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Biomedical subjects

B Sheridan

Publications and source records attributed to B Sheridan.

At least 91 records · Page 5Linked to original sources
PubMed1990

Studies on the pathogenesis of hypertension in Cushing's disease and acromegaly.

The pathogenesis of the hypertension associated with Cushing's syndrome and with acromegaly is poorly understood. We have investigated the possible roles of sodium retention, activation of the renin-angiotensin system and increased sympathetic nervous system activity in untreated patients. In 11 patients with Cushing's disease, seven of whom were hypertensive, total exchangeable sodium was normal despite increased levels of the mineralocorticoid hormones, 11-deoxy-corticosterone and corticosterone. The renin-angiotensin system was also normal. Cardiac sensitivity to the beta-receptor agonist isoprenaline was increased, but this was not due to an increase in beta-adrenoceptor density. Hypertension in Cushing's disease is neither sodium-dependent nor angiotensin II-mediated, but increased cardiac sensitivity to catecholamines, by increasing cardiac output, may contribute to the pathogenesis of hypertension. In nine patients with acromegaly (three of whom were hypertensive) total exchangeable sodium was elevated. Although no correlation between blood pressure and exchangeable sodium was found, hypertension in acromegaly is probably sodium dependent. No evidence was found for a pathogenetic role for either the renin-angiotensin-aldosterone or the sympathetic nervous system.

Acromegaly↗
PubMed1989

Selective toxicity of purine nucleosides to human leukaemic cells.

The in vitro cytotoxicity of various purine nucleosides and purine enzyme inhibitors, alone or in combination, and of the alkylating agent mafosfamide (Asta Z7557), incubated for 4 and 24 h have been studied in 17 leukaemic cell lines and normal bone marrow (BM). The purine nucleosides and their analogues included: 2'chlorodeoxyadenosine (CdA), 2'deoxyadenosine (AdR), 3'deoxyadenosine (3'AdR) (cordycepin), adenosine (AR), adenine arabinoside (Ara-A), deoxyguanosine (GdR) and guanine arabinoside (Ara-G). Purine enzyme inhibitors included 2-deoxycoformycin (dCF) and 8-aminoguanosine (8-AG). Cytotoxicity was based on inhibition of (i) incorporation of 3H-leucine into cell proteins and (ii) colony forming units--granulocytic/monocytic (CFU-GM) and for mixed cell colonies (CFU-GEMM). Marked and selective inhibition of T-cell growth was shown by the combinations dCF with either AdR or Ara-A, 8-AG and GdR and by CdA or Ara-G alone; these compounds even at high concentrations produced only partial inhibition of the growth of normal bone marrow CFU-GM and CFU-GEMM except for CdA which completely inhibited the formation of CFU-GEMM colonies. The combination dCF + cordycepin and alkylating agent mafosfamide were, however, toxic to all the cell lines at the concentrations employed, as well as to CFU-GM and CFU-GEMM. The high therapeutic index of some of the purine nucleosides with a relatively short exposure time makes them candidates for selective in vitro removal of residual neoplastic cells in autologous bone marrow transplantation (ABMT) for T-ALL.

Adenosine Deaminase Inhibitors↗
PubMed1989

Calcium homeostasis and exercise.

Calcium homeostasis is altered by strenuous physical exercise. The mechanism is unclear. Our study was designed to investigate this relationship, particularly any associated changes in the calcium regulating hormones. Six subjects carried out a strenuous exercise programme for 10 min on a bicycle ergometer. Blood samples were analysed for ionized calcium, total calcium, calcitonin and pH. Plasma parathormone was assayed using a new and very sensitive N-terminal assay. Serum ionized calcium was significantly elevated by exercise at 50% of maximum aerobic capacity (VO2 max). The rise persisted until the late recovery phase, when it fell significantly below resting levels. Plasma parathormone levels were initially depressed by moderate exercise (50% VO2 max.) but were significantly elevated during and immediately after severe exercise. Our results suggest that exercise stimulates the hormonal, osteolytic influences acting on the skeleton, with increases in plasma parathormone and mobilisation of calcium stores. These changes may provide a supply of raw material allowing the osteogenic mechanical forces initiated by exercise to produce a positive skeletal balance. In view of the possible relevance of these findings to the understanding and management of osteoporosis we feel that this area merits further study.

