James A. Schulak

Effect of Splenectomy on First Cadaver Kidney Transplants

A prospective study was begun in January 1975 to evaluate the effect of splenectomy on graft and patient survival in recipients of first cadaver kidney transplants. Ninety-two cases were evaluated. Splenectomy increased the survival of both grafts and recipients. The benefit from splenectomy compensated readily for the perioperative morbidity of splenectomy and the long-term increased risk of sepsis from certain bacteria for the asplenic patient. Splenectomy exerted its effect by reducing the incidence and intensity of rejection episodes. It was not clear whether the observation resulted from a direct immunosuppressive effect of splenectomy or from the increased tolerance to azathioprine observed in asplenic recipients. Finally, splenectomy negated an effect of race that had been observed earlier for survival of cadaver transplants and recipients.

Physiologic aspects of intrasplenic autotransplantation of pancreatic fragments in the dog after 24 hours of cold storage

Abstract This report confirms the efficacy of using partially digested pancreatic fragments for endocrine replacement in the pancreatectomized dog and intrasplenic autotransplantation model. In addition, the feasibility of short-term cold storage preservation is demonstrated. Dogs transplanted with either freshly prepared or 24-hr cold storage preserved (4°C) islet grafts maintained nearly normal fasting glucose levels. In contrast, 48-hr preservation was unsuccessful in that recipients of these grafts became diabetic and had survival rates similar to pancreatectomized, nontransplanted controls. The successfully transplanted dogs have remained normoglycemic during a 5-month follow-up period and have had satisfactory glucose responses in IVGTTs. However, α- and β-cell reactivity as measured by insulin and glucagon determinations remains abnormal.

Effect Of Warm Ischemia On Segmental Pancreas Transplantation In The Rat

This study was performed to determine the effect of warm ischemia on post-transplantation endocrine function of rat segmental pancreas transplants. Diabetic (streptozotocin) rats were recipients of syngeneic vascularized grafts in all experiments. Thirty-, 60-, and 90-min periods of absolute ischemia at 37 C in addition to approximately 30 min of anastomosis time did not impair control of glucose metabolism as manifested by daily serum glucose values or response to intravenous glucose challenge when compared with control rats transplanted with freshly harvested pancreata. However, when the ischemic period was lengthened to 120 min, only one of five recipients had normal glucose values post-transplant. Islet morphology in the 30-, 60-, and 90-min ischemia groups was not different from controls. On the other hand, after 120 min of ischemia, islets were decreased in number, appeared smaller in size, and had undergone degeneration. For comparison, renal isografts using kidneys with 90 min of warm ischemia failed. These data suggest that in this model, islets in segmental pancreas transplants are more tolerant of warm ischemia than kidneys.

Inhibition of endothelin-1 improves survival and vasculopathy in rat cardiac transplants treated with cyclosporine.

Background. In animal models, endothelin-1 (ET-1) blockade attenuates transplant vasculopathy and chronic allograft dysfunction even in the absence of cyclosporine (CsA). As CsA has side effects and ET-1 antagonism alone has significant benefits, we postulated that allograft survival could be significantly improved by combining an endothelin-converting enzyme inhibitor with low-dose CsA. Methods. Survival of Lewis to Fisher 344 rat heterotopic cardiac allografts was determined in untreated animals and compared with those treated with high-dose CsA (62 mg/kg i.m. on day 2), low-dose CsA (25 mg/kg), an endothelin-converting enzyme inhibitor, phosphoramidon (PA, 10 mg/kg/day), or low-dose CsA + PA. Results. Untreated allografts had a median survival of 16 days compared with 20 days for low-dose CsA. Grafts treated with PA survived for 28 days, and combination of PA and low-dose CsA improved median survival to 47 days (P <0.01). Median survival with combination therapy was similar to that for high-dose CsA (42 days). To explore mechanisms underlying the benefits of combination therapy, cardiac allografts treated as above (n=4 each group) were explanted at 20 d and analyzed for parenchymal rejection, neointimal vasculopathy, myocardial fibrosis, and macrophage infiltration. Low-dose CsA alone but not PA improved parenchymal rejection; in contrast, PA alone but not low-dose CsA improved vasculopathy. Both parenchymal rejection and vasculopathy were improved by combination therapy with low-dose CsA and PA. Unlike CsA, inhibition of ET-1 biosynthesis significantly reduced myocardial fibrosis in allografts. Conclusions. These results suggest that the combination of low-dose CsA and endothelin-converting enzyme inhibition may prove useful to improve long-term graft survival while minimizing potential side effects of CsA.

Evidence for a role of the stomach in serum calcium regulation.

Abstract Gastrin, histamine, cholecystokinin, and the cholecystokinin-octapeptide all result in hypocalcemia in the rat. A gastric factor, and not the release of calcitonin from the thyroid gland, seems most important in mediating these changes in serum calcium concentration. Neither the administration of secretin, V.I.P., G.I.P., nor highly purified insulins resulted in any significant change in serum calcium concentrations in this animal. We conclude that under certain circumstances the stomach may play a role in serum calcium regulation.

