Alagille syndrome: family studies

Alagille syndrome (AGS) is one of the major forms of chronic liver disease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity of interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically investigated parents in 14 families with an affected child. Clinical examination was supplemented by liver function tests, echocardiography, radiographic examination of the spine and forearm, ophthalmological assessment, and chromosome analysis. Six parents had typical anomalies in two or more systems pointing to the presence of autosomal dominant inheritance. Systematic screening of parents for the features defined in this study should improve the accuracy of genetic counselling.     

Effects of growth hormone-releasing factor and(or) thyrotropin-releasing hormone on growth, feed efficiency, carcass characteristics, and blood hormones and metabolites in beef heifers

The objective of this study was to determine the effect of long-term administration of a growth hormone (GH)-releasing factor analog (GRFa) and(or) thyrotropin-releasing hormone (TRH) on growth, feed efficiency, carcass characteristics, and blood hormones and metabolites in beef heifers. Crossbred heifers (n = 48; 345.9 +/- 2.8 kg) were divided into four equal groups: control (vehicle), 1 microgram of GRFa (human GRF 1-29 analog).kg BW-1.d-1, 1 microgram of TRH.kg BW-1.d-1, or GRFa + TRH. Daily s.c. injections continued for 86 d. Blood samples were collected from half of the heifers after injection on d 1, 36, and 78. On d 89, all heifers were slaughtered. Treatments did not affect (P > .05) ADG but GRFa + TRH decreased (P < .05) ADFI relative to all other treatments. Feed conversion efficiency tended (P < .10) to be improved in the groups given GRFa alone or TRH alone. Treatment with GRFa and(or) TRH did not affect carcass weight, dressing percentage, conformation score, backfat thickness, or weights of liver, kidneys, pituitary, and ovaries. The GRFa + TRH treatment reduced (P < .05) fat score and increased (P < .05) longissimus muscle area relative to other treatments. The GRFa treatments reduced (P < .05) the weight and fat percentage of the mammary gland and increased (P < .05) heart weight. Treatment with TRH alone failed to stimulate GH on d 1, 36, and 78. Treatment with GRFa alone increased (P < .05) GH above controls on d 36, whereas GRFa + TRH increased (P < .05) GH on d 1, 36, and 78. Treatment with GRFa alone increased (P < .05) IGF-I only on d 1, whereas GRFa + TRH was without effect on all days. Across sampling days, treatments had little effect on blood concentrations of insulin, triiodothyronine, nonesterified fatty acids, urea nitrogen, and glucose. The GRFa alone and GRFa + TRH decreased (P < .05) and TRH alone increased (P < .05) thyroxine concentrations. In conclusion, with the dose and administration regimen used, GRFa and(or) TRH yielded small but positive improvements in animal performance.     

Contributions of empirical research to medical ethics

Empirical research pertaining to cardiopulmonary resuscitation (CPR), clinician behaviors related to do-not-resuscitate (DNR) orders and substituted judgment suggests potential contributions to medical ethics. Research quantifying the likelihood of surviving CPR points to the need for further philosophical analysis of the limitations of the patient autonomy in decision making, the nature and definition of medical futility, and the relationship between futility and professional standards. Research on DNR orders has identified barriers to the goal of patient involvement in these life and death discussions. The initial data on surrogate decision making also points to the need for a reexamination of the moral basis for substituted judgment, the moral authority of proxy decision making and the second-order status of the best interests standard. These examples of empirical research suggest that an interplay between empirical research, ethical analysis and policy development may represent a new form of interdisciplinary scholarship to improve clinical medicine.     

Perceptions of elder abuse and help-seeking patterns among African-American, Caucasian American, and Korean-American elderly women

Thirteen scenarios were used to measure and compare the perceptions of elder abuse and help-seeking behaviors of African-American, Caucasian American, and Korean-American elderly women. Significant group differences existed in their perceptions of elder abuse with regard to six scenarios, and the Korean-American women were substantially less likely to perceive a given situation as abusive than the other groups. The three groups also showed significant differences in their intended use of formal and informal sources of help in the case of elder abuse.     

Demonstration of Epstein-Barr viral DNA in paraffin-embedded tissues of Burkitt's lymphoma from Argentina using the polymerase chain reaction and in situ hybridization

Burkitt's lymphoma (BL) is the most frequent non-Hodgkin's lymphoma in children in Argentina. Although epidemiologic studies have linked Epstein-Barr virus (EBV) to more than 90% of African BL cases but to only 10-20% of American and French cases, increased EBV-specific antibody titers were demonstrated in 73% of Argentinian patients with BL. To characterize the relationship between EBV and BL in Argentina, we analyzed paraffin-embedded tissues from 16 cases of BL for the presence of EBV DNA using the polymerase chain reaction (PCR) and in situ hybridization (ISH). PCR analysis showed that only 4 of 16 specimens contained the EBV BamW fragment, and these specimens were all from cases diagnosed in 1984. Results of ISH performed with a specific biotinylated DNA probe against the NotI/PstI fragment of EBV correlated with the PCR findings. EBV sequences were detected with ISH in 70-90% of the tumor cells from the 4 positive cases. These data may suggest an epidemic outbreak of EBV-related BL in 1984 superimposed on sporadic cases of BL, for which EBV may not have been an essential factor. This study also demonstrates the value of using molecular techniques on archival tissue to track epidemiologic trends.     

Jitter reduction through feedback for picosecond pulsed InGaAsPlasers

Following a comparison of picosecond-pulse generation techniques, feedback schemes are reported for the generation of picosecond pulse trains with improved jitter for both multicontact and conventional single-contact InGaAsP-InP lasers. Subpicosecond jitter is achieved for Q-switched laser sources using a novel optoelectronic feedback scheme. The use of resonant electrical feedback is shown to improve the timing jitter of gain-switched pulses by up to six times. Pulse-to-pulse timing jitter as low as 250 fs is demonstrated for a hybrid of optical and electrical feedback schemes. Limits for timing jitter in diode lasers are established for optoelectronic, electrical, and optical feedback schemes, and the key picosecond pulse generation schemes are compared in terms of timing jitter for the first time     

Permanent neuronal cell loss in the inferior olive of adult rats exposed to alcohol during the brain growth spurt: a stereological investigation

The purpose of this study was to examine whether exposure of rat pups to alcohol postnatally over a period of brain development similar to that of the human 3rd trimester results in a permanent loss of cells in the inferior olivary nucleus. It was hypothesized that a deficit of neurons in the inferior olive, the sole source of climbing fibers, may contribute to the cerebellar dysfunction observed following exposure to alcohol during development. Sprague-Dawley rat pups were artificially reared and administered alcohol over postnatal days 4-9. One artificially reared group received a daily alcohol dose of 4.5 g/kg, administered as a 10.2% solution in 2 of 12 daily feedings (10.2% group). This pattern of alcohol administration resulted in high peak blood alcohol concentrations with near total clearance. The other artificially reared group was fed a diet made isocaloric to the alcohol-containing diet (gastrostomy control group). Pups were allowed to grow to adulthood and killed on postnatal day 115. The total number of neurons in the inferior olivary nucleus was estimated using unbiased stereological methods. Exposure to alcohol resulted in a significant deficit in the number of neurons in the inferior olive at 115 days of age. The total number of neurons in the alcohol-exposed group was 40.12 +/- 8.7 x 10(3), compared with 53.37 +/- 3.7 x 10(3) in the artificially reared controls. These results indicate that there is a permanent deficit of neurons in the inferior olive after postnatal exposure to alcohol.(ABSTRACT TRUNCATED AT 250 WORDS)