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Biomedical subjects

J M Ham

Publications and source records attributed to J M Ham.

At least 19 recordsLinked to original sources

Resource utilization and outcome of liver transplantation for alcoholic cirrhosis. A case-control study.

Liver transplantation for alcoholic cirrhosis remains controversial at some transplantation centers. We compared resource utilization and outcome in alcoholic and nonalcoholic cirrhotic patients undergoing liver transplantation. Data were collected from 56 patients who underwent transplantation for alcohol-related cirrhosis from August 1985 to February 1991 and compared with data from a control group matched for age, sex, Child-Pugh class, and date of transplantation. No significant differences were noted in the resource utilization variables examined or in outcome (as assessed by indicators of early graft function, frequency of sepsis, incidence of rejection, renal function, and retransplantation rate). One-year survival was not significantly different (75% for the alcoholic cirrhotic group vs 76% for the nonalcoholic cirrhotic group). We conclude that liver transplantation for end-stage alcohol-related cirrhosis provides excellent results and that resource utilization appears to be equivalent to that for patients undergoing transplantation for non-alcohol-related cirrhosis.

Actuarial Analysis

Biochemical and histopathological correlation in liver transplant: the first 180 days.

It is not known whether the histopathology of the liver allograft can be predicted from biochemical measurements in serum with the same confidence as in the native liver. To answer this question we compared the histopathological diagnoses in 170 biopsy specimens from 70 adult transplant recipients obtained during the first 180 days, with the concentrations of the serum bilirubin and the activities of AST, ALT and alkaline phosphatase measured at the same time. The most frequent diagnosis was cholestasis (n = 45), which was mild, moderate or severe and which may have been complicated by rejection (n = 28) or ischemia (n = 14). Hepatitis (n = 14), ischemia with rejection (n = 6) and spotty focal necrosis (n = 6) were diagnosed less frequently. Fifteen biopsy specimens were reported as histopathologically normal. In general, biochemical measurements discriminated poorly between different histopathological diagnoses. The histopathologically normal liver often showed an abnormal pattern of enzymes and an increase in the serum bilirubin level. As a result histopathologically normal biopsy specimens were indistinguishable biochemically from those with hepatitis. When two pathological conditions were found to coexist (e.g., cholestasis with either rejection or ischemic necrosis, or ischemic necrosis with rejection), the effect on the serum biochemistry was usually not additive and in some instances returned the biochemical abnormalities toward normal. With the exception of the serum bilirubin level, which increased with the severity of uncomplicated cholestasis, we could not identify a specific pattern of biochemical changes corresponding to a given histopathological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Preoperative risk factor assessment in liver transplantation.

BACKGROUND: Despite the increasing success of liver transplantation, there is lack of objective data defining appropriate candidate suitability. This study was undertaken to determine preoperative risk factors that independently or in combination affected outcome after orthotopic liver transplantation. METHODS: We reviewed data on 229 consecutive adult liver transplant recipients. Thirty-one preoperative risk factors recorded at the time of listing and immediately before transplantation were analyzed. Outcome variables included hospital mortality rates, bacterial or fungal sepsis, and the need for renal support. RESULTS: The overall hospital mortality rate was 15.7%. Patients who were in the intensive care unit immediately before transplantation had the highest hospital mortality rate (32.6%; p = 0.006), incidence of bacterial sepsis (51%; p = 0.001), fungal infection rate (27.6%; p = 0.001), and need for renal support (38.7%; p = 0.001). Preoperative renal dysfunction was significantly associated with sepsis and was reflected in higher hospital mortality rates (29.5%; p = 0.011). Child-Pugh class C was associated with higher mortality rates (23.9%; p = 0.017), an increased incidence of bacterial (37.2%; p = 0.020) and fungal infection (20.3%; p = 0.049), and a 30.4% requirement for postoperative renal support (p = 0.004). CONCLUSIONS: These results emphasize the need for earlier referral and transplantation in patients with advanced liver disease. Further studies are needed to refine identified risk profiles and devise strategies to decrease morbidity and mortality rates.