Gastrin-induced hypocalcemia in thyroparathyroidectomized rats

Abstract The influence of gastrin on calcium homeostasis was studied in both thyroid intact and thyroparathyroidectomized (TPTX) rats. Either synthetic human gastrin I or porcine gastrin was injected intravenously into fasted, anesthetized male rats. Venous blood was collected before gastrin administration and both at 30 and 60 min after injection. Gastrin doses of 12–50 μg/rat induced a significant hypocalcemic response in thyroid intact rats. Similarly, gastrin doses of both 12 and 25 μg/rat also produced a significant decrease in serum calcium in TPTX rats. These studies strongly suggest that gastrin-induced hypocalcemia in the rat is not solely dependent upon the thyroid release and subsequent action of calcitonin.

Salvage of thrombosed forearm polytetrafluoroethylene vascular access grafts by reversal of flow direction and venous bypass grafting

A technique is described for salvage of looped forearm polytetrafluoroethylene (PTFE) vascular access grafts that fail because of thrombosis due to cephalic vein outflow obstruction. It entails reversal of blood flow direction through the graft and construction of a new venous outflow in the medial upper arm. This procedure was performed in nine patients and, at the present time, has increased the graft life by an average of 6.2 months (range: 2 to 14 months) in eight. We conclude that this is a useful alternative to abandoning failed looped forearm PTFE grafts that have cephalic vein outflow obstruction.

Histamine-induced hypocalcemia in the rat

The effect of histamine and betazole hydrochloride (Histalog) on serum calcium homeostasis in the rat was studied in these experiments. Either histamine base, histamine phosphate, betazole, or the appropriate control solution was injected intravenously into fasted, anesthetized 80-100 g male rats. Venous blood was collected before and at 30 and 60 min postinjection. Histamine base in doses of 0.5-2.0 mg/rat induced a significant hypocalcemic response 30 min postinjection which returned to baseline by 60 min. Likewise, the administration of 1.375 mg/rat of histamine phosphate (equivalent to 0.5 mg histamine base) also resulted in a significant fall in serum calcium concentration. However, betazole administration, in doses as high as 10 mg/rat, did not lower the serum calcium concentration. In the histamine experiments neither total protein nor hematocrit values differed from control at the time of hypocalcemia. Therefore the changes in serum calcium concentration cannot be explained by hemodilution. These experiments demonstrate that in the rat the administration of histamine results in a hypocalcemic response similar to that previously observed with gastrin.

The importance of the stomach in mediating histamine-induced hypocalcemia in the rat☆

The effect of histamine on serum calcium homeostasis was studied in the rat. After the intravenous administration of 0.5-1.0 mg histamine base to fasted Holtzman rats weighing 80-100 g, a significant lowering of serum calcium (Ca) level occurred 30 min after injection (decrease in Ca, 1.4-1.9 mg/100 ml), but normocalcemia returned at 60 min. Repeat intravenous injections of histamine 1.0 mg resulted in repeated lowering of the serum Ca level. Hypophosphatemia did not accompany the hypocalcemia. Thyroparathyroidectomy (TPTX) did not eliminate the calcium-lowering effect of histamine in acute TPTX animals but did so in more chronic TPTX animals in which the mean serum Ca was 7.6 mg/100 ml or less. Gastrectomy, however, completely eliminated the calcium-lowering effect of histamine given in doses of up to 2 mg/rat (20 mg/kg of body weight), despite the presence of an intact thyroid gland. These studies support the role of a gastric factor and not the thyroid secretion of calcitonin in mediating this response in the rat.

Arteriovenous grafts have higher secondary patency in the short term compared with autologous fistulae

BACKGROUNDnTo estimate patency of arteriovenous fistulas (AVFs) and grafts (AVGs) for dialysis access.nnnMETHODSnRecords of all adult patients who had a dialysis access placed from January 2008 to June 2011 were retrospectively reviewed.nnnRESULTSnA total of 494 patients with 655 accesses (390 AVFs, 265 AVGs) were examined. We found that AVG fared worse in assisted primary patency. But AVG had superior secondary patency up to 1.2 years (hazard ratio [HR] .6, confidence interval [CI]: [.4 to .8]) and was no different than AVF after 1.2 years. (HR 1.6, CI: [.9 to 3.1]). On univariate analysis, dialysis catheters negatively impacted assisted primary patency (HR 1.4, CI: [1.09 to 1.77]).nnnCONCLUSIONSnAVG can be maintained with higher rates of secondary patency in the short term and are no different in the long term. This result suggests that in patients with limited life expectancy an AVG may be an effective alternative to an AVF to reduce both catheter time and associated complications.