Continuous sulfa prophylaxis for urinary tract infection in renal transplant recipients

During a 12 to 25 month follow-up period, 252 renal transplant recipients maintained with continuous sulfa prophylaxis were observed for evidence of bacteriuria. Although symptoms were rare, positive cultures were obtained in 6 percent of the patients who responded to conventional antibiotic outpatient therapy. Compared with sulfisoxazole, trimethoprim-sulfamethoxazole led to slightly fewer infections, especially with gram-negative organisms. Toxicity from sulfa was minimal and occasional leukopenia reversed by temporarily withholding azathioprine. Continuous sulfa prophylaxis in renal transplant patients is therefore safe and effective in minimizing the incidence of urinary tract infection, as well as other opportunistic infections known to be treatable by sulfa agents.     

Transplantation of the adult kidney into the very small child. Technical considerations

Transplantation of adult kidneys into very small children is not performed in most centers because of concerns regarding the technical difficulty of the procedure. Advantages of the procedure include the possibility of living related donor transplantation and the increased availability of adult donor kidneys as compared with pediatric cadaver donor kidneys. We have transplanted adult kidneys into 12 children aged 11 months to 3.5 years who weighed 5,400 to 8,800 g. Ten children received living related donor and two cadaver donor grafts. Herein we describe in detail the pretransplant management, surgical strategies, intraoperative management, surgical techniques, and postoperative management which we use for transplantation of adult kidneys into very small children. Intraoperative and postoperative complications have been described to illustrate the evolving clinical principles in this area. Since 10 of the children are presently alive, 8 with their original grafts, 16 months to 9 years after transplantation, we advocate this approach for suitable small children with terminal renal failure.     

Predictive value of thallium stress testing for coronary and cardiovascular events in uremic diabetic patients before renal transplantation

Coronary artery disease and the ability of noninvasive exercise perfusion imaging with thallium-201 to predict future coronary and cardiovascular events was prospectively evaluated in a group of 85 insulin-dependent diabetic renal transplantation candidates. Sixty patients received renal allografts (36 living related donors, 24 cadaver donors) after a thallium stress test; the actuarial 2 year patient survival rate after transplantation was 84 percent. Twenty-five patients remained on dialysis, and the 2 year actuarial survival rate from onset of dialysis was 41 percent, significantly lower than the actuarial survival rate of transplanted patients (p less than 0.01). Thirteen transplanted patients had positive thallium stress test results, and 6 (46 percent) had cardiovascular events (two fatal). In contrast, of 47 transplant patients with negative thallium stress test results, only 13 (28 percent) had cardiovascular events (four fatal). Five patients treated by hemodialysis only had positive test results and three (60 percent) had cardiovascular events (two fatal), whereas of 20 hemodialysis patients with negative test results, 9 (45 percent) suffered cardiovascular events (four fatal). In this study, cardiovascular events included arrhythmia, stroke, and pulmonary embolism. Within the total group, 4 of 18 patients (22 percent) with a positive test result (22 percent) had a fatal myocardial infarction, whereas only 3 of 67 patients (4 percent) with a negative result had a fatal myocardial infarction (p less than 0.05). In comparison, 24 of 85 patients had a history or electrocardiographic evidence of preexisting cardiovascular disease, and 13 (54 percent) had subsequent cardiovascular events (5 of 11 patients with positive test results and 8 of 13 patients with negative results). In summary, renal transplant candidates with positive thallium stress test results appear to be at increased risk compared with those with negative results for the development of fatal myocardial infarction, but thallium stress testing is no more predictive for future coronary and cardiovascular events than is a history or an abnormal electrocardiogram.     

Hyperplasia of pancreatic duct epithelium produced by exposure to sodium deoxycholate

Severe epithelial hyperplasia was produced in a canine model by the perfusion of the main pancreatic duct with 15 mM of deoxycholate at rates as low as 1.5 ml/day in 6 to 14 days. At higher rates (5 ml/day) deoxycholate caused complete epithelial cell lysis in the duct closest to the tip of the cannula with hyperplastic changes downstream from this section. Perfusion with a buffer solution alone and cannulation alone produced none of these changes in similar duct segments. No hyperplasia was seen in the up-stream cannula obstructed duct, even in the presence of severe atrophy. Long-term (81 days) perfusion with 3 mM of deoxycholate at 3 ml/day resulted in more severe hyperplasia that still appeared benign. When glycine-conjugated deoxycholate was perfused through the duct, hyperplasia but no cell lysis was seen. In vitro, deoxycholate caused epithelial cell lysis in pancreatic duct fragments at concentrations of 0.5 mM and above. The results of this study suggest that secondary bile salts or other similar surface-active cytotoxic agents present in the biliary tree or duodenum may play a more important role in the pathogenesis of pancreatic ductal epithelial hyperplasia associated with pancreatic cancer than ductal obstruction.     

