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Biomedical subjects

D R Miller

Publications and source records attributed to D R Miller.

At least 73 records · Page 4Linked to original sources
PubMed1996

Melanoma awareness and self-examination practices: results of a United States survey.

BACKGROUND: Skin cancers are common and there has been a dramatic increase in their incidence, particularly melanoma. However, little is known about awareness of melanoma and early detection practices in the general U.S. population. OBJECTIVE: In 1995, the American Academy of Dermatology increased their efforts to promote awareness of melanoma. This study was conducted to document current knowledge of melanoma and self-examination practices. METHODS: In February 1995, a telephone survey was conducted in a nationally representative sample of 1001 persons at least 18 years of age (3% margin of error) that included questions on knowledge, attitudes, and practices regarding early detection of melanoma. RESULTS: Almost 42% of those surveyed were unaware of melanoma, and only 26% of those who were aware could identify its specific signs. Most recognized at least one common risk factor for melanoma (e.g., sun exposure, fair skin). However, many did not distinguish melanoma from other skin cancers in terms of risk factors, signs of early disease, and body site distribution. The lowest measures of melanoma knowledge and attitudes were found among those who are male, nonwhite, and parents, and those with the lowest level of education and income. More than half (54%) did not conduct a self-examination. This practice was most frequently reported by women, white persons, and the elderly, as well as those with a greater knowledge of melanoma. CONCLUSION: Our research documents deficiencies in knowledge and practices related to early detection of melanoma in the general U.S. population and supports the need for public education about melanoma.

Adult↗
PubMed1996

Evaluation of the American Academy of Dermatology's National Skin Cancer Early Detection and Screening Program.

BACKGROUND: Increasing incidence and mortality rates from cutaneous melanoma are a major public health concern. As part of a national effort to enhance early detection of melanoma/skin cancer, the American Academy of Dermatology (AAD) has sponsored an annual education and early detection program that couples provision of skin cancer information to the general public with almost 750,000 free skin cancer examinations (1985-1994). OBJECTIVE: To begin to evaluate the impact of this effort, we determined the final pathology diagnosis of persons attending the 1992-1994 programs who had a suspected melanoma at the time of examination. METHODS: We directly contacted all such persons by telephone or mail and received pathology reports from those who had a subsequent biopsy. RESULTS: We contacted 96% of the 4458 persons with such lesions among the 282,555 screenings in the 1992-1994 programs. We obtained a final diagnosis for 72%, and the positive predictive value for melanoma was 17%. Three hundred seventy-one melanomas were found in 364 persons. More than 98% had localized disease. More than 90% of the confirmed melanomas with known histology were in situ or "thin" lesions (< or = 1.50 mm thick). The median thickness of all melanomas was 0.30 mm. The 8.3% of AAD cases with advanced melanoma (metastatic disease, regional disease, or lesions > or = 1.51 mm) is a lower proportion than that reported by the 1990 Surveillance, Epidemiology and End Result Registry. The rate of thickest lesions (> or = 4 mm) and late-stage melanomas among all participants was 2.83 per 100,000 population. Of persons with a confirmed melanoma, 39% indicated (before their examination) that without the free program, they would not have considered having a physician examine their skin. CONCLUSION: The 1992-1994 free AAD programs disseminated broad skin cancer educational messages, enabled thousands to obtain a free expert skin cancer examination, and found mostly thin, localized stage 1 melanomas (usually associated with a high projected 5-year survival rate). Because biases impose possible limitations, future studies with long-term follow-up and formal control groups should determine the impact of early detection programs on melanoma mortality.

Adult↗
PubMed1996

Glucoprivation counteracts effects of testosterone on daily torpor in Siberian hamsters.

We tested whether 1) glucose availability is a signal for initiation of torpor in male hamsters and 2) glucoprivation can override the inhibitory effects of androgens on daily torpor. Male hamsters maintained at ambient temperatures of 8-16 degrees C were injected with 2-deoxy-D-glucose (2DG), a glucose analogue that interferes with cellular glucose oxidation. 2DG (2,000-2,500 mg/kg body mass) induced torpor within 1 h of treatment in normal adult males in reproductive condition and in those bearing testosterone (T)-filled capsules that produced supraphysiological blood T concentrations; body temperatures were reduced from 37 to 25 degrees C for several hours. Latency to torpor was increased and duration of torpor was decreased in the T-treated hamsters. Food intake decreased substantially both on the day of torpor and on the succeeding day. Glucoprivation appears to counteract the potent inhibitory effect of androgens on torpor and induces a hypometabolic state that results in overall energy savings.

