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Biomedical subjects

A D Muir

Publications and source records attributed to A D Muir.

At least 19 recordsLinked to original sources

Treatment and outcomes of oesophageal perforation in a tertiary referral centre.

OBJECTIVE: The diagnosis and management of oesophageal perforation continues to challenge clinicians. We present our experience of perforated oesophagus in a Tertiary Referral Centre for Thoracic and Oesophageal Surgery. METHODS: Between 1985 and 2000, 75 patients (40 male) with oesophageal perforation were treated in out unit; age range 24-89, median 63. Retrospective review of these cases has been performed. RESULTS: There were 12 deaths (16%). With increases in time from perforation to diagnosis, there was a stepwise increase in the mortality rate. Immediate diagnosis 5%; early diagnosis (1-24h) 14%; late diagnosis (>24h) 44% (P>or=0.002). Site of perforation, aetiology, and treatment strategy had no influence on mortality. The only independent predictor of mortality identified was time to diagnosis from perforation (beta 0.429, P=0.001). Time to definitive management in those undergoing an operative procedure had no influence on outcome with multivariate analysis. CONCLUSIONS: Prompt recognition of the diagnosis of oesophageal perforation and rapid institution of supportive measures, followed by an appropriate, patient specific treatment option optimises the chance of a successful outcome. The wide range of presentation of oesophageal perforation necessitates individualisation of treatment.

Adult↗

Quantitation of the lignan secoisolariciresinol diglucoside in baked goods containing flax seed or flax meal.

Samples of commercially prepared white, whole wheat, flax, and multigrain breads were analyzed by a rapid RP-HPLC method for the presence of the lignan secoisolariciresinol diglucoside (SDG). SDG was detected only in products containing flax, with concentrations ranging from 0.06 to 1.98 microM/g of DW (19-602 microM/loaf). Full-fat flax meal, powdered aqueous alcohol extracts of flax seed, and SDG were added to a white bread mix and baked into loaves in a domestic bread maker. Quantitative recovery of SDG from the test breads was observed when SDG was added; however, when flax meal or aqueous alcohol extracts were added, only 73-75% of the theoretical yield of SDG was recovered. SDG was also detected in commercially prepared flax cookies, bagels, and muffins with concentrations ranging from 0.26 to 2.93 microM/g of DW. The extent of grinding of the flax seed was also shown to have a significant effect on the recovery of SDG from both flax meal breads and baked goods, with extraction of SDG from finely ground samples greater than that from course material.

Bread↗

Protective effect of secoisolariciresinol diglucoside against streptozotocin-induced diabetes and its mechanism.

OBJECTIVES: Reactive oxygen species (ROS) have been implicated in the development of streptozotocin (STZ)-induced diabetes mellitus. Secoisolariciresinol diglucoside (SDG) isolated from flaxseed is an antioxidant. An investigation was made of the effects of SDG on the development of STZ-induced diabetes in rat, to determine if SDG can prevent/reduce the development of diabetes and if this prevention/reduction is associated with reduction in oxidative stress. DESIGN AND METHODS: The rats were divided into 4 groups: Group I, Control; Group II, SDG (22 mg/kg body wt, orally) for 24 days; Group III, STZ (80 mg/kg intraperitoneally); Group IV, SDG in the dose similar to Group II three days prior to STZ and 21 days thereafter. Oxidative stress was assessed by measuring serum and pancreatic lipid peroxidation product malondialdehyde (MDA), pancreatic antioxidant reserve (pancreatic-CL) and oxygen free radical producing activity of white blood cells (WBC-CL). A diagnosis of diabetes was made on the basis of glucosuria and was confirmed at the time of sacrifice (21 days after STZ treatment) by the presence of hyperglycemia. At the end of the protocol blood samples were collected for estimation of glucose, MDA and WBC-CL, and pancreas were removed for estimation of MDA and antioxidant reserve. RESULTS: Incidence of diabetes was 100% in Group III and 25% in Group IV. SDG prevented the development of diabetes by 75%. Development of diabetes was associated with an increase in serum and pancreatic MDA, and in WBC-CL, and a decrease in pancreatic antioxidant reserve. Prevention of diabetes by SDG was associated with a decrease in serum and pancreatic MDA and WBC-CL and an increase in pancreatic antioxidant reserve. CONCLUSIONS: These results suggest that STZ-induced diabetes is mediated through oxidative stress and that SDG is effective in reducing the STZ-induced diabetes mellitus.

