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Biomedical subjects

R D Gordon

Publications and source records attributed to R D Gordon.

At least 217 records · Page 12Linked to original sources

Kidney transplantation in Pittsburgh: experience and innovations.

1. The introduction of combined CsA and steroid treatment as the baseline immunosuppressive medication significantly enhanced the results of kidney transplantation in our series. But various other preexisting recipient or donor conditions may still have an important effect on kidney transplant survival and should not go unrecognized. 2. Living-related kidney transplants were almost totally abandoned at our institution. Reasons for this approach are the increased availability of cadaveric donor organs, the improved results with cadaveric transplants under CsA and the possible risks to the living donors. 3. Combined liver/kidney transplants have been shown to offer a favorable treatment modality for patients with endstage liver and renal failure. 4. A newly developed center-oriented Transplant Information Management System (TIMY) significantly facilitates the clinical and research tasks in our department. 5. An integrated, computerized scoring system for equitable allocation of donor organs has proven to be highly effective during routine clinical use.

Adolescent↗

The Denver-Pittsburgh liver transplant series.

Liver transplantation is now the preferred treatment for many diseases leading to end-stage liver disease. Transplantation for cancer has been disappointing and there is a significant recurrence rate after transplantation in hepatitis B-virus carriers. Additional strategies will have to be developed if we are to improve the results of transplantation for these patients. The role of immunological factors in liver transplantation continues to reveal significant differences from their role in renal transplantation and will continue to be an interesting area of study for years to come.

Adolescent↗

Clinical considerations in orthotopic liver transplantation.

Progress in immunosuppression, surgical techniques, and perioperative care has promoted orthotopic liver transplantation from an experimental procedure to an accepted clinical treatment. Orthotopic liver transplantation, in turn, has changed the treatment of terminal liver disease from care that is largely treatment of symptoms and support to cure, but at the price of major surgery and life-long immunosuppression. This article reviews the current status of liver transplantation as practiced at the University of Pittsburgh.

Graft Rejection↗

Liver transplantation in patients with patent splenorenal shunts.

Patent distal splenorenal shunts (Warren shunt) have been reported to cause decreases in the portal perfusion pressure and the total hepatic blood flow. Such hemodynamic alterations could have adverse effects on the transplanted liver. The experience with hepatic replacement in four patients with patent Warren shunts is reported. Operative findings were phlebosclerotic portal veins of small size and diminished portal blood flows. Hepatofugal collateral channels created by the construction of the Warren shunt were eliminated by division of the shunt and splenectomy in three patients and splenectomy alone in the other. All patients recovered; thus the presence of a patent Warren shunt should not be a contraindication for hepatic transplantation.

Adult↗

Immunoaffinity isolation of Na+ channels from rat skeletal muscle. Analysis of subunits.

Polyclonal antiserum and monoclonal antibodies raised against the sodium channel from rat skeletal muscle sarcolemma have been immobilized on Sepharose and used to immunoaffinity purify this channel directly from skeletal muscle without the intervening purification of surface membranes. These antibodies isolate a approximately 260-kDa protein from whole muscle, although each purifies predominantly a 150-kDa component when isolated sarcolemmal membranes are used as starting material. A 45-kDa band is also found in the material purified from sarcolemma but not that obtained from whole muscle. In addition, these immunoaffinity columns isolate a 38-kDa band from both whole muscle and sarcolemma that copurifies with the 260-kDa protein. In some preparations this component appears as two closely spaced bands of 37 and 39 kDa. These small subunits coelute with the 260-kDa subunit when thiocyanate gradients are used to displace protein bound to the immunoaffinity columns and behave as integral components of the sodium channel. Estimates of stoichiometry were made for the large and small subunits of the muscle channel protein. After correction for labeling efficiency, values consistent with a ratio of one 260-kDa subunit to one 38-kDa subunit were obtained. We conclude that the rat skeletal muscle sodium channel contains a large alpha subunit of approximately 260 kDa that is sensitive to proteolytic nicking during the isolation of sarcolemmal membranes. In addition, at least one 38-kDa beta subunit is associated with each alpha subunit in the native channel.

Animals↗

Indications for liver transplantation in the cyclosporine era.

