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Biomedical subjects

M Christie

Publications and source records attributed to M Christie.

11 recordsLinked to original sources

New observations on midline defects: coincidence of anophthalmos, microphthalmos and cryptophthalmos with hypothalamic disorders.

Four children with severe congenital eye anomalies are described of which three had related symptoms. Two had bilateral anophthalmia, the optic nerves not detectable by computed cranial tomography and magnetic resonance imaging, and the third child had bilateral microphthalmia and coloboma iridis. The fourth patient had bilateral cryptophthalmia as part of Fraser syndrome. All four patients were of small stature. In three of them growth hormone deficiency was demonstrated which was of hypothalamic origin as shown by growth hormone releasing hormone tests. In the fourth child hypogonadotropic hypogonadism and tertiary thyroid deficiency were diagnosed which responded well to thyroxine treatment. Pathogenetically the described disorders are due to congenital defects of midline structures as a common "developmental field".

Abnormalities, Multiple

The unexpected relocation of elderly in-patients in response to a threatened strike.

A threatened strike by non-professional hospital employees caused a teaching hospital to halve its in-patient numbers. This paper describes this unexpected, involuntary intervention in patient care in the Department of Geriatric Medicine. Fifty-three patients were discharged, 46 patients were transferred for 12 days to another hospital and 29 remained in the department. There was no evidence of important disruption in patient-care nor exacerbation of patient-distress as seen in ratings of patients' social, emotional and physical functioning. It is suggested that important factors in achieving successful unexpected relocation are: selection of patients who are medically stable albeit with significant physical and mental disability; the preparation and participation of patients and staff; and the continuation of patient care by nursing staff familiar to the patients.

Aged

Chronic TNF infusion causes anorexia but not accelerated nitrogen loss.

It has been proposed that many of the physiologic and metabolic changes that occur during critical illness and malignancy are mediated by the cytokine tumor necrosis factor alpha/cachectin (TNF). To test this hypothesis, a study of the metabolic responses that occurred during 5 days of continuous intravenous (I.V.) infusion of TNF both in rats and tumor-bearing humans was conducted. TNF administration was associated with anorexia, fluid retention, acute phase responses, and negative nitrogen balance. In both species, changes in nitrogen balance were related to the onset of anorexia and not to the development of hypermetabolism and accelerated net tissue breakdown. TNF may represent the primary afferent stimulus inducing many of the metabolic changes that occur during critical illness, but it is not solely responsible for the accelerated net proteolysis that occurs in these patients.

Acute Disease

Revelation of specificity of 64K autoantibodies in IDDM serums by high-resolution 2-D gel electrophoresis. Unambiguous identification of 64K target antigen.

Antibodies in serums from newly diagnosed insulin-dependent (type I) diabetes mellitus (IDDM) patients and individuals experiencing early phases of beta-cell destruction specifically immunoprecipitate a minor pancreatic islet cell membrane protein of 64,000 Mr (64K). In this report, we demonstrate the use of two-dimensional (2-D) gel electrophoresis to unambiguously identify the 64K antigen. By nonequilibrium pH-gradient gel electrophoresis in the first dimension and sodium dodecyl sulphate-polyacrylamide gel electrophoresis in the second dimension, the 64K protein separates into two components, designated alpha and beta, that differ in size but display identical charge heterogeneity. The high resolution of the 2-D method efficiently separates the 64K components from background proteins in immunoprecipitates from crude detergent lysates of islets. The background proteins were identified as major cellular proteins carried nonspecifically through the immunoprecipitation procedure. The high affinity and specificity of the 64K autoantibodies were demonstrated by the exclusive and greater than 1000-fold purification of this minor protein by immunoprecipitation with IDDM serums. The 2-D analyses did not reveal additional proteins specifically immunoprecipitated by IDDM serums, suggesting that the 64K protein is the only protein antigen specifically and consistently recognized by IDDM autoantibodies in the relatively stringent conditions of immunoprecipitation. Moreover, the 2-D analyses demonstrate that purification of membrane protein fractions from both human and rat islets before the immunoprecipitation efficiently removes background proteins and substantially increases the specificity of 64K autoantibody measurements by traditional methods.

Animals

Antibodies to a Mr-64,000 islet cell protein in Swedish children with newly diagnosed type 1 (insulin-dependent) diabetes.

