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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 163 records · Page 9Linked to original sources
PubMed1989

Catecholamine clearance is not enhanced by increasing levels within the physiological range.

If rising plasma catecholamine levels enhance their own clearance, such a mechanism could be protective, and its absence predispose to hypertension. In normal subjects and in mild essential hypertensives serial increases in plasma noradrenaline (NA) and adrenaline (ADR) generated by intravenous infusion were used to test the effect of rising plasma levels on clearance. Plasma NA and ADR were measured radio-enzymatically, venous clearance of NA by isotopic infusion and clearance of ADR by increment in arterial plasma levels. Serial increases in NA and ADR through the physiological range did not lead to increased plasma clearance: in fact, NA and NA clearance were significantly negatively correlated. For ADR, a circulating hormone, any effect on clearance may be biologically important. Chronic increases in circulating ADR due to mental stress have been suggested as an etiological factor in essential hypertension, working through enhanced noradrenergic transmission. The significance of these findings for NA, a local neurotransmitter rather than a circulating hormone, depends on the extent to which changes in plasma clearance reflect changes in tissue clearance.

Adolescent↗
PubMed1989

Liver transplantation: an unfinished product.

Liver transplantation has become an extraordinarily valuable and useful operation, but one that is not perfect and that has not been exploited to anything like its full potential. Better immunosuppression may become available soon as exemplified by developments with the Japanese drug, FK506. Improved preservation with the UW solution is already here. With these advantages, liver transplantation is certain to become far more widely used than at any time in the past. Examples were cited of innovative approaches using liver transplantation for the treatment of hepatic malignancies.

Animals↗
PubMed1989

[Long-term results of orthotopic liver transplantation during the cyclosporin era. 393 orthotopic liver transplantations accomplished in 313 consecutive patients at the Pittsburgh Transplantation Center].

During the cyclosporine era 1980-1984, 393 consecutive orthotopic liver transplantations (OLT) were performed in 313 patients at the University of Pittsburgh. This paper analyses the long-term results in this group of patients who have been followed-up for a minimum of three years. The results of OLT for different indications are discussed. The five-year survival rates after OLT for metabolic diseases, biliary atresia, primary biliary cirrhosis, posthepatic cirrhosis and primary hepatobiliary cancer are 75%, 68%, 60%, 58.9%, 53.2% and 23.8%, respectively. Recurrence of the primary disease after OLT is rare for benign diseases but rather frequent for malignant ones. The incidence of retransplantation for delayed rejection and for extrahepatic complications is discussed. The quality of life for most of the long-term survivors is good. Because of its good long-term results, OLT should become the therapy of choice in a lot of acute and chronic hepatopathies.

Cyclosporins↗
PubMed1988

Orthotopic liver transplantation for alcoholic cirrhosis.

Fifteen patients with Laennec's cirrhosis underwent orthotopic liver transplantation between 1963 and the end of 1979. The first eight patients died perioperatively or within two months, but four of the next seven patients had long survival; three are still alive after 11 to 14 years. After the introduction of cyclosporine therapy, 41 more patients with alcoholic cirrhosis were treated with liver transplantation from 1980 to June 1987. The one-year survival is 73.2%, and, after one to three years, 28 (68%) of the recipients are living. Of the 35 patients in the combined old and new series who lived for six months or longer, only two returned to alcohol abuse. Social and vocational rehabilitation has been the rule in these recipients who were selected primarily because of urgency of need, because they or their families insisted on treatment, and because they and their families thereby committed themselves to long-standing programs of alcoholism care.

Adult↗
PubMed1988

Occurrence of cytomegalovirus hepatitis in liver transplant patients.

