Roux-en-Y venting jejunostomy in pancreatic transplantation: a novel approach to monitor rejection and prevent anastomotic leak.

INTRODUCTION: Pancreatic transplantation (PTx) with portal venous delivery of insulin and enteric drainage of the exocrine secretion is more physiologic than bladder-systemic (BS) drainage. With portal-enteric (PE) PTx, the diagnosis of acute rejection (AR) requires a percutaneous biopsy. The roux-en-y (RNY) venting jejunostomy in patients with PEPTx offers a novel approach to monitor rejection and prevent anastomatic leaks. METHODS: From January 1996 to December 1998, we performed 17 simultaneous kidney/pancreas transplants (SKPTx). The initial 4 patients underwent BS drainage and the subsequent 13 patients underwent RNY venting jejunostomy with PE drainage. All patients were treated with quadruple therapy. There were 9 males, 14 patients were Caucasian with a mean age of 32 yr (range 30-54 yr), and a mean pre-transplantation duration of diabetes of 25 yr. Six patients underwent endoscopic donor duodenal biopsy through the jejunostomy to rule out clinically suspected AR. Gastrograffin was inserted into the jejunostomy to examine the integrity of anastamosis when indicated. In 9 out of 13 patients, the venting jejunostomy was taken down 9-12 months post-transplantation after allograft function was stable. RESULTS: Actual patient, kidney, and pancreas graft survival rates were 100, 100 and 94%, respectively, after a mean follow-up of 16 months. Renal allografts functioned immediately in 89% of patients. The mean length of hospital stay was 19 d. Four (23%) patients (2 with BS drainage and 2 with PE drainage) suffered an AR episode in the first month, and 4 (23%) patients had five AR from 3-36 months post-transplantation. Other complications were post-operative bleeding in 3 patients, wound infection in 2 patients and a proximal duodenal stump leak in 1 patient. In patients with clinical rejection, endoscopy through the venting jejunostomy showed inflamed, friable doudenal mucosa and doudenal biopsy findings were compatible with AR. CONCLUSION: These preliminary results suggest that RNY venting jejunostomy with PE drainage can be used safely to diagnose and monitor pancreas AR and to diagnose and prevent anastamotic leaks. This technique will be even more useful to visualize transplanted duodenal mucosa, collect pancreatic secretions (amylase) for analysis and perform endoscopic retrograde cholangiopancreatography if needed to obtain pancreatic biopsies.

Pyogenic liver abscess.

BACKGROUND: A current assessment of liver abscesses should allow for better understanding of the pathogenesis of the disease and improve the effectiveness of diagnosis and treatment. Amebic liver abscess occurs more commonly than pyogenic liver abscess on a worldwide basis. However, in the United States, pyogenic liver abscess predominates. The purpose of our study was to evaluate the etiology, management, morbidity, and mortality of all patients admitted to our medical center with diagnoses of pyogenic liver abscess between 1983 and 1996. METHODS: A retrospective chart review was performed on all patients admitted to our medical center, Louisiana State University Medical Center, Shreveport, with diagnoses of pyogenic liver abscess. RESULTS: Twenty patients were admitted with diagnoses of pyogenic liver abscess. The subjects were 65% (13/20) male and 65% (13/20) African-American and had an average age of 52 years. The most common presenting symptoms were fever and pain. The most common physical finding was right upper-quadrant tenderness. The most common etiologies of pyogenic liver abscesses were cryptogenic, trauma, and biliary, while portal vein was the source for only 10% of the cases. The right lobe of the liver was involved in 95% of the cases, and 70% of these liver abscesses were solitary. Computed tomography (CT)-and ultrasound-guided percutaneous drainage were performed in 85% (17/20) of patients with liver abscesses. One patient was treated by open drainage, three patients were treated with antibiotics alone, and three patients did not respond to aspiration and catheter placement, which subsequently required open drainage. The culture results were as follows: 50% were gram-negative organisms, 25% were gram-positive organisms, 10% were anaerobic organisms, and 15% of the abscess were sterile. Sixty percent of the positive abscess cultures were polymicrobial. CONCLUSIONS: CT scan- and ultrasound-guided percutaneous drainage of pyogenic liver abscesses were safe and effective methods of treatment. The right lobe of the liver was involved in 95% of cases. Although no one species predominated, gram-negative bacteria were the most common organism cultured, and 60% of the abscesses were polymicrobial. There was no in-house mortality in this review.

