Living-donor versus cadaveric liver transplantation for non-resectable small hepatocellular carcinoma and compensated cirrhosis: a decision analysis.

BACKGROUND: Cadaveric liver transplantation is effective for nonresectable early hepatocellular carcinoma. However, the scarcity of cadaveric organs has prompted some centers to use living donors, which guarantees transplantation, but entails a risk to the donor. In the absence of controlled trials, decision analysis can be used to help explicate the tradeoffs involved when considering living donor versus cadaveric liver transplantation for nonresectable early hepatocellular carcinoma. METHODS: Using a Markov model, a hypothetical cohort of patients with Child's A cirrhosis and a single 3.5-cm tumor received one of three strategies: 1) no transplant; 2) intent to perform cadaveric liver transplantation; or 3) living donor liver transplantation. Data were obtained from natural history and retrospective studies. All probabilities in the model were varied simultaneously using a Monte Carlo simulation. RESULTS: Living-donor liver transplantation was the best strategy, improving life expectancy by 4.5 years compared with cadaveric liver transplantation. This strategy remained dominant even when varying severity of cirrhosis, age, tumor doubling time, tumor growth pattern, blood type, regional transplant volume, initial tumor size, and rate of progression of cirrhosis. CONCLUSIONS: Living-donor liver transplantation should confer a substantial survival advantage for patients with compensated cirrhosis and non-resectable early stage hepatocellular carcinoma.

Alagille syndrome with colonic polyposis.

Alagille syndrome is a rare inherited condition, which typically manifests during the first year of life as an episode of prolonged cholestasis. Although the pattern of inheritance is autosomal dominant with almost complete penetrance, highly variable expression may delay the diagnosis, and with passing time the clinical findings may be more difficult to recognize. This has clinical implications, as patients with Alagille syndrome are at risk for late complications such as hepatocellular carcinoma. We report a case of a 35-yr-old patient with Alagille syndrome who was diagnosed with colonic polyposis raising the possibility of an association between the two.

A novel histological lesion in glucocorticoid-responsive chronic hepatitis.

In patients with chronic hepatitis, the diagnosis of autoimmune hepatitis is made on the basis of increased gamma-globulin levels and the presence of circulating autoantibodies. Because these test results are not abnormal universally in patients with autoimmune hepatitis, liver biopsy remains an important part of the evaluation. The classical histological finding in autoimmune hepatitis is lymphocytic infiltration of the portal triads and periportal zone (zone 1) with periportal hepatocyte necrosis. This case report describes 4 patients with glucocorticoid-responsive hepatitis, presumably autoimmune in nature, who had pericentral necrosis (zone 3) with relative sparing of the portal areas in their liver biopsy specimens, a previously undescribed histological finding in autoimmune hepatitis.

Identification of cholecystokinin-B/gastrin receptor domains that confer high gastrin affinity: utilization of a novel Xenopus laevis cholecystokinin receptor.

A hallmark of the mammalian brain cholecystokinin (CCK) receptor, CCK-B/gastrin (CCK-BR), is its high affinity for two structurally related peptides, CCK and gastrin. Previous radioligand binding experiments suggested that the predominant CCK receptor from Xenopus laevis brain shares high affinity for sulfated cholecystokinin octapeptide but has > or = 1000-fold lower affinity for gastrin. To determine the molecular basis for this pharmacological divergence between mammalian and lower vertebrate receptors, we isolated a cDNA encoding the X. laevis brain CCK receptor (CCK-XLR). CCK-XLR shares approximately 50% homology at the amino acid level with both the human CCK-BR and the peripheral CCK-A receptor subtypes. The recombinant X. laevis receptor has a distinct pharmacological profile of agonist and antagonist affinities and as such offers a useful tool for structure-function studies. We used CCK-XLR to map the human CCK-BR domains that confer high affinity for gastrin. A series of chimeric CCK-BR/CCK-XLR constructs was generated and pharmacologically characterized. While maintaining wild-type affinity for sulfated cholecystokinin octapeptide, receptors with increasing amino-terminal contributions from CCK-BR demonstrated a stepwise increase in gastrin affinity. Further dissection of the amino-terminal third of the human receptor, a domain that confers a > 250-fold increase in gastrin affinity, revealed the importance of interactions among at least three subdomains. Additional structural requirements for gastrin affinity mapped to a segment spanning transmembrane domains IV and V.

The successful treatment of autoimmune hepatitis with 6-mercaptopurine after failure with azathioprine.

Although the treatment of choice for autoimmune hepatitis is glucocorticoids, their side effects make long-term use undesirable. Therefore, other immunosuppressive agents have been used to replace glucocorticoids in the long-term treatment of autoimmune hepatitis, including azathioprine, a purine analogue. It is derived from 6-mercaptopurine, and these two drugs are often used interchangeably. However, these drugs have different toxicity profiles and may have clinically relevant differences in immunosuppressive activity in individual patients. We report 3 patients with autoimmune hepatitis who either could not tolerate or failed to improve on azathioprine but responded well to 6-mercaptopurine.

Silo filler's disease in New York State.

