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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 343 records · Page 19Linked to original sources

Dexamethasone suppression in essential hypertension: effects on cortisol and blood pressure.

Hypothalamic-pituitary-adrenal axis (HPA) function was examined in normotensive (n = 20) and hypertensive (n = 16) men, by measurement of basal cortisol levels, diurnal variation and the response to dexamethasone suppression. Comparison between groups did not reveal any differences in basal cortisol concentrations, in their diurnal variation, or in response to dexamethasone suppression. In separate studies, treatment with dexamethasone did not alter blood pressure in normal men (n = 6) but produced a small fall in pressure in hypertensive subjects (n = 8), compatible with the notion that the HPA might contribute to blood pressure elevation in some subjects with essential hypertension.

Adult↗

Biochemical properties of sodium channels in a wide range of excitable tissues studied with site-directed antibodies.

Antibodies against a peptide (SP19) corresponding to a highly conserved, predicted intracellular region of the sodium channel alpha subunit bind rat brain sodium channels with a similar affinity as the peptide antigen, indicating that the corresponding segment of the alpha subunit is fully accessible in the intact channel structure. These antibodies recognize sodium channel alpha subunits from rat or eel brain, rat skeletal muscle, rat heart, eel electroplax, and locust nervous system. alpha subunits from all these tissues except rat skeletal muscle are substrates for phosphorylation by cAMP-dependent protein kinase. Disulfide linkage of alpha and beta 2 subunits was observed for both the RI and RII subtypes of rat brain sodium channels and for sodium channels from eel brain but not for sodium channels from rat heart, eel electroplax, or locust nerve cord. Treatment with neuraminidase reduced the apparent molecular weight of sodium channel alpha subunits from rat and eel brain and eel electroplax by 22,000-58,000, those from heart by 8000, and those from locust nerve cord by less than 4000. Our results provide the first identification of sodium channel alpha subunits from rat heart and locust brain and nerve cord and show that sodium channel alpha subunits are expressed with different subunit associations and posttranslational modifications in different excitable tissues.

Animals↗

Heart-rate spectral analysis: a noninvasive probe of cardiovascular regulation in critically ill children with heart disease.

Children may die suddenly and unexpectedly following cardiac surgery, even while receiving intensive medical care, when current noninvasive and invasive monitoring techniques fail to warn us of an impending problem. This report examines the efficacy of heart-rate spectral analysis, a noninvasive method that quantitates the beat-to-beat fluctuations in heart rate, in characterizing and tracking cardiovascular regulatory status. A total of 45 heart-rate fluctuation studies, performed on selected patients, at the bedside, using heart-rate spectral analysis, were retrospectively correlated with clinical events. The spectral pattern of 18 patients who sustained a cardiac arrest differed significantly from the others in the study group (p less than 0.0001).

Adolescent↗

Hormonal responses in pubertal males to pulsatile gonadotropin releasing hormone (GnRH) administration.

Twenty-two boys (9 with delayed puberty and 13 with short stature) ages 12.3 - 17.8 yr, and 10 adult males with idiopathic hypogonadotropic hypogonadism (ages 17.3 - 41.1 yr) have been studied following pulsatile, sc GnRH therapy (240 ng/kg/pulse) over 6 days. Mean pre- and post-therapy LH and FSH concentrations were estimated by 15 min blood sampling over 3-h periods immediately before and at the end of the treatment period. There were significant correlations between the mean pre- and posttreatment LH and FSH concentrations (r = 0.82, p less than 0.001 and r = 0.51, p less than 0.02, respectively) for the 2 groups of peripubertal boys when assessed together. Nine of the 10 adults with hypogonadism showed proportionately greater gonadotropin increments following pulsatile therapy when compared with the peripubertal boys. Standard bolus GnRH tests (100 micrograms iv) did not differentiate between the three groups of patients before pulsatile GnRH therapy. Bolus GnRH tests could predict the subsequent response to pulsatile therapy in the peripubertal boys only. There was no significant change in LH increments following the GnRH bolus tests in either group, after pulsatile GnRH administration (p greater than 0.1). Early response to pulsatile GnRH administration is dependent upon the maturity of the hypothalamic-pituitary-testicular axis in males with delayed puberty or short stature. Patients with hypogonadotropic hypogonadism do not show this relationship.

Adolescent↗

Predictive value of computerized tomography in the presurgical evaluation of primary carcinoma of the cervix.