The use of FDG-positron emission tomography for the evaluation of colorectal metastases of the liver.

Each year at least 130,000 people in the United States are diagnosed with colorectal carcinoma. Approximately 14,000 of these patients will have liver metastases, and 20 per cent of these patients will die from these metastases. Surgical resection is the only possible chance for cure in patients with only intrahepatic metastases, and extrahepatic disease is a contraindication to glucose metabolism. Positron emission tomography (PET) allows the in vivo study of the uptake and use of glucose in human cells. Here, we review our experience with the use of PET imaging for the diagnosis and management of colorectal metastases of the liver. We conducted a retrospective chart review of 14 patients undergoing PET imaging for known or suspected hepatic metastases from colorectal carcinoma. Results of CT, magnetic resonance imaging, and PET images were compared with pathological specimens. CT scan identified 7 lesions, and PET identified 31 intrahepatic lesions. Of the 6 patients who underwent surgery, CT identified 4 (20%) and PET identified 17 (85%) of the 20 intrahepatic metastases histologically confirmed. The accuracy (number of lesions) of CT and PET was 20 per cent and 85 per cent, respectively. CT scans had a sensitivity (number of patients) of 50 per cent, and PET had a sensitivity of 100 per cent in patients undergoing surgical resection. PET imaging altered the management in 49 per cent of patients. Twenty-one per cent of patients had their surgery cancelled due to previously undiagnosed extrahepatic metastases. Twenty-one per cent of patients had negative CT scans and underwent surgery on the basis of their PET images, and all had histologically proven disease. One patient avoided a second-look laparotomy when PET revealed a lesion seen on CT to be false positive. PET is an ideal imaging modality to detect intra- and extrahepatic metastases from colorectal carcinomas and would aid in the surgical management of these patients.

Can low volume liver transplant centers be successful? The Regional Transplant Center of Willis-Knighton & Louisiana State University Medical Center. The first 120 liver transplants.

The development of orthotopic liver transplantation represents this century's most significant advance in the management of liver disease. In the 1980s the vast majority of liver transplants were performed at several large centers; however, in this decade, improvements in techniques and success rates have allowed live transplantation to expand to regional centers across the country, particularly in the southeast. This proliferation of regional centers and the widening disparity between organ availability and numbers of recipients have created tremendous controversy at the national level regarding the allocation scheme used to distribute livers to recipients. The large programs today are advocating change to a national waiting list which would eliminate local priority and jeopardize the existence of smaller regional centers. Furthermore, the large programs favor establishing a limited number of megacenters where all liver transplants would take place, arguing that low volume centers cannot perform liver transplants with acceptable complication and survival rates. At the Regional Transplant Center of Willis-Knighton Hospital and Louisiana State University Medical Center in Shreveport (WK/LSUMC) we performed 122 liver transplants between July 1, 1991 and December 31, 1997. The purpose of this study was to examine our complication and survival rates and compare them to national averages. The actuarial graft survival at 1, 2, and 3 years in this series compared to the national average respectively was 76% and 70%, 66% and 66%, 62% and 62%. The actuarial patient survival (WK/LSUMC vs National) at 1, 2, and 3 years was 80% and 80%, 75% and 75%, 70% and 74%. The rate of retransplantation was 8% with a national average of 10% to 20%. Our rate of graft primary non-function was 5% with the national average being 2% to 10%. The rate of vascular thrombosis of the graft in this series was 2% with a national rate of 5%. The differences in these results were not statistically significant (P < .05). Low volume transplant centers can perform liver transplant successfully, allowing the regionalization of the treatment of choice for end-stage liver disease.

