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Biomedical subjects

Michael J Murphy

Publications and source records attributed to Michael J Murphy.

At least 19 recordsLinked to original sources

Seasonal pasture myopathy in horses in the midwestern United States: 14 cases (1998-2005).

OBJECTIVE: To determine clinical signs, diagnostic findings, tissue tremetone concentrations, and clinical outcome or postmortem findings in horses evaluated for acute severe nonexertional rhabdomyolysis initially attributed to white snakeroot toxicosis. DESIGN: Retrospective case series. ANIMALS: 14 horses. PROCEDURES: Records of the University of Minnesota Veterinary Medical Center or Diagnostic Laboratory were searched from 1998 to 2005. Inclusion criteria included serum creatine kinase (CK) activity > 45,000 U/L, severe nonexertional myonecrosis of proximal postural muscles at necropsy, or signs of weakness without palpably firm muscles on physical examination. Vitamin E and selenium concentrations were measured in 6 horses; tremetone concentration was measured in 7. RESULTS: Clinical signs occurred during unfavorable weather conditions. Clinical signs of generalized weakness (n = 11 horses), muscle fasciculations (10), lethargy (6), and prolonged recumbency (4) were common. Serum CK activity ranged from 46,487 to 959,499 U/L (reference range, 82 to 449 U/L), and aspartate transaminase activity was > 1,500 U/L (reference range, 162 to 316 U/L). Two horses survived with aggressive antioxidant and fluid treatment. Postmortem examination revealed acute severe myonecrosis with lipid accumulation primarily in neck, proximal forelimb and hind limb, intercostal, and diaphragm muscles. Histopathologic signs of myocardial necrosis were detected in 7 horses. Vitamin E and selenium concentrations were within reference limits. Tremetone was not detected in liver or urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Cases of rhabdomyolysis have been attributed to white snakeroot toxicosis; however, tremetone was not detected in any horses. Similarities exist between cases of seasonal pasture myopathy and cases of atypical myopathy in Europe.

Adenosine Triphosphatases↗

Cutaneous metastasis of renal cell carcinoma with Zellballen-like inflammatory reaction pattern on immunohistochemical studies.

Skin tumors show variable infiltration by subtypes of inflammatory cells. The composition of these cellular infiltrates, particularly tumor-associated macrophages and dendritic cell numbers, may be responsible for skin tumor progression or regression. In addition, these cells may give rise to diagnostic dilemmas on immunohistochemical studies. The authors report on the local inflammatory reaction to a metastatic renal cell carcinoma to the skin. Histologic examination and immunohistochemical studies demonstrated zellballen-like changes with S-100-positive spindled cells identified around and within tumor cell nests. The role of tumorassociated macrophages and dendritic cells in the skin is discussed.

Aged↗

Does lean rather than fat mass provide the link between birth weight, BMI, and metabolic risk? EarlyBird 23.

BACKGROUND: High birth weight predicts subsequent obesity, but paradoxically, a reduced risk of subsequent cardiovascular disease compared with low birth weight. This apparent paradox might be explained if high birth weight programmed a greater proportion of subsequent lean mass, which carries less cardiovascular risk than fat tissue. AIM: The aim of this study was to test the hypothesis that the direct correlation between birth weight and subsequent body mass index (BMI) represents an association between birth weight and lean tissue, and to assess the metabolic impact of this relationship. METHODS: A total of 234 healthy prepubertal children (133 boys, 101 girls, mean age 5.9 yr +/- 0.3 standard deviation) were studied. Birth weights were obtained from maternity records. Lean mass was measured by bioelectrical impedance. Anthropometric measures included height, weight (BMI), waist circumference, and subcutaneous fat mass (FM). Insulin resistance was assessed by the homeostasis model method. Metabolic correlates of insulin resistance included total and high-density lipoprotein cholesterol, triglycerides, and sex-hormone-binding globulin. RESULTS: Birth weight correlated significantly with lean mass in boys (r = 0.41, p < 0.001) and girls (r = 0.27, p < 0.01). Adjusting for BMI did not improve the correlation further. After adjustment for FM, lean mass correlated inversely with triglycerides in boys only (r = -0.41, p < 0.01). Birth weight correlated inversely with triglycerides in boys (r = -0.18, p < 0.05); after adjustment for lean mass, this correlation was not significant. INTERPRETATION: In boys, the relationships between birth weight, triglycerides, and lean mass are consistent with the hypothesis. Overall, our findings provide limited evidence in support of the argument that higher birth weight predicts lower metabolic risk because it marks programming of more lean mass.

