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Biomedical subjects

D Carmichael

Publications and source records attributed to D Carmichael.

At least 19 recordsLinked to original sources

Concurrent secretion of aldosterone and cortisol from an adrenal adenoma - value of MRI in diagnosis.

A 43-year-old female with a 24-years history of hypertension presented for further investigation and management of primary hyperaldosternoism. Postural studies were not conclusive and magnetic resonance (MR) imaging demonstrated a 27 x 18 mm lesion of the right adrenal gland which showed no signal loss during in and out of phase imaging. Although these appearances were considered to be atypical of those seen on MR in patients with aldosterone producing adrenal adenomas the patient underwent an adrenalectomy with removal of a 3 x 3 x 2 cm right adrenal mass. Post-operatively she became hypotensive and a 0900 hours serum cortisol was undetectable (< 50 nmol/l), consistent with adrenal insufficiency. Following the administration of hydrocortisone there was normalization of the blood pressure and subsequent adrenal stimulation tests confirmed the presence of functioning adrenal tissue albeit with an inadequate response. Cortisol measurement from preoperative samples revealed loss of normal diurnal rhythm whereas DHEAS levels both pre and postoperatively were undetectable, consistent with ACTH supression resulting from autonomous cortisol secretion in addition to aldosterone. Concurrent secretion of cortisol should always be considered in Conn's adenomas particularly when atypical radiological features are present.

Adenoma↗

Competency development in public health leadership.

The professional development of public health leaders requires competency-based instruction to increase their ability to address complex and changing demands for critical services. This article reviews the development of the Leadership Competency Framework by the National Public Health Leadership Development Network and discusses its significance. After reviewing pertinent literature and existing practice-based competency frameworks, network members developed the framework through sequential use of workgroup assignments and nominal group process. The framework is being used by network members to develop and refine program competency lists and content; to compare programs; to develop needs assessments, baseline measures, and performance standards; and to evaluate educational outcomes. It is a working document, to be continually refined and evaluated to ensure its continued relevance to performance in practice. Understanding both the applications and the limits of competency frameworks is important in individual, program, and organizational assessment. Benefits of using defined competencies in designing leadership programs include the integrated and sustained development of leadership capacity and the use of technology for increased access and quality control.

Curriculum↗

With cap in hand.

Explore the source record for details and available documents.

Family Practice↗

Secretory leukoprotease inhibitor attenuates lung injury induced by continuous air embolization into sheep.

Continuous air embolization (CAE) into the pulmonary arterial circulation of sheep results in functional and structural changes of chronic pulmonary hypertension. Release of elastin peptides into lung lymph during CAE and attenuation of CAE-induced pulmonary hypertension by neutrophil depletion suggest that neutrophil elastase may contribute to these changes. To investigate this notion, we treated awake sheep with a potent neutrophil elastase inhibitor, recombinant secretory leukoprotease inhibitor (SLPI) (100 mg/day by aerosol), during 12 days of CAE (CAE+SLPI; n = 7). Controls included sheep receiving CAE + vehicle (VEH) (n = 6), VEH alone (n = 3), and SLPI alone (n = 3). SLPI significantly attenuated the CAE-induced increases in lung lymph flow (day 8; 2.3 +/- 0.5 vs. 5.6 +/- 1.7 ml/15 min), protein clearance (day 8; 1.36 +/- 0.32 vs. 3.08 +/- 0.84 ml/15 min), and elastin peptide concentration (day 8; 243 +/- 41 vs. 398 +/- 44 ng/ml). SLPI delayed the onset of sustained pulmonary hypertension from day 8 to day 12. Both CAE groups showed similar structural changes in the pulmonary arteries. SLPI was well tolerated in control sheep and did not affect hemodynamics or structure. We conclude that serine proteases may contribute to the early initiation of chronic pulmonary hypertension but do not play a striking role in its eventual development.

Aerosols↗

Insulin-mediated inhibition of the induction of tyrosine aminotransferase by dexamethasone.