The differential diagnosis of liver dysfunction after orthotopic liver transplantation can be difficult. Cytomegalovirus (CMV) hepatitis is one possibility. This report reviews our experience with 17 cases of pathologically proven CMV hepatitis following liver transplantation and demonstrates the need for percutaneous liver biopsies to establish the diagnosis. There were seven pediatric patients (ages 2-11 years, five males, two females) and ten adult patients (ages 17-53 years, eight males, two females). The most common symptoms were prolonged fever (15 patients, with a mean duration of 22 +/- 5.5 days), elevation in total bilirubin (14 patients), and elevation in liver enzymes (15 patients); all symptoms were also found in rejection. Leukopenia and thrombocytopenia, reported to frequently occur with CMV infection, were found in only three and five patients, respectively. Twelve patients with the above symptoms underwent percutaneous biopsy on one or more occasions to differentiate CMV hepatitis from rejection. The diagnosis was made at retransplantation in five patients. CMV hepatitis followed treatment for acute rejection in 14 patients and occurred without additional immunosuppression in three patients. All patients were maintained on cyclosporine and prednisone. Acute rejection episodes were treated with a 5-day tapering dose of steroids (17 courses in 12 patients), OKT3 monoclonal antibody [Ortho (4 patients)] antithymocyte globulin [Upjohn (2 patients)], and azathioprine (1 patient). CMV was isolated from urine (nine patients), blood (nine patients), throat (seven patients), lungs (two patients), and other organs (two patients). CMV was cultured from the liver biopsy specimens in five of the seven attempts in pediatric patients. When the diagnosis was confirmed in the absence of rejection, immunosuppression was routinely lowered. When rejection occurred concomitantly with CMV hepatitis, therapy had to be individualized. Retrospectively, three patients treated for rejection were noted at retransplantation to have only CMV hepatitis, and all three patients died. A high index of suspicion and the judicious use of liver biopsies is essential in order to differentiate CMV hepatitis from other causes of posttransplant liver dysfunction.

Adolescent↗
PubMed1988

Renal artery reconstruction for harvesting injuries in kidney transplantation with particular reference to the use of vascular allografts.

At the University of Pittsburgh during the calendar year 1986, an arterial injury occurred during harvesting in 20 (7.5%) of the 270 grafts used to perform kidney transplantation (KTx). Four cases required reconstruction, using extension iliac arterial allografts from cadaveric donors of the same blood type; 6 patients, remodelling of the aortic patch in multiple arteries; 4 cases, repairs for injuries to the smaller segmental/polar arteries; 6 cases, a combination of the above techniques. These ex vivo arterial reconstructions are described and the use of donor arterial homografts is emphasized. No deaths have occurred at an average follow-up of 19 months. The postoperative acute tubular necrosis (ATN) rate was significantly higher (90%) compared with non-reconstructed kidneys during the same year (30%). The 1-year graft survival of kidneys undergoing arterial reconstruction (75%) was statistically no different than the overall kidney-transplant survival. Whenever extension iliac allografts were utilized, the cyclosporin-steroid immunosuppression required to control the kidney rejection contributed to the long-term patency rate of the graft. Since the number of organs available for grafting is limited, reconstruction of injured renal vessels has become justified, allowing valuable kidneys to be used that would otherwise be lost.

Adult↗
PubMed1988

Transplantation for primary biliary cirrhosis.

Primary biliary cirrhosis is a frequent indication for liver transplantation. The purpose of this report is to present our experience with liver transplantation for primary biliary cirrhosis. Attention is given to the causes of hepatic dysfunction seen in allografts. In addition, we review the postoperative problems encountered and the quality of life at time of last follow-up in patients with transplants for primary biliary cirrhosis. A total of 97 orthotopic liver transplant procedures were performed in 76 patients with advanced primary biliary cirrhosis at the University of Pittsburgh from March 1980 through September 1985. The transplant operation was relatively easy to perform. The most common technical complications experienced were fragmentation and intramural dissection of the recipient hepatic artery, which required an arterial graft in 20% of the cases. Most of the postoperative mortality occurred in the first 6 mo after transplantation, with an essentially flat actuarial life survival curve from that time point to a projected 5-yr survival of 66%. Common causes of death included rejection and primary graft nonfunction. Thirteen of the 76 patients had some hepatic dysfunction at the time of the last follow-up, although none were jaundiced. Recurrence of primary biliary cirrhosis could not be demonstrated in any of the patients. Antimitochondrial antibody was detected in the serum of almost all of the patients studied postoperatively for it. Most important, almost all of the 52 surviving patients have been rehabilitated socially and vocationally.

