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Biomedical subjects

G Mitchell

Publications and source records attributed to G Mitchell.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1993

Surgical and metabolic aspects of liver transplantation for tyrosinemia.

Tyrosinemia is the diagnosis of a very small percentage of patients undergoing liver transplantation worldwide. Tyrosinemia is endemic within our referral area however, and fully one-third of the liver transplantations at our institution are done for this disease. Since 1986, 15 patients with tyrosinemia (TYR) and 31 patients with various other indications (non-TYR) have undergone a total of 51 liver transplantations. The 36-month actuarial survival for TYR patients is 87%, compared with 74% for non-TYR patients. Liver transplantation for hereditary tyrosinemia and other metabolic disorders without portal hypertension or previous portohepatic operations is notably easier to perform. Intraoperative blood loss was less, length of hospital stay was shorter, and incidence of infections was lower in TYR than in non-TYR patients. Less than 10% of TYR patients had foci of hepatocellular carcinoma at the time of transplantation. For this reason, and while most patients with tyrosinemia will eventually require liver transplantation, our results do not support systematic early transplantation before the age of two years.

Adolescent↗
PubMed1993

Development of a dual function sensor system for measuring pressure and temperature at the tip of a single optical fiber.

A dual function sensor system has been developed for measuring pressure and temperature at the tip of a single optical fiber. The sensor contains three parts: a filter band-edge shift temperature based spectral modulation pressure sensor. The sensor system uses a separate and distinct LED for interrogating each sensor, three 100/140 microns step-index fused couplers for managing light, and separate paired photodiode assemblies for analyzing the return light signal from each sensor. In bench tests, each sensor performed to specification and, importantly, there was no crosstalk between sensors. This dual function sensor design has potential catheter applications where catheter size must be kept to an absolute minimum.

Equipment Design↗
PubMed1993

Views from Capitol Hill--11 congressional leaders paint varying reform scenarios. Interview by Marybeth Burke.

The following exclusive interviews with top congressional health care leaders were conducted by Washington-based reporter Marybeth Burke. In the interviews, Burke found that congressional health care leaders are optimistic yet cautious that comprehensive health care reform legislation will pass in 1993 under President Clinton. Some members of Congress believe that the election of a president committed to action on the issue drastically improves the outlook for reform. Others say that long-term controversy over reform will not resolve itself overnight. Lawmakers expect the issue to heat up quickly as soon as Clinton hands Congress a legislative reform package, but they are reluctant to predict quick enactment.

Competitive Medical Plans↗
PubMed1993

Foxed by the foxglove.

The art of general practice is to identify important causes of common, often undifferentiated symptoms. This article presents two cases of clinical digoxin toxicity in the presence of normal or low serum digoxin levels. Standard teaching says that symptoms are related directly to toxic serum levels, but this appears to be not always the case.

Aged↗
PubMed1993

A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec.

We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with Leigh disease, by the severity of the biochemical defect in different tissues. The activity in skin fibroblasts, amniocytes, and skeletal muscle of cytochrome oxidase is 50% of normal, while in kidney and heart it is close to normal values. Brain and liver, on the other hand, have very low activities. The defect in activity appears to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence.

Acidosis, Lactic↗
PubMed1993

Clinical, metabolic, and genetic aspects of cytochrome C oxidase deficiency in Saguenay-Lac-Saint-Jean.

Thirty-four children with lactic acidosis and Leigh encephalopathy due to cytochrome C oxidase (COX) deficiency distributed in 28 families have recently been identified in northeastern Quebec, particularly in the Saguenay-Lac-Saint-Jean (SLSJ) region. The segregation analysis was consistent with an autosomal recessive mode of inheritance. The incidence was estimated at 1/2,063 live births between 1979 and 1990, and the carrier rate was estimated at 1/23 inhabitants in SLSJ. In SLSJ, the places of origin of the COX-deficient children and their parents did not show a clustered nonuniform distribution. The genealogical reconstruction of 54 obligate carriers identified 26 ancestors common to all of them. Twenty-two were 17th-century Europeans, suggesting that the COX-deficient gene was introduced in the French-Canadian population by early settlers. These results support the hypothesis of a founder effect for COX deficiency in northeastern Quebec. Clinical findings are reported for 15 of these COX-deficient patients, age 6 mo to 11 years. Moderate developmental delay, hypotonia, ataxia, strabismus, and mild facial dysmorphism were frequent. Eleven children died in episodes of fulminant metabolic acidosis. The patients had elevated blood and cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, and normal blood pH. Leigh disease and microvesicular steatosis of the liver were present in all affected patients for whom postmortem examination was performed. This biochemically uniform group of patients showed a wide range of clinical severity.

Acidosis, Lactic↗
PubMed1992

Single-strand conformational polymorphisms (SSCP): detection of useful polymorphisms at the dystrophin locus.

We searched for DNA polymorphisms in seven amplified fragments of the dystrophin gene. Three fragments exhibited variable mobilities during nondenaturing strand-separating gel electrophoresis (SSGE). These variants were due to single base changes (three transversions and one transition). Three were intronic (upstream from exons 17, 15, and 48) and one was in exon 48. The frequencies of these sequence variants were determined in a sample of 54 normal X chromosomes of Caucasian origin. One of these DNA polymorphisms was observed in every 650 bp tested and the average heterozygosity was 0.05% per base pair (0.08% if exons were excluded). Such a detection density and the fact that single-strand conformational polymorphisms do not depend on the presence of any specific sequence makes them especially valuable as genetic markers. In the dystrophin locus this approach could allow simultaneous detection of frequent deletions.

