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Biomedical subjects

R A Krom

Publications and source records attributed to R A Krom.

At least 73 records · Page 4Linked to original sources
PubMed1995

Intracerebral hemorrhage in liver transplant recipients.

OBJECTIVE: To analyze possible causative mechanisms for intracranial hemorrhage after orthotopic liver transplantation. DESIGN: We conducted a retrospective survey of medical records and a case-control comparison in patients who had undergone liver transplantation during the period 1986 through 1992. MATERIAL AND METHODS: In a group of 8 patients with intracranial hemorrhage after orthotopic liver transplantation and a control series of 207 patients who had undergone liver transplantation but did not have intracranial hemorrhage, we summarized pertinent clinical and laboratory data and statistically analyzed potential risk factors for hemorrhage. RESULTS: In the eight study patients, intracerebral hematomas were located in the parietal or frontal lobe in six, the cerebellum in one, and the putamen in one. Autopsy demonstrated a Candida-associated mycotic aneurysm in one of the eight patients, and one had disseminated aspergillosis. No statistically significant differences in thrombocytopenia, hypertension, extracranial bleeding sites, or cyclosporine-related neurotoxicity were found when these patients were compared with the control series. Bacteremia or fungemia was found in five of the eight patients with intracerebral hemorrhages (62%) but in only 11% of the control group (P = 0.03; Fisher's exact test). CONCLUSION: Overwhelming infections, thrombocytopenia, or both may have a role in intracerebral hemorrhage after liver transplantation.

Adolescent↗
PubMed1995

Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue.

We have previously reported that low hepatic tissue cyclosporine levels correlate with early cellular rejection after liver transplantation. The aim of this study is to determine whether there is a similar relationship in patients treated with FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28 = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection were compared with 7 patients immunosuppressed with FK506 with cellular rejection who underwent a total of 23 liver biopsies, including 9 biopsies that showed rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There was no significant difference between the nonrejection and current rejection groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P = .50). In contrast, the median hepatic tissue concentration of FK506 was significantly higher in the nonrejection group than it was in the current rejection group, 144 ng/g versus 48 ng/g (P = .02). In the current rejection group, 7 of 9 hepatic tissue concentrations of FK506 were < 100 ng/g, and in the nonrejection group, 18 of 25 hepatic tissue concentrations were > 100 ng/g. Low hepatic tissue concentrations of FK506 correlate with the occurrence of early cellular rejection after liver transplantation, in contrast to plasma concentrations of FK506. A hepatic tissue concentration of FK506 < 100 ng/g is 78% sensitive and 72% specific for cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Failure of hepatopulmonary syndrome to resolve after liver transplantation and successful treatment with embolotherapy.

The hepatopulmonary syndrome is an uncommon accompaniment of chronic liver disease. The outcome of this disorder after orthotopic liver transplantation is variable. We describe a patient with the hepatopulmonary syndrome who underwent orthotopic liver transplantation for autoimmune hepatitis. Her platypnea and orthodeoxia failed to improve postoperatively. Pulmonary angiography showed large pulmonary arteriovenous shunts that were successfully treated with coil embolotherapy.

Adult↗
PubMed1994

The role of portosystemic shunts for variceal bleeding in the liver transplantation era.

