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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 19 recordsLinked to original sources

Occupation, smoking, and the risk of high-grade invasive bladder cancer in Missouri.

Numerous epidemiological studies have established that occupational exposures and smoking are the two major known risk factors for the development of bladder cancer. Using data from the Missouri Cancer Registry, we investigated the hypothesis that individuals with occupationally-related bladder cancer are more likely to have a more invasive form of the disease. Data were analyzed for 2,893 white males diagnosed with primary bladder cancer in Missouri between 1984 and 1988. Of the 1,415 cases whose occupational status was recorded, 236 (17%) were employed in high-risk occupations. Cases with high-grade disease were more likely to have been employed in a high-risk occupation, after adjustment for age and smoking (adjusted odds ratio [AOR] = 1.7, 95% confidence interval [CI] = 1.1-2.6). High-risk workers under 60 years of age were most at risk for developing high-grade bladder tumors (AOR = 2.3, 95% CI = 1.0-5.3). There was no overall association between high-risk occupation and late-stage disease (AOR = 1.1, 95% CI = 0.7-1.5), but it was present in the men younger than 60 years of age (AOR = 2.0, 95% CI = 1.0-3.8). No association was found between tobacco use and grade (AOR = 1.1, 95% CI = 0.8-1.5), but cases with late-stage disease were more likely to be smokers (AOR = 1.5, 95% CI = 1.1-1.9). When occupations were examined individually, motor vehicle operators, truck drivers, vehicle mechanics, other mechanics, and janitors were among those most likely to be diagnosed with high-grade or late-stage tumors. Although further studies are necessary to confirm these results, they suggest that surveillance and targeted screening of workers in high-risk occupations may result in a greater yield of early invasive cancers and possibly decrease the mortality associated with this disease.

Aged

Cumulation and reversal with prolonged infusions of atracurium and vecuronium.

A randomized, double-blind study was undertaken to compare the tendencies for cumulation, and reversal characteristics of atracurium (ATR) and vecuronium (VEC) when administered by continuous infusion for long surgical procedures under balanced anaesthesia. Eligible subjects were between 50 and 75 yr of age and were free of neuromuscular disease. Patients in the ATR group (n = 25) received a loading dose of atracurium 0.25 mg.kg-1, followed by an infusion initially set at 5.0 micrograms.kg-1.min-1. In the VEC group (n = 25) patients received a loading dose of vecuronium 0.05 mg.kg-1, followed by an infusion at 1.0 microgram.kg-1.min-1. During surgery, the infusions of both ATR and VEC were titrated in increments or decrements of 12.5% to maintain first twitch (T1) suppression of 90-95%. Neuromuscular block was measured by recording the integrated evoked electromyographic response (EMG) of the first dorsal interosseous muscle in response to supramaximal TOF stimuli on the ulnar nerve. The durations of infusion were similar for the two groups (164 +/- 42 and 183 +/- 67 min for ATR and VEC, respectively). The infusion rates of ATR (mean +/- SD) remained between 4.0 +/- 0.7 and 5.0 +/- 1.0 microgram.kg-1.min-1 throughout the study period. In contrast, a progressive decrease (P less than 0.05) in the infusion rate of VEC, from 1.0 to 0.47 +/- 0.13 micrograms.kg-1.min-1, was observed during the study period. The number of adjustments required to maintain 90-95% T1 suppression decreased between the second and fourth hours of administration, but were similar at corresponding times when comparing the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

A comparison of transcutaneous end-tidal and arterial measurements of carbon dioxide during general anaesthesia.

