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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 325 records · Page 18Linked to original sources
PubMed1990

Immunophenotype of vascular rejection in renal transplants.

Understanding of the pathogenesis of vascular rejection processes encountered in renal transplants is limited. Although initially and still widely thought to be antibody mediated, it is commonly difficult to demonstrate deposition of immunoglobulin (Ig) in affected arteries. We studied the vascular lesions present in 22 transplanted human kidneys with a panel of antibodies and lectins to evaluate the presence of granulocytes (Leu M1), leukocytes (anti-CD45), B cells (L26), T cells (UCHL-1), monocyte/macrophages (HAM 56), endothelial proliferation (Ulex I factor VIII-related antigen), and smooth muscle proliferation (HHF 35). Active (cellular) vascular rejection showed intimal infiltration of T lymphocytes and monocytes/macrophages (Mac) but not B lymphocytes. Lesions of greater chronicity (reduction in cellularity, increase in intimal stromal matrix) showed progressive diminution of the T cell infiltrate but persistence of Mac accompanied by increased smooth muscle cells. Endothelial alterations were limited to disruption and lifting from supporting stroma by infiltrating inflammatory cells; proliferative changes as detected by increased numbers of cells binding Ulex I were not identified. The cell infiltrates were similar in large (renal artery) and small (interlobular) arteries. Evidence for specific deposition of Ig was not present in cases studied by immunofluorescence studies. These studies suggest vascular rejection is commonly mediated by cellular immune mechanisms and the general supposition equating vascular rejection occurring beyond the peritransplant period with humoral rejection is mistaken. Persistent Mac in chronic lesions may be limited to scavenger functions, but their presence suggests activity in modulating intimal proliferation analogous to current hypotheses for such a role for Mac in atherosclerosis.

Arteries↗
PubMed1990

An evaluation of human chorionic gonadotrophin (HCG) therapy in boys with delayed puberty.

Fifty male patients with delayed pubertal development (chronological age 13.3-17.6 years; bone age 9.5-14 years) were treated with human chorionic gonadotrophin (HCG) 1500-2000 units twice weekly for six months to promote pubertal development and accelerate growth. Response was compared with an untreated control group of 28 patients (chronological age 12.5-17.5 years; bone age 7.0-13.0 years). Forty-four of 46 patients in the treatment group achieved genital stage 3 or 4 by the end of therapy; untreated patients either remained unchanged or advanced only one genital stage during this period. Testicular volumes increased from a median 4.5 ml (range 1-12 ml) to 9 ml (range 3.5-15 ml) in the treated patients. In untreated patients testicular volume increased from 6.0 ml (range 2-10 ml) to 9.5 ml (range 4-20 ml) over the same period. In patients initially growing at less than 7.0 cm/year height velocity increased from 3.9 cm/year (range 0-6.6 cm/year) to 12.7 cm/year (range 8.9-16.8 cm/year) during therapy, falling to 6.0 cm/year (range 0-12 cm/year) in the three-month period immediately following treatment. Patients initially growing at greater than 7.0 cm/year showed variable responses to treatment. Prepubertal patients showed the greatest acceleration in annual growth compared with controls. Treated patients with an initial skeletal age less than 12.0 years showed either a final height (when known) which was less than initially predicted or a significant reduction in predicted height following treatment. Skeletal age greater than 12.0 years was not associated with excess osseous maturation. In conclusion, pre-pubertal children growing at less than 7 cm/year show the greatest benefit from HCG therapy, but final height may be prejudiced if initial bone age is less than 12 years.

Adolescent↗
PubMed1989

Comparison of ultrasound and lateral chain urethrocystography in the determination of bladder neck descent.

Several methods exist to determine the position of the bladder neck, an important mechanism of urinary continence. Radiologic screening is widespread but involves irradiation and may be imprecise. We compared perineal ultrasound scanning and radiologic scanning of the bladder neck by use of a chain and catheter and found good correlation between the two techniques. Ultrasound scanning is preferred, as it avoids irradiation, is accurate, is portable, and is readily available in most gynecologic departments.

Catheterization↗
PubMed1989

Studies of intestinal lymphoid tissue. XII. Epithelial lymphocyte and mucosal responses to rectal gluten challenge in celiac sprue.

