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Biomedical subjects

J M Howell

Publications and source records attributed to J M Howell.

At least 91 records · Page 5Linked to original sources

Distribution of Cu, Zn, and Fe in the soluble fraction of the kidney in normal, copper-poisoned, and thiomolybdate-treated sheep.

Twenty-seven sheep were used in two experiments to study the distribution of copper (Cu), zinc (Zn), and iron (Fe) in the kidney cytosol of control, Cu-loaded, and thiomolybdate (TM)-treated sheep. A comparison was made of the patterns of distribution on Sephadex G-75 of Cu, Zn, and Fe from the cytosol of fresh and frozen kidneys and after thawing of frozen cytosol. In both Cu-dosed and TM-treated sheep, the absolute level of Cu increased in the cytosol, but the percent of Cu decreased. The percent recovery of Cu from the frozen kidney was comparable to that from fresh kidney, but the extraction of Cu from the supernatant of frozen cytosol was approximately 10% less. This was due to a loss of Cu in a precipitate that formed when the frozen cytosol was thawed. Most of the Cu in the cytosol from the kidney of Cu-loaded sheep was in a metallothionein (MT)-like protein fraction and was trichloroacetic acid (TCA) soluble. In contrast, that from the cytosol of TM-treated sheep was mostly in a high molecular weight fraction that was TCA insoluble. The chromatograms obtained from cytosol derived from frozen kidneys, or cytosol that had itself been frozen, contained a similar distribution of Cu, Zn, and Fe, but the peak heights were lower in the latter samples.

Animals↗

A practical radiographic comparison of short board technique and Kendrick Extrication Device.

Cervical spine immobilization is necessary during the prehospital care of most trauma patients. Earlier studies performed in controlled, indoor settings suggested short board technique (SBT) was the standard against which other methods of cervical stabilization should be measured. Our study approximated the prehospital setting by comparing the use of tape, SBT, and Philadelphia collar (PC) with tape, the Kendrick Extrication Device (KED), and PC after immobilization in and extrication from a compact car. Seven men were immobilized with KED and SBT in addition to PCs and tape. These subjects were extricated and then taken by ambulance stretcher across a 50-yd length of concrete to the radiology suite. Flexion, extension, lateral bending, and rotation were measured. KED-PC (16 degrees +/- 8 degrees) was statistically superior to SBT-PC (41 degrees +/- 5 degrees) in limiting rotation (P less than .001). KED-PC and SBT-PC were similar in their abilities to limit extension (8 degrees +/- 4 degrees vs 6 degrees +/- 5 degrees), flexion (4 degrees +/- 2 degrees vs 4 degrees +/- 4 degrees), and lateral bending (13 degrees +/- 5 degrees vs 17 degrees +/- 6 degrees). In an approximation of the prehospital setting, tape, a PC, and either KED or SBT substantially limit extension, flexion, and lateral bending of the normal cervical spine. KED-PC is more beneficial in rotation.

Adolescent↗

Scalp laceration repair without prior hair removal.

The effect on the infection rate of hair removal prior to scalp laceration repair has not been studied prospectively in the outpatient setting. Concern exists that not removing skin hair may lead to an increased incidence of serious wound infections. Sixty-eight scalp lacerations were repaired without hair removal and examined prospectively for infection. No infections were noted at 5-day follow-up. The mean patient age was 21.8 +/- 19.8 years, and the mean laceration length was 2.5 +/- 2.0 cm. The mean time from injury to repair of laceration was 2.2 +/- 2.8 hours. Sixty-three lacerations (92.7%) were repaired within 3 hours of injury. A prospective, randomized study in a select patient population to examine the effect of prior hair removal on infection rate is warranted.

Adolescent↗

Multiple implantation of normal amnion into cattle with generalized glycogenosis type II.

One normal and two carrier calves, and two calves affected by generalized glycogenosis type II were given multiple transplants of normal bovine amnion inserted below the external oblique abdominal muscle in the flank. The interval between transplants was approximately 5 months. The amniotic tissue was not acutely rejected but a host versus graft reaction did occur. The level of acid alpha-glucosidase activity in the amniotic tissue fell rapidly but was still present 2 months after transplantation. Enzyme levels in blood or other tissues did not rise. Excess glycogen deposition and muscle damage occurred in the affected calves and appeared to progress at a rate similar to that in untreated affected animals. One of the affected animals died aged 16 months, which was the same age as the longest surviving non-treated animal in our herd. The other treated animal died aged 24 months.

Amnion↗

Ischemic injury to the spinal cord as a cause of transient paraplegia.