A randomized, prospective study was performed to evaluate the accuracy of a new transcutaneous carbon dioxide (CO2) monitor (Fastrac) during general anaesthesia. Twenty-two adult patients undergoing elective surgery were subjected to three different levels of minute ventilation by varying their respiratory rates in a randomized cross-over design. Simultaneous measurements of transcutaneous CO2 (PTCCO2) and arterial CO2 (PaCO2) were obtained at three levels of minute ventilation (low, medium and high). End-tidal CO2 (PETCO2) values were also recorded from a mass spectrometer (SARA) at each time period. A total of 66 data sets with PaCO2 ranging from 28-62 mmHg were analyzed. The PTCCO2 values demonstrated a high degree of correlation with PaCO2 over the range of minute ventilation (y = 0.904x + 6.36, r = 0.92, P less than 0.001). The PETCO2 measurement also demonstrated a generally good correlation with PaCO2 (y = 0.62x + 9.21, r = 0.89, and P less than 0.01). However, the PETCO2-PaCO2 gradients (mean 7.0 +/- 3.1 mmHg) were greater than the PTCCO2-PaCO2 gradients (mean 2.3 +/- 2.4 mmHg) at all three levels of minute ventilation (P less than 0.05). These differences were greatest when PaCO2 was in the high range (48-60 mmHg). We conclude that the new Fastrac CO2 monitor is accurate for monitoring carbon dioxide levels during general anaesthesia. The new transcutaneous devices provide an effective method for non-invasive monitoring of CO2 in situations where continuous, precise control of CO2 levels is desired.

Adult

Healing of partial thickness porcine skin wounds in a liquid environment.

This study employs a liquid-tight vinyl chamber for the topical fluid-phase treatment of experimental wounds in pigs. Continuous treatment with normal saline significantly reduced the early progression of tissue destruction in partial thickness burns. Uncovered burns formed a deep layer of necrosis (0.49 +/- 0.004 mm, mean +/- SD) although burn wounds covered with empty chambers demonstrated less necrosis (0.14 +/- 0.01 mm), fluid-treated wounds formed no eschar, and little tissue necrosis could be detected (less than 0.005 mm). Topical treatment with hypertonic dextran increased water flux across burn wounds by 0.24 ml/cm2/24 hr (mean, n = 95) over saline-treated wounds during the first 5 days after wounding. When partial thickness burn and excisional wounds were immersed in isotonic saline until healed, the daily efflux of water, protein, electrolytes, and glucose across the wound surface declined during healing to baseline values found in controls (saline-covered unwounded skin). The declining protein permeability was used as a reproducible, noninvasive, endogenous marker for the return of epithelial barrier function. Saline-treated excisional wounds healed within 8.6 +/- 0.6 days (mean +/- SD, n = 27) and burn wounds within 12.1 +/- 1.4 days (mean +/- SD, n = 15). Healing of fluid-treated wounds occurred without tissue maceration and showed less inflammation and less scar formation than healing of air exposed wounds (no attempt was made to compare rates of healing between air- and fluid-exposed wounds). We consider the fluid-filled chamber a potentially very useful diagnostic, monitoring, and delivery system for wound-healing research and for human wound therapy.

Animals

Practices and beliefs concerning screening family members of patients with melanoma. Results of a survey of New England dermatologists.

BACKGROUND: First-degree relatives of patients with melanoma are roughly two to eight times more likely than the general public to be diagnosed with melanoma. Several organizations recommend regular screening for these and other persons at high risk for melanoma. However, there are no data as to how frequently such persons receive skin cancer examinations. OBJECTIVE: Our purpose was to determine the current screening recommendations and practices of dermatologists regarding family screening for melanoma. METHODS: With a one-page questionnaire, we surveyed dermatologists attending a 1989 meeting of the New England Dermatological Society. RESULTS: Seventy-three dermatologists completed the questionnaire. Most dermatologists (70%) reported that they encouraged screening of family members of patients with melanoma but also reported that family members infrequently appeared for skin examinations. CONCLUSION: Although most dermatologists encouraged screening of first degree relatives of melanoma patients, there appears to be infrequent acceptance by the patient of these recommendations. Recording family screening in the patients' charts, reminders to patients, and distributing literature on familial melanoma may increase acceptance by the patient of these recommendations.

