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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 127 records · Page 7Linked to original sources

The syndrome of hypertension and hyperkalemia with normal GFR (Gordon's syndrome): is there increased proximal sodium reabsorption?

The syndrome of hypertension and hyperkalemia, hyperchloremic acidosis with normal glomerular filtration rate (Gordon's syndrome) is characterised by volume expansion, suppressed renin and reduced mineralocorticoid-induced renal clearance of potassium. The clinical and biochemical defects are aggravated by high salt diet and corrected by low salt diet, leading to the hypothesis of excessive sodium reabsorption in the nephron proximal to where aldosterone acts. In this study, we used lithium clearance as a marker of proximal sodium reabsorption in three patients with Gordon's syndrome, in order to further localise the site in the nephron of defective sodium handling. Fractional excretion of lithium was decreased, and absolute and fractional proximal reabsorption of sodium was increased compared to normal controls. In addition, absolute distal reabsorption of sodium was decreased, consistent with decreased mineralocorticoid activity. Fractional excretion of potassium was markedly decreased and did not rise with increased distal delivery of sodium during saline infusion. However, after severe dietary sodium restriction had elevated plasma aldosterone (lowering plasma potassium levels to normal), fractional excretion of potassium was raised by saline infusion. Reduced lithium clearance in patients with Gordon's syndrome supports the hypothesis of increased proximal sodium reabsorption in this condition.

Absorption↗

Synthesis and characterization of an N-terminal-specific 125I-photoaffinity derivative of mu-Conotoxin GIIIA which binds to the voltage-dependent sodium channel.

An N-terminal, iodinatable photoaffinity derivative of mu-Conotoxin GIIIA, 4-Azido-salicylyl-mu-Conotoxin GIIIA (CTXASA), was synthesized by solid phase peptide synthesis. The binding of 125I-CTXASA to the voltage dependent sodium channel from electroplax of Electrophorus electricus was specific, as demonstrated by saturation binding experiments. Using autoradiography, 125I-CTXASA labeled a protein with a molecular mass of 260 kDa, consistent with the apparent molecular mass of the sodium channel. This labeling could be suppressed by excess of tetrodotoxin and mu-Conotoxin GIIIA.

Affinity Labels↗

Hepatic artery reconstruction for hepatic artery thrombosis after orthotopic liver transplantation.

We evaluated the efficacy of reconstruction of the hepatic artery for intraoperative or postoperative thrombosis in orthotopic liver transplantation. Of 37 grafts with artery thrombosis, 13 (35.1%, 6 intraoperative and 7 postoperative) underwent reconstruction of the hepatic artery. The arterial flow was reestablished and maintained in 5 (38.5%) of the 13. Recurrent thrombosis in the other 8 grafts developed 2 to 24 days (mean, 13.8 days) after transplantation. Reconstruction was successful in 50% (4/8) of the adults, compared with only 20% (1/5) of the children. Satisfactory results were obtained when a definitive cause of thrombosis could be identified. We conclude that early recognition and correction of the cause of hepatic artery thrombosis during or after orthotopic liver transplantation, especially in adults, is often a graft-saving and lifesaving procedure worthy of consideration.

Adolescent↗

Liver transplantation for the Budd-Chiari syndrome.

A retrospective study was performed that analyzed 23 patients who had an orthotopic liver transplantation for the Budd-Chiari syndrome with end-stage liver disease. Patient follow-up was as long as 14 years. The technical considerations relevant to the Budd-Chiari syndrome were discussed. There have been no serious complications of postoperative anticoagulation. Three patients, all of whom died, had recurrence of the Budd-Chiari syndrome. No other patient has had evidence of recurrent Budd-Chiari syndrome on postoperative liver biopsies. One-, 3-, and 5-year actuarial survival was 68.8%, 44.7%, and 44.7%, respectively. It was concluded that orthotopic liver transplantation is the most effective treatment for patients with the Budd-Chiari syndrome and end-stage liver disease.

Adolescent↗

Some aldosterone-producing adrenal tumours also secrete cortisol, but present clinically as primary aldosteronism.