Adult

Chemotactic cytokine (IL-8 and MCP-1) gene expression by human whole blood.

The salient features of systemic or local inflammation are the myriad of cellular and humoral interactions that result in elicitation of inflammatory leukocytes. In this study using specialized connective tissue, intact whole blood, we demonstrate the gene expression of two novel chemotactic factors. The buffy-coat cellular expression of neutrophil chemotactic/activating factor/interleukin 8 (IL-8) and monocyte chemotactic/activating protein (MCP-1) mRNA were time and dose-dependent in response to either lipopolysaccharide or zymosan stimulation. This system with the complexity of tissue provides a unique model for the determination of chemotactic cytokine gene expression.

Antigens

Liver transplant for fulminant hepatic failure.

Fulminant hepatic failure is a challenging indication for liver transplantation because of associated multiple organ failure, profound neurologic abnormalities and coagulopathy. Sixteen patients have undergone emergent orthotopic liver transplantation for this indication at the University of Michigan, Ann Arbor, Michigan. Despite the associated problems, patient survival (68.2% at 2 years), intra-operative blood product utilization and duration of surgery were comparable to patients receiving liver transplants for other indications. All patients experienced complete recovery from preoperative neurologic abnormalities. Recurrent viral hepatitis did occur but did not result in allograft loss. For selected patients, orthotopic liver transplantation is excellent therapy for patients presenting with fulminant hepatic failure.

Adolescent

Obesity and renal transplantation.

In this study, we examined the influence of pre-existing obesity (weight more than 120 per cent of ideal body weight) on outcome after renal transplantation. Among 263 cyclosporine-treated recipients of renal allografts, 223 (85 per cent) were nonobese and 40 (15 per cent) were obese prior to transplantation. Obese and nonobese recipients were similar with regard to age, sex, renal diagnosis, history of prior transplant, donor source, pretransplant blood pressure, pretransplant antihypertensive agents, diabetic recipients with insulin requirements more than 40 units per day and pretransplant serum cholesterol. Duration of hospitalization was similar (26 +/- 25 versus 25 +/- 14 days; p = NS). There was a significantly higher incidence of wound infections in obese recipients (17.5 versus 6.3 per cent; p = 0.036); other complications occurred with similar incidence. Preoperative per cent of ideal body weight correlated with post-transplant weight gain during the first post-transplant year (p = 0.00002). After one year, obese recipients had gained 14.2 +/- 2.2 kilograms compared with 8.9 +/- 0.6 kilograms for nonobese patients (p = 0.002). Mean doses of prednisone, azathioprine and cyclosporine were similar at three, six and 12 months post-transplant. There were no differences in blood cyclosporine, serum cholesterol or blood glucose levels at any time. Blood pressure measurements were similar throughout the first post-transplant year. There was no difference in the incidence or number of rejection episodes. Actuarial patient survival rate for nonobese patients was 93 per cent at three years. For obese patients, three year actuarial patient survival rate was 90.5 per cent (p = NS). Actuarial graft survival rate among nonobese patients was 71.8 per cent at three years. For obese patients, three year actuarial graft survival rate was 64.5 per cent (p = NS). In conclusion, obese patients with end stage renal disease are good candidates for renal transplantation. Obesity does not seem to constitute a major risk factor, the most notable adverse outcomes being an increased incidence of wound infection and continued weight gain through the first post-transplant year.

Actuarial Analysis

Tumor necrosis factor-alpha gene expression in human whole blood.

