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Biomedical subjects

J E Hay

Publications and source records attributed to J E Hay.

At least 19 recordsLinked to original sources
PubMed2001

A controlled trial of calcitonin therapy for the prevention of post-liver transplantation atraumatic fractures in patients with primary biliary cirrhosis and primary sclerosing cholangitis.

BACKGROUND/AIMS: Accelerated bone loss occurs early after liver transplantation (OLT) and, in cholestatic patients with pre-existing osteopenia, causes spontaneous fracturing. This study aimed to investigate the efficacy of calcitonin, a powerful inhibitor of bone resorption, in preventing or reducing the accelerated rate of bone loss and fracturing which occurs in patients with primary biliary cirrhosis and primary sclerosing cholangitis early after OLT. METHODS: Sixty-three patients undergoing OLT for primary biliary cirrhosis (n = 26) and primary sclerosing cholarigitis (n = 37) were randomized to receive: (a), 100 IU/day of salmon calcitonin subcutaneously for the first 6 months posttransplant; or (b), no therapy. At pretransplant, and at 4 and 12 months after OLT, patients were investigated clinically, biochemically, by bone mineral density of the lumbar spine, and by radiographs of the thoracolumbar spine, chest and site of any bone pain. RESULTS: The bone mineral density of the lumbar spine fell equally at 4 months in both groups, from 0.85 to 0.81 g/cm2 in calcitonin-treated patients (n = 29) and from 0.88 to 0.82 g/cm2 in controls (n = 34); at 12 months, both groups had stabilized to 0.83 g/cm2. Fracturing was the same in both groups. CONCLUSIONS: Calcitonin therapy for the first 6 months after OLT is unable to prevent or reduce accelerated bone loss or spontaneous fractures which occur in the first posttransplant year.

Adult↗
PubMed1999

Recurrence of primary sclerosing cholangitis following liver transplantation.

Recurrence of primary sclerosing cholangitis (PSC) following liver transplantation has been suggested; however, it has not been fully defined because of numerous complicating factors and the lack of diagnostic criteria. In the present study, we investigated the recurrence of PSC by developing strict criteria and applying them to a large cohort of PSC patients who underwent liver transplantation. Between March 1985 and June 1996, 150 PSC patients underwent liver transplantation at the Mayo Clinic; mean follow up was 55 months. The incidence of nonanastomotic biliary strictures and hepatic histologic findings suggestive of PSC were compared between patients transplanted for PSC and a non-PSC transplant control group. Our definition of recurrent PSC was based on characteristic cholangiographic and histologic findings that occur in nontransplant PSC patients. By using strict criteria, 30 patients with other known causes of posttransplant nonanastomotic biliary strictures were excluded leaving 120 patients for analysis of recurrence of PSC. We found evidence of PSC recurrence after liver transplantation in 24 patients (20%). Of these, 22 out of 24 patients showed characteristic features of PSC on cholangiography and 11 out of 24 had compatible hepatic histologic abnormalities with a mean time to diagnosis of 360 and 1,350 days, respectively. Both cholangiographic and hepatic histologic findings suggestive of PSC recurrence were seen in nine patients. The higher incidence and later onset of nonanastomotic biliary strictures in patients with PSC compared with a non-PSC control group is supportive of the fact that PSC does recur following liver transplantation. We were unable to identify specific clinical risk factors for recurrent PSC, and the overall patient and graft survival in patients with recurrent PSC was similar to those without evidence of recurrence. Our observations provide convincing evidence that PSC frequently recurs in the hepatic allograft using strict inclusion and exclusion criteria.

Adult↗
PubMed1999

Long-term results of patients undergoing liver transplantation for primary sclerosing cholangitis.

