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Biomedical subjects

M E Cooper

Publications and source records attributed to M E Cooper.

At least 145 records · Page 8Linked to original sources
PubMed1996

Limitations of cognitive status exams: a case-based discussion.

Despite their extensive use in psychiatric and medical settings, brief mental status examinations have significant limitations that are easily overlooked in the pressure-cooker environments within which they are commonly used. Although undoubtedly of value as quick screening devices, the sheer brevity of these instruments all but guarantees limited validity. Brief examinations perform best with grossly impaired cases, alerting clinicians to the fact that something is badly amiss in patients who are significantly confused, disoriented, aphasic, or otherwise severely impaired. Very poor scores are accordingly frequently useful. Moderate or even perfect scores, however, will frequently be misleading, because patients with compromised brains often obtain them (Nelson et al. 1986). One such case follows.

Adult↗
PubMed1996

Renal sodium handling in experimental diabetes: role of NO.

Recent studies have suggested that diabetes is a state of increased renal nitric oxide (NO) activity as assessed by urinary excretion of nitrites and nitrates (NOx), and that NO synthase inhibitors reverse the increased glomerular filtration rate (GFR) observed in experimental diabetes. In addition to being a potent vasodilator in the renal vasculature, NO also plays a role in modulation of renal sodium excretion. To explore the role of NO in diabetes-associated alterations in renal excretory function, renal haemodynamic and sodium handling parameters were evaluated in conscious control (C) and streptozotocin diabetic rats (D) and correlated to the renal activity of NO, as assessed by urinary excretion of its metabolites NOx. To further explore this issue, the changes in renal haemodynamics and sodium handling were also assessed after NO synthase inhibition with a non-pressor dose of L-nitro-arginine-methyl-ester (L-NAME) and after administration of the NO donor, glyceryl trinitrate (GTN). Systolic blood pressure was not different between C and D rats. D rats exhibited marked hyperglycaemia (P < 0.001), and increases in GFR (P < 0.001), renal plasma flow, filtration fraction, urinary sodium excretion (UNaV, P < 0.001), filtered load of sodium (FLNa, P < 0.01), and a decrease in fractional reabsorption of sodium (FRNa, P < 0.0001). In contrast, total reabsorption of sodium (TRNa) was increased in D rats compared to C rats (P < 0.001). The urinary excretion of NOx was markedly increased in D rats (P < 0.01). Regression analyses performed in D rats revealed a close relationship between UNaV and GFR and a weaker correlation with urinary NOx. Although FRNa correlated only with urinary excretion of NOx, there was a strong relationship between TRNa and GFR. In contrast to D rats, control rats demonstrated only a relationship between TRNa and GFR and no other correlations were found. In D rats, NO inhibition with L-NAME (1 mg/kg body weight) resulted in a marked decrease in GFR and urinary NOx associated with decreases in FLNa and TRNa but did not influence FRNa. In contrast, in C rats the post-L-NAME decrease in NOx was not associated with significant changes in GFR and renal sodium handling. GTN-treated C rats exhibited a renal vasodilatory response and an increase in natriuresis and urinary NOx whereas no renal changes were observed in D rats during GTN administration. The present data indicate that changes in renal sodium handling before and after NO modulation in experimental diabetes are related to changes in GFR rather than to the renal activity of NO. Therefore, in contrast to the effects on renal haemodynamics, NO does not play an important role in the altered renal sodium handling observed in experimental diabetes.

Animals↗
PubMed1996

Kinins or nitric oxide, or both, are involved in the antitrophic effects of angiotensin converting enzyme inhibitors on diabetes-associated mesenteric vascular hypertrophy in the rat.