Tumor necrosis factor-alpha (TNF) is recognized as a principal mediator of a variety of pathophysiologic and immunologic events. Lipopolysaccharide (LPS) challenge, either in vitro or in vivo, results in significant TNF production. In this study we present data demonstrating LPS-induced TNF mRNA expression and bioactivity using an in vitro tissue system of whole blood (WB). The kinetics of LPS-induced TNF production by WB was significantly accelerated as compared to isolated cultured peripheral blood monocytes (PBM). At post-LPS challenge, plasma from WB demonstrated a rapid rise in TNF bioactivity, peaking by 4 hr (1,021 units/ml/10(6) cells), plateauing between 4 and 8 hr, and then decreasing over the next 16 hr. In contrast, the highest measured TNF bioactivity from PBM did not occur until the 24-hr time-point (175 units/ml/10(6) cells). Whole blood buffy-coat TNF mRNA was assessed by Northern blot analysis, and demonstrated significant TNF mRNA accumulation at 1 hr and a peak 2 hr post-LPS challenge. By 8 hr TNF mRNA was undetectable. Concomitant administration of LPS with either prostaglandin E2 (10(-6)M) or Dexamethasone (10(-6)M) resulted in significant suppression of LPS-induced TNF production. This data supports WB as a useful in vitro medium for the molecular and cellular analysis of TNF. As specialized connective tissue, WB may provide an important environment to study the pharmacologic manipulation of TNF mRNA and bioactivity.

Blood Physiological Phenomena

Blood ordering for haematemesis.

The blood ordering practices for acute upper gastrointestinal bleeding were assessed in 162 consecutive patients presenting with haematemesis admitted via the Accident and Emergency Centre. The patients were classified according to their estimated blood loss and haemoglobin level at the time of admission, and the amounts of blood ordered and given in the next 24 h were determined. The crossmatch: transfusion (CT) ratio was very high in one group (14.9), although the overall ratio of 2.4 was acceptable. There were marked variations in the ordering pattern of different medical officers, possibly because of the absence of clear guidelines. From the data obtained, a set of guidelines for ordering blood in this clinical condition was developed. It was estimated that if these guidelines had been used, there would have been a reduction of one-third of all units crossmatched, and that the overall CT ratio would have been reduced to 1.6.

Blood Grouping and Crossmatching

Partial cholecystectomy.

An alternative to cholecystostomy and standard cholecystectomy for 'difficult' gall bladders has been described previously. The procedure, partial cholecystectomy, involves leaving in situ part or all of the wall of the gall bladder which lies directly in relation to the liver and/or structures in the porta hepatis. Eleven such procedures have been performed over a 5 year period, and the common indication in all was severe inflammation or fibrosis in the region of Calot's triangle. One patient developed a self-limiting postoperative bile leak. One patient has formed bile duct stones and appears to have oriental cholangiohepatitis. In the remainder of the patients, there has been no recurrence of biliary tract symptoms. The procedure is definitive and safe, and may usually be performed when cholecystostomy would have been undertaken.

Aged

Pancreatitis and pancreas divisum: aetiological and surgical considerations.

It has been suggested that acute pancreatitis occurs more commonly in patients with pancreas divisum and that these patients may respond to surgery aimed at improving pancreatic ductal drainage. We have studied the incidence of pancreas divisum in patients referred for endoscopic retrograde cholangio pancreatography (ERCP) and the results of surgical sphincteroplasty in a separate series of such patients. Twenty-three patients with pancreas divisum were identified among 336 successful pancreatograms (Group A), an incidence of 6.8%. The incidence of pancreas divisum in patients having ERCP for documented pancreatitis was 13% (11 of 86) compared with 4.8% (12 of 250) in those having ERCP for other indications. This difference was statistically significant (P less than 0.05). However, pancreas divisum was not the sole risk factor for pancreatitis in the majority of our patients; most also had one of the commonly recognized causes for their pancreatitis. There is dispute about the indications for surgery in patients with recurrent acute pancreatitis and pancreas divisum, but without any other risk factor. We have reviewed the results of operations on 13 patients with pancreas divisum (Group B) treated in four different hospitals. Surgical sphincteroplasty was carried out on 10 patients with documented pancreatitis and seven of these had good results. Three patients who had operations for pain without documented pancreatitis were not improved.