Liver transplantation is the only effective therapeutic option for patients with end-stage liver disease due to primary sclerosing cholangitis (PSC). In this study, we analyzed a single center's experience with 150 consecutive PSC patients who received 174 liver allografts. Mean follow-up was 55 months. Actuarial patient survival at 1, 2, 5, and 10 years was 93.7%, 92.2%, 86.4%, and 69.8%, respectively, whereas graft survival was 83.4%, 83.4%, 79.0%, and 60. 5%, respectively. The main indication for retransplantation was hepatic artery thrombosis, and the major cause of death was severe infection. Patients with PSC had a higher incidence of acute cellular and chronic ductopenic rejection compared to a non-PSC control group. Chronic ductopenic rejection adversely affected patient and graft survival. Biliary strictures, both anastomotic and nonanastomotic, were frequent and occurred in 16.2% and 27.2% of patients, respectively. The incidence of recurrent PSC was 20%. A negative impact on patient survival was not seen in patients with either postoperative biliary strictures or recurrence of PSC. Six patients (4%) had cholangiocarcinoma and 1 patient died related to recurrence of malignant disease. Seventy-eight percent of PSC patients had associated inflammatory bowel disease, most commonly chronic ulcerative colitis, which did not adversely impact patient outcome posttransplantation. Nine patients required proctocolectomy after liver transplantation; 5 because of intractable symptoms related to inflammatory bowel disease and 4 due to the development of colorectal carcinoma/high-grade dysplasia. Our data show that liver transplantation provides excellent long-term patient and graft survival for patients with end-stage PSC.

Cause of Death↗
PubMed1999

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Acetaminophen↗
PubMed1998

Bone disease in patients with primary sclerosing cholangitis: prevalence, severity and prediction of progression.

BACKGROUND/AIMS: Osteopenia is a common complication in some chronic cholestatic liver diseases. Our aims were to determine the prevalence and severity of bone disease in patients with primary sclerosing cholangitis; and identify risk factors to predict the presence and progression of osteopenia. METHODS: Eighty-one patients involved in a randomized trial of ursodeoxycholic acid were analyzed. Bone mineral density of the lumbar spine was determined at entry and at annual intervals. RESULTS: Bone mineral density of the lumber spine in primary sclerosing cholangitis patients was significantly lower than expected when compared to normal values adjusted for age, sex and ethnic group at entry (p<0.005), and after 1 year (p<0.05), 2 years (p<0.05), 4 years (p<0.005) and 5 years of follow-up (p<0.005). Seven patients (8.6%) had bone mineral density of the lumber spine below the fracture threshold at entry. These patients were significantly older, had a longer duration of inflammatory bowel disease and more advanced primary sclerosing cholangitis. The rate of bone loss in primary sclerosing cholangitis patients and expected in normal controls was 0.01+/-0.02 g x cm(-2) x year(-1) and 0.003+/-0.003 g x cm(-2) x year(-1), respectively (p = NS), and was similar in patients receiving placebo and ursodeoxycholic acid. Age was the only variable inversely related with baseline bone mineral density of the lumber spine (p<0.0001). None of the variables predicted progression of the bone disease. CONCLUSIONS: Severe osteoporosis occurs in few patients with primary sclerosing cholangitis, but it should be suspected in patients with longer duration of inflammatory bowel disease and more advanced liver disease. Its presence, severity and progression cannot be accurately evaluated by routine clinical, biochemical, or histological variables. Ursodeoxycholic acid does not affect the rate of bone loss in primary sclerosing cholangitis.

Adult↗
PubMed1998

Osteoporosis.

Osteopenia, in the form of osteoporosis, is a common complication of chronic cholestatic liver diseases and, although its cause is poorly understood, it appears to be intimately related to the cholestasis itself. With more patients surviving longer with successful liver transplantation, the clinical significance of such osteopenia has increased, and a traumatic fracturing has become a major cause of morbidity in this patient population. Noninvasive diagnosis is easy, and serial measurements allow assessment of disease progression. Although no effective therapy can treat or prevent this complication, supportive measures can improve skeletal well-being, especially in high-risk individuals who are candidates for liver transplantation.

Bone Diseases, Metabolic↗
PubMed1998

Liver transplantation for primary biliary cirrhosis and primary sclerosing cholangitis: does medical treatment alter timing and selection?