Our surgical heritage. The Paget tradition revisited

Sir James Paget (1814 to 1899) is well-known for his classic article on breast and bone disease. However, the life of this famous English surgeon, pathologist, physiologist, and botanist should not go unnoticed. His early dedication to botany and science primed him for the position of one of the most respected physicians of his time. His life was one of continuing progress, starting with his association with the then unstable St. Bartholomew's Hospital in 1834 and culminating in the late 19th century with numerous awards, and clinical and administrative positions, as well as honorary titles bestowed upon him by royalty and colleagues. His ability as an orator was unmatched, and his philosophy regarding the practice of medicine as well as everyday life offer much to us today.     

Giant duodenal ulcer

Benign giant duodenal ulcer appears to be a unique type of generalized peptic ulcer disease. Massive hemorrhage, perforation, and obstruction are frequent complications. The disorder is best diagnosed endoscopically and treated with one of the standard acid-reducing procedures.     

Double renal transplants from pediatric donors to adult recipients

Ten pairs of kidneys from pediatric cadaver donors have been transplanted in patients with renal failure. Preservation by perfusion and transplantation are carried out by way of the distal aorta after the proximal aorta and vena cava are closed. Seven of the ten pairs of kidneys have normal function sixteen to twenty-four months later. Since pediatric donors appear to be unusually frequent, this technic permits transplantation of pediatric kidneys into adults and provides adequate renal mass for normal function.     

Treatment of rat heart allograft recipients with postoperative total lymphoid irradiation (TLI)

Pretransplant total lymphoid irradiation (TLI) plus donor bone marrow can result in donor-specific tolerance, but graft-versus-host disease is not consistently avoided. TLI may have greater applicability as an adjuct to generalized immunosuppressive treatment. In a clinical trial, preoperative TLI posed problems for patients with a high percentage of cytotoxic antibodies who sometimes had a long wait for a transplant after completion of TLI. It would be logistically advantageous if TLI could be given in the perioperative period. We investigated the feasibility of this approach in an ACI (RT-1^a) to Lewis (RT-1^l) rat heart allograft model. Untreated recipients rejected the grafts at a mean of 6.1 days. TLI 400 or 600 rads administered as one dose 1 day preoperative did not prolong graft survival (rejected a mean of 5.6 and 6.3 days). A dose fraction schedule previously found to be effective when given preoperatively, 200 rads × 5 consecutive days, did not prolong graft survival when administered beginning the first day postoperatively (mean rejection at 6.3 days). Higher dose fractions were effective: 300 rads × 3, 300 rads × 5, 400 rads × 3, and 400 rads × 4 gave mean rejection times of 11.8, 16.8, 11.5, and 13.6 days, respectively. Combining 600 rads preoperative with 200 rads × 5 days postoperative did not prolong graft survival. Six hundred rads preoperative plus 300 rads × 3 days postoperative prolonged graft survival, but was no more effective than 300 rads × 3 days postoperative alone. The most effective schedule for postoperative TLI was 300 rads × 3, 0 rads × 2, and 200 rads × 5 days; this treatment delayed rejection to 25 days. In conclusion, one dose preoperative TLI has no effect on heart allograft survival, but postoperative TLI in dose fractions of 300 rads is effective in delaying rejection. Postoperative TLI may be an alternative treatment for patients who must wait for suitable crossmatch negative cadaver kidneys.     

Gastrin cell populations after highly selective vagotomy in the dog.

Highly selective vagotomy was performed on five dogs. Postoperatively, gastrin cell (G cell) hyperplasia occurred in all dogs. Mean preoperative G cell numbers increased from 350 to 530/cm mucosal length (p less than 0.02). Antral tissue gastrin also increased by 100 per cent (6.7 x 10(6) to 13.7 x 10(6) pg/gm tissue, p less than 0.05). Basal and stimulated serum gastrin were unchanged following highly selective vagotomy. The cause for G cell hyperplasia is not clear, but is probably multifactorial.     

