Factors associated with severe intracranial hypertension in candidates for emergency liver transplantation.

Cerebral edema is the leading cause of death in patients with fulminant hepatic failure (FHF). Emergency OLT is often a life-saving therapy for FHF but severe cerebral edema is a contraindication to transplantation. We attempted to identify clinical and biochemical factors associated with the development of severe intracranial hypertension in FHF. Fever, psychomotor agitation, and arterial hypertension were more frequently observed preceding episodes of severe intracranial hypertension, and more than 50% of FHF patients with uncontrolled intracranial hypertension sustained severe brain injury in our series. These observations suggest that vigorous treatment of fever, arterial hypertension, and agitation are important aspects of the intensive care management of FHF patients to maintain their OLT candidacy.

National transplantation Pregnancy Registry--outcomes of 154 pregnancies in cyclosporine-treated female kidney transplant recipients.

Outcomes of pregnancies from 115 female kidney transplant recipients maintained on cyclosporine before and during pregnancy were obtained from questionnaires, hospital records, and telephone interviews. The mean age of conception was 29 years with a mean transplant interval of 2.2 years. There were 156 outcomes (2 sets of twins): ectopic 1%, therapeutic abortion 12%, miscarriage 16%, stillborn 2.6%, live birth 68.6%. The incidence of prematurity (< 37 weeks) was 56%, and that of low birthweight (< 2500 g) 49.5%. Complications occurred in 21.7% of newborns, but with only 1 neonatal death. Liveborn infants had a mean gestational age of 35.6 weeks (term 37-42 weeks) and a mean birthweight of 2407 g. The incidence of drug-treated hypertension prior to pregnancy was 51.7%; of diabetes prior to pregnancy, 11.7%; of preeclampsia, 24.8%; and of rejection during pregnancy or within 3 months postdelivery 14.5%. When infants born to women with or without a given risk factor were compared, mothers with pregnancy drug-treated hypertension had significantly lower-birth-weight infants (2250 vs. 2603 g, P = 0.028 by Wilcoxon). Similarly, mothers with prepregnancy creatinine > or = 1.5 mg/dl had smaller infants (2090 vs. 2505 g, P = 0.031 by Wilcoxon). There was a trend toward lower birth-weight in infants of diabetic recipients. Of 107 recipients interviewed, 12(11%) experienced graft loss, 8 associated with graft dysfunction or rejection during pregnancy. There was 1 graft loss during pregnancy due to rejection and 8 grafts were lost within 2 years of the pregnancy. There was one maternal death 4.3 years postpregnancy. For the 8 recipients who lost their graft within 2 years of pregnancy, outcomes included 1 miscarriage and 7 live births. The 7 live births had a mean gestational age of 35.7 weeks and a mean birth-weight of 2194 g. Five of 8 recipients who had graft loss within 2 years of pregnancy were in the drug-treated hypertensive group. Prepregnancy factors that appear to increase the risk to the newborn of a female kidney transplant recipient include maternal drug-treated hypertension, diabetes, and serum creatinine > or = 1.5 mg/dl. More data are needed before specific prepregnancy predictors for maternal graft loss can be determined in this population.

Reproductive function after liver transplantation.

Successful pregnancy outcomes are possible after liver transplantation. Although there are risks to the mother and fetus, there has not been an increased incidence of malformations noted in the newborn of liver recipients. Close, coordinated care involving the hepatologist, surgeon, and high-risk obstetrician is essential to ensure a favorable outcome. Immunosuppression peripartum should be maintained at appropriate levels. Of note, a small subset of recipients may suffer worsened graft function during pregnancy. Recurrent liver disease, especially viral hepatitis, and CMV infection appear to pose significant risks to mother and offspring, respectively, although the magnitude of the risks is unknown. It therefore would seem prudent to consider pregnancy only in female liver recipients who have passed at least 1 year with stable graft function. In addition, new immunosuppressive regimens further add to the lack of information regarding pregnancy safety. The NTPR is an ongoing database to collect information and pregnancy outcomes. That information should be helpful in counseling recipients and in pregnancy management.

The relationship between dialysis graft pressure and stenosis.

RATIONALE AND OBJECTIVES: Pressure measurements during dialysis have been used to screen for venous outlet stenosis, but the relationship between the degree of stenosis and pressure has not been defined. METHODS: To determine this relationship, failing or failed dialysis grafts (n = 34) were studied with angiography and pressure measurements from the segment of the graft near the arterial anastomosis. RESULTS: By linear regression, the relationship between the highest grade stenosis in or central to the graft and pressure was as follows: percent stenosis = 55 systolic graft pressure/systolic blood pressure+13 (r = 0.75). CONCLUSIONS: There is a positive correlation between the severity of stenosis and graft pressure, confirming the use of this measurement in screening for stenosis. It is hypothesized that this relationship is the result of progressive elimination of the normal pressure drop between the artery and arterial limb of the graft as the degree of stenosis increases.

Insertion and recovery of a new retrievable vena caval filter. Work in progress.

