Early diagnosis of rejection. Correlation of enzymuria and histological findings after renal transplantation in the rat.

One hundred renal transplants were performed between different rat strain combinations. Posttransplant renal function was monitored using serum creatinine levels, creatinine clearance rates, and N-acetyl-beta-D-glucosaminidase (NAG) enzymuria. These biochemical measurements were compared with the morphological appearances of the transplanted kidney. Rises in NAG enzymuria proved to be useful diagnostic indicators of graft rejection with a false positive rate of only 6%. In 78% of the rejection episodes, the urinary NAG level rose 2 days before any elevation in serum creatinine concentration. There was a close correlation among increasing NAG enzymuria, decreasing renal function, and the structural events of rejection--indicating that the routine measurement of tubular enzymuria would be of value in the prediction and diagnosis of renal allograft rejection.

Central pontine myelinolysis and cyclosporine neurotoxicity following liver transplantation.

In a recent series of 44 liver transplants we identified both extrapontine myelinolysis (EPM) - characteristic of cyclosporine neurotoxicity - and central pontine myelinolysis (CPM) in 5 recipients posttransplant. An additional 2 recipients had EPM only posttransplant. MRIs performed in 4 asymptomatic recipients were normal. Large perioperative shifts in serum sodium, hypomagnesemia, and high cyclosporine levels may play a role in the development of these lesions, although the evidence from this study is inconclusive. In addition to supportive care, dilantin was started in patients who had seizures; aggressive magnesium replacement was initiated for hypomagnesemia, and cyclosporine levels were reduced in all patients. All patients demonstrated a slow steady recovery and all but 2 are at home at the time of writing. CPM may be more prevalent than previously appreciated following liver transplantation, although its prognosis may not be as dismal.

Expression of E-cadherin in human colorectal cancer.

AIM: To investigate the expression of E-cadherin, a calcium-dependent cell-cell adhesion molecule in colorectal carcinoma. Antibodies to E-Cadherin were used to establish the association of their expression with the clinicopathological characteristics of this disease using immunohistochemical methods. METHODS: Immunohistochemical analysis for E-cadherin was carried out in formalin-fixed, paraffin-embedded sections of neoplastic colorectal tissues and non-neoplastic ones adjacent to the lesion from 49 patients who underwent surgery, by the standard peroxidase-antiperoxidase method. Expression of this antigen in normal and malignant epithelium and stromal cells was compared. RESULTS: Both neoplastic and normal tissues showed expression of E-cadherin. There was, however, higher expression of E-cadherin in epithelial cells in both tumour and normal tissues than stromal cells. The percentage of expression in epithelial cells of well-differentiated tumours was significantly higher than moderately differentiated tumours. Loss of normal membranous expression and the presence of cytoplasmic and mixed staining were found frequently in tumour tissues (p = 0.004). This loss of membranous expression, however, did not correlate with Duke's staging, tumour grade, sex, size or site of the tumour. CONCLUSION: This study suggests that the lower expression of E-cadherin in less differentiated tumours may explain their aggressive nature, although loss of membranous expression was not significantly correlated to Duke's staging, tumour grade, sex, size and site of tumour.

Blood ordering habits for elective surgery: time for change.

A prospective study was carried out for 6 months to determine the efficacy of blood ordering routines for elective surgery. It was found that only 23% of procedures needed preoperative crossmatching of blood (transfusion index 'TI' greater than 0.5). There was an excessive over-ordering of blood for 77% of the operations (crossmatch/transfusion ratio greater than 2.5). In addition, the transfusion index for the latter group showed that there was no need to prepare blood preoperatively (TI less than 0.5). A transfusion tariff is worked out which abandons crossmatching for the majority of procedures (cholecystectomy, thyroidectomy and surgery for duodenal ulcer excluding gastrectomy). Instead a 'group and screen' policy is suggested.

Conserving blood in preparation for elective surgery.

A prospective study was carried out for a period of 6 months (September 1987 to 28 February 1988) to evaluate the possible misuse of blood transfusion service in the department of surgery, Amiri Teaching Hospital, Kuwait. There was a monthly wastage of 45 +/- 13 units of blood. Five hundred and eleven units of blood were crossmatched but never transfused. The time taken by the blood bank technicians in crossmatching blood which was never used amounted to 54.4% of the normal working hours. An annual loss of about US$25000.00 was calculated to have occurred.

