The "presyrinx" state: a reversible myelopathic condition that may precede syringomyelia

The purpose of this investigation was to develop a brief self-report inventory which could be used to evaluate treatment outcome for anorexia and bulimia nervosa. The Multifactorial Assessment of Eating Disorders Symptoms (MAEDS) was constructed to measure six symptom clusters which have been found to be central to the eating disorders: depression, binge eating, purgative behavior, fear of fatness, restrictive eating, and avoidance of forbidden foods. The factor structure of the MAEDS was found to be stable and it was found to have satisfactory reliability and validity. Normative data were collected so that raw scores could be converted to standardized scores. While still in the experimental stages, the MAEDS shows promise as a valid and economical measure of treatment interventions for anorexia and bulimia nervosa.     

PROGRESSIVE MICROCRACKING IN UNIDIRECTIONAL BRITTLE MATRIX COMPOSITES

Abstract

In this work we investigate the initiation of microcracking in a unidirectional Nicalon^TMfibre, glass-ceramic (CAS) matrix composite under flexural loading. We find that damage develops and grows in these composites as a continual initiation of new transverse cracks in a more-or-less random manner, as well as growth of existing cracks, within the matrix. Initial cracks are usually of limited extent, being stopped when they encounter the nearest fibres, in a mode idealized by the so-called full-cell cracking model. Each new crack that initiates under increasing load yields another data point, provided the precracked state of stress and crack geometry at the initiation site can be determined. The latter conditions are satisfied since the zone of influence of each crack can be determined analytically and the full-cell cracking mode geometry receives at least partial validation. Analysis is accomplished by use of an axisymmetric micro mechanical model based on Reissner's variational principle in which variable fibre spacing can be recognized. In a semi-empirical failure model, the matrix axial stress just prior to crack initiation is computed and assumed to act on an unbounded matrix containing a penny-shaped crack having a radius dictated by the local fibre spacing, s. This model is geometrically appropriate for the case of large localized fibre spacings. Statistical information on s and the critical matrix mode I stress intensity factor is presented, and the average value seems to be consistent with expectation based upon measurements on monolithic samples of the matrix material. Application of the micromechanical model shows that, at least for the predominant range of s, sufficient energy is available to mobilize annular matrix cracks at stresses predicted by the semi-empirical model, and also that interfacial crack deflection is expected rather than fibre penetration. In accordance with this observation, very few fibre breaks were seen in the test programme. Finally, some comments regarding the practical consequences of this work are offered and the conventional view of a constant microcracking stress level in a steady-state model is dismissed, at least for the class of composites considered.     

Point mutations in the beta chain CDR3 can alter the T cell receptor recognition pattern on an MHC class I/peptide complex over a broad interface area

To study how the T cell receptor interacts with its cognate ligand, the MHC/peptide complex, we used site directed mutagenesis to generate single point mutants that alter amino acids in the CDR3beta loop of a H-2Kb restricted TCR (N30.7) specific for an immunodominant peptide N52-N59 (VSV8) derived from the vesicular stomatitis virus nucleocapsid. The effect of each mutation on antigen recognition was analyzed using wild type H-2Kb and VSV8 peptide, as well as H-2Kb and VSV8 variants carrying single replacements at residues known to be exposed to the TCR. These analyses revealed that point mutations at some positions in the CDR3beta loop abrogated recognition entirely, while mutations at other CDR3beta positions caused an altered pattern of antigen recognition over a broad area on the MHC/peptide surface. This area included the N-terminus of the peptide, as well as residues of the MHC alpha1 and alpha2 helices flanking this region. Assuming that the N30 TCR docks on the MHC/peptide with an orientation similar to that recently observed in two different TCR-MHC/peptide crystal structures, our findings would suggest that single amino acid alterations within CDR3beta can affect the interaction of the TCR with an MHC surface region distal from the predicted CDR3beta-Kb/VSV8 interface. Such unique recognition capabilities are generated with minimal alterations in the CDR3 loops of the TCR. These observations suggest the hypothesis that extensive changes in the recognition pattern due to small perturbations in the CDR3 structure appears to be a structural strategy for generating a highly diversified TCR repertoire with specificity for a wide variety of antigens.     

Adrenal adenoma and hematoma mimicking a collision tumor at MR imaging

Fas ligand (FasL), a cell surface molecule belonging to the tumor necrosis factor family, binds to its receptor Fas, thus inducing apoptosis of Fas bearing cells. In the present study we assessed the expression of Fas, activation molecule interleukin (IL)-2 receptor alpha chain (CD25) and an index of functional activity such as thymidine uptake under mitogen stimulation of tumor associated lymphomonocytes (TALM) from 7 neoplastic effusions of advanced cancer patients. The same parameters were studied in peripheral blood mononuclear cells (PBMC) of 7 patients with cancer of different sites and in 7 normal subjects. The proliferative response to phytohemagglutinin (PHA), measured as [3H]-thymidine uptake, of TALM was significantly lower than that of PBMC of cancer patients. The expression of CD25 on unstimulated fresh TALM was slightly higher than that of PBMC from normal subjects: after 24 h of PHA stimulation the CD25 was expressed both on TALM and PBMC from normal subjects. The expression of Fas was assessed on unstimulated TALM, PBMC from cancer patients and normal subjects immediately after (by 2 h, t0) the cell separation, and at different times (24 h and 48 h) thereafter, and on PHA-stimulated TALM, PBMC from cancer patients and normal subjects after 24 h and 48 h of culture (in RPMI 1640). At all times (t0, 24 h and 48 h) the Fas expression by unstimulated TALM was significantly higher than that of PBMC from normal subjects: the Fas expression by PBMC from cancer patients was roughly in the same range as PBMC from normal subjects. At 24 h the Fas expression by PHA-stimulated TALM was significantly higher than that of PBMC from normal subjects, whereas at 48 