Animals↗

A novel treatment for lupus nephritis: lignan precursor derived from flax.

BACKGROUND: Flaxseed has renoprotective effects in animal and human lupus nephritis. We have recently extracted the lignan precursor (secoisolariresinol diglucoside) (SDG) to determine if this more palatable derivative of flaxseed would exert renoprotection similar to the whole flaxseed in the aggressive MRL/lpr lupus mouse model. METHODS: 131 MRL/lpr mice were randomly assigned to saline gavage, 600, 1,200 and 4,800 microg lignan gavage groups. At 7 weeks, 6 animals underwent platelet aggregating factor (PAF) lethal challenge and 40 were studied with urine collection to determine the levels of secoisolariresinol, enterodiol and enterolactone in the gavaged animals. A baseline study of 10 saline gavaged animals took place at 6 weeks. 25 animals in the saline gavage, 600 and 1200 microg lignan groups were studied at 14 and 22 weeks for GFR, spleen lymphocyte S-phase and organ weight studies. RESULTS: Metabolic studies indicated that secoisolariresinol is the major metabolite absorbed and the lowest lignan dose provides a lengthening in survival for the PAF lethal challenge. Body weight, fluid and water intake studies demonstrated that the lignan was well tolerated. Changes in proteinuria, GFR and renal size showed a time- and dose-dependent protection for the lignan precursor. Cervical lymph node size and spleen lymphocyte cells in the S-phase demonstrated modest dose-dependent reductions in the lignan gavaged groups. CONCLUSION: SDG was converted in the gut to secoisolariresinol, which was absorbed and well tolerated by the MRL/lpr mice. Renoprotection was evidenced, in a dose-dependent fashion, by a significant delay in the onset of proteinuria with preservation in GFR and renal size. This study suggests that SDG may have a therapeutic role in lupus nephritis.

4-Butyrolactone↗

Reduction of hypercholesterolemic atherosclerosis by CDC-flaxseed with very low alpha-linolenic acid.

Flaxseed (Type I flaxseed) with 51-55% alpha-linolenic acid in its oil and richest source of plant lignans, has been shown to reduce hypercholesterolemic atherosclerosis by 46% without lowering serum lipids. Antiatherogenic activity was claimed to be due to its alpha-linolenic acid and/or lignan content. If alpha-linolenic acid component of flaxseed is responsible for antiatherogenic activity, then, CDC-flaxseed (Type II flaxseed) which has similar oil and lignan content but has very little (2-3% of the total oil) alpha-linolenic acid would have no antiatherogenic effect. An investigation, therefore, was made of Type II flaxseed on high cholesterol diet-induced atherosclerosis and serum lipids [total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C)] in rabbits. Rabbits were assigned to four groups: Group I, Control; Group II, Type II flaxseed diet (7.5 g/kg orally daily); Group III, 1% cholesterol diet; Group IV, 1% cholesterol diet supplemented with Type II flaxseed (7.5 g/kg orally daily). Blood samples were collected before (0 time) and after 4 and 8 weeks of experimental diets for measurement of serum lipids. Aorta was removed at the end of 8 weeks for assessment of atherosclerotic plaques. Serum TC, LDL-C, TC/HDL-C, and LDL-C/HDL-C were lower in Group IV as compared to Group III by 14 and 31%, 17 and 32%, 28 and 34% and 24 and 32%, respectively, at 4 and 8 weeks. HDL-C was not affected by Type II flaxseed in hypercholesterolemic rabbit. TG and VLDL-C were markedly increased in Group IV as compared to Group III. Type II flaxseed reduced the development of atherosclerosis by 69%. Histological changes in the atherosclerotic regions were qualitatively similar in Groups III and IV. Results indicate that reduction in hypercholesterolemic atherosclerosis by Type II flaxseed is due to a decrease in serum TC and LDL-C. In conclusion, antiatherogenic activity of Type II flaxseed is not due to alpha-linolenic acid.

Animals↗

Characterization of the reflective materials and organelles in the bright irides of North American blackbirds (Icterinae).