Spinal cord ischemia presenting as acute paraplegia is an uncommon occurrence not previously reported in the emergency medicine literature. Paraplegia due to spinal ischemia is seen most commonly after intraoperative aortic manipulation; however, acute hypotension and prolonged cardiopulmonary resuscitation are also reported settings. The differential diagnosis of acute, non-traumatic paraplegia includes mechanical spinal cord compression, acute transverse myelitis, and polyneuritis.

Acute Disease↗

Histochemical study of the accumulation of copper in the liver of sheep.

Six Merino sheep were dosed orally with a 0.2 per cent solution of copper sulphate, six others were undosed controls. Liver biopsies were obtained and stained for copper by the p-dimethylaminobenzylidene rhodanine (DMABR), rubeanic acid (RA) and ferricyanide (FCN) methods for examination by light microscopy. The initial and most marked accumulations of copper were found within the hepatocytes of the centrilobular zones. Increased copper loading resulted in copper deposition extending through the midlobular to the periportal zones. The deposition of copper was unequal between hepatocytes and with increasing copper loading isolated hepatocytes became packed with copper containing granules. Copper appeared within Kupffer cells and macrophages of portal triads. The first Kupffer cells to be positively stained and the greatest number of such cells were adjacent to the central veins. Accumulation of copper was demonstrated with hepatocytes at copper concentrations equivalent to 44.3 micrograms copper g-1 liver wet weight. The FCN method provided a more satisfactory demonstration of intracellular copper than the RA technique and the latter was better than the DMABR method. However, the DMABR technique provided the clearest morphological details.

Animals↗

Effects of intravenously administered tetra-thiomolybdate on the distribution of copper in the liver and kidney of copper loaded sheep: a histochemical study.

The effects of intravenously administered thiomolybdate on the liver and kidney of copper loaded sheep were studied using 16 ewes in three groups. Copper, iron and molybdenum concentrations were determined by spectrophotometry and the distribution of copper in the liver and kidney was studied histochemically. Following thiomolybdate administration, the concentration of copper in the liver was reduced, that of molybdenum increased and the concentration of copper and molybdenum in the kidney increased. The reduction of copper concentration in the liver was associated with reductions in the number and size of granules in hepatocytes which stained positively for copper and in the number of Kupffer cells containing positively staining granules. The decrease in the amount of copper in hepatocytes appeared to be greater than that in Kupffer cells. This effect was greatest in the centrilobular zones and least in the periportal zones. The increased concentration of copper and molybdenum in kidney was associated with an increase in the number and size of granules staining positively for copper in the epithelial cells of the proximal convoluted tubules which suggested an uptake of copper-molybdenum complexes by the lysosomes of these cells.

Animals↗

An ultrastructural study of the kidney of normal, copper poisoned and thiomolybdate-treated sheep.

Histological, ultrastructural and kidney function techniques were used to assess changes in the kidney of sheep given either copper (Cu) or Cu and the Cu complexing agent thiomolybdate (TM), or TM alone. Kidney function was normal in sheep given Cu and TM together or TM alone. In these animals the cells lining cortical tubules accumulated Cu within numerous, large, electron-dense lysosomes. Sheep given Cu alone developed haemolysis, impaired kidney function and a variety of morphological defects including an increase in number of large lysosomes in cells of the cortical tubules. There was a breakdown of the glomerular endothelial lining and fusion of foot processes. Cells of the cortical tubules showed degeneration and necrosis and an increase in microbodies and rough endoplasmic reticulum. Cortical and medullary blood vessels were dilated, with evidence of breakdown of the endothelial lining. Copper appeared to injure kidney tissue at three sites, tubular epithelium, glomerular basal lamina and capillary blood vessels. Changes reported here are similar to the renal lesions in cadmium toxicity.

Animals↗

Alkaline ingestions.

Alkaline ingestion is a potentially life-threatening problem that may confront the emergency physician. It is similar to many other toxins in that children and those who attempt suicide are its most common victims; however, implications in terms of initial stabilization and definitive care are quite distinct. Mucosal exposure to lye results in a quick, deep liquefactive necrosis. Consequently, blind nasotracheal intubation may result in the perforation of damaged tissues in the pharynx and trachea. For similar reasons, the blind passage of a nasogastric tube is contraindicated. The use of diluents in this setting is controversial. If a diluent is used, water and milk are considered the liquids of choice. They may be used to irrigate oropharyngeal burns, but are contraindicated in the face of respiratory compromise, shock, liquid lye ingestion, and perforation of the esophagus or stomach. Cathartics and charcoal are not used after alkaline ingestion. Cathartics, however, are used in miniature alkaline battery ingestions to diminish bowel transit time. Esophagoscopy should be done within 12 to 24 hours after ingestion to directly observe the extent of damage. This procedure should be stopped at the first sign of injury to protect against iatrogenic esophageal perforation. Steroids should be started for circumferential esophageal burns and in those patients with significant injury who are unable to undergo esophagoscopy. IV antibiotics are administered for gastrointestinal perforation and may be used concomitantly with steroids. Miniature alkaline batteries lodged in the esophagus must be removed immediately. The available modalities include fluoroscopy-directed Foley catheter removal, endoscopy, and surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Bovine generalised glycogenosis type II. Uptake of lysosomal alpha-glucosidase by cultured skeletal muscle and reversal of glycogen accumulation.