Are all successful renal transplants really successful?

We previously described a small group of renal transplant recipients considered to have successful allografts statistically, but who did not benefit clinically. These were patients in whom the grafts survived greater than 6 months but less than 3 years. This expanded study evaluates 179 consecutive renal transplant recipients divided into three groups. Group 1 (n = 18), group 2 (n = 41), and group 3 (n = 120) have patients with graft survival less than 6 months, between 6 months and 3 years, and greater than 3 years, respectively. Mean age, cause of renal failure, HLA match, and immunosuppressive regimen were not statistically different in any group. The number of acute rejection episodes, number of hospitalizations, and number and seriousness of complications were significantly greater in group 2 patients compared with the other groups. Patients in group 2 experienced five times the number of acute rejections (P < 0.0001), three times the number of hospitalizations (P < 0.0001), and two times the number of complications (P < 0.0001) compared with group 3 patients. In conclusion, those transplant recipients whose grafts survived longer than 6 months but less than 3 years were the most unfortunate. They experienced repeated and serious complications and spent many days in the hospital at great expense. A study with more sensitive methods of detecting presensitization might impact on graft performance in the future.

Spontaneous bacterial peritonitis in liver failure.

Cirrhosis of the liver results from a variety of mechanisms that cause progressive hepatic injury. It is the sixth leading cause of death in all patients between the ages of 35 and 55. This study attempts to correlate the morbidity and mortality of spontaneous bacterial peritonitis in liver failure patients to numerous etiologic and clinical variables. A retrospective review of 26 patients with spontaneous bacterial peritonitis associated with chronic liver disease was performed in a university hospital. Demographics (age and gender), clinical variables (etiology of liver failure, Child's classification, prior history of ascites, fever, abdominal pain, encephalopathy, and upper gastrointestinal hemorrhage), and laboratory variables (ascitic polymorphonuclearcyte count and cultures, serum albumin, bilirubin, creatinine, and prothrombin time) were studied. All of the patients had Child's C liver disease. Mortality rate was 46 per cent. Alcohol (46%) and hepatitis (30%) were the most common etiologies. Escherichia coli and Klebsiella pneumoniae were the most common culture isolates. All of the infections were monomicrobial. The only significant predictor of mortality (P < 0.05) in this study was the peritoneal fluid polymorphonuclear (PMN) cell count. PMN count >1000 PMN/mm3 was associated with a mortality of 88 per cent. Few patients with spontaneous bacterial peritonitis are ultimately transplanted.

Small-bowel tumors.

BACKGROUND: The rarity, delayed presentation, and diagnostic difficulty of small-bowel tumors prompted this study. STUDY DESIGN: Charts were reviewed retrospectively for 85 patients with 89 small-bowel tumors (22 primary malignant, 23 primary benign, and 44 metastatic) over a 10-year period (1986-1996) at Louisiana State University Medical Center-Shreveport and two affiliated hospitals in Shreveport. RESULTS: Of the primary malignant tumors, 10 carcinoids and 11 duodenal adenocarcinomas were identified. Most primary benign tumors were adenomatous or hyperplastic polyps, diagnosed by esophagogastroduodenoscopy. Metastatic tumors accounted for nearly 50% of all small-bowel tumors. Across all three tumor types, the most common presenting signs and symptoms were abdominal pain and nausea and vomiting. In addition, patients with benign tumors were more commonly presented with gastrointestinal hemorrhage, and those with metastatic tumors were more likely to present with obstruction. The mean interval from the onset of signs and symptoms to operation was 54 days for primary malignant tumors and 330 days for primary benign tumors. Esophagogastroduodenoscopy and computed tomography of the abdomen were occasionally helpful in diagnosis. Among the 22 primary malignant tumors, curative resections were performed in 11 patients (for 9 carcinoids and 2 adenocarcinomas) and palliative resections were performed in 10 patients (for 9 adenocarcinomas and 1 myxoliposarcoma). One patient had carcinomatosis from colon cancer and an incidentally discovered ileal carcinoid; this carcinoid was not included in this group of resections for primary malignant small-bowel tumors. All operations for 39 (of 44) patients with metastatic tumors were palliative. The remaining 5 (of 44) patients had metastatic duodenal cancer (confirmed by esophagogastroduodenoscopy or endoscopic retrograde cholangiopancreatography with biopsy) and did not undergo laparotomy. Surgical complications occurred more commonly with metastatic than with primary malignant tumors. Patients with primary malignant tumors had a 5-year survival rate of 36%. CONCLUSIONS: These findings demonstrate that small-bowel tumors are difficult to diagnose because of delayed presentation, nonspecific signs and symptoms, and lack of accurate diagnostic studies. If the overall survival of patients with small-bowel tumors is to be improved, clinicians must have a high index of suspicion and be willing to perform exploratory celiotomy early.

