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Biomedical subjects

M R Moore

Publications and source records attributed to M R Moore.

At least 145 records · Page 8Linked to original sources
PubMed1987

Effects of lead in the laboratory mouse. Development and social behaviour after lifelong exposure to 12 microM lead in drinking fluid.

The effects of chronic exposure to 12 microM lead, from conception onwards, on development and social behaviour were investigated in the laboratory mouse. Lead was administered as 0.25% solution of lead acetate in the drinking fluid. This level of exposure did not affect reproductive success, but caused decreased birthweight and retarded early development in offspring of treated dams. Mortality prior to weaning was significantly greater in pups treated with lead, and animals treated with lead had significantly reduced body weights throughout their lives. Levels of lead in tissues were greatly increased in all treated animals, with females showing significantly higher levels than males. Behaviour was assessed by ethological methods in paired encounters between unfamiliar animals in a novel environment. At age 3-4 weeks Exploratory Behaviour and Social Investigation were significantly increased and Immobility was significantly decreased in animals of both sexes treated with lead. Social Investigation was also increased at age 7-8 weeks but Exploratory Behaviour was decreased. At age 15-16 weeks Non-Social Activity was increased in males and decreased in females, although Social and Sexual Investigation was not affected in these male-female encounters. Lead-treated males, aged 17-18 weeks, showed significantly shorter latencies to aggression towards unfamiliar males than did controls.

Administration, Oral↗
PubMed1987

Wide tourniquets eliminate blood flow at low inflation pressures.

Previous recommendations for use of pneumatic tourniquets in extremity surgery suggest parameters for maximum pressure and time limits without regard for optimum cuff width. Wide cuffs produce lower readings of blood pressure relative to narrow cuffs, presumably because the wide cuffs arrest flow at lower inflation pressure. We investigated three tourniquet sizes and the inflation pressure required to eliminate flow to the upper extremity using an ultrasonic Doppler device to monitor blood flow in the radial artery of ten normal subjects (arm circumference 24.5 to 37 cm). Arterial flow was always eliminated at the lowest pressure using the widest tourniquet cuff. Significantly lower inflation pressures will eliminate blood flow if wider tourniquet cuffs are used; therefore, use of a wider tourniquet cuff may result in a reduced incidence of tourniquet complications.

Adult↗
PubMed1987

Compartment syndrome of the thigh complicating surgical treatment of ipsilateral femur and ankle fractures.

A 26-year-old man presented with ipsilateral femur and ankle fractures. The patient was treated with interlocking nail of his femur fracture, followed by open reduction and internal fixation of his ankle fracture under tourniquet control. Postoperatively, the patient developed compartment syndrome of his thigh with elevated pressures, requiring decompressive fasciotomies. This case illustrates the possible complication of treating a femur fracture with intramedullary nailing and then immediately applying a tourniquet to treat an ipsilateral extremity fracture. Because of the complication with this patient, we feel the procedure should be staged, or a tourniquet should be avoided if possible.

Adult↗
PubMed1987

Antipyrine metabolism in acute hepatic porphyria in relapse and remission.

Antipyrine kinetics following a single oral dose were obtained in porphyric patients in attack and in remission and in controls. The clearance of antipyrine was significantly lower during an acute porphyric attack (median: 0.34 ml min-1 kg-1; range: 0.1-0.71, P less than 0.05) than in patients in remission (median: 0.53 ml min-1 kg-1; range: 0.28-0.87) or controls (median: 0.52 ml min-1 kg-1; range: 0.32-0.93). There was a significant negative correlation between weight-adjusted antipyrine clearance and the urinary excretion of the porphyrin precursors, delta-aminolaevulinic acid (r = 0.86, P less than 0.001) and porphobilinogen (r = 0.82, P less than 0.002). These data suggest that the more severe the porphyric attack, the greater the impairment of hepatic monooxygenase activity.

5-Aminolevulinate Synthetase↗
PubMed1987

Effect of rifampicin on haem and bilirubin metabolism in man.