Adipose Tissue↗

Reflective testing: what do patients think?

INTRODUCTION: Reflective testing refers to the practice of adding on tests by laboratory staff. Little is known about what patients think of this practice. METHODS: We surveyed patients attending a general practice surgery and patients attending hospital outpatient clinics. We sought their views about the practice of adding on tests and about the information they received from requesting clinicians about their investigations. RESULTS: In both groups of patients, large majorities favoured an approach in which relevant additional tests are performed without consulting the requesting clinician or patient first. Most patients also felt that the requesting clinicians had provided a satisfactory explanation about what tests were to be performed and why. CONCLUSION: Most patients are content to let NHS professionals add on relevant tests if this is felt to be in their interest.

Clinical Chemistry Tests↗

Little evidence for early programming of weight and insulin resistance for contemporary children: EarlyBird Diabetes Study report 19.

OBJECTIVE: The aim of this study was to evaluate whether adaptive responses made to the uterine or very early infant environment are affecting the current metabolic health of young children in the United Kingdom. METHODS: Participants were 300 healthy children and their parents from the EarlyBird Diabetes Study cohort. Children were recruited from randomly selected schools at 5 years of age. Retrospective measures were maternal prepregnancy weight (n = 230), maternal fasting glucose levels at 28 weeks of pregnancy (n = 27), birth weight, and infant weight at ages 3 and 6 weeks. Prospective measures were insulin resistance, height, weight, and percentage of body fat (sum of 5 skinfold measurements) at ages 5, 6, 7, and 8 years. RESULTS: Maternal third-trimester fasting glucose levels were associated positively with birth weight but were not associated with either weight or insulin resistance for the same children at 8 years. Birth weight was unrelated to insulin resistance at 8 years. There were no relationships between weight change in the first weeks of life and weight, percentage of fat, or insulin resistance at 8 years. Longer breastfeeding correlated inversely, although weakly, with percentage of body fat for boys only. Current weight was correlated with insulin resistance at 8 years. CONCLUSIONS: For these contemporary children, neither the gestational environment nor early postnatal growth predicted insulin resistance, which was best predicted by current weight. There was no evidence that predictive adaptive responses made by the fetus or infant affected the child's weight or insulin resistance later in childhood.

Adult↗

Spontaneous development of a de novo suprasellar arachnoid cyst. Case report.

Arachnoid cysts are commonly thought to arise from either congenital defects or trauma. In this article the authors report the spontaneous development of a suprasellar third ventricular arachnoid cyst whose origin was not clearly congenital or traumatic. At the age of 4 months, the patient presented with hypertonia, and a magnetic resonance (MR) imaging study showed no abnormalities. At the age of 2 years, the boy presented with headaches and projectile emesis, symptoms that prompted further imaging studies. An MR image of the brain revealed a suprasellar cyst and obstructive hydrocephalus. The cyst was endoscopically fenestrated, which led to long-term symptom resolution.

Arachnoid Cysts↗

Girls at five are intrinsically more insulin resistant than boys: The Programming Hypotheses Revisited--The EarlyBird Study (EarlyBird 6).

OBJECTIVE: Recent studies of type 2 diabetes in young populations consistently show a predominance of affected girls over boys. Girls are more insulin resistant than boys. We aimed in the present report to establish how much of the sex difference in insulin resistance is intrinsic. METHODS: EarlyBird is a community-based, nonintervention cohort study of 307 healthy children from school entry at age 5 years. It asks the question: which children are insulin resistant and why? Anthropometric measures, physical activity, resting energy expenditure, and insulin resistance and its metabolic correlates were measured. RESULTS: At 5 years, insulin resistance was 35% higher in girls than in boys. Girls carried 26% more subcutaneous fat despite similar body weights. However, after correcting for anthropometric variables and physical activity, girls remained 33% more insulin resistant than boys. Triglycerides were significantly higher in girls, and high-density lipoprotein cholesterol and sex hormone-binding globulin were significantly lower. CONCLUSIONS: Sex-linked genes may account for the intrinsic sex difference observed. These genes may have an important impact on the development of insulin resistance and the metabolic syndrome and may help to explain the female preponderance of type 2 diabetes in children. Their identification may also help in understanding the pathogenesis of insulin resistance.

