Clinical features of hepatocellular carcinoma that occur after sustained virological response to interferon for chronic hepatitis C

Background and Aim: This study investigated the clinical features of hepatocellular carcinoma in patients with sustained virological response to interferon for hepatitis C viral (HCV) infection. Methods: A total of 7715 patients with HCV infection were treated with interferon and followed up for more than 1 year after withdrawal of interferon in 64 Japanese hospitals and clinics between July 1988 and August 2001. Sustained virological response was obtained in 2515 (32.6%) patients. Of these 2515 patients, clinical data were collected for 38 patients in whom hepatocellular carcinoma developed. Sustained virological response was defined as HCV RNA negativity more than 6 months after the termination of interferon. Results: All patients were HCV RNA negative at the time of diagnosis of hepatocellular carcinoma. The median period until the detection of hepatocellular carcinoma was 4.7 years (range 1.4–9.0 years). There were significant improvements in hepatic function including serum albumin, aspartate aminotransferase, alanine aminotransferase, indocyanine green test, platelet count and histological activity grade in comparison with those before interferon therapy and at the onset of hepatocellular carcinoma. The maximum tumor size in patients without medical follow‐up for 1 year or more (median: 60 mm) was significantly larger than in patients who were periodically followed up for 6 months or less (median: 25 mm) (P = 0.002). Conclusions: The present findings emphasize the importance of regular medical follow up of patients with HCV infection, as even patients showing a sustained virological response to interferon and in whom hepatic function has improved have the potential to develop hepatocellular carcinoma.     

Analysis of the circumstances at the end of life in children with cancer: Symptoms, suffering and acceptance

BACKGROUND: In an effort to improve the quality of life of children with cancer, this study analyzes the signs and symptoms at the end of life in such children. It is hoped that these data will contribute to the development of appropriate programs to address the challenges faced by these children. PROCEDURE: Between 1994 and 2000, 28 children died after treatment for cancer at Hamamatsu University Hospital, Japan. The circumstances, signs and symptoms at the end of life of these children were analyzed through their medical records. RESULTS: Of the 28 children, the underlying diseases were leukemia/lymphoma (LL group; n=11), brain tumors (BT group; n=7), and other solid tumors (OST group; n=10). Records showed poor appetite (100%), dyspnea (82.1%), pain (75.0%), fatigue (71.4%), nausea/vomiting (57.1%), constipation (46.4%) and diarrhea (21.4%) among these children. Anxiety was reported in 53.6% of the entire group of 28 children; however, no child in the BT group manifested anxiety. However, disturbance of consciousness was reported in all children in the BT group, which was significantly greater than in the other groups. Awareness, fear or acceptance of the imminence of his/her own death as indicated by verbal expression was reported in nine children (32.1%). CONCLUSIONS: Using the data obtained in the present study, we describe situations faced in the terminal care of children. It is important to address the problems revealed by this analysis in order to achieve improvements in both the physical and psychological care of children with terminal cancer.     

Melatonin treatment for rhythm disorder

Abstract We tried melatonin treatment in two patients with non-24 h sleep-wake syndrome, who did not respond to treatments by vitamin B₁₂, bright light therapy, or hypnotics. In one patient, melatonin 5–10 mg improved difficulty in falling asleep and in waking, although it failed to improve the sleep-wake rhythm. In another patient, melatonin 3 mg successfully changed the sleep-wake rhythm from free-running pattern to delayed sleep phase pattern. However, melatonin re-administration after a 4-month drug-free interval failed to improve his free-running sleep-wake rhythm. These results suggest that melatonin acted as a sleep inducer in one patient and as a phase setter in the other, although the effect on the latter patient was transient.     

Complete response, as determined by prostate-specific antigen level, to chlormadinone acetate withdrawal persisting longer than 2 years in patients with advanced prostate cancer: Two case reports

Antiandrogen withdrawal syndrome (AWS) is a well-established phenomenon in prostate cancer. However, responses to AWS are usually of limited duration, and a complete response (CR) is extremely rare. We present two patients who exhibited a chemical CR for more than 2 years after the discontinuation of steroidal antiandrogen chlormadinone acetate use. Whether patients who respond to antiandrogen withdrawal include a group of patients with a better prognosis remains uncertain. However, considering that the usual survival period of patients with hormone-resistant prostate cancer is approximately 12 months, both of the patients reported here, who are present in excellent physical condition, exhibiting an improved quality of life, and attending their hospital as outpatients, obviously acquired a prolonged survival because of AWS.     