Activities of Daily Living↗
PubMed1988

Diagnosis of unilateral renovascular hypertension: comparative effect of intravenous enalaprilat and oral captopril.

The effectiveness of 2 angiotensin converting enzyme inhibitors, intravenous enalaprilat and oral captopril, in stimulating renin secretion was compared in 47 hypertensive patients with suspected renovascular hypertension. Both inhibitors were more effective stimuli to renin secretion than head-up tilting of the patient. In patients with unilateral renovascular hypertension single doses of angiotensin converting enzyme inhibitors increased the renal venous renin ratio compared to the recumbent ratio. This therapy reduced the number of false negative studies more effectively than head-up tilting and was tolerated better. Contralateral suppression of renin in the unaffected kidney, an important ancillary diagnostic marker of unilateral renovascular hypertension, was preserved. No false positive studies owing to the use of angiotensin converting enzyme inhibitors acutely were apparent. Mean arterial pressure decreased by 5 minutes with intravenous enalaprilat and by 20 minutes with oral captopril, and it continued to decrease gradually for at least 2 hours. No significant syncopal symptoms were observed with either inhibitor. Plasma renin activity increased by 5 and 15 minutes with enalaprilat and captopril, respectively. Plasma aldosterone levels decreased by 10 minutes with enalaprilat and by 30 minutes with captopril, and these changes increased in magnitude during the 2 hours of observation. To achieve the maximum diagnostic effectiveness from the renal venous renin ratio, single dose angiotensin converting enzyme inhibitors warrant consideration for routine use. Intravenous enalaprilat may be preferable because of certain achievement of an effective blood level.

Administration, Oral↗
PubMed1988

Experience with Orthoclone OKT3 monoclonal antibody in liver transplantation.

Experience with the use of Orthoclone OKT3 monoclonal antibody for the treatment of acute cellular rejection in a series of 130 human orthotopic liver transplantations is reviewed. Treatment was highly effective in reversing rejection, in reducing the rate of retransplantation, and in lowering patient mortality. OKT3 was also useful for cyclosporine sparing in patients with poor renal function, hypertension, or CNS toxicity. There was a significant incidence of opportunistic infection associated with the use of OKT3.

Adrenal Cortex Hormones↗
PubMed1988

Orthotopic liver transplantation for primary sclerosing cholangitis.

The incidence or diagnostic rate of sclerosing cholangitis is increasing. Because of the lack of effective medical or surgical therapy for patients with end-stage liver disease and sclerosing cholangitis, results with orthotopic liver transplantation were examined. The results of 55 consecutive liver replacements for this disease were reviewed. The 1- and 2-year actuarial survival rates are 71% and 57%, respectively. Orthotopic liver transplantation for end-stage liver disease from sclerosing cholangitis has emerged as the most effective therapy.

Adenoma, Bile Duct↗
PubMed1988

A new Australian kindred with the syndrome of hypertension and hyperkalaemia has dysregulation of atrial natriuretic factor.

A family with the syndrome of hypertension and hyperkalaemia affecting six members in two generations is reported from Australia, where the first two sporadic cases were described. All family members had hyperkalaemia, hyperchloraemia and normal creatinine clearance. Only one affected adult and no affected children were hypertensive, possibly because of habitual low-salt diets. Plasma potassium fell significantly during fludrocortisone acetate administration, and urine potassium increased during saline infusion, consistent with renal tubular responsiveness to mineralocorticoid. Low plasma renin activity and pressor hyper-responsiveness to angiotensin II suggested sodium volume overload, but atrial natriuretic factor (ANF) was normal or only slightly elevated when compared with clearly elevated levels in primary aldosteronism. Plasma ANF was unresponsive to the usually reliable stimulus of angiotensin infusion in the two brothers affected and to saline infusion in one of them. These findings are consistent with a renal tubular avidity for sodium, leading to volume expansion, suppression of renin, and, depending on dietary sodium intake, hypertension. A role for dysregulation of ANF in the pathophysiology is possible.