Animals↗
PubMed1996

Gonadectomy in the spring reinstates hibernation in male golden-mantled ground squirrels.

We tested the hypothesis that continued secretion of gonadal steroids is necessary to suppress hibernation in male golden-mantled ground squirrels in the weeks after the terminal arousal in spring. Juvenile and adult males were gonadectomized or sham gonadectomized 1 wk after the terminal arousal; 64% of castrated and none of the shamcastrated animals resumed hibernation. Latency to resumption of torpor was 9 +/- 2 days from the time of castration, and squirrels underwent 4.3 +/- 0.9 bouts before permanently regaining euthermia. Among squirrels that resumed hibernation, bout duration was significantly shorter and torpor was shallower after castration. Castration as late as 3 wk after the terminal arousal reinstated hibernation. We suggest that the terminal arousal of male squirrels in the spring is provoked by a steroid-independent mechanism similar to that operating earlier in the hibernation season; abandonment of hibernation is contingent on concomitant sustained increases in androgen secretion during the first few weeks of euthermia.

Aging↗
PubMed1996

Cutaneous melanoma mortality among the socioeconomically disadvantaged in Massachusetts.

OBJECTIVES: To identify groups for melanoma prevention and early detection programs, this study explored the hypothesis that survival with cutaneous melanoma is disproportionately lower for persons of lower socioeconomic status. METHODS: Massachusetts Cancer Registry and Registry of Vital Records and Statistics data (1982 through 1987) on 3288 incident cases and 1023 deaths from cutaneous melanoma were analyzed. Mortality/incidence ratios were calculated and compared, predictors of late stage disease were examined with logistic regression analysis, and a proportional hazards regression analysis that used death registration as the outcome measure for incident cases was performed. RESULTS: Lower socioeconomic status was associated with a higher mortality/incidence ratio after adjustment for age and sex. For education, the mortality/incidence ratio was 0.37 in the lower group vs 0.25 in the higher group (rate ratio = 1.48, 95% confidence interval [CI] = 1.08, 2.03). Late stage disease was independently associated with lower income (rate ratio for lowest vs highest tertile = 1.64, 95% CI = 1.20, 2.25), and melanoma mortality among case patients was associated with lower education (rate ratio = 1.52, 95% CI = 1.09, 213). CONCLUSIONS: Melanoma patients of lower socioeconomic status may be more likely to die from their melanoma than patients of higher socioeconomic status. Low- SES communities may be appropriate intervention targets.

Adult↗
PubMed1996

Characterization of hepatic nitric oxide synthase: identification as the cytokine-inducible form primarily regulated by oxidants.

Induction of hepatic nitric oxide synthase (NOS) by tumor necrosis factor-alpha (TNF alpha), interleukin-1 beta (IL-1 beta), interferon-gamma (IFN gamma), interleukin-6 (IL-6), and lipopolysaccharide was assessed as activity and immunoreactive protein. Hepatic NOS activity was cytosolic and had cofactor requirements consistent with inducible nitric oxide synthase (NOS2). NOS induction by TNF alpha was dose dependent from concentrations of 0.06 to 60 nM and was increased 2-3-fold by IFN gamma. NOS induction was reflective of total TNF alpha binding to hepatocyte receptors. Hepatocyte TNF alpha binding fit a biphasic curve with high affinity (K(d) = 1.4 nM, Bmax = 3157 sites) and low affinity (K(d) = 157 nM, Bmax = 204,948 sites) elements. NOS2 activity was induced by lipopolysaccharide, IL-1 beta, TNF alpha, and IFN gamma but not by IL-6. All cytokine stimuli were inhibited by antioxidants. Oxygen radical generation was directly measured as dichlorofluoroscein fluorescence in isolated mitochondria. Mitochondria from TNF alpha-treated hepatocytes generated more oxygen radicals than did controls. Antioxidants reduced mitochondrial generation of oxygen radicals. Activation of the transcription factor nuclear factor-kappa B by TNF alpha, IFN gamma, and IL-1 beta was assessed by gel shift analysis. Cytokine treatment increased nuclear factor-kappa B binding, and the addition of antioxidants or rotenone inhibited cytokine activation. Taken together, these data suggest that oxygen radicals, possibly generated by mitochondria, play a major role in NOS2 induction by cytokines.

