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Biomedical subjects

M T Jones

Publications and source records attributed to M T Jones.

At least 55 records · Page 3Linked to original sources
PubMed1988

Effect of difluoromethylornithine on the LH surge and subsequent ovulation in the rat.

Female Wistar-derived rats with regular oestrous cycles were injected s.c. at 15.00 h on pro-oestrus with difluoromethylornithine (DFMO), a specific inhibitor of ornithine decarboxylase. The drug (10-100 mg/rat) caused a dose-related reduction in the concentration of LH in plasma taken at 19.00 h (the time of the peak of the LH surge in this colony). There was also a dose-related reduction in the pituitary content of total polyamines. The reduction in the plasma concentration of LH was not due to the shifting of the time of the peak of the surge, as concentrations were significantly lower than control from 17.00 to 21.00 h, the overall reduction in total LH release being approximately 50%. The number of ova in the oviducts at 06.00 h next morning was significantly reduced by treatment with 50 mg DFMO/rat, by an average of 70%. Injection of DFMO enhanced the fall in plasma oestradiol concentrations seen between 15.00 and 19.00 h, in a dose-related manner. It also prevented the rise in progesterone concentrations seen in control animals during this period. The ability of DFMO to prevent the rise in plasma concentrations of LH was not secondary to the effects of the drug on ovarian steroid production because DFMO also significantly reduced the LH surge in animals ovariectomized on dioestrus and given appropriate replacement injections of oestradiol and progesterone.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

A new model for assessment of lung preservation.

No completely satisfactory experimental model exists to compare different techniques of preservation currently used in the distant procurement of a lung allograft. A canine model of left lung transplantation is described in which an inflatable cuff is placed around each pulmonary artery. Each cuff is connected to a subcutaneous reservoir, which allows alternate occlusion of either pulmonary artery. Functional assessment of lung function is made during ventilation of both lungs and after a 10-minute period of perfusion to the native lung alone and then to the transplanted lung alone. Systemic and pulmonary artery pressures are recorded continuously, and measurement of arterial blood gases and oxygen uptake are made immediately after the operation and again at 3 days. The animal is then put to death and the lungs are excised and weighed. Five dogs underwent transplantation of the donor lung immediately after excision (mean ischemic time = 55 +/- 7 minutes). Similar values for oxygen tension and oxygen uptake were obtained postoperatively for the right lung (oxygen tension = 420 mm Hg, oxygen uptake = 101 ml/min) and the left lung (oxygen tension = 368 mm Hg, oxygen uptake = 108 ml/min). However, carbon dioxide tension was elevated (right lung = 41 mm Hg, left lung = 52 mm Hg). Mean pulmonary artery pressure increased during allograft perfusion (right lung = 14 mm Hg, left lung = 24 mm Hg), although systemic blood pressure was unchanged. Similar results were observed at 3 days. The mean weight of the native lung was 101 +/- 2 gm and that of the transplanted lung, 128 +/- 6 gm. This model achieves consistent survival and allows serial observations of the functional adequacy of an allograft compared with a normal contralateral lung.

Animals↗
PubMed1988

Experimental and clinical double lung transplantation.

We have previously demonstrated the technical feasibility of an en bloc double lung transplantation in acute canine experiments. We have now conducted survival experiments in cynomolgus monkeys. Profound hypothermia and circulatory arrest were used to avoid the need for cardiopulmonary bypass in these very small animals. Because of the complexities of this technique, few long-term survivals resulted, but these experiments did confirm excellent lung function and satisfactory tracheal healing. On the basis of these experiments, we have performed our first clinical double lung transplantation on a 42-year-old woman with end-stage emphysema caused by alpha 2-antitrypsin deficiency. The patient has returned to normal activities with excellent lung function.

Adult↗
PubMed1988

Management of general surgical problems after cardiac transplantation.

