Novel frameshift mutations in CRX associated with Leber congenital amaurosis.

Mutations in CRX, a photoreceptor-specific transcription factor, can cause Leber congenital amaurosis (LCA), cone-rod dystrophy (CORD), and retinitis pigmentosa (RP), all of which feature severe visual impairment. Upon screening 55 patients with Leber congenital amaurosis, 75 patients with cone-rod dystrophy, 13 with cone dystrophy, and 36 with recessive or isolate RP for changes in the CRX sequence, we found two patients with Leber congenital amaurosis who carried heterozygously one of two novel frameshift mutations. The first mutation, Tyr191(1-bp del), was a de novo change and the second change, Pro263(1-bp del) was inherited from the proband's affected father. Both mutations are predicted to encode mutant versions of CRX with altered carboxy termini. We also found a previously reported missense mutation, Arg41Gln, heterozygously in a 47-year-old patient with a form of RP. The missense change Val242Met was found in an isolate case of CORD and no controls; however, its pathogenicity remains uncertain because only limited segregation analysis was possible. A nonpathogenic missense change, Ala158Thr, was found to be a variant present at relatively high frequency among African-Americans.

Manometric assessment of the effect of the diaphragmatic crural sling in gastro-oesophageal reflux: implications for surgical management.

A manometric method to measure the effect of contraction of the crural sling of the diaphragm on intraoesophageal pressure is described. The manometric crural pressure was measured in 57 patients with gastro-oesophageal reflux disease, documented by 24-h ambulatory pH monitoring, and compared between patients with and without hiatal hernia. Repeat measurements were made in 33 patients who underwent antireflux surgery that incorporated a crural repair. Mean crural pressure in 41 patients with hiatal hernia was 5.0 mmHg, compared with 15.0 mmHg in 16 without hiatal hernia (P < 0.01). In the 33 patients undergoing antireflux surgery, mean crural pressure rose from 7.1 mmHg before operation to 11.6 mmHg afterwards (P < 0.02) overall, and from 4.7 to 10.1 mmHg (P < 0.01) in the 26 patients with hiatal hernia. These results confirm a measurable contribution of the diaphragmatic crural sling to resting pressure at the high-pressure zone. The crural pressure is deficient in patients with hiatal hernia compared with that in those with reflux but no hernia. The mean crural pressure is increased in patients by antireflux surgery, particularly in those with hiatal hernia. The results provide objective support for the role of the crural diaphragm in the antireflux mechanism and the rationale of performing crural repair during antireflux surgery, particularly in the presence of hiatal hernia.

Laparoscopic 'physiological' antireflux procedure: preliminary results of a prospective symptomatic and objective study.

The 'physiological' antireflux procedure has been shown to be as effective as Nissen fundoplication in reflux control, but with a significant reduction in the incidence of mechanical complications. This technique was attempted laparoscopically in 26 patients in a prospective study involving independent symptomatic, manometric and pH assessment performed before operation and at a mean of 5.5 months after operation. The procedure was successfully completed laparoscopically in 23 (88 per cent) patients. Mean hospital stay was 3.8 days and mean time to return to work 1.8 weeks. There was neither mortality nor reoperation; 91 per cent of patients obtained symptomatic relief (82 per cent Visick grade 1). There was no gas-bloat or inability to belch or vomit. All 14 patients who underwent objective testing had a normal oesophageal pH profile, the mean percentage total time that pH < 4 falling from 11.0 to 1.1 (P < 0.001). Lower oesophageal sphincter characteristics, including relaxation, were similar to control values. These preliminary results suggest symptomatic and objective results comparable to those following open surgery, but with the benefits of a shorter hospital stay and time off work. In addition to a lower incidence of mechanical complications, the relative ease of performance of this procedure confers an additional advantage over Nissen fundoplication when performed laparoscopically.

Occupational carpal tunnel syndrome in Washington State, 1984-1988.

BACKGROUND: There are no published population-based studies of occupational carpal tunnel syndrome (OCTS) using a strict case definition. Most studies are either industry specific or present patient self-report of symptoms. METHODS: We conducted a population-based incidence study of OCTS using the Washington State Workers' Compensation database. Incident OCTS claims were identified with paid bills for physician reported ICD codes 354.0 and 354.1. RESULTS: There were 7,926 incident OCTS claims identified for the years 1984-1988, which yields an industry-wide incidence rate of 1.74 claims/1,000 FTEs. The mean age (37.4 years) and female/male ratio (1.2:1) in this population differ from those reported in nonoccupational carpal tunnel studies (mean age, 51 years; female/male ratio, 3:1). The female-specific OCTS incidence rate increased significantly during the study period. The highest industry specific OCTS rates were found in the food processing, carpentry, egg production, wood products, and logging industries. CONCLUSION: Demographic differences and industry-specific rates consistent with workplace exposures suggest that OCTS is distinct from CTS occurring in nonoccupational settings. Workers' compensation data proved useful in identifying high risk industries.