Comprehensive germline mutation analysis and clinical profile in a large cohort of Brazilian xeroderma pigmentosum patients.

BACKGROUND: Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related to the DNA repair system. OBJECTIVES: To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP. METHODS: Twenty-seven families were screened for germline variants in eight XP-related genes. RESULTS: All patients (N = 32) were diagnosed with bi-allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251-1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non-melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma. CONCLUSIONS: We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP-related genes, unexpected non-skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.

Immunoexpression of MMPs-1, -2, and -9 in ameloblastoma and odontogenic adenomatoid tumor.

OBJECTIVE: The aim of this study was to evaluate and compare the expression of metalloproteinases-1, -2, and -9 in solid ameloblastoma and adenomatoid odontogenic tumor. METHODS: A total of 20 cases of solid ameloblastoma and 10 cases of adenomatoid odontogenic tumors were selected and immunohistochemically assessed. Metalloproteinases-1, -2, and -9 immunoexpression and their distribution pattern were noted and semiquantitatively scored. The scores obtained were statistically analyzed. RESULTS: Matrix metalloproteinase (MMP)-1 showed a predominant expression in both tumors and was found in stroma and parenchyma. For MMP-2, there was a varied expression, with 80% and 60% of immunoreactive tumor cells in ameloblastoma and adenomatoid odontogenic tumor respectively. Regarding stromal cells, 65% of ameloblastomas and 80% of adenomatoid odontogenic tumors showed positivity. There was immunoexpression of the MMP-9 in parenchymal and stromal cells in all cases of both tumors analyzed. A statistically significant difference in the expression of MMP-1 in relation to the expression of MMP-2 and -9 in ameloblastomas (P < 0.001) was observed. CONCLUSION: The results suggest that these metalloproteinases are related to growth and progression of tumors analyzed, and particularly in ameloblastoma, its highest aggressiveness may be, in part, a result of the active participation of the stromal cells and their products, such as the MMPs studied.

Surgery in the United Kingdom.

Surgery in the United Kingdom has been practiced for nearly 2000 years. It has evolved as a result of the experiences of warfare and the introduction of the scientific basis of surgery. The influence of the 4 surgical royal colleges in setting standards for training and examinations has ensured that new surgeons are equipped for independent practice as consultants. Responsibility for the National Health Service rests with the government, which determines the number of trainee surgeons in the various surgical specialties. Conflicts between service provision and training are highlighted, as are the pressures on academic institutions to meet the demands of clinical surgery. The government's National Health Service plan for England promises a major expansion in undergraduate places and an increase of 7500 consultants in all specialties by 2004. Time will tell if these changes lead to an improvement in surgical services and a reduction in waiting times.

Perianal Paget's disease associated with cloacogenic carcinoma: report of a case.

A case of perianal Paget's disease associated with a cloacogenic carcinoma is presented. There was no clinical evidence of the Paget's disease, which was confined to a very small area. The points of particular interest were (1) the association of Paget's disease with a cloacogenic carcinoma, and (2) the dissimilarity between the pagetoid cells and the carcinoma cells. The histologic differences between the two cell types support the view that perianal Paget's disease and underlying carcinomas represent a multicentric reaction to an unknown stimulus.

Traumatic avulsion of the ureter with obstruction, pseudocyst formation and hypertension.

A further case of traumatic avulsion of the upper ureter is described; it was complicated by hypertension and treated by removal of the pseudocyst. Delay in diagnosis should not be a contraindication to reconstructive surgery which should always be attempted if the kidney is functioning. The possibility of renal artery ischaemia should be considered when hypertension develops in the presence of a pseduocyst.

Acute renal failure in tropical Africa.

Between 1972 and 1975, 55 adult patients with acute renal failure were admitted to the renal unit of Korle Bu Hospital. Fourteen patients died, giving an overall death rate of 25%. Massive intravascular haemolysis after a short febrile illness was the commonest cause of acute renal failure. Clinically these patients presented with blackwater fever but in only one could Plasmodium falciparum malaria be confidently diagnosed. In half the patients various bacterial and viral infections (especially typhoid) could be incriminated as causing this blackwater fever syndrome. The incidence of glucose-6-phosphate dehydrogenase deficiency was 22.5%, but we could not confirm the impression of a greater predisposition to acute renal failure in patients with this enzyme defect.

Occupational hazards in window cleaning.

Accidental falls involving window cleaners treated at the Middlesex Hospital over five years are reviewed. Failure to use safety belts and the lack of suitable anchorage points were contributary factors in all 20 patients. The use of protective equipment and the provision of anchorage points should be enforced. While the doctor's duty is to treat injuries he also has the opportunity to draw attention to their prevention.