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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 91 records · Page 5Linked to original sources
PubMed1996

Inability of hyperglycemia to counter the ability of glucagon to increase net glucose output and activate glycogen phosphorylase in the perfused rat liver.

We examined the ability of hyperglycemia to alter the ability of glucagon to activate phosphorylase and stimulate glucose output in perfused rat livers. The livers were perfused with a Krebs-Henseleit buffer containing washed bovine erythrocytes and albumin at 37 degrees C for 90 or 120 minutes, In the first 60 minutes, the livers were perfused with insulin (10 microU/mL), glucagon (11 pg/mL), and glucose (105, 230, or 440 mg/dL). In the second 30 or 60 minutes, the glucagon concentration in the perfusate was elevated to 44, 88, 176 or 352 pg/mL or the infusion of glucagon was terminated. In the presence of glucose at 105 mg/dL, the termination of glucagon infusion decreased phosphorylase activity and glucose output. In contrast, the elevation of glucagon from 11 to 352 pg/mL activated phosphorylase and increased net glucose output in a dose-dependent manner. A linear correlation was observed between net glucose output and glycogen phosphorylase activity. An elevation of the glucose concentration from 105 to 230 or 440 mg/dL decreased net glucose output from 0.81 +/- 0.03 to 0.66 +/- 0.09 or -0.004 +/- 0.21 mg/min/100 g body weight, respectively, but did not cause significant change in phosphorylase-a activity (105 mg/dl, 50 +/- 11; 230 mg/dL, 40 +/- 2; 440 mg/dL, 69 +/ 3 mU/mg protein). The elevation of the glucagon concentration from 11 to 88 microU/mL in the presence of glucose at 105, 230, or 440 mg/dL increased net glucose output by 0.65 +/- 0.06, 0.61 +/- 0.08 or 0.64 +/- 0.26 mg/min 100 g body weight and raised phosphorylase-a activity by 65 +/- 5, 82 +/- 11, or 55 +/- 4 mU/mg protein, respectively. These results suggest that hyperglycemia decreases net hepatic glucose output without changing the activity of phosphory-lase-a. Further hyperglycemia does not alter the ability of glucagon to activate phosphorylase or to stimulate net hepatic glucose output.

Animals↗
PubMed1996

Mutation analysis in Canadian families with choroideremia.

Choroideremia (CHM) is an X-linked heritable progressive dystrophy of the choroid and retina. The condition predominantly affects males beginning in early childhood and eventually results in blindness after a period of 30-40 years. The CHM gene was localized to Xq21 and cloned in the past few years. The gene encodes for Rab escort protein-I, a protein involved in the isoprenylation of intracellular proteins. With the isolation of the gene, a number of mutations have been identified in patients affected by CHM using molecular techniques. Our group reports the characterization of mutations in four Canadian families affected by CHM. In addition, an intragenic polymorphism was identified in exon 5. Finding the mutations in these families will result in accurate predictive testing for carriers, avoid unnecessary repeated examination of at-risk individuals, and add to our understanding of the cause of this disorder.

Adaptor Proteins, Signal Transducing↗
PubMed1995

Effect of infarct artery patency on prognosis after acute myocardial infarction. The Survival and Ventricular Enlargement Investigators.