Adult↗
PubMed1989

Partially compensated hypoadrenalism presenting with persistent skin pigmentation.

A 33-year-old female presented in 1966 with striking pigmentation, typical of Addison's disease, and amenorrhea. Endocrine assessment then showed normal basal serum cortisol and urinary hydroxysteroid levels, but serum cortisol did not respond to stimulation with either exogenous ACTH or lysine vasopressin. Steroid replacement treatment was started. Treatment was discontinued by the patient on her own initiative and after some yr she was lost to follow-up. Reassessment in 1986 showed a pigmented patient who had continued in good health. She had a normal basal serum cortisol level with circadian variation. Plasma ACTH levels were high but showed diurnal rhythmicity and suppressed incompletely with 2 mg or 8 mg of dexamethasone/24 h. Plasma aldosterone levels were normal and showed appropriate postural changes, but plasma renin levels were high. This patient has an immunological profile of autoimmune disease with positive adrenal, thyroid microsomal and gastric parietal cell antibodies with a history of a premature menopause which may also be of autoimmune origin. She has been seen over a 20-yr period and despite her appearance still has no biochemical evidence of glucocorticoid or mineralocorticoid deficiency. It is suggested that the patient had compensated hypoadrenalism, with serum cortisol levels maintained in the normal range by high plasma ACTH levels and serum aldosterone levels maintained by high renin levels. The long term result of the high ACTH levels was increased skin pigmentation.

Adrenal Insufficiency↗
PubMed1989

Basal and saline-stimulated levels of plasma atrial natriuretic factor in acromegaly.

We have studied plasma ANF before and after a 4-h intravenous infusion of normal saline in eight subjects with active acromegaly and in eight age and sex-matched control subjects. Plasma ANF, serum aldosterone and blood pressure were measured basally and after 2 and 4 h and plasma renin activity basally and after 4 h. Basal plasma ANF was similar in each group (4.4 +/- 1.5 pmol/l (mean +/- SEM) in acromegalic subjects and 5.3 +/- 0.7 pmol/l in controls NS). Plasma ANF did not rise significantly after saline in the acromegalic group (2-h value, 5.9 +/- 0.9; 4-h value, 5.1 +/- 0.9 pmol/l) but did rise significantly in the control group (2-h value, 8.9 +/- 1.9; 4-h value 9.5 +/- 1.3 pmol/l, both values P less than 0.05 vs basal level). The 4-h ANF value was significantly higher in the control group than in the acromegalic group (P less than 0.05). Basal and stimulated serum aldosterone values were similar in the two groups. Plasma renin activity suppressed to a lesser extent in the acromegalic group after 4 h. The facts that basal plasma ANF was not raised in acromegalic subjects and did not respond to saline stimulation demonstrate that an abnormality of ANF control may be an important factor in the aetiology of the expanded sodium status of patients with acromegaly and hence may contribute to the hypertension seen in patients with growth hormone excess.

Acromegaly↗
PubMed1989

Plasma ACTH responses to cortisol infusion are similar in patients with primary hypoadrenalism and patients studied some years after bilateral adrenalectomy for Cushing's syndrome.

