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Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 73 records · Page 4Linked to original sources

Effects of 3,4-methylenedioxymethamphetamine in decomposing tissues on the development of Parasarcophaga ruficornis (Diptera:Sarcophagidae) and detection of the drug in postmortem blood, liver tissue, larvae, and puparia.

Larvae of Parasarcophaga ruficornis (Fabricius) (Diptera: Sarcophagidae) were reared on tissues from rabbits administered different dosages of 3,4-methylenedioxymethamphetamine to study the effects of this drug on the development of this insect species. The rabbits were given 11, 22.5, and 67 mg of the drug via ear vein infusion. These dosages correspond to a 0.5, 1.0, and 2.0 median lethal dose. Larvae from colonies fed on tissues from the rabbit receiving 67 mg and the control developed more rapidly from hours 24 through 114. The period required for completion of larval development was significantly shorter for the larvae from the colony fed on liver tissues from the rabbit receiving the 67 mg dosage. This colony also had the lowest total mortality rate during development. No significant differences were observed among the colonies in the duration of the puparial period. Analyses by liquid chromatography/mass spectrometry of the larvae and empty puparial cases following base extraction detected the drug in quantities directly related to the dosage of the drug administered to the rabbits serving as a food source. These results have implications for the determination of time since death when gauged by the development of this insect species.

Animals↗

A case of chrysiasis.

Chrysiasis and chrysoderma are terms used to describe permanent pigmentation of the skin due to the parenteral administration of gold salts. A case of chrysiasis, including a photomicrograph of the characteristic orange-red birefringence of gold in tissue when viewed under cross-polarized light, is presented. A review of the literature on the pathogenesis of the pigmentation seen in this disorder is also presented.

Aged↗

The forensic application of testing hair for drugs of abuse.

Hair testing is only used by the Federal Bureau of Investigation (FBI) when other information exists that indicates drug use and can remove a person from suspicion or associate them with criminal activity. The detection of cocaine in hair has been the FBI's first priority in hair testing for drugs of abuse because of its prevalence. Several cases when hair testing was used are reported in this chapter. Further, analysis of over 100 samples was performed on hair obtained from a medical examiner's random autopsy collection. Sixty-five percent of the samples tested positive for cocaine or opiates. The results of hair testing for drugs of abuse were found to be consistent with autopsy toxicology reports. The analysis of hair washes and nails from the autopsy samples suggests external contamination of hair with drugs is not widespread.

Forensic Medicine↗

Colcemid alters S phase and other parameters in skin during chronic exposure to benzo(a)pyrene.

The administration of Colcemid for collecting mitotic figures in a carcinogenesis study, using benzo(a)pyrene (BaP), diminished the experimental differences between exposed and control mice. A dose-related increase in noncollected mitotic index (n-mitotic index) was seen in keratinocytes in the dorsal epidermis of mice which received four weekly treatments of BaP at 16, 32 and 64 micrograms in 50 microliters of acetone. In contrast, the number of mitotic figures collected for 4 hr by Colcemid block (c-mitotic index) was depressed at 16 micrograms, unchanged at 32 micrograms, and elevated at 64 micrograms of BaP. Weekly treatments with 4,8 or 16 micrograms BaP for 3-8 months induced an elevation in both n-mitotic and c-mitotic indices. The differences in results produced by the two methods of determining mitotic index depended upon dose and duration of treatment with BaP. The administration of Colcemid to acetone-treated mice increased the labeling index (number of labeled cells) and reduced the rate of DNA synthesis (low grain count per keratinocyte nucleus). After chronic application of BaP, Colcemid abrogated the increase in labeling index, but produced no additional effect on the number of grains per labeled keratinocyte. The modifying effect of Colcemid was greatest when administered during the peak of the tissue response to BaP. A number of significant changes in morphology of the skin associated with chronic exposure to BaP were attenuated by the use of Colcemid.

Animals↗

Epidermal cytokinetics, DNA adducts, and dermal inflammation in the mouse skin in response to repeated benzo[a]pyrene exposures.