Insulin-mediated regulation of glucocorticoid-induced expression of the liver-specific gene tyrosine aminotransferase was studied in a clone of the Reuber rat hepatoma cells. Insulin inhibited dexamethasone-induced chloramphenicol acetyltransferase expression from approximately 4 kb of TAT 5' flanking sequence. The degree of this inhibition was comparable to the response of the endogenous gene. A construct of approximately 3 kbp of 5' flanking sequence exhibited no significant basal expression but retained sensitivity to glucocorticoids and to insulin inhibition of the glucocorticoid response. Results of further analysis of the insulin response in deletion constructs and constructs containing glucocorticoid responsive elements ligated to a heterologous promoter suggest that in addition to the glucocorticoid response elements a region close to the start site in the TAT promoter is necessary for insulin to inhibit glucocorticoid-mediated induction of expression.

Animals↗

Insulin-responsive tyrosine aminotransferase transcription requires multiple promoter regions.

This study used transient transfection analysis to determine the DNA regions which mediate basal and insulin-sensitive transcription from the gene encoding tyrosine aminotransferase (TAT; EC 2.6.1.5). Basal expression requires at least parts of two regions: a region at -3600 and a region from -208 to + 62. Insulin sensitivity requires at least one region of the promoter not required for basal expression. Thus, insulin cannot act solely by direct modification of any of the components required for basal transcription. Previous results from this laboratory suggest that the insulin effects on basal and glucocorticoid-induced TAT transcription require different regions of the proximal promoter.

Animals↗

Renal function after long-term low-dose cyclosporin for psoriasis.

Two groups of patients receiving cyclosporin A (CyA) for psoriasis had their renal function assessed by measurement of glomerular filtration rate (GFR) and effective renal plasma flow (ERPF). The first group comprised 13 patients who had taken low dose (average 3 mg/kg per day) CyA for an average period of 2.5 years. Seven of the 13 had a normal GFR of 108 (77-121) ml/min (median; range). In the other six patients the GFR was low at 63 (50-77) ml/min and CyA was discontinued for periods ranging from 3 to 17 weeks. The GFR rose in all six patients, to 79 (60-91) ml/min; this change was significant (P less than 0.05). The six patients restarted CyA because their psoriasis recurred and after a mean interval of 15 weeks the GFR had fallen in all six to 63 (46-80) ml/min (P less than 0.05) and the ERPF decreased from 339 (231-414) ml/min to 244 (177-321) ml/min (P less than 0.05). In the second group of 11 patients measurements were made prior to starting CyA and after taking CyA for a mean of 9 weeks. The GFR fell in eight out of 11 subjects, the GFR for the 11 patients being 117 (72-128) ml/min before taking CyA and 97 (51-122) ml/min after CyA (P less than 0.02). The ERPF was measured in nine of the 11 patients and fell in seven of the nine. The ERPF for the nine patients before CyA was 490 (296-642) ml/min and for the 11 patients after CyA was 410 (195-543) ml/min (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes.

The comparative pharmacokinetics of free doxorubicin and doxorubicin entrapped in cardiolipin liposomes was evaluated in rats at a dose of 6 mg/kg i.v. Doxorubicin was entrapped in cardiolipin liposomes by using 11.2 mumol of drug, 5.6 mumol of cardiolipin, 28.5 mumol of phosphatidylcholine, 19.5 mumol of cholesterol, and 11.1 mumol of stearylamine. The peak plasma concentration with free doxorubicin at 5 min was 1.7 micrograms/ml which was reduced to 0.3 micrograms/ml by 1 h. With cardiolipin liposomes, the peak plasma concentration of doxorubicin achieved at 5 min was 20.9 micrograms/ml. The plasma levels of doxorubicin decreased gradually and by 1 h the drug concentration in plasma was 10 micrograms/ml. The plasma levels of free doxorubicin and doxorubicin entrapped in liposomes were fitted to a 3-compartment computer model. The terminal half-life with free doxorubicin in plasma was 17.3 h whereas it was 69.3 h with drug entrapped in liposomes. The area under the plasma concentration curve with liposomal doxorubicin was 81.4 micrograms X h X ml-1 compared to 1.95 micrograms X h X ml-1 observed with free doxorubicin. The steady state volume of distribution with free doxorubicin was about 23-fold higher than liposomal doxorubicin. The terminal half-life with free doxorubicin in cardiac tissue was 17.9 h compared to 12.6 h with drug encapsulated in liposomes. The terminal half-lives in liver and spleen following administration of liposomal doxorubicin were 15- and 2.3-fold higher, respectively, compared to free drug; furthermore, the concentration X time values of liposomal doxorubicin in liver were 26-fold higher and in spleen 6-fold higher than the free drug. Free doxorubicin and doxorubicin entrapped in liposomes demonstrated 17 and 20% excretion in bile of the injected dose, respectively, in rats. The present studies demonstrate that liposomal encapsulation of doxorubicin significantly alters its pharmacokinetics in plasma and tissues compared to free drug.