Over a 6-year period at the University Hospital in London, Ont., 101 patients underwent heart transplantation and 5 heart-lung transplantation. The authors review the general surgical problems identified from the charts of 13 of these patients. In the early postoperative period (within 30 days), laparotomy was required for pancreatitis (one), perforated peptic ulcer (two), cholecystectomy (one), pancreatic cyst (one) and appendicitis (one). In addition, a spontaneous colocutaneous fistula and spontaneous pneumoperitoneum occurred; both were managed conservatively. Later, three patients required cholecystectomy; one underwent a below-knee and a Symes amputation for dry gangrene and one surgical correction of a lymphocele. The incidence of surgical problems (13%) indicates an increased susceptibility in this group of patients. Four of the 13 patients died. Pancreatitis is a well-recognized complication of cardiac surgery; it is frequently associated with a normal or only slightly elevated serum amylase level, making a definitive diagnosis without laparotomy almost impossible. Persistence of abdominal signs should signal the need for exploratory surgery. During the early postoperative period and in the absence of multiorgan failure, immediate operation for an acute abdomen is usually successful. Despite the additional risk, cardiac transplantation does not preclude later surgery, but immunosuppression must be continued and carefully monitored.

Abdomen, Acute↗
PubMed1987

Plasma corticotropin-releasing hormone concentrations during pregnancy and parturition.

Plasma CRH was measured in maternal plasma throughout the third trimester of pregnancy, during labor, and postpartum. CRH levels were also measured in arterial and venous umbilical cord plasma samples. In normal pregnant women, plasma CRH increased from 50 +/- 15 (+/- SEM) pg/mL at 28 weeks gestation (n = 41) to 1462 +/- 182 pg/mL at 40 weeks (n = 55) and 1680 +/- 101 pg/mL (n = 65) in labor. Women with pregnancy-induced hypertension (n = 49) had plasma CRH levels significantly elevated above this normal range. Similarly, women who subsequently went into premature labor had raised levels several weeks before the onset of labor. After delivery, plasma CRH returned to normal within 15 h. Total plasma cortisol levels varied little throughout the third trimester, but increased during labor and remained elevated 2-3 days postpartum. There was, therefore, no correlation between plasma cortisol and CRH, implying that this placental CRH is not primarily involved in the control of the maternal hypothalamo-pituitary adrenal axis during pregnancy. The concentrations of CRH in umbilical cord plasma samples were considerably lower than those in the maternal circulation and were close to those in normal nonpregnant adults.

Adolescent↗
PubMed1987

Recovery of the components of the hypothalamo-pituitary-adrenocortical axis in the rat after chronic treatment with prednisolone.

Male Wistar-derived rats (200-250 g) were treated for 14 days with prednisolone 21-sodium succinate at a concentration of 1035 mumol/l in their drinking water. The drug was then replaced with normal tap water and groups of animals were killed at various times during recovery, trunk blood being collected after decapitation. At the same time, hypothalamic slices, anterior pituitary gland fragments and adrenals were removed and their responsiveness assessed by exposure to appropriate stimuli in vitro. Tissues were also extracted to measure changes in content of hormones during recovery. Treatment with prednisolone produced marked reductions in body weight gain, adrenal weight and pituitary ACTH content, but no significant change in hypothalamic corticotrophin-releasing factor (CRF) bio- or immunoreactivity. The ACTH content was restored by 5 days after withdrawal but adrenal weight remained significantly reduced after 9 days of recovery. The responsiveness of the hypothalamus to acetylcholine in vitro was markedly inhibited and was still significantly reduced 7 days after withdrawal. The responsiveness of the anterior pituitary gland to synthetic CRF or arginine vasopressin and that of the adrenal gland to ACTH added in vitro were restored simultaneously after 7 days of withdrawal. In vivo, recovery was assessed by measurement of the response to laparotomy stress. Treatment with prednisolone prevented the increase in the plasma concentrations of ACTH and corticosterone produced by stress, and these responses recovered by 5 days (corticosterone) and 7 days (ACTH) after withdrawal. The abolition of the circadian rhythms of ACTH and corticosterone by treatment was also reversed by 5 days after withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1987

Surgical repair of acquired ventricular septal defect. Determinants of early and late outcome.