1. Two patients with angiotensin-responsive aldosterone-producing adenoma (APA) and one with adrenal cortical carcinoma demonstrated autonomous secretion of cortisol as well as of aldosterone. 2. The response of cortisol and of aldosterone to ACTH did not differentiate between the two APA which secreted cortisol and the eight which demonstrated normal suppression with dexamethasone. 3. Concurrent autonomous secretion of cortisol as well as aldosterone may occur in patients who present clinically with primary aldosteronism. 4. Biochemical distinctions between adenomas may reflect differences in their cellular composition.

Adenoma↗

Suppressor calcium infusion raises plasma atrial natriuretic peptide concentrations in humans.

1. Calcium was infused in normal subjects in subpressor dosage to examine the effects of raised calcium levels on atrial natriuretic peptide (ANP) concentrations. 2. Calcium infusion progressively raised serum ionized and total calcium concentrations significantly, without raising mean arterial pressure or heart rate. 3. Plasma ANP concentrations increased significantly by 5 min of infusion and increased further by 15 min (approximately 40%) to levels which were maintained to 60 min. 4. Urinary sodium excretion increased by 140% during calcium infusion. 5. Calcium may affect secretory as well as contractile functions of the atrial myocyte.

Adult↗

A renin-secreting tumour sensitive to changes in central blood volume (presumably via sympathetics) but not to circulating angiotensin II.

1. A 17 year old female presented with severe hypertension, hypokalaemia and elevated levels of plasma renin activity due to a renin-secreting tumour. 2. Renin was responsive to posture, low sodium diet, saline infusion and frusemide, but relatively unresponsive to raising or lowering circulating levels of angiotensin II. 3. Renal venous renin levels lateralized to the side of the tumour with good contralateral suppression when measured with control of posture and avoidance of prior stimulation, with and without angiotensin converting enzyme inhibition. 4. Levels of atrial natriuretic peptide were elevated and responsive to posture, saline infusion and angiotensin infusion. 5. The tumour was evident on computerized tomography, but not on intravenous pyelography or renal angiography. 6. Responsiveness of renin secretion to normal stimuli in reninoma may make diagnosis difficult, and renal vein sampling under controlled conditions is necessary.

Adolescent↗

Biochemical correction in the syndrome of hypertension and hyperkalaemia by severe dietary salt restriction suggests renin-aldosterone suppression critical in pathophysiology.

1. Plasma potassium and chloride concentrations were raised and plasma renin activity, aldosterone, bicarbonate and arterial pH were reduced in two brothers with the syndrome of hypertension and hyperkalaemia with normal glomerular filtration rate (Gordon's syndrome), on unrestricted or moderately restricted sodium diets. 2. These abnormalities were corrected in both patients within 10 days of severe sodium restriction. 3. Pressor sensitivity to cold and angiotensin II decreased on low sodium diet, associated with a fall in blood pressure. 4. Increasing distal tubular sodium delivery by infusion of normal saline increased fractional excretion of potassium when aldosterone had been stimulated by severely restricted sodium diet, but not when aldosterone levels were low on unrestricted sodium diet. 5. These findings are consistent with excessive sodium reabsorption as the primary renal lesion in Gordon's syndrome, leading to volume expansion and suppression of renin and aldosterone. Severe dietary sodium restriction leading to volume contraction, by stimulating renin and aldosterone and promoting kaliuresis, corrects the abnormalities.

Adult↗

Effect of graded adrenaline infusion on arterial adrenaline clearance in normotensive and hypertensive man.

1. Arterial adrenaline (ADR) levels were measured during graded ADR infusions in normotensives (NT) and in mild hypertensives (HT), in order to test the hypothesis that ADR enhances its own clearance in NT. 2. Although infusion of ADR resulted in similar arterial ADR levels in NT and HT, increases in systolic blood pressure (SBP) and heart rate (HR) and decreases in diastolic blood pressure (DBP) were greater during ADR infusion in HT than in NT. 3. Twenty minutes after cessation of infusion, SBP and HR remained elevated in HT but not in NT. 4. No evidence was found supporting enhanced ADR clearance during increasing ADR levels in NT or HT.

Adult↗

Transplant information management system: a center-oriented approach to transplant data management.

TIMY is the ideal management system for novice data-entry personnel as well as for the research staff, nurses, and physicians at our facility. Access to data through the use of menus and security systems makes TIMY a user-friendly database. It has excellent data export capabilities so that more complex data analysis can be performed using dedicated software such as SPSS/PC, BMDP, or SAS. This provides great flexibility as well as the power needed for the study of complex data sets.