Haem and bilirubin metabolism was studied in seven healthy volunteers during 4 weeks treatment with rifampicin 600 mg at night. The serum unconjugated bilirubin concentration increased 2-3 fold in the first 24 h of treatment (P less than 0.01) and subsequently fell to below pretreatment values (P less than 0.05) during the third and fourth weeks of rifampicin therapy. In each subject, the activity in leucocytes of delta-aminolaevulinic acid (ALA) synthase increased and that of protoporphyrinogen (proto) oxidase decreased during the first week of therapy. The mean ALA synthase activity was most markedly increased on day 4 being seven-fold its pretreatment value (P less than 0.01), and the mean proto oxidase activity most depressed on day 2 at 50% its pretreatment value (P less than 0.02). There was increased urinary excretion of porphobilinogen (PBG) during the first week of therapy and increased excretion of porphyrins and PBG during the third week of treatment. The increase in ALA synthase activity and haem precursor excretion can be explained by the combination of increased haem demand for haemoprotein induction and partial block in haem synthesis due to reduced proto oxidase activity.

Adult↗
PubMed1987

Studies in laboratory animals to assess the safety of anti-inflammatory agents in acute porphyria.

The safety of various anti-inflammatory drugs in acute porphyria was assessed by examining their effect on rat hepatic haem synthesis. Azapropazone, chloroquine, and gold increased delta-aminolaevulinic acid (ALA) synthase activity, indicating that they are liable to precipitate porphyric crises. Aspirin, ibuprofen, indomethacin, ketoprofen, flurbiprofen, phenylbutazone, naproxen, prednisolone, and penicillamine did not increase ALA synthase activity and should be safe in porphyria. Though these animal studies can be used as a guide to prescribing in patients with acute porphyria, some caution is still required as species may vary in their response to inducing agents.

5-Aminolevulinate Synthetase↗
PubMed1987

Porphyrin metabolism and haem biosynthesis in Gilbert's syndrome.

Studies in 14 patients with unconjugated hyperbilirubinaemia caused by Gilbert's syndrome have revealed abnormalities of the enzymes of haem biosynthesis measured in peripheral blood cells. The activity of the penultimate enzyme of haem biosynthesis protoporphyrinogen (PROTO) oxidase was reduced at 3.1 +/- 2.6 nmol PROTO/g protein/h (mean +/- ISD) compared with 8.2 +/- 5.1 in controls (p less than 0.005). This was associated with a compensatory increase in the activity of the initial and rate controlling enzyme of the pathway delta-aminolaevulinic acid (ALA) synthase at 866 +/- 636 nmol ALA/g/protein/h compared with 156 +/- 63 in controls (p less than 0.001). Unlike variegate porphyria in which there is a genetic deficiency of PROTO oxidase there was no increased excretion of porphyrins or their precursors in Gilbert's syndrome. Accentuation and subsequent correction of the unconjugated hyperbilirubinaemia with rifampicin produced reciprocal changes in PROTO oxidase activity indicating that bilirubin may be inhibiting the activity of this enzyme.

5-Aminolevulinate Synthetase↗
PubMed1987

Pathogenesis of acute porphyria.

The pathogenesis of the clinical manifestations of acute porphyria has been considered in the light of their pathological changes and their aberrations of the haem biosynthetic pathway. These manifestations may be explained almost entirely upon a neurogenic basis. A number of hypotheses have been considered to explain the clinical, pathological and biochemical features. Of these hypotheses two seem more impressive: (i) the neurological manifestations may be explained by a deficiency of haem in neural tissues; (ii) the porphyrin precursor 5-aminolaevulinic acid (ALA) may have in addition specific pharmacological activity.

Acute Disease↗
PubMed1987

The Harderian gland, its secretory duct and porphyrin content in the woodmouse (Apodemus sylvaticus).

The Harderian gland of the woodmouse (Apodemus sylvaticus) consists of tubules lined by a single layer of epithelial cells with a surrounding layer of myoepithelial cells. The epithelium contains two cell types, one with numerous small, clear, lipid vacuoles (Type I), the other with large electron-dense ones (Type II). Each type is further subdivided into cells where the smooth endoplasmic reticulum exhibits pronounced vacuolation (Ia and IIa). The lipid vacuoles frequently coalesce and are released by exocytosis. They possess a multilamellar cap; similar multilamellar whorls (without a vacuole) are also seen. Polytubular complexes are a feature of Type II cells; tubules are in continuity with the smooth endoplasmic reticulum. Peroxisomes are also present. Fenestrated capillaries occur frequently in the interstitium, and (where no myoepithelial cell intervenes) the basal surface of the gland epithelial cell is covered with microvilli. There is no morphologically distinct duct system within the gland. The extraglandular duct is lined by columnar epithelium except at the opening on to the nictitating membrane where there is stratified squamous epithelium, with melanocytes and nests of mucus-secreting cells. The porphyrin content of the gland is low and solid intraluminal deposits are not seen.

