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The gene SURF1 encodes a factor involved in the biogenesis of cytochrome c oxidase, the last complex in the respiratory chain. Mutations of the SURF1 gene result in Leigh syndrome and severe cytochrome c oxidase deficiency. Analysis of seven unrelated patients with cytochrome c oxidase deficiency and typical Leigh syndrome revealed different SURF1 mutations in four of them. Only these four cases had associated demyelinating neuropathy. Three mutations were novel splicing-site mutations that lead to the excision of exon 6. Two different novel heterozygous mutations were found at the same guanine residue at the donor splice site of intron 6; one was a deletion, whereas the other was a transition [588+1G>A]. The third novel splicing-site mutation was a homozygous [516-2_516-1delAG] in intron 5. One patient only had a homozygous polymorphism in the middle of the intron 8 [835+25C>T]. Western blot analysis showed that Surf1 protein was absent in all four patients harboring mutations. Our studies confirm that the SURF1 gene is an important nuclear gene involved in the cytochrome c oxidase deficiency. We also show that Surf1 protein is not implicated in the assembly of other respiratory chain complexes or the pyruvate dehydrogenase complex.

The pyruvate dehydrogenase complex (PDHc) is a multienzyme complex consisting of three catalytic and two regulatory enzymes, as well as a less well defined subunit called protein X. PDHc deficiency is a common cause of congenital lactic acidosis. Most patients with PDH deficiency have a mutation in the alpha chain of the PDH E1 enzyme. Very few patients have been described in whom the basic defect of a PDH deficiency is situated in the X protein. We studied a boy with severe lactic acidosis and developmental delay in whom a deficiency of PDH activity led to further investigations. Immunochemical analysis with anti-PDHc antibodies demonstrated an absence of the X component. This report is the fourth family in which an abnormal protein X has been found. In cases with PDH deficiency where no mutation of the PDHE1 alpha gene is found, further investigations by means of immunoblotting with specific antibodies against the different subunits should be performed.

We report studies of four patients with pyruvate dehydrogenase complex (PDH) deficiency caused by mutations in the E1 alpha subunit. Two unrelated male patients presented with Leigh syndrome and a R263G missense mutation in exon 8. This mutation has previously been described in males with the same phenotype. The two other patients had different novel mutations: (1) an 8-bp deletion at the C-terminus (exon 11) was found in one allele of a young girl suffering from microcephaly and (2) a C88S missense mutation (exon 3) in a boy who only presented with motor neuropathy. These mutations were not found in the mothers of any of the four cases. Immunoblot analysis revealed decreased immunoreactivity for the E1 alpha and E1 beta subunits in three out of the four patients. These findings confirm that: (1) PDH deficiencies are genetically heterogeneous, (2) the R263G mutation is more frequent in male cases than are other mutations and this amino acid is a hot spot for gene mutations, (3) the last eight amino acids may be important for the conformation of the tetrameric E1-PDH enzyme, and (4) the amino acids at positions 88, 263 and 382-387 are essential for the linking of the alpha subunit with the beta subunit and for the activity of the holoenzyme.

Background: Spitz nevus has clinically been described as a dome-shaped usually nonpigmented papular or nodular lesion variable in color from pink to red. Objectives: To give an exhaustive description of the clinical features of the Spitz nevus from a large series of 247 patients. Methods: A retrospective analysis of the clinical features of 247 Spitz nevi excised from 1974 to 1993 has been performed. We evaluated the following features: age, sex, anatomical location, clinical and histopathologic features; descriptive statistics were calculated and relationships among the above variables were assessed. Results: Most lesions were pigmented (71.7%), located on the lower extremities (43.3%), more frequent in the first decade (55.8%) and in females (57.9%). The nonpigmented type was more frequent in the head or neck region, whereas the pigmented types were more frequent on the lower extremities. Besides, these types showed different histopathologic features: the spindle cells usually predominated in the flat pigmented type, whereas dome-shaped types were usually composed of both spindle and epithelioid cells. Conclusions: In our patients, the pigmented Spitz nevi were more common than the nonpigmented ones; furthermore pigmented and nonpigmented Spitz nevi showed different anatomical locations and different histopathologic features.