OBJECTIVE: To review our experience with portosystemic shunts during the era of liver transplantation at the Mayo Clinic to provide insight into the selection of patients for these procedures. DESIGN: We reviewed the charts of a cohort of 57 patients who underwent portosystemic shunting between 1985 and 1990 for the management of variceal bleeding. A follow-up survey by letter and telephone was also conducted. SETTING: The Mayo Clinic, a tertiary referral center. PATIENTS: These patients were not considered transplantation candidates at the time of the shunt because of active alcoholism, extensive portal vein thrombosis, coexistent myelodysplastic syndromes, or malignant neoplasms. INTERVENTION: Portosystemic shunts; the exact type was at the surgeon's discretion. OUTCOME: Survival after shunt surgery among patients with various liver diseases. RESULTS: Twenty-two patients died during follow-up after being shunted for bleeding, and one of the shunted patients subsequently required liver transplantation. Comparison of Kaplan-Meier survival curves between various groups of patients indicated that patients who were actively alcoholic had a poorer chance of survival (P < .003) than did those who were abstinent. Patients with portal vein obstruction or chronic cholestatic liver disease appeared to do better after shunt surgery than did patients with other causes of portal hypertension. Other factors such as age, Child-Pugh score, or presence of malignant neoplasms did not reliably predict outcome from portosystemic shunts. CONCLUSIONS: In well-selected patients who may not be deemed candidates for liver transplantation, portacaval shunts can be effectively employed to prevent bleeding from esophageal varices that are resistant to obliteration by sclerotherapy.

Cause of Death↗
PubMed1994

FK506-induced neurotoxicity in liver transplantation.

We report FK506-induced neurotoxicity in 14 of 44 consecutive patients following orthoptic liver transplantation. In 10 of these 14 patients, postural hand tremors were found in the first weeks following surgery, transient apraxia of speech in 3, and generalized tonic-clonic seizures were noted in 2 patients. Other manifestations included nightmares, agitation, and acute delirium. Reduction of the FK506 dose resulted in resolution of symptoms, but in 1 patient mild speech difficulties and in 3 patients a fine tremor remained. Blood and plasma levels of FK506 were similar in patients with and without neurotoxicity. FK506 neurotoxicity in patients with liver transplantation commonly results in transient neurological manifestations. The incidence of neurotoxicity in FK506 is dramatically reduced in maintenance doses of 0.075 mg/kg twice a day.

Adult↗
PubMed1994

A case of Aspergillus fumigatus peritonitis complicating liver transplantation.

A 55-year-old male underwent orthotopic liver transplantation for sub-fulminant hepatitis B/delta infection superimposed on probable genetic hemochromatosis with early cirrhosis. Pre-operatively, he demonstrated serologic evidence of cytomegalovirus reactivation and developed cytomegalovirus viremia when ganciclovir was discontinued post-operatively. His post-operative course was complicated by chronic ductopenic rejection, biliary anastomotic leak, and persistent confusion and malaise. At the time of laparotomy for repair of the bile leak, nodular peritoneal lesions were noted, with biopsy and culture showing angioinvasive Aspergillus fumigatus. Despite administration of amphotericin B, the patient continued to have culture-confirmed evidence of infection at follow-up peritoneoscopy. Oral itraconazole was begun, but the patient died of liver failure secondary to progressive ductolpenic rejection. At autopsy, Aspergillus organisms were seen in histologic sections taken from the small bowel; there was no evidence of disseminated disease.

Aspergillus fumigatus↗
PubMed1994

Liver transplantation and alcohol: who should get transplants?

Medical selection criteria should be the same for all patients with end-stage liver disease and should aim for an acceptable outcome of the liver transplant procedure in matter of survival and quality of life, taking the scarce resources into account. The psychiatric selection criteria should aim at avoidance of recidivism of alcohol use in alcoholic patients. At least 6 mo of sobriety should be required. The patient must have a stable and supportive environment and should participate in an alcohol counseling program. A multicentered trial using uniform scoring criteria such as the Alcohol Prognosis Scale is needed to better define the selection of patients with alcoholic liver disease and long-term outcome of alcoholism after transplantation.

Alcoholism↗
PubMed1994

Nephrotoxic effects of primary immunosuppression with FK-506 and cyclosporine regimens after liver transplantation.