BACKGROUND: In patients with acute myocardial infarction (MI), early restoration of patency of the infarct-related artery (IRA) leads to preservation of left ventricular function and improved clinical outcome. However, there is evidence that the benefits associated with a patent IRA are out of proportion to the observed improvement in ventricular function and may result not only from salvage of ischemic myocardium but also from the opening of the IRA beyond a narrow postinfarct time window. The objectives of this study were (1) to assess the effect of IRA patency on outcome of patients after acute MI with left ventricular dysfunction while controlling for differences in left ventricular ejection fraction and the extent of coronary disease and (2) to determine the effect of angiotensin-converting enzyme (ACE) inhibitor therapy on patients with patent as well as occluded infarct arteries. METHODS AND RESULTS: The Survival and Ventricular Enlargement (SAVE) study consisted of 2231 patients with a documented MI and a left ventricular ejection fraction < or = 40%. They were randomized to the ACE inhibitor captopril (50 mg TID) or placebo 3 to 16 days after MI and were followed for an average of 3.5 years. Left ventricular ejection fraction, measured with radionuclide left ventriculography, was repeated at the end of the follow-up period. The 946 patients in whom the patency of the IRA was established before randomization form the basis of this study. At cardiac catheterization averaging 4.2 days after infarction, 30.7% of patients had an initially occluded IRA. After revascularization, 162 of the 946 patients (17.1%) were left with an occluded IRA at the time of randomization. The 162 patients with persistently occluded IRAs and 784 with patent IRAs had similar clinical baseline characteristics, but those with occluded arteries had a slightly lower ejection fraction than the 784 patients with patent infarct arteries (30% versus 32%, P = .01). Cox proportional-hazards analyses showed that the independent predictors of all-cause mortality were hypertension (relative risk [RR] 1.94, P < .001), number of diseased coronary arteries (RR 1.68, P < .001), occluded IRA (RR 1.49, P = .039), ejection fraction (RR 1.36, P < .001), age (RR 1.10, P = .030), and use of beta-adrenergic receptor blocking agents (RR 0.60, P = .007). Independent predictors of a composite end point consisting of cardiovascular mortality, morbidity, or reduction of ejection fraction of > or = 9 units were occluded IRA (odds ratio [OR] 1.73, P = .002), hypertension (OR 1.71, P < .001), number of diseased vessels (OR 1.38, P < .001), ejection fraction (OR 1.18, P = .003), use of beta-adrenergic receptor blocking agents (OR 0.67, P = .007), and randomization to captopril (OR 0.70, P = .009). CONCLUSIONS: IRA patency within 16 days after MI predicts a favorable clinical outcome, independent of the number of obstructed coronary arteries or of left ventricular function. The beneficial effect of ACE inhibition is independent of patency status of the IRA. These findings support the need for additional, prospective clinical trials of late reperfusion in MI patients.

Adrenergic beta-Antagonists↗
PubMed1995

Prenatal diagnosis of Smith-Lemli-Opitz syndrome is possible by measurement of 7-dehydrocholesterol in amniotic fluid.

Amniocentesis was performed at 17.3 weeks in a pregnancy with severe intrauterine growth retardation. Cytogenetic studies on amniocytes were normal, 46,XX, and the pregnancy was continued. The diagnosis of Smith-Lemli-Opitz syndrome was suspected in the neonatal period and confirmed by the presence of 7-dehydrocholesterol (7-DHC) in the plasma (0.4 mmol/l, normal = not detectable) associated with a low total cholesterol concentration (0.4 mmol/l, normal = 2.56 +/- 0.23). Retrospective analysis of the amniotic fluid sample revealed an elevated level of 7-DHC (0.022 mmol/l; normal = undetectable). Therefore measurement of 7-DHC levels in amniotic fluid during the second trimester of pregnancy is useful for the prenatal diagnosis of Smith-Lemli-Opitz syndrome in families at risk and should be considered in cases of severe growth retardation of unknown aetiology for which amniotic fluid is available and in which a normal chromosomal pattern in amniocytes is present.

Adult↗
PubMed1995

Morphologic change in rabbit femoral arteries induced by storage at four degrees Celsius and by subsequent reperfusion.

PURPOSE: Cold-stored arteries function well as microvascular autografts, but little is known of the morphologic changes that occur in them during cold storage or of further changes during reperfusion. METHODS: In part A of the study, rabbit femoral arteries were stored at 4 degrees C for up to 6 months. In part B rabbit femoral arteries were stored at 4 degrees C for up to 6 months, inserted as end-to-end autografts into contralateral femoral arteries, and reperfused for 24 hours. Tissue was examined by histologic study, transmission and scanning electron microscopy, histochemical study, immunohistochemical study, and tissue culture. RESULTS: Cell viability declined gradually at 4 degrees C, so that by 4 weeks no viable cells remained. However, the extracellular framework and elastic lamellae remain intact. If cold-stored arteries are reinserted as autografts for 24 hours, this accelerates breakdown of necrotic cells and reduces the thickness of the medial wall and internal elastic lamina but does not alter the extracellular framework. CONCLUSIONS: Cold storage results in acellular vascular grafts with intact extracellular frameworks. After 24 hours reperfusion there is no major change to the extracellular framework.

Actins↗
PubMed1995

Composition and viscosity of interstitial fluid of rabbits.

Open-ended plastic tubes were used as capsules for obtaining interstitial fluid from rabbits. The capsule was a 2.5 cm long plastic tube with an inner diameter of 6 mm. Three small incisions were made in the dorsal mid-line of the anaesthetized rabbit; two capsules were inserted into each incision. A sample of capsular fluid was obtained 6 weeks later by inserting a hypodermic needle through the skin. The volume of fluid obtained from the capsule was sufficient for the analysis of total protein, albumin, albumin:globulin ratio, colloid osmotic pressure and the fluid viscosity. Despite the significantly lower total protein, albumin, globulin and colloid pressure of intracapsular fluid compared with plasma, the intracapsular fluid was found to have a greater viscosity. It is our opinion that the increased viscosity of the intracapsular fluid is due to the presence of a high molecular weight substance other than albumin and globulin, possibly hyaluronan.

