Familial Parkinson's disease: possible role of environmental factors

We report here six families with Parkinson's disease in whom the onset of symptoms tended to occur at approximately the same time irrespective of the age of the patient. The mean difference in the time of onset in different generations was 4.6 years while the mean difference in age of onset in children and parents was 25.2 years. We construe this pattern of age separation within families as suggestive of an environmental rather than genetic cause. Support for this view derives from the lack of correlation between occurrence of the disease and the degree of consanguinity. We conclude that our findings are in accord with the hypothesis which attributes the cause of some cases of Parkinson's disease to early, subclinical environmental damage followed by age-related attrition of neurons within the central nervous system.     

Crohn's disease presenting with acute colonic perforation.

Crohn''s disease is well known for its multiple intestinal complications. The chronic nature and fibrous inflammation which invariably accompanies this disease explains the relative rarity of free intestinal perforation. The true incidence of free bowel perforation is difficult to assess but 1-2% is the anticipated occurrence during the course of illness. We present a case of Crohn''s disease which presented for the first time with acute colonic perforation, an extremely rare entity, and review the current world literature.     

Treatment of essential blepharospasm with quetiapine.

A 69-year-old male with blepharospasm unresponsive to several medications who was successfully treated with quetiapine is described. His symptoms were largely alleviated by low doses, but he experienced sedation, which permitted him to take the medication at bedtime only.     

Cisapride decreases prolonged episodes of reflux in infants

Twenty-nine infants (2-4 months old), with pathological gastroesophageal reflux assessed by 24-h esophageal pH monitoring, were studied. Cisapride or placebo was randomly added to positional treatment, prone-antiTrendelenburg position, which was applied to all infants. The pH monitoring was repeated after 13-16 days of treatment and revealed a significant improvement in both groups for most parameters. But the number of reflux episodes lasting longer than 5 min and the total number of reflux episodes had not decreased significantly in the placebo group. Only in the number of reflux episodes lasting longer than 5 min was improvement during treatment significantly greater in the cisapride group. This suggests cisapride both prevented reflux and improved esophageal clearance. These results suggest that in addition to other therapeutic measurements, such as positional treatment (which was previously demonstrated to be effective in this age group), cisapride might be of benefit in the treatment of gastroesophageal reflux disease.     

Shared executive dysfunctions in unaffected relatives of patients with autism and obsessive-compulsive disorder.

BACKGROUND: Executive dysfunctions have been studied as a potential endophenotype associated with the genetic basis of autism. Given that recent findings from clinical and molecular genetic studies suggest that autism and obsessive-compulsive disorder (OCD) could share a common pattern of heritability, we assessed executive functions as a possible common cognitive endophenotype in unaffected family members of individuals with either autism or OCD. METHODS: Five tests assessing executive functions (Tower of London, verbal fluency, design fluency, trail making and association fluency) were proposed to 58 unaffected first-degree relatives (parents and siblings) of probands with autism and 64 unaffected first-degree relatives of OCD patients. Results were compared with those of 47 healthy controls matched for age, sex, and level of education. RESULTS: In the Tower of London test, both groups of unaffected relatives showed significantly lower scores and longer response times compared with controls. No differences were observed between autism and OCD relatives and healthy controls in the four other tasks (verbal fluency, design fluency, trail making test and association fluency). CONCLUSIONS: Our findings show the existence of executive dysfunction in the unaffected first-degree relatives of probands with OCD, similar to those observed in the relatives of patients with autism. These results support and extend previous cognitive studies on probands indicating executive dysfunctions in autism and OCD. Planning and working memory processes could thus represent a common cognitive endophenotype in autism and OCD that could help in the identification of genes conferring vulnerability to these disorders.     

Carboxylic acid replacement structure-activity relationships in suosan type sweeteners. A sweet taste antagonist. 1.

N-(4-Cyanophenyl)-N'-(2-carboxyethyl)urea (2), an analogue of suosan [1,N-(4-nitrophenyl)-N'-(2-carboxyethyl)urea], is a known high-potency sweetener derived from beta-alanine. Sulfonic and phosphonic acid analogues of 2 were prepared to develop structure-activity relationships through modification of the carboxylic acid region of this family of sweeteners. Neither of the carboxylic acid replacements resulted in sweet analogues. However, we found that N-(4-cyanophenyl)-N'-[(sodiosulfo)methyl]urea (7) is an antagonist of the sweet taste response. The bitter taste response to caffeine, quinine, and naringin was also antagonized. Antagonist 7 was found to inhibit the sweet taste perception of a variety of sweeteners. Antagonist 7 had no effect on the sour or salty taste response.     

Loss of Heterozygosity at the α-Inhibin Locus on Chromosome 2q Is Not a Feature of Human Granulosa Cell Tumors

The α-inhibin gene has been shown in knockout mouse models to be a suppressor of granulosa tumorigenesis in the mouse. To determine if α-inhibin has the same function in humans, we have assessed the frequency of loss of heterozygosity (LOH) of the α-inhibin gene locus on chromosome 2q in 17 human granulosa cell tumors and 36 epithelial ovarian cancers. LOH was detected in 12 of 36 (33.3%) epithelial tumors but in only 1 of 17 (6%) granulosa cell tumors. These data suggest that in contrast to the suggestions from the mouse model α-inhibin does not function as a granulosa cell tumor suppressor gene in the human. Furthermore, analysis of the TP53 gene in the granulosa cell tumors failed to detect either LOH or point mutations, indicating that they have a developmental pathway distinct from that of epithelial ovarian tumors.     

Risk factors for suicide attempts among alcohol dependent patients.

Suicidal behavior is a common and important problem among alcohol dependent patients. The study was designed to examine risk factors for attempting suicide in 499 alcohol dependent patients. Those who had attempted suicide (N = 198) were more likely to be female, report a family history of suicidal behavior, report more childhood trauma, report greater levels of aggressive behavior, began heavy drinking earlier, and were more likely to have received antidepressant medication. Logistic regression analysis showed that gender, family history, and childhood sexual abuse history made significant and independent contributions to the risk of a suicide attempt. Thus, developmental, personality, family history, social, and comorbidity risk factors may differentiate alcohol dependent patients who have attempted suicide from those who have not.