The reflective materials in the iris stroma of bright-irised American blackbirds (Icterinae, Emberizidae) and the red-eyed vireo (vireo olivaceus) (Vireonidae) were characterized using high-performance liquid chromatography (HPLC) and diode-array detection. Two purines, guanine and hypoxanthine, and two pteridines, leucopterin and xanthopterin, were detected in large amounts in all bright irides. The brown iris of the red-winged blackbird (Agelaius phoeniceus) by comparison contained only small amounts of these and additional unidentified compounds. The absolute and relative amounts of light-absorbing compounds in the iris varied somewhat among species of blackbirds with bright irides, and markedly within one species (brewer's blackbird, Euphagus cyanocephalus) between sexes and age classes that very in eye color. Differences in the types, numbers, and sizes of pigment organelles in the irides appeared to underlie the differences in amounts of light-absorbing compounds. Guanine was the most abundant light-absorbing compound in all bright irides, accounting for about 90% of the total absorption at 250 nm. A wide range of concentrations of guanine, from 96 to 9 micrograms per iris, produced bright irides. The primary pigment organelles of pigment cells in bright irides were reflecting platelets, which typically appeared as open spaces on electron micrographs. In the red-eyed vireo there were in addition red pterinosome-like pigment organelles in the pigment cells on the anterior surface of the iris stroma. Guanine was present even in irides with no overt reflecting platelets.

Animals↗

Effects of Sainfoin (Onobrychis viciifolia Scop.) Condensed Tannins on Growth and Proteolysis by Four Strains of Ruminal Bacteria.

Sainfoin leaf condensed tannins inhibited growth and protease activity in Butyrivibrio fibrisolvens A38 and Streptococcus bovis 45S1 but had little effect on Prevotella ruminicola B(1)4 or Ruminobacter amylophilus WP225. Tannins bound to cell coat polymers in all strains. Morphological changes in B. fibrisolvens and S. bovis implicated the cell wall as a target of tannin toxicity.

Journal Article↗

Repetitive nocturnal arterial oxygen desaturation and silent myocardial ischemia in patients presenting for vascular surgery.

OBJECTIVE: To determine whether nocturnal respiratory abnormality (cyclic oxygen desaturation and tachycardia) is associated with nocturnal myocardial ischemia in older individuals with ischemic heart disease. DESIGN: Non-invasive monitoring on a single occasion. SETTING: Tertiary care referral hospital. PATIENTS: Thirty four consecutive older (68.5 +/- 6 yrs) patients referred for elective abdominal or carotid reconstructive vascular surgery. RESULTS: Seven patients (21%) had moderately severe nocturnal respiratory abnormality, defined by more than 50 dips in arterial oxygen saturation and increases in heart rate during the night. Two of these seven had clinical risk factors for ischemic heart disease and had nocturnal myocardial ischemia. Ten patients (29%) developed ischemia at some time during the study, of whom seven hand known ischemic heart disease, hypertension, and/or angina. Those with increased nocturnal ischemia showed very low frequency (1-2 cycles per minute) cyclic heart rate oscillations and repetitive nocturnal episodes of arterial oxygen desaturation, similar to patients with sleep apnea. CONCLUSION: Repetitive nocturnal cyclic arterial desaturation and cyclic increases in heart rate are associated with nocturnal myocardial ischemia in individuals with clinical risk factors for ischemic heart disease. Further investigation in a large patient sample utilizing non-invasive monitoring of saturation, heart rate, and blood pressure may provide definitive evidence regarding causation of some of the nocturnal myocardial ischemia occurring in older individuals with vascular disease.

Aged↗

Effects of Condensed Tannins on Endoglucanase Activity and Filter Paper Digestion by Fibrobacter succinogenes S85.