Dermatology

Who discovers melanoma? Patterns from a population-based survey.

BACKGROUND: Melanoma is external and potentially detectable by many persons but little is known about who first discovers these lesions. An understanding of discovery patterns can shape future public and professional education programs. OBJECTIVE: Our purpose was to assess patterns of melanoma discovery and to determine the patients' role in finding their own lesions. METHODS: With a written, mailed questionnaire, we conducted a population-based statewide survey of 216 incident cases of melanoma in Massachusetts. RESULTS: Approximately half (53%) of melanomas were self-discovered, whereas the remainder were detected by medical providers (26%), family members (17%), and others (3%). Nearly one third of persons said they could not see their own lesions easily. Compared with men, women were more likely to discover their own lesions (66% vs 42%, p = 0.001) and those on their spouses (23% vs 2%, p less than 0.001). CONCLUSION: Improving early detection and reducing mortality of melanoma will require both public and professional education programs, with particular emphasis on targeting men at highest risk of this disease.

Adult

Comparison of techniques for estimating nutrient intake: the Framingham Study.

We compared estimates of nutrient intake by three diet assessment methods (24-hour recall, 3-day food record, food frequency questionnaire) in a random sample of 73 females and 77 males from the Framingham Offspring/Spouse Study. The results differed according to analytic method. Estimates of group mean intake from the 24-hour recall and 3-day records were similar in both women and men, with differences of less than 10% for most nutrients. The estimates of mean intake calculated from the food frequency questionnaire generally differed from those obtained by the other methods, with higher estimated intakes in women and generally lower estimated intakes in men. Spearman rank correlations between the individuals' nutrient intakes estimated by the three diet assessment methods were modest (r = 0.08-0.68, most below 0.50) and comparable in the comparisons of the 24-hour recall or food frequency questionnaire with the 3-day records. Our data suggest the interchangeability of the recall and record methods and their preference over the food frequency questionnaire for mean estimates of group nutrient intake. The food frequency questionnaire appears to be of some utility in ranking individuals according to the usual intake, although these data are not informative in comparing this method with multiple days of recall or records beyond 3 days. This research underscores the need to develop and evaluate short methods of diet assessment in specific populations of interest.

Adult

Treatment of nonsteroidal anti-inflammatory drug-induced gastropathy.

The etiology, natural history, epidemiology, prevention, and treatment of nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) effects are reviewed. Current evidence suggests that NSAIDs cause acute cellular damage by a topical effect that is exacerbated by impaired healing. Although acute gastric injury from NSAIDs is rapid and almost uniform from patient to patient, not all patients develop serious chronic injury. Some adaptation to the effects of NSAIDs does occur. Endoscopic studies have found that 14-31% of long-term NSAID users have gastric or duodenal ulcers. Data on individual drugs are inconsistent, but they suggest that enteric-coated aspirin, salsalate, and ibuprofen cause the lowest incidence of GI hemorrhage. Preventive measures tested to date include reduction in gastric acid production (histamine H2-receptor antagonists) and attempts to increase mucosal defenses (sucralfate or misoprostol). Misoprostol is the only drug with FDA-approved labeling for prevention of NSAID-induced gastropathy. NSAID-related ulcers heal in most patients within two to three months when they are treated with H2-receptor antagonists with or without antacid, omeprazole, or misoprostol. In patients with multiple risk factors, prophylaxis with misoprostol would be appropriate unless the clinician is concerned solely about reactivation of a duodenal ulcer, in which case an H2-receptor antagonist would also be appropriate. Full-dose treatment with H2-receptor antagonists, omeprazole, or misoprostol will heal NSAID-induced ulcers, even when NSAID therapy is continued.

Anti-Inflammatory Agents, Non-Steroidal

Endocrine control of inflammation: rheumatoid arthritis double-blind, crossover clinical trial.