The immunopathologic, structural, and functional changes within rectal mucosa of known celiac sprue subjects were quantitated during local challenge with a peptic-tryptic digest of gluten. In the celiac sprue patients challenged with 2 g of digest, major effects occurred in lamina propria, submucosa, and local microvasculature. The lamina propria swelling was biphasic, starting 1-2 h after challenge with widespread extravascular deposition of fibrinogen, indicative of increased microvascular permeability, receding by 24 h postchallenge. A rapid fall in mast cells together with granule discharge suggested their involvement in this response. The late-phase swelling (48-72 h) was preceded by a rapid influx of neutrophils and basophils, the latter showing evidence of degranulation beyond 72 h. Reestablishment of vessel lumina, a rise in mast cells, and loss of neutrophils indicated tapering of the inflammatory cellular cascade by 96 h. Lymphocytes, first seen to enter the lamina by 2 h postchallenge, increased progressively, thereby resulting in substantial infiltration between 36 and 96 h. A marked rise in epithelial lymphocytes, maximal at 6-8 h, waned by 24 h. Volumes of surface and crypt epithelium remained constant throughout. In another challenge series with 4 g of gluten digest, electrical potential difference across rectal mucosa decreased significantly 12 h postchallenge, but the associated decreases in net sodium and chloride absorptive fluxes were insignificant. It is concluded that rectal mucosa is sensitized to gluten in celiac sprue disease and thus offers a promising and convenient in vivo substrate for investigative and diagnostic purposes.

Adult↗
PubMed1989

Asymptomatic bacteriuria in normal and high-risk pregnancy.

A routine urine culture was performed in 1130 normal pregnant women and in 211 high-risk pregnancies (136 diabetics and 75 women with a previous urinary tract infection). Asymptomatic bacteriuria was found in 5.9% of the normal pregnancies, 12.5% among the diabetics and in 18.5% of the previous urinary tract infection patients. The higher incidence of a clinical urinary tract infection among patients with asymptomatic bacteriuria was found statistically significant (p less than 0.001) in all three groups. A high correlation was found between a negative urine culture in early pregnancy and the absence of development of cystitis and pyelonephritis in later pregnancy. The incidence of asymptomatic bacteriuria in normal pregnant women who developed cystitis later in pregnancy was 33.3% and in those developing pyelonephritis, 66%. In the two high-risk pregnancy groups, the incidence of asymptomatic bacteriuria among those developing clinical infection was even higher, 58.3 and 85.7%, respectively, among the diabetics, and 60 and 66.6% respectively, among the previous urinary tract infection patients.

Bacteriuria↗
PubMed1989

Electroconvulsive therapy.

Electroconvulsive therapy (ECT), introduced in 1938 by Cerletti, has been of value in the treatment of depression in spite of the use of stimuli which were usually standardized and the wide variation in the inter-electrode impedance and in the resistivity of the tissues traversed. Accurate measurement of the peak current and the peak voltage in a large number of treatments has shown the need for a considerable choice of constant current values. The lack of measurements accounts for much of the variability in the clinical results.

Animals↗
PubMed1989

Localization of tissue factor in the normal vessel wall and in the atherosclerotic plaque.

Tissue factor (TF)-producing cells were identified in normal human vessels and atherosclerotic plaques by in situ hybridization and immunohistochemistry using a specific riboprobe for TF mRNA and a polyclonal antibody directed against human TF protein. TF mRNA and protein were absent from endothelial cells lining normal internal mammary artery and saphenous vein samples. In normal vessels TF was found to be synthesized in scattered cells present in the tunica media as well as fibroblast-like adventitial cells surrounding vessels. Atherosclerotic plaques contained many cells synthesizing TF mRNA and protein. Macrophages present as foam cells and monocytes adjacent to the cholesterol clefts contained TF mRNA and protein, as did mesenchymal-appearing intimal cells. Significant TF protein staining was found deposited in the extracellular matrix surrounding mRNA-positive cells adjacent to the cholesterol clefts and within the necrotic cores. These results suggest that deposition of TF protein in the matrix of the necrotic core of the atherosclerotic plaque may contribute to the hyperthrombotic state of human atherosclerotic vessels.

Arteries↗
PubMed1989

The hypertensive effect of synthetic glucocorticoids in man: role of sodium and volume.