OBJECTIVE: To determine the roles played by kinins/nitric oxide and angiotensin II in the antitrophic effects of angiotensin converting enzyme inhibitors on mesenteric arteries after 3 weeks of streptozotocin diabetes by using blockers both of the angiotensin II AT1 receptor and of the bradykinin B2 receptor. DESIGN: Male diabetic Wistar rats were randomly allocated to receive no treatment, the angiotensin converting enzyme inhibitors perindopril or ramipril, the AT1 receptor blocker ZD7155, the bradykinin B2 receptor blocker Hoe 140, the nitric oxide synthase inhibitor NG-nitro-L-arginine-methyl ester, concomitant administration of perindopril plus subcutaneous Hoe 140, perindopril plus NG-nitro-L-arginine, or ramipril plus Hoe 140 (Hoe 140 administered via an Alzet mini-osmotic pump). METHODS: After 3 weeks, the rats were killed, their blood collected and their mesenteric vessels removed. The mesenteric vascular weight was measured and the media wall: lumen area ratio was assessed using quantitative histomorphometric techniques. RESULTS: Diabetes was associated with an increase in mesenteric weight and media wall:lumen area ratio. The angiotensin converting enzyme inhibitors, perindopril and ramipril, and the AT1 receptor antagonist ZD7155 reduced blood pressure and attenuated vascular weight and media wall:lumen area ratio. Concomitant administration of an angiotensin converting enzyme inhibitor with the kinin antagonist Hoe 140, administered either subcutaneously or via a mini-osmotic pump, or of the nitric oxide synthase inhibitor NG-nitro-L-arginine attenuated the effect of the angiotensin converting enzyme inhibitor on the mesenteric vascular weight and wall:lumen area ratios. Treatment with Hoe 140 or NG-nitro-L-arginine alone affected none of these parameters. CONCLUSION: The antitrophic effect of angiotensin converting enzyme inhibitors on diabetic mesenteric arteries is mediated by inhibition of angiotensin II and by actions on the kinin-nitric oxide pathway.

Angiotensin II↗
PubMed1996

Effects of liver transplantation and resection on lipid parameters: a longitudinal study.

BACKGROUND: The liver plays a vital role in the production and clearance of a large number of lipoproteins and is an important determinant of the plasma levels of various lipids including cholesterol, as well as apoproteins such as apoprotein (a). METHODS: To explore the role of the liver in the regulation of lipids and apoprotein concentrations, a serial prospective study measuring lipid parameters and apoprotein (a) levels over 6 months was performed in individuals undergoing hepatic resection for isolated hepatic metastases, transplantation for end-stage liver disease and in individuals undergoing colorectal surgery for malignancy. RESULTS: In the group with hepatic resection, there was a rapid decrease in total, high density lipoprotein (HDL) and low density lipoprotein (LDL) cholesterol in the immediate postoperative period. However, these changes could be explained by fasting and surgical intervention as a similar phenomenon was observed in the control subjects. In patients undergoing liver transplantation, total cholesterol decreased over the the immediate postoperative period but had fully recovered by day 40. Apoprotein (a) was low pre-operatively, remained low over the first week but had risen by day 10. Apoprotein (a) at day 40 correlated with the apoprotein (a) level of the donor (r = 0.80, P < 0.01) but not of the recipient's pre-operative level and this correlation persisted 6 months after hepatic transplantation. CONCLUSIONS: The liver has a large reserve and is able to maintain lipoprotein production and removal despite greater than 50% removal. The major cause of reduced plasma lipid concentrations in the postoperative period relates to other factors such as fasting and handling of the gut during surgery. In liver transplantation, apoprotein (a) levels resemble those of the donor within 2 weeks of organ donation, consistent with the liver being the major site of production of this apoprotein.

Adult↗
PubMed1996

Amylin binding in rat renal cortex, stimulation of adenylyl cyclase, and activation of plasma renin.