A dysfunction in the endocrine control system for inflammation in rheumatoid arthritis serves as the theoretical basis for chronic inflammation in the study design described. Eighteen patients with rheumatoid arthritis, who acted as their own controls, were brought to a minimum symptom state through conventional means, trained, and allowed to control subsequent flares by a patient-initiated, flare-response prednisone regimen. The six-month trial was double-blind with a crossover at midpoint. While continuing stable non-steroidal anti-inflammatory and disease modifying antirheumatic drug therapies, the patients averaged additional 57% and 75% reductions from baseline in tender joint count and total pain score, respectively, on the prednisone therapy. The prednisone therapy was differentiated by improvement from that of a placebo by six of the nine parameters evaluated. The adverse events were no more frequent with prednisone than with placebo use. The efficacy of prednisone was increased threefold while reducing consumption by 40% when compared to the predecessor 5-mg prednisone/day clinical trial.

Adult

Breast cancer risk after estrogen replacement therapy: results from the Toronto Breast Cancer Study.

The authors examined noncontraceptive estrogen use in relation to breast cancer risk in women under age 70 in a case-control study conducted in Toronto, Canada. Cases were 607 women with incident primary breast cancer, identified at the time of hospitalization for treatment. They were compared to 1,214 controls matched to the cases on neighborhood and decade of age. Information was obtained through personal interviews conducted in the subjects' homes. Most estrogen users had taken conjugated estrogens, and only 7% had also taken progestogens. Compared with never use, the estimated relative risk for ever use of unopposed conjugated estrogens was 0.9 (95% confidence interval (Cl) 0.6-1.2) after allowance for multiple confounding factors. Relative risk estimates for most duration categories were close to 1.0; the estimate for the longest duration category, greater than or equal to 15 years of use, was elevated (1.5, 95% Cl 0.6-3.8), but there was not a significant trend with increasing duration. The estimate for current use or use that ended less than 12 months before interview and had lasted for at least 5 years was 0.9 (95% Cl 0.4-1.9). The results provide evidence against an increase in risk among women who used unopposed conjugated estrogens for less than 15 years and for recent users; for women with durations of at least 15 years, an increase could not be ruled out.

Adult

The inappropriateness of conventional use of the correlation coefficient in assessing validity and reliability of dietary assessment methods.

Accuracy and precision of nutritional data are crucial in estimating effects in nutritional epidemiology. Because it is known that such data are usually flawed, studies have been designed to estimate both the validity of diet assessment methods in measuring "true" diet and the reliability of these methods in providing nutrient data that are at least reproducible. In these studies, validity and reliability have often been gauged by computing correlation coefficients between two or more estimates of diet and testing the coefficient's departure from 0. We propose that the correlation coefficient may be inappropriate in these studies as a measure of association. If correlation coefficients are presented, we suggest that one should also present confidence intervals and test the departure of the coefficient from approximately 1 rather than 0. We have examined this approach using dietary data from various studies. We have computed 95% confidence intervals of the correlation coefficients and have tested H0:rho = 0.95 as an approximation of rho = 1.00. In all of the studies selected, comparisons produced correlation coefficients statistically significantly different from both 0.95 and 0. Due to the dependence of the correlation coefficient on factors unique to individual studies, it is recommended that other techniques be used to assess agreement between nutrient scores derived in reliability or validation studies. Viable options include linear regression, analyses of the standard deviations of the differences between scores, and examinations of the intraclass correlation coefficient.

Diet

Bolus administration of esmolol for controlling the haemodynamic response to tracheal intubation: the Canadian Multicentre Trial.

