Genetics of vitamin D 1alpha-hydroxylase deficiency in 17 families

Vitamin D-dependent rickets type I (VDDR-I), also known as pseudo-vitamin D-deficiency rickets, appears to result from deficiency of renal vitamin D 1alpha-hydroxylase activity. Prior work has shown that the affected gene lies on 12q13.3. We recently cloned the cDNA and gene for this enzyme, mitochondrial P450c1alpha, and we and others have found mutations in its gene in a few patients. To determine whether all patients with VDDR-I have mutations in P450c1alpha, we have analyzed the P450c1alpha gene in 19 individuals from 17 families representing various ethnic groups. The whole gene was PCR amplified and subjected to direct sequencing; candidate mutations were confirmed by repeat PCR of the relevant exon from genomic DNA from the patients and their parents. Microsatellite haplotyping with the markers D12S90, D12S305, and D12S104 was also done in all families. All patients had P450c1alpha mutations on both alleles. In the French Canadian population, among whom VDDR-I is common, 9 of 10 alleles bore the haplotype 4-7-1 and carried the mutation 958DeltaG. This haplotype and mutation were also seen in two other families and are easily identified because the mutation ablates a TaiI/MaeII site. Six families of widely divergent ethnic backgrounds carried a 7-bp duplication in association with four different microsatellite haplotypes, indicating a mutational hot spot. We found 14 different mutations, including 7 amino acid replacement mutations. When these missense mutations were analyzed by expressing the mutant enzyme in mouse Leydig MA-10 cells and assaying 1alpha-hydroxylase activity, none retained detectable 1alpha-hydroxylase activity. These studies show that most if not all patients with VDDR-I have severe mutations in P450c1alpha, and hence the disease should be referred to as "1alpha-hydroxylase deficiency."     

Merkel cell carcinoma of the eyelid

The different methods that are available for the assessment and quantification of "brittle nails" and for the evaluation of various therapeutical approaches are compared. At this time, measurement of the swelling properties is the best documented and most reliable method for studying the treatment of brittle nails. Reliable qualitative data can also be obtained by scanning electron microscopy. Measurement of the transonychial water loss and assessment of thickness and density of nails by ultrasound have also been used successfully, but the methodology still has to be improved and the reproducibility, confirmed.     

Brain tissue luminescence in the millisecond range

Luminescence signals, which persisted for a few milliseconds, were registered in some areas of rat brain surface. The amplitude of the signal was shown to depend on the location of the area. The strongest signals were registered in the areas that are known from physiological studies to possess light sensitivity. It is proposed to use this effect in studies of brain tissue light sensitivity.     

Improved early morbidity and mortality after Fontan operation: the Mayo Clinic experience, 1987 to 1992

OBJECTIVES: This study sought to evaluate changes in early morbidity and mortality as well as predictors of outcome in our most recent 339 patients undergoing modified Fontan operations. BACKGROUND: The Fontan operation is the preferred definitive palliation for patients with functional single ventricles. Previously reported early mortality rates after Fontan operation have been substantial. METHODS: Records of 339 consecutive patients who had a Fontan operation at the Mayo Clinic between 1987 and 1992 (recent cohort) were reviewed. This cohort was compared with the previous 500 patients who had Fontan operations performed between 1973 and 1986 (early cohort). RESULTS: Recently, overall early mortality after Fontan has decreased significantly compared with that for the early cohort (from 16% to 9%, p = 0.002). This decline occurred despite increased anatomic complexity of patients. Short-term posthospital survival has also improved significantly in recent patients. One-year survival improved to 88% from 79%, and 5-year survival to 81% from 73% (p = 0.006). Patients with common atrioventricular valves and those who took daily preoperative diuretic medication or had either postoperative renal failure or elevated postbypass right atrial pressure were at increased risk for early mortality. Young age was not found to be a risk factor for early mortality. Early mortality for patients with heterotaxia decreased dramatically: recent 30-day mortality was 15% compared with 41% in the early heterotaxy cohort. CONCLUSIONS: Many factors may have contributed to decreased early mortality after Fontan. Improved patient selection, younger age at time of operation, refinements in surgical techniques and postoperative management may all have had important roles. Proposed technical modifications of the Fontan operation must be evaluated in light of these improved results.     

Clinical discrepancy between Schi?tz and Perkins Tonometry in juvenile glaucoma

BACKGROUND: In infantile glaucoma Schiotz and Perkins tonometry are often divergent. However, empirical data about the quantitative relation of Schiotz' and Perkins' measurements are lacking for this group of patients. PATIENTS AND METHODS: 363 comparative IOP measurements by applanantion and indentation tonometry under general anesthesia were performed in 51 children (0-10 years) with infantile glaucoma during 01/01/88 and 30/06/95 at the University Eye Clinic Cologne. RESULTS: Correlation coefficient of both methods was 0.75 (p < 0.001). Schiotz tonometry surmounted Perkins tonometry in 78.8% of measurements. Differences of Schiotz and Perkins IOP measurements showed a normal distribution with mean value 4.37 +/- 5.8 mm Hg. Discrepancy between both methods increased significantly (p < 0.001) in eyes with corneal opacities (5.29 +/-6.35 mm Hg) compared with clear cornea (3.40 +/- 4.98 mm Hg). Discrepancy of Schiotz-Perkins tonometry was not influenced by axial length of the eye, corneal diameter and age of the patient. DISCUSSION: Marked discrepancy of applanation and indentation tonometry in infantile glaucoma is frequent. Decision for surgery should not base on tonometry alone, but on evaluation of additional clinical criteria like optic disc cup, corneal morphology and individual anamnesis.     

Pain in multiple system atrophy

Nijmegen breakage syndrome (NBS), a rare autosomal recessive condition also known as ataxia telangiectasia (AT) variants V1 and V2, is characterised by microcephaly, typical facies, short stature, immunodeficiency, and chromosomal instability. We report the clinical, immunological, chromosomal, and cell biological findings in 42 patients who are included in the NBS Registry in Nijmegen. The immunological, chromosomal, and cell biological findings resemble those in AT, but the clinical findings are quite different. NBS appears to be a separate entity not allelic with AT.