It has been suggested that the first-phase feedback of steroid feedback on ACTH secretion is abnormal in Cushing's disease patients studied after adrenalectomies. We have performed hydrocortisone infusions (100 mg over 2 h) in 15 patients who had previously undergone bilateral adrenalectomy for Cushing's disease. None had had any pituitary-directed therapy and none had a pituitary macroadenoma. Their responses were compared with a group of seven hypoadrenal patients. A significant rise in serum cortisol was observed between 5 and 10 min in both groups. The first significant fall in ACTH occurred between 30 and 45 min in both groups. There was no abnormality of first-phase feedback in the Cushing's group and our results do not therefore support previous speculation that such an abnormality provides evidence for a higher central nervous system (CNS) aetiology of Cushing's disease.

Adrenal Insufficiency↗
PubMed1989

Bilateral inferior petrosal sinus sampling as a routine procedure in ACTH-dependent Cushing's syndrome.

Bilateral inferior petrosal sinus sampling was successfully performed in 12 of 13 consecutive patients with ACTH-dependent Cushing's syndrome. Ten of the patients subsequently had transsphenoidal pituitary microsurgery. Eight patients in whom the inferior petrosal sinus to peripheral vein ACTH level ratio was 1.5 or greater were found to have a pituitary adenoma. One of the remaining two patients who had ratios less than 1.5 had pituitary hyperplasia while the other had no identified abnormality. In five of the patients with pituitary tumour a ratio above 1.5 was present on only one side. Bilateral petrosal sampling is therefore always necessary. Tumour localization within the pituitary was only poorly predicted by either petrosal sinus sampling (four of eight) or computed tomography scanning (three of eight). If petrosal sinus sampling is used early in the differential diagnosis of ACTH-dependent hypercortisolism, then the use of other differential diagnostic tests may not always be necessary.

Adenoma↗
PubMed1989

Variations in the plasma concentration of atrial natriuretic factor across 24 hours.

There is little information available concerning the presence or absence of a normal variation in the circulating concentration of atrial natriuretic hormone throughout a 24 h period. We have examined this in 8 normal subjects (aged 23-35 years) on a fixed 120 mmol Na+ diet. Circulating levels of ANH, plasma renin activity, serum aldosterone and serum cortisol were determined two-hourly during 24 h in a supine position. There was a significant change in the concentration of each of these four hormones during the study period (P less than 0.05). ANH: peak 8.5 (22.00 h), nadir 4.0 (12.00 h) (pmol/l); PRA: peak 1.7 (04.00 h), nadir 0.8 (22.00 h) (microgram.l-1.h-1); aldosterone: peak 350 (14.00 h), nadir 143 (22.00 h) (pmol/l); cortisol: peak 346 (08.00 h), nadir 51 (22.00 h) (nmol/l). Peak plasma ANH occurred at 22.00 h and with the exception of times 20.00 h and 10.00 h this value was significantly higher than all the other time means (P less than 0.05). The only other significant differences were between plasma ANH at 20.00 h and 06.00 h, 08.00 h, 12.00 h and 14.00 h, respectively (P less than 0.05). From midnight until 18.00 h, there was no significant difference between any of the time means. There was a peak in PRA at 04.00 h, while peak serum aldosterone and serum cortisol occurred at 14.00 h and 08.00 h, respectively. This study suggests that ANH may display a diurnal rhythm. Our findings provide further physiological evidence that plasma ANH and PRA may have a reciprocal relationship.

Adult↗
PubMed1989

A weight-related intravenous dexamethasone suppression test distinguishes obese controls from patients with Cushing's syndrome.

To establish a rapid test for Cushing's syndrome we measured serum cortisol during and following iv dexamethasone infusion (5 micrograms.kg-1.h-1 for 5 h from 10.00 h) in simple obesity (N = 19) and in Cushing's syndrome (N = 12). We had first established that 5 micrograms.kg-1.h-1 was the lowest dose which consistently lowered serum cortisol in simple obesity. In obesity, serum cortisols ranged from undetectable (less than 30) to 48 nmol/l at 17.00, less than 30 to 37 at 19.00 and less than 30 to 38 at 08.00 h the following day. Serum cortisol at these three times did not show any overlap between simple obesity and Cushing's syndrome. Having established these findings we proceeded to study a group of patients with polycystic ovarian disease. These patients behaved differently. Their values at 17.00 and 19.00 h did not overlap those of Cushing's syndrome. However, at 08.00 h, 5 of the 7 had values within the range seen in Cushing's syndrome with a mean of 290 +/- 99 nmol/l. In conclusion, 17.00 and 19.00 h serum cortisol levels distinguish between Cushing's syndrome and both simple obesity and polycystic ovarian disease. However, in the latter, cortisol suppression is less prolonged than in simple obesity. This finding may be important for our understanding of the pathogenesis of the disease.

