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Biomedical subjects

J M Howell

Publications and source records attributed to J M Howell.

At least 19 recordsLinked to original sources

The effect of copper and heliotrope on the composition of bile in sheep.

The effects of interrupting the enterohepatic circulation (EHC) of bile salts for seven hours and of feeding copper and heliotrope alone and combined for 13 weeks, on bile flow and excretion of copper, zinc, iron and alpha-mannosidase were studied in sheep. Interruption of EHC reduced bile flow rate and increased the concentration of copper, zinc, iron and bile acids while alpha-mannosidase's activity remained stable. Changes in concentration were related to changes in bile volume for copper and zinc only. Total output per hour was not changed. Biliary concentration of copper correlated with alpha-mannosidase's activity in control sheep and those given copper or heliotrope, supporting the hypothesis that lysosomes are involved in biliary secretion of copper in sheep. Increasing the intake of copper increased the rate of excretion of copper in bile. Copper output was lower when heliotrope was fed alone.

Animals

Steroids for the treatment of corrosive esophageal injury: a statistical analysis of past studies.

Caustic esophageal injury causes substantial morbidity and mortality. However, the use of corticosteroids to treat this problem has been evaluated in a limited number of studies because adequate sample size is difficult to obtain. We analyzed 361 subjects with corrosive esophageal injury derived from 10 retrospective and three prospective publications. We divided cases into those treated with corticosteroids and antibiotics (T) and those that received neither modality (NT) based on inclusion and exclusion criteria. Forty-one percent of NT cases developed esophageal stricture and 19% of T cases developed this complication (P less than .01). There were no reported strictures among 72 first-degree esophageal burns (combined T and NT cases). The T group contained 54 strictures among 228 patients (24%) with either second- or third-degree burns. The NT group of 25 patients with the same burn severity suffered 13 strictures (52%) (P less than .01). Reports of death and gastrointestinal hemorrhage did not increase among steroid-treated patients. We do not recommend corticosteroid therapy for first-degree esophageal injuries. However, this therapy may be useful in preventing strictures among patients with second- or third-degree corrosive esophageal burns.

Adult

Outpatient wound preparation and care: a national survey.

STUDY OBJECTIVE: To sample the practice styles of emergency physicians caring for acute traumatic wounds. DESIGN: Written survey. SETTING: US emergency departments obtained from the American College of Emergency Physicians mailing list. SUBJECTS: Randomly selected ACEP members. MAIN RESULTS: One hundred fifty-one of 285 (53%) survey mailings were returned. Eighty-six percent of respondents were primarily clinicians, and the majority (61.6%) worked in EDs with annual patient visits between 21,000 and 50,000. The majority of respondents (64.2%) were certified by the American Board of Emergency Medicine. Nineteen percent managed wounds based on provider preference despite the existence of written wound management protocols. We identified a variety of practices that are contrary to current literature and textbook recommendations. Fifty-eight (38%) soaked wounds, whereas 21% used either 10% povidone iodine or hydrogen peroxide to cleanse wounds. One hundred one (67%) scrubbed the entire wound surface using, among other methods, cotton gauze (59%) or a coarse, bristle-laden sponge (38%). Forty (27%) irrigated wounds using techniques that have not been proven to deliver the 5 to 8 psi necessary for adequate tissue cleansing. Delayed primary closure, a treatment option for lacerations at increased risk for infection, was infrequently or never practiced by 76% of respondents. All respondents administered IV antimicrobials at least occasionally for simple outpatient lacerations. CONCLUSION: Methods of preparing, treating, and following outpatient wounds vary among emergency physicians, and these results support the idea that no de facto standard of care exists for this clinical problem. Outpatient wound care techniques routinely practiced (ie, soaking, scrubbing, use of full-strength hydrogen peroxide or full-strength povidone iodine) may be harmful based on limited animal and human research, whereas other proven techniques (ie, delayed primary closure) are infrequently practiced by many emergency physicians.

Ambulatory Care

Mesothelioma in horses.

