New monoclonal antibodies reacting with bile ducts: further insights into the pathogenesis of bile ductular proliferation in biliary diseases.

We have produced a range of monoclonal antibodies which stain human intrahepatic bile ducts of different sizes. Amongst 26 monoclonal antibodies produced, five clones reacted specifically with bile ducts of different sizes, of which three have been maintained in culture and their viability following freezing and thawing confirmed. Staining patterns varied between normal adult liver tissue, normal fetal liver tissue and a variety of hepatobiliary diseases. The antibodies provide further evidence of the immunological heterogeneity of the human intrahepatic biliary tree and support the hypothesis that proliferating bile ductules are derived from periseptal hepatocytes. The preparation of the antibodies, their staining reactions in normal adult, normal fetal and a variety of liver diseases are described.     

The right to an heir in the era of assisted reproduction

The latest remarkable technological advances in assisted reproduction, which enable cryopreservation of spermatozoa, embryos and ovarian tissue, raise difficult and debatable legal, social, ethical and moral issues concerning the right to posthumous reproduction. Furthermore, reports on the attitudes of the general public and of centres licensed for infertility treatment in the United Kingdom found that the majority of women and centres support the idea of posthumous reproduction. In this paper we review the data published on this issue, and after considering the various aspects, we conclude that each case should be discussed and authorized by a multidisciplinary committee that includes physicians, clergy, psychiatrists, psychologists, sociologists and other appropriate parties. In our opinion, the main principles that should guide this committee would allow posthumous reproduction in the context of marriage when a prior consent exists. For unmarried persons, post-mortem donation of gametes should be done only anonymously, if they are in agreement with existing laws concerning infertility treatments in every country and after appropriate consent and proper counselling. Moreover, any case which involves consanguinity or a possibility of incest should be forbidden, both for ethical and genetic reasons. In a case of pre-existing siblings, they should be consulted and their informed consent should be granted in advance so as to avoid legal problems in the inheritance of property.      

Scanning and transmission electron microscopic observations of the acute morphological response of the mouse urinary bladder to 4-ethylsulfonylnaphthalene-1-sulfonamide

A total of 75 BALB/cStCrlfC3H/Nctr male weanling mice were administered either 0 or 250 ppm of 4 ethylsulfonylnaphthalene-1-sulfonamide (ENS) in the diet for periods up to 14 days to evaluate the early morphological changes of the transitional epithelium of the urinary bladder with scanning (SEM) and transmission (TEM) electron microscopy. Primary TEM changes included hyperplasia of the epithelium, loosening of the intercellular junctions, autophagic vacuoles and electron dense granules in the mitochondria. Primary SEM changes included sloughing of epithelial cells, irregularity in the size and shape of the transitional epithelial cells and the presence of microvilli. Although pleomorphic microvilli were present after only three days of treatment with ENS, it appears that they are a transient observation in a series of morphological changes. The reversibility or transient nature of the pleomorphic microvilli may indicate that they are an acute toxic response and may not necessarily indicate a preneoplastic change.     

Batch variation and pharmacokinetics of oral sustained release melatonin-loaded sugar spheres in human subjects

The three different batches of an oral sustained release melatonin (MT) delivery system were prepared by aqueous-based fluid-bed coating of the sugar spheres for the evaluation ofin vitro release characteristics and plasma concentration profiles in human subjects. The MT contents in 20% coated sugar spheres of three batches (B1, B2 and B3) were 3.3+/-0.08, 2.4+/-0.1 and 2.5+/-0.13 mg per gram of coated sugar spheres, respectively. The release profiles of three different batches had a very similar fashion. However, the release half-lives (T(50%)) of MT from B1, B2 and B3 was 3.70+/-0.2, 5.2+/-0.2 and 4.9+/-0.07h, respectively. Plasma concentration profiles of sustained release 0.2mg melatonin-loaded sugar spheres containing 10% immediate release melatonin in gelatin capsules (B1 and B2) were then evaluated in human subjects. Thein vivo plasma concentration profiles of the two batches (B1 and B2) were very similar each other and located between the physiological endogenous ranges. The time to reach the peak concentration (T(max)) was more advanced in case of B1 when compared to B2. However, there was no statistically significant difference in the maximum concentration (C(max)) and the area under the curve (AUC) between B1 and B2. The AUC of melatonin-loaded sugar spheres containing 10% and 20% immediate release MT in human subjects had a good linearity between dose and AUC, regardless of the fraction of immediate release MT, indicating the first order elimination process of MT within these doses. The current oral sustained release MT delivery system may be utilized to treat circadian rhythm disorders if it is proven to be more clinically useful when compared to immediate release MT.     

Use of the Threat Index with family members waiting during surgery

We describe the use of the 40-item Threat index (TI) with family members (N = 206) of surgical patients who also completed Templer's (1970) Death Anxiety Scale, the Death-of-Self and Dying-of-Self subscales of the Collett-Lester (1969) Fear of Death Scale, and the Death Acceptance subscale of Reker and Peacock's (1992) Life Attitude Profile-Revised. Word sets from the 40-item TI that are part of the 25- and 7-item versions of the TI produced strong alphas and correlatians to their parent instrument. Regression analyses indicated that selftideal-self scores and previous experience as a hospital patient were significant associated with TI scores. We conclude that if the time available for completion and scoring of the TI is limited, the shorter versions can be used, although their alpha strengths are slightly lower than that of the full TI and the respondent's age influences the scores.