Technical aspects of segmental pancreatic autotransplantation in dogs

Heterotopic segmental pancreatic autotransplantation in dogs is more appropriate than allograft models for the investigation of several problems associated with transplantation. We have defined the anatomic variations of blood supply in the pancreatic tail and designed various modifications of vascular anastomosis to the iliac vessels in order to eliminate technical failures, such as thrombosis, as much as possible. In 187 of 240 dogs (77.9 percent), the pancreatic artery originated from the splenic artery and the pancreatic vein entered the splenic vein (normal anatomy). The main venous variation was direct confluence of the pancreatic and portal veins (12.1 percent), and the main arterial variation was origin of the pancreatic artery from the superior mesenteric artery (10 percent). Ninety-seven animals with normal anatomy qualified for a comparative study of seven methods of segmental pancreatic autotransplantation. Venous anastomoses were always performed in an end-to-side fashion between the splenic and external iliac veins. Arterial anastomosis techniques follow. Group I: interposition of the splenic artery into the external iliac artery; (14 days, failure rate 50 percent), Group II: end-to-end arterial anastomosis of the splenic artery to a long external iliac artery segment with the graft directed caudad, resulting in an acute curve to the vessel loop (8 dogs, failure rate 38 percent); Group III: end-to-end arterial anastomosis to a long external iliac artery with the graft directed cephalad, resulting in a gentle curve to the vessel loop (11 dogs, failure rate 36 percent); Group IV: end-to-end arterial anastomosis to a short external iliac artery stump (20 dogs, failure rate 20 percent); Group V: same as in Group IV with the addition of a distal splenic arteriovenous fistula (12 dogs, failure rate 17 percent); Group VI: end-to-side anastomosis of the splenic artery to the external iliac artery (31 dogs, failure rate 6 percent); Group VII: same as in Group VI but with the addition of an arteriovenous fistula of the distal splenic vessels (1 dog, failure rate 0). The end-to-side technique proved to be straight-forward and reliable. The low failure rate with this method allows metabolic preservation and other aspects of pancreatic transplantation to be studied and the results to be interpreted without the influence of a high complication rate from the operation itself.     

Enhanced cardiac efficiency with dobutamine after global ischemia

Dopamine and dobutamine are used in low output states following cardiopulmonary bypass but the consequences of increased inotropic activity on myocardium recovering from ischemia is unknown. Dogs on cardiopulmonary bypass were subjected to 20 min of normothermic global ischemia followed by 20 min of reperfusion. Dopamine or dobutamine (both at 10 μg/kg/min) or normal saline infusion was begun and 10 min later the dogs weaned from cardiopulmonary bypass while the infusions continued. Serial measurements were made of regional myocardial and systemic blood flow (15 μm radiolabeled spheres), myocardial oxygen consumption, creatine phosphate, and ATP levels. On bypass mean aortic pressure was decreased and heart rate, oxygen consumption, and left ventricular blood flow were increased by both catecholamine infusions (P < 0.01), but neither drug lowered ATP or creatine phosphate levels. Renal blood flow was decreased in dobutamine-treated dogs (P < 0.01). Off bypass, heart rate and mean aortic pressure were similar in all groups. While both drugs increased left ventricular blood flow to a similar extent (P < 0.01), dopamine treatment raised cardiac output by only 30% (P < 0.05) and dobutamine treatment increased cardiac output by 85% (P < 0.01). In addition, myocardial oxygen consumption was increased in dopamine-treated dogs (P < 0.05) while values in dobutamine animals were similar to controls. Therefore, dobutamine seems advantageous to dopamine following bypass because it increases cardiac output (by increasing stroke volume) but does not increase myocardial oxygen consumption. Both drugs are potentially detrimental on bypass because they greatly increase heart rate and oxygen consumption and, in addition, dobutamine causes an unexplained fall in renal blood flow.     

