New mutation causing hereditary hepatitis in the laboratory rat

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight. The affected rats showed a high lethality and histological changes of the liver with focal necrosis of enlarged hepatocytes without inflammatory cell response. Genetic tests indicate that at least a single autosomal recessive gene is responsible for the major cause of hepatitis. Furthermore, liver cancer appears in long survived rats after recovery from jaundice as well as a few asymptomatic rats without jaundice. The LEC rats thus provide an animal model useful for the basic and clinical studies of hepatitis and liver cancer, including their pathogenesis, prevention, and treatment.     

Neonatal jaundice: the surgical viewpoint.

There is good evidence that neonatal hepatitis, biliary hypoplasia, biliary atresia and choledochal cyst are different stages of one disease process for which the term infantile obstructive cholangiopathy has been suggested. Thanks to the work of Kasai and the operation of hepatic portoenterostomy the surgical outlook has greatly improved, although in North America it still leaves much to be desired. One cannot procrastinate too long in the hope that the patient''s condition will improve spontaneously, because the surgical results are much better when the operation is performed before the patient is 10 weeks old. This article outlines the steps that should be followed in investigating neonatal jaundice, the nonsurgical measures that can be taken in an attempt to reverse or alleviate the underlying condition, and the specific role of the pediatric surgeon in the management of choledochal cyst and biliary atresia.     

新生儿肠道双歧杆菌数量影响因素与其婴儿期腹泻关系

目的探讨新生儿肠道双歧杆菌数量的相关影响因素,并明确它们与婴儿期腹泻的关系。方法以120例新生儿为研究对象,生后5-7 d均做大便双歧杆菌定量培养,并做相关因素的准确登记,同时严密观察随访至1岁,准确记录其发生腹泻情况。结果母亲分娩方式、临产期及产后是否使用抗生素、母亲妊娠期饮食习惯以及新生儿黄疸期长短与新生儿肠道双歧杆菌数量有相关性。新生儿黄疸期长、母亲临产期及产后使用抗生素均是婴儿腹泻的危险因素;阴道分娩、母亲喜发酵制品及喜素食均是婴儿腹泻的保护因素。结论为避免导致新生儿肠道双歧杆菌数量不足的影响因素,提倡阴道分娩、临产期及产后不用抗生素、妊娠期多食发酵制品和素食,并尽量设法缩短新生儿黄疸时间,以减少婴儿腹泻的发生。     

Lábrea hepatitis in Salvador, Bahia? (Presentation of a possible case)

A case of a four-year-old boy from Salvador, Bahia, Brazil, with a probable Lábrea hepatitis is reported. He ran a rapid course of fever, jaundice, abdominal pain, agitation, coma and death. Histologically, the liver presented widespread hepatic cell lytic and coagulative necrosis, acute fatty changes, mononuclear cell infiltration and cholestasis. The study of the case raises the question whether Lábrea hepatitis can occur outside the Amazonian region, or else its clinico-pathological features lack specificity.     

History of the research on differentiating Hepatitis A and B]

The numerous researches devoted to 'jaundice' during the Second World War have brought to light the existence of an infectious type of hepatic jaundice or 'homologous serum jaundice' following parenteral injection of vaccines containing human serum and blood transfusions, which were carried out on a large scale at the time. This type of serum jaundice was then gradually differentiated from 'catarrhal', contagious or epidemic jaundice by clinical trials along with large series of animal studies. Finally, the epidemiological, clinical and biological data obtained made it possible to establish, between 1944 and 1954, the viral etiology of these two types of jaundice: the A virus, present in the patients' blood and stools, was considered to be the agent responsible for epidemic hepatitis; the B virus, present primarily in the blood, was held to be responsible for serum hepatitis.     

Cell-mediated Immune Responses in Chronic Liver Diseases

Studies of the cell-mediated response to liver antigens, using the leucocyte migration test, in 163 patients with various liver disorders showed that abnormal responses were almost confined to active chronic hepatitis (53% abnormal), primary biliary cirrhosis (64%), and cryptogenic cirrhosis (29%). The test was also abnormal in five out of seven patients with jaundice due to drug hypersensitivity and in one patient with acute infectious hepatitis at a time when mitochondrial antibodies were present in the serum. More of those with active chronic hepatitis on prednisone or azathioprine had normal tests than of those who were untreated, and in 8 out of 10 examined serially during therapy there was an accompanying improvement in leucocyte migration. Abnormal responses to salivary gland or kidney antigens were also found in nearly half of those with features of Sjögren''s syndrome or renal tubular acidosis as part of a multisystem involvement—this, though occurring in cryptogenic cirrhosis, was found with greater frequency in active chronic hepatitis and primary biliary cirrhosis. These cell-mediated immune responses, perhaps triggered by the initial damage to the liver from viral or other agents, may be responsible both for the perpetuation of the liver disease and, because of common surface antigens, for the damage to other organs.     