Aggressive surgical management of necrotizing fasciitis serves to decrease mortality: a retrospective study.

Necrotizing fasciitis is an aggressive soft-tissue infection that in the past has carried a significant mortality rate. One of the most important determinants of outcome is recognition of the disease process. This is followed by aggressive resuscitation measures and radical debridement at the initial operation to control the infectious spread at the outset. The objective of this study is to help reveal the benefits of aggressive early surgical debridement in the treatment of necrotizing fasciitis. A retrospective review of the medical records of 68 patients between the years 1980 and 1996 with the diagnosis of necrotizing fasciitis was performed. The patients were assigned to two groups, Group A (21; 31%), who had delay in therapy or inadequate preliminary therapy and Group B (47; 69%), who underwent aggressive surgical debridement from the outset. Concomitant disease processes were noted. The medical records of 68 patients were studied. Age ranged from 13 to 67 (mean, 52) years of age. There were 38 (56%) females, 21 (64%) of the patients were African-American, 24 (73%) of the patients had concomitant disease processes, 29 (42%) of the patients had a history of tobacco use, 11 (16%) of the patients had a history of alcohol consumption, and 11 (16%) of the patients were obese. Mortality in Group A was 8 of 21 patients (38%). Mortality in Group B was 2 of 47 patients (4.2%). The difference in mortality was found to be statistically significant (P = 0.0007). Early recognition and expeditious initial wide excision and debridement along with appropriate antibiotic coverage and support of systemic effects of necrotizing fasciitis serve to decrease morbidity and mortality. We believe the above is an absolute necessity followed by frequent washing and minor debridement of the wound until granulating tissue is observed. This can then be followed by procedures to close/cover the surgical defect (i.e., split-thickness skin grafts or various coverage flaps).

Surgical and nonsurgical management of primary and metastatic liver tumors.

