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Biomedical subjects

S Dean

Publications and source records attributed to S Dean.

At least 19 recordsLinked to original sources

Morphometric analysis on myocardial injury related to the use of high volume potassium cardioplegic solution during ischemic arrest.

We correlated the effects of high volumes of K+ cardioplegic solution on myocardial structure and function in 16 dogs following open-heart surgery. Eight animals received high volume potassium cardioplegic solution (25 cc/kg body weight, every 30 min) during 90 min of ischemic arrest (HVK-C group). The others received sufficient cardioplegic solution to maintain complete electrical arrest as defined by voltage monitoring criteria (VM group). Cardiac index (CI), left ventricular stroke work index (LVSWI), and myocardial contractility (dp/dt) were determined before arrest and after 90 min of ischemia and 45 min of reperfusion. Biopsies were taken for EM ultrastructure and ATP estimation. Morphometric analysis of EM micrographs found increased volume of damaged mitochondria (DMR) (p less than 0.025), damaged myofibrils (DMF) (p less than 0.001), intermyofibrilar edema (p less than 0.005), T-tubule and sarcoplasmic reticulum (p less than 0.05) in the HVK-C group. Left ventricular (LV) function was more depressed in animals receiving HVK-C. CI decreased by 1.8 +/- 0.4 l/min/square meter (p less than 0.01), LVSWS fell by 3.3 +/- 0.8 gm-m/beat/Kg (p less than 0.01), dp/dt decreased by 684 +/- 135 (p less than 0.0025). ATP decreased by 26% in HVK-C and by 12% in VM group (0.1 less than p less than 0.05). Structural damage (scores of injured volume of mitochondria and myofibrils) correlated with post-ischemic depression of LV function (Cardiac output and myocardial contractility), r = -0.72 and -0.66 (p less than 0.001 and 0.004).

Adenosine Triphosphate

The relationship of mast cells and their secreted products to the volume of fibrosis in posttransplant hearts.

A series of 96 posttransplant endomyocardial biopsies taken from 11 patients was subjected to quantitative analysis of mast cells and fibrosis. Ultrastructural analysis showed that mast cell numbers were increased and there was obvious degranulation in some posttransplant hearts. Activated mast cells and their secreted products, which contain heparin and histamine, are toxic to the hearts and may contribute to interstitial and perimyocytic fibrosis. The numbers of mast cells and granules were correlated with volume of fibrosis (r = 0.63, P less than 0.025; r = 0.73, P less than 0.01). There were differences between the release of mast cell granule contents seen in the posttransplant hearts and the rapid and massive reaction of anaphylactic degranulation of mast cells. Some mast cells progressively lost their dense granule contents, displaying a variety of piecemeal degranulation that indicates a slow degranulation process. These events occurred from the first week; they lasted from weeks to months. The fibrosis developed quickly in the cases with more mast cells and degranulation. The cases with fewer mast cells and granules showed only mild increases in the volume of fibrosis. Mast cells appeared as early as the first posttransplantation week. Patients with greater numbers of mast cells underwent more severe rejection episodes. This study demonstrated that mast cells play an early and important role in the perimyocytic and interstitial fibrosis of posttransplant hearts. Mast cells may also be important in the inflammatory process of rejection reaction. The severity of fibrosis appears related to the density of mast cells and their granules.

Fibrosis

Comparative epidermal Langerhans cell migration studies in epidermal and epidermal/dermal equivalent grafts.

Immigration of Langerhans cell precursors from the peripheral blood to the skin was studied in human grafts placed on severe combined immunodeficient (SCID) mice. Monocyte fractions of human blood were injected intraperitoneally to SCID bearing either reconstituted (Langerhans cell free) epidermal sheets (E) or living skin equivalents (E/D) consisting of both epidermis and dermis. A range of immunocytochemical and ultrastructural markers was employed to monitor the colonization of the grafts, i.e., CD1a/c, Birbeck granules. In situ hybridization with probes against Alu sequences of human DNA were employed together with immunostaining for MHC class I mouse and human antigens to document graft survival. Although unequivocal LC were detected within E grafts, including both human (CD1a positive) and murine (NLDC-145 positive), no migration was achieved in the E/D situations.

Animals

Elimination of matrix effects in electrothermal atomic absorption spectrophotometric determinations of bismuth in serum and urine.