Aldosterone↗
PubMed1988

Point of view: why hypertension is overdiagnosed and overtreated in 1987.

1. The decision whether arterial blood pressure (BP) is elevated or normal is usually based on inadequate data: few readings in the presence of great variability of BP; levels higher in the presence of the doctor; and diastolic BP often higher sitting and standing than lying. 2. Assessments of response and of the need for increases in drug dosage are also based on insufficient data. 3. Increased morbidity and mortality from stroke and heart attack, and incomplete correction with treatment have been interpreted as suggesting further benefit from aggressive reduction of BP to 'normal' in all patients. 4. The emergence of powerful drugs with few side-effects, and the promise of lowering office BP to 'normal' as monotherapy, has removed the hesitation to treat 'mild' hypertension. 5. Attempts to lower sitting office diastolic BP to 'normal' have led to increasing drug dosage, dose-related, drug-specific side-effects, and lethargy due to hypotension. 6. Newer self-measurement BP units can be used easily by most patients, cost less than five visits to the doctor and provide a cheap method of obtaining sufficient data on which to base informed management decisions. Supported by normal echocardiographic left ventricular mass, normal 'home BP' (including lying diastolic) permits many mild hypertensives to remain off medications. 7. Non-drug therapy avoids or reduces long-term drug therapy, with its side-effects.

Antihypertensive Agents↗
PubMed1988

Response of atrial natriuretic peptide to adrenaline and noradrenaline infusion in man.

1. Atrial natriuretic peptide (ANP) levels were significantly increased during both adrenaline and noradrenaline infusions, in the physiological range, in normal subjects and in patients with essential hypertension. 2. During adrenaline infusion significant increases in both circulating adrenaline and noradrenaline levels were observed. Mean arterial pressure was unaltered. Changes in heart rate were not significant. 3. During noradrenaline infusion, significant increases in circulating noradrenaline and mean arterial pressure were also observed. Heart rate and plasma adrenaline levels were unaltered. 4. Fluctuations in sympathetic nervous system activity may be involved in the regulation of ANP via adrenoceptor stimulated release of ANP. Other known regulators such as atrial stretch and increasing heart rate may modify this response.

Atrial Natriuretic Factor↗
PubMed1988

Effects of volume expansion and contraction on plasma levels of atrial natriuretic peptide in man.

1. Effects of saline infusion and blood removal on atrial natriuretic peptide (ANP) in normal subjects were examined in order to better define the magnitude of acute central volume regulatory influences on ANP. 2. Plasma ANP levels increased progressively during volume expansion with saline infusion, increasing by 18% after 30 min and by 93% after 120 min, and did not change during recumbency alone. 3. Plasma ANP levels immediately after a standard blood donation performed semirecumbent were significantly lower than before blood donation; they fell by 18%. 4. The magnitude of the fall in ANP induced by blood donation correlated significantly with basal plasma ANP. 5. In man, ANP responds to both increases and decreases in central blood volume, consistent with a role for ANP in blood volume homeostasis.

Adolescent↗
PubMed1988

Adrenal transitional zone steroids, 18-oxo and 18-hydroxycortisol, useful in the diagnosis of primary aldosteronism, are ACTH-dependent.

1. The adrenal cortical 'hybrid' steroids 18-oxocortisol (18-OF) and 18-hydroxycortisol (18-OHF) are elevated in patients with typical angiotensin-unresponsive aldosterone-producing adenoma (AII-unresponsive APA) and fall to normal following surgical removal of the adrenal containing the tumour. Since 18-OF was six times the upper limit of normal pre-operatively, the tumour was the site of overproduction of hybrid steroids. 2. The failure of angiotensin-responsive APA to overproduce the hybrid steroids may be linked to their more 'normal' production of cortisol, which falls significantly on removal of the tumours. 3. Hybrid steroid levels were also normal in patients with idiopathic hyperplasia of the adrenals (IHA) and in low renin essential hypertension. 4. In AII-responsive APA, glucocorticoid-suppressible hyperaldosteronism (GSH) and IHA, the hybrid steroids showed brisk responses to stimulation by ACTH and suppression by dexamethasone of endogenous ACTH. 5. Long-term suppression by dexamethasone of hybrid steroids in GSH is consistent with ACTH dependence, rather than angiotensin dependence. 6. Studies of the regulation of hybrid steroid secretion in various categories of hypertension will further define the biosynthetic distinctiveness which is already useful diagnostically.