acid alpha-glucosidase (EC 3.2.1.20) was purified from fetal bovine muscle by affinity chromatography on concanavalin A and Sephadex G-100 and added to the culture medium of mature muscle cultures from animals affected by glycogenosis type II. The enzyme activity in homogenates of treated cultures was significantly increased within 4 h of the addition of enzyme, was maximal by 18 h and the internalised activity was stable for at least 48 h after the removal of the enzyme from the culture medium. The acid alpha-glucosidase activity was internalised with an uptake constant of 300 nM and a Vmax of uptake of 133 nmol/h per mg protein. The glycogen concentration in affected cultures treated with exogenous acid alpha-glucosidase for 24 h had decreased by 20% and after a further 24 h of culture was comparable to the concentration observed in cultures from non-affected animals.

Animals↗

The epidemiology of squamous cell carcinoma of the perineal region of sheep: abattoir and flock studies.

The roles of age, tail length and the Mules operation in the epidemiology of squamous cell carcinoma in ewes were studied. The prevalence of the disease in adult sheep slaughtered at 2 abattoirs was 0.08%. No cases occurred in lambs. Of all adult sheep condemnations before slaughter, 38.5% were due to squamous cell carcinoma. Of these sheep, 73.3% had a single lesion of the vulva (62.9%), tail (6.6%), or anus (3.8%), while 26.7% had lesions at more than one site. The number of lesions was significantly greater (p less than 0.01) in sheep with a radical Mules operation than in those with a modified Mules operation or not mulesed. Tails were significantly shorter (p less than 0.01) in affected than unaffected sheep. Small keratinised outgrowths on the skin of the tail and perineum were considered on histological grounds to be precursors of squamous cell carcinomas. On one affected farm 4% of ewes were culled in one year for gross lesions of squamous cell carcinomas. A further 3.5% of sheep with gross lesions and 25.3% with precursor lesions remained in the flock, undetected by the farmer. Gross lesions were not observed in ewes under 3 years of age, whereas precursors occurred in all age groups, including one-year-old ewes. The prevalence of lesions increased with age, from 0.43% in 5-year-old ewes to 5.14% in 6-year-old and 41% in 7-year-old ewes. Discriminant analysis indicated that age of ewe, tail length and the width of the healed Mules operation were important determinants of squamous cell carcinoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Abattoirs↗

X-ray microanalysis of liver and kidney in copper loaded sheep with and without thiomolybdate administration.

The distribution of elements in the cells of the liver and kidney of normal sheep, of sheep chronically intoxicated with copper and in sheep given copper and thiomolybdate was studied by atomic absorption spectrophotometry, electron microscopy and electronprobe X-ray microanalysis. Copper concentrations were increased in the liver and kidney during the pre-haemolytic and haemolytic stages of the disease. In addition iron concentrations were markedly increased in the kidney during haemolysis. Copper and molybdenum concentrations were increased in the kidney of sheep receiving copper and thiomolybdate or thiomolybdate alone. By electronprobe X-ray microanalysis at the pre-haemolytic and haemolytic stages, copper together with small amounts of calcium and chromium were found in lysosomes of liver cells. In addition, in animals killed during haemolysis, high concentrations of iron were found in apical lysosomes of kidney proximal tubule cells. Copper and molybdenum were found in apical lysosomes of kidney tubule cells in animals given copper and thiomolybdate or thiomolybdate alone. The accumulation of copper with molybdenum and sulphur in the lysosomes of thiomolybdate treated copper intoxicated animals was demonstrated for the first time and may indicate the sequestration within lysosomes of a copper-molybdenum-protein complex.

Animals↗

Cardiomyopathy in generalised glycogenosis type II in cattle.