125I-labeled rat amylin binds to specific sites in the cortex of rat kidney, which can be distinguished from those for 125I-labeled salmon calcitonin (sCT) and 125I-labeled rat alpha-calcitonin gene-related peptide (alpha-CGRP) on the basis of regional distribution. These sites have a high affinity (approximately 1 nM) for amylin, and 125I-amylin binding is potently inhibited by the peptide antagonists AC413 and sCT-(8-32), whereas CGRP-(8-37) is a poor inhibitor of binding. Furthermore, incubation with guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) inhibits 125I-amylin binding by > 90%, indicating that binding is dependent on coupling to G proteins. In renal cortex, amylin stimulated adenylyl cyclase activity three- to fourfold, and this was inhibited by AC413 and sCT-(8-32) but not by CGRP-(8-37). Amylin activated plasma renin twofold, and this was blunted by prior administration of AC413 but not CGRP-(8-37). We speculate that amylin may play an important role in renal physiology and that in states of hyperamylinemia, as found in obesity and the insulin resistance syndrome, this peptide may be involved in the genesis and development of hypertension.

Adenylyl Cyclases↗
PubMed1996

Diabetic vascular injury and ACE. Potential for pharmacological prevention of complications of later life.

Experimental studies have indicated that angiotensin converting enzyme (ACE) inhibitors have multiple actions on the kidney and blood vessels which include both haemodynamic and antitrophic effects. Inhibition of angiotensin II and potentiation of bradykinin have both been postulated to be major mechanisms in mediating the effects of ACE inhibitors. Clinical studies have indicated that these agents postpone end-stage renal failure in macroproteinuric patients with insulin-dependent diabetes mellitus (IDDM). Indeed, these drugs are useful in both hypertensive and normotensive diabetic patients with macroproteinuria. In IDDM patients with microalbuminuria, ACE inhibitors have been shown to decrease albuminuria and to retard the development of overt renal disease. The role of these agents in patients with non-insulin-dependent diabetes mellitus (NIDDM) and early or overt renal disease remains to be clearly delineated. However, preliminary studies suggest a similar beneficial renoprotective effect of ACE inhibitors in NIDDM. It should be appreciated that the presence of micro- or macroproteinuria in NIDDM is a predictor of cardiovascular rather than renal morbidity and mortality. The possibility of cardiovascular protection, in addition to renal protection, being conferred by these drugs needs to be considered in both IDDM and NIDDM, although this issue has not been evaluated in detail.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

Genetic segregation analyses of serum IgG2 levels.

Summary : The aim of this study was to determine whether there was evidence for a genetic component in the immune response as measured by IgG2 levels. The study was motivated by our studies of early-onset periodontitis (EOP), a group of disorders characterized by rapid destruction of the supporting tissues of the teeth in otherwise healthy individuals. EOP has two subforms, localized juvenile periodontitis (LJP) and a generalized form (G-EOP). IgG2 levels are elevated in LJP but not G-EOP individuals; and African-American IgG2 levels are higher than Caucasian levels regardless of EOP status. IgG2 levels were determined in 123 EOP families and in 508 unrelated non-EOP control individuals. Segregation analysis under the regressive model approach of Bonney was used to analyze IgG2 levels for evidence of major locus segregation. After adjusting for LJP status, race, sex, and age, the best fitting model was an autosomal codominant major locus model (accounting for approximately 62% of the variance in IgG2), plus residual parent/offspring and spousal correlations. Smoking and GM23 are also known to affect IgG2 levels. If additional adjustments are made for smoking and GM23, the best-fitting model is still a codominant major locus but with no significant residual correlations.

Black People↗
PubMed1996

Acute care of the spinal cord injured.

In 1993, there were 583 new spinal cord injuries in Canada (Canadian Paraplegic Association, 1993). Seventy-five percent of those were males and sixty-seven percent were between the ages of 16 and 40. Motor vehicle accidents account for the highest percentage of injuries, while falls and sports are second and third respectively. The impact of this type of injury has many far reaching implications, not only on the individual and their family but also on society as a whole. These patients are surviving and living longer than before. Care of these patients has advanced considerably. Nurses caring for these patients must be experts in their field, having a solid understanding of the multiple system effects of traumatic spinal cord injury (SCI) and their implications.