Animals↗
PubMed1986

Porphobilinogen deaminase and the synthesis of porphyrin isomers in the Dubin-Johnson syndrome.

Porphyrin synthesis was studied in a family of 9.3 of whom had the Dubin-Johnson syndrome (DJS). Subjects with DJS had modest increases in urinary porphyrin concentration with a marked increase in the series I isomer of coproporphyrin (tetracarboxylic) as well as in the octa-, hepta-, hexa- and penta-carboxyl porphyrins. Activity of erythrocyte porphobilinogen deaminase (PBG-D) was also increased. Non-expressing carriers in the family had normal levels of urinary porphyrins but modest increases in both series I isomer accumulation and PBG-D activity. These results may provide a rationale for the altered synthesis of porphyrin in DJS.

Adolescent↗
PubMed1986

Chester porphyria: a clinical study of a new form of acute porphyria.

Acute porphyria afflicts a large kindred in Chester that stems from a marriage in 1896 that has produced 200 descendants; this is the largest porphyric kindred to be identified in the United Kingdom. Six members aged 51 or under died from the condition over the past eight years. The diagnosis of porphyria was overlooked in some as the symptoms may mimic those of other acute illnesses, so that incomplete or incorrect death certificates have been issued. Psychosis, hypertension, and renal complications are particularly common. The porphyric members of the kindred show a previously undescribed hereditary disorder in which the characteristic enzymatic defects of acute intermittent porphyria and variegate porphyria coexist in the same subject. Acute porphyria is poorly understood by hospital and general practitioners, and this has caused anxiety in the kindred. A register of the kindred has been established, and families at risk should be offered biochemical screening, education, and genetic counselling.

Acute Disease↗
PubMed1986

The effects of ethanol and lead, alone and in combination, on the severity of arrhythmias induced by coronary artery occlusion, and by noradrenaline, in anaesthetised rats.

The aim of this study was to investigate whether chronic (3 or 10 months) administration, via the drinking water, of lead (25 ppm) and/or ethanol (25% v/v) altered the susceptibility of the heart to arrhythmias induced either by coronary artery occlusion or noradrenaline infusion in pentobarbitone-anaesthetised male Sprague-Dawley rats. The cardiac effects of acute intravenous infusions of ethanol (17, 33 and 66 mg kg-1 min-1) were also measured. Chronic exposure to ethanol and/or lead in the drinking water had no marked effect on the severity of arrhythmias occurring within the initial 30 min of coronary artery occlusion. In control rats and in those administered ethanol and/or lead for 10 months, noradrenaline (16 micrograms kg-1 min-1 given IV 1 h post-occlusion for a 15-min period) induced a similar number of ectopic beats during the infusion period, although these arrhythmias persisted beyond the infusion period in treated animals only. There was a significant accumulation of lead in the bone but not in the blood of lead-treated rats. Blood ethanol concentrations varied considerably between animals, ranging from 0 to 319 mg %. Ethanol (66 mg kg-1 min-1) given acutely and yielding a blood concentration of 174 mg % had a slight antiarrhythmic effect in this model.

Anesthesia↗
PubMed1986

The prevention of porphyrin loss from tissues during routine histological processing: quantitative studies on the Harderian gland.

The rodent Harderian gland is an important site of porphyrin biosynthesis and storage. Porphyrins are visible at the light and electron microscope level as large intraluminal accretions, as large interstitial accretions surrounded by foreign body giant cells, or as small interstitial deposits within free macrophages. Since porphyrins are soluble in a wide range of solvents, it is important to employ histological routines which minimize porphyrin loss during processing in addition to giving good tissue preservation. In this quantitative investigation, these requirements were optimally achieved with fixation in 3% buffered glutaraldehyde and the use of amyl acetate as a clearing agent.