The effect of condensed tannins from birdsfoot trefoil (Lotus corniculatus L.) on the cellulolytic rumen bacterium Fibrobacter succinogenes S85 was examined. Condensed tannins inhibited endoglucanase activity in the extracellular culture fluid, at concentrations as low as 25 mug ml. In contrast, cell-associated endoglucanase activity increased in concentrations of condensed tannins between 100 and 300 mug ml. Inhibition of endoglucanase activity in both the extracellular and the cell-associated fractions was virtually complete at 400 mug of condensed tannins ml. Despite the sharp decline in extracellular endoglucanase activity with increasing concentrations of condensed tannins, filter paper digestion declined only moderately between 0 and 200 mug of condensed tannins ml. However, at 300 mug ml, filter paper digestion was dramatically reduced and at 400 mug ml, almost no filter paper was digested. F. succinogenes S85 was seen to form digestive grooves on the surface of cellulose, and at 200 mug ml, digestive pits were formed which penetrated into the interior of cellulose fibers. Cells grown with condensed tannins (100 to 300 mug ml) possessed large amounts of surface material, and although this material may have been capsular carbohydrate, its osmiophilic nature suggested that it had arisen from the formation of tannin-protein complexes on the cell surface. The presence of electron-dense extracellular material suggested that similar complexes were formed with extracellular protein.

Journal Article↗

Postoperative hypoxaemia after major abdominal vascular surgery.

We have studied the severity and duration of nocturnal hypoxaemia before operation and for the first five nights after operation after elective major abdominal vascular surgery. Oxygen supplementation was almost 100% effective in keeping oxygen saturation greater than 90% during the early postoperative period; however, 50% of patients spent prolonged periods with an SpO2 less than 85% during at least one night after operation. The risk of severe hypoxaemia persists well beyond the current prescription of supplementary oxygen in these high risk patients. A significant association exists between the mean preoperative overnight saturation value and the nocturnal saturation observed subsequently in the later postoperative period.

Adult↗

Late postoperative nocturnal dips in oxygen saturation in patients undergoing major abdominal vascular surgery. Predictive value of pre-operative overnight pulse oximetry.

Twenty-four patients (23 male) who presented for aortic reconstructive surgery were studied with pulse oximetry on a pre-operative night and during the first five postoperative nights. Patients with five or more dips in oxygen saturation of greater than 4% (with a prompt recovery back toward baseline of 3% or more) per hour of monitoring were classified as having a significant abnormality of respiration. Pre-operatively, four of 24 patients (17%) demonstrated such an abnormality. Postoperatively, 12 patients (50%) met these criteria on at least one of the first five postoperative nights and six of these had two or more nights with severe episodic hypoxaemia. Frequent severe episodic dips in arterial oxygen saturation (to less than 85% saturation) occurred in the late postoperative period at a time when oxygen therapy would usually have been discontinued. Pre-operative overnight pulse oximetry studies fail to predict the development of abnormal respiratory patterns in the postoperative period in the majority of patients.

Adult↗

Haemodynamic effects of periodic ventilation: abolition with supplementary oxygen.

A 63-yr-old man was noted to breathe with a periodic pattern of ventilation during sleep, both before and after operation for coronary artery grafting, and 6 weeks later after aortic aneurysm repair. Periodic ventilation was associated with cyclic oxygen desaturations and increases in heart rate and arterial pressure. Administration of oxygen was found to abolish consistently the periodic pattern and the associated haemodynamic changes.

Hemodynamics↗

Preoperative silent myocardial ischaemia: incidence and predictors in a general surgical population.

We have studied before operation 156 patients aged more than 40 yr presenting for elective vascular or non-vascular surgery, using ambulatory ECG monitoring to detect silent myocardial ischaemia (SMI). The prevalence of SMI was 18.2% in the vascular group (n = 102) and 7.6% in the non-vascular group (n = 54). A history of ischaemic heart disease, or an abnormal ECG suggestive of a previous myocardial infarction, predicted a high risk of SMI (28% compared with 9% in the absence of these variables). However, a significant amount of SMI (36% of the total) occurred in patients without one of the defined risk factors. In addition, 24 of the patients with abdominal aortic disease underwent cardiac gated blood pool (MUGA) scans. Abnormal ventricular wall function was observed in 62.5% of the patients. Twenty-nine percent of the patients studied with MUGA scans had SMI and 21% had ejection fractions less than 40%. A significant association (P less than 0.05) existed between the presence of SMI and a ventricular ejection fraction of less than 40%.

Adult↗

Postoperative myocardial ischaemia: temporal association with nocturnal hypoxaemia.