Animals↗
PubMed1995

Clinical effect of converting antidepressant therapy from fluoxetine to sertraline.

The effect of replacing fluoxetine with sertraline at two dosage-conversion ratios was studied. Outpatients at a Veterans Affairs mental health clinic who were being treated with fluoxetine were randomly assigned to receive either 50 or 75 mg of sertraline hydrochloride for every 20 mg of fluoxetine (as the hydrochloride salt) or to continue to receive their current dosage of fluoxetine. The subjects were given the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory (BDI) at baseline and were re-examined at one-month intervals for three months with the HDRS and BDI and the Clinical Global Impression of Change. Each patient was re-evaluated by the same blinded investigator. A total of 45 patients (42 men and 3 women) completed the study. The final overall response did not differ significantly among the three groups. There were also no significant differences among the groups in the proportions of patients with HDRS and BDI scores classified as improving, worsening, or not changing. Improvement was more common in patients receiving the higher dosage of sertraline. Few adverse effects were reported. Outpatients receiving fluoxetine were switched to sertraline therapy without a loss of control of depression and without substantial adverse effects.

1-Naphthylamine↗
PubMed1995

The early detection of and screening for melanoma. International status.

Cutaneous melanoma is an increasingly common public health problem in industrialized nations. In theory, education and early detection should decrease melanoma morbidity and mortality, because the lesion is external and visible, risk factors are known, and thin tumors are associated with a high 5-year survival rate. The efficacy of early detection and screening programs, however, remains untested by randomized trials. Some early data are available from melanoma prevention and control efforts that have begun in many nations over the past decade. Textbook definitions of cancer screening are particularly challenging when applied to skin cancer control. Although some propose that there are rigid differences among screening, education, and early detection of skin cancer, the visible nature of this cancer makes early detection through education and screening inextricably intertwined. This article discusses the intermediate measures of education and screening within the context of the American Academy of Dermatology programs. Over the next few decades, screening and education for melanoma and other skin cancer will receive increasing worldwide attention. Multiple strategies will be required to combat increasing incidence and mortality rates. Screening and educational programs have been implemented worldwide, but data on their effects are only just being collected. Future collaborative work in melanoma/skin cancer prevention, education, and early detection holds promise as a way to decrease mortality and save lives.

Australia↗
PubMed1995

Edrophonium requirements for reversal of deep neuromuscular block following infusion of mivacurium.

Mivacurium is a new non-depolarizing muscle relaxant consisting of three stereoisomers. The two active isomers (cis-trans and trans-trans) undergo rapid metabolism by plasma cholinesterase (t1/2 beta < 2 min). Due to its rapid elimination, the need for reversal of mivacurium-induced neuromuscular block is controversial, and to date there have been no studies evaluating reversal of deep blocks. The object of the current investigation was to establish the lowest effective dose of edrophonium required to reverse deep mivacurium-induced neuromuscular block. One hundred ASA Class I and II patients undergoing outpatient surgery in two teaching institutions were studied in this randomized, placebo-controlled double-blind trial. Under balanced propofol/nitrous oxide/alfentanil anaesthesia, a continuous infusion of mivacurium was adjusted to maintain between 5-10% of control T1 amplitude. Upon completion of surgery, neuromuscular block was reversed by injecting normal saline (Group PLAC), edrophonium 0.125 mg.kg-1 (Group EDR-1), 0.25 mg.kg-1 (Group EDR-2), or 0.50 mg.kg-1 (Group EDR-3), in addition to a corresponding dose of atropine. Spontaneous recovery, from a T1 response of < 10% to a TOF ratio > or = 0.7, required 13.5 +/- 2.6 min (PLAC Group). In comparison, patients in the EDR-1 group required 9.2 +/- 2.6 min (P < 0.01). Higher doses of edrophonium conferred no advantage. Four patients (4%) had not achieved a TOF ratio of > or = 70%, 20 min after reversal, and required additional edrophonium. Two patients (PLAC group), had dibucaine numbers and cholinesterase levels consistent with an EUEA genotype, whereas the two patients with delayed recovery in the EDR-1 group had characteristics of a normal genotype. We conclude that a very low dose of edrophonium (0.125 mg.kg-1) hastens reversal of deep mivacurium-induced neuromuscular block by approximately four minutes, and that edrophonium doses exceeding 0.125 mg.kg-1 provide no additional benefit. Heterozygous patients with atypical plasma cholinesterase levels, as well as certain individuals with normal dibucaine numbers and plasma cholinesterase activity, are at risk for prolonged neuromuscular block, but the block is easily reversed with edrophonium.