To determine the predictive value of abdominal-pelvic CT scan in assessing pelvic and paraaortic node metastases in untreated cervical carcinoma, the preoperative CT scans of 61 patients were compared with the gross and microscopic surgical findings. Although 75% of enlarged pelvic nodes on CT contained metastases, and 97% of patients with negative pelvic nodes had negative CT scans (specificity = 97%), histologically positive pelvic nodes were often missed on CT scan (sensitivity = 25%). For paraaortic nodes the CT scan had a specificity of 100% and a sensitivity of 67%. No paraaortic nodes were enlarged in stages I-IIA (0/51). CT scans are recommended for routine evaluation of paraaortic nodes in stages II-IV, but are not warranted in pretreatment evaluation of the pelvic nodes in stage I.

Carcinoma↗

Prolonged hypogonadism in male patients with rheumatoid arthritis during flares in disease activity.

The pituitary-gonadal axis was assessed in 10 male patients during hospital admissions lasting 3-6 weeks (median 3 weeks) for flares for rheumatoid arthritis. Despite significant improvements in the Ritchie indices from median 16 (range 9-23) to 8.5 (range 5-20) (p less than 0.01) and ESR from median 67 mm/h (range 46-115 mm/h) to 58 mm/h (range 15-116 mm/h) (p less than 0.05) there were no significant changes in serum testosterone, LH, FSH, prolactin (PRL), cortisol or androstenedione during the admission periods. At follow-up (median 14 months, range 5-18 months after admission) there were further improvements in articular indices (median 7, range 3-13; p = NS) and ESR (median 20 mm/h, range 4-62 mm/h; p less than 0.05) and rheumatoid factor titres had fallen from median 1/1025 (range 1/126 to 1/1024) to median 1/512 (range 1/64 - 1/512). One patient showed biochemical features of progressive testicular failure. In the remaining patients, serum and derived free testosterone levels were significantly increased (p less than 0.01 respectively) and serum LH reduced (p less than 0.01). There were no changes, at this time, in prolactin, cortisol or androstenedione. Rheumatoid flares appear to be associated with prolonged suppression of testicular function.

Adult↗

Effects of indomethacin on steroid-induced changes in pressor responsiveness in man.

1. It has been shown previously that hydrocortisone (F) increases pressor responsiveness in normal subjects. The present study examined the role of vasodilator prostanoids in determining these changes. 2. Pressor responsiveness to angiotensin II (AII) (1-8 ng/kg per min) and phenylephrine (PE) (0.3-0.9 microgram/kg per min) was examined in six normal men receiving: no treatment (day 1); 100 mg indomethacin p.o. (INDO) in three divided doses over 20 h (day 2); 200 mg F for 5 days, 50 mg 6 hourly p.o. (day 6); F plus 100 mg INDO (day 7). 3. Blood pressure, body weight and plasma glucose rose with F and plasma potassium fell. F alone produced significant increases in response to AII at 2 ng/kg per min, for systolic pressure (SBP), diastolic pressure (DBP) and mean arterial pressure (MAP), and at 1 ng/kg per min for DBP. The threshold for SBP, DBP and MAP rises with AII was decreased by F. Responses to PE following F were greater at 0.6 microgram/kg per min for SBP, DBP and MAP and the threshold for all parameters fell. 4. INDO alone had no significant blood pressure or metabolic effects and no effect on the magnitude of the blood pressure rise with AII, but decreased the threshold dose for effects on MAP. INDO had no effect on the magnitude of the pressure rise with PE, but decreased the threshold dose for effects on SBP. 5. INDO did not modify responsiveness or threshold to AII following F. Responsiveness to PE was unchanged and threshold fell for SBP only during INDO.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Platelet-derived growth factor mRNA detection in human atherosclerotic plaques by in situ hybridization.

Platelet-derived growth factor (PDGF) mRNA, and mRNA for its receptor, have been localized to specific cell types within the human atherosclerotic plaque, using in situ hybridization. The predominant cell types found to express PDGF A and B chain mRNA are mesenchymal-appearing intimal cells and endothelial cells, respectively, with little or no expression detected in macrophages. The distribution of PDGF receptor mRNA containing cells was also examined and found to be localized predominantly in the plaque intima.

Arteriosclerosis↗

Cerebral oedema in diabetic ketoacidosis.

Modern management of diabetic ketoacidosis has reduced mortality of this condition from inevitable death in the pre-insulin era to less than 5% in specialised centres. Most fatalities now reflect the underlying disease which has caused metabolic decompensation, such as acute myocardial infarction, cerebrovascular accident or septicaemia. However patients may still die as a direct result of the metabolic disturbances per se and the rare complication of cerebral oedema in diabetic ketoacidosis is almost invariably associated with fatal outcome.

Adult↗

CT densitometry of pulmonary nodules in a frozen human thorax.