Three patients presenting for elective aortic surgery were studied before operation and for up to 3 days after operation with ambulatory electrocardiographic monitoring and nocturnal pulse oximetry. Supplementary oxygen was administered for the first 2 days after operation and withdrawn on the 3rd morning after operation. Heart rate remained increased for the first 3 days after operation. Two patients developed episodes of myocardial ischaemia during the first 48 h after operation while their arterial oxygen saturation remained greater than 90%. On the third day, and during the third night after operation, both the severity and duration of myocardial ischaemia increased markedly, associated with arterial hypoxaemia. A temporal relationship between decreases in oxygen saturation and fluctuations in ST segment level were observed in the three patients.

Aged↗

Postoperative obstructive sleep apnoea. Haemodynamic effects of treatment with nasal CPAP.

A 74-year-old man presenting for aortic reconstructive surgery showed severe, previously undiagnosed obstructive sleep apnoea during overnight oximetry monitoring before operation. Postoperatively, in the first 4 hours following extubation, he suffered 238 episodes of respiratory obstruction. These events were associated with frequent arousals, large fluctuations in systolic and diastolic blood pressure. Administration of nasal continuous positive airways pressure abolished the obstructions and allowed an uninterrupted night's sleep, with a significantly reduced blood pressure. Subsequent dips in oxygen saturation as a result of respiratory obstruction recurred on the fifth postoperative night. We conclude that pre-operative overnight oximetry may be useful in identifying those patients at risk of postoperative upper airway obstruction. Use of nasal continuous positive airway pressure may prevent the occurrence of early postoperative obstruction and the associated haemodynamic changes.

Aged↗

The effects of controlled oxygen therapy on ventricular function in patients with stable and decompensated cor pulmonale.

We made simultaneous measurements of pulmonary hemodynamics, cardiac output, and right ventricular ejection fraction (RVEF) to assess the right ventricular function in 14 patients with pulmonary arterial hypertension as a result of chronic obstructive pulmonary disease (COPD). From these measurements, the right ventricular end-systolic pressure/volume relationship could be calculated and used to assess right ventricular contractility. Eight of the patients were clinically stable, without edema, and 6 presented acutely with gross edema, indicating decompensated cor pulmonale. Measurements were made at rest, while breathing air and oxygen. Although mean pulmonary arterial pressure (Ppa) was similar in those with (Ppa = 33 +/- 6 mm Hg) and without edema (Ppa = 30 +/- 8 mm Hg, p greater than 0.05), RVEF was lower in edematous (RVEF = 0.23 +/- 0.11) compared with non-edematous patients (RVEF = 0.47 +/- 0.04, p less than 0.01). Cardiac output was normal in both groups. The mean right ventricular end-systolic pressure/volume ratio (P/V) was lower in those patients with edema (P/V = 0.41 +/- 0.27), as compared with those without edema (P/V = 1.69 +/- 0.35, p less than 0.05), as a result of an increase in right ventricular end-systolic volume index. Similarly, left ventricular end-systolic volumes were higher in edematous than in non-edematous patients. Breathing 1 to 3 L/min of oxygen for 30 min decreased total pulmonary vascular resistance (p less than 0.05) in those patients without edema, but not in patients with edema. Oxygen did not change RVEF, left ventricular ejection fraction (LVEF), or the ventricular end-systolic P/V relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Effect of alcohol and aldehyde dehydrogenase inhibitors on the toxicity of 3-nitropropanol in rats.

The nitrocompounds 3-nitropropanol (NPOH) and 3-nitropropionic acid (NPA) were shown to be equally toxic when injected intraperitoneally into male Wistar rats. The LD50 for NPOH was 0.58 mmol/kg and for NPA it was 0.56 mmol/kg. NPOH was rapidly metabolized to NPA but this conversion was suppressed by prior administration of ethanol or 4-methylpyrazole to inhibit alcohol dehydrogenase. Administration of ethanol or 4-methylpyrazole before NPOH protected rats from intoxication. However, if the alcohol dehydrogenase inhibitors were given after the nitroalcohol, toxicity still occurred. Administration of the aldehyde dehydrogenase inhibitor diethyldithiocarbamic acid had little effect on the conversion of NPOH to NPA and did not alter the toxicity of NPOH. It was concluded that NPOH and NPA are equally toxic to rats but that NPOH is toxic due to its being rapidly converted to NPA.

1-Propanol↗