Embryonic stem cells: advances toward potential therapeutic use

Established lines of human pluripotent stem cells provide a convenient tool for investigating cell differentiation in a way that is pertinent to human embryonic development, providing insights into the causes of birth defects and diseases such as cancer that involve aberrant cell proliferation and differentiation. In principle, human pluripotent stem cells, including embryonic stem and embryonic germ cells, are capable of differentiating into all of the cell types that are present in the adult human. They therefore have the potential to provide a source of tissues for replacement in diseases in which native cell types are inactivated or destroyed. Intense media and public interest has surrounded the announcement of human pluripotent stem cells derivation, focusing on the ethical implications of embryo-related work and on the prospects of an unlimited source of tissues for transplantation-based treatments. Recent studies have focused on identifying method for culture of these cells and inducing their differentiation into specific cell types.     

Laparoscopic cholecystectomy for triple gallbladder

A very rare case involving true triplication of the gallbladder in a 38-year-old man with no other congenital abnormalities is reported. All three gallbladders had signs of chronic inflammatory disease and lithiasis. Acute cholecystitis and a double gallbladder were diagnosed preoperatively, but the diagnosis of a second accessory gallbladder was made only at the time of surgery. The patient underwent successful laparoscopic cholecystectomy. When a triplicate gallbladder is encountered, complete dissection of Calots triangle and intraoperative cholangiographic evaluation should be performed to prevent damage to the biliary duct system. All three gallbladders should be removed to avoid unnecessary reoperation. All of this can be accomplished readily by laparoscopic surgery.     

Confidentiality and the ethics of medical ethics

In this paper we consider the use of cases in medical ethics research and teaching. To date, there has been little discussion about the consent or confidentiality requirements that ought to govern the use of cases in these areas. This is in marked contrast to the requirements for consent to publish cases in clinical journals, or to use personal information in research. There are a number of reasons why it might be difficult to obtain consent to use cases in ethics. Many cases concern people who are incompetent, and thus unable to give consent. Often the material is of a sensitive nature, it is not clear who should give consent, or the ethicist has no access to those involved. We argue that the use of cases in ethics research and teaching can be justified by appeal to the public interest argument, and suggest a number of areas for discussion and clarification.     

Modified mandated choice for organ procurement

Presumed consent to organ donation looks increasingly unlikely to be a palatable option for increasing organ procurement in the UK following the publication of the report into events at Alder Hey and elsewhere. Yet, given that the alternative to increasing the number of cadaveric organs available is either to accept a greater number of live donations, or accept that people will continue to die for the want of an organ, public policy makers remain obliged to consider other means of increasing the procurement rate. In this paper, we meet the main objections to mandated choice (namely that it undermines autonomy and that mandated donation is preferable). We have modified the traditional approach to mandated choice to take into account the force of the objection that mandated donation is preferable, by accepting that people can and do make bad decisions about organ donation and proposing that all accompanying public education and information about cadaveric donation should be directed in favour of donation.     

Prediction of mortality in nursing home residents: impact of passive self-harm behaviors

OBJECTIVE: The aim of this study was to determine whether indirect self-destructive behaviors predict mortality in nursing home residents. METHOD: This cross-sectional study with follow-up after 2 years and 3 months surveyed 593 residents in 10 nursing homes in the eastern suburbs of Sydney, Australia. The following instruments were used: Harmful Behaviors Scale (HBS), Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Functional Assessment Staging Scale, Resident Classification Index, Cumulative Illness Rating Scale, Even Briefer Assessment Scales for Depression, and the suicide item from the Structured Hamilton Depression Rating Scale. Diagnoses of depression, dementia, and psychosis were obtained from nursing home records. Mortality data were obtained in August 1999. RESULTS: At follow-up, 297 (50.1%) residents were still alive with a mean survival time of 565.4 days. Survival analyses found that mortality was predicted by older age, male gender, lower level of functioning, lower levels of behavioral disturbance on the BEHAVE-AD, and higher scores on the HBS "passive self-harm" factor-based subscale, which includes refusal to eat, drink, or take medication. DISCUSSION: These results suggest that passive self-harm behaviors predict mortality in nursing home residents.     