Accidents, Traffic↗
PubMed1996

Renal protection and angiotensin converting enzyme inhibition in microalbuminuric type I and type II diabetic patients.

BACKGROUND: Many studies have emphasized the role of antihypertensive drugs and in particular angiotension converting enzyme (ACE) inhibitors in the retardation of diabetic nephropathy. Although these studies have focused predominantly on patients with overt proteinuria, more recently a number of investigators have explored the role of ACE inhibitors in both type I and type II diabetic patients with an earlier phase of diabetic renal disease known as microalbuminuria. These agents are now being considered as renoprotective agents not only in hypertensive patients but also in those with 'normal' blood pressure. Initially, studies in type I diabetic patients showed that ACE inhibition was effective in retarding the increase in albuminuria which was observed in placebo treated groups. More recently, several multi-centre placebo controlled studies have been performed suggesting that prolonged treatment not only reduced albuminuria but also preserved renal function. The role of ACE inhibition in microalbuminuric type II diabetic patients is less well characterised although several studies have recently described beneficial effects of ACE inhibition on albuminuria and possibly on renal function. REVIEW: Although ACE inhibitors have been clearly shown to reduce urinary albumin excretion in diabetic patients, the issue as to whether they confer a specific benefit over other classes of antihypertensive agents remains controversial. Several meta-analyses have suggested that ACE inhibitors are more potent at decreasing albuminuria or proteinuria than other antihypertensive agents, for a given reduction in blood pressure. The Melbourne Diabetic Nephropathy Study Group has instituted a study which is placebo-controlled and is confined to normotensive type I and type II diabetic patients. The ACE inhibitor perindopril has been compared not only with placebo but also with the dihydropyridine calcium channel blocker, nifedipine. Preliminary analysis reveals that after 12 and 24 months of treatment, perindopril is more effective in reducing albuminuria than placebo or nifedipine. CONCLUSION: ACE inhibitors are a promising class of antihypertensive agents in diabetic patients with microalbuminuria. These drugs should be considered as first line agents in such patients, even in the absence of systemic hypertension.

Albuminuria↗
PubMed1995

Adrenomedullin and calcitonin gene-related peptide in the rat isolated kidney and in the anaesthetised rat: in vitro and in vivo effects.

The effects of adrenomedullin and calcitonin gene-related peptide (CGRP) were compared in the rat isolated perfused kidney and in the anaesthetised rat. Adrenomedullin and CGRP both elicited concentration-dependent vasodilator responses from perfused kidneys (adrenomedullin was less potent than CGRP). These responses were blocked by CGRP-(8-37) (1 microM). Adrenomedullin and CGRP elicited dose-dependent hypotension in anaesthetised rats (adrenomedullin was less potent than CGRP). The hypotensive responses to CGRP, but not those to adrenomedullin, were antagonized by CGRP-(8-37) (12 nmol/kg/min). These studies indicate that the in vivo response to adrenomedullin may be mediated through CGRP-(8-37) insensitive receptors.

Adrenomedullin↗
PubMed1995

The relative roles of advanced glycation, oxidation and aldose reductase inhibition in the development of experimental diabetic nephropathy in the Sprague-Dawley rat.