A new retrievable inferior vena cava (IVC) filter was tested in nine pigs. Insertion was through a 14 French sheath using both the femoral and jugular approaches. All insertions were successful, and there was a 100% postinsertion IVC patency rate (8/8 pigs at one week and 1/1 pig at one month). Addition of an apical hook to the filter design allowed transjugular retrieval of two filters at one week postinsertion. Three of nine filters migrated to the upper IVC. The filter's design allows paraxial blood flow despite trapped thrombus and inhibits filter tilting. In vitro, the filter captured 95% to 100% of 5 X 5 mm clots. If problems with migration can be solved, the new filter may provide effective short- and long-term prophylaxis against pulmonary embolism.

Risks of subsequent pregnancies on mother and newborn in female heart transplant recipients.

BACKGROUND: Female heart transplant recipients are able to carry pregnancies successfully. This study evaluates the effect of subsequent pregnancies on newborn and maternal outcomes and graft survival. METHODS: Subjects were identified through a previously reported multicenter study, case reports from literature review, and recipients entered in the National Transplantation Pregnancy Registry. A retrospective analysis was completed of 35 heart transplant recipients with first pregnancies (FP) and 12 who had one or two additional pregnancies (P>1). Newborns were assessed for gestational age, neonatal birth weight, and complications. Maternal data included pregnancy outcome, peripartum complications, including infection and rejection, current graft function, and recipient survival. RESULTS: Forty-seven pregnancies (35 FP and 12 P>1) from 35 heart transplant recipients were studied. FP outcomes included 26 live births (one set of twins), four miscarriages, and six therapeutic abortions, whereas P>1 outcomes included 11 live births (one set of twins), and two miscarriages. There was no significant difference between mean birth weights (2353+/-986 gm vs 2588+/-521 g, P>1 vs FP; mean+/-SD; p=NS) or prematurity incidence (<37 weeks; 50% vs 40%; p=NS) for the live-born infants. Compared with the FP group, there was a trend toward increased neonatal complications in P>1 (40% vs 12%; p=NS). Complications were significantly more common in premature newborns compared with full-term newborns (33% vs 5%; p < 0.05). No structural malformations were identified in the live-born infants. Maternal complication rates were the same in both groups (40%). Of 28 recipients available for follow-up, the maternal survival rate was 75% for the FP group and 89% for the P> group. Mean rejection rate per year was slightly increased after pregnancy in the P>1 group. Surviving recipients had similar graft function by echocardiographic left ventricular ejection fraction. CONCLUSIONS: Post-heart transplantation pregnancies often have successful outcomes, but there is a high incidence of prematurity and low birth weight. Subsequent pregnancies do not seem to significantly increase the incidence of complications in either the newborn or mother or increase graft rejection or failure. Larger studies of posttransplantation pregnancies may provide more definitive information.

Use of freshly isolated capillary endothelial cells for the immediate establishment of a monolayer on a vascular graft at surgery.

Endothelial seeding of vascular graft surfaces may lead to a less thrombogenic surface. We examined the feasibility of using microvessel endothelial cells derived from human fat for seeding purposes. Human fat was treated with collagenase for 24 minutes, washed, and purified in a Percoll gradient separation. This yielded 1.25 +/- 0.45 X 10(6) cells/gm of fat. After a 1-hour incubation on plasma-coated Dacron, 2.8 +/- 1.5 X 10(4) cells remained firmly adherent to the surface. When exposed to flow for 2 hours at a shear stress of 0 to 80 dyne/cm2, between 50% and 100% of the initially adherent cells remained adherent. Statistical analysis of this data failed to demonstrate a strong relationship between the number of adherent cells and the shear rate. Scanning electron microscopy demonstrated endothelial cells in various stages of attachment to the plasma-coated Dacron. Although most cells were still round and only focally attached to the surface, some cells were maximally flattened, forming cell-to-cell contact. Because of the high cell yield and the firm adherence characteristics, we conclude that microvessel endothelial cells may offer the possibility for confluent endothelial cell seeding of a graft at the time of surgical implantation without the need for cell culture.

Drug safety issues in pregnancy following transplantation and immunosuppression: effects and outcomes.

Successful pregnancy outcomes are possible after solid organ transplantation. While there are risks to mother and fetus, there has not been an increased incidence of malformations noted in the newborn of the transplant recipient. It is essential that there is closely coordinated care that involves the transplant team and an obstetrician in order to obtain a favourable outcome. Current data from the literature, as well as from reports from the National Transplantation Pregnancy Registry (NTPR), support the concept that immunosuppression be maintained at appropriate levels during pregnancy. At present, most immunosuppressive maintenance regimens include combination therapy, usually cyclosporin or tacrolimus based. Most female transplant recipients will be receiving maintenance therapy prior to and during pregnancy. For some agents, including monoclonal antibodies and mycophenolate mofetil, there is either no animal reproductive information or there are concerns about reproductive safety. The optimal (lowest risk) transplant recipient can be defined by pre-conception criteria which include good transplant graft function, no evidence of rejection, minimum 1 to 2 years post-transplant and no or well controlled hypertension. For these women pregnancy generally proceeds without significant adverse effects on mother and child. It is of note that the epidemiological data available to date on azathioprine-based regimens are favourable in the setting of a category D agent (i.e. one that can cause fetal harm). Thus, there is still much to learn regarding potential toxicities of immunosuppressive agents. The effect of improved immunosuppressive regimens which use newer or more potent (and potentially more toxic) agents will require further study.