The medical records of 267 patients who had liver tumors, primary and metastatic, from 1988 to 1995 were retrospectively reviewed. Two hundred thirteen patients (80%) had metastatic disease, and 54 patients (20%) had primary liver disease. Their clinical manifestations and laboratory values were evaluated as factors predictive of diagnosis and survival. There was a significant increase in the occurrence of upper abdominal pain, weight loss, extrahepatic symptoms due to the metastatic origin, and hepatomegaly. Metastases from colorectal primary lesions were synchronous in 34 patients and metachronous in 31 patients. Stomach, lung, and pancreatic primaries were more commonly synchronous. Breast metastases were more commonly metachronous. Elevated serum glutamic-oxaloecetic transaminase and alkaline phosphatase and decreased albumin were the most common liver test abnormalities at diagnosis. Carcinoembryonic antigen values were elevated in the majority of colon cancer patients. Eighty-one percent of patients with primary liver cancer had elevated levels of alpha-fetoprotein, 40 per cent were seropositive for hepatitis B, and 23 per cent were seropositive for hepatitis C. Seventy-nine patients (30%) underwent surgery for their cancer, 37 (47%) had resections, 38 (48%) were unresectable, and 4 (5%) underwent liver transplantation. The patients who underwent surgery had a 32 per cent 5-year survival rate compared to a 0 per cent 5-year survival in the patients who did not have surgery (p = 0.0001). The patients who had resections had a better survival rate than those deemed unresectable at surgery (62% versus 0% at 5-years with p = 0.0008). The perioperative morbidity rate was 16 per cent, with lobectomies having the best rate and trisegmentectomies having the worst. Perioperative mortality rate was zero for all liver resections. Hepatic resection and, in selected patients, liver transplantation are the only two available therapeutic modalities that produce long-term survival with a possible cure in patients with primary and metastatic liver tumor.

Nonoperative therapy for acute necrotizing pancreatitis.

Acute necrotizing pancreatitis is a highly morbid and lethal condition. We performed a retrospective study of all patients admitted to Louisiana State University Medical Center between 1980 and 1995 with a diagnosis of pancreatitis (N = 617) and specifically examined those (N = 26) who developed acute necrotizing pancreatitis. During the period 1980 to 1989, there were 7 patients who progressed to acute necrotizing pancreatitis. Six of these seven patients died (mortality, 86%). These patients were managed with multiple operations for debridement and necrosectomy. The age ranged from 31 to 86 years in this group, with a mean of 58.5. The patients' total hospital days ranged from 2 to 125 days with a mean of 63.5 days. In 1989, we adopted an initial nonoperative approach to necrotizing pancreatitis and began using CT-guided catheter drainage for this condition. During this time period, 19 patients have progressed to necrotizing pancreatitis. The range of hospital days was from 13 to 90 days, with a mean of 43.8 days. There were 2 deaths in this last group, resulting in a mortality rate of 10.5 per cent. All of these patients were treated nonoperatively in the acute phase of their illness. Two patients (15.8%) subsequently underwent laparotomy and drainage when the collections were not amenable to CT-guided drainage. Morbidity in this population approached 70 per cent; however, the mortality was only 10 per cent compared to 86 per cent in the previous group. Although nonoperative therapy has its associated morbidity, and although we understand the controversy surrounding the management of this condition, it appears at least in this population to have much less mortality than those who were treated operatively in the acute phase.

Serologic allogeneic chimerism.

BACKGROUND: At least some transplanted livers secrete soluble human leukocyte antigens (sHLA) of donor phenotype into the body fluids of recipients. The individuals in whom this phenomenon occurs are by definition serologic allogeneic chimeras. Because an allogeneic transplanted liver may induce tolerance to itself and other organs in animals of the donor strain, and because maintenance of a soluble antigen in the circulation of any animal in sufficient quantity for a sufficient period generally leads to tolerance, this phenomenon may be biologically important. This study was performed to determine how common this phenomenon is and whether it occurs after transplantation of organs other than the liver. METHODS: We studied 445 serum samples obtained from transplant recipients (liver, n=12; kidney, n=18; and heart, n=8) before and at various intervals after transplantation. All patients studied had allografts that had functioned for more than 1 year. We used an enzyme-linked immunosorbent assay to quantitate sHLA-A2 and sHLA-A1/A3/A11 (as a cross-reacting group). Donor and recipient combinations were selected in which measurable allotypes in donors were not present in recipients. In some instances, an additional allotype was present in a recipient but not in a donor. RESULTS: All liver transplant recipients had detectable donor sHLA in their serum samples after transplantation. In 72% of kidney and 50% of heart transplant recipients, donor sHLA was found persistently in serum samples obtained after transplantation. Interestingly, all heart transplant recipients of HLA-A3, but none of HLA-A2, had detectable donor sHLA in their serum samples, a finding that may be due to technical reasons. High and stable serum concentrations of donor sHLA characterize long-term stable allograft function. CONCLUSIONS: Donor sHLA is produced by all transplanted livers, most transplanted kidneys, and at least half of (but probably more) transplanted hearts. The hypothesis that donor sHLA may be tolerogenic to liver transplants can be expanded to include kidney and heart transplants.