Adult↗
PubMed1989

Relationship between basal and sodium-stimulated plasma atrial natriuretic factor, age, sex and blood pressure in normal man.

The relationships between plasma atrial natriuretic factor (ANF), blood pressure (BP) and age have not been clearly defined. We measured plasma ANF levels and BP in 128 normal subjects (65 male; 63 female; mean age 48 years, range 20-87 years) on no medication. In subjects of 75 years or less (n = 120) plasma ANF was 5.7 +/- 0.3 pmol/l (mean +/- SEM). Plasma ANF did not differ between sexes (males 5.6 +/- 0.4 pmol/l, females 5.9 +/- 0.4 pmol/l). There was a positive correlation between plasma ANF and age, correlation coefficient (r) = 0.46, systolic BP (r = 0.44), diastolic BP (r = 0.22) and mean BP (r = 0.37) (all P less than 0.01), but after multiple linear regression analysis plasma ANF only related significantly (P less than 0.01) to age and systolic BP once other factors had been excluded. We also measured plasma ANF after erect and supine posture and during a 21IV normal saline infusion given over 4 hrs (n = 24; age range 21-62 years) after an overnight fast. Mean plasma ANF was 5.9 +/- 1.1 pmol/l erect, 7.4 +/- 1.6 pmol/l supine and rose to 10.1 +/- 1.4 pmol/l after saline (both P less than 0.05 vs basal). Response to saline was assessed as the area under the curve of hourly measurements. Neither this nor peak ANF during saline infusion correlated with age. We conclude that basal plasma ANF is influenced by age and systolic BP but plasma ANF response to acute saline stimulation is not.

Adult↗
PubMed1989

Effects of low-dose marine oils on intimal hyperplasia in autologous vein grafts.

The effects of low-dose cod-liver oil on intimal hyperplasia of vein grafts were examined in 45 adult mongrel dogs undergoing peripheral arterial reconstruction. Fifteen animals served as the control group, 15 animals were fed a fish-oil supplement containing 240 mg of eicosapentaenoic acid daily, and a further 15 animals received 480 mg of eicosapentaenoic acid daily. Segments of undistended external jugular vein were anastomosed to bilaterally divided femoral arteries. The grafts were harvested at 6 weeks and intimal thickness was measured with a computerized interactive image analyzing system. Serum cholesterol level, prothrombin time, partial thromboplastin time, bleeding time, and platelet counts were measured before the operation and at 2, 4, and 6 weeks after the operation. Plasma levels of thromboxane B2 and prostaglandin F1 alpha and serum levels of eicosapentaenoic acid were measured before and 4 weeks after the operation. Serum cholesterol level increased similarly and significantly in all animals. Serum levels of eicosapentaenoic acid rose proportionately with the oral ingestion of fish oil but did not affect coagulation parameters. Plasma thromboxane B2 and prostaglandin F1 alpha were not significantly affected by the ingestion of marine oils. Intimal thickness was 39 +/- 5 microns in the control dogs. Ingestion of 240 mg of eicosapentaenoic acid reduced intimal thickness to 24 +/- 3 microns at 6 weeks (p less than 0.01). Increasing the dose by a factor of 2 did not decrease intimal thickness further, the intima being 23 +/- 2 microns (p less than 0.005). Our data indicate that small doses of fish oil will reduce intimal proliferation in autologous vein grafts and that marine oils may exert their beneficial effects on intimal hyperplasia by a mechanism other than their known effects on prostanoid metabolism.