A sensitive and precise electrothermal atomic absorption spectrophotometric method for determining bismuth concentration is described. Protein precipitation and the use of a palladium modifier reduce the problems of foaming and permit the use of a higher ashing temperature. The detection limit of the assay is 0.9 nmol/L. Total CVs (intra- and interassay) for serum ranged from 3.5% to 15.1% and for urine from 4.8% to 14.5% at concentrations of 60.0 and 6.0 nmol/L, respectively. Analytical recoveries of bismuth added to serum and urine were 102% and 103% over the same range. The method is robust and reproducible and can be accurately calibrated with aqueous standards.

Adult

Immunoalkaline phosphatase with cerium-based cytochemistry for double staining at the transmission electron microscopic level.

Immunoelectron microscopic localization of surface antigens on lymphocytes is possible using alkaline phosphatase combined with cerium-based cytochemical methods. Distinctive electron-dense deposits are easily identified at sites of antibody binding. Mouse splenocytes showing surface immunoglobulin localization and human peripheral blood lymphocytes stained for the MHC-Class II antigen HLA-DR illustrate the results. Double staining for murine Ia antigen by the alkaline phosphatase procedure, combined with immunogold labeling of antigens identified on dendritic cells, i.e., NLDC-145, demonstrates the utility of the cerium cytochemical method.

Alkaline Phosphatase

An assessment of population-based and Bayesian methods to individualize digoxin doses shortly after the start of therapy for atrial fibrillation.

The accuracy of population-based methods and of Bayesian analysis to predict individual digoxin pharmacokinetic variables have been evaluated by their ability to predict a measured peak and trough serum digoxin concentration. We studied 13 digitalized patients (three women) whose mean (range) age and weight was 65.8 (60-78) years and 76.6 (68-101.6) kg and who had stable renal function. The population-based methods (using a clearance of 48.87 + 0.87 x creatinine clearance in ml/h/kg and volume of distribution, in litres, of either 7.3 x weight (kg) or 269 + 3.12 x creatinine clearance) were more than adequate for clinical purposes. The mean prediction errors of a measured steady-state peak concentration from these two population methods were -0.074 and 0.013 microgram/l respectively, whilst those of a measured trough concentration were -0.058 and 0.005 microgram/l. Bayesian analysis, using a sample drawn 11 h after the dose on day five of therapy, gave overall the least biased and most precise of the revised estimates. The mean prediction errors of peak and trough values using this sample were 0.069 and -0.005 microgram/l respectively. As expected, the closer the sample was drawn to the time of the trough concentration the more precise were the Bayesian-derived predictions. The value of the Bayesian technique to individualize digoxin doses could not be validated because it was not possible to distinguish between this and the population methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Effects of statutes requiring psychiatrists to report suspected sexual abuse of children.

OBJECTIVE: Reporting of child sexual abuse is mandatory in all 50 states. Conceptual distinctions between privileged communications and mandatory reporting are reviewed, and the impact of recent changes in Maryland's reporting laws is examined. METHOD: Beginning in 1964 Maryland law required reporting if abuse was suspected when a physician examined a child. In 1988 reporting of disclosures by adult patients about child sexual abuse that occurred while they were in treatment was mandated. In 1989 all patient disclosures, even about such abuse that occurred before treatment, became reportable. During the period of statutory changes, the Johns Hopkins Sexual Disorders Clinic had kept track of adult patients who referred themselves for treatment and adult patients' disclosures of child sexual abuse. This allowed analysis of the impact produced by changes in the reporting requirements. RESULTS: 1) Mandatory reporting of disclosures about prior child sexual abuse deterred undetected adult abusers from entering treatment. The rate of self-referrals when such reporting became mandatory in 1989 dropped from approximately seven per year (73 over a 10-year period) to zero. This may have caused some unidentified children to remain at risk. 2) Mandatory reporting deterred patients' disclosures about child sexual abuse that occurred during treatment. In 1988 the disclosure rate during treatment dropped from approximately 21 per year to zero. This deprived clinicians of information important for early intervention. 3) Mandatory reporting failed to increase the number of abused children identified. The number identified secondary to such disclosures was zero. CONCLUSIONS: Optimal protection of children, as well as treatment for adult patients, may be better accomplished by legislation that supports options other than reporting.

Adult

Tail docking.

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Animal Welfare

Doxazosin in combination with atenolol in essential hypertension: a double-blind placebo-controlled multicentre trial.