Adjuvants, Anesthesia↗
PubMed1995

Periodontitis in the baboon: a potential model for human disease.

Advances in periodontics with respect to disease activity, microbiology and immunology have demonstrated the multifactorial nature of periodontal diseases. This serves to underscore the need for an ideal animal model for periodontal research. Non-human primates are most similar to man in comparison to other animal models. The baboon is an Old World monkey that has infrequently been used in periodontal research. Periodontal exams were accomplished on 116 baboons (Papio anubis, P. cynocephalus) ages 5 to 30 years with one baboon year being roughly equivalent to 3 to 4 human years. The study population consisted of 29 males and 87 females. Clinical parameters including probing depth, attachment level, mobility, plaque index and gingival index were collected. Radiographs were taken on 25 animals and correlated to clinical findings. Results showed a significant increase in mean probing depth and mean attachment level with age (p = 0.0001). Disease prevalence and severity were not significantly different between genders. Mobility was uncommon; however, the prevalence and severity of furcation involvement increased with age. Radiographs suggested horizontal and isolated vertical bone loss. Plaque and gingival indices were at sustained high levels for all age groups and showed a statistically significant increase with age. Some baboons were found to develop a naturally-occurring periodontitis that increased in severity with age. This primate may be a suitable model for studies in human periodontal disease.

Age Factors↗
PubMed1994

Treatment of overt isolated testicular relapse in children on therapy for acute lymphoblastic leukemia. A report from the Childrens Cancer Group.

BACKGROUND: Fifty-seven children with acute lymphoblastic leukemia (ALL) receiving therapy who experienced overt isolated testicular relapse while in bone marrow remission were entered into a study that featured an intensive retreatment regimen. METHODS: The objective was to determine whether a change in chemotherapy and local irradiation would prevent subsequent marrow relapse and increase the survival rate. The regimens used (modified Berlin-Frankfurt-Munster or modified New York) delivered acceptable therapy based on analyses of toxicity data. RESULTS: Overall survival at 5 years from the time of testicular relapse was 47%, with an event-free survival of 43%. Events have been documented in 28 of 55 evaluable children. Analysis of these patients revealed that 23 children had bone marrow relapse, 4 children had central nervous system relapse, and 1 child had testicular relapse. In addition, two patients were removed from the study for toxicity, one child for infection (mucormycosis), and five children had a bone marrow transplantation while in remission and became ineligible to continue in the study. Two children were removed at the request of their parents, and nine children were lost to follow-up. CONCLUSION: Because of their high risk of developing systemic relapse, boys with ALL who experience isolated overt testicular relapse during active therapy should be retreated with intensive treatment.

Adolescent↗
PubMed1994

Intravenous infusion anaesthesia and delivery devices.

During the past decade, major advances have taken place with regard to intravenous infusion anaesthesia. New opioid analgesics, iv anaesthetics, and muscle relaxants have become available, which are characterized by a rapid onset of action, short duration of clinical effect, and favourable side effect profiles. Optimal administration of these drugs is often best achieved by continuous infusion, rather than a more traditional technique of intermittent bolus administration. New concepts in pharmacokinetic modelling also provide an enhanced appreciation of the factors which determine rates of recovery upon discontinuation of an intravenous infusion. Pharmacokinetic principles guide rational selection of the iv anaesthetic drugs according to both procedure and patient-specific requirements. In addition, improvements in the new programmable syringe infusion pumps provide a degree of simplicity and accuracy in operation, which make iv infusion of one, two or three components of the anaesthetic state a simple and practical reality for most procedures. In this CME article, these issues will be reviewed according to the following outline: Historical considerations; Rationale for continuous infusion of iv anaesthetic drugs; Pharmacokinetic and pharmacodynamic considerations; Infusion schemes; New techniques, new indications; IV anaesthetic delivery systems; Pharmacoeconomic considerations; Conclusions.