Splenectomy in high-risk primary renal transplant recipients

One hundred sixty-five high-risk patients who were either 50 years of age or older or had diabetes mellitus, or both underwent primary renal transplantation. One hundred eight had splenectomy and 57 did not. Graft and patient survival were analyzed in regard to whether splenectomy had been performed at all and whether it had been performed 30 days or more before transplantation, less than 30 days before, or at the time of transplantation. Also, the influence of age, diabetes, blood transfusions, blood type, donor type, HLA mismatch, pretransplantation dialysis, and percentage of performed antibodies were analyzed, as were complications and causes of death. Differences in patient survival were not significant in any one of these categories, although survival in the splenectomized group was generally better. The incidence of infection and sepsis was comparable in both groups and was responsible for death in 34 percent of the patients who underwent splenectomy compared with 22 percent of those who did not (no significant difference). Splenectomy improved cadaver donor renal allograft survival (p = 0.001) in the diabetic patients (p = 0.015) and in those 50 years of age or older (p = 0.026) but it did not improve survival in those who received living related donor kidneys. No significant differences were detectable in regard to the timing of splenectomy. The effect of splenectomy was significant in the patients who had not received transfusions (p = 0.003). It also improved survival in the transfused patients. Splenectomy in high-risk diabetic patients and patients 50 years of age or older does not seem to be associated with increased mortality.     

The postoperative course and quantitative aspects of rat islet and segmental pancreas isografts

Duct-ligated segmental pancreas transplants with systemic venous drainage were compared to intrahepatic islet grafts for beta-cell mass (proportional to tissue insulin content) and function in diabetic Lewis rats. Rats were serially killed to measure insulin in the segmental pancreas grafts and in the liver of the islet recipients. Segmental pancreas weight was maximum and insulin concentration and content lowest (P less than 0.05) on Day 3 when acute inflammation was present. At 21 days, there was no inflammation, and graft weight had decreased, but not to Day 0 level because of normal growth; insulin concentration was similar on Days 21 and 0. At 3 months, moderate fibrosis of the graft was present, but both total insulin and insulin concentration had increased (P less than 0.05). In the recipients of islet grafts, total insulin in the liver on Day 1 was only 43% of that contained in the original islet preparation, but by 3 months the insulin content in the liver had increased to that transplanted. IVGTT K values were similar in normal rats (-3.5 +/- 0.7%) and in recipients of segmental pancreas (-4.5 +/- 1.6%) and islet (-4.0 +/- 1.5%) grafts at 3 months post transplant. Acute segmental graft pancreatitis resolved, followed by an increase in beta-cell mass. Islet cell damage during transplantation is either reversible or residual viable islets proliferate, and provide metabolic control equivalent to segmental pancreas transplants, even though the final beta-cell mass is less.     

Differences in susceptibility to rejection of mouse pancreatic islet allografts disparate for class I or class II major histocompatibility antigens

Pancreatic islet B cells express class I but not class II antigens, and removal of Ia positive passenger cells from H-2 allogeneic islets by anti-Ia serum and complement leads to permanent allograft survival. A test was made of whether the same result can be achieved by genetically removing the Ia stimulus by performing mouse islet allografts in congenic donor-recipient combinations differing at the H-2 K only, D only, or K + D regions. Mice disparate for class I antigens (H-2 K, D, and K + D) alone reject islet allografts, suggesting that Ia positive passenger cells may be involved in presentation of class I disparities. Established islet allografts appear to be sensitive to rejection induced by injection of donor strain splenocytes when donor and recipient differ for class I (H-2 D alone and D + I) but not class II (H-2 I alone) antigens. These results are consistent with the hypothesis that pancreatic islet allografts do not express class II target antigens, but do express class I antigens that in long-established pancreatic islet allografts are capable of acting as targets but not in initiating an immune response.     

The temporary intestinal stoma?

Various operative circumstances dictate temporary total diversion of the small intestine. Among these are severe peritonitis, multiple suture lines, fistulas, questionable vascular integrity, and an ileoanal anastomosis. The operative procedure is largely identical to creating a permanent Brooke ileostomy. The distal end of the intestine is closed and sutured in a side-to-side orientation to the proximal intestine just inside the peritoneal exit. A tube is left in the distal intestine for subsequent radiologic study. A major merit of this variation is the ease with which intestinal continuity can be restored. Because the two segments of intestine are tacked together, they are easily retrieved through a small circumstomal incision, and a side-to-side anastomosis can be constructed.     

