A comparison of transnasal and transoral oesophagogastroduodenoscopy.

Transnasal oesophagogastroduodenoscopy (OGD) with a narrow-bore endoscope has been demonstrated to be feasible in unsedated volunteers. The aim of the study was to compare efficacy, safety, patient tolerance and costs between this novel approach to OGD and standard sedated OGD. Sixty day patients were enrolled for either sedated transoral endoscopy with a standard calibre endoscope or for unsedated transnasal endoscopy with a narrow-bore (5.3 mm diameter) endoscope. Visualization was unsatisfactory in one examination in each group. The only complications were minor epistaxis in four of the transnasal group and oxygen desaturation below 90% in two of the sedated transoral group. On a 1 (very uncomfortable) to 5 (very comfortable) visual analogue scale, the mean transnasal group score was 3.09, compared with 3.86 in the transoral group (P = 0.013). In the transnasal group, mean procedure room time was 15 min compared with 20 min in the transoral group (P < 0.0003), and mean recovery room time was 7 min compared with 37 min (P < 0.0001). Consumable and pharmaceutical costs were reduced by 65 and 92%, respectively. This study demonstrates that unsedated transnasal OGD is a safe and effective route for OGD and has acceptable patient tolerance. The safety and decreased recovery times offer major cost savings and the potential for this method of OGD to become an office procedure for the investigation of the upper gastrointestinal tract.

D2 dopamine receptor TaqI A alleles in medically ill alcoholic and nonalcoholic patients.

The prevalence of TaqI A alleles of the D2 dopamine receptor (DRD2) gene was examined in two subgroups of medically ill nonalcoholics (more prevalent and less prevalent substance users, MPSU and LPSU, respectively) and in two subgroups of medically ill alcoholics (more severe and less severe alcoholics, MSA and LSA, respectively). The prevalence of the A1 allele in the 80 nonalcoholic and 73 alcoholic patients was 30.0% and 52.1%, respectively (P = 0.009). In the four subgroups of these patients, the prevalence of this allele was: LPSU = 18.2%, MPSU = 34.5%, LSA = 44.4% and MSA = 58.3%. Linear trend analysis showed that as the use of substances and severity of alcoholism increase, so does A1 prevalence (P = 0.001). Specific, subgroup comparisons showed A1 prevalence in MSA to be about 3-fold (P = 0.007) and 1.5-fold (P = 0.04) higher than in LPSU and MPSU subgroups, respectively. Similarly, in a combined analysis of independent studies, A1 prevalence in MSA was higher when compared to LSA (P < 5 x 10(-3), MPSU (P < 10(-4) and LPSU (P < 10(-8) subgroups. There was virtually no difference in the prevalence of the A1 allele between LSA and MPSU subgroups. None of the specific medical or neuropsychiatric complications of alcoholism was associated with the A1 allele. In conclusion, the severity of alcohol dependence in alcoholics and of substance use behaviors in controls are important variables in DRD2 allelic association. The present report and converging lines of evidence suggest that the DRD2 locus could represent a prominent gene risk factor for susceptibility to severe alcoholism. However, other genes and environmental factors, when combined, still play the larger role.

D2 dopamine receptor gene and cigarette smoking: a reward gene?

There is now growing evidence that the less prevalent allele (A1) of the D2 dopamine receptor (DRD2) gene is strongly associated with severe alcoholism. Similarly, subjects who abuse illegal drugs or who are obese also show a significantly higher prevalence of the A1 DRD2 allele compared to controls. Moreover, cigarette smokers, both past and current, demonstrate significantly higher prevalence of the A1 allele than nonsmokers. In as much as alcohol, cocaine, opiates, nicotine and food are known to increase brain dopamine levels and activate the mesocorticolimbic dopaminergic reward pathways of the brain, it is hypothesized that an inherited deficit of D2 dopamine receptor numbers in brain reward areas of A1 allelic subject predisposes them to substance abuse problems.

Allelic association of the D2 dopamine receptor gene with cocaine dependence.