Between January 1970 and June 1985, 60 patients underwent surgical repair of postinfarction ventricular septal defect. The preoperative cineangiograms of all patients were reviewed to measure left ventricular ejection fraction and to quantitatively assess right ventricular function by measuring the percentage reduction in right ventricular midcavity diameter. There were 23 early deaths (within 30 days) and 14 late deaths occurring between 1 and 92 months after operation. Of the 23 long-term survivors, 87% are in New York Heart Association Class I or II. The early mortality was significantly higher for inferior infarction (58%) than for anterior infarction (25%). Early mortality was also influenced by the time interval between infarction and operation (under 1 week 41%, over 4 weeks 22%). Early survival was favored by good preoperative right ventricular function; the percentage reduction in right ventricular midcavity diameter was 16.5% +/- 9.5% (mean +/- standard deviation) for the early death group and 26.7% +/- 10.6% for the early survival group. However, the early outcome was not influenced by left ventricular function before operation. Conversely, long-term survival was favored by preserved preoperative left ventricular function; left ventricular ejection fraction was 26.2% +/- 9.3% for the late death group and 35% +/- 8.5% for the late survival group. Long-term survival was not, however, affected by right ventricular function before operation. The results of surgical closure of postinfarction ventricular septal defect have improved between two successive time frames in this series, which is the largest to date.

Aged↗
PubMed1986

The effect of ovine corticotrophin releasing factor (oCRF), bromocriptine and TRH on the secretion of ACTH and alpha-MSH in Nelson's syndrome and Cushing's disease.

The circulating levels of ACTH and alpha-melanocyte stimulating hormone (alpha-MSH) were measured in 9 patients with Nelson's syndrome after the administration of saline, ovine corticotrophin releasing factor (oCRF), bromocriptine or TRH. The concentrations of ACTH were grossly elevated and alpha-MSH levels ranged from undetectable to higher than the normal range. In seven of eight subjects there was a rapid corticotrophic response, but no change in the alpha-MSH level, following oCRF. This response was delayed in one subject. Following oCRF injection, the plasma oCRF profile was variable but circulating oCRF was detectable even at the end of the experiment in all cases. There was no significant change in circulating ACTH or alpha-MSH following either bromocriptine or TRH. Cultured tumour cells from one case of Cushing's disease showed a corticotrophic response but no change in alpha-MSH to oCRF and the response was enhanced by vasopressin. Bromocriptine added to the same tumour depressed ACTH secretion without affecting the output of alpha-MSH. The present data suggest that the tumours in these subjects are responsive to oCRF and arise from corticotrophs rather than melanotrophs.

Adrenocorticotropic Hormone↗
PubMed1986

Effect of beta-propiolactone on blood group antibody detection.

A panel of 50 blood group antibodies covering a range of blood group antigens has been tested in the presence of 0.25% beta-propiolactone as a possible means of reducing infectivity of high-risk HTLV III/HBsAg samples. 11/50 (22%) antibodies could not be detected by the indirect antiglobulin test, and 6/40 (15%) were undetectable by the two-stage papain technique.

Blood Group Antigens↗
PubMed1986

Effect of sodium phosphonoformate on blood group antibody detection.

A panel of 47 blood group antibodies covering a range of blood group antigens has been tested in the presence of 680 mumol concentration sodium phosphonoformate as a putative chemical additive to serum to reduce infectivity of 'high risk' HTLV-III/HBsAg samples. No inhibitory effect could be demonstrated using the indirect antiglobulin test or prepapainized cell test.

Acquired Immunodeficiency Syndrome↗
PubMed1985

A correlative study of the binding of dexamethasone in hypothalamic blocks in vitro with its ability to inhibit the release of bioactive corticotrophin-releasing factor.

Rat hypothalamic blocks incubated in vitro were used to study the characteristics of binding of [3H]dexamethasone and other steroids to cytosolic binding sites. Cytosols prepared following incubation of the tissue with [3H]dexamethasone for 2 h contained specifically bound steroid in amounts that depended upon the concentration of potassium (but not sodium) ions in the extracting buffer. There was an increase in bound [3H]dexamethasone extracted as the potassium ion concentration increased up to 0.1 M, but not beyond. Dexamethasone, when added to hypothalami in vitro caused a biphasic inhibition of bioactive corticotrophin-releasing factor (CRF) release, and the extent of the second phase of inhibition was dose-related. 11-Epicortisol, when added in a 100-fold molar excess over dexamethasone was able to prevent the second phase of inhibition caused by the latter steroid, as in the binding studies it was able to cause a 50% reduction in the binding of [3H]dexamethasone. In the functional studies it was shown that 11-epicortisol was able to "rescue" the tissue from dexamethasone-mediated delayed inhibition of CRF secretion if added to the blocks 30 min (but not later) after the agonistic steroid.