Advanced glycation is an important pathogenic mechanism in the development of diabetic complications. However, other biochemical processes, such as the polyol pathway or lipid and protein oxidation which can interact with advanced glycation can also yield tissue fluorescence and may also be implicated in the genesis of diabetic microangiopathy. Aminoguanidine is an inhibitor of advanced glycation, but it is not known if all of its effects are mediated by this mechanism. The present study explores the relative contributions of aldose reductase, oxidative stress and advanced glycation on the development of aortic and renal fluorescence and urinary albumin excretion in streptozotocin diabetic rats. The study groups included non-diabetic (control), streptozotocin diabetic rats and diabetic rats receiving aminoguanidine, the anti-oxidants butylated hydroxytoluene and probucol and the aldose reductase inhibitor, ponalrestat. Serial measurements of glycaemic control and urinary albumin excretion were performed every 8 weeks. At 32 weeks, animals were killed, tissues removed and collagen extracted for measurement of fluorescence. Diabetic rats had increased fluorescence in aorta, glomeruli and renal tubules. Aminoguanidine prevented an increase in fluorescence at all three sites suggesting that diabetes-related tissue fluorescence is predominantly due to advanced glycation. Ponalrestat retarded fluorescence in aorta only and butylated hydroxytoluene attenuated fluorescence at the renal sites but not in the aorta. Diabetic rats had increased renal cortical sorbitol levels. Ponalrestat normalized renal cortical sorbitol levels but aminoguanidine did not affect this parameter. The only agent to decrease plasma thiobarbituric acid reactive substances was butylated hydroxytoluene. Diabetic rats developed albuminuria over the 32-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuminuria↗
PubMed1995

Comparison of effects of ACE inhibition with calcium channel blockade on renal disease in a model combining genetic hypertension and diabetes.

The aim of this study was to compare the renal effects of angiotensin converting enzyme (ACE) inhibition with calcium channel blockade in a model combining genetic hypertension with diabetes. Streptozotocin diabetes was induced in spontaneously hypertensive rats (SHR). The animals were then randomized to receive no treatment, the ACE inhibitor, perindopril, or the dihydropyridine calcium antagonist lacidipine. Body weight, systolic blood pressure, glycemic control, renal function, and albumin excretion rate (AER) were assessed serially over the 32-week study period. At week 32 the animals were killed and glomerular volume was measured. Both antihypertensive regimens significantly reduced systolic blood pressure in diabetic SHR. There was no significant difference in glycemic control, serum creatinine, or glomerular filtration rate among the three groups at week 32. The ACE inhibitor perindopril significantly reduced AER and glomerular hypertrophy over the 32 weeks, whereas the calcium antagonist lacidipine failed to reduce AER or glomerular hypertrophy. Thus, in contrast to the effects of ACE inhibition, calcium channel blockade with lacidipine, despite significantly reducing blood pressure, failed to reduce renal injury in this model. These results support the hypothesis that antihypertensive regimens may differ in their capacity to protect the diabetic kidney, despite similar effects on systemic blood pressure.

Albuminuria↗
PubMed1995

SPARC gene expression is reduced in early diabetes-related kidney growth.

Renal enlargement is a characteristic feature of diabetes in humans and experimental animals that may predict subsequent renal disease. The biological processes involved in diabetes-related kidney growth are complex and involve changes in extracellular matrix, cell hypertrophy and hyperplasia. Secreted protein acidic and rich in cysteine (SPARC) is an extracellular matrix protein with anti-adhesive, antiproliferative and matrix remodeling properties. We examined kidney SPARC gene expression and protein content in early experimental diabetes. By Northern blot analysis, kidney SPARC mRNA fell in diabetic animals at day 1 to 40 +/- 15% of controls levels (mean +/- SEM, P < 0.01) to 42% +/- 11% on day 3 (P < 0.01) with a further decrease at day 7 to 29 +/- 7% (P < 0.001). In situ hybridization demonstrated SPARC mRNA within glomeruli renal interstitial cells and in blood vessels but not in tubular epithelial cells. SPARC mRNA was decreased in diabetic rats within a change in the pattern of distribution. By immunofluorescence, SPARC protein was detected in glomeruli and tubular basement membrane. Diabetes was associated with a decrease in SPARC protein at both sites. These data demonstrate that the onset of diabetes-related kidney growth is associated with a reduction in SPARC mRNA and protein. In the context of the known biological actions of SPARC, the findings in the present study implicate this matrix protein in the pathogenesis of diabetes related kidney growth.