OBJECTIVE: We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A (CSA) in liver transplant recipients. DESIGN: Between October 1990 and October 1991, 37 patients were enrolled in an open-labeled, randomized study of two immunosuppressive regimens after liver transplantation. MATERIAL AND METHODS: Of the 23 men and 14 women, 20 received FK-506 plus prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function was assessed before and after transplantation (day 1, month 1, month 4, and month 12) by measurements of serum creatinine (SCr) and glomerular filtration rate (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK-506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2 and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid chromatography) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated withdrawal of study medication for more than 48 hours. Mean patient age and values for SCr and GFR were comparable between the two groups at entry. RESULTS: Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up, although patients who received FK-506 had a significantly (P < 0.05) lower GFR when measured at 12 months than did patients treated with CSA (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and 10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients, all of whom were in the FK-506 group. These severe nephrotoxic reactions to FK-506 occurred early after transplantation, often during intravenous administration of the drug, and were not associated with poor liver allograft function or drug levels outside the therapeutic range. CONCLUSION: Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients. In this trial, however, we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506.

Acute Kidney Injury↗
PubMed1994

Orthotopic liver transplantation for preoperative early-stage hepatocellular carcinoma.

OBJECTIVE: To report our experience with orthotopic liver transplantation (OLT) for highly selected patients with early-stage hepatocellular carcinoma (HCC). DESIGN: We retrospectively analyzed the demographic, clinical, pathologic, and survival data on 21 patients with HCC who underwent OLT at the Mayo Clinic between 1985 and 1993. MATERIAL AND METHODS: The 21 patients were categorized into three groups: (1) those with incidental HCC (no evidence of HCC preoperatively), (2) those with a unicentric hepatic lesion without vascular invasion, and (3) those with an increased serum alpha-fetoprotein (AFP) concentration but no detectable mass lesion in the liver. RESULTS: For the seven patients with incidental HCC, the 2-year disease-free survival was 68.5%. For the eight patients with a mass lesion, the 2-year disease-free survival was only 50%. Operative staging revealed more advanced stage disease than had been found on preoperative assessment in five of these eight patients. For the six patients with an increased serum AFP value but no mass lesion, the 2-year disease-free survival was 80%. Tumor recurrence was the major cause of all deaths in this series. CONCLUSION: Disease-free survival for patients with radiographic early-stage HCC was suboptimal because of understaging of the disease preoperatively. In contrast, our initial experience with OLT for patients with an increased serum AFP value in the absence of a mass lesion in the liver was favorable.

Adult↗
PubMed1994

Cyclosporine-induced hypertension after transplantation.

OBJECTIVE: To describe the features and mechanisms of posttransplantation hypertension and suggest appropriate management of the disorder. DESIGN: We review our own experience and reports from the literature on hypertension in cyclosporine A (CSA)-treated transplant recipients. RESULTS: Soon after immunosuppression with CSA and corticosteroids, hypertension develops in most patients who undergo transplantation. The blood pressure increases, which are usually moderate, occur universally because of increased peripheral vascular resistance. Disturbances in circadian patterns of blood pressure lead to loss of the normal nocturnal decline, a feature that magnifies hypertensive target effects. Changes in blood pressure sometimes are severe and associated with rapidly developing target injury, including intracranial hemorrhage, left ventricular hypertrophy, and microangiopathic hemolysis. The complex mechanisms that underlie this disorder include alterations in vascular reactivity that cause widespread vasoconstriction. Vascular effects in the kidney lead to reduced glomerular filtration and impaired sodium excretion. Many of these changes affect local regulation of vascular tone, including stimulation of endothelin and suppression of vasodilating prostaglandins. Effective therapy includes use of vasodilating agents, often calcium channel blocking drugs. Caution must be exercised to avoid interfering with the disposition of CSA or aggravating adverse effects relative to kidney and electrolyte homeostasis. CONCLUSION: Recognition and treatment of CSA-induced hypertension and vascular injury are important elements in managing the transplant recipient.

Antihypertensive Agents↗
PubMed1994

Soluble T lymphocyte markers in the diagnosis of cellular rejection and cytomegalovirus hepatitis in liver transplant recipients.

