants, as well as on the Medicine Residency Program.

Career Choice

Cryptococcus neoformans fails to induce nitric oxide synthase in primed murine macrophage-like cells.

Nitric oxide (NO) is a microbiostatic gas generated by activated murine macrophages. Cytokine signals, gamma interferon (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) act synergistically to induce production of a macrophage nitric oxide synthase (NOS). A variety of intracellular pathogens, when recognized by macrophages primed with IFN-gamma, induce NOS by eliciting TNF-alpha secretion, which then functions as a positive autocrine signal. In cell culture assays, a murine macrophage cell line (J774), primed with IFN-gamma, was tested for NOS induction upon challenge with virulent Cryptococcus neoformans. C. neoformans failed to induce macrophage NOS as measured by nitrite production. This was true irrespective of the C. neoformans-to-J774 ratio. Other nonpathogenic Cryptococcus species likewise failed to induce NOS, yet Saccharomyces cerevisiae, Histoplasma capsulatum, and Candida albicans were efficient inducers of NOS. Conditions which promoted attachment and/or phagocytosis of C. neoformans did not lead to NOS induction (including opsonization with specific antibodies against C. neoformans). Assays for transcriptional repressors of NOS were negative. Tests for consumption of nitrite by measurement of additional products of NOS induction were negative. No TNF-alpha was detected by enzyme-linked immunosorbent assay in supernatants from C. neoformans-J774 cocultures. A mutant C. neoformans strain with a minimal, but visible, polysaccharide capsule also failed to induce NOS; however, several nonencapsulated mutants of C. neoformans did induce NOS. Failure of C. neoformans to act as an inducer of NOS may be related to the virulence of this pathogen in mice; C. neoformans is a unique example of a facultative intracellular pathogen which fails to induce NOS in primed macrophages. The mechanism appears to involve the failure of TNF-alpha secretion once the macrophage comes in contact with the fungus. The presence of the polysaccharide capsule appears to mask the signal necessary for TNF-alpha secretion and, ultimately, NOS induction.

Amino Acid Oxidoreductases

Dietary fat, sugar, and fiber predict body fat content.

OBJECTIVE: This study was conducted to determine the relationships among the specific components of dietary fat and carbohydrate and body fatness in lean and obese adults. DESIGN: Body composition determination was performed on each subject by hydrostatic weighing at residual volume. Subsequently, the individual components of dietary fat and carbohydrate were examined relative to body fatness using a 3-day food diary and a food frequency questionnaire. SUBJECTS: Subjects were 23 lean (11.1 +/- 2.9% body fat) men, 23 obese (29.2 +/- 3.8% body fat) men, 17 lean (16.7 +/- 3.3% body fat) women, and 15 obese (42.7 +/- 3.9% body fat) women who volunteered for free diet and body composition analyses. Inclusion criteria were 15% body fat for lean men, 25% for obese men, 20% for lean women, and 35% for obese women. STATISTICAL ANALYSIS PERFORMED: Group comparisons for dietary variables were made with a multivariate analysis of variance. RESULTS: No differences were found between lean and obese subjects for energy intake or total sugar intake, but obese subjects derived a greater portion of their energy from fat (33.1 +/- 2.6% and 36.3 +/- 2.3% for obese men and women, respectively, vs 29.1 +/- 1.3% and 29.6 +/- 2.0%, lean men and women, respectively). Percent of fat intake for saturated, monounsaturated, and polyunsaturated fats was not different among groups. Obese subjects derived a greater percentage of their sugar intake from added sugars than lean subjects (38.0 +/- 3.5% vs 25.2 +/- 2.0%, respectively, for men; 47.9 +/- 8.0% vs 31.4 +/- 3.4%, respectively, for women). Dietary fiber was lower for obese men (20.9 +/- 1.8 g) and women (15.7 +/- 1.1 g) than for lean men (27.0 +/- 1.8 g) and women (22.7 +/- 2.1 g). APPLICATIONS/CONCLUSIONS: Obesity is maintained primarily by a diet that is high in fat and added sugar and relatively low in fiber. Alterations in diet composition rather than energy intake may be a weight control strategy for overweight adults.

Adipose Tissue

Pott's disease caused by Mycobacterium xenopi: case report and review.

