Germline mutations in the neurofibromatosis type 2 tumour suppressor gene

The recent identification of the NF2 tumour suppressor genehas enabled large scale screening for pathological mutationsin the gene. We have sought germline mutations In the NF2 geneby SSCP and heteroduplex analysis of cDNA and genomic DNA samplesfollowed by cloning and sequencing of mutant alleles. In thepresent report we describe 11 putative pathological mutations,including five nonsense mutations, three short insertions ordeletions cauing frameshifts and three missense mutations. Moststop mutations and frameshift mutations were found In Individualsexpressing a severe phenotype while one of the three missensemutations was associated with a mild phenotype. Four unrelatedNF2 patients of the 93 tested were found to have identical nonsensemutations caused by a C to T transition (C169) in a CpG dinucleotide,which is a potential mutational hotspot in the NF2 tumour suppressorgene.     

Aggressive angiomyxoma with gastrointestinal communication: a case report

We report the imaging findings of an abdominal aggressive angiomyxoma, which communicated with the gastrointestinal tract. The literature on this rare tumor is reviewed.     

Stress injury of the distal radial growth plate

We report 21 cases of stress injury of the distal radial growth plate-occurring in gymnasts before skeletal maturity. The injury appears to be caused by inability of the growth plate to withstand rotational and compressive forces. Our observations have confirmed that the skeletal age of gymnasts is retarded, which increases the length of time during which the epiphysis is at risk of damage.     

Are current processes for nuclear emergency management in Europe adequate?

We describe the results of process mapping of nuclear emergency management procedures in four European countries. We find clear differences and explore these in relation to their suitability for building a shared understanding across the emergency management team of the evolving situation and a balanced appreciation of the uncertainties. Our findings indicate that there are some issues that cause concern in that the procedures may run smoothly and efficiently but they may also risk underestimating uncertainty or ignore key issues that have only been identified by a minority of experts or models. We are concerned that they do not facilitate the building of shared mental models that the literature such as that on highly reliable organisations has shown is important.     

The relationship of the transcutaneous oxygen tension, pulse waves and systolic pressures to the risk for limb amputation in patients with peripheral arterial disease and skin ulcers or gangrene.

AIM: Our aim was to determine how the risk associated with presence of low transcutaneous oxygen tension (tcPO2) for subsequent major amputation in patients with skin ulcers or gangrene and peripheral arterial disease, compares with the risks associated with low peripheral pressures and low amplitude of pulse waves. Secondly, we determined whether combination of measurements of oxygen tension with that of the pressures or pulse wave amplitude predicts amputation better than pressure, wave or oxygen tension measurements alone. METHODS: Measurements were carried out to obtain foot tcPO2, ankle and toe pressures, pressure indices, and toe pulse wave amplitude in 75 limbs with skin lesions and arterial disease of 66 patients referred to the vascular laboratory. These variables were related to the risk of a subsequent major amputation during a median time of 4.2 years, using Cox proportional hazards model. RESULTS: Low oxygen tension was associated with increased risk of amputation (relative risks 2.16 and 2.55 for tcPO2 < or = 10 mmHg and < or = 20 mmHg, respectively, P<0.05; relative risk 2.22 for tcPO2 < or = 30 mmHg, P=0.07). The relative risks associated with cutoff values of ankle and toe pressures and pressure indices varied from 2.53 (toe < or = 20 mmHg, P<0.05) to 5.83 (ankle < or = 50 mmHg, P<0.001) and the relative risk associated with low wave amplitude (< or = 4 mm) was 3.41, P<0.01. The cutoff values of tcPO2 became insignificant when included in the models together with each pressure variable or pulse amplitude separately. In contrast, wave amplitude remained significantly associated with increased risk of amputation after controlling for each pressure variable (P<0.05). CONCLUSIONS: TcPO2 < or = 10 mmHg and < or = 20 mmHg are related significantly to increased risk of amputation in patients with skin lesions and arterial disease, but these relative risks are similar in magnitude or smaller than those associated with low cutoff values of pressures, pressure indices or pulse wave amplitude. Low wave amplitude does provide significant information in addition to peripheral pressures with respect to the risk of amputation. On the other hand, low tcPO2 does not provide significant information in addition to peripheral pressures or pulse wave amplitude.     

Structure-function studies in a series of carboxyl-terminal octapeptide analogues of anaphylatoxin C5a.

The synthesis and structure-activity relationships of C-terminal octapeptide analogues of anaphylatoxin C5a have been studied. The introduction of hydrophobic amino acids into the N-acetylated native octapeptide (N-Ac-His-Lys-Asp-Met-Gln-Leu-Gly-Arg-OH) (1) has led to an analogue with 100 times more activity than the native octapeptide in inhibiting the binding of 125I-labeled anaphylatoxin C5a to human neutrophil membrane receptors. The observed apparent binding Ki's for the compounds (8-10) are in the range of 1-3 microM, and they possess nearly full agonist activity, despite the fact that these analogues are one-eighth or -ninth the size of the natural ligand anaphylatoxin C5a.     

Natural history of morbid obesity without surgical intervention.

BACKGROUND: To study the mortality among morbidly obese patients qualifying for bariatric surgery. Mortality from bariatric surgery for morbid obesity has been widely reported; however, little is known about the mortality in morbidly obese patients who defer surgery. METHODS: Consecutive patients evaluated for bariatric surgery with an initial encounter between 1997 and 2004 were identified. The Social Security Death Index and office records were used to identify mortality through 2006. We conducted telephone interviews to determine whether the 305 patients who did not undergo bariatric surgery at our institution had undergone the surgery elsewhere. Using Cox proportional hazards models, we compared the mortality in patients undergoing surgery with that of those who did not. To evaluate bias resulting from missing data, we conducted analyses assuming that all patients with missing data had (1) undergone surgery and (2) not undergone surgery. RESULTS: A total of 908 patients underwent bariatric surgery (880 patients at our institution and 28 patients elsewhere). A total of 112 patients did not undergo surgery. Data regarding surgery on 165 patients could not be obtained. The mortality in those patients who did not undergo surgery was 14.3% compared with 2.9% for those who did undergo surgery. Adjusting for age, gender, and body mass index, patients who had undergone surgery had an 82% reduction in mortality (hazard ratio 0.18, 95% confidence interval 0.09-0.35, P <.0001). Sensitivity analysis, assuming that all patients with missing data received surgery resulted in an 85% mortality reduction (P <.001) and assuming that patients did not receive surgery resulted in a 50% mortality reduction (P = .04). CONCLUSIONS: Mortality among morbidly obese patients without surgery was 14.3% during the study period. Surgical intervention offered a 50%-85% mortality reduction benefit.