Pleural mesothelioma and pericardial mesothelioma with spread to the pleural cavity were diagnosed in 2 horses. Clinical signs included respiratory distress, depression and pleural pain. The affected body cavities contained copious, serous effusions containing very large neoplastic mesothelial cells with densely-staining cytoplasm, hyperchromic nuclei and prominent, often multiple, nucleoli. Ultrastructurally, the neoplastic cells appeared as solid aggregates, with profuse microvillous borders and neolumen formation. Cytological examination, together with confirmative ancillary diagnostic tests, including electron microscopy and immunocytochemistry, may be used to obtain an ante-mortem diagnosis of mesothelioma.

Animals

Current and future trends in wound healing.

New adjuncts to outpatient wound care focus on diminishing infection rates and improving the speed and effectiveness of laceration repair. This article provides an overview of growth factors, proteolytic enzymes, topical antimicrobial agents, and new materials that facilitate wound closure. Also, the pathophysiology of surface wound repair is summarized.

Animals

Alkalinity of non-industrial cleaning products and the likelihood of producing significant esophageal burns.

Alkaline cleaning products are a cause of serious esophageal injury. Over time, legislation has diminished the concentration of many such non-industrial solutions and solids; however several products presently do not list either the pH or relative concentrations of alkaline constituents. This study measures the pHs of several non-industrial cleaning products containing either ammonium chloride, sodium hydroxide, or potassium hydroxide. Three pH measurements were performed on each of 10 non-industrial alkaline cleaning products (eight liquid, two solid). Two 0.1% ammonium chloride solutions had pHs of 12.06 +/- 0.00 and 12.06 +/- 0.01, whereas a pH of 12.43 +/- 0.00 was recorded in a 0.2% ammonium chloride solution. Concentrations of sodium hydroxide and potassium hydroxide were listed on only one of five liquid cleaning product labels. The pHs for these five products varied between 12.83 +/- 0.009 and 13.5 +/- .0.2. The pHs of three sodium hydroxide solutions differed from values reported in Micromedex (Micromedex Inc, Denver CO) by up to 0.32 pH units. Ten percent (v/v) solutions of two solid lye products had pHs of 13.62 +/- 0.008 and 13.74 +/- 0.02. The investigator found that selected non-industrial cleaning products, including ammonia solutions, retain the ability to cause clinically important esophageal damage.

Ammonium Chloride

Natural bone marrow transplantation in cattle with Pompe's disease.

Adding acid alpha-glucosidase to cultures of Pompe's disease muscle has resulted in enzyme uptake and reduction in concentration of glycogen. However, bone marrow transplantation has been unsuccessful as a treatment. Immune rejection may have contributed to this failure. Twin calves share a placenta and carry lymphoreticular cells of each other's type, they become lymphoreticular chimeras in utero and immune rejection does not occur. One natural and three sets of twins produced by embryo transfer were studied in Pompe's disease cattle. Chimerism persisted throughout life and the situation was analogous to a transplant of histocompatible bone marrow stem cells. The activity of acid alpha-glucosidase in leucocytes and in biopsies of the semitendinosus muscle and the mean activity in diaphragm, spleen and lymph node obtained after death from affected twins were significantly higher than in single affected calves. Glycogen concentration was lowered in liver, spleen and lymph node but not in muscles. The affected twins showed clinical signs and changes in muscle similar to those seen in affected single calves. It is concluded that bone marrow transplantation is unlikely to be a successful treatment for Pompe's disease.

Animals

Experimental copper and heliotrope intoxication in sheep: morphological changes.

Young Merino wethers were used to determine the effects of copper and heliotrope, fed together or separately, on the development of toxicity and the concentration of trace elements in the liver and kidney. In one experiment copper and heliotrope were given concurrently, in a second experiment heliotrope was fed for 12 weeks and copper administration commenced 8 weeks later. The 10 sheep fed heliotrope alone did not show signs of clinical illness but one died and was found to have severe liver damage. Eleven sheep were given copper alone and three developed the clinical signs and lesions of haemolysis. Fourteen sheep were given copper and heliotrope and 13 became ill. Of these, three developed haemolysis, eight became jaundiced and two became weak without developing jaundice. The concentrations of copper in the livers of control and heliotrope-treated sheep, were comparable. In the animals given copper alone, the concentration of copper in the liver was twice as high as that in controls and in those given heliotrope and copper, it was three times as high as in the liver of control sheep. Feeding heliotrope alone induced the histological changes of pyrrolizidine alkaloid toxicity in the liver, but this was not associated with an excessive accumulation of copper or the development of clinical illness. However, it did predispose the animals to the effects of a second toxin since giving heliotrope and copper concurrently, or giving copper subsequent to feeding heliotrope, markedly enhanced the toxicity of the two substances and caused an excessive accumulation of copper in the liver.