Database Management Systems↗

Immunological characterization and localization of the Na+/Ca2(+)-exchanger in bovine retina.

The sodium/calcium exchanger was purified from bovine retinal rod outer segment membranes and used for the immunization of New Zealand White rabbits. A polyclonal antibody was produced which was found to bind specifically to the 230 kDa Na+/Ca2(+)-exchanger protein as assessed by Western blotting. The antibody did not bind to the high-molecular-weight "rim protein," thereby demonstrating that this protein is distinct from the rod outer segment of Na+/Ca2(+)-exchanger. We used the polyclonal antibody for immunohistochemically localizing the exchange protein in bovine retina. Fluorescent light microscopy revealed intensive immunolabeling of the photoreceptor outer segments, whereas other retinal cell layers exhibited minimal binding. Using the electron microscopic immunogold method, we found specific antibody binding to the extracellular side of rod outer segment plasma membrane. Rod disk membranes, rod inner segments, and cone photoreceptors displayed no significant labeling. We therefore conclude that the Na+/Ca2(+)-exchanger is localized primarily in the rod outer segment plasma membrane, the most appropriate localization considering its proposed role in the process of vertebrate phototransduction.

Animals↗

Analysis of surgical complications after 397 hepatic transplantations.

The results of 397 consecutive orthotopic hepatic transplantations in 333 recipients were reviewed. One or more surgical complications developed in 172 of 323 patients (55 per cent), excluding ten intraoperative deaths. The six month mortality rate among the patients with surgical complications (55 of 172; 32 per cent) was statistically higher than that among patients without such complications (16 of 151; 11 per cent) (p less than 0.001; chi-square, 58.36). Surgical complications included exploratory laparotomy for bleeding or infection in 74 (22 per cent), reconstruction of the bile duct for biliary obstruction or leakage in 55 (17 per cent), external biliary drainage for biliary leakage in four (1 per cent), tracheostomy in 80 (24 per cent), thoracotomy in 12 (4 per cent) and splenectomy in seven (2 per cent). The incidence of biliary obstruction (16 per cent mortality rate) and leakage (48 per cent mortality rate) was 18 per cent (34 of 193) and 2 per cent (four of 193) each after choledochocholedochostomy, which was 3 per cent (five of 187) and 9 per cent (17 of 187) each after choledochojejunostomy. Biliary obstruction (16 per cent mortality rate) was more common after choledochocholedochostomy (p less than 0.005; chi-square, 23.01), whereas the incidence of more serious biliary leakage (48 per cent mortality rate) was higher after choledochojejunostomy (p less than 0.005; chi-square, 8.97). It is concluded that orthotopic hepatic transplantation remains an unforgiving extensive surgical procedure, in which choledochocholedochostomy remains the first-choice reconstruction of the biliary tract because of its lower mortality.

Adult↗

Synthesis and characterization of mu-conotoxin IIIa.

mu-Conotoxin IIIa, a voltage-dependent sodium channel neurotoxin, has been synthesised using solid-phase peptide synthesis employing 9-fluorenylmethoxycarbonyl chemistry. After cleavage from the resin, the peptide was isolated by reverse-phase HPLC and then the six acetamidomethyl groups were removed by treatment with mercuric acetate. The reduced product so formed was purified by reverse-phase HPLC. Protocols were developed to optimize the oxidation of the cysteine residues to form disulphide bonds. Protocols employed using air oxidation together with 2-mercaptoethanol were the most effective. As complete oxidation was never obtained the oxidised peptide was purified by reverse-phase HPLC. The activity of our products was monitored using [3H]saxitoxin binding to eel membranes. The oxidised product was able to completely block [3H]saxitoxin binding in a competitive manner. Lineweaver-Burke analysis of [3H]saxitoxin binding gave a Ki of 1.5 nM, IC50 was determined as 26.6 nM. It was also shown that the pure synthetic mu-conotoxin IIIa had the same retention time on reversephase HPLC as the natural conotoxin IIIa. Thus an active toxin has been synthesised that can be used to probe sodium channels.

Binding Sites↗