Pancreas allograft rejection: correlation of transduodenal core biopsy with Doppler resistive index.

PURPOSE: To determine the usefulness of sonographically obtained resistive indexes (RIs) in the diagnosis of pancreas allograft rejection. MATERIALS AND METHODS: Findings were studied from 78 transduodenal pancreas allograft biopsies that were ultrasound-guided and cystoscopically directed. The 78 biopsies included 40 that were compared directly with baseline RI data. Biopsies were categorized by result and correlated with concurrent RIs (including 26 RIs obtained within 24 hours of biopsy) with the chi2 test for categoric variables and the Student t test for continuous variables. Sensitivity, specificity, and positive and negative predictive values were calculated with standardized formulas. RESULTS: The mean RIs between the no rejection, mild acute rejection, and moderate acute rejection groups were not statistically significantly different; however, the mean RI associated with chronic rejection was statistically significantly higher (P < .05) than that in the other groups. The sensitivity, specificity, and positive and negative predictive values of either an elevated RI (> 0.70) or greater than 10% increase in the RI above the baseline value in the diagnosis of acute rejection were approximately 50%. CONCLUSION: Neither the absolute level of the RI nor the relative increase was correlated with acute rejection proved at biopsy. Changes in RIs after pancreas transplantation were a poor indicator of acute rejection, but the absolute value of the RI was elevated in cases of chronic rejection.

Pancreas transplants: efficacy of US-guided cystoscopic biopsy.

Between December 1991 and June 1993, the authors performed cystoscopic transduodenal biopsy of pancreas transplants in 35 consecutive patients (18 men and 17 women, aged 22-48 years [mean, 34 years]). The first 12 biopsies were performed under direct visualization and the last 23 were performed with ultrasonographic (US) guidance. Specimens were adequate for pathologic diagnosis in nine of 12 (75%) and in 22 of 23 (96%) biopsies, respectively. US-guided biopsy of pancreas transplants is safe and effective and gives increased diagnostic yield.

Cholelithiasis in pancreas and kidney transplant recipients with diabetes.

BACKGROUND: Vascularized pancreas transplantation (PTx) for type I diabetes mellitus results in euglycemia at the expense of chronic immunosuppression, hyperinsulinemia, and dyslipidemia. However, the effect of PTx on native biliary lithogenesis remains unknown. METHODS: To address this issue, we retrospectively studied 72 consecutive pancreas transplant recipients and compared them with patients both with (n = 35) and without (n = 52) diabetes mellitus undergoing kidney transplantation alone (KTA). All patients underwent pretransplantation abdominal ultrasonography, which was repeated at 6- to 12-month intervals after transplantation. PTx recipients were managed with quadruple immunosuppression with OKT3 induction. Kidney transplant recipients received cyclosporine and prednisone. RESULTS: Seventeen (30.4%) of 56 evaluable PTx recipients had gallstones at a mean interval of 13 months (range, 5 to 24) after PTx. Eleven patients underwent open cholecystectomy (with one surgical exploration of common bile duct for choledocholithiasis), three underwent laparoscopic cholecystectomy, and the other three are being managed expectantly. Gallstone analysis revealed predominantly cholesterol stones. The incidence of cholelithiasis in kidney transplant recipients with and without diabetes mellitus was 27.3% and 12.2%, respectively (p = 0.04). CONCLUSIONS: Pancreas transplant and kidney transplant recipients with diabetes are predisposed to the development of gallstones compared with recipients without diabetes. An interaction between diabetes mellitus-induced gallbladder dysmotility and cyclosporine-induced cholestasis may be a possible mechanism. We recommend serial ultrasonographic examinations in pancreas transplant and kidney transplant recipients, and cholecystectomy in pancreas transplant recipients with cholelithiasis should be considered.

The AIUM/ACR antepartum obstetrical sonographic guidelines: expectations for detection of anomalies.

A survey was sent to 52 physicians considered experts in obstetrical sonography asking them to comment on the probability of observing various fetal abnormalities when the AIUM/ACR guidelines for a level one obstetrical sonogram were followed. Although definite trends were noted in several areas, there was much diversity in opinion concerning what should or should not be seen when the guidelines were followed. Given the fairly specific nature of the AIUM/ACR guidelines, we were uncertain why the responses were not in more uniform agreement.

The choroid plexus pseudocyst: sonographic identification and characterization.

