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D R Miller

Publications and source records attributed to D R Miller.

At least 91 records · Page 5Linked to original sources

A cross-national investigation of diet and bladder cancer.

The existence of a large unexplained portion of attributable risk, and the marked variation in bladder cancer rates globally, have stimulated an interest in the role of nutrition in cancer of the urinary bladder. For this cross-national comparison study, we had complete data available for 50 countries. Using stepwise regression followed by general linear modelling, age-truncated (45-74 years), world-standardised, sex-specific bladder cancer mortality rates were regressed on an array of nutritional and socioeconomic independent variables in an effort to identify important predictors of bladder cancer mortality. Separate principal components analyses were used to summarise the nutritional and the socioeconomic (SES) variables. In the stepwise analyses, using food scores expressed in kcal/day per capita (as opposed to the nutritional components), total fat consistently entered the model first, and explained the greatest share of variability (R2) for both males and females. General linear models were fitted that included total fat, tobacco, alcohol, the three SES components (comprising seven socioeconomic predictors) and two food categories found significant in stepwise modelling, roots/tubers and vegetable oil. The R2 values were 0.84 for male rates and 0.77 for female rates, meaning that these study factors account for 84% of bladder cancer mortality in men and 77% in women. Substitution of the nutritional components for the foods resulted in general linear models with slightly higher R2 values (0.85 for males, 0.77 for females), but with attenuated fat effects. Results are discussed in light of biological plausibility.

Aged↗

Absence of a reservoir of Epstein-Barr virus (EBV) in normal tongue epithelium.

We examined human tongue epithelium and serum samples at autopsy for evidence of latent Epstein-Barr virus (EBV) infection. Although clinical serology revealed anti-EBV antibodies in most sera indicating past EBV infection, we found no Epstein-Barr nuclear antigen (EBNA)-coding sequences in tongue tissue by polymerase chain reaction (PCR), or Epstein-Barr-encoded RNA (EBER1) by in situ hybridization. Tongue epithelium does not appear to be a natural reservoir for latent EBV in immunocompetent hosts.

Adolescent↗

Reduced glucose availability induces torpor in Siberian hamsters.

Siberian hamsters kept in long photoperiods (16 h light/day) at 10 degrees C do not display torpor when provided with food ad libitum but do reduce their body temperatures (Tb) from 37 degrees C to as low as 15 degrees C for several hours each day in response to food restriction. Female hamsters maintained in a long photoperiod and fed ad libitum were injected with 2-deoxy-D-glucose (2-DG), a glucose analogue that reduces cellular glucose oxidation, or mercaptoacetate (MA), a drug that disrupts fatty acid oxidation. Dosages of 2-DG in excess of 1,500 mg/kg body mass reliably induced torpor with latencies of approximately 50 min from time of injection to a decrease in Tb below 30 degrees C; 79% of females displayed torpor at a dosage of 2,500 mg/kg. MA was uniformly ineffective in inducing torpor and did not increase incidence of torpor when combined with 2-DG treatment or food restriction. Decreased availability of glucose may be the major metabolic signal for inducing torpor in Siberian hamsters; availability of fatty acids appears to play little if any role in regulating this behavior.

Animals↗

Hippocampal interneuron activity in unanesthetized rats: relationship to the sleep-wake cycle.

Evoked population spikes and interneuronal discharges were recorded throughout the sleep-wake cycle in hippocampal regions CA1 and dentate gyrus (DG) of ten chronically implanted rats. During quiet wakefulness (QW) and slow-wave-sleep (SWS) (non-theta rhythm states), the primary shock of paired stimuli evoked in CA1 both high amplitude population spikes and multiple interneuron discharges when compared to active wakefulness (AW) and rapid-eye-movement (REM) sleep (theta rhythm states). A second shock was delivered to CA1 afferents 60 ms after the first shock. This second shock evoked a small population spikes during non-theta states, whereas it evoked higher amplitude population spikes in theta states. The second shock also evoked unit interneuron discharges in non-theta states but not in theta states. In the dentate gyrus, identical primary afferent stimulation evoked similar interneuron activity and uniform amplitude population spikes throughout the sleep-wake cycle. In contrast, the secondary shocks evoked a striking potentiation of the field population spike during sleep, SWS and REM sleep compared to AW and OW. Evoked DG interneuron spikes following the second population spike were greater in number during SWS compared to the other stages. Our findings suggest that hippocampal field potentials and interneuron activity recorded in vivo are regionally regulated, have unique state-dependent expression and are strongly influenced by inhibitory feed-forward mechanisms.