Complications encountered with the use of the Greenfield filter.

The Greenfield filter can be used with a low complication rate provided one adheres to certain principles. First, preoperative venography to define the inferior vena caval anatomy will help avoid difficulties associated with anatomic variations. At the time the study is carried out, it would be extremely useful if the radiologist places a radiopaque marker at the level of the renal veins. This will ensure that filters will be placed in the infrarenal position when appropriate, thus preventing occasional inadvertent discharge, particularly into the right renal vein. Second, use of a guide wire greatly facilitates passage of the introducer and accurate intracaval positioning. Third, intraoperative technical errors must be recognized and promptly corrected. Finally, meticulous postoperative follow-up is essential, and recurrent embolism or any change in filter position requires repeat roentgenography of the vena cava to guide appropriate corrective treatment.

Comparison of Doppler US and CT angiography for evaluation of renal artery stenosis.

RATIONALE AND OBJECTIVES: The authors compared Doppler ultrasound (US) with computed tomographic (CT) angiography in the evaluation of stenosis of the main renal artery. MATERIALS AND METHODS: Fifty-six patients who had undergone conventional angiography of the renal arteries participated in a prospective comparison of Doppler US (45 patients) and CT angiography (52 patients). US evaluation included both the main renal artery and segmental renal arteries. RESULTS: There were 27 main renal arteries with at least 50% stenosis in 20 patients. In 36 patients, there was no significant stenosis. All cases of main renal artery stenosis detected with Doppler US of the segmental arteries were also identified with Doppler US of the main renal artery. The by-artery sensitivity (63%) of US of the main renal artery was greater than that (33%) of US of the segmental arteries. CT angiography was more sensitive (96%) than Doppler US (63%) in the detection of stenosis, but the specificity of CT (88%) was similar to that of US (89%). The difference in the area under the receiver operating characteristic curve (AUC) between CT (AUC = 0.94) and US (AUC = 0.82) was statistically significant (P = .038). CONCLUSION: Doppler US of the main renal artery is more sensitive than Doppler US of segmental arteries in the detection of stenosis. CT angiography is more accurate than Doppler US in the evaluation of renal artery stenosis.

Results of liver transplantation for nodular regenerative hyperplasia.

Liver transplantation has been performed in individuals with a pretransplant clinical diagnosis of cirrhosis but with nodular regenerative hyperplasia histologically. The purpose of this report is to investigate the results of liver transplantation in patients proven to have nodular regenerative hyperplasia post-transplant. A retrospective review was undertaken of four patients who underwent liver transplantation with a histologic diagnosis of nodular regenerative hyperplasia. All were felt to be cirrhotic on clinical grounds. Final histology of the explanted liver was confirmed by a single pathologist. Their ages ranged from 39 to 54 years, and three of the four were male. Three had pretransplant needle liver biopsies, two percutaneous and one transjugular. All revealed nonspecific reactive changes. Ultrasound and MRI were interpreted as consistent with cirrhosis in four of four and three of four cases, respectively. Portal vein flow was hepatopedal in three and absent in one. Pretransplant clinical characteristics and frequency were as follows: bleeding varices two, clinical ascites three, encephalopathy three, and impaired hepatic synthetic function two. All four patients underwent successful liver transplantation. There were no episodes of acute rejection. All are alive and well with normal graft function 2 to 4 years post-transplant. We conclude the following. 1) Patients with clinical end-stage liver disease due to underlying nodular regenerative hyperplasia can successfully undergo transplantation. 2) Nodular regenerative hyperplasia can present with signs and symptoms of liver failure, is difficult to diagnose by needle biopsy, and can be difficult to discriminate clinically from cirrhosis. 3) Although each case must be individually evaluated transplantation may be the optimal therapy in patients presenting with complications of liver failure.

Serum amino acids following human orthotopic liver transplantation.

Our findings indicate that serum amino acid changes after OLT are complex and influenced by multiple factors including sepsis and use of parenteral hyperalimentation with exogenous amino acids. Additional factors which may influence the rate of normalization of amino acids after OLT include the presence of malnutrition (frequently observed before OLT) and the extent of pretransplant portal-systemic shunting. Our results demonstrate that the presence of septic complications and the use of CPN are important determinants of the postoperative levels of several amino acids, including the BCAA/AAA ratio. Our logistic regression model using the BCAA/AAA ratio predicted the occurrence of sepsis after OLT 77% of the time. Prospective assessment and validation of this model is under way.