The clinical, electrocardiographic and postmortem findings in five cattle affected by generalised glycogenosis type II are described. Three of the affected animals showed generalised muscle weakness for some months before being killed at 11, 15 and 16 months of age. Of the remaining two, one developed severe respiratory distress when 3 months old and died within 6 h of first being noticed to be ill. The other animal showed respiratory distress on exertion at 5 months of age, became recumbent and died when 7 months old. The sum of the QRS complex amplitudes in ECG leads I, II, a VR, aVL and aVF of the affected animals was significantly increased from the control or carrier animals, but only the two affected animals which showed clinical and pathological signs of congestive heart failure had increased heart weight to body weight, left and right ventricular weight to body weight ratios. In view of the lack of correlation between the increased QRS amplitudes and the presence of cardiac enlargement, it is suggested that the increased QRS amplitudes are a reflection of a conduction disorder. It is further suggested that QRS complex abnormalities in generalised glycogenosis in man, particularly in the late onset form may be due to a similar phenomenon.

Animals↗

Hemimelia and low marking percentage in a flock of Merino ewes and lambs.

Hemimelia at a prevalence of 11% of lambs marked, and low marking percentage (51%) was observed in a flock of mixed age Merino ewes and their lambs. Hemimelia occurred in one or 2 limbs of affected lambs. Lambs from other flocks on the farm were unaffected, and the condition was not reported from other farms. The condition had not occurred in the past, and has not recurred. No infectious or hereditary factors were implicated in the aetiology of the condition. Grazing Western Australian Blue Lupin stubble by the affected flock during and after joining was the only known difference between this flock and others on the farm.

Animals↗

Hepatic damage in sheep fed annual ryegrass, Lolium rigidum, parasitised by Anguina agrostis and Corynebacterium rathayi.

Annual ryegrass (Lolium rigidum) parasitised by Anguina agrostis and Corynebacterium rathayi causes neurological signs and brain lesions thought to be associated with a vasoconstrictor effect of the toxic grass. In three separate experiments of six to 112 days duration parasitised ryegrass was fed to 21 adult sheep. The concentrations of many blood constituents were examined, liver biopsies taken, necropsies performed and tissues other than brain examined by light and electron microscopy. The invariable finding was liver damage indicated by increased plasma concentrations of liver specific enzymes and bilirubin. There was diffuse vacuolation of hepatocytes due to gross distension of cisternae of rough endoplasmic reticulum, as well as necrosis of individual hepatocytes, fatty change, biliary hyperplasia and hepatocytic regeneration. The changes were not typical of experimental hepatic ischaemia and may have been due to a cytopathic effect of toxic annual ryegrass.

Animal Feed↗

Skeletal-muscle alpha-glucosidases in bovine generalized glycogenosis type II.

The skeletal muscle of cattle suffering from generalized glycogenosis type II was shown to lack acid alpha-glucosidase (EC 3.2.1.3) activity. Furthermore, there was no evidence of enzymically inactive proteins that cross-reacted with antibodies raised against acid alpha-glucosidase from the muscle of normal animals.

Animals↗

Infantile and late onset form of generalised glycogenosis type II in cattle.

A herd of cattle which produces calves with generalised glycogenosis type II has been established. Seven affected animals have been born and their disease status as indicated by a decreased acid alpha-glucosidase activity and excessive glycogen deposition in muscle, can be detected on the day of birth. Two animals have died of heart failure aged 3 and 5 months and have shown cardiomegally. Five animals were clinically normal until 9 months of age when they failed to maintain weight gain, showed muscle weakness and four were killed aged between 12 and 16 months after showing difficulty in rising. All affected animals had abnormal ECG tracings and had elevated levels of CK, LDH and HBDH in serum. Excessive amounts of glycogen were deposited in voluntary, cardiac and smooth muscle, and in cells of the nervous system. The muscles showed a vacuolar myopathy. Both the infantile and late onset forms of generalised glycogenosis type II are present in this herd of cattle. The condition appears to be controlled by a recessive allele at a single autosomal locus.

Animals↗

Intravenous administration of thiomolybdate for the prevention and treatment of chronic copper poisoning in sheep.

1. Twenty-six sheep were used in experiments designed to test the effectiveness of ammonium tetrathiomolybdate in the prevention and treatment of chronic copper poisoning. 2. Intravenous injections of 100 mg ammonium tetrathiomolybdate twice weekly (a) prevented the occurrence of haemolytic crisis in sheep repeatedly dosed with copper sulphate and (b) minimized tissue damage and prevented further haemolytic crisis when given to sheep already in haemolysis. 3. Thiomolybdate prevented excessive deposition of Cu in the liver of sheep receiving orally large amounts of Cu and decreased liver Cu levels in sheep that were not given additional Cu. In the latter sheep, 50 mg ammonium tetrathiomolybdate given twice weekly did not produce histologically-detectable tissue damage even though liver and kidneys contained high levels of molybdenum, and kidneys contained elevated levels of Cu. 4. It is concluded that chronic Cu poisoning can be successfully prevented or treated by intravenous injection of appropriate doses of ammonium tetrathiomolybdate.

Animals↗