Activity Cycles↗

Etiology of melanoma.

Although the precise etiology of melanoma remains unknown, much data link sunlight to melanoma. The imperfect evidence associating sun exposure (particularly UVB radiation) with melanoma emerges from human data, obviating problems inherent in extrapolation from animal and other models. However, the mechanism by which sunlight might possibly initiate or promote melanoma remains obscure. Some clarification should emerge from the potential isolation of genes that carry susceptibility to melanoma in families prone to the disease; such work could serve as a basis to distinguish genetic and environmental influences in melanoma [167]. Continued studies of faulty DNA repair in XP patients may elucidate the steps in mutagenesis and carcinogenesis. Future case-control studies must address the limits on the accuracy of recall and the limits on statistical methods to separate the cluster of phenotypic risk needed in determining biologically effective dose. Animal and in vitro studies must contribute more insight. Further research in the South American opossum models appears promising [72]. Although ozone depletion has been documented, there has been little definitive evidence of subsequent increase of UVB at the Earth's surface. Nevertheless, the threat posed by ozone depletion deserves continued environmental action and public education. The role of precursor lesions, particularly dysplastic nevi/atypical moles, must be clarified with future research. The distribution of melanoma among various work forces suggests that occupational risk factors may play an important role in the etiology of this disease [168-170]. The consistent reports of excess melanoma among accountants, clerical workers, professional workers, and teachers deserve further study. Furthermore, evidence of excesses in printing and press, petrochemical, and the telecommunications industries require follow-up. Carefully planned studies that account for nonoccupational risk factors are recommended. Research over the last four decades has brought much information about melanoma etiology. More work is needed to learn the precise cause and ultimately to prevent avoidable mortality from malignant melanoma.

Animals↗

Diet, menopause, and serum cholesterol levels in women: the Framingham Study.

Cross-sectional relationships between diet and total serum cholesterol levels were studied in a sample of 428 women from the Framingham Heart Study Cohort, aged 37 to 70 years, from 1957 to 1960. Multiple linear regression was used to control for total calorie intake, systolic blood pressure, physical activity, Metropolitan relative weight, glucose intolerance, and cigarette smoking. There was little evidence for a relationship between total serum cholesterol and dietary fat intake; whereas a marginally significant direct association was found with total fat in postmenopausal women, total and plant fat and cholesterol were inversely associated, and only cholesterol was significant in premenopausal women. A consistent inverse association was observed between total serum cholesterol levels and intake of protein, particularly from plant sources, and a weak inverse association was found with complex carbohydrate intake. Serum cholesterol in women may be influenced by a number of dietary factors and appears to differ according to menopausal status.

Adult↗

Consumption of meat and fruit in relation to oral and esophageal cancer: a cross-national study.

Using data from 59 countries, we conducted an international comparison study to identify nutritional predictors of age-adjusted oral and esophageal cancer mortality rates. Statistical models accounted for per capita tobacco disappearance data, alcohol consumption, and various measures of socioeconomic status. For oral cancer, stepwise regression results showed protective effects for milk/dairy products (B = -0.030, p < 0.0001) and cabbage consumption (B = -0.391, p = 0.01) and increased risk from vegetable oil (B = 0.072, p = 0.04) and excess animal fat calories (B = 0.344, p < 0.0001) as well as marginally increased risk from cereals (B = 0.008, p = 0.08). Results were obtained after accounting for all background factors, including sex (model R2 = 0.52). For esophageal cancer, stepwise results indicated protective effects for fruit (B = -0.046, p = 0.0006) and total caloric intake (B = -0.013, p < 0.0001) and increased risk from vegetable oil (B = 0.061, p = 0.04) and meat (B = 0.031, p < 0.0001) consumption (model R2 = 0.55). When analyzed separately by sex, results were similar, indicating that the risk factors are probably the same in both sexes, even though women consistently have fewer deaths, on average, from these cancers. On the basis of results from stepwise regression models, we also fitted general linear models for mortality rates of each cancer site, and results were similar in terms of magnitude and direction of effects. Although the evidence provided by this type of analysis using data aggregated by country is limited in terms of control for potential confounding effects and modeling of possible effect modification, an effect of high meat, animal product, or vegetable oil and low fruit and cabbage consumption is consistent with the known biology of these tumors.