Animals↗

Track condition and racing injuries in thoroughbred horses.

The incidences of fractures and soft tissue injuries during 68397 starts of thoroughbred horses at New York Racing Association tracks were analyzed concerning track condition, dirt and turf tracks, environmental conditions, length of races, location of fractures on the track, and age of horses. It was concluded that the conditions evaluated are of no importance in the occurrence of racing injuries to thoroughbred horses.

Animals↗

Toxic effects of food-borne fluoride in silver foxes.

Chronic ingestion of excessive amounts of fluoride from commercial fox food is associated with agalactia in vixens resulting in the starvation deaths of large numbers of kits in three fox herds. Evidence of infectious disease or poor management could not be found and a causal relationship between fluoride and high kit mortality is suggested.

Animal Feed↗

Hypokalemia and massive transfusion.

To investigate the etiology of the hypokalemia that is more commonly associated with massive transfusions than hyperkalemia, we determined the plasma potassium concentrations of 26 stored packed cell preparations and reviewed a series of 15 patients who received massive transfusions with whole blood or packed cells. Our results confirm that stored packed cell preparations, like stored whole blood preparations, are hyperkalemic, and suggest that metabolic alkalosis, catecholamine release, and hemorrhagic shock are important factors in the development of hypokalemia associated with massive blood transfusions. In view of the association of hypokalemia and hyperkalemia with massive transfusion, plasma potassium levels should be carefully monitored in patients receiving massive transfusions.

Adult↗

Plasma cholinesterase and trophoblastic disease. Gestational trophoblastic disease and reduced activity of plasma cholinesterase.

A case of prolonged action of suxamethonium in a patient with gestational trophoblastic disease is reported. Postoperatively the patient was found to have markedly reduced plasma cholinesterase activity (363 IU/litre) with a normal cholinesterase phenotype. Consequently plasma cholinesterase activity and phenotype were measured in six other patients with the condition and these results compared with those of 22 patients with normal first trimester pregnancies undergoing therapeutic abortion. Plasma cholinesterase phenotype was normal in all patients studied. The activity was significantly decreased (p less than 0.05) from the normal range (620-1370 IU/litre) in all patients with trophoblastic disease. In the 22 patients with normal pregnancies, 14 had activity values in the abnormal range (less than 620 IU/litre) while the mean cholinesterase activity of the group as a whole was significantly decreased (561.8 IU/litre, p less than 0.05) below the normal range. These results confirm the presence of a decrease in plasma cholinesterase activity in early pregnancy and provide new evidence for a decrease in activity in a pseudopregnancy state.

Adult↗

The evolution of renal osteodystrophy in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Since the introduction of continuous ambulatory peritoneal dialysis by Popovich et al [1] and the subsequent modification of the technique by Oreopoulos et al [2], an increasing number of patients with end-stage renal disease are maintained on this new treatment modality. To date, there has not been any report of the effect of CAPD on the evolution of renal osteodystrophy which is one of the major complications of chronic renal failure. In this report we will present the results of our radiological and biochemical studies of renal osteodystrophy in 28 patients who have been on CAPD from 6 to 23 months.

Adult↗