Animals↗
PubMed1994

The voices of reform. The final stretch. Interview by Renee Blankenau.

Following a complex research and development process last year that led to the drafting of a comprehensive health care reform proposal, President Bill Clinton presented the U.S. Congress and the nation with an outline for reform in September, and followed up with a detailed plan and with a reform bill in October. Now it's Congress' turn to respond. Hospitals & Health Networks' senior editor Renee Blankenau interviewed 11 members of Congress whose views represent a broad spectrum of congressional opinion. What version of federal reform will emerge this year? These legislators have the inside track.

Forecasting↗
PubMed1994

The role of the general practitioner in palliative care.

Palliative care tests the general practitioner's generalist skills. The work is not easy. We are trying to control symptoms that progress, feeling at times like the driver of a car with no brakes. It can evoke emotions of disturbing intensity. However, it is intensely rewarding work as well. The privilege of sharing life's journey with a patient, helping to enhance his or her quality of life, is one open to very few in our society. It is a privilege we should eagerly accept, as we are invited to stand with our patients facing their final challenge.

Family Practice↗
PubMed1993

Breeding experiments to combine the X-linked sparse-fur (spf) mutation with the autosomal recessive BALB/cByJ strain: testing the biochemical phenotype of double-mutant mice as a model for ammonia: fatty acyl CoA synergism.

Breeding experiments were conducted to combine the X-linked sparse-fur (spf) mutation with ornithine transcarbamylase deficiency and the autosomal recessive deficiency of short-chain acyl CoA dehydrogenase (SCAD) in BALB/cByJ mice. We obtained spf/Y (scad/scad), spf/+ (scad/scad) and spf/spf (scad/scad) double mutants amongst the F2 progeny, which were tested and separated on the basis of urinary orotate and the GC/MS analysis of urinary butyrylglycine, methylsuccinate and ethylmalonate. The testing of the biochemical type was feasible both on the basis of a 24-h urine collection form adult mice kept in metabolic cages and on the basis of urine spots collected on filter paper from younger progeny. It is postulated that the spf/Y (scad/scad) double-mutant may serve as a useful animal model to study the ammonia: fatty acyl CoA synergism.

Acyl Coenzyme A↗
PubMed1993

Effects of dehydration and rehydration on plasma vasopressin and aldosterone in horses.

We have investigated the change in plasma vasopressin and aldosterone concentrations in Namib (desert-adapted) and in control horses from a subtropical region, during an acute 12% dehydration and during rehydration, while food was available. During dehydration, vasopressin concentrations increased significantly in both groups of horses, but the increase was significantly greater in Namib horses than in control horses. During rehydration, vasopressin levels fell, but fell significantly less in Namib horses. The change in vasopressin concentration correlated significantly with plasma osmolality (r = 0.88, p < 0.001), and the relationship between these two variables was the same for both groups of horses during the dehydrated and rehydrated states. Aldosterone concentrations fell up to 48-h dehydration in both groups, but decreased significantly more in desert horses. From 48-h dehydration and during rehydration, aldosterone concentrations increased and the increase was sustained longer in Namib than in control horses. Changes in plasma osmolality did not correlate significantly with changes in aldosterone concentration. There were significant correlations between faecal moisture (%) and both vasopressin and aldosterone concentrations (r = -0.72, p < 0.008; r = 0.80, p < 0.002, respectively). During the 12% dehydration, the Namib horses sustained higher plasma osmolalities and consequently vasopressin levels than the control horses. We conclude that plasma osmolality in conjunction with these two hormones plays a significant role in water homeostasis in horses.

Acclimatization↗
PubMed1993

Update on multiple sclerosis therapy.

Multiple sclerosis is a demyelinating disorder of the central nervous system characterized by exacerbations and remissions of symptoms. This article deals with symptomatic therapy involving treatment of spasticity, fatigue, neurobehavioral disorders, paroxysmal disorders, pain, bladder dysfunction, and cerebellar dysfunction. This article also reviews immunosuppressive therapies including treatment of acute exacerbations or overall progression of the disorder with resultant accumulation of disability.

Amantadine↗