Anthropometry↗

Effect of oral administration of dantrolene sodium on serum creatine kinase activity after exercise in horses with recurrent exertional rhabdomyolysis.

OBJECTIVE: To determine the effect of oral administration of dantrolene sodium on serum creatine kinase (CK) activity after exercise in horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 2 healthy horses and 5 Thoroughbreds with RER. PROCEDURE: 3 horses received 2 doses of dantrolene (4, 6, or 8 mg/kg, p.o., with and without withdrawal of food) 2 days apart; 90 minutes after dosing, plasma dantrolene concentration was measured spectrofluorometrically. On the basis of these results, 5 Thoroughbreds with RER from which food was withheld received dantrolene (4 mg/kg) or an inert treatment (water [20 mL]) orally 90 minutes before treadmill exercise (30 minutes, 5 d/wk) during two 3-week periods. Serum CK activity was determined 4 hours after exercise. Plasma dantrolene concentration was measured before and 90 minutes after dosing on the first and last days of dantrolene treatment and before dosing on the first day of the inert treatment period, RESULTS: 90 minutes after dosing, mean +/- SEM plasma dantrolene concentration was 0.62 +/- 0.13 and 0 microg/mL in the dantrolene and inert treatment groups, respectively. Serum CK activity was lower in dantrolene-treated horses (264 +/- 13 U/L), compared with activity in water-treated horses (1,088 +/- 264 U/L). Two horses displayed marked muscle stiffness on the inert treatment. CONCLUSIONS AND CLINICAL RELEVANCE: In 5 horses with RER from which food had been withheld, 4 mg of dantrolene/kg administered orally provided measurable, though variable, plasma concentrations and significantly decreased serum CK activity after exercise in 4 of those horses.

Administration, Oral↗

The sensitivity and specificity of "caterpillar bodies" in the differential diagnosis of subepidermal blistering disorders.

Caterpillar bodies are eosinophilic, elongated, segmented bodies located within the roofs of blisters and are considered to represent a specific histopathologic feature of porphyric bullous eruptions, including porphyria cutanea tarda and erythropoietic protoporphyria. The possibility that similar or identical bodies may be present in other disorders prompted further study exploring the specificity of caterpillar bodies in the differential diagnosis of subepidermal vesiculobullous disorders. Seventy-six cases exhibiting subepidermal clefting were reviewed by light microscopy. "Classic" caterpillar bodies were present in porphyria cutanea tarda (6 of 14) and 1 case representing either venous stasis-associated bulla or possibly bullosis diabeticorum. Caterpillar body-like clusters were present in porphyria cutanea tarda (5 of 14), erythropoietic protoporphyria (1 of 3), bullous pemphigoid (7 of 24), and junctional or dystrophic epidermolysis bullosa (3 of 5). In some cases, classic caterpillar body and caterpillar body-like clusters coexisted in a blister roof. Caterpillar bodies or caterpillar body-like clusters were not identified in any cases of dermatitis herpetiformis, linear IgA bullous dermatosis, bullous erythema multiforme, epidermolysis bullosa acquisita, or wound-healing reactions. In contrast to caterpillar bodies, caterpillar body-like clusters were negative for PAS or Type IV collagen stains. In conclusion, caterpillar bodies appear to represent a specific feature of porphyria cutanea tarda (specificity, 98%) but were present in less than half of those cases in this study (sensitivity, 43%). Caterpillar body-like clusters are less specific and may be present in porphyria cutanea tarda, erythropoietic protoporphyria, pseudoporphyria, bullous pemphigoid, epidermolysis bullosa, and epidermolysis bullosa acquisita.

Adult↗

Preventable factors in childhood that lead to insulin resistance, diabetes mellitus and the metabolic syndrome: the EarlyBird diabetes study 1.