茵陈蒿汤联合西药治疗母儿ABO血型不合疗效分析

目的：评价中西药结合治疗对母儿ABO血型不合的疗效以及新生儿溶血发生与孕次关系的探讨。方法：对314例抗体滴度≥l：64的ABO母儿血型不合孕妇（20-45岁）进行研究,其中246例孕期给予以中西药结合治疗（茵陈蒿汤联合25%葡萄糖液、维生素C、维生素E、苯巴比妥）,68例作为对照,观察孕妇IgG抗A/B抗体效价变化及新生儿溶血发生情况。结果：治疗组抗体效价降低与对照组相比,差异有统计学意义（P〈0.05）,治疗组新生儿溶血发生率与对照组相比,差异有统计学意义（P〈0.05）。孕次越大,新生儿溶血的发生率越高。结论：中西药结合治疗对降低孕妇IgG抗A/B效价及防治新生儿溶血疗效满意,新生儿溶血发生可能与孕次呈正相关。     

Prophylaxis against hepatitis A for travel.

OBJECTIVE--To develop a rational practice policy for prophylaxis against hepatitis A for travellers to high risk areas. DESIGN--18 Month prospective study of consecutive patients who requested prophylaxis against hepatitis A. SETTING--Inner city general practice. SUBJECTS--104 Patients aged 15-61 (mean 30) assessed for risk factors for hepatitis A and put into groups depending on predictions from the risk factors of their immunity. MAIN OUTCOME MEASURES AND RESULTS--All patients were screened for antibody to hepatitis A virus. Of 52 patients with no risk factors 47 had no antibody and were thus susceptible to hepatitis A. All 27 patients with major risk factors (having been brought up in an endemic area or with a history of jaundice) were immune. Of 25 patients with minor risk factors (a history of previous travel in high risk areas, drug abuse, having lived in a squat or travelled rough, or having lived with someone who had jaundice) 12 were immune (p less than 0.001, chi 2 test). CONCLUSIONS--All travellers requesting prophylaxis against hepatitis A should be assessed for risk factors for previous exposure to hepatitis A. Those with no risk factors could be immunised with human normal immunoglobulin without screening. The remainder should be tested for hepatitis A antibody and those found to be susceptible should be immunised.     

新生儿母乳性黄疸150 例分析

目的:探讨新生儿母乳性黄疸诊断及治疗。方法:回顾性分析150例母乳性黄疸患儿的临床资料。给予思密达1.5g·d和蓝光等治疗,部分患儿停喂母乳。结果:早发型母乳性黄疸治疗5～7天后黄疸全部消退。迟发型母乳性黄疸停母乳3天,92.6%黄疸消退。结论:新生儿母乳性黄疸采用药物等综合治疗效果显著,预后良好。     

Enterotropic mouse hepatitis virus infection in nude mice

The cause of emaciation and diarrhea in athymic nude mice was found to be hyperplastic typhlocolitis resulting from infection with enterotropic mouse hepatitis virus (MHV). The disease was reproduced in experimentally-inoculated nude mice using intestinal homogenates from affected mice and cell culture-derived virus. Material derived from an experimental mouse was passed into neonatal Swiss mice and caused acute typhlocolitis. Virus failed to grow in NCTC-1469 cells and 17Cl-1 cells, which are normally permissive for MHV, but grew to low titer in a mouse rectal carcinoma cell line, CMT 93. These results show that an enterotropic strain of MHV can cause chronic enteric disease in athymic nude mice. The pattern of infection differs markedly from the more common MHV wasting syndrome in nude mice caused by non-enteric strains of MHV.     

Pruritus and Jaundice

The records of 147 patients who had pruritus and jaundice (11% of a series of 1262 patients with jaundice) were reviewed in an effort to delineate more clearly the etiology of jaundice associated with pruritus.Fifty-two had obstructive jaundice caused by neoplasm, 51 had obstructive jaundice not caused by neoplasm, 42 had pruritus associated with hepatogenous jaundice, and two had jaundice and pruritus associated with a lymphoma.Pruritus occurred in 17% of all patients with non-neoplastic obstructive jaundice and in 45% of patients with neoplastic obstructive jaundice. Hepatogenous jaundice was the cause of pruritus in almost one-third of the patients in this series-occurring in 20% of patients with infectious hepatitis and in 7% of patients with cirrhosis.This large series confirms the clinical impression that pruritus occurs most often in association with extrahepatic biliary obstruction, and as well re-emphasizes the common association of pruritus with hepatogenous jaundice.     

新生儿肠道双歧杆菌数量与其相关影响因素的探讨

目的　探讨影响新生儿肠道双歧杆菌数量的相关因素。方法　以重庆医科大学附属二院和重庆市妇幼保健院的12 0例新生儿为研究对象,每例生后5～7d,均采集新鲜大便做双歧杆菌定量培养,并做10个相关因素的准确登记。结果　母亲分娩方式、临产期及产后是否使用抗生素、母亲妊娠期饮食习惯以及新生儿黄疸期长短与新生儿肠道双歧杆菌数量有相关性( P均<0 .0 1)。结论　提倡阴道分娩、临产期及产后不用抗生素、妊娠期多食发酵制品和素食,并尽量设法缩短新生儿黄疸时间,均有益于新生儿肠道双歧杆菌数量相对充足     

Unexplained hepatitis following halothane.