Soluble fraction of class I human histocompatibility leukocyte antigens in the serum of liver transplant recipients.

In previous studies we reported a solid-phase, enzyme-linked immunoassay (ELISA) that can be used to quantitate the soluble fraction of human histocompatibility leukocyte class I antigens (S-HLA-I) and study their relevance in transplantation. In this study we determined the concentration and distribution of S-HLA-I in patients with end-stage liver disease (ESLD), as well as in liver transplant recipients. Sera were obtained from 51 patients with ESLD and 40 donor-recipient pairs. We analyzed the S-HLA-I in sera obtained from liver donors, as well as from liver transplant recipients (patients with ESLD), with sera from the latter obtained before and at various intervals up to 3 yr after transplantation. The results of the analyses justify the following conclusions: 1) Patients with ESLD had mean values of S-HLA-I (909 +/- 596 ng/ml) greater than those for the normal population (643 ng/ml) (P < 0.05); the S-HLA-I secretion decreased with increasing severity of liver disease. 2) Patients with tumors had mean S-HLA-I levels (399 ng/ml) significantly lower than those in patients with ESLD related to other causes. 3) In liver transplant recipients the S-HLA-I levels stabilized at approximately 1 month after transplant and remained relatively stable thereafter (mean level 950 +/- 536 ng/ml). The observed levels were also greater than those for the normal population (P < 0.05). 4) Preoperative and postoperative S-HLA-I values in liver transplant recipients demonstrated a biphasic distribution, dividing patients into high- and low-secretor groups. 5) During the post-transplant observation period, of these selected liver transplant recipients there was no difference between high- and low-secretor groups in the incidence of rejection (high, 70%; low, 67%), graft survival (high, 95%; low, 94%), or patient survival (high, 95%; low, 94%). 6) Measurement of the total amount of S-HLA-I, containing yet undefined ratios of both donor and recipient S-HLA-I, cannot be used to predict a state of tolerance in liver transplant recipients.

OKT3 induction therapy: influence of duration on rejections and infections.

Anti-lymphocytes induction therapy in renal transplants remains controversial relative to efficacy and cost benefit. It has been suggested that shortening the duration of induction therapy from 14 to 7 d would provide adequate efficacy at less cost. Our objective was to compare the efficacy and complications of short (7 d or less, group A) versus standard (14 d or more, group B) duration of OKT3 induction therapy in renal allograft recipients. We performed a retrospective review of all renal allografts performed between July 1989 and September 1994. Two groups were identified based on the duration of OKT3 induction therapy. There were no significant differences between group A or B in the distribution of age, sex, race, degree of HLA matching, and etiology or renal failure. Patients in group B experienced fewer rejections at 3 and 12 months (p = 0.0236 and p = 0.0065, respectively) as well as fewer viral infections during the first year of follow-up (p = 0.0435). No difference on the mean number of bacterial or fungal infections existed between the two groups. There were no statistically significant differences in patient or graft survival, although patients in group B had a tendency towards increased 1-yr graft survival.

Soluble HLA class II concentrations in normal individuals and transplant recipients. Comparison with soluble HLA class I concentrations.