For a decade or more, poor nutrition during gestation, expressed as low weight at birth, was held to be the factor responsible for insulin resistance later in life. Birth weights, however, are rising and insulin resistant states, such as diabetes mellitus, faster still. Alternative explanations are needed to explain insulin resistance in contemporary industrialised populations. EarlyBird is a non-intervention prospective cohort study that asks the question 'Which children develop insulin resistance, and why?' It is unique in taking serial blood samples from a young age with which to monitor the behaviour of insulin resistance and its metabolic correlates. This, the baseline report of the EarlyBird Study, describes the rationale, design and methodology of the study, and the profile of the population at entry. It situates the anthropometric, physical activity and dietary status of the EarlyBird children and provides a detailed metabolic profile of the British 5 year-old in the year 2000.

Adult↗

Dermal absorption of a liquid diphacinone rodenticide causing coagulaopathy.

Rare cases of coagulaopathies from dermal absorption of hydroxycoumarin derivatives have been reported. We report the first case of dermal absorption of an indandione derivative rodenticide causing severe coagulopathy. An 18-y-o male worker at a pest exterminating company spilled a concentrated liquid preparation of 0.106% diphacinone in his boot. He did not remove the boot or wash the area for 6 to 8 h. Seven days later he presented to the emergency department with flank pain, hematuria and epistaxis. Laboratory values were PT > 40 sec, PTT > 90, Hb 16.2, and platelets 273. Urinalysis reported gross hematuria with RBCs too numerous to count. Prolonged bleeding was noted at i.v. puncture sites. Initial therapy included i.m. injection of vitamin K and nasal packing. The patient's religious beliefs precluded the use of blood products. The patient was admitted for observation until PT was controlled. He was discharged on high dose vitamin K p.o. dose titrated to the international normalized ratio measured every 48 h. After 2 w, a dose of 100 mg vitamin K/d was set and the patient was followed as an outpatient for 3 mo. Vitamin K therapy was tapered and discontinued 60 d post-exposure with no further elevation in PT. Diphacinone was detected in a serum sample drawn 60 d post-exposure using gradient and isocratic HPLC methods with fluorescence and UV detection. Factors increasing the dermal absorption of the diphacinone were: prolonged skin contact in a confined area and exposure to a concentrated solution.

Accidents↗

Rodenticides.

Rodenticides are second only to insecticides in the prevalence of pesticide exposure. Hundreds of rodenticide products currently exist, yet only a handful of them are involved in most toxicoses of companion animals. The most commonly reported toxicoses in the United States are those caused by anticoagulant rodenticides, bromethalin, cholecalciferol, strychnine, and zinc phosphide. The pathophysiologic findings, diagnosis, and treatment of each of these five rodenticides are discussed.

Aniline Compounds↗

Practical evaluation and management of cutaneous lymphoma.

UNLABELLED: Accurate evaluation of patients with suspected or known cutaneous lymphoma requires the integration of many sources and types of information, including clinical evaluation, microscopic analysis of tissue, immunophenotyping, gene rearrangement studies, clinical staging, and longitudinal observation. Diagnoses should be based on knowledge of specific lymphoma types as described in modern classification systems. Management of patients with cutaneous lymphoma requires collaboration among dermatologists, dermatopathologists, hematopathologists, and medical, surgical and radiation oncologists. (J Am Acad Dermatol 2002;46:325-57.) LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should better understand how to evaluate and manage patients for suspected or established lymphoma of the skin. Components include the clinical history and physical examination, optimal biopsy and tissue handling, interpretation of pathology and adjunctive test results, clinicopathologic correlation, and therapy. Participants should also understand the basis for establishing a specific diagnosis of cutaneous lymphoma based on current classification and staging.

Antineoplastic Agents↗

Histochemical demonstration of the heterogeneity of the epithelium of proximal tubules in the chick mesonephros.

Proximal tubules (PT) in 7-10-day old chick mesonephros were examined histochemically to evaluate their structural and functional properties related to the absorption capacity of the epithelium and its possible alterations leading to cystically dilated tubules (CDT). Alkaline phosphatase activity at the apical cell membrane was demonstrated in varying intensities in large PT. A similar heterogeneity was also detected in the expression of proteoglycans (Lewis(x) antigen) localized in the apical part of the epithelial cell membrane but not in the basolateral membrane parts (beta-catenin, Na(+),K(+)-ATPase). In analogy, the ability to accumulate trypan blue was found in the same cell population. We hypothesize that epithelial cells in proximal tubules of nephrons with a defective apical cell membrane cause reduced fluid absorption and subsequent overfilling and dilation of the tubules.

Alkaline Phosphatase↗