We report a case of Mycobacterium xenopi infection of the spine in a 70-year-old woman. The findings of our case and of five other published reports of bone or joint infection with M. xenopi illustrate the problems with diagnosis and management of infection with this organism. Detection of M. xenopi in clinical specimens may require prolonged incubation at 37 degrees C or incubation at higher temperatures. Furthermore, M. xenopi may be misidentified as Mycobacterium avium-Mycobacterium intracellulare complex. For these reasons, human infection due to M. xenopi may be underrecognized. The optimal therapy for human infection with M. xenopi is unknown.

Aged

RWJ-22108--a novel airway tissue--selective calcium channel blocker.

RWJ-22108 is a novel calcium entry blocker that has potential therapeutic use as an antiasthmatic agent. Although displaying typical potent inhibition of 45Ca uptake into aortic rings (IC50 = 7.1 nM) and displacement of [3H]nitrendipine from cardiac membranes (IC50 = 137 nM), RWJ-22108 demonstrates tissue selectivity in the inhibition of KCl-induced contractions. RWJ-22108 inhibits the calcium-dependent contraction of canine bronchiolar smooth muscle with an IC50 of 5.7 nM. The IC50 femoral artery/IC50 bronchiolar ratios are 2.85, 8.02, 1.47 and 1.96 for nifedipine, RWJ-22108, verapamil, and gallopamil, respectively. Furthermore, this selectivity ratio (range 2.8-5.5) of RWJ-22108 is also observed when inhibition of other pulmonary and cardiovascular smooth muscles are compared. Using canine tracheal muscle and rabbit aortae, the IC50 aorta/IC50 trachea ratio is 1.75 for RWJ-22108 compared to approximately 0.5 for several calcium blocker standards. These results indicate that in vitro RWJ-22108 is a bronchoselective calcium channel blocker.

Animals

Successful weight loss in a self-taught, self-administered program.

There is little evidence concerning the effectiveness of self-help materials for weight control. The purpose of this research was to evaluate a self-help weight-loss program. Obese (body fat > or = 25.0%, range = 25.0-48.6%, mean +/- SEM = 36.5 +/- 1.3%) men (n = 14) and women (n = 21) were given a workbook detailing a behavior modification approach to weight loss that emphasizes self-monitoring of diet and exercise behaviors, and then sent home for 6 months to learn how to lose weight on their own. A group of 9 controls (CONT) who did not get a workbook were used for comparison. ANOVA showed that the experimental group (EXP) lost 8.1 +/- 0.9 (mean +/- SEM) kg body weight, 6.4 +/- 0.8 kg fat, and 3.9 +/- 0.6% body fat; all significant over time (p < 0.001) and different from the CONT (p < 0.0001) who showed no change in these variables. The EXP also reduced their fat intake (% of joules) from 36.1 +/- 1.0% to 27.9 +/- 1.3% (p < 0.0001), increased their carbohydrate intake from 45.7 +/- 1.2% to 50.0 +/- 1.7% (p < 0.007) and their protein intake from 16.3 +/- 0.05% to 20.7 +/- 0.7% (0 < 0.03), all of which were significantly different (p < 0.03) than the CONT who did not change. Dietary fiber increased in the EXP from 19.8 +/- 1.4 to 27.3 +/- 2.2 g/d (p < 0.001) even with a significant reduction in energy intake (11.3 +/- 0.6 vs. 8.9 +/- 0.5 Mj/d; p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Predicting max HR and the HR-VO2 relationship for exercise prescription in obesity.

This research derived regression equations for predicting maximal heart rate (MHR) and examined the relationship between relative oxygen consumption (VO2) and heart rate (HR) in obese (N = 86, body fat > 30%, hydrostatic weighing) compared with normal-weight (N = 51, body fat < or = 30%) adults. Simultaneous measurements of HR and VO2 were recorded at rest and every minute during a maximal graded exercise test. When MHR was regressed on age, two distinct equations for the obese and normalweights were generated. The relationship between %MHR and %max VO2 was similar between groups (r = 0.83, obese; r = 0.87 normalweights). Likewise, when %max VO2 was regressed on %max heart rate range similar equations were derived fro the obese (r = 0.81) and normalweights (r = 0.84). Correlation between Karvonen's predicted HR at a submaximal VO2 and the true HR at that VO2 was 0.88, regardless of adiposity. These data indicate that when predicting MHR in normalweights the equation 220-Age can be used, but for obese individuals the equation 200-0.5 x Age is more accurate; each having 12 as a standard error of estimate. Once MHR is determined, either the straight percentage technique or Karvonen's method would be appropriate for prescribing exercise intensity for both populations.

Adipose Tissue

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.

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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