To determine the prevalence of neurofibromatosis 1 (NF1) among 6-year-old children in Germany.Setting and Patients: A total of 152 819 children aged 6 years in 6 German states were screened for NF1 during routine medical examinations at elementary school enrollment in cooperation with local health departments in 2000 and 2001.Main Outcome Measure: The prevalence of NF1 among 6-year-old German children was estimated to be 1:2996 (95% confidence interval, 1:2260 to 1:3984).Results: Fifty-one NF1 cases were identified and confirmed by evaluation by appropriate medical specialists.

Neurofibromatosis 1 (NF1) is one of the most common autosomal dominant diseases. Although there is a considerable variability in clinical expression, NF1 is almost fully penetrant in adult patients and may be associated with a variety of skeletal anomalies. Spinal deformities are the most common skeletal manifestation, with an incidence estimated from 10-25% in various studies. Some NF1 patients have a dystrophic form of scoliosis, which is characterized by early age at onset and rapid progression. Complications have been reported during spinal instrumentation of dystrophic curves due to soft, non-resistant vertebral bony tissue, suggesting that an alteration of bone quality may occur in NF1 patients. Recent studies have suggested that decreased bone mineral density (BMD) may occur among patients with NF1. We performed a cross-sectional study on 104 adults with NF1, using quantitative ultrasonometry (QUS) to investigate whether decreased BMD is a general phenomenon in NF1 patients. The data reveal that BMD, as measured by age- and gender- adjusted Z-scores, is significantly lower in NF1 patients than in the normal reference population. The decrease in BMD appears to be even more marked among NF1 patients with scoliosis that requires surgical treatment. The findings indicate that NF1 produces a generalized alteration of bone in addition to the focal osseous dysplasias of the vertebrae, tibia, and sphenoid wing that characterize this condition. The pathological mechanism underlying these bony changes remains to be elucidated.

A retrospective cohort study was carried out in a cardboard factory in Germany to investigate the association between exposure to trichloroethene (TRI) and renal cell cancer. The study group consisted of 169 men who had been exposed to TRI for at least 1 year between 1956 and 1975. The average observation period was 34 years. By the closing day of the study (December 31, 1992) 50 members of the cohort had died, 16 from malignant neoplasms. In 2 out of these 16 cases, kidney cancer was the cause of death, which leads to a standard mortality ratio of 3.28 compared with the local population. Five workers had been diagnosed with kidney cancer: four with renal cell cancers and one with a urothelial cancer of the renal pelvis. The standardized incidence ratio compared with the data of the Danish cancer registry was 7.97 (95% CI: 2.59-18.59). After the end of the observation period, two additional kidney tumors (one renal cell and one urothelial cancer) were diagnosed in the study group. The control group consisted of 190 unexposed workers in the same plant. By the closing day of the study 52 members of this cohort had died, 16 from malignant neoplasms, but none from kidney cancer. No case of kidney cancer was diagnosed in the control group. The direct comparison of the incidence on renal cell cancer shows a statistically significant increased risk in the cohort of exposed workers. Hence, in all types of analysis the incidence of kidney cancer is statistically elevated among workers exposed to TRI.(ABSTRACT TRUNCATED AT 250 WORDS)

The study supports the human nephrocarcinogenicity of trichloroethylene.

Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p,,0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's r = 20.572, p,0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications. N eurofibromatosis 1 (NF1) is an autosomal dominant disease caused by mutations of the NF1 gene on chromosome 17. [1][2][3] Multiple café au lait spots and cutaneous neurofibromas occur in almost all affected individuals. Less frequent but more serious manifestations include plexiform neurofibromas, central nervous system gliomas, malignant peripheral nerve sheath tumours (MPNSTs), and NF1 vasculopathy.4 5 At least 10% of people with NF1 have characteristic focal bony abnormalities such as sphenoid wing lesions, dystrophic scoliosis, or tibial pseudarthrosis. In addition, people with NF1 frequently have a generalized skeletal abnormality, evidenced by mild short stature 6 and decreased bone mineral density. 7-10Vitamin D regulates calcium homeostasis and plays a key role in bone metabolism.11 Patients with NF1 with severe osteomalacia respond favourably to vitamin D therapy, 12 and topical vitamin D treatment has been reported to reduce the pigmentation in café au lait spots, one of the cardinal features of NF1. 13 We measured serum 25-hydroxyvitamin D concentrations in a series of patients with NF1 and assessed the relationship of these concentrations to the number of dermal neurofibromas reported by the patients. METHODSThis study was approved by the ethics committee of Hamburg University. We measured serum 25-hydroxyvitamin D concentrations in 69 unselected adults with NF1 diagnosed by standard clinical criteria.14 For comparison, we also measured serum 25-hydroxyvitamin D levels in 58 apparently healthy employees of the testing laboratory. After assessment by the laboratory medical officer, fasting blood samples were taken and stored at 280˚C until analysis. Individuals with diseases of the gastrointestinal tract, liver, kidneys, parathyroid glands, or skin which can affect vitamin D metabolism were excluded from both groups, as were individuals known to be taking supplemental vitamin D or to have unusually high ultraviolet light exposure. Serum concentrations of 25-hydroxyvitamin D were measured by an automated chemiluminescence prot...

A previous cohort-study in a cardboard factory demonstrated that high and prolonged occupational exposure to trichloroethene (C2HCl3) is associated with an increased incidence of renal cell cancer. The present hospital-based case/control study investigates occupational exposure in 58 patients with renal cell cancer with special emphasis on C2HCl3 and the structurally and toxicologically closely related compound tetrachloroethene (C2Cl4). A group of 84 patients from the accident wards of three general hospitals in the same area served as controls. Of the 58 cases, 19 had histories of occupational C2HCl3 exposure for at least 2 years and none had been exposed to C2Cl4; of the 84 controls, 5 had been occupationally exposed to C2HCl3 and 2 to C2Cl4. After adjustment for other risk factors, such as age, obesity, high blood pressure, smoking and chronic intake of diuretics, the study demonstrates an association of renal cell cancer with long-term exposure to C2HCl3 (odds ratio 10.80; 95% CI: 3.36-34.75).

To investigate possible persistent nephrotoxic effects of trichloroethylene (TRI), a retrospective study was carried out on 39 workers exposed to high levels of TRI from 1956 to 1975. Total protein levels in urine, as well as serum and urine creatinine and serum urea were unchanged in comparison with the control. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) was applied to differentiate between tubular and/or glomerular dysfunction. Urinary excretion of alpha-1-microglobulin and glutathione transferase (GST) alpha, as markers of proximal tubular damage, were correlated with the SDS-PAGE patterns of urinary proteins both in the TRI exposed and the control group. GST alpha was found in elevated concentrations in the urine of the TRI-exposed workers. No increase of urinary GST alpha was observed in the control group, even when alpha-1-microglobulin was elevated as a result of non-toxic damage. Both in the control and exposed groups, GST pi, a marker of distal tubular damage, was in the normal range. The results show that chronic exposure to high doses of TRI causes persistent changes to the proximal tubular system of the kidney and that GST alpha excretion into the urine is a marker well suited for quantitation of the extent of renal damage.

Suspected nephrocarcinogenic effects of trichloroethene (TRI) in humans are attributed to metabolites derived from the glutathione transferase (GST) pathway. The influence of polymorphisms of GSTM1 and GSTT1 isoenzymes on the risk of renal cell cancer in subjects having been exposed to high levels of TRI over many years was investigated. GSTM1 and GSTT1 genotypes were determined by internal standard controlled polymerase chain reaction. Fourty-five cases with histologically verified renal cell cancer and a history of long-term occupational exposure to high concentrations of TRI were studied. A reference group consisted of 48 workers from the same geographical region with similar histories of occupational exposures to TRI but not suffering from any cancer. Among the 45 renal cell cancer patients, 27 carried at least one functional GSTM1 gene (GSTT1 +) and 18 at least one functional GSTT1 gene (GSTT1 +). Among the 48 reference workers, 17 were GSTM1 + and 31 were GSTT1 +. Odds ratio for renal cell cancer were 2.7 for GSTM1 + individuals (95% CI, 1.18-6.33; P < 0.02) and 4.2 for GSTT1 + individuals (95% CI, 1.16-14.91; P < 0.05), respectively. The data support the present concept of the nephrocarcinogenicity of TRI.