Hepatic dysfunction following liver transplantation is often caused by cellular rejection or infection with cytomegalovirus. These etiologies can at times be difficult to differentiate. We measured the levels of soluble T lymphocyte markers sIL2R, sCD4, and sCD8 in serum as possible diagnostic indicators of cellular rejection and cytomegalovirus hepatitis. Pretransplant levels, and serial post-transplant levels of soluble T lymphocyte markers were measured in five control patients without cellular rejection or cytomegalovirus infection, ten patients with cellular rejection, and six patients with cytomegalovirus hepatitis. In all cases, cellular rejection and cytomegalovirus hepatitis were documented with liver histology. For each group of patients, we calculated the mean ratio of the post-transplant marker level divided by the pre-transplant level. We found an elevation in the mean ratio of sIL2R in patients with cellular rejection shortly before or at the time of diagnosis of rejection as compared to the transplant control group. Levels of sCD8 were not significantly increased in patients with cellular rejection. We found a more pronounced elevation in the mean marker ratios of both sIL2R and sCD8 in patients with cytomegalovirus hepatitis which were higher compared not only to the transplant control group but also compared to the cellular rejection group. The rise of serum levels preceded the histologic diagnosis of cytomegalovirus hepatitis and detection of cytomegalovirus in blood cultures. Increased serum levels of sIL2R with concomitant elevation of sCD8 suggest the diagnosis of cytomegalovirus hepatitis over cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)

Biomarkers↗
PubMed1994

Detection of cytomegalovirus DNA in sera of liver transplant recipients.

We prospectively studied the utility of the amplification of cytomegalovirus (CMV) DNA in the sera of liver transplant recipients in order to predict symptomatic CMV infection, thus enabling preemptive therapy with antiviral agents. Serum samples obtained at biweekly intervals from 20 sequential liver transplant recipients for at least 8 weeks following transplantation were tested by the PCR amplification procedure. Results were correlated with blood and urine cultures, histopathological findings from infected organs, and clinical manifestations. Six patients (30%) developed symptomatic CMV infection; in five (83%) of these patients, CMV DNA was detected prior to symptomatic CMV infection, and in one (17%) of these patients, CMV DNA was detected at the time of symptomatic CMV infection. CMV DNA was detected a mean of 13 days (range, 0 to 23 days) prior to the onset of symptomatic CMV infection. In addition, CMV DNA was detected in the sera of four of five patients with asymptomatic viremia and two patients with asymptomatic viruria. Lastly, the PCR was negative for sera from seven patients with no evidence of CMV infection. We found that PCR was able to detect the presence of CMV DNA in the sera of liver transplant recipients at a sensitivity of 92% and a specificity of 100% for CMV infection, while the sensitivity and specificity for symptomatic infection were 100 and 57%, respectively.

Base Sequence↗
PubMed1994

Etiology and incidence of unconjugated hyperbilirubinemia after orthotopic liver transplantation.

OBJECTIVES: Gilbert's syndrome, or slow bilirubin glucuronidation phenotype, is a common cause of benign hyperbilirubinemia in the general population. There have been only two previously reported cases of Gilbert's syndrome occurring in patients after liver transplantation. This study was conducted to determine the frequency of Gilbert's syndrome in liver transplant recipients. METHODS: The charts of all patients followed by the Mayo Liver Transplant Clinic for 1 yr or more after transplantation, as of June 1992, were reviewed to identify all patients with a consistent pattern of unconjugated hyperbilirubinemia greater than two times the upper limits of normal and with a normal conjugated bilirubin level. These patients were further evaluated to exclude all other causes of hyperbilirubinemia, including biliary obstruction, rejection, viral infection, cholestatic liver disease, and hemolysis. RESULTS: Five of 229 patients (2.2%) had a consistent pattern of unconjugated hyperbilirubinemia. Only three patients (1.3%) had no other identifiable cause of hyperbilirubinemia. CONCLUSIONS: This study was performed to determine the incidence of unconjugated hyperbilirubinemia and particularly to determine the incidence of Gilbert's disease in liver transplant recipients. The apparently low frequency of Gilbert's after liver transplantation may reflect the masking of the diagnosis by other transplant-associated pathology or donor selection bias because of unexplained hyperbilirubinemia. Post-transplant patients who fit the Gilbert's syndrome profile of unconjugated hyperbilirubinemia should have a postprandial bilirubin drawn as a first step. The awareness of this syndrome may avoid a costly and invasive evaluation in the liver transplant recipient.