Amniocentesis has been advocated by some authors when fetal choroid plexus cysts are discovered, because of their reported association with karyotype abnormalities. We have noted an oval hypoechoic structure projecting into the adjacent choroid plexus, which simulates a cyst when imaged across its short axis, in 39 of 50 consecutive fetuses. This presumably normal structure or pseudocyst may represent the corpus striatum. Knowledge of its existence and benign nature will help avoid diagnostic errors and unnecessary amniocenteses.

MR of the knee: the significance of high signal in the meniscus that does not clearly extend to the surface.

On MR images of the knee it is sometimes impossible to determine with confidence if a focus of high signal in the meniscus is confined to the substance of the meniscus or if it extends to involve the surface. This is a critical differentiation because the latter represents meniscal tears that can be found and treated at arthroscopy, whereas the former represents degeneration, tears, or perhaps normal variants that cannot be detected or treated arthroscopically. We make an equivocal diagnosis of a tear when it is difficult to decide if signal in a meniscus involves the meniscal surface. We studied MR scans of the knee in 142 consecutive patients for the presence of such equivocal tears. Their prevalence was 14% (20/142); 17 were in the posterior horn of the lateral meniscus and three were in the posterior horn of the medial meniscus. In 13 cases with arthroscopy/arthrotomy correlation, no tears were found. In one of the 20 patients in whom the meniscus was removed during arthroplasty, histologic examination of the meniscus showed separation of collagen bundles, which was caused by meniscal degeneration confined to the substance of the meniscus. These results suggest that a meniscal tear is unlikely when MR scans show a focus of high signal in a meniscus that does not unequivocally extend to involve the surface of the meniscus.

Evaluation of elastase and antielastase balance in patients with chronic bronchitis and pulmonary emphysema.

On the basis of the "protease-antiprotease imbalance" theory for the pathogenesis of pulmonary emphysema, we hypothesized that measurement of elastase burden and antielastase capacity in the alveolar space might correlate with emphysema. To evaluate this, the severity of emphysema, the elastase burden, and the elastase inhibitory capacity were estimated in 28 patients with chronic bronchitis and variable degrees of emphysema, none of whom had congenital deficiency of alpha-1-protease inhibitor, and all of whom underwent bronchoalveolar lavage. Emphysema was assessed by both computed tomography and diffusing capacity. To examine "elastase burden," elastase:alpha-1-protease inhibitor complex and free elastase activity in alveolar lavage fluids were measured. To evaluate "antielastase" capacity, elastase inhibiting capacity in alveolar lavage fluid was measured. Elastase burden correlated directly and antielastase capacity correlated inversely with emphysema. These data provide direct support for the "protease-antiprotease imbalance" theory of emphysema in a group of smokers without congenital deficiency of alpha-1-protease inhibitor.

Bowel function of healthy men consuming liquid diets with and without dietary fiber.

The importance of the level of dietary fiber intake on bowel function was measured in 16 healthy young males consuming self-selected and liquid enteral diets. Subjects consumed liquid Ensure as their sole nutrient source plus 0 (diet a), 30 (diet c), and 60 (diet d) g/day soy fiber, a fiber source high in hemicellulose that was added to the Ensure. Further, to examine whether heat processing affects the physiologic action of fiber, subjects consumed Enrich, an enteral formula similar to Ensure, which contains 30 g of the same soy fiber (diet b). The four diets were consumed in randomized order each for 10 days. Daily wet stool weight averaged 144.6 g on the self-selected diet and decreased significantly to 67.3 g when Ensure was consumed alone. Average stool weights on diets (b), (c), and (d) were 114.6, 100.2, and 150.3 g/day, respectively. Average fecal dry weights for the four diets were 19.1, 28.7, 25.0, and 30.3 g/day for (a-d), respectively. Gastrointestinal transit time, as measured with radiopaque pellets, was longest on the Ensure diet, 72.4 hr, and approximately 2 days on the fiber-supplemented diets and the self-selected diet. Thus, soy fiber's physiologic effect on laxation was not changed by heat processing. Also, although stool weights were larger on higher fiber intakes, transit rates were similar on all the fiber-containing diets.

Oxygenation alters red cell folate levels.