Acute renal failure: the tip of the iceberg?

This study reports the experience, during a six-year period, of the Aberdeen Renal Unit in the treatment of patients with acute renal failure. The combination of a relatively stable population base and a single regional dialysis centre has allowed the incidence of acute renal failure to be assessed. Approximately 30 patients per million population were dialysed annually for acute renal failure; 69 per cent of these patients (20.5 per million population per year) were dialysed for acute reversible intrinsic renal failure (ARIRF) and mortality in this group was 44 per cent. Patients with more severe disease at the time of presentation to the renal unit, as defined by a clinical severity score, had significantly reduced survival rates. However, it was not possible to predict the outcome in individual cases; ten of 24 patients with clinical severity scores which indicated a poor prognosis survived the period of oliguria and were discharged from hospital. The fact that other renal units dialyse fewer patients per million population per year for ARIRF probably reflects a reluctance to refer patients whose general condition appears poor. As the overall mortality rate reported in this study does not differ significantly from rates reported previously from centres treating a smaller proportion of patients, such decisions may not be correct. It is well known that facilities in Britain for treating patients with end-stage renal disease are inadequate; it now appears likely that some patients who might benefit from acute dialysis are being denied treatment for a potentially reversible disease process.

Is venous reflux a common disease in post-thrombotic patients with unilateral deep vein thrombosis episode?

OBJECTIVES: To investigate reflux development and changes in resting venous diameters in the DVT and the non-DVT lower limbs. METHODS: Twenty subjects (40 limbs) with acute unilateral proximal DVT diagnosed by ultrasound, who were treated with low-molecular-weight-heparin (LMWH), followed by at least three months of oral warfarin therapy, were enrolled in the study. The limbs were classified according to CEAP (clinical, aetiologic, anatomic, pathophysiology) clinical classification on a scale of 0-6. Duplex ultrasound (DUS) was employed to assess DVT resolution, vein diameter and venous reflux in both limbs at intervals of zero, three, six and 12 months. Venous reflux was defined as a valve closure time more than 1 s. RESULTS: There were 13 men and seven women, average age was 40.8 years and average body mass index 27.7 kg/m2. In the DVT limbs at three, six and 12 months, deep veins were non-occluded in 40%, 60% and 85%, respectively. By 12 months, 16 (80%) had developed venous reflux, mostly in the femoral (FV) and popliteal veins (PV); eight limbs (40%) were in clinical classes 4-6. In the contralateral 20 non-DVT limbs, four limbs developed borderline reflux at the sapheno-femoral junction (SFJ) after six months and mean diameters of SFJ, FV and PV increased significantly. CONCLUSIONS: Venous reflux is highly likely to occur in DVT limbs within a year follow-up period. Venous dilatation can occur in the contralateral unaffected lower limb, consistent with a systemic effect. Our results are suggestive and further studies are needed.

Hemorrhoidectomy and sphincterotomy. A prospective study comparing the effectiveness of anal stretch and sphincterotomy in reducing pain after hemorrhoidectomy.

The effectiveness of two maneuvers, anal stretch (group 1) and sphincterotomy (group 2), were evaluated in reducing posthemorrhoidectomy pain. The study included 133 patients in group 1 and 125 patients in group 2. Immediate follow-up results showed that 18.4 percent of patients in group 2 required narcotic analgesics in the first 24 hours as compared with 100 percent of group 1 patients (P less than .01). Urinary retention developed in 4 percent of the patients in group 2 and 39 percent of the patients in group 1 (P less than .01). Pain associated with the first postoperative motion was severe in 96.2 percent of those in group 1 as compared with 6.4 percent of patients from group 2 (P less than .01). Moreover, long-term follow-up showed that 57.3 percent of group 1 patients continued to suffer from fecal soiling for ten weeks as compared with 6.4 percent in group 2 who suffered only 4.5 weeks (P less than .01). The routine performance of sphincterotomy through one of the hemorrhoidectomy wounds significantly reduced posthemorrhoidectomy pain and complications.