Bilirubin↗
PubMed1994

Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does not result in sustained improvement in kidney function and causes cellular and ductopenic rejection.

Twelve consecutive liver transplant recipients with stable allograft function and cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an attempt to halt and possibly reverse renal damage. Only patients who met the following criteria were included: (a) triple immunosuppression with cyclosporine, azathioprine and prednisone; (b) stable graft function for at least 1 yr without rejection; and (c) serum creatinine greater than 2.1 mg/dl or renal clearance less than 35 ml/min. Cyclosporine was reduced by 50 mg every 3 wk until discontinuation, prednisone was temporarily increased from 10 to 20 mg/day and azathioprine was maintained at 2 mg/kg/day. Sustained improvement in kidney function in the 12 patients was minimal, with the mean serum creatine level decreasing from 2.5 +/- 0.5 mg/dl (mean +/- S.D.) at study entry to 2.4 +/- 1.2 mg/dl after a mean follow-up of 18 +/- 6 mo. In six patients, histologically confirmed cellular rejection developed after a mean of 5 +/- 6 mo from the time that cyclosporine withdrawal was begun. Two of six patients with rejection responded to bolus steroid therapy and are in stable condition at this writing with low-dose cyclosporine (2.8 and 3.2 mg/kg/day). Two patients initially responded to bolus steroids but later exhibited ductopenic rejection; one responded to treatment with FK 506 and the other died of sepsis. The two remaining patients were steroid unresponsive. One responded to treatment with OKT3 and is now stable on low-dose cyclosporine (2.3 mg/kg/day), but in the other ductopenic rejection developed and the patient died of sepsis during rescue therapy with FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗
PubMed1993

Liver cell adenoma at the age of 3 years and transplantation 19 years later after development of carcinoma: a case report.

A 3-yr-old child underwent biopsy of a nonresectable liver cell adenoma. She was well thereafter, but at the age of 22 yr, she underwent orthotopic liver transplantation because the lesion had grown. The alpha-fetoprotein level was 4,300. The specimen showed poorly differentiated hepatocellular carcinoma in a noncirrhotic liver. At this writing, the patient is well 32 mo after transplantation.

Adenoma↗
PubMed1993

Diagnostic features and clinical outcome of ischemic-type biliary complications after liver transplantation.

The clinical significance and outcome of nonanastomotic strictures and dilatations involving only the biliary tree of the graft with a radiological appearance of biliary ischemia is unknown. Therefore we analyzed the grafts of 128 patients to evaluate the biochemical, radiological and histological features that prompted the diagnosis of ischemic-type biliary stricture and the clinical outcome of this complication. Ischemic-type biliary strictures were diagnosed in 25 patients (19%). Initial graft function was similar in all patients, whether or not this complication developed. Most ischemic-type biliary strictures occurred between 1 and 4 mo after orthotopic liver transplantation. However, the appearance of ischemic-type biliary stricture in the month after transplantation was predictive for a poor outcome in all six grafts with early onset of ischemic-type biliary strictures. Eighteen patients (72%) were treated with biliary stents and repeated dilatations. Long-term patency was achieved in 88% of these patients. Repeat transplantation was performed in six patients (24%); five survived. Finally, patients with ischemic-type biliary strictures spent more time in the hospital during the first year after orthotopic liver transplantation than did patients without the complication (62 +/- 27 days vs. 37 +/- 20 days; p < or = 0.001). This was due to repeated hospitalizations and a higher incidence of retransplantation. One-year graft survival was lower in patients with ischemic-type biliary strictures than in patients without ischemic-type biliary strictures (69% vs. 88%; p = 0.006). However, 1-yr patient survival was similar in the two groups (91% vs. 89%). In conclusion, early appearance of ischemic-type biliary stricture features is associated with poor graft prognosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