The influence of (1) calcium concentration, (2) exposure technique, (3) reconstruction algorithm, (4) nodule size, and (5) nodule location on the CT attenuation values (CT density) of pulmonary nodules was examined in a frozen human thorax. Nodules with calcium concentrations of 0-310 mg/ml and diameters of either 0.95 or 1.59 cm were inserted into a frozen, unembalmed human thorax. The nodules were placed either at the lung apex or 4 cm below the tracheal carina. Each nodule was scanned on a GE CT 9800 scanner; five different exposure techniques were used. The slice thickness was uniformly 1.5 mm. As expected, increasing the kilovoltage caused a significant decrease in CT nodule density in all nodules with calcium concentrations greater than 80 mg/ml. The inverse relationship between kilovoltage and nodule density was exaggerated with increasing calcium concentration. A high-resolution (bone) algorithm gave a significantly higher CT number than did a smoothed (standard) algorithm, regardless of nodule size and location, but this difference could be attributed almost entirely to the edge-enhancement effect of the bone algorithm. The CT density of the larger nodules was significantly higher than that of the smaller nodules at calcium concentrations greater than 65 mg/ml for both standard and bone algorithms. Densities were significantly higher in the mid lung than in the apex with a standard algorithm, but this was not the case with a bone algorithm. The GE CT 9800 scanner had a linear response between CT density and increasing calcium concentration within the confines of a human thorax. A high-resolution (bone) reconstruction algorithm has higher spatial resolution but does show an edge-enhancing effect not found with the smoothed algorithm. Two major variables in CT densitometry for pulmonary nodules are the kilo electron voltage of the X-ray beam and the reconstruction algorithm used; these two parameters should be standardized, with a high kilovoltage and high-resolution algorithm favored on the GE CT 9800 scanner.

Absorptiometry, Photon↗

Identification of an intracellular domain of the sodium channel having multiple cAMP-dependent phosphorylation sites.

Cyclic AMP-dependent protein kinase catalyzes the incorporation of 3-4 mol of phosphate into the alpha subunit of rat brain sodium channels in vitro or in situ. Digestion of phosphorylated sodium channels with CNBr yielded three major phosphorylated fragments of 25, 31, and 33 kDa. These fragments were specifically immunoprecipitated with site-directed antisera establishing their location within an intracellular loop between the first and second homologous domains containing residues 448 to 630 of sodium channel RI or residues 450-639 of sodium channel RII. Five of the seven major tryptic phosphopeptides generated from intact sodium channel alpha subunits were contained in each of the 25-, 31-, and 33-kDa CNBr fragments, indicating that most cAMP-dependent phosphorylation sites are in this domain. Since CNBr digestion of sodium channels which had been metabolically labeled with 32P in intact neurons yielded the same phosphorylated fragments, the phosphorylated region we have identified is the major location of phosphorylation in situ. Only serine residues were phosphorylated by cAMP-dependent protein kinase in vitro, while approximately 16% of the phosphorylation in intact neurons was on threonine residues that must lie outside the domain we have identified. Since this domain is phosphorylated in intact neurons, our results show that it is located on the intracellular side of the plasma membrane. These results are considered with respect to models for the transmembrane orientation of the alpha subunit.

Amino Acid Sequence↗

Mechanisms leading to hypogonadism in men with burns injuries.

A profound and persistent depression of serum testosterone concentrations was found in 19 men with burns injuries. This could not be explained by changes in sex hormone binding globulin capacity, hyperprolactinaemia, classical primary testicular failure, or a hypogonadotrophic state. Pulsatile release of luteinising hormone was found in control subjects but was absent or diminished in burnt patients with low serum testosterone concentrations. In addition, these patients showed reduced biological activity of luteinising hormone as measured by bioassay even though normal concentrations of luteinising hormone were detected by radioimmunoassay. The temporary hypogonadism after burns injury and possibly in other clinical states may be related to hypothalamic dysfunction, which leads to abnormal generation of luteinising hormone releasing hormone and non-pulsatile secretion of luteinising hormone of reduced biological activity.

Adult↗

Replication of arterial smooth muscle cells in hypertension and atherosclerosis.

Smooth muscle proliferation has been recognized as central to the pathology of both major forms of vascular disease: atherosclerosis and hypertension. Recent advances in our knowledge of the mechanisms of control of proliferation suggest that events occurring in adult animals may recapitulate portions of the developmental biology of the smooth muscle cell. This review will consider the current state of knowledge of the mechanisms controlling smooth muscle proliferation in these 2 diseases, put that knowledge into the context of what is known about smooth muscle biology and offer 2 hypotheses as to possible roles of smooth muscle developmental biology in manifestations of atherosclerosis and hypertension in adult humans.

Animals↗