Animals↗
PubMed1988

Cyclical Cushing's syndrome presenting as short stature in a boy with recurrent atrial myxomas and freckled skin pigmentation.

A young male patient demonstrated unusual features of Cushing's syndrome, atrial myxomas and freckled skin pigmentation. At 4.5 years of age he presented with intermittent swelling of his face and abdomen associated with weight gain and mild hypertension. A left atrial myxoma, suspected from routine physical examination, was surgically removed at 6.1 years of age. The initial mild symptoms clinically thought to be due to Cushing's syndrome, persisted intermittently without any consistent biochemical abnormality. At 10 years of age height velocity decreased and at 12 years early osteoporosis was observed radiologically. Repeated dexamethasone tests revealed a paradoxical increase in cortisol and corticotrophin from normal basal levels. Further investigation showed a cyclical pattern of hypercortisolism. The removal of a pituitary microadenoma failed to correct the features of Cushing's syndrome or prevent intermittent hypercortisolism. At 15.3 years a second left atrial myxoma was removed. This was followed by bilateral adrenalectomy. Histologically the features were consistent with primary pigmented nodular adrenocortical disease. This is the first patient described with cyclical Cushing's syndrome as part of this unusual complex of disorders.

Child, Preschool↗
PubMed1988

Conventional dose intravenous pulsatile GnRH therapy does not induce ovulation in polycystic ovarian disease.

The value of pulsatile GnRH therapy for induction of ovulation in patients with polycystic ovarian disease remains unclear. Intravenous pulsatile GnRH therapy was administered to a defined group of 5 patients with polycystic ovarian disease; all were infertile, had an LH:FSH ratio of greater than 2:1 on two or more occasions, and had multiple cysts on ovarian ultrasonography. All had failed to respond to clomiphene citrate. The 5 patients received increasing doses of GnRH (5-40 micrograms/pulse) continuously for up to 6 weeks. The response was evaluated by serial hormone levels and ovarian ultrasonography. During nine treatment periods no patient ovulated, and in only one did the LH:FSH ratio revert to normal. Four patients have subsequently had wedge resection of the ovaries and in each case the diagnosis of polycystic ovarian disease was confirmed. Pulsatile GnRH therapy was of no value in the management of this group of infertile patients with strictly defined polycystic ovarian disease.

Adult↗
PubMed1988

Effect of various low-dose concentrations of verapamil cardioplegia on small-amplitude electrical activity during cardioplegic arrest.

The effect of verapamil cardioplegia on atrioventricular conduction was examined in 19 dogs. During 90 minutes of ischemic arrest, five dogs received multidose potassium cardioplegia, containing 1.2 mg/L of verapamil (group 1), five received potassium cardioplegia containing 600 micrograms/L of verapamil (group 2) and nine animals received cardioplegia containing 300 micrograms/L of verapamil (group 3). Atrioventricular conduction was measured in all groups before bypass, after 90 minutes of ischemia and after 45 minutes of reperfusion. Specially designed plunge electrodes were used to monitor the electrical status of the heart during arrest in group 3 and, in addition, left ventricular function and concentration of high-energy phosphates were determined before and after ischemic arrest. Conduction was prolonged in four group 1 dogs and in two group 2. Atrioventricular conduction was measured in six group 3 dogs; five had prolonged conduction and one experienced second-degree heart block. Small-amplitude electrical potentials were recorded from the myocardium in two of nine dogs in group 3. Persistent electrical activity was associated with continued use of high-energy phosphates and resulted in decreased left ventricular function after 90 minutes of ischemic arrest. Our data indicate that small doses of verapamil will delay atrioventricular conduction and will not prevent small-amplitude electrical activity.

Animals↗