DNA, Single-Stranded↗
PubMed1992

Normal conduction in pathways traversing an asymptomatic multiple sclerosis plaque.

A 31-year-old woman developed right facial myokymia as the initial manifestation of multiple sclerosis (MS). An MRI scan revealed a focal signal abnormality confined to the left dorsolateral pontomedullary region. Brain-stem auditory evoked potentials (BAEPs), somatosensory evoked potentials (SEPs), and blink reflex (BR) failed to show a conduction abnormality through the left brain-stem lesion. Instead, BAEP and BR indicated a conduction defect in the right pons and EMG showed myokymic discharges in right facial muscles. Our findings provide rare documentation of normal conduction through a presumably asymptomatic MS plaque. The abnormal MRI signal likely represents tissue edema, rather than demyelination. This case demonstrates that physical findings in MS patients may correlate better with electrophysiological abnormalities than with MRI abnormalities.

Adult↗
PubMed1992

Effects of dehydration and rehydration on the intravascular space in horses.

1. The resistance of sub-tropical horses, and desert-dwelling horses to 72 hr dehydration/24 hr rehydration was investigated via changes in red cell parameters and plasma protein concentration. 2. Red cell count, haemoglobin and haematocrit increased up to 48 hr dehydration. Between 48 and 72 hr dehydration these parameters decreased, implying a fluid shift onto the intravascular space from the interstitium/hindgut. Most parameters had regained baseline values by 24 hr rehydration. 3. Mean cell volume, mean cell haemoglobin, mean cell haemoglobin concentration and total plasma protein were not significantly different between breeds at, or between most stages of hydration. 4. Protection of plasma volume during dehydration/rehydration was aided by maintaining intravascular protein (especially albumin) levels. Red cells were transiently dehydrated and overhydrated but resisted osmolysis.

Animals↗
PubMed1992

Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene.

We tested the use of a modified method of single-strand conformational polymorphism (SSCP) analysis for the detection of point mutations in the human ornithine-delta-aminotransferase gene. Using a combination of three different electrophoretic conditions, we detected 20/20 known mutations. In a prospective study of 24 previously uncharacterized mutant OAT genes, we found 13 different mutations accounting for 19 (79%) of the 24. We conclude that SSCP is an efficient technique with high sensitivity and specificity.

Base Sequence↗
PubMed1992

Development of a medical fiber-optic pH sensor based on optical absorption.

A new fiber-optic pH sensor system has been developed. The sensor uses an absorbtive indicator compound with a long wave-length absorption peak near 625 nm; change in absorption over the pH range 6.8 to 7.8 is reasonably linear. The sensor is interrogated by a pulsed, red LED. Return light signal is split into short and long wave-length components with a dichroic mirror; the respective signals are detected by photodiodes, and their photocurrents are used to form a ratiometric output signal. In laboratory tests, the sensor system provided resolution of 0.01 pH, accuracy of +/- 0.01 pH, and response time of 30-40 s. Following gamma sterilization, laboratory sensor testing with heparinized human blood yielded excellent agreement (e.g., r = 0.992 for n = 42) with a clinical blood gas analyzer. Excellent sensor performance and low cost, solid-state instrumentation are hallmarks of this sensor-system design.

Absorption↗
PubMed1992

Type 1 hereditary tyrosinemia. Evidence for molecular heterogeneity and identification of a causal mutation in a French Canadian patient.

Type 1 hereditary tyrosinemia (HT1) is a metabolic disorder caused by a deficiency of fumarylacetoacetate hydrolase (FAH). Using a full-length FAH cDNA and specific antibodies, we investigated liver specimens from seven unrelated HT1 patients (six of French Canadian and one of Scandinavian origin). The expression of FAH in livers of these individuals was analyzed at several molecular levels including mRNA, immunoreactive material (IRM), and enzymatic activity. Four phenotypic variants were differentiated by these assays: (i) presence of FAH mRNA without any IRM or enzymatic activity, (ii) decreased FAH mRNA, IRM, and enzymatic activity, (iii) moderately decreased FAH mRNA and IRM with severely reduced enzymatic activity, and (iv) undetectable FAH mRNA, IRM, and enzymatic activity. These various molecular phenotypes suggest that this disorder may be caused by a variety of FAH mutations. Interestingly, we found no apparent relationship between the clinical and the molecular phenotypes, except that patients with absent IRM and enzymatic activity tend to have higher levels of serum alpha-fetoprotein and an earlier clinical onset. To further analyze the molecular basis of HT1, the FAH cDNA of a patient designated as variant A was amplified and sequenced. An A-to-T transversion, which substitutes asparagine16 with isoleucine (N16I), was identified. This patient was heterozygous as shown by direct sequencing of the amplified region and hybridization with allele-specific oligonucleotide probes. The N16I allele originates from the father and the second allele appears not to be expressed in the liver of the proband. CV-1 cells transfected with the mutant cDNA produced FAH mRNA, but no protein or hydrolytic activity, as predicted by the "A" phenotype of the patient. This is the first demonstration of heterogeneity in the expression of FAH at the levels of protein, mRNA, and enzymatic activity in the livers of HT1 patients and is the first identification of a causal mutationin this disease.

Adolescent↗
PubMed1992

Fit-ins. Even a bad day has lessons for us.

It is a bad day at the office. Four patients present with intractable dilemmas: two exhibit self abusing behaviour, and the other two behave in ways that affect others. What can the GP do in these circumstances?

Adolescent↗