Giant salivary calculi: an orocervical fistula caused by a submandibular gland calculus.

Large calculi of the salivary glands are rare. They may go undetected for many years. The authors report three cases of giant submandibular gland calculi. In one patient, the calculus was an incidental finding. In all patients, the mass was in the substance of the gland; in one, the configuration of the mass was unusual and it had eroded through the floor of the buccal cavity forming an orocervical fistula (the first such report) and in another the mass occupied a small portion of Wharton's duct. The histopathologic findings in all three cases were of nonspecific chronic inflammation. All the patients made a smooth recovery and had no complaints at follow-up.

Reinforced primary repair of early distal oesophageal perforation.

OBJECTIVE: To describe our surgical technique for, and results of, reinforced primary repair in benign distal oesophageal perforation in early cases. DESIGN: Retrospective study. SETTING: Tertiary care hospital, Kuwait. PATIENTS: 15 patients with iatrogenic or traumatic benign distal oesophageal perforation. INTERVENTION: Primary repair with reinforcement using pleura, pericardial flap, or gastric fundus. Of the 3 patients with achalasia, 2 had oesophagomyotomy alone and 1 had oesophagomyotomy with fundoplication. Associated distal obstruction caused by reflux stricture was treated by dilatation and fundoplication in 1 patient. MAIN OUTCOME MEASURES: The causes of perforation, presence of underlying oesophageal disease, time to operation, postoperative leakage, mortality, and follow-up. RESULTS: Perforation was caused by instrumentation in 10 patients, trauma in 3, and ingested foreign bodies in 2. 6 patients had pre-existing oesophageal diseases: achalasia in 3, hiatus hernia in 2, and reflux stricture in 1. 10 patients presented within 12 hours, and 5 patients more than 12 hours after the perforation. 4 postoperative leaks developed. One patient perforated a stress gastric ulcer and then developed pneumonia and died of multiple organ failure. At follow-up, all 14 surviving patients were able to eat a normal diet. 2 patients who had gastric fundus used as a reinforcement tissue developed mild gastro-oesophageal reflux and oesophagitis. Both responded to medical treatment. CONCLUSION: Primary repair and tissue reinforcement of benign distal oesophageal perforation is safe in early cases and obviates the need for a second operation.

Necrotizing fasciitis.

Ten cases of necrotizing fasciitis are reviewed. Three patients died but only two of these deaths were due to uncontrolled septicaemia. All isolated organisms were sensitive to a combination of piperacillin and ampicillin which we now regard as the initial antibiotic combination of choice. Prompt and aggressive surgical debridement remains the cornerstone of management.

Key features distinguishing post-transplantation lymphoproliferative disorders and acute liver rejection.

Post-transplantation lymphoproliferative disorder (PTLD) and acute rejection are two serious complications of orthotopic liver transplantation that can have a similar histologic appearance. We undertook the present study to assess the best way to distinguish these two entities. We studied histologic features, immunophenotyping, and Epstein-Barr virus (EBV) status, as assessed by immunohistochemical stain and in situ hybridization (ISH), in three groups: Group I, 8 cases of PTLD post-orthotopic liver transplantation with liver involvement; Group II, 15 cases diagnosed with acute liver rejection (control group); and Group III, a subset of 6 biopsy specimens from 4 patients of Group I whose graft rejection was diagnosed within the 2 months preceding the diagnosis of PTLD. The mean proportion of plasma to plasmacytoid cells in most cases from Group I was more than 40%, whereas from Group II it was less than 25% (P = .0001). There was a higher number of B lymphocytes than T lymphocytes in Group I. The numbers of mitotic figures and immunoblasts were significantly different in the two groups (P < .0001 and P = .0005, respectively), being higher in the patients with PTLD. EBV immunostain was most specific for the diagnosis of PTLD (75% positive in Group I, negative in Group II). ISH for EBV-encoded RNA was positive in 87% of cases in Group I and only 6.6% of cases in Group II (P = .0005). In Group III, four of the six liver biopsy specimens had a low plasma cell count and were negative for EBV studies. The other two biopsy specimens in this group had 70 to 80% plasma cell infiltrate, in addition to positive EBV immunostain and ISH in one, for which tissue was available for study. We conclude that viral studies and assessment of the number of plasma cells and B lymphocytes can help to distinguish between acute rejection and early PTLD.