Full clinical and laboratory details of 203 patients with postoperative jaundice were submitted to a panel of hepatologists. All patients whose jaundice may have had an identifiable cause were excluded, which left 76 patients with unexplained hepatitis following halothane anaesthesia (UHFH). Hepatitis in 95% of these cases followed multiple exposure to halothane, with repeated exposure within four weeks in 55% of cases. Twenty-nine patients were obese, 52 were aged 41-70, and 53 were women. Thirteen patients died in acute hepatic failure. Rapid onset of jaundice after anaesthesia, male sex, and obesity in either sex were poor prognostic signs. Of the clinical stigmata of hypersensitivity, only eosinophilia was impressive. The UHFH group had a much greater incidence of liver kidney microsomal (LKM) and thyroid antibodies and autoimmune complement fixation than those patients whose jaundice related to identifiable factors. Thirteen of the 19 patients with LKM antibodies also had thyroid antibodies. In six patients retested two to three years later LKM antibodies had disappeared, although thyroid antibodies persisted. Rapidly repeated exposure to halothane may cause hepatitis, but such a complication is probably rare. Possibly obese women with a tendency to organ-specific autoimmunity may be more at risk. Nevertheless, the comparative risks of rapidly repeated halothane or non-halothane anaesthesia cannot be determined from the present data. If alternative satisfactory agents are available halothane should be avoided in patients with unexplained hepatitis after previous exposure, although in three to five patients with UHFH who were re-exposed to halothane jaundice did not recur.     

Factors influencing the incidence of neonatal jaundice.

A retrospective study of 12 461 single births confirmed an association between maternal oxytocin infusion and neonatal jaundice. The effect of oxytocin on jaundice was independent of gestational age at birth, sex, race, epidural anaesthesia, method of delivery, and birth weight, each of which was significantly associated with neonatal jaundice. The effect of oxytocin was, however, small, producing a calculated mean increase in peak plasma bilirubin concentration of 8.6 mumol/1 (0.5 mg/100 ml); this excess was independent of sex and less than the effect of the baby being born one week earlier.     

Identification and Cloning of the Human Homolog (JAG1) of the RatJagged1Gene from the Alagille Syndrome Critical Region at 20p12

Notch proteins are a family of closely related transmembrane receptors proven to be instrumental in cell fate decisions. Recently, Notch ligands Delta and Jagged have been identified inDrosophilaand rat, respectively. We have isolated the human homolog of the ratJagged1gene,JAG1,from a CpG island in a YAC clone covering the Alagille syndrome critical region at chromosome 20p12 (tel–SNAP–D20S186–cen). Alagille syndrome is an autosomal dominant disorder characterized by neonatal jaundice, paucity of intrahepatic bile ducts, and abnormalities of the heart, skeleton, and eyes. The humanJagged1(JAG1), therefore, appears to be a strong candidate gene for this disease. Here we describe the identification, full-length cDNA cloning, expression patterns, and precise physical location of this gene within the Alagille syndrome critical region.     

Non-B hepatitis in Melbourne: a serological study of hepatitis A virus infection.

A study was performed to establish the value of immune adherence haemagglutination tests for antibody to hepatitis A virus in the diagnosis of non-B hepatitis. Infection with hepatitis A virus was confirmed in 14 out of 16 patients from six families and seven out of nine patients in whom the source of infection was unknown. One additional patient, who had had two episodes of jaundice, was shown to have had an attack of hepatitis A followed by an attack of hepatitis B. In patients with acute hepatitis A antibody detectable by immune adherence haemagglutination becomes detectable three or four weeks after the onset of symptoms and reaches peak levels about five weeks later.     

Ward design and neonatal jaundice in the tropics: report of an epidemic.

Architectural modifications to an existing tropical obstetric ward involved extension of the roof overhangs to a width of several metres. These extensions excluded most of the daylight from the ward. An alarming increase in the incidence of jaundice (bilirubin concentration greater than or equal to 240 mumol/l (greater than or equal to 14 mg/100 ml] from 0.5% to 17% in newborn infants occurred after the modifications. Tropical obstetric wards and nurseries should continue to be built with windows facing north-south for coolness. They should, however, have as many windows as possible and the roof overhangs should be limited to about 1 m to allow adequate indirect sunlight to enter, giving a high intensity of illumination, and help prevent neonatal jaundice.     

Use of oxytocin and incidence of neonatal jaundice.

A retrospective controlled study using data from the Cardiff Births Survey examined a possible relation between oxytocin administration to induce or accelerate labour and the subsequent development of neonatal jaundice. Among 10 591 infants born in Cardiff between 1970 and 1972 the incidence of neonatal jaundice was higher in infants born after oxytocin administration than among others. Analysis by gestational age at delivery, birth weight, Apgar score, length of labour, sedative and analgesic therapy during labour, and suppression of lactation showed that this association held within all these categories except among small immature infants, who are at high risk of jaundice in any case.