Sera from 40 Swedish children diagnosed as having Type 1 (insulin-dependent) diabetes mellitus during a one year period along with 40 age and geographically matched control subjects were tested for antibodies to a Mr-64,000 islet protein by immunoprecipitation of 35S-methionine-labelled rat islet amphiphilic proteins. Of the 40 diabetic patients, 29 (73%) were found to be positive whereas all 40 control subjects were negative. Samples were also tested for titres of islet cell cytoplasmic antibodies by indirect immunofluorescence on frozen sections of human pancreas. In the diabetic group, 30 of the 40 patients (75%) were positive for islet cell cytoplasmic antibodies compared with 2 of the 40 control subjects (5%). A comparison of levels of antibodies to the Mr-64,000 protein with islet cell cytoplasmic antibodies revealed a weak (rs = 0.46), but significant (p less than 0.01) correlation between the two tests. There was no effect of age or sex on levels of antibodies to the Mr-64,000 protein. These results in population-based diabetic children and control subjects demonstrate a high frequency of antibodies to the Mr-64,000 protein at the time of clinical onset.

Animals

A comparative clinical trial of fluoxetine, mianserin and placebo in depressed outpatients.

Fluoxetine, a selective serotonin reuptake inhibitor, was compared with mianserin and placebo in a double-blind study. In total, 81 depressed patients were included. Patients were rated weekly on the Hamilton Depression Rating Scale (HDRS) and the Montgomery & Asberg Depression Rating Scale (MADRS). The duration was 6 weeks, and 52 patients completed the study. Significantly more patients on fluoxetine improved than patients on placebo. For mianserin no significant differences were found with either fluoxetine or placebo. Mean HDRS at the end of the study was also statistically significantly lower for fluoxetine, but not for mianserin, than placebo. Subscores of the MADRS showed improved sleep on mianserin at weeks 2 and 3. Suicidal feelings were reduced to a greater degree on fluoxetine than on mianserin and placebo at weeks 6 and 7. Fluoxetine induced weight loss, while patients on mianserin gained weight. Side effects were present in most patients on the two active drugs; those on fluoxetine experienced nausea and vomiting, and those on mianserin drowsiness.

Adolescent

The control of hydatid disease and ovine cysticercoses in the Australian Capital Territory and southern New South Wales.

A survey of human hydatid disease in New South Wales and the Australian Capital Territory over the period 1968 to 1973 was made from hospital records in Sydney and Canberra. The 162 new cases found represent an incidence, of 0-57 per 100,000 per annum, but the 20 patients living in the Central West Statistical Division of New South Wales at the time of admission to hospital represent an incidence of 12-6 per 100,000 per annum in that area. A survey of A.C.T. farms revealed dogs carrying the causative parasite Echinococcus granulosus on five out of 44 properties (11-4%). Community attitudes favoured control measures but displayed a misplaced faith in anthelmintic drugs. The high regional prevalence on the Australian mainland reveals a need to restrict availability of anthelmintics and extend the vigorous control measures employed successfully in Tasmania.

Adolescent

Cloning and expression of a rat D2 dopamine receptor cDNA.

Dopamine receptors are classified into D1 and D2 subtypes on the basis of their pharmacological and biochemical characteristics. The D2 dopamine receptor has been implicated in the pathophysiology and treatment of movement disorders, schizophrenia and drug addiction. The D2 dopamine receptor interacts with guanine nucleotide-binding proteins to induce second messenger systems. Other members of the family of receptors that are coupled to G proteins share a significant similarity in primary amino-acid sequence and exhibit an archetypical topology predicted to consist of seven putative transmembrane domains. We have taken advantage of the expected nucleotide sequence similarities among members of this gene family to isolate genes coding for new receptors. Using the hamster beta 2-adrenergic receptor gene as a hybridization probe we have isolated related genes including a cDNA encoding the rat D2 dopamine receptor. This receptor has been characterized on the basis of three criteria: the deduced amino-acid sequence which reveals that it is a member of the family of G-protein-coupled receptors; the tissue distribution of the mRNA which parallels that of the D2 dopamine receptor; and the pharmacological profile of mouse fibroblast cells transfected with the cDNA.

Animals

Comic relief.

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Aged