Few studies have investigated the chronic cytokinetic effects of carcinogen exposure in the mouse skin. We report two experiments involving the repeated application of benzo[a]pyrene (BaP) to the dorsal skin of female Ha/ICR mice. In the first experiment, the cytokinetic, inflammatory, and DNA adduct responses were studied daily over a 9-day period encompassing the fourth and fifth weekly applications of BaP at doses of 16, 32, and 64 micrograms. The second experiment involved the same cytokinetic measurements at 1, 3, 5, and 8 months, and the weekly BaP doses were 4, 8, and 16 micrograms. The first study showed that after each application of 32 or 64 micrograms BaP, there was a wave of slow DNA synthesis in the epidermis which peaked at 24 hr, in coincidence with a wave of BaP-DNA adducts, followed by the appearance of dead and damaged keratinocytes. For the first few days after BaP application there was a depression in the mitotic rate which recovered several days before the next BaP application. There was a predominantly monocytic dermal inflammation throughout the observation period. In the second experiment, at the lower BaP doses, there was proliferative depression at 1 month, without dermal inflammation. With continued exposure, the proliferative depression changed to a dose-dependent increase in the rate of proliferation and dermal inflammation. The level of BaP-DNA adducts was followed in the 4 micrograms/week dose group, which showed a threefold increase after 4 months with the appearance of inflammation and heightened cell proliferation. These results suggest that the delayed inflammatory reaction, possibly based on a cell-mediated immune reaction to BaP, might have been responsible for the late cytokinetic responses and the associated increase in the level of BaP-DNA adducts.

Animals↗

Differential effects of nonhydroxylated flavonoids as inducers of cytochrome P450 1A and 2B isozymes in rat liver.

Flavanone, flavone, and tangeretin differentially affected the activities of cytochrome P540 1A and 2B isozymes in rat liver. Flavone and, to a lesser extent, tangeretin, increased activities of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and pentoxyresorufin O-dealkylase (PROD), whereas flavanone mainly enhanced PROD activity. Immunoblot analysis indicated that flavone and tangeretin increased cytochrome P450 1A1, 1A2, and 2B1,2 forms, whereas flavanone only enhanced the cytochrome P450 2B isozymes. Northern blot study showed that flavone and tangeretin increased the level of the cytochrome P450 1A2 mRNAs. The concentration of the other mRNAs were slightly or not affected by flavonoids. These results suggest that the induction of P450 1A2 by flavone and tangeretin might involve a transcriptional and/or post-transcriptional mechanism.

Animals↗

Cell proliferation and nuclear abnormalities are increased and apoptosis is decreased in the epidermis of the p53 null mouse after topical application of benzo[a]pyrene.

Cell proliferation and cell death in mouse epidermis are altered by topical application of benzo[a]pyrene (BaP), a procarcinogen, which yields metabolites that can form DNA adducts. The mitotic rate, nuclear abnormalities, labelling index, grain density, necrosis and apoptosis were compared in the epidermis of TSG-p53 null (p53-/-) and C57BL wild-type (wt) mice after weekly treatments with BaP to determine whether the absence of the p53 gene altered cytokinetic responses to DNA damaging agents in vivo. Acetone alone or 64 micrograms BaP in 50 microliters acetone was applied to the clipped dorsum of mice once, or in four consecutive weekly treatments. Indices of cell proliferation and cell death were the same in both wt and p53-/- mice treated only with acetone. One application of BaP depressed mitosis and slowed the rate of DNA synthesis in both genotypes. After four applications of BaP the number of keratinocytes in S phase increased substantially, while there was no further slowing in the rate of S phase in the wt and p53-/- mice. Cell proliferation rates and numbers of cells with nuclear abnormalities were higher and there were fewer apoptotic cells and apoptotic bodies in the p53-/- mice than in the wt mice. Numbers of 'sunburn' cells were similar in both types.

Acetone↗

The clinical usefulness of the preoperative bleeding time.

OBJECTIVES: To determine the clinical utilization of the Simplate bleeding time test as a preoperative screen, to examine the clinical utilization of the bleeding time test by multiple surgical services, and to correlate the indicators of bleeding risk (bleeding history, thrombocytopenia, prolonged prothrombin time/activated partial thromboplastin time, increased creatinine, and medications known to interfere with platelet function) with the bleeding time and the occurrence of clinically significant perioperative bleeding. DESIGN: Retrospective data analysis. SETTING: A large tertiary-care hospital. PATIENTS: One hundred sixty-seven consecutive surgical patients tested for preoperative bleeding time. MAIN OUTCOME MEASURES: The occurrence of clinically significant perioperative bleeding and the positive and negative predictive value of the preoperative screening bleeding time test. RESULTS: Patients with a positive bleeding history were more likely to have an abnormal bleeding time (P = .04), but there was no statistically significant association between patients with an abnormal bleeding time and the other indicators of bleeding risk examined or the occurrence of clinically significant perioperative bleeding. The positive predictive value of the preoperative bleeding time was 5%, and the negative predictive value was 95%. CONCLUSIONS: Screening for preoperative bleeding time is not a reliable test for assessing the risk of clinically significant perioperative bleeding and should not be used for this purpose.