Liver transplantation is a highly effective treatment for patients with advanced primary biliary cirrhosis and primary sclerosing cholangitis. Transplantation is indicated when the patient's survival with transplantation is better than without or, earlier than this, if the patient's quality of life is intolerable from intractable fatigue or pruritus. Medical therapies for chronic cholestatic liver diseases are very limited. Ursodeoxycholic acid therapy in primary biliary cirrhosis reduces cholestasis and prolongs transplant-free survival; no other drugs are of proven efficacy in primary biliary cirrhosis, and none have any benefit on the disease progression of primary sclerosing cholangitis. Aggressive endoscopic therapy may produce symptomatic and biochemical improvement in primary sclerosing cholangitis but should be done without the expectation of retarding disease progression. Bilirubin is one of five criteria of the Child-Turcotte-Pugh score, which is necessary for the United Network for Organ Sharing listing for orthotopic liver transplantation. In addition, it is a major prognostic indicator in all the predictive models for primary biliary cirrhosis. Bilirubin reduction with ursodeoxycholic acid therapy in primary biliary cirrhosis appears to parallel disease severity, and prognostic models utilizing bilirubin retain their predictive power for survival even in treated patients. In summary, medical therapies for chronic cholestatic liver disease have very little effect on disease progression and, subsequently, on the timing or selection for transplantation. Liver transplantation is the only definitive therapy for primary biliary cirrhosis and primary sclerosing cholangitis.

Cholagogues and Choleretics↗
PubMed1997

Auditory and inspiratory gasp-evoked sympathetic skin response: age effects.

The sympathetic skin response (SSR) has been employed to assess peripheral neuropathy as an index of sympathetic sudomotor activity. A variety of stimuli can be used to elicit the SSR, but their relative ease of use and reliability have not been studied. In addition, the extent to which age affects the SSR remains unresolved. We compared two different stimuli, a sudden loud noise and an inspiratory gasp, whilst recording SSRs from the hand and foot. We also investigated the effects of age on SSR amplitude and latency in 58 healthy volunteers (ages 13-79). SSRs evoked by the auditory stimulus were recorded in all subjects, while gasp-induced SSRs were not elicited in two subjects. We found that SSRs evoked by the auditory stimulus had less inter- and intra-subject latency and waveform variability than the gasp-induced response. The increased latency variability associated with the inspiratory gasp technique was probably due to triggering errors. Our results confirmed that the amplitude of the SSR is extremely variable and appears to be affected by many factors. Auditory-evoked SSR latencies revealed a significant non-linear increase with age, while SSRs evoked by an inspiratory gasp did not demonstrate age dependence. We conclude that an auditory stimulus is superior to an inspiratory gasp in evoking SSRs, both in terms of consistent appearance and reduced latency variability. As the SSR latency increases significantly with age, this effect should be carefully considered when interpreting the response.

Acoustic Stimulation↗
PubMed1996

Use of fatty donor liver is associated with diminished early patient and graft survival.

It is well known that implantation of donor livers with severe fatty infiltration (>60%) is frequently associated with early hepatic dysfunction and an increased incidence of primary nonfunction after liver transplantation. The outcome of donor livers with less fatty infiltration has not been well defined. We, therefore, studied the outcome of 59 liver transplantations in which donor livers with up to 30% fat were used. Patient outcome was compared to a time-matched control group of 57 patients. The two groups were similar in terms of age, gender, preservation time, primary diagnosis, and UNOS status. We compared both groups with regard to 4-month and 2-year patient and graft survival. We also assessed the incidence of ischemic type biliary strictures and hepatic artery thrombosis, and evaluated the causes of graft loss in both groups. We found that use of donor livers with up to 30% fatty infiltration was associated with a significant decrease in 4-month graft survival (76% vs. 89%, P<0.05) and in 2-year patient survival (77% vs. 91%, P<0.05). Primary nonfunction and primary dysfunction formed the main cause of graft loss and mortality. Multivariate analysis showed that fatty infiltration is an independent predictive factor for outcome after transplantation. We conclude that liver allografts with up to 30% fat lead to diminished outcome after liver transplantation. However, this diminished outcome should be viewed with respect to the increasing mortality on the national waiting list.

Adult↗
PubMed1996

Total joint arthroplasty in orthotopic liver transplant recipients.