One hundred seventy orthotopic liver transplants were performed under conventional immunosuppression with azathioprine and steroids with 1- and 5-year survivals of 32.9 per cent and 20.0 per cent, respectively. Since the introduction of cyclosporine-prednisone therapy in March 1980, 313 primary orthotopic liver transplants have been performed. Actuarial survivals at 1 and 5 years have improved to 69.7 per cent and 62.8 per cent, respectively. Biliary atresia is now the most common indication for liver replacement. In adults, primary biliary cirrhosis and sclerosing cholangitis have become more common indications for transplantation, and alcoholic cirrhosis and primary liver malignancy as indications have declined. Early enthusiasm for liver transplantation in patients with hepatic cancer has been tempered by the finding that recurrence is both common and rapid. An increasing number of patients with inborn errors of metabolism originating in the liver are receiving transplants, including patients with Wilson's disease, tyrosinemia, alpha-1-antitrypsin deficiency, glycogen storage disease, familial hypercholesterolemia, and hemochromatosis. Survival in this group of patients has been excellent (74.4 per cent at 1 and 5 years). A hemophiliac who received a transplant for postnecrotic cirrhosis has survived and may have been cured of his hemophilia. About 20 per cent of patients require retransplantation for rejection, technical failure, or primary graft failure. Only four of the patients receiving retransplants under conventional immunosuppression survived beyond 6 months, and all died within 14 months of retransplantation. Sixty-eight patients have received retransplants under cyclosporine-prednisone. Thirty-one patients are surviving, all for at least 1 year. Six of the twelve patients requiring a third transplant are alive 2 to 3 years after the primary operation. An aggressive approach to retransplantation in the patient with a failed graft is justified.

Adult↗

Distinguishing aldosterone-producing adenoma from other forms of hyperaldosteronism and lateralizing the tumour pre-operatively.

In 14 hypertensive patients aldosterone/cortisol ratio was always lower in a peripheral vein or low IVC than in either adrenal vein. In four patients with a right-sided aldosterone-producing adenoma (APA), the aldosterone/cortisol ratio in peripheral vein was always higher than in the left adrenal vein. If only the left adrenal vein is cannulated, right-sided APA can still be diagnosed with certainty. In three patients with glucocorticoid-suppressible hyperaldosteronism, urinary excretion of both 18-oxocortisol and 18-hydroxycortisol was elevated. In four patients with APA excretion of 18-oxocortisol was elevated. In two of three patients with bilateral adrenal hyperplasia (BH), excretion of both steroids was normal. 75Se-selenomethylcholesterol scanning correctly lateralized five APA, but falsely lateralized a patient with BH. Results with CT scans were often misleading.

Adenoma↗

The syndrome of hypertension and hyperkalaemia with normal GFR. A unique pathophysiological mechanism for hypertension?

Based on 28 reported patients, constant features of the syndrome of hypertension and hyperkalaemia are hyperkalaemia, hyperchloraemia, normal renal glomerular function and, in all adult patients, hypertension. Inconstant features include short stature, intellectual impairment and muscle weakness. Levels of renin and aldosterone are low, but respond to dietary salt restriction and diuretic therapy, both of which reverse the hypertension and hyperkalaemia. The basic abnormality is excessive renal sodium retention, leading to chronic suppression of renin and aldosterone; the latter is then hyporesponsive to the hyperkalaemic stimulus. Dietary salt loading or impaired production of any natriuretic or chloriuretic factor (for example atrial natriuretic peptide or renal natriuretic prostaglandins) would predispose to development of the syndrome. With normal GFR, this appears to be a unique mechanism for hypertension and hyperkalaemia.

Adult↗

Plasma levels of atrial natriuretic peptide in man in primary aldosteronism, in Gordon's syndrome and in Bartter's syndrome.

Plasma levels of ANP were measured in normal subjects and in three conditions associated with disturbed volume homeostasis. Levels of ANP were appropriately raised in seven patients with primary aldosteronism, and fell to normal following removal of an aldosterone-producing adenoma in six and dexamethasone treatment in one patient with glucocorticoid-suppressible hyperaldosteronism. The level of ANP in one patient with Gordon's syndrome (a condition associated with plasma volume expansion) was lower than in the patients with primary aldosteronism, both before and after saline infusion. This is consistent with reduced ANP responsiveness in this condition. responsiveness in this condition. Levels of ANP were inappropriately elevated in three patients with Bartter's syndrome (a condition with plasma volume contraction) and rose further during saline infusion. This is consistent with primary hypersecretion of ANP.

Adult↗