Osteogenesis imperfecta: the audiological phenotype lacks correlation with the genotype

Background

Neurofibromatosis 1 (NF1), a common autosomal dominant disorder, was shown in one study to be associated with a 15-year decrease in life expectancy. However, data on mortality in NF1 are limited. Our aim was to evaluate mortality in a large retrospective cohort of NF1 patients seen in France between 1980 and 2006.

Methods

Consecutive NF1 patients referred to the National French Referral Center for Neurofibromatoses were included. The standardized mortality ratio (SMR) with its 95% confidence interval (CI) was calculated as the ratio of observed over expected numbers of deaths. We studied factors associated with death and causes of death.

Results

Between 1980 and 2006, 1895 NF1 patients were seen. Median follow-up was 6.8 years (range, 0.4-20.6). Vital status was available for 1226 (65%) patients, of whom 1159 (94.5%) survived and 67 (5.5%) died. Overall mortality was significantly increased in the NF1 cohort (SMR, 2.02; CI, 1.6-2.6; P < 10^-4). The excess mortality occurred among patients aged 10 to 20 years (SMR, 5.2; CI, 2.6-9.3; P < 10^-4) and 20 to 40 years (SMR, 4.1; 2.8-5.8; P < 10^-4). Significant excess mortality was found in both males and females. In the 10-20 year age group, females had a significant increase in mortality compared to males (SMR, 12.6; CI, 5.7-23.9; and SMR, 1.8; CI, 0.2-6.4; respectively). The cause of death was available for 58 (86.6%) patients; malignant nerve sheath tumor was the main cause of death (60%).

Conclusions

We found significantly increased SMRs indicating excess mortality in NF1 patients compared to the general population. The definitive diagnosis of NF1 in all patients is a strength of our study, and the high rate of death related to malignant transformation is consistent with previous work. The retrospective design and hospital-based recruitment are limitations of our study. Mortality was significantly increased in NF1 patients aged 10 to 40 years and tended to be higher in females than in males.     

Crystallization and preliminary X-ray analysis of botulinum neurotoxin type A.

Botulinum neurotoxin serotype A was isolated from liquid culture of Clostridium botulinum. The pure Mr approximately 150,000 neurotoxin, composed of Mr approximately 50,000 light and Mr approximately 100,000 heavy chains, has been crystallized in three different crystal morphologies; all three have the same crystal form. The most suitable crystal form for X-ray analysis are bipyrimidal and crystallize in the hexagonal space group P3(1)21 (or P3(2)21) with one dimer per asymmetric unit. The unit cell dimensions are a = b = 170.5 A, c = 161.7 A. The crystals diffract to 3 A resolution.     

Rhodamine 123 alters the mitochondrial ultrastructure of cultured L1210 cells

Exposure of exponentially growing L1210 cells in vitro to 5-10 micrograms/ml of rhodamine 123 (R123) for 16-48 hr inhibits cell proliferation and induces cell arrest in the G1A phase of the cell cycle. The cells remain viable during the arrest and resume growth after removal of R123; extended exposure to R123 is cytotoxic. Exposure to R123 results in morphological alterations in mitochondria of all cells observed; specifically, mitochondria of R123-treated cells are characterized by a distention of the intracristal spaces and a significant increase in the number of matrix granules. Gross morphological changes of mitochondria include formation of extended organelles and the appearance of doughnut-shaped structures.     

The passive cutaneous anaphylaxis (PCA) test in Cryptococcosis

Summary The PCA test appeared to be a useful indicator of past infection due toCryptococcus neoformans when the extracellular starch antigen was used. The whole cell antigen, crude cell wall antigen, ruptured cell antigen, crude carbohydrate antigen and the crude capsular polysaccharide antigen were not found to be effective.Serums from the nine rabbits injected withC. neoformans showed some degree of reactivity in the PCA test with the homologous extracellular starch antigen. Serums from rabbits injected withC. diffluens andC. laurentii gave no response.None of the rabbits exhibited evidence of previous sensitization and none were obviously infected. Six rabbits injected withC. neoformans were skin tested 4 weeks later with all of the antigens. Positive tests were obtained in four rabbits but only with the cell wall antigen or the ruptured cell antigen. PCA activity was not observed in the serums of mice injected with strains ofC. neoformans although some came from mice showing lesions and some came from fatally infected mice.Of the 500 human serums tested for PCA activity using the extracellular starch antigen, only one reacted strongly and with a sufficiently high titer to suggest previous infection. Serums from three cases of cryptococcosis failed to react.This investigation was supported by Communicable Disease Center grant CC 00151-01.The material in this paper is taken in part from a dissertation presented to the Graduate School of The University of Arizona in partial fullfilment of the requirements for the Ph.D. degree.     

For Coccidioidomycosis — A possible source of infectious spores and of therapeutic agents

Summary Thirty-nine plant samples collected from the desert and from the cactus garden of The University of Arizona were examined for their ability to support the growth ofCoccidioides immitis in agar culture. On this basis and the location of the fungal growth as well as the degree of development of the fungus, the plants could be divided into five categories. No fungal growth was observed over a period of eight weeks in association with five of the plants. Four plants permitted growth of the mold within the agar medium only. Another five allowed some growth on the plant material but sporulation was never encountered. The largest group consisted of twenty plants on which the fungus grew moderately and sporulated lightly. In association with five plants,C. immitis grew well and sporulated heavily.The findings suggest that some plants may contain substances that would be therapeutically useful and that others might serve as natural hosts on which the highly infective spores could be abundantly produced.