The objective of the present study was to examine allelic prevalence of the D2 dopamine receptor (DRD2) gene in male cocaine-dependent (CD) Caucasian (non-Hispanic) subjects and to determine the relationship of DRD2 alleles to family history and selected behavioral measures. The prevalence of the A1 allele in CD subjects (n = 53) was 50.9%. It was significantly higher than either the 16.0% prevalence (P < 10(-4)) in non-substance abusing controls (n = 100) or the 30.9% prevalence (P < 10(-2)) in population controls (n = 265) wherein substance abusers were not excluded. Similarly, a significantly higher prevalence (P < 10(-2)) of the B1 allele was found in CD subjects (n = 52) compared with non-substance abusing controls (n = 53); 38.5% vs. 13.2%. Logistic regression analysis of CD subjects identified potent routes of cocaine use and the interaction of early deviant behaviors and parental alcoholism as significant risk factors associated with the A1 allele. The cumulative number of these three risk factors in CD subjects was positively and significantly (P < 10(-3)) related to A1 allelic prevalence. The data showing a strong association of the minor alleles (A1 and B1) of the DRD2 with cocaine dependence suggest that a gene, located on the q22-q23 region of chromosome 11, confers susceptibility to this drug disorder.

P3 in young boys as a predictor of adolescent substance use.

Event-related potentials were recorded during a visual, continuous performance task from 36 boys before use of alcohol or other drugs began. The boys were sons of 13 recovering alcoholics who themselves had a family history of alcoholism, 11 nonalcoholics with a family history of alcoholism, and 12 nonalcoholics with no family history of alcoholism. Four years after electrophysiological assessment, a behavioral questionnaire was administered (mean age = 16.1 years). A Substance Use score was derived from reported use of alcohol and other drugs, and from highly correlated delinquent behavior scores. P3s of lowest amplitude were associated with the highest adolescent Substance Use. The combination of reduced amplitude and prolonged latency of both target and nontarget P3 significantly predicted adolescent Substance Use scores after correction for subjects' age. Although this is the first electrophysiological predictor of adolescent substance use we are aware of, the effect was small, indicating the utility of P3 as a vulnerability marker for substance abuse disorders is likely to depend on its joint use with other measures.

Genetic predisposition in alcoholism: association of the D2 dopamine receptor TaqI B1 RFLP with severe alcoholics.

Previous studies have shown an association of the 3' Taq1 A1 allele of the D2 dopamine receptor (DRD2) gene with severe alcoholism. The recent demonstration of a new polymorphism located closer to the regulatory regions of this gene, permits an associational analysis of these 5' Taq1 B alleles with alcoholism and a comparison with the 3' Taq1 A alleles. Restriction fragment length polymorphism methodology was used to analyze a total of 133 blood samples of nonalcoholics, less severe alcoholics, and severe alcoholics. In white subjects (n = 115), no significant difference in the prevalence of the B1 allele is found between nonalcoholics (n = 30) and less severe alcoholics (n = 36). However, the prevalence of this allele is significantly higher in severe alcoholics (n = 49) when compared to either nonalcoholics (p = 0.008) or less severe alcoholics (p = 0.005). When Taq1 B and Taq1 A alleles of the DRD2 gene are compared in whites, the prevalence of the A1 allele is significantly higher than the B1 allele only in the severe alcoholic group. In conclusion, alleles in both the 5' and 3' region of the DRD2 gene associate with severe alcoholism. This suggests that the DRD2 gene may have an etiological role in some severe alcoholics.

Association of the A1 allele of the D2 dopamine receptor gene with severe alcoholism.

In a blinded study, 159 subjects composed of nonalcoholics (N = 43), less severe alcoholics (N = 44), severe alcoholics (N = 52) and young children of alcoholics (CoAs, N = 20) were studied for their allelic association with the D2 dopamine receptor (D2DR) gene utilizing peripheral lymphocytes as the DNA source. The combined alcoholic group compared to the nonalcoholic group showed a significantly greater association with the A1 allele of the D2DR gene. Furthermore, an even more robust association was found when severe alcoholics were compared to nonalcoholics. CoAs also showed a significantly greater association with the A1 allele than nonalcoholics but not when compared to alcoholics. Analysis of risk of alcoholism severity suggests that it comprises of two independent components: family history of alcoholism and presence of the A1 allele. Genotype and allelic frequency of the D2DR gene were also analyzed with respect to race. A higher percentage of blacks compared to whites had the A1/A1 genotype, and A1 allelic frequency in the total sample of blacks was significantly greater than in the total sample of whites. Moreover, frequency of the A1 allele was significantly greater in severe alcoholics compared to nonalcoholics in both whites and blacks. However, due to the small sample size of blacks, these racial differences need to be further studied. This study, of the largest sample of alcoholics to date, strongly affirms association of severe alcoholism with the A1 allele of the D2DR gene.