Animals

Precipitous hypotension in the emergency department caused by Capnocytophaga canimorsus sp nov sepsis.

A 20-year-old man presented to the emergency department (ED) with an injured right hand, fever, and a history of dog exposure. This splenectomized individual developed hypotension less than 90 minutes after arriving in the ED with normal vital signs. He later developed overwhelming sepsis, gangrene, disseminated intravascular coagulation (DIC), respiratory insufficiency, retroperitoneal hematoma, and renal insufficiency. Blood cultures grew Capnocytophaga canimorsus sp nov (formerly Dysgonic Fermenter-2). Sepsis, gangrene, and DIC are more likely to occur in asplenic individuals exposed to this organism. Many physicians use prophylactic outpatient penicillin therapy in asplenic or functionally asplenic victims of dog and cat bites. However, a brief admission or stay in an observation unit may be indicated for these high-risk individuals.

Adult

Effect of intravenously administered tetrathiomolybdate on plasma copper concentrations of copper-loaded sheep.

Chronic copper toxicity was induced in 14 ewes in two groups by oral dosing with CuSO4. Copper dosing was stopped in sheep of groups 1 and 2 at the first rise of serum acid phosphatase activity and on the first day of haemolysis, respectively. Thiomolybdate was administered intravenously (i.v.) to sheep of group 2 at the rate of 100 mg on the first day of haemolysis and at 24-h intervals, with a maximum of 3 doses during haemolysis. Thiomolybdate was also given intravenously at a dose of 50 mg twice weekly for 11 weeks to four sheep of group 1 after the cessation of copper dosing (group 1B) and to five sheep of group 2 at the end of haemolysis. Plasma copper concentration was determined before and 24 h after each injection of 50 mg thiomolybdate and "elevations" of plasma copper concentration were seen after each injection of thiomolybdate. The differences between plasma copper concentrations observed before and after each thiomolybdate injection for doses 1 to 11 were significantly higher than those seen for doses 12 to 22. Following thiomolybdate administration, the copper content of the liver of sheep in groups 1B and 2 was reduced much more than in sheep of group 1A, in which copper dosing also ceased but which did not receive thiomolybdate. It was concluded that the high plasma copper response to thiomolybdate doses 1 to 11 was due to an influx of copper into the bloodstream from the heavily copper-loaded liver cells. The lower plasma copper response during the latter part of thiomolybdate administration was due to a gradual reduction in the amount of copper entering the bloodstream from the liver cells, as these cells became depleted of copper. Some of this copper may become part of the glomerular filtrate and be taken up by the cells of the proximal convoluted tubules of the kidney or may be excreted in the urine.

Animals

Aerobic bacteria cultured from the mouth of the American opossum (Didelphis virginiana) with reference to bacteria associated with bite infections.

The American opossum inflicts bite injuries both when hunted for food and when accidentally provoked when handled in captivity. This study involved aerobically culturing organisms from the mouths of seven wild opossums (Didelphis virginiana). Isolates included streptococci, coagulase-positive and -negative staphylococci, Aeromonas spp., Citrobacter freundii, Eikenella corrodens, and Escherichia coli.

Animals

The impact of dedicated physician staffing on patient flow and quality assurance parameters in an Air Force emergency department.

A retrospective audit of 17,028 emergency charts at USAF Medical Center, Scott was performed over two time periods to compare patient waiting times and selected quality assurance parameters with two methods of physician staffing. Phase 1 consisted of 4 months when the Emergency Department (ED) was manned with five physicians assigned only to that department. Non-departmental physicians supplemented the full-time staff. Phase 2 was the corresponding 4 months the following year when the ED was staffed with six emergency physicians, and non-emergency physician coverage was minimal. The difference in daily census between the two periods of time was not statistically significant. The time required to be seen by a physician decreased from an average of 25.6 minutes per patient in phase 1 to 13.7 minutes per patient in phase 2. Time to disposition also decreased from 71.9 minutes per patient in phase 1 to 59.5 minutes per patient in phase 2. In the second phase the number of "positive" x-ray findings increased, while the number of incomplete charts and patients who left without being seen by a physician diminished.