Expulsion of Hymenolepis nana from mice with congenital deficiencies of IgE production or of mast cell development

The roles of IgE and mast cells on expulsion of adult Hymenolepis nana from the intestine were examined in mice. IgE-dependency was determined by comparing congenitally IgE-deficient SJA/9 and IgE-producing SJL/J mice infected with 50 H. nana eggs. Anti-H. nana IgE antibody was detected at three weeks post infection (p.i.) in SJL but not in SJA mice. The number of adult worms in the intestines of SJA and of SJL mice were similar at two weeks, but significantly more were found in SJA mice at three weeks p.i. Treatment of mice with anti-ɛ antibody also resulted in an increased worm burden at three weeks, suggesting participation of IgE in expulsion of H. nana. Intestinal mastocytosis was induced by infection regardless of the IgE status of the mice. Mast cell-dependency was tested in mast cell-deficient W/W^u and in normal littermate +/+ mice infected with 100 H. nana eggs. Anti-H. nana antibody was detected in both groups of mice at three weeks p.i. Worm expulsion seemed to be mast cell dependent because expulsion was less complete in W/W^u mice at three weeks p.i. Peripheral blood eosinophilia was comparable at three weeks p.i. in both IgE and mast cell sufficient and deficient mice. These results suggest that IgE and mast cells participate in the expulsion of H. nana adults from intestine in mice.     

A Ro/SS-A auto-antibody positive mother's infant revealed congenital complete atrioventricular block,followed by insulin dependent diabetes mellitus and multiple organ failure

We experienced a congenital complete atrioventricular block infant who was born from a Ro/SS-A antibody positive mother. Ro/SS-A antibody was also found in this baby which was presumed to be mediated by the maternal placenta. Temporary cardiac pacing was required at birth and pacemaker implantation was performed at 9 months. At 11 months of age, the baby fell into shock and experienced multiple organ failure because of diabetes mellitus-induced coma. The association between congenital complete heart block and the Ro/SS-A antibody is well known. However, the accompaniment of insulin-dependent diabetes mellitus has not been reported previously. As the Ro/SS-A antigen appears in the cytoplasm of many tissues, the possibility of an association between Ro/SS-A antibody and diabetes mellitus is difficult to deny. We report this rare case to draw attention to the possibility that babies who are born from an Ro/SS-A antibody positive mother may develop diabetes mellitus as well as congenital complete heart block.     

EFFECTS OF SEED SAPONINS OF THEA SINENSIS L. (RYOKUCHA SAPONIN) ON ALCOHOL ABSORPTION AND METABOLISM

We evaluated the effects of the seed saponins of Thea sinensisL. on alcohol absorption and metabolism in rats and mice. Anethanolic extract from the seeds of T. sinensis was orally administeredto the rats 1 hr before or 0.5 hr after administration of ethanol(2 g/kg), and the blood ethanol assayed 0.5, 1, 2, 3, and 4hr after ethanol administration. The ethanol level decreasedafter both pie- and post- administration of the extract. Theextract was further purified to obtain a saponin fraction whichwas orally administered to mice 1 hr before ethanol administration.Blood, liver, and stomach were obtained 0, 1, 3, and 6 hr afterethanol administration, and the ethanol, acetaldehyde, acetate,and acetone concentrations in each specimen were measured byhead space gas chromatography. The saponin fraction decreasedthe ethanol levels in the blood and liver but increased thatin the stomach five-fold over the control level, suggestinginhibition of alcohol absorption. The ethanol disappearancetime from the blood was shortened, suggesting the promotionof alcohol disappearance. The acetate and acetone levels wereunaffected. However, the acetaldehyde level decreased in theblood, liver, and stomach. The decreases in the ethanol andacetaldhyde levels in the liver suggested the protective effectsof the seed saponins on the liver. The saponins did not directlyinhibit hepalic alcohol dehydrogenase activity. The seed saponinsof T. sinensis seem to suppress alcohol absorption by slowinggastric emptying and by inhibiting absorption across the cellmembranes of the digestive tract.     

Modification by Nickel of Instrumental Thermoregulatory Behavior in Rats1

Modification by Nickel of Instrumental Thermoregulatory Behaviorin Rats. WATANABE, C, WEISS, B., COX, C, AND ZIRIAX, J. (1990).Fundam. Appl. Toxicol. 14, 578–588. The effects of NiCl₂on the colonic temperature and thermoregulatory behavior (TRB)of rats were examined. TRB was evaluated in an instrumental(operant) setting in which rats were required to press a leverto obtain convectional heat (SEEK) or to avoid heat (ESCAPE).Orthogonal polynomial regression was used to describe the responsepatterns in both the SEEK and ESCAPE situations. Two milligramsper kilogram of Ni (ip) caused rapid, transient hypothermiaat an ambient temperature of 21°C. When given access toheat reinforcement, rats responded for heat at a lower rateimmediately after 2 or 5 mg/kg of Ni (up to 5–15 min)than after saline. Subsequently, response rates rose 30 minor more after Ni injection. A converse pattern was found withthe heat escape situation. These observations, confirmed bytwo contrasting procedures, indicate that the changes were thermoregulatoryin nature and cannot be explained by nonspecific sup-pressiveor excitatory effects of Ni. They further suggest that Ni-inducedhypothermia results from an altered body temperature set point.The subsequent reversal in behavior probably arises from a directaction of Ni on autonomic effector mechanisms. The origin andbiological significance of these findings require further investigation.Physical requirements and response topography are discussedas critical variables in the interpretation of experiments requiringsimilar responses under different ambient temperatures.