Animals↗
PubMed1985

The measurement and characterisation by high pressure liquid chromatography of immunoreactive alpha-melanocyte stimulating hormone in human plasma.

Immunoreactive alpha-MSH was found in human plasma and in normal subjects ranged from less than 10-45 pg/ml. Plasma alpha-MSH concentrations were within the normal range in 13 out of 15 subjects during the last trimester of normal pregnancy and only just outside the normal range in the remaining two. Elevated plasma alpha-MSH concentrations were found in 6 of the 11 patients with Nelson's syndrome and in 10 of the 11 patients with pituitary dependent Cushing's disease. Separation on high pressure liquid chromatography (HPLC) revealed two major peaks of immunoreactivity. These peaks, which were identified as des-acetyl alpha-MSH and alpha-MSH were similar in size in normal subjects and Cushing's disease. In Nelson's syndrome, on the other hand, there was a greater proportion of des-acetyl alpha-MSH and it is possible that this peptide is secreted from tumour cells of anterior lobe origin. Although there was no correlation between the circulating alpha-MSH and the degree of pigmentation the high concentrations of plasma immunoreactive alpha-MSH in Cushing's disease and the HPLC profiles in Nelson's syndrome could provide useful information as to the localization of the defects in these particular disorders.

Adolescent↗
PubMed1985

Relationship between adrenocorticotrophin bioactivity in blood and cerebrospinal fluid of rhesus monkeys.

Adrenocorticotrophin levels, measured by a cytochemical bioassay, were determined in the plasma and cerebrospinal fluid (CSF) of adult female rhesus monkeys which were ovariectomized and receiving oestrogen replacement therapy. In control monkeys, ACTH bioactivity was found in both CSF (10.2 +/- 1.8 ng/l) and plasma (186 +/- 51 ng/l) in samples taken at 14.00 h (lights on: 07.00-19.00 h). Dexamethasone treatment (0.2 mg/kg) twice daily for 4 days suppressed plasma ACTH levels (52.8 +/- 25.2 ng/l) but had no effect on CSF levels (7.6 +/- 2.7 ng/l). Raising plasma ACTH, either by daily injections of a long-acting preparation of ACTH (1-24) for 6 days or by bilateral adrenalectomy (and subsequently with-drawing cortisol replacement therapy) also resulted in no detectable changes in ACTH levels in the CSF. A regression analysis between ACTH in the plasma and CSF from samples taken throughout the experiments showed no correlation. In contrast, measurement of ACTH by radioimmunoassay, whilst satisfactory for determination of this peptide in plasma, could not identify authentic ACTH in the CSF. It is concluded that bioactive ACTH does not enter the CSF in detectable quantities from either the peripheral vascular compartment or from the animal's own pituitary gland, and that reducing ACTH secretion from the pituitary also has no effect on levels of ACTH in the CSF. This is in marked contrast to other pituitary peptide hormones, including prolactin, which is secreted together with ACTH during 'stress' but which, unlike ACTH, enters the CSF relatively easily.

Adrenalectomy↗
PubMed1984

Effect of hypothalamic neuropeptides on corticotrophin release from quarters of rat anterior pituitary gland in vitro.

The effect of six hypothalamic peptides on the basal release of ACTH and that induced by arginine vasopressin (AVP) or by ovine corticotrophin releasing factor (oCRF) from fragments of the rat anterior pituitary gland incubated in vitro was investigated. Dose-response curves to AVP and to oCRF were obtained, and the response to a low dose of oCRF was potentiated by a low dose of AVP. Basal release of ACTH was not affected by any of the peptides in concentrations in the range 10(-12) to 10(-6) mol/l, and only substance P (SP) and somatostatin (SRIF) inhibited significantly the response to oCRF in a dose-related manner. The responses to a range of doses of oCRF or AVP were reduced by 10(-8) and 10(-6) mol SP or SRIF/l, and to a greater extent by the higher dose. Except in the case of 10(-6) mol SRIF/l on the response to AVP, the response was not further diminished by preincubation of the tissue with the peptide before the stimulating agent was added. The inhibition of the responses to AVP or oCRF by 10(-9) mol SP/l was not potentiated by its combination with either 5 X 10(-10) or 10(-8) mol SRIF/l; the inhibitory effects were merely additive. The results suggest that although SRIF and SP are able to modulate the release of ACTH from the anterior pituitary gland, they do so only at a high concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