Foot infections in diabetics: the antibiotic choice.

The authors studied 59 diabetics with foot infections to determine the organisms responsible and the sensitivity to antibiotics. All infections were polymicrobial (aerobic and anaerobic). On average 3.2 isolates per culture were obtained from the depth of the infection. The commonest organisms in order of frequency were: Staphylococcus aureus, beta-hemolytic streptococci, Proteus sp., Bacteroides sp., enterococci, Klebsiella sp. and Pseudomonas aeruginosa. A combination of piperacillin and cloxacillin is recommended as initial therapy for foot infections in diabetic patients because it was found to be effective for 73% of the causative microorganisms.

Biliary reconstruction without T tubes or stents in liver transplantation: report of 502 consecutive cases.

Although T tubes and stents are widely used as part of the routine biliary reconstruction in liver transplantation, they have inherent complications and there is no proof that they are beneficial to healing. We do not use T tubes or anastomotic stents, and we reviewed our experience with 502 consecutive, whole-size liver grafts to determine the incidence and nature of biliary complications. Duct-to-duct (D-D) and Roux-en-Y loop-to-duct (RY-D) anastomoses were performed in 321 and 176 cases, respectively. In 62% of cases, the donor gallbladder was transplanted and an external catheter cholecystostomy was fashioned to provide for postoperative cholangiography. In the remaining cases the gallbladder was removed. Biliary complications of all types occurred after 13.5% of the transplants. Anastomotic complications (stricture, obstruction, or leak) occurred in 8.2% of the cases, and they were least frequent (4.0%) with RY-D reconstructions. Gallbladder-related complications accounted for one quarter of all biliary complications, and they outweighed the advantage of convenient access to the biliary tree for cholangiography. Four patients (0.9%) died of biliary complications. We conclude that routine reconstruction of the biliary tract without T tubes or stents is a safe technique in liver transplantation. Retaining the donor gallbladder as a method of providing cholanglography is not necessary.

Prolonged survival of rat renal allografts after multiple allogeneic pregnancies: strain specificity and role of erythrocyte antibody rosette inhibiting antibodies.

The influence of allogeneic pregnancies on the survival of subsequent rat renal allografts was investigated in three rat strain combinations. Multiple but not single pregnancies produced significantly more long-term surviving kidney grafts than were found in virgin animals; the effect was specific for paternal antigens, as multiple pregnancies by an unrelated strain did not prolong kidney graft survival. In the multiparous groups, those animals with long-surviving grafts had significantly higher levels of non-cytotoxic antibodies against paternal strain B-lymphocytes (detected by the erythrocyte antibody rosette inhibition assay) than did animals which rejected their grafts. The results show that multiple pregnancies may produce a state of specific unresponsiveness to paternal antigens, similar to enhancement, which is marked by the presence of non-cytotoxic antibodies against paternal B-lymphocytes. It is suggested, therefore, that enhancement may be one of the protective mechanisms which prevent rejection of the fetus during pregnancy.

Renal function in rats treated with cyclosporin following unilateral nephrectomy.

The effects of oral cyclosporin A (25 mg/kg/day) on renal function and structure in groups of normal, laparotomized and unilaterally nephrectomized DA rats was assessed over a 4-week period. In each group, the drug caused impairment of function, although there was evidence of improvement during the course of the study. Cyclosporin A toxicity was most marked in the nephrectomized animals, where histological examination at 4 weeks revealed extensive damage to proximal straight tubular cells. Only minimal structural damage was observed in the two other groups. Cyclosporin A concentrations in whole blood and kidney were estimated by radioimmunoassay at 4 weeks. Similar drug levels were found in normal, laparotomized and nephrectomized animals, except for an unexplained fall in blood levels in the laparotomy group. The significance of these observations is discussed in the context of current knowledge concerning the physiological effects, toxicology and pharmacology of cyclosporin A.