Doxazosin (mean dose 11 mg) given once daily in combination with 100 mg atenolol (n = 44) was compared with placebo and atenolol (n = 43) in a double-blind, multicenter study in patients with mild to moderate essential hypertension. In the atenolol/doxazosin-treated group, standing blood pressure significantly decreased by 17.0/12.3 mm Hg compared to 6.2/6.7 mm Hg in the atenolol/placebo group whereas supine blood pressure decreased by 13.2/9.8 mm Hg and 9.2/6.0 mm Hg, respectively in the two groups. Serum lipids did not change significantly in either group. The majority of side-effects reported were mild and transient. This study confirms that doxazosin may be safely combined with a beta-blocker. Doxazosin proved to be well tolerated and effective in patients with blood pressure refractory to atenolol alone.

Adolescent

Outpatient or short-stay skin grafting with early ambulation for lower-extremity burns.

Lower-extremity burns and skin grafts to these wounds have traditionally required extended hospitalization. We have used early tangential excision of the burn wounds and application of an Unna boot to fresh skin grafts in an attempt to shorten the hospitalization for such patients. Over a six-month period, 9 patients were treated with Unna boots to fresh skin grafts on the lower extremity. The average hospital stay was 0.9 days (range, 0 to 3 days). Graft take was 85% to 100%; no regrafting was required. Ambulation was begun 24 hours postoperatively. The technique described is a safe, effective, and inexpensive alternative to prolonged immobilization and hospitalization in patients with lower-extremity skin grafts.

Ambulatory Care

Transforming growth factor beta: a promotor of late connective tissue injury following radiotherapy?

Transforming growth factor beta (TGF-beta) is a peptide which has a fundamental role in controlling proliferation of many cell types. Its main effect upon connective tissues in vivo is to stimulate growth. It can result in endothelial cell proliferation but tends to inhibit epithelial cell growth. Damage to the connective tissues and the vasculature are the principal findings in late radiotherapy damage. Following the initial cellular depletion after radiotherapy, an abnormal proliferation of these tissues occurs, which does not respond to normal feedback mechanisms. Immunocytochemical staining for TGF-beta has been performed upon six patients who had received pre-operative radiotherapy and three patients who had surgery alone for large bowel tumours. Transforming growth factor beta was found in relation to the pathological changes of late radiation damage in the non-tumour-bearing tissues of four out of six previously irradiated patients, but in none of the non-irradiated patients. This paper proposes that TGF-beta activity may modulate late post-radiation changes.

Connective Tissue

Heart rate reactions to standard laboratory challenges and a naturalistic stressor.

Extreme high and low heart rate reactors were selected on the basis of responses to two laboratory stressors; a video game, and mental arithmetic. The heart rates of the same subjects were then recorded during a public speaking competition. Heart rate reactions to this more naturalistic stressor were generally in line with the laboratory-based designations.

Adult

Nadolol in combination with indapamide and xipamide in resistant hypertensives.

Twenty-four hypertensive patients have been studied. All had blood pressure recordings greater than 160/95 mmHg on 3 occasions whilst taking a beta blocker and two other antihypertensive agents in therapeutic doses. Compliance was checked by intermittent urine analysis for the relevant beta-blocker. These difficult to control hypertensives were treated with nadolol alone, nadolol plus indapamide and nadolol plus xipamide each for 2 months in random order. The aim was to reduce the blood pressure to below 160/95 mmHg. The supine blood pressure on nadolol alone (167/100 mmHg) was comparable to that on the previous three drug regimens (157/100 mmHg), the other two treatments were more effective (145/90 and 148/93 mmHg respectively). Hypokalaemia (serum potassium below 3.5 mmol/l) occurred in six individuals but occurred more frequently on xipamide than on indapamide.

Adult

Circadian rhythm in the elderly: a study using a cortisol-specific radio-immuno-assay.

Plasma cortisol levels and diurnal variation have been examined in 30 elderly patients and compared with a control group of 29 middle-aged healthy subjects. The elderly patients had normal plasma cortisol levels which exhibited the diurnal variation seen in the younger age group. In spite of microscopic degenerative changes in the adrenals with age their secretory function and response to hypothalamic pituitary stimulation appear to remain normal.

Age Factors

A pharmacological and in vitro comparison of three oral cephalosporins.

The pharmacology of cephradine, cephalexin and a new oral cephalosporin, cefaclor, has been compared in six volunteers. Cefaclor was absorbed rapidly and was cleared from the serum more rapidly than the other two agents. This was probably partially due to its instability in serum at body temperature, which was investigated. Against a wide range of common pathogens cefaclor was the more active oral cephalosporin. In particular the activity against Neisseria gonorrhoeae and Haemophilus influenzae was of interest.

Administration, Oral