Consumer Behavior

Lysosomes in the pathogenesis of liver injury in chronic copper poisoned sheep: an ultrastructural and morphometric study.

Chronic copper poisoning was induced in sheep by oral dosing with CuSO4. The distribution of copper between hepatocytes was unequal and, with increasing liver copper concentration, isolated hepatocytes packed with electron-dense lysosomes were seen. These cells underwent degeneration and necrosis. During the pre-haemolytic period, the concentration of Cu in the liver increased and the volume density, numerical density and mean volume of hepatocyte lysosomes increased in a linear fashion, indicating that there was proliferation as well as increase in the size of lysosomes. However, in animals killed during haemolysis, the numerical density had decreased but the volume density was little changed which indicates that lysosomal production may have diminished. It is postulated that the necrosis of hepatocytes packed with electron-dense lysosomes may be due to the accumulation of toxic amounts of copper in the cytosol, resulting from a reduced uptake of copper into the lysosomal system of these cells, and that the susceptibility of liver cells to Cu-induced damage may be increased if lysosome production is diminished.

Animals

Intracellular distribution of copper in the liver of copper-loaded sheep--a subcellular fractionation study.

Eighteen ewes in two groups were dosed orally with CuSO4 to induce chronic Cu toxicity. Copper dosing was stopped at the first rise of acid AP activity in the serum in group 1 sheep and on the first day of haemolysis in group 2 sheep. Liver samples were obtained 1 week prior to the start of Cu dosing, at the first rise of acid phosphatase (AP) activity in serum and on the first day of haemolysis. These liver samples were homogenized and were separated into nuclear (N), heavy mitochondrial (MH), light mitochondrial (ML), microsomal (MI) and cytosolic (CY) fractions by centrifugation. The Cu concentration and specific activities of AP were determined in the liver, LH and subcellular fractions. The composition of the fractions was studied by light and electron microscopy. In the predosing biopsies, the concentration and percentage of Cu and the total specific activity of AP were highest in the ML fractions. With increasing Cu loading, the concentration of Cu in all fractions increased; the percentage of Cu increased in the N and MH fractions, decreased in the ML and MI fractions and was maintained at a constant level in the CY fractions. The total specific activities of AP in LH, N, MH, MI and CY fractions were increased and the activity was highest in the MH fraction. The results indicate that the increase in the concentration of Cu in liver cells was predominantly in lysosomes and cytosol. Furthermore, it is suggested that the necrosis of isolated hepatocytes observed in chronic Cu-poisoned sheep may be due to a saturation of the uptake of Cu into the lysosomal system of the cell, leading to the accumulation of toxic levels of Cu in the cytosol.

Acid Phosphatase

Intravenously administered tetra-thiomolybdate and the removal of copper from the liver of copper-loaded sheep.

Eighteen ewes divided into two groups were dosed orally with CuSO4 in order to induce chronic Cu toxicity. Copper dosing was stopped at the first rise of serum acid phosphatase activity in sheep of group 1 and on the first day of haemolysis in sheep of group 2. Tetra-thiomolybdate was administered intravenously to five group 1 sheep (group 1B) and to group 2 from the cessation of Cu dosing. Following thiomolybdate administration, in groups 1B and 2, there was a reduction in the concentration of Cu in the liver and liver fractions, the number and size of electron-dense lysosomes in particulate liver fractions, the volume density and the mean volume of electron-dense lysosomes in hepatocytes and the number of necrotic cells in the liver. Thiomolybdate appeared to remove Cu from the lysosomes and the cytosol of Cu-loaded liver cells. However, neither the total specific activity of acid phosphatase in liver homogenate and liver fractions nor the numerical density of electron-dense lysosomes in hepatocytes decreased significantly. This may be due to the production of new lysosomes in the liver cells. Furthermore, following thiomolybdate administration, Mo concentration in the liver and liver fractions increased indicating that Mo of thiomolybdate was entering liver cells. The percentage distribution of Cu and Mo in the liver fractions was similar. This may suggest that Mo is bound to Cu and that they remain together with each fraction. The decrease in Cu concentration may indicate that the liver retains its ability to excrete copper via bile.

Acid Phosphatase