Hyperinsulinism and hyperammonemia syndrome has been reported as a cause of moderately severe hyperinsulinism with diffuse involvement of the pancreas. The disorder is caused by gain of function mutations in the GLUD1 gene, resulting in a decreased inhibitory effect of guanosine triphosphate on the glutamate dehydrogenase (GDH) enzyme. Twelve unrelated patients (six males, six females) with hyperinsulinism and hyperammonemia syndrome have been investigated. The phenotypes were clinically heterogeneous, with neonatal and infancy-onset hypoglycemia and variable responsiveness to medical (diazoxide) and dietary (leucine-restricted diet) treatment. Hyperammonemia (90-200 micromol/L, normal

We have previously reported a genetic study of a neonatal lactic acidosis linked to a pyruvate dehydrogenase complex deficiency due to the absence of the protein X subunit. This rare autosomal recessive disorder is associated with specific deletions in this polypeptide which is encoded by the HsPDX1 gene, located on chromosome 11p1.3. The pathology of the patient was considered to arise from a large homozygous deletion (78del85) found at the 5' end of the HsPDX1 coding sequence. Her heterozygous mother underwent prenatal diagnosis during a subsequent pregnancy. Chorionic villus samples were used for three independent studies: (1) normal levels of the protein X component of the PDH complex were detected by immunoblotting; (2) RT-PCR analysis showed no deletion at the 5' end of the cDNA but the presence of a distinct heterozygous deletion (965del59) at its 3' end inherited from the father; (3) haplotype analysis revealed the presence of the father's mutated allele and the mother's normal allele. It was concluded that the fetus was heterozygous for this separate 3' deletion, so, it was likely to be not affected. This study permitted us to characterize more precisely the genetic abnormalities of the HsPDX1 cDNA occurring in each family's member.

This double-blind randomized study was designed to compare the efficacy and safety of calcipotriol ointment (50 microg/g) with betamethasone dipropionate (64 mg/g) and salicylic acid (0.03 g/g) ointment in the treatment of nail bed psoriasis. Fifty-eight patients applied the given drug to the affected nails twice a day for 3-5 months, depending on clinical response. Efficacy was assessed monthly on the basis of nail thickness, measured in millimetres. Photographs of the treated nails were taken at baseline, and after 3 and 5 months. Tolerability was assessed at 3 and 5 months. In patients with fingernail psoriasis, after 3 months of treatment subungual hyperkeratosis was reduced from 2.3 +/- 0.1 mm (mean +/- SEM) to 1.5 +/- 0.1 mm (-26.5%) in the calcipotriol group and from 2.3 +/- 0.1 mm to 1.6 +/- 0.1 mm (-30.4%) in the betamethasone dipropionate and salicylic acid group [not significant (NS) between treatments, analysis of variance (ANOVA)]. After 5 months, responders showed a 49.2% reduction in hyperkeratosis in the calcipotriol group (from 2.8 +/- 0.1 mm to 1.4 +/- 0.2 mm) and 51.7% (from 2.1 +/- 0.1 mm to 1.0 +/- 0.1 mm) in the betamethasone dipropionate and salicylic acid group (P0.001 from baseline, NS between treatments, ANOVA). In patients with toenail psoriasis, after 3 months of treatment there was an overall reduction in hyperkeratosis from 2.6 +/- 0.1 mm to 2.1 +/- 0.1 mm (-20.1%) in the calcipotriol group and from 3.0 +/- 0.1 mm to 2.3 +/- 0.1 mm (-22. 9%) in the betamethasone dipropionate and salicylic acid group (P0.001 from baseline, NS between treatments, ANOVA). By the end of the fifth month there was a 40.7% reduction in hyperkeratosis in the calcipotriol group (from 2.1 +/- 0.1 mm to 1.2 +/- 0.1 mm) and 51.9% in the betamethasone dipropionate and salicylic acid group (from 2.7 +/- 0.1 mm to 1.3 +/- 0.1 mm; P0.0001 from baseline, NS between treatments, ANOVA). The results of the study show that calcipotriol is as effective as a combination of a topical steroid with salicylic acid in the treatment of nail psoriasis and represents a safe alternative in the topical treatment of nail psoriasis.