In previous studies, administration of adrenocorticotrophin (ACTH; 0.5 mg i.m. b.d. for 5 days) to normal subjects produced an adrenally dependent rise in blood pressure (BP) of some 20 mmHg, accompanied by an increase in cardiac output and an increase in plasma volume. The BP and metabolic effects of ACTH (increase in plasma glucose, fall in eosinophils, increase in body weight and urine sodium retention) were reproduced by infusion of the glucocorticoid (GC) cortisol at rates (6-8 mg/h) which reproduced the blood concentrations of the steroid achieved with ACTH administration. Oral administration (hydrocortisone 200 mg daily) produced similar changes qualitatively, although the cortisol concentrations and increase in pressure (12 mmHg) were less. Plasma volume was increased. To determine the role of urine sodium retention and plasma volume expansion in the hypertension, we gave synthetic steroids to six normal subjects for 5 days, at doses which were calculated to be similar for GC activity, but which had little or no mineralocorticoid (MC) activity. Prednisolone (40 mg/day), methylprednisolone (32 mg/day), triamcinolone (40 mg/day) and dexamethasone (8 mg/day) all produced equivalent GC effects (increase in plasma glucose, increase in total white cell count, fall in direct eosinophil count). There were no MC effects with any of the steroids. Body weight did not increase and urinary sodium excretion increased rather than decreased. Plasma volume (125I human serum albumin) and haematocrit were unchanged. BP rose with all four steroids: systolic BP rose by 13 mmHg with prednisolone, by 9 mmHg with methylprednisolone, by 10 mmHg with triamcinolone, and by 6 mmHg with dexamethasone. Diastolic BP increases were 8, 11, 8 and 7 mmHg, respectively. Thus, neither MC activity nor an increase in plasma volume is essential for steroids to induce an increase in blood pressure. Therefore, screening of synthetic GCs to minimize MC activity will not prevent hypertensive complications.

Adult↗
PubMed1989

Detection of cardiac allograft rejection and myocyte necrosis by monoclonal antibody to cardiac myosin.

Indium 111-labeled monoclonal antibody to cardiac myosin was examined for efficacy in the detection of cardiac graft rejection and rejection-related myocyte necrosis. Heterotopic heart transplants were performed in isogenic and allogenic groups of rats (n = 56). At selected intervals posttransplant, uptake of injected antibody in the donor and native hearts was determined by gamma scintillation scanning. Indium uptake was compared to histologic results graded for the severity of rejection and the presence of myocyte necrosis. The donor heart uptake of labeled antibody was significantly greater in both moderate rejection and severe rejection than in lesser degrees of rejection (P = 0.05). The donor/native heart antibody uptake ratio (AUR) in both severe and moderate rejection were significantly different from no or mild rejection (P = 0.05). In pooled grafts without myocyte necrosis, both the absolute donor heart antibody uptake and the donor/native heart AUR were significantly greater in grafts with moderate or severe rejection than in those with no or mild rejection (P less than 0.001). Among grafts with moderate or severe rejection, those with myocyte necrosis had greater donor heart antibody uptakes and greater donor/native heart AUR than grafts without myocyte necrosis (P less than 0.001). The grade of rejection and the presence of histologic myocyte necrosis appear to be closely related but independent variables, both of which influence antibody uptake. It is concluded that monoclonal antibody to cardiac myosin may be a useful noninvasive tool that could distinguish moderate or severe rejection from lesser degrees of rejection and that could detect the presence of myocyte necrosis.

Animals↗
PubMed1989

Acute hormonal and renal effects of oral dilevalol in normal men.

1. Acute hormonal and renal effects of dilevalol (200 mg), a non-selective beta-blocking drug with vasodilator properties, were compared with placebo in six normal men on constant sodium intake. 2. Control and treatment blood pressures were lower with dilevalol than placebo, although the pattern of blood pressure fall was similar in both. 3. Plasma active renin and aldosterone concentrations were lower on dilevalol than placebo after 4 h of recumbency (P less than 0.05). 4. Total plasma renin, renin substrate, cortisol and atrial natriuretic peptide concentrations were similar on dilevalol and placebo. 5. There were no differences in glomerular filtration rate and no deleterious biochemical or haematological changes on dilevalol or placebo.

Administration, Oral↗
PubMed1989

A clinical study of the dynamics of parasystole.

A mathematical model for pure parasystole and modulated parasystole leads to a number of quantitative predictions. The predictive power of the model is examined by confronting it with data obtained from a 16-year-old symptomatic male born with a ventricular septal defect that was surgically closed at 5 years of age. A diagnosis of ventricular parasystole and inducible ventricular tachycardia was made following a syncopal episode. The physiological variables required by the model to make specific predictions are the sinus and ectopic cycle lengths and the ventricular refractory period. From these three variables, a two-dimensional parameter space is constructed consisting of the ratio of the refractory period to the sinus cycle length and the ratio of the ectopic to sinus cycle length. For any set of parameters, predictions are made concerning the number of sinus beats between ectopic beats. The different behaviors exhibited in the electrocardiographic (ECG) data agree with theoretical predictions.

Adolescent↗
PubMed1989

Prolactin response to TRH is unaltered by pulsatile infusion of LHRH.

Eleven boys with constitutional delay of puberty and 7 patients with hypogonadotrophic hypogonadism underwent standard thyrotrophin-releasing hormone (TRH) tests prior to and following 6 days' pulsatile infusion of luteinizing hormone-releasing hormone (240 ng/kg/pulse). There were no significant differences in basal, peak or incremental prolactin responses to TRH between the 2 groups of patients and there were no differences in the magnitude of prolactin response to TRH in either group of patients during pulsatile therapy when compared with preinfusion responses.