A multicentre trial was designed to determine the dose-response and side-effects of esmolol when administered as a single iv bolus prior to induction of anaesthesia for controlling the haemodynamic response to tracheal intubation. Five hundred and forty-eight patients from 12 university-affiliated centres across Canada were randomized prospectively to receive either placebo (PLAC) or esmolol (E) in a dose of 100 mg (E100) or 200 mg (E200). Study medication was given immediately before induction of anaesthesia with thiopentone 3-5 mg.kg-1 and succinylcholine 1.5 mg.kg-1. Low-dose narcotic (fentanyl 2-3 micrograms.kg-1 or sufentanil 0.3 micrograms.kg-1) or moderate dose narcotic (fentanyl 4-7 micrograms.kg-1) was also given at five of the participating centres, whereas patients in the remaining seven centres received no narcotic. Patients who received PLAC and no narcotic had greater HR and SBP values after tracheal intubation than patients who received either E100 or E200 (P less than 0.005). The proportion of patients whose maximum HR exceeded 110 min-1 was also greater in the PLAC group (22/180) than in either the E100 (10/187) or E200 (9/181) groups (P less than 0.05), but was not different when comparing E100 with E200. Esmolol was less effective in controlling blood pressure, but, in combination with low-dose narcotic, esmolol suppressed the SBP response to tracheal intubation. In the presence of moderate-dose narcotic, however, a decrease in SBP occurred in all three groups following induction of anaesthesia (P less than 0.003), with the largest decrease (17 +/- 4%) occurring in patients who had received E200. The overall incidence of hypotension (SBP less than 90 mmHg) was greater in the E200 group (33%) than either the E100 (25%) or PLAC (16%) groups (P less than 0.05). Other side-effects, such as bradycardia, bronchospasm or pain on injection, occurred no more frequently in either esmolol group than with placebo. It is concluded that a 100 mg bolus of esmolol is safe and effective for controlling the haemodynamic response to tracheal intubation. This dose of esmolol combined with a low dose of narcotic (fentanyl 2-3 micrograms.kg-1 or equivalent) results in effective control of both heart rate and blood pressure, while avoiding important side-effects.

Adrenergic beta-Antagonists

Inhibited morphological terminal differentiation and enhanced proliferation of cultured mouse epidermal cells at different concentrations of dimethyl sulphoxide.

Dimethyl sulphoxide (DMSO), at concentrations of 1-2%, induces terminal differentiation in several different cell types in vitro and enhances the growth of newborn mouse epidermal cells in primary culture under conditions that also permit terminal differentiation. We have found that DMSO concentrations approaching 4% reversibly inhibited (with little overt toxicity) terminal differentiation of normal epidermal cells from newborn SENCAR mice. Cells cultured in medium containing 4% DMSO and calcium in excess of 1 mM did not stratify extensively or slough large amounts of keratinized debris into the medium as occurred in control cultures, nor did they form large numbers of squamous cells or keratin bundles, as revealed by light and electron microscopy. The number of detergent-insoluble cornified envelopes was similarly reduced. Long-term growth of epidermal colonies in secondary culture was optimum in 1% DMSO, this concentration also permitting normal terminal differentiation of these cells. Since DMSO had these effects on epidermal cells in vitro, it may also affect epidermal cell proliferation and terminal differentiation in vivo, an important consideration should DMSO ever be approved for topical use in the US.

Animals

Steady-state pharmacokinetics of hydroxychloroquine in rheumatoid arthritis patients.

Steady-state pharmacokinetics of hydroxychloroquine (HC) sulfate (Plaquenil) were studied in five volunteers with rheumatoid arthritis who had taken 6 mg/kg/d of the drug for at least six months. Blood samples were drawn at 0, 1, 2, 4, 6, 8, 12, and 24 hours following an oral dose. Both whole blood and plasma were assayed by an HPLC method for HC and its metabolites desethylhydroxychloroquine, desethylchloroquine, and didesethylchloroquine. A 24-hour urine collection was obtained and assayed for the same compounds. The pharmacokinetics of HC and its metabolites conformed to the model predicted by single-dose studies. During the 24-hour period the absorption phase and both early and late distribution phases were seen. Variation in mean maximum/minimum concentration was 40 percent. Renal clearance accounted for only 16 percent of unchanged HC (22 percent of total drug and metabolites) and did not correlate with creatinine clearance.

Administration, Oral