Psoriasis is present all over the world and its prevalence varies in the different populations and different geographical areas. For example, Northern European countries seem to have rates of incidence which are greater than those known for Southern Europe. However, today there is still a lack of adequate data to allow comparisons at an international level.In Italy in 1994 the AISP (Interdisciplinary Association for the Study of Psoriasis) co-ordinated the recording of monthly case histories and clinical results relating to psoriasis in patients observed in dermatology centres homogeneously distributed throughout Italy. The results were extrapolated from the overall case series.A sample of nearly 8000 cases was collected, most presenting psoriasis vulgaris. This pathology, prevalent in males, first appears at an age somewhere between the teens and twenties. Numerous factors may be involved, and onset is mainly attributed to stress, viral or bacterial infections and pharmacological therapy. Over 90% of cases lost between 1 and 7 working days in the course of the year. Local anti-psoriasis treatment in monotherapy was administered more frequently than systemic therapy or combined therapy.The results of this first Italian epidemiological study confirm that psoriasis is homogeneously distributed throughout the country. About 50% of patients avail themselves of specialist cures, even several times in the course of the year, and use a wide range of therapies which may be more or less demanding. The internal socio-economic cost of the disease is evident, particularly in terms of working days lost and/or medical expenses.

TachoComb is a new, ready-to-use hemostatic agent consisting of a collagen sheet coated on one side with human fibrinogen, bovine thrombin, and bovine aprotinin. The product was used in 125 surgical operations (vascular, hepatic, urological and ENT) in which secondary hemostasis was required. It was placed over the cut surface or over the edges of the wound. The investigating surgeons expressed their opinion on the intra- and postoperative hemostatic efficacy, and routine laboratory tests were done postoperatively. TachoComb had good hemostatic efficacy in 67.2% of cases, and very good in 22.4%. No noteworthy systemic changes were observed. As an adjuvant to obtain complete hemostasis in surgery, TachoComb is effective, practical and quick to use, and is very well tolerated.

Most of the mutations causing deficiency of the pyruvate dehydrogenase (PDH) complex are in the X-linked E1 alpha gene. We have developed a rapid screening method for the detection of mutations in this gene using reverse transcription of total RNA, polymerase chain reaction amplification of the whole coding region of the gene and single-strand conformation polymorphism (SSCP) analysis. With this method, we studied eight patients with a PDH complex deficiency, using cultured fibroblasts. In all patients, aberrant SSCP patterns were found and, after sequencing of the corresponding fragments, we were able to identify six new mutations and two mutations already described previously. The mutations are point mutations leading to amino acid substitutions (5) and direct repeat insertions (3). The presence of the mutations was confirmed in genomic fibroblast DNA. The 4 female patients were shown to carry both a normal and a mutated E1 alpha gene.

Pyruvate dehydrogenase (PDH)-E1 alpha deficiency has recently been studied at the molecular-genetic level. The gene is situated on the X chromosome. We report on an unusual mutation in a familial E1 alpha deficiency. In fibroblasts, PDH deficiency was diagnosed in a young infant presenting with Leigh's encephalomyelopathy and in a maternal nephew with episodes of "malaises." In the two affected children as well as their mothers we found a silent mutation in exon 6 of the PDH-E1 alpha and an aberrant splicing of exon 6 in some of the cDNA clones. This case emphasizes the need for both genomic and cDNA analysis in cases where a PDH-E1 alpha deficiency is strongly suspected.