Aged↗

Increased neurite outgrowth induced by inhibition of protein tyrosine kinase activity in PC12 pheochromocytoma cells.

Genistein and other inhibitors of protein tyrosine kinases were examined for effects on neurite elongation and growth cone morphology in the rat PC12 pheochromocytoma cell line. Genistein increased the rate of neurite elongation in PC12 cells grown on a collagen/polylysine substratum after priming with nerve growth factor (NGF), but had no effect on undifferentiated cells. Steady-state levels of phosphotyrosine-modified proteins (105, 59, 52, and 46 kDa) were reduced in NGF-primed cells by genistein treatment. The target of genistein action did not appear to be the NGF receptor/trk tyrosine kinase because the presence of NGF in cultures of NGF-primed cells was not necessary for genistein-stimulated neurite outgrowth. The tyrosine kinase inhibitors tyrphostin RG508964 and herbimycin A also increased the rate of neurite elongation in NGF-primed PC12 cells. Video-enhanced differential interference contrast microscopy revealed that growth cones of genistein-treated cells had less complex morphologies and were less dynamic than untreated cells, with short filopodia restricted to the leading edge, unlike untreated cells whose growth cones exhibited longer, more numerous filopodia and lamellipodia, which remodeled continuously. These results suggest that protein tyrosine kinase activity in PC12 cells negatively regulates neurite outgrowth and directly or indirectly affects growth cone morphology.

Adenosine Triphosphate↗

Ethanol-induced suppression of hippocampal long-term potentiation is blocked by lesions of the septohippocampal nucleus.

Systemic ethanol increases synaptic inhibition and suppresses long-term potentiation (LTP) in the dentate gyrus of the rat hippocampus. Local application of ethanol directly into the dentate gyrus of anesthetized rats increased the perforant path to dentate feed-forward inhibition, but had no effect on LTP. Local application of ethanol to the medial septum, a subcortical structure with major input to the dentate, increased recurrent inhibition. Selective disruption of septodentate input produced by lesions of the septohippocampal nucleus blocked the effects of systemic ethanol on LTP. These findings are the first to demonstrate that septodentate input is necessary for ethanol to increase recurrent inhibition and suppress LTP in the dentate gyrus and suggest an important role for extrahippocampal modulation of both short- and long-term plasticity in the hippocampus.

Afferent Pathways↗

Effects of alfentanil on the hemodynamic and catecholamine response to tracheal intubation.

A randomized, placebo-controlled study was conducted in 60 ASA Class I, II, and III patients to determine the dose response of alfentanil in moderating the cardiovascular and catecholamine response to tracheal intubation (INT). Patients were randomly allocated into one of four groups to receive either 15 micrograms/kg alfentanil (A15), 30 micrograms/kg alfentanil (A30), 45 micrograms/kg alfentanil (A45), or normal saline (control), given intravenously (i.v.) before induction of anesthesia. One minute after administration of 4.0 mg/kg thiopental and 1.5 mg/kg succinylcholine i.v., tracheal intubation was performed using direct laryngoscopy. In response to INT, increases in heart rate, systolic blood pressure, and systemic vascular resistance occurred in the control group. These changes were significantly more than corresponding changes of heart rate, systolic blood pressure, and systemic vascular resistance in all three alfentanil groups (P < 0.05). In contrast, cardiac index and ejection fraction decreased moderately in every group during the study period, but there were no differences among groups with respect to either cardiac index or ejection fraction at corresponding times following INT. In the control group, epinephrine and norepinephrine serum concentrations increased by 152 +/- 52% and 58 +/- 62%, respectively, following INT (different from A30 and A45, P < 0.05). However, up to a dose of 30 micrograms/kg (A30), a dose-dependent decrease in the maximum percent changes of both epinephrine and norepinephrine occurred in response to INT. A larger dose of alfentanil was no more efficacious as the catecholamine response to tracheal intubation was not significantly different when comparing the A45 and A30 groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Nutrition and health risks in the elderly: the nutrition screening initiative.