Adrenal Glands↗
PubMed1988

Altering angiotensin levels by administration of captopril or indomethacin, or by angiotensin infusion, contributes to an understanding of atrial natriuretic peptide regulation in man.

1. Plasma atrial natriuretic peptide (ANP) levels were positively correlated with plasma renin activity (PRA) levels, when blood volume and blood pressure (BP) were not raised in normal subjects (NLS) or patients with postoperative aldosterone-producing adenoma (APA), Bartter's syndrome (BS), Addison's disease, anorexia nervosa, diuretic abuse or salt-losing congenital adrenal hyperplasia. 2. Angiotensin II infusion raised ANP levels in NLS, and patients with BS, pre- and postoperative APA, only when BP rose, suggesting that this effect might be mediated by the rise in BP. 3. Captopril lowered aldosterone and ANP levels in renal artery stenosis, but falling BP levels could mediate this effect. Captopril lowered aldosterone and BP in BS, but did not lower ANP, perhaps because angiotensin remained elevated. 4. Indomethacin lowered ANP when PRA was initially normal or raised (NLS and BS), but not when PRA was suppressed (APA). This effect could not be mediated by BP, which rose, but could be mediated by renin-angiotensin, which fell. 5. Factors other than central blood volume and atrial stretch may modulate ANP levels. Plasma angiotensin II may be such a factor, and may exert an important influence at high levels, especially when blood volume is low.

Adolescent↗
PubMed1988

Glucocorticoid-suppressible aldosteronism: a disorder of the adrenal transitional zone.

Glucocorticoid-suppressible aldosteronism (GSA) is a rare form of hyperaldosteronism in which the increased secretion of aldosterone and the elevation of blood pressure are corrected when ACTH secretion is suppressed. Two 17-hydroxylated analogs of 18-hydroxycorticosterone and aldosterone, 18-hydroxycortisol and 18-oxocortisol, which had been identified in the urine of patients with hyperaldosteronism due to an adrenal adenoma and in bullfrog adrenal tissue incubated with cortisol, are produced in greater than normal quantities in patients with GSA. The excretion of 18-hydroxycortisol and 18-oxocortisol in nine patients with GSA was 2914 +/- 923 (+/- SD) nmol/day [1108 +/- 351 micrograms/day; normal, 165 +/- 94 nmol/day (63 +/- 36 micrograms/day)] and 141 +/- 77 nmol/day [53 +/- 29 micrograms/day; normal, 3.2 +/- 2.4 nmol/day (1.2 +/- 0.9 micrograms/day)], respectively. The excretion of aldosterone 18-oxoglucuronide was 53 +/- 18 nmold/day [19.4 +/- 6.8 micrograms/day; normal, 16.9 +/- 7.5 nmol/day (6.1 +/- 2.7 micrograms/day)]. Aldosterone excretion was elevated in six patients and within the normal range in three patients. The degree of abnormality in 18-hydroxycortisol and 18-oxocortisol excretion was significantly greater than that in aldosterone. Dexamethasone administration decreased excretion of the three steroids to the normal range. ACTH administration for 3 days resulted in an exaggerated increase in the excretion of these steroids, suggesting ACTH dependence of these steroids in patients with GSA. The excessive production of these steroids, which are 17- and 18-hydroxylated, indicate that they are produced by hybrid-type cells which we have called transitional cells, which are also capable of producing aldosterone. These findings are consistent with the postulate that cytochrome P-450-corticosterone methyl oxidase fails to disappear normally in the zona glomerulosa cells as they migrate to the zona fasciculata and acquire 17-hydroxylase activity. This abnormality explains the supernormal conversion of cortisol to 18-hydroxycortisol and 18-oxocortisol and the ACTH dependence of aldosterone secretion in GSA.

Adolescent↗