Anesthesia, Intravenous↗
PubMed1994

Optimizing sedation following major vascular surgery: a double-blind study of midazolam administered by continuous infusion.

A randomized, double-blind study was undertaken to determine the dose requirements, recovery characteristics, and pharmacokinetic variables of midazolam given by continuous infusion for sedation in patients following abdominal aortic surgery. Thirty subjects, 50-75 yr, scheduled to undergo aortic reconstructive surgery, entered the study. Following a nitrous oxide-isoflurane-opioid anaesthetic technique, patients were randomly allocated to receive one of three loading doses (0.03, 0.06 or 0.1 mg.kg-1) and initial infusion rates (0.5, 1.0 or 1.5 micrograms.kg-1.min-1) of midazolam, corresponding to groups low (L), moderate (M) and high (H). The infusion of midazolam was adjusted to maintain sedation levels of "3, 4 or 5," which permitted eye opening in response to either verbal command or a light shoulder tap, using a seven-point scale ranging from "0" (awake, agitated) to "6" (asleep, non-responsive). Additionally morphine was given in increments of 2.0 mg iv prn for analgesia. On the morning after surgery, midazolam was discontinued, and the tracheas were extubated when patients were awake. Blood samples were taken during, and at increasing intervals for 48 hr following discontinuation of the infusion, and analyzed by gas chromatography. The desired level of sedation was maintained during more than 94% of the infusion period in all three groups, with a maximum of three dose adjustments per patient, for treatment which lasted 16.3 +/- 0.6 hr. There was, however, an increase in both the infusion rates and mean plasma concentrations from Group L to Group H (P < 0.05), which corresponded to an inverse relationship of morphine requirements during the period of sedation (P < 0.05, Group H vs Group L). Optimal midazolam infusion rates and resulting plasma concentrations at the times the infusions were discontinued (in parentheses) were as follows-Group L: 0.60 +/- 0.18 microgram.kg-1.min-1 (76 +/- 32 ng.mL-1), Group M: 0.90 +/- 0.52 microgram.kg-1.min-1 (133 +/- 71 ng.mL-1), and Group H: 1.34 +/- 0.69 microgram.kg-1.min-1 (206 +/- 106 ng.mL-1). Times to awakening were longer in Group H: 3.1 +/- 3.4 hr, than in Group L: 1.1 +/- 0.8 h, P < 0.05. Pharmacokinetic variables were found to be dose-independent over the range of infusion rates. Mean values were t1/2 beta = 4.4 +/- 1.5 hr, CL = 5.94 +/- 1.69 mL.min-1.kg-1, Vd = 3.13 +/- 1.07 L.kg-1.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1994

Impaired neurite outgrowth of src-minus cerebellar neurons on the cell adhesion molecule L1.

The nonreceptor tyrosine protein kinases pp60c-src, p59fyn, and pp62c-yes are localized in growth cones of developing neurons, but their function is undefined. To determine whether these tyrosine kinases were capable of regulating substrate-dependent axon growth, cultures of cerebellar neurons from wild-type, src-, fyn-, and yes- mice were analyzed for neurite outgrowth on the neural cell adhesion molecule L1 or the extracellular matrix protein laminin. The rate of neurite extension on L1 was reduced in src-, but not in fyn- or yes- neurons. Neurite extension on laminin was unaltered in src-, fyn-, or yes- neurons, indicating that pp60c-src, p59fyn, or pp62c-yes is not likely to participate in integrin-dependent axon growth. These results demonstrate that pp60c-src is a component of the intracellular signaling pathway in L1-mediated axonal growth and suggest that Src-related nonreceptor tyrosine kinases may have distinct, nonredundant functions in the nervous system.

Animals↗