Case-control study of parental age, parity and socioeconomic level in relation to childhood cancers

BACKGROUND: Parental ages, parity, and social class have been found in some studies to be associated with particular childhood cancers. Further investigation is warranted because of conflicting findings, biases, and the need to test specific hypotheses. METHODS: A case-control study was conducted (England and Wales, ages 0-14 years). Cases were ascertained from the National Registry of Childhood Tumours, and were born and diagnosed during 1968-1986. Birth record controls were matched 1:1 to cases on date of birth, sex and area. Information on variables of interest for both groups came from birth records. In all, 10 162 pairs could contribute to matched analyses. RESULTS: The odds ratio (OR) for retinoblastoma resulting from assumed new germ cell mutations among children of fathers aged > or =45 years was 3.0 (95% CI : 0.2-41.7). The risk of childhood acute lymphoblastic leukaemia (ALL) was significantly higher among children of older mothers and fathers, and significant trends with increasing mothers' (P < 0.001) and fathers' (P = 0.002) ages were found. There was a strong and significant protective effect of increasing parity on risk of childhood ALL. The adjusted OR for parity of > or =5 (versus 0) was 0.5 (95% CI : 0.3-0.8). Children in more deprived communities had a lower risk of ALL; but this was not significant after confounders were allowed for. There was no significant effect of social class based on parental occupation on ALL risk, but the numbers were small in those analyses. CONCLUSIONS: The associations between ALL and parental ages did not disappear when children with Down syndrome were excluded, suggesting an additional explanation beyond known links. The strong ALL association with parity may be because of an unknown environmental risk factor.     

Levels of vaginal secretory leukocyte protease inhibitor are decreased in women with lower reproductive tract infections

OBJECTIVE: Secretory leukocyte protease inhibitor contributes resistance to primary human immunodeficiency virus infection in the oral cavity. However, the levels of this inhibitor in the genital tract of women with sexually transmitted diseases or vaginitis are not well described. The objective was to determine vaginal inhibitor levels in women with symptomatic and asymptomatic genital infections. STUDY DESIGN: We tested 207 nonpregnant women for Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis, Candida species, and bacterial vaginosis by standard methods. A second group of symptom-free pregnant women (N = 231) was also studied. Secretory leukocyte protease inhibitor was measured by enzyme-linked immunosorbent assay, and results were compared by nonparametric methods. RESULTS: Vaginal levels of secretory leukocyte protease inhibitor in both groups were significantly lower in women with any sexually transmitted disease than in those without infection (P<.0001). Patients with bacterial vaginosis and those with bacterial vaginosis with yeast vaginitis also had decreased levels (P<.025). CONCLUSIONS: Levels of secretory leukocyte protease inhibitor in vaginal fluid are decreased in women with lower genital tract infection. This may represent a common mechanism of increasing susceptibility to infection with human immunodeficiency virus.     

Calorie restriction in nonhuman primates: mechanisms of reduced morbidity and mortality

Long term chronic calorie restriction (CR) of adult nonhuman primates significantly reduces morbidity and increases median age of death. The present review is focused upon an ongoing study of sustained adult- onset calorie restriction, which has been underway for 15 years. Monkeys, initially calorie restricted at about 10 years of age, are now approximately 25 years old. The median life span of these restricted monkeys is increasing, now exceeding that of ad libitum (AL)-fed monkeys. In our laboratory, maximum life span for AL-fed monkeys appears to be about 40 years. Thus, whether CR can also increase maximal life span, as it does in rodents, cannot be determined for at least another 15 years. The earliest detectable positive benefit on morbidity in these monkeys was previously reported as the prevention of obesity. Current evidence, as reviewed here, suggests that much obesity- associated morbidity is also mitigated by sustained calorie restraint in nonhuman primates. Furthermore, probably because of the prevention of obesity, diabetes has also been prevented. Recent findings include the identification of extraordinary changes in the glycogen synthesis pathway, and on the phosphorylation of glycogen synthase in response to insulin. This calorie restriction-induced prevention of morbidity does not require excessive leanness, but is clearly present when body fat is within the normal range of 10 to 22%, and this is likely to be true in humans as well.      

Microbiology and pathogenesis of acute salpingitis as determined by laparoscopy: What is the appropriate site to sample?

Acute salpingitis is a polymicrobial disease. Neisseria gonorrhoeae and anaerobic gram-positive cocci were the predominant microorganisms isolated from the fallopian tubes of salpingitis patients. Gonococci were isolated from the fallopian tubes in eight of 35 (23%) patients; anaerobic bacteria were recovered from 10 of 35 (28.5%). Although Chlamydia trachomatis was not recovered from the fallopian tube exudate, there was abundant serologic evidence of chlamydial infection in the salpingitis patients. Twenty-three percent of patients with paired sera had a fourfold rise in IgM and IgG titer, which was consistent with systemic chlamydial infection. Comparison of cultures obtained via laparoscopy and culdocentesis suggested that culdocentesis is not an accurate reflection of the microbial milieu in the fallopian tube.