Folate activity is consistently higher in deoxygenated than oxygenated human blood as measured by both radioassay and Lactobacillus casei growth. Red cell, but not serum, folate levels are rapidly mutable: when fully oxygenated, the mean red cell folate level of 15 samples was 489 ng/ml; after deoxygenation the mean rose to 553 ng/ml; following re-oxygenation the mean returned to 488 ng/ml. Transport of folate across the red cell membrane apparently does not contribute to these changes in folate levels, since agents known to inhibit permeation (N-ethyl-maleimide, p-chlormercuriphenyl sulfonic acid and ethacrynic acid) do not affect the rise with deoxygenation. Moreover, new synthesis of folate compounds seems unlikely, since the changes are observed in energy-depleted cells. Instead, direct binding of folate to haemoglobin is suggested by experiments in which the rise with deoxygenation was not seen in red cells exposed to carbon monoxide or treated with cyanate. Similar changes also occur in vivo: canine red cell, but not serum folate levels are significantly higher (P less than 0.05) in samples collected from five different veins compared with blood from the paired artery (carotid-jugular, renal, mesenteric, splenic, femoral) of four animals. Thus red cell folate levels are predictably influenced by the levels of oxygenation of the erythrocyte both in vitro and in vivo, possibly by reversibly binding to haemoglobin.

Effects of pH on 5-methyltetrahydrofolic acid transport in human erythrocytes.

We measured the effects of external pH on influx, efflux and net steady-state levels for 14CH3H4PteGlu1. Initial rates of uptake were inversely proportional to external pH. Lowering the pH of the suspending medium increased influx by enhancing the affinity of the carrier: the apparent Km values at pH 6, 7.2 and 8.1 were 0.14, 0.25 and 0.63 microM respectively. In contrast, Vmax was independent of external pH. Efflux rate constants at pH 6, 7.5 and 8.5 were 0.034, 0.059 and 0.067/min respectively. consequently, lowering the external pH increased steady-state levels of 14CH3H4PteGlu1.

Protein A adsorption of acute myelogenous leukemia serum induces in vitro blast lysis.

We studied cytotoxic activity of acute myelogenous leukemia (AML) sera for AML blasts before and after immunoadsorption with Staphylococcus aureus, Cowan I (SAC), which contains protein A. We found in vitro that incubation with treated AML sera reduced viability to 42.7% of control (p less than 0.01) for autologous and 21.0% of control (p less than 0.01) for allogeneic blasts. Normal peripheral blood cells were not killed by treated AML sera. Wood 46 strain of Staphylococcus aureus, which does not contain protein A, did not significantly reduce AML blast viability (94.8%, p greater than 0.4), while Sepharose-bound protein A reduced viability to 63.8% (p less than 0.01). Cytotoxicity does not appear to be complement-mediated, byt cytotoxic activity is trypsin-sensitive and is contained in the immunoglobulin fraction. This model for study of the tumoricidal action of protein A adsorption should be useful for predicting utility of plasma adsorption as a therapeutic adjunct in the future.

Inhibition of 5-methyltetrahydrofolic acid transport by amphipathic drugs.

Numerous chemically unrelated drugs after the membrane transport of folate compounds. To investigate drug structure-activity relationships, we measured the effect of amphipathic drugs (that is, compounds with polar-apolar character) on 5-methyltetrahydrofolic acid permeability of human erythrocytes. All drugs tested were inhibitory, but only compounds that exist at least partially in the anionic form were highly active. Ethacrynic acid, sulfinpyrazone, phenylbutazone, sulfasalazine, and furosemide were effective transport inhibitors in micromolar concentrations. In contrast, compounds that are capable of forming cations at physiologic pH, such as chlorpromazine, procaine, tetracaine, and papaverine, were inhibitory only in millimolar concentrations or caused hemolysis before major inhibition was seen. Inhibitory activity correlated with drug dissociation constant (r = 0.87). A double-reciprocal plot analysis of drug effect on 5-methyltetrahydrofolic acid transport showed changes in both Km and Vmax (indicating a mixture of competitive and noncompetitive inhibition) by ethacrynic acid, sulfasalazine, and phlorizin. Inhibitory activity of a series of eight phenoxyacetic derivatives, including ethacrynic acid, correlated highly with measurements of liposolubility (r = 0.87) but only weakly with the Hammet substituent constant (r = 0.56). These results suggest that the effect of amphipathic drugs on 5-methyltetrahydrofolic acid transport is influenced by drug pKa and by the presence of hydrophobic substituents, but is relatively independent of electron-attracting groups.