Adolescent↗
PubMed1989

Intimal fibromuscular hyperplasia at the venous anastomosis of PTFE grafts in hemodialysis patients. Clinical, immunocytochemical, light and electron microscopic assessment.

Failure of arteriovenous communications used for chronic hemodialysis was studied during sequential 5-year periods after placement of either endogenous Brescia-Cimino (B-C) fistulas (50 patients) or polytetrafluoroethylene (PTFE, Gore-Tex) grafts (66 patients). Venous stenosis near the anastomosis was the reason for failure in 45% of PTFE grafts compared with 16% of B-C fistulas (p less than 0.001). Failure occurred, on average, 16 months after PTFE graft placement compared with 22 for B-C fistulas (p = NS). Proximal vein segments removed from five failed and two functioning PTFE graft communications were studied using light and electron microscopy and immunocytochemical techniques. All venous segments removed during surgical shunt repair exhibited a marked intimal hyperplasia. The intimal cellular component was almost exclusively smooth muscle. Accumulation of intracellular lipid droplets was not seen. Foam cells as well as extracellular lipid deposits were absent; macrophages and lymphocytes were absent from the zone of proliferation. Ultrastructural examination revealed a large proportion of extracellular matrix surrounding smooth muscle cells in the neointima. Collagen and elastin were present in the extracellular matrix, in greatest concentration deeper in the intima. Closer to the lumen, most of the extracellular volume consisted of proteoglycan. Hemosiderin was absent from the lesions as were consistent signs of luminal and intimal fibrin. Uniform intimal gradients of actin, collagen, and proteoglycan suggest that this is a steadily progressive, rather than episodic, proliferative response. These clinical and histologic observations and an analysis of hemodynamic stresses support the postulate that upstream release of platelet-derived growth factor, and possibly, shear-induced intimal injury stimulate this response. This myointimal proliferative process provides a readily accessible model of fibromuscular hyperplasia in humans; its understanding may lead to effective methods for its prevention and may provide clues to the pathogenesis of arteriosclerosis.

Adult↗
PubMed1989

Observations of interactions of depressed women with their children.

Dysfunctional interactions between mothers with major affective disorders and their children may contribute to the children's high risk of disorder. This study investigated the behavior of mothers with recurrent unipolar depression, bipolar disorder, or chronic medical illness and of normal subjects toward their children during a directly observed conflict discussion task. In addition, lifetime history of depression, current mood, and chronic stress were investigated as predictors of maternal interaction. Unipolar depressed women displayed relatively more negative, less positive, and less task-focused behaviour toward their children. Current mood and chronic stress, more than psychiatric history, contributed to the prediction of interaction style.

Adolescent↗
PubMed1989

The effects of pulsatile GnRH infusion upon the diurnal variations in serum LH and testosterone in pre-pubertal and pubertal boys.

The aim of the present study was to determine the effects of exogenous GnRH pulsatile infusions on the diurnal variations of LH and testosterone secretion which occur in late pre-puberty and early puberty. GnRH infusions were administered to 12 short stature males in pre-puberty or early puberty, over 6-day periods. In 6 patients, GnRH doses of 2.5, 7.5 and 15 micrograms/pulse were used and 24-h profiles of serum LH and testosterone were measured before and at the end of the infusions. In the remaining 6 patients GnRH was administered at a dose of 7.5 micrograms/pulse and profiles between 21.00 and 06.00 h the following day were determined. Pre-infusion profiles demonstrated nocturnal LH and testosterone rises in all patients. Median pre-infusion serum LH prior to midnight was 2.2 U/l (range 1.0-5.4) rising to 3.7 U/l (range 1.9-10.7) during GnRH administration (p less than 0.005). After midnight, median pre-treatment serum LH concentration was 4.3 U/l (range 2.7-7.5) which remained unaltered by GnRH administration (median 4.8 U/l, range 2.9-7.9, p greater than 0.05). Median pre-therapy serum testosterone before midnight was 0.8 nmol/l (range 0.1-7.1) rising significantly (p less than 0.05) to 4.1 nmol/l (range 0.2-8.0). Following therapy, post-midnight median serum testosterone rose from 4.8 (range 0.4-9.4) to 7.0 nmol/l (range 0.5-13.9, p greater than 0.05). Diurnal variation in LH and testosterone secretion, therefore, is maintained during exogenous GnRH administration to pre-pubertal and pubertal boys. Response to exogenous GnRH pulses may be significantly influenced by endogenous GnRH.

Adolescent↗