Animals↗
PubMed1995

Vascular albumin permeability and hypertrophy in a rat model combining streptozotocin-induced diabetes and genetic hypertension.

OBJECTIVE: To investigate the effects of hypertension and diabetes mellitus on vascular albumin permeability and hypertrophy in 11-week-old Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) with and without 3 weeks of streptozotocin-induced diabetes. METHODS: Vascular albumin permeability was measured as tissue content of intravenously injected Evans blue dye. RESULTS: Diabetic rats showed hypertrophy of the kidneys, and hypertensive rats showed hypertrophy of the heart. In the mesenteric artery there was an additive hypertrophic effect of diabetes and hypertension. The Evans blue content in kidneys was higher in diabetic SHR than in diabetic and in control WKY rats. The kidney: plasma Evans blue ratio was higher in diabetic SHR than in the other three groups, and the heart: plasma Evans blue ratio was higher in diabetic SHR than in control WKY rats or control SHR. The Evans blue content and tissue: plasma Evans blue ratio did not differ in aorta, mesenteric artery or skeletal muscle among the groups. There was no positive correlation between vascular albumin permeability and hypertrophy in any of the tissues studied. CONCLUSION: There was no relationship between vascular albumin permeability and hypertrophy, but increased vascular albumin permeability was found in kidneys and hearts of rats with both diabetes and hypertension. This suggests an additive or synergistic effect of diabetes and hypertension in producing vascular changes.

Animals↗
PubMed1995

Acute renal hemodynamic effects of ACE inhibition in diabetic hyperfiltration: role of kinins.

Angiotensin converting enzyme (ACE) inhibitors not only reduce angiotensin II (ANG II) levels but also inhibit kinin degradation. The relative roles of ANG II and bradykinin in the acute action of ACE inhibitors on renal hemodynamic parameters in rats after 3 wk of diabetes were explored using antagonists of the ANG II type 1 (AT1) and the bradykinin B2 receptors. Conscious control and streptozotocin diabetic male Sprague-Dawley rats were randomized to receive vehicle, the ACE inhibitor, ramiprilat, the B2-receptor blocker, HOE-140, the AT1-receptor blocker, valsartan, or the combination of ramiprilat and HOE-140. Systolic blood pressure, glomerular filtration rate (GFR), renal plasma flow (RPF), filtration fraction and urinary flow, and sodium excretion were assessed before and during treatment. Diabetic animals had higher GFR and a tendency toward increased RPF and filtration fraction compared with control animals. Acute ramiprilat infusion decreased GFR significantly in diabetic but not in control animals. Valsartan and the combination of ramiprilat and HOE-140 reduced blood pressure to a similar degree to ramiprilat alone, yet did not reduce GFR. No decrease in GFR was observed in any control rat groups. Ramiprilat decreased RPF in diabetic rats but increased RPF in control rats. No such effects on RPF were observed with valsartan. HOE-140 alone did not influence any renal parameter in the diabetic rats. Diabetic rats had increased urinary flow and sodium excretion, but these parameters were not influenced by any drug regimen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1995

Amylin stimulates plasma renin concentration in humans.

Although insulin resistance and hypertension are commonly associated, the underlying cause for this association remains unknown. Plasma concentrations of the recently described hormone amylin, which is cosecreted with insulin by the pancreatic beta cell, are reported to be elevated in various states of insulin resistance, including hypertension and obesity. Preliminary studies by our group have suggested that there are amylin binding sites in the kidney. In nine healthy humans an infusion of human amylin that resulted in steady state plasma amylin levels in the subnanomolar range led to significant increases in plasma renin and aldosterone concentrations. These changes occurred in the absence of significant changes in plasma electrolytes, catecholamines, vasopressin, total renin, or osmolality. Diastolic pressure at 30 minutes and plasma glucose at 60 minutes rose modestly. Since amylin has both metabolic and renal actions, this peptide may be an important link between hypertension, insulin resistance, and the renin-angiotensin system.

Adolescent↗