Eight total hip and two total knee arthroplasties were performed from 1986 to 1991 in eight patients who had orthotopic liver transplantation. The indications for joint arthroplasty were avascular necrosis of the femoral head in five hips, pathologic femoral neck fracture caused by osteopenia in three hips, avascular necrosis of femoral and tibial condyles in one knee, and posttraumatic arthritis in one knee. Six patients (75%) had significant osteopenia. The mean interval between liver transplantation surgery and hip or knee joint arthroplasty was 2 years (8-48 months). The patients who had hip arthroplasty were followed for a mean of 4.85 years (2-8 years), and those who had a knee arthroplasty after a hip arthroplasty, for a mean of 3.5 years (2-5 years) after the knee arthroplasty. In the patients who had hip arthroplasty, the mean Harris hip score was improved from 34 to 82 points. In the two patients who had a knee arthroplasty, the mean score was improved to 100 points both for pain and function of the knee and for overall function from mean preoperative knee scores of 49 and 25 points, respectively. Radiographs did not reveal any loosening of the components. None of the patients required reoperation and there were no serious postoperative complications.

Adult↗
PubMed1996

Clinical comparison of isolator, Septi-Chek, nonvented tryptic soy broth, and direct agar plating combined with thioglycolate broth for diagnosing spontaneous bacterial peritonitis.

Spontaneous bacterial peritonitis is a life-threatening complication of cirrhotic ascites. Optimal patient management depends on the isolation of the causal organism from ascitic fluid. To evaluate culture techniques for the diagnosis of spontaneous bacterial peritonitis, we prospectively compared three blood culture system, the Isolator system, a lysis-centrifugation system, the Septi-Chek system, a biphasic culture system, and a nonvented tryptic soy broth system, all inoculated at the bedside, and our standard method of direct inoculation of specimens after transport to the laboratory onto agar plates and into thioglycolate broth. The results showed that the Septi-Chek and nonvented tryptic soy broth systems each recovered statistically significantly more pathogens than either the Isolator system (P = 0.0084) or the standard method (P = 0.00098). The Isolator system recovered more pathogens than the standard plate method, but this difference was not statistically significant. Both the Isolator system and the standard plate method recovered more contaminating microorganisms than the Septi-Chek or nonvented tryptic soy broth system. The Isolator system required the most processing time compared with the processing times required by any other method.

Adult↗
PubMed1996

Liver transplantation for primary sclerosing cholangitis: impact of risk factors on outcome.

The results of liver transplantation in patients with PSC are excellent and the quality of life is markedly improved. Indeed, liver transplantation is the therapy of choice for patients with end-stage PSC. However, in an age of cost containment, it appears that there are several advantages to offering transplant to patients with PSC a little bit earlier rather than later in the course of their disease. It appears that we can further improve survival, decrease morbidity, decrease blood usage, and avoid the risk of developing a cholangiocarcinoma, which occurs sporadically but not infrequently in the PSC patient. In addition, avoidance of right upper quadrant surgery, such as biliary or shunt surgery, appears to offer several advantages by decreasing resource utilization and possibly decreasing mortality. Although the UNOS selection guidelines recommend transplantation of the sickest patient, there appears to be accumulating evidence that transplantation in patients earlier in the course of their end-stage liver disease may improve survival, decrease morbidity, and also importantly, decrease the cost associated with this expensive procedure. Ideally, we would recommend consideration for liver transplantation all PSC patients who have (1) a Mayo risk score of > 4.8 in whom malignancy is ruled out, (2) cirrhosis and complications of portal hypertension such as variceal bleeding, refractory ascites, or portosystemic encephalopathy, or (3) disabling symptoms such as fatigue, pruritus, or recurrent bacterial cholangitis. We believe that biliary surgery to treat dominant strictures should be avoided and that such strictures should be approached either endoscopically or radiographically, which should include brushings, biopsies, and histology to reasonably exclude the diagnosis of cholangiocarcinoma. Finally, we continue to search for risk factors and for early markers of cholangiocarcinoma so these patients can be identified early and this devastating complication can be avoided by early transplantation.

Cholangitis, Sclerosing↗
PubMed1995

Bone disease in cholestatic liver disease.

Osteopenia in the form of osteoporosis is a common clinical problem associated with chronic cholestatic liver disease, and clinical morbidity from atraumatic fractures is increasing as more patients with PBC and PSC undergo successful liver transplantation. In the absence of symptomatic fractures, the clinical diagnosis may not be evident and must be sought by specific means to assess bone mineral density. The clinical problem has now been defined, but much remains unknown, from etiologic mechanisms to effective therapies. At present, it seems reasonable to provide aggressive supportive therapy in an attempt to maximize skeletal well-being until more effective therapies for osteopenia become available.

Bone Diseases↗
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↗