Olsalazine in the treatment of active ulcerative colitis: a placebo controlled clinical trial and assessment of drug disposition.

The efficacy, safety and disposition of olsalazine was assessed in patients with left-sided ulcerative colitis or proctitis in a double-blind placebo controlled trial. Thirty patients with a mild-to-moderate attack of ulcerative colitis were randomly allocated to olsalazine capsules, 1 g b.d., or placebo for 6 weeks. Good clinical response was found in six patients receiving olsalazine and in two receiving placebo. Improvement in sigmoidoscopic findings and histological appearance of rectal biopsies was also seen more often in olsalazine-treated patients. Plasma concentrations of olsalazine were significantly higher in patients who improved. Olsalazine showed an advantage over placebo which needs to be confirmed by further studies; it was safe in sulphasalazine-sensitive patients but appeared to cause watery diarrhoea in two patients.

The influence of smoking on the healing of duodenal ulcer treated with oxmetidine or cimetidine.

The influence of smoking on duodenal ulcer healing was examined during a double blind study of 83 patients randomly allocated to oxmetidine or cimetidine treatment. Smoking habits were recorded but patients were not advised to change these. Smokers and nonsmokers were similar clinically and did not differ in compliance with medication. Both H2-receptor antagonists were equally effective and after four weeks of treatment ulcers were healed in 76% of patients. Ulcer healing occurred significantly less frequently in smokers (69%) than nonsmokers (89%). Smokers with healed ulcers consumed fewer cigarettes per day (mean +/- SE: 15.8 +/- 1.4) than those whose ulcers did not heal (22.2 +/- 2.7). When smokers were grouped according to daily cigarette consumption, a direct relationship was found between increasing cigarette consumption and decreasing frequency of ulcer healing. No reduction in ulcer healing was apparent in patients who smoked nine cigarettes a day, or less.

The significance of lowered jejunal disaccharidase levels.

Disaccharidase estimations on 115 consecutive jejunal biopsies are reported. The patients were divided into four groups: 1. Normal jejunal biopsy light microscopy, not milk intolerant, 82 cases. 2. Normal jejunal biopsy light microscopy, milk intolerant, eight cases. 3. Patients with giardiasis, 11 cases. 4. Coeliac disease patients, 14 cases. The lowest disaccharidase levels were found in coeliac disease, with giardiasis cases showing intermediate levels. Poor correlation of lactase levels with milk intolerance was found. Three cases in Group 1 showing lowered lactase levels were given metronidazole and showed remission of clinical symptoms, raising the possibility that they had undiagnosed infections with Giardia lamblia.

The diagnosis of giardiasis.

Four methods of diagnosing giardiasis are compared. Examination of smear preparations made from the jeunal biopsy specimen showed positive results in all of the 20 consecutive cases of giardiasis reported. The test was more reliable than examination of histological sections of the jejunal biopsy, wet preparations of jejunal aspirate, or faecal smears.

Early gastric carcinoma.

Seven cases of early gastric carcinoma are reported. This condition by definition refers to a carcinoma confined to the mucosa and submucosa only. The definition depends upon the depth of spread and not the surface area covered by tumour or the period over which it is believed to have been present. Each patient had a history indistinguishable from one of benign ulceration. All seven patients had barium meal studies, and in only two was the possibility of malignancy raised. In the other five patients the ulcers demonstrated radiologically were considered benign. Fibreoptic endoscopy was done in six cases; in three the appearances were suspicious of malignancy, and in the remaining three the lesions appeared benign. Biopsy specimens taken at endoscopy contained carcinomatous tissue in all six cases. The patients all had partial gastrectomy, and no recurrence has yet been found. The longest follow-up period is 36 months.