Animals↗
PubMed1986

Effects of lead in the laboratory mouse--2. Development and social behaviour after lifelong administration of a small dose of lead acetate in drinking fluid.

Administration of 0.13% lead acetate solution as drinking fluid to breeding mice was without significant effect on the numbers of live or dead births or on weight of pups at 1 day. The appearance of fur was delayed and the body weights at 21 days and 31-38 weeks were smaller than in controls. On weaning, the treated offspring received 0.13% lead acetate as drinking fluid. Concentrations of lead in bone and brain were markedly raised above control levels at 18 and 34 weeks, being greatest at 34 weeks. There were no significant sex differences. The behaviour of the treated offspring in social encounters was shown by ethological procedures to differ from that of controls. The most consistent change after treatment with lead was enhancement of social and sexual investigation. This was seen in females at 26-27 weeks when encountering male partners, in isolated males at 32-33 weeks encountering male partners and in group-housed males and females in single sex encounters at 17-18 weeks. At 17-18 weeks, the duration of this behaviour was increased in treated females in the first 3 min and in treated males in the final 5 min of the 20 min period of observation. Behavioural changes in juvenile mice at 6--7 weeks occurred only during the final 5 of the 20 min observation. At 3--4 weeks only a marginal difference in behaviour was detectable, this being in the treated females. Overall the behavioural effects of lead differed between males and females and were different in juveniles from those seen in adulthood.

Aging↗
PubMed1986

Effects of 1.2 microM lead in the laboratory mouse: developmental and behavioural consequences of chronic treatment.

Lead acetate, as a 0.025% (1.2 microM) solution in the drinking fluid, did not adversely affect the reproductive success in breeding mice, weights of pups at birth or cause delays in development. At 21 days, the treated offspring showed reduced weights but these returned to normal values in adulthood. Offspring of treated mice were given 1.2 microM lead acetate as drinking fluid after weaning. The mean daily intake of lead amounted to 2.4 and 2.6 mg/100 g body wt in females and males respectively and caused significant increases in the concentrations of lead in bone and brain. Sequestration of bone was greater in females than males. The behaviour of the offspring was examined by ethological analysis of social encounters between pairs of unfamiliar mice of similar treatment groups in a neutral cage. Evidence of enhanced reactivity to the test situation was seen in treated males at age 3-4 weeks by increased social investigation during the first 3 min of the 20 min encounter, at 7-8 weeks by decreased immobility in the final 5 min of the test and at 18-19 weeks by an increased duration of exploratory behaviour. However, when encountering females at 30-31 weeks, the treated males showed more immobility than did the controls. Treated females at 3-4 weeks, in the first 3 min of the test, showed a decreased frequency of exploratory behaviour and increased immobility, but at 7-8 and 18-19 weeks they showed enhancement of social and sexual investigation. Behaviour was unaltered at 30-31 weeks in encounters with unfamiliar males.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗
PubMed1986

Effects of lead in the laboratory mouse. 1. Influence of pregnancy upon absorption, retention, and tissue distribution of radiolabeled lead.

Whole-body retention and excretion following a single oral dose of radiolabeled lead (203Pb) in chronically lead-exposed pregnant BK:W mice were examined over 10-13 days. This was compared with values in similarly treated nonpregnant females and in ip injected females. Whole-body and bone retention were greater in injected than in orally dosed nonpregnant females; gastrointestinal absorption was estimated from this difference. Whole-body retention in the pups was measured at birth and at the end of the experiment. Whole-body retentions in pregnant females and in their pups at birth were significantly raised after treatment at Gestational Day 17, but not after treatment at Gestational Day 11, 14, 20, 23, or 26. Pup body burdens at birth were significantly and positively correlated with maternal retention. Measurement of radioactivity in bone, kidney, brain, heart, and liver of adults at the end of the experiments showed significantly increased levels in bone and kidney from females treated at Gestational Day 17 and in bone from females treated at Gestational Day 11. Lead excretion did not differ significantly among the groups but the total lead content of the femur was significantly raised in females treated at Gestational Days 17 and 26. Thus, these experiments provide evidence that lead absorption and retention in mice are markedly increased in the latter stages of pregnancy.

Animals↗