Down's syndrome

We discuss the ethical, psychosocial, economic, and medical dimensions of the treatment and management of a child with Down's syndrome and a congenital heart defect.     

Viral infections in the mouth

Oral hairy leukoplakia (OHL) and Kaposi's sarcoma (KS) are commonly encountered in the HIV-infected patient. A unique feature of OHL is non-cytolytic high level of replication of Epstein–Barr virus (EBV) in the glossal epithelium. The expression of viral-encoded anti-apoptotic proteins concomitant to replicative proteins probably underlies this phenomenon. The question of whether OHL arises from activation of EBV latent in the tongue, or from superinfection by endogenous EBV shed via non-glossal sites or by exogenous EBV remains unresolved. Human herpesvirus 8 (HHV8) is now seen as necessary but not sufficient cause of KS. Expression of HHV8-encoded oncogenic proteins in endothelial cells probably explains the aberrant proliferation of these cells in KS lesions. Studies into why KS is so commonly observed at the palate in HIV-infected patients may provide important clues to its pathogenesis.     

A time series investigation of three nicotine regulation models.

Time series data were collected twice daily for 62 days from 10 individuals on three variables related to smoking habit strength: number of cigarettes smoked, salivary cotinine, and carbon monoxide. The two purposes of this study were: (a) to evaluate which time series model(s) best fits each of the measures; and (b) to determine which model of nicotine regulation is consistent with the data. Three models of nicotine regulation were considered: (a) nicotine fixed effect; (b) nicotine regulation; and (c) multiple regulation. These models provide different predictions about the size and direction of the lag-one autocorrelation. Each measure was described in terms of one of a family of time series models represented mathematically as ARIMA (p, d, q). Models varied by individual, but a single model described the majority of subjects for all three variables. The clearest model identification was for the number of cigarettes smoked where an ARIMA (1, 0, 0) model with a moderate to strong negative dependency fit the majority of the subjects. This provided strong support for the multiple regulation model. An appendix provides a brief review of time series methodology.     

Olanzapine reduces craving for alcohol: a DRD4 VNTR polymorphism by pharmacotherapy interaction.

Separate investigations have suggested that olanzapine, a D4 antagonist, decreases craving after a priming dose of alcohol and that the DRD4 variable number of tandem repeats (VNTR) polymorphism influences the expression of craving after a priming dose of alcohol. The present study tested the hypothesis that olanzapine may be differentially effective at reducing cue-elicited craving based on individual differences in DRD4 VNTR in a sample of heavy social drinkers. Participants were randomly assigned to receive olanzapine (5 mg) or a control medication (cyproheptadine, 4 mg) prior to consuming three alcoholic drinks. Participants completed subjective measures of craving and euphoria after each drink. Participants who were homozygous or heterozygous for the 7 (or longer) repeat allele of the DRD4 VNTR were classified as DRD4 L, while the other participants were classified as DRD4 S. The findings indicated that olanzapine reduces craving for alcohol at baseline for both DRD4 S and DRD4 L individuals, but only reduces craving after exposure to alcohol cues and after a priming dose of alcohol for DRD4 L individuals.     

Immunisation with phage displaying peptides representing single epitopes of the glycoprotein G can give rise to partial protective immunity to HSV-2

Filamentous phage displaying peptides representing single epitopes of the glycoprotein G of HSV-2 (gG2) were used as immunogens via the subcutaneous route in Balb/c mice without additional adjuvant. The phage were isolated from a random phage peptide display library and contain 15-mer peptide inserts that mimic epitopes of gG2. In each case, an antibody response to gG2 was generated that was dependent on the dose of phage administered and on the presence of the peptide insert. Phage displaying epitopes of gG2, which map to amino acids 551-570, were the most immunogenic; interestingly, this region of gG2 is frequently recognised by patients infected with HSV-2. The data also provide interesting information as regards choice of peptide mimics for use as immunogens because, surprisingly, the most antigenic of the individual clones was the least immunogenic. In two of the experiments, mice immunised with phage displaying a single epitope of gG2 were protected against challenge with a lethal dose of whole HSV-2. This suggests a possible role for phage-displayed peptides in inducing protective immunity against pathogens and provides a model system for investigating the underlying mechanisms.     

Obesity, hypertension, and renal disease in relatives of Bardet-Biedl syndrome sibs

The Bardet-Biedl syndrome is a rare autosomal recessive disorder characterized by pigmentary retinopathy, obesity, polydactyly, hypogonadism, and mental retardation. Renal abnormalities, hypertension, acquired heart disease, and hepatic fibrosis also occur in homozygotes. Two adult Bardet-Biedl sibs, a man with hypertension and cardiomegaly and a woman with biliary cirrhosis, and 75 relatives in 5 generations of the extended family were identified. Hospital records for major illnesses, death certificates, and autopsy reports were examined. The frequent observation of obesity, hypertension, diabetes mellitus, and renal disease in first-degree relatives, obligate gene carriers, and other blood relatives raise the possibility that Bardet-Biedl heterozygotes are also predisposed to these disorders.     

Mechanism of slowing of mucociliary transport induced by SO2 exposure

Responses of nasal mucociliary transport mechanisms to exposure to 6 ppm SO₂ were studied in chickens in vivo. This model takes advantage of the natural cleft palate which exposes the mucociliated base of the nasal septum. Exposure to 6 ppm SO₂ decreased the mucociliary transport rate along the base of the nasal septum. The minimum force required to move an iron particle along this area of mucous membrane by use of a magnetic field in vivo increased significantly after SO₂ exposure, while the minimum force required to move an iron particle on a pool of mucus collected from the same chicken and tested in vitro showed no change after SO₂ exposure. The elastic recoil distance of mucus was measured both in vivo and in vitro. The in vivo recoil distance decreased significantly after SO₂ exposure, while SO₂ exposure did not change recoil distance in vitro. It is proposed that exposure of chickens to SO₂ results in the formation of multiple points of adhesion of strands of mucus between the acinar gland cells and the emergent extracellular mucus or adhesion of a mucous blanket to the cilia, causing mucociliary transport to be retarded or static.