Twenty new cases of Silo filler's disease (SFD) have been collected, documenting the incidence and clinical features of exposure to nitrogen oxides present in freshly filled silos. Cases of SFD were identified using a statewide computerized discharge diagnosis system. Fifteen of these were identified in the index period, allowing us to calculate an approximate annual incidence of 5.0 cases/100,000 silo-associated farm workers/yr in New York State. All cases occurred during harvest periods, with 80% in September and October. Corn silage was the gas source in 18 (90%). All cases involved young white men (mean age, 31.5 yr). The most common presenting feature was dyspnea. All victims entered a silo during the peak danger period, and only one used recommended ventilation techniques. Four cases ended in death (20% mortality). Silo filler's disease, although rare, is a potentially devastating disease involving otherwise young, healthy farm workers. It is readily prevented.

The dangers of dairy farming: the injury experience of 600 workers followed for two years.

In order to better understand the work-related injuries sustained on central New York dairy farms, we undertook a two-year population-based study of 600 farmers and farm workers on 201 dairy farms. During the observation period, 1984-1986, 151 persons had 200 injuries, giving an injury rate of 16.6%/year (166 injuries/1,000 workers/year). Men were injured more often than women (p less than or equal to 0.01). Injured workers were older (p less than or equal to 0.01), worked more hours (p less than or equal to 0.001), and had heavier workloads than noninjured workers (p less than or equal to 0.001). The growing and harvest seasons had the most injuries; winter the fewest. More than 2/3 of the injuries occurred in the afternoon. Owners/operators, often the most experienced, knowledgeable people on the farms, were most often hurt. Those working more than 60 hours/week, with greater than 30 acres under tillage/worker, had a relative risk of 2.76 compared with all other workers. The attributable risk for this group was 51%. There were two fatalities, both involved owner/operators. Our findings suggest that previous studies may have underestimated the risks faced by farmers. Dairy farming in central New York is very dangerous work. Those who own and operate these dairy farms are most often hurt and killed. Analysis of events on individual farms will be reported separately.

Histamine and endotoxin contamination of hay and respirable hay dust.

Three distinct samples collected from a barn in which an outbreak of respiratory problems occurred were examined for possible etiologic agents. No causal relationship could be established from the results of this study; however histamine concentrations as high as 0.5 ng/mg for bulk hay (in the absence of measurable creatinine levels) along with 6138.3 endotoxin units/mg of hay were present in the samples. Both endotoxin and histamine could be recovered from respirable hay dust. The authenticity of the histamine found in the hay was evaluated with high-performance liquid chromatography and radioimmunoassay. Histamine release caused by hay extracts was evaluated with the use of leukocytes from the farmer and a referent. Histamine is known to modulate the immune system, but the role of occupational or environmental exposure to histamine in respiratory disease is unknown.

Occupational hearing loss in New York dairy farmers.

A study of 49 randomly selected, full-time dairy farmers was performed to assess the prevalence and nature of hearing loss in this population. An age- and sex-matched group of rural, non-farmers was also studied. Medical, occupational, and recreational histories were taken and standard audiometric testing was administered. Sixty-five percent of farmers had hearing loss in the higher frequencies and 37% had losses in the mid-frequency range as compared to 37% and 12% of non-farmers respectively (p less than .01). Farmers' left ears were more severely affected. The age of the subjects and the number of years spent farming were highly correlated with hearing loss. Correlation and regression analyses supported the hypothesis that the difference in the prevalence of hearing loss between the dairy farmers and the non-farmers was due to occupational noise exposure on the farm.

Occupational health and the rural worker: agriculture, mining, and logging.

More than 50 million Americans live in rural areas. These rural residents often work for small businesses or in the extraction industries (farming, mining, and logging). Because of the size of the businesses, the mandate of the Occupation Safety and Health Administration (OSHA) does not cover these workers and they are seldom afforded the same protection as urban workers. This review focuses on the special health problems facing farm workers, farmers, miners, and loggers. Farm workers are often ill and are affected by psychological illness, injuries, parasites, skin diseases, and the dangers of agrichemicals. Farm owners also face the hazards of stress and have very high rates of suicide. In addition, they are often injured on the job and suffer the highest rate of job related fatality of any work group. The complex farm environment presents a continuous threat to the lungs. This danger has worsened with the increased use of confinement buildings for poultry, hogs, and cattle. As farming has changed with increased mechanization, attendant medical problems have arisen. These "illnesses of innovation" are important. Mining and logging also are dangerous occupations with acute and chronic problems including respiratory illness, vascular problems, and malignancy. The decade of the 1990s must be one of increased attention to rural occupational health care and research.

Hepatotoxicity due to pemoline (Cylert): a report of two cases.

Pemoline (Cylert) is an agent used to treat attention deficit disorders and other behavioral syndromes. There have, however, been three published reports of mild hepatic dysfunction in five patients coincident with pemoline therapy. We report two further cases of probable pemoline hepatotoxicity. One case involved a mild aminotransferase elevation in a 6-year-old who was on pemoline for 5 months. The second case, in an 11-year-old, developed hepatic failure with marked prolongation in prothrombin time nonresponsive to parenteral vitamin K, deep jaundice, and submassive hepatic necrosis. This patient had a long history of pemoline usage. Pharmacokinetics are briefly discussed. A spectrum of hepatic disease due to pemoline is considered and the importance of obtaining aminotransferase values before, during initiation, and throughout treatment is stressed.