We developed an ELISA to quantify soluble HLA class II (S-HLA-II) in 702 sera obtained from normal subjects, patients with end-stage renal disease, and recipients of renal, hepatic, and cardiac transplants. Concentrations of S-HLA-II were detectable in 124 of 126 normal individuals. The distribution of normal values described a monophasic curve with a skewed distribution. In transplant recipients, there were no differences between preoperative and posttransplant values, but values in liver patients were significantly higher than in kidney patients, and values for heart patients were lowest of all groups. There were periodic variations in concentrations in individual patients, but these were unrelated to rejection, infection, or any other apparent clinical event. S-HLA-II was consistently present in the urine. All of these observations contrast with previous observations concerning soluble HLA class I (S-HLA-I) molecules, which were almost the precise reverse. It seems likely that these clear differences in S-HLA-II and S-HLA-I concentrations relate to different physiologic processes in either production, function, or elimination.

Transplantation and quality of care for end-stage renal disease: 1993.

We describe a group of renal transplant recipients whose allografts are in general considered to be successful statistically, but who are not greatly benefitted clinically. Grafts in these recipients survive somewhat longer than 6 months, but generally less than 3 years. Many of these individuals are chronically ill. They have many hospitalizations, experience most of the complications associated with transplantation, and incur more mortality and less benefit. Research initiatives need to be focused on this group of patients. A major study of more sensitive methods of detecting presensitization might be beneficial.

Soluble HLA class I in the serum of transplant recipients.

BACKGROUND: Soluble HLA, Class I (S-HLA-I) has been found in serum, plasma, body fluids, peritoneal dialysates, and urine. S-HLA-I may be a product of membrane shedding, proteolysis, and/or alternate gene splicing. Previous assays to quantitate S-HLA-I were cumbersome, required radioisotope labeling procedures, or the purification of Class I antigen preceding antigen quantitation. The authors developed a solid-phase, enzyme-linked immunoassay that can be used to quantitate S-HLA-I and to study its relevance in transplantation. METHODS: A solid-phase enzyme-linked immunoassay employing monoclonal anti-Class I to catch S-HLA-I present in plasma and peroxidase-labeled monoclonal anti-beta 2-microglobulin (B2M) to quantitate bound S-HLA-I was employed. Values were correlated with rejection and infection episodes. Pre and postoperative determinations were made from the sera of liver, heart, and kidney recipients. Size chromatography was used to compare the molecular weight of S-HLA-I from baseline and peak serum concentrations obtained during rejection episodes (2 liver, 1 heart, 1 kidney), and from 1 kidney recipient with a wound infection. RESULTS: All 9 liver recipients and 12 heart recipients demonstrated a fall in S-HLA-I, or very low initial values, for the first 10 days and then a progressive increase in values substantially above preoperative concentrations. Values from renal recipients were more variable. There were temporary increases in S-HLA-I preceding or during 16 of 20 (80%) biopsy-proven rejections (all reversible), and in 9 of 11 (83%) episodes of infection (bacterial, viral, and fungal). In heart and liver rejection, as well as the wound infection, the sera contained increased S-HLA-I, which was almost all of the same molecular weight (approximately 52,000 daltons). In serum from the one patient with renal rejection, two additional S-HLA-I peaks occurred, one with a molecular weight near 1,000,000 daltons and the second at a molecular weight approximately 11,000 daltons suggesting cellular breakdown of the donor organ. CONCLUSION: In summary, different patterns of S-HLA-I concentrations occur after kidney transplantation. Most liver and heart recipients reached a steady state higher than preoperative levels. Transient increases in S-HLA-I occurred with rejection and infection. In one severe rejection episode, larger and smaller fractions of S-HLA-I were detected and may represent cell membrane breakdown.

HLA in human serum--quantitation of class I by enzyme immunoassay.