Bleeding Time↗

An atypical piloleiomyoma presenting as a nonhealing ulcerated nodule.

Piloleiomyomas are benign smooth muscle tumors arising from the arrectores pilorum muscles in the skin. They vary in size and number, and are often spontaneously painful or sensitive to touch and cold. An unusual case of an ulcerated and painless piloleiomyoma is presented.

Diagnosis, Differential↗

Microvillar cells of the olfactory epithelium: morphology and regeneration following exposure to toxic compounds.

In recent years microvillar cells (MVC) have been identified in the olfactory epithelium of numerous species, including rodents, canines, and primates. However, there is no consensus on the morphologic or histochemical features of this cell, nor is the function of these cells currently known. Previous studies have examined MVC during development and in the mature olfactory epithelium, but not after toxic insult. A microvillar cell, defined by specific morphologic criteria, was studied in adult male Long-Evans rats exposed via inhalation to either 200 ppm methyl bromide for 4 h/day, 4 days/week for 2 weeks, or to 635 micrograms/m3 nickel for 6 h/day for 16 consecutive days, and sacrificed serially over several months. The pattern of recovery for MVC differed according to the severity and specificity of the insult to the olfactory epithelium. With methyl bromide, all cell types were completely depleted from olfactory epithelium immediately after injury, including MVC. MVC were slow to repopulate the epithelium, and appeared only when olfactory epithelium was complete in other respects. With nickel exposure, where the major effect was a gradual decrease in sustentacular cells with a thinning of the apical cytoplasm thickness, MVC showed a decline during exposure, but reappeared during recovery. In both cases, there was no difference in olfactory function, even when MVC were absent from the olfactory epithelium. A mature olfactory epithelium appears to be necessary to support the presence of this MVC, suggesting that it is not crucial to the regeneration processes or recovery of olfactory function, but perhaps plays some role, as yet undefined, in the unperturbed olfactory epithelium.

Animals↗

Hairy elbows.

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Child↗

Behavioral, histological, and neurochemical effects of nickel (II) on the rat olfactory system.

Experimentally, inorganic, sulfated nickel compounds (Ni2+) have been shown to produce histological lesions in the nasal mucosa of rats, more specifically, atrophy of the olfactory epithelium. The present project was designed to assess the effects of inhalation of nickel sulfate hexahydrate on behavioral, histological, and neurochemical aspects of the olfactory system. Male Long-Evans rats were exposed to either background air (control) or 635 micrograms Ni/m3 for 16 consecutive days, 6 hr/day. Exposure resulted in selective lesions to the olfactory epithelium. The number of bipolar sensory receptor cells was slightly reduced and there was a significant decrease in the thickness of the olfactory epithelium. This was due primarily to a significant loss of the sustentacular cell population, with a thinning of the apical cytoplasm, concomitant with a reduction in the number of microvilli at the surface of these cells. Significant decreases in carnosine level, consistent with the nickel sulfate exposure, were observed. However, there were no changes in olfactory function as measured by either absolute threshold or two-oder discrimination tasks.

Administration, Inhalation↗

Fever of unknown origin.

The causes of fever in a child can vary from minor brief illnesses to life-threatening infectious, malignant, or autoimmune diseases. The physician often has to evaluate children with fevers of as yet undiagnosed cause lasting fewer than 2 weeks, in whom it is important to determine whether localizing findings are present. Fever without localizing signs and fevers complicating chronic disease and resulting from specific localized infection are considered in the sections concerning infectious causes, immunodeficiency diseases, and rheumatic diseases. The diagnostic and therapeutic approaches to the child with both prolonged fever and fever of unknown origin are then discussed, with emphasis on rheumatic diseases.

Child↗

Scleroderma in children.

Childhood scleroderma may present in a variety of clinical forms that differ in clinical presentation, extracutaneous features, clinical course, and outcome. All include hardening of the skin as a major feature. This article reviews these various entities, focusing on primarily the clinical features. In addition, current concepts regarding pathogenesis and treatment are discussed.

Adolescent↗