OBJECTIVES: The Nutrition Screening Initiative is a national collaborative effort committed to the identification and treatment of nutritional problems in older persons. METHODS: A 14-item checklist of characteristics associated with nutritional status was administered to a random sample of Medicare beneficiaries, aged 70 years and older, in New England. Regression analysis was used to derive item weights that would predict poor nutrient intakes and low perceived health status. Sensitivity and specificity values were reviewed to define low, moderate, and high nutritional risk scores. RESULTS: A revised checklist containing 10 yes/no items was adopted. Scores of 6 or more points defined persons at high nutritional risk. Twenty-four percent of the Medicare population was estimated to be at high nutritional risk according to the checklist. Among those in the high-risk group, 56% perceived their health to be "fair" or "poor" and 38% had dietary intakes below 75% of the recommended dietary allowances for three or more nutrients. CONCLUSIONS: The Nutrition Screening Initiative Checklist is a brief, easily scored instrument that can accurately identify noninstitutionalized older persons at risk for low nutrient intake and health problems.

Aged↗

Alloy particle shape and sensitivity of high-copper amalgams to manipulative variables.

Compressive strength, dimensional change during hardening and residual mercury content of three high-copper spherical particle amalgams (Tytin, Logic and Valiant), two admix amalgams (Dispersalloy and Permite C) and a conventional lathe-cut amalgam (New True Dentalloy) were determined as a function of condensation pressure and trituration time. The properties of the three amalgams containing non-spherical particles were markedly dependent on condensation pressure in the range 3 MPa to 14 MPa. Specimens condensed at 3 MPa showed substantially lower strength, greater expansion during hardening and higher residual mercury contents than did specimens condensed at 14 MPa. The three high-copper spherical particle amalgams, on the other hand, were comparatively insensitive to condensation pressure. Variations in trituration time between 5 and 12 seconds had little effect on the properties of any of the amalgams.

Copper↗

Variation in condensation pressure during clinical packing of amalgam restorations.

Clinical measurements were made of the condensation pressures applied by a specialist prosthodontist to each amalgam increment during the packing of two pinned Class II restorations. The technique employed involved taking simultaneous video recordings of the operative procedures and the output of a strain gauge stress measuring system attached to the plugger. The condensation pressure applied during each thrust of the plugger could then be related directly to a particular stage of the packing process. In Cavity A, a maxillary left second premolar, an "admix" amalgam containing both spherical and lathe-cut particles was used while Cavity B, a mandibular right first molar, was filled with a spherical particle amalgam. The measurements indicated that the condensation pressures applied decreased substantially as the filling of each cavity proceeded. A marked reduction accompanied the change from a 1.5 mm diameter to a 2.5 mm diameter plugger but in addition, the dentist modified the force applied to each plugger according to the particular task which he was undertaking. For Cavity A, the condensation pressure applied during the filling of the base of the mesial proximal box was 12.6 +/- 1.9 MPa whereas the final increment was subjected to a condensation pressure of only 2.2 +/- 0.7 MPa. Corresponding figures for Cavity B were 7.6 +/- 2.0 MPa and 1.9 +/- 0.5 MPa.

Dental Alloys↗

Use of serotonergic drugs for treating depression in older patients.

The selective serotonin reuptake inhibitors (SSRIs) offer a relatively new alternative to traditional tricyclic antidepressants (TCAs) in the treatment of depression in older adults. The two drug classes are equally effective, but SSRIs tend to cause fewer sedating, anticholinergic, or hypotensive effects and are unlikely to affect cardiac conduction. SSRIs also have a wider therapeutic window and are safer in cases of overdose. Potential side effects include GI distress, worsening of headaches, insomnia, and sexual dysfunction. Drawbacks of using SSRIs are their potential for drug interactions and relatively high cost.

Aged↗

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↗