A solid-phase, enzyme-linked immunoassay was used to quantitate the soluble fraction of HLA-class I. The sera of 318 individuals were studied, as well as the urine of six individuals with normal renal function. The stability of blood concentrations of the soluble HLA was also evaluated. The data justify the following six conclusions. (1) All normal people have circulating HLA (mean = 357 ng/ml). (2) The population can be divided into one group of low secretors (mean = 162.4 +/- 65.2 ng/ml) and another group of high secretors (mean = 540.7 +/- 185.9 ng/ml) (P less than 0.01). (3) Blood levels in each individual are reasonably consistent over short (days) and long (years) periods of time. (4) The mean concentration of soluble HLA-class I in all renal failure patients was 590 ng/ml, significantly higher than normal (P = less than 0.05); it was highest in patients on peritoneal dialysis (mean = 683 ng/ml) in spite of substantial chronic loss in peritoneal dialysate. (5) Renal allograft recipients with stable allograft function also had mean values greater than normal at 554 ng/ml (P less than 0.05). (6) Soluble HLA-class I was not detected in the urine of individuals with normal renal function.

Identification, characterization, and quantitation of soluble HLA antigens in the circulation and peritoneal dialysate of renal patients.

Human lymphocyte antigen (HLA) class I and class II antigens and beta 2 microglobulin (B2M) were identified in peritoneal dialysate (PD) and serum from patients with end-stage renal disease (ESRD) using monoclonal antibodies in an enzyme-linked immunoassay. The HLA class I and class II antigens each exhibited approximate molecular weights of 50,000 to 60,000 daltons by chromatography on Sepharose CL 6B. Class I antigens in serum and PD fluid were associated with B2M. Free B2M (Mr 11,500) also was detected in both sera and PD fluids. Unlike class I antigens, class II antigens were not found to have attached B2M. Class I and class II antigens eluted from 2-diethylaminoethanol ion exchange gradient columns at 0.07 mol/L (molar) phosphate buffer pH 7.2 and migrated with alpha 2-beta 1 mobility in agarose electrophoresis. Class I antigens were purified from ESRD patients' PD fluid by solid-phase immunoaffinity chromatography. Enzyme-linked immunoassay demonstrated that this purified protein was composed of a class I heavy chain and B2M. Class I allospecificity was confirmed by neutralization on known HLA typing antisera in a microcytotoxicity assay. Soluble HLA class I antigen preparations specifically inhibited blast transformation of responder lymphocytes in mixed lymphocyte culture reactions. Inhibition was dose dependent and ranged from 0% to 95%. The presence of soluble HLA antigens in body fluids may play an important part in the immunologic tolerance to self. This study demonstrates a ready source of large quantities of soluble HLA for detailed analysis.

Bowel injury as a result of penetrating scrotal trauma: review of associated injuries.

We report a case of bowel injury as a result of an isolated gunshot wound to the scrotum. Our experience with penetrating scrotal trauma reveals a high rate of associated injuries, the most common being trauma to the soft tissue of the thigh. Our case emphasizes the importance of a thorough preoperative and operative evaluation of patients with penetrating scrotal trauma.

Effects of fentanyl and nitrous oxide on contractility of blood-perfused papillary muscle of the dog.

The effects of fentanyl, nitrous oxide, and their combination on myocardial contractility were investigated in the papillary muscle preparation perfused by a donor dog. With a conscious donor, fentanyl infused directly into the arterial blood perfusing the papillary muscle produced a dose-related depression of developed tension. However, blood concentrations of fentanyl required to obtain the depression were in the range of 30-120 micrograms/ml. The ED50 for fentanyl for suppression of papillary muscle contractility was 89 +/- 9 micrograms/ml. When the donor dog was given nitrous oxide (N2O,80% and O2,20%), the developed tension of the papillary muscle decreased 25 +/- 5%. Fentanyl administered during nitrous oxide anesthesia caused a decrease in developed tension that was not significantly different from that obtained without N2O anesthesia (18 +/- 4% vs 13 +/- 4% for 30 micrograms/ml, and 61 +/- 5% vs 58 +/- 4% for 100 micrograms/ml). The results suggest that fentanyl produces a direct negative inotropic effect only in concentrations that are 2-3 orders of magnitude higher than its blood concentrations in fentanyl-induced anesthesia. When fentanyl and nitrous oxide are used together their interaction is not significantly different from additive.