Cholangiopancreatography, Endoscopic Retrograde

The hepatic artery in liver transplantation.

Hepatic artery complications after liver transplantation are uncommon, but represent an important cause of morbidity and mortality. In addition, these complications tax an already limited supply of donor organs because of the frequent need for retransplantation in this group of patients. In this study, we examined the incidence of hepatic arterial anomalies in donors and recipients of orthotopic liver transplants, focusing on the techniques that are available for hepatic arterial reconstruction and on the occurrence of hepatic arterial complications. A total of 77 liver transplants were carried out in 68 patients. Standard recipient anatomy was present in 60 of 68 patients (88%). Anomalous vessels were identified in eight patients (12%), including six cases of replaced right hepatic artery (9%) and two cases of replaced left hepatic artery (3%). Donor liver arterial anatomy was standard in 62 cases (80%). Anomalous arterial supply was identified in 15 of 77 donor livers (20%), including replaced left hepatic artery in nine (12%) and replaced right hepatic artery in six (8%). A variety of methods were used to manage the anomalous vessels. There was one hepatic artery pseudoaneurysm, three cases of hepatic artery thrombosis (4%), and one patient developed a dissection of the native celiac axis. In primary transplants, utilization of the recipient's proper hepatic artery was associated with a significantly higher risk of hepatic artery thrombosis (P less than 0.04) when compared with the common hepatic artery or the branch patch technique. Use of a Carrel patch on the donor artery was associated with a significantly reduced incidence of hepatic artery thrombosis (P less than 0.0003). For retransplantation, it is recommended that a more proximal recipient anastomotic site be chosen. An innovative method is described that provides increased length of the donor arterial supply without the use of an arterial graft.

Hepatic Artery

Liver transplantation at the University of Michigan.

Liver transplantation is a highly successful therapy for liver diseases that were previously debilitating and often fatal within a few months. One-year actuarial patient survival for our first 162 patients is 74.7%. Our results have improved since the inception of the program despite the fact that the indications have been extended to higher risk patients such as those with fulminating hepatitis or thrombosed portal veins. The prognosis following transplantation for each specific indication needs to be defined, especially for hepatitis, alcoholic cirrhosis and individual cancers. We believe that a more conservative approach to immunosuppression, close attention to intravenous and enteral nutrition, and aggressive treatment of complications (including prompt reoperation when indicated) have been important improvements in our management practices.

Adolescent

Model of TPN-associated hepatobiliary dysfunction in the young pig.

Gallbladder 'sludge' and cholestasis are two common complications associated with total parenteral nutrition (TPN), but the aetiology of each is uncertain. An animal model has been developed in the young pig which demonstrates these two complications. Five female piglets, of Landrace Large White Cross variety weighing 4.5-5.9 kg, received nutritional support for 2 weeks with a continuous infusion of TPN solution at a dose of 150 kcal kg-1 day-1. The solution was 35 per cent dextrose, 5 per cent L-amino acids with conventional electrolyte, mineral and vitamin additives. No lipid was used in the solution. Five weight-matched animals were used as controls. All animals in the TPN group developed 'sludge' in their gallbladders, decreased basal bile flow, decreased bile salt excretion and a diminished response to bile salt stimulated bile flow, as compared with controls. There was no abnormality in routine liver function tests or liver histology. It is concluded that TPN therapy in this animal model is associated with the appearance of gallbladder 'sludge', and cholestasis as demonstrated by direct bile flow studies. It is suggested that this bile flow abnormality is due to a decrease in bile salt dependent and bile salt independent fractions of canalicular bile flow. The model provides the opportunity to investigate TPN related hepatobiliary dysfunction in an animal that has similar liver function to man and comparable nutritional requirements.

Animals