Cell-free supernatant from hepatocyte cultures improves survival of rats with chemically induced acute liver failure

Current support or replacement therapies for fulminant hepatic failure are frequently inadequate. Hepatocyte transplantation has been found to permit or facilitate recovery from chemically induced liver failure in rats. The mechanisms are unclear, but function of the transplanted cells or stimulation of host liver regeneration by factors released from the cells could improve survival; there is evidence from experiments by other investigators using cell fractions to support the latter hypothesis. We compared intact cells and the supernatant from cultured liver cells for their influence on the survival of Fischer male rats with d-galactosamine (d-Gal) induced acute liver failure (ALF). All treatments were given 20 to 24 hr after poisoning. Cell supernates were injected intrasplenically (sp), intraperitoneally (ip), or intravenously (iv). Liver cells (2 × 10⁷) suspended in Hanks' solution were injected intrasplenically. Untreated rats and rats treated with Hanks' solution or culture medium alone had a 94–100% mortality, with all deaths occurring between 38 and 74 hr after poisoning. Improved survival was seen in all experimental groups: 47% of the rats receiving intact liver cells survived; 50, 55, and 62% of the rats receiving cell-free supernate by the sp, ip, or iv routes, respectively, survived. A chronologic electron micrographic study of livers from rats serially sacrificed in parallel experiments showed that recovery from morphological changes induced by d-Gal occurred in treated rats. These studies demonstrate that intact hepatocytes are not required to improve survival in rats with drug-induced ALF. Improved survival may be achieved by factors liberated by cultured hepatocytes that enhance the regeneration of the damaged liver. Supernatant from cultured liver cells may have a therapeutic potential in acute hepatic failure.     

Delayed-type cutaneous hypersensitivity to Thomsen-Friedenreich (T) antigen in patients with pancreatic cancer

The delayed-type hypersensitivity skin reaction to human erythrocyte-derived Thomsen-Friedenreich (T) antigen was studied in 40 patients with pancreatic disease and in 158 control subjects and its sensitivity and specificity were compared with the carcinoembryonic antigen (CEA) blood levels. The skin reaction to T was positive in 22 of 25 patients with biopsy-proven adenocarcinoma of the pancreas (sensitivity, 88%). In these patients, the CEA levels were elevated above 3.5 ng/ml in 12 of 23 (52%). The skin test to T antigen was negative in 11 of 12 patients with chronic pancreatitis (specificity, 92%), but CEA levels were normal in only five of nine with pancreatitis (56%). Two of the patients with pancreatic carcinoma and one of those with pancreatitis were anergic to mumps and dermatophytin antigens and had thus an invalid skin test. The positive response rate to T antigen was significantly greater (P less than 0.005) in the cancer group than the group with pancreatitis; the CEA response was not significantly different. There were no positive responses to T in 82 healthy volunteers. Among 76 patients with chronic disease including six with malignant tumors of the mesoderm and central nervous system, there were four positive responses: two in heavy smokers and two in patients with chronic lung infection. The specificity of the test overall in 158 controls was thus 97.5%.     

Successful transplantation of ectopic kidneys from living related donors

Two ectopic pelvic kidneys were transplanted from living donors into well matched recipients. Both kidneys have good function at two and four years post transplantation and there has been no evidence of infection post transplantation. Such kidneys can be utilized when there is no evidence of obstruction or infection in the donor and when the contralateral kidney is normal.     

The university of Glasgow and the Johns Hopkins schools of surgery

Glasgow's medical faculty traces back to the illustrious 16th century surgeon Peter Lowe. Its regius professorship, which dates from 1815, has been occupied by many luminaries including Joseph Lister, William Macewen, Charles Illingworth and Andrew W. Kay. William Macewen was Johns Hopkins's first choice for professor, but the opportunity was then awarded to William Halsted (1889–1922), who developed America's first great school of surgeons, a tradition restored by Blalock from 1941 to 1964.     

Tuberculous joint disease in transplant patients.

Three patients with tuberculosis, all manifesting monarticular joint involvement, among 845 renal allograft recipients at the University of Minnesota are reported on. Clinical symptoms, methods of diagnosis, and optimal antibiotic regimes are discussed. The physician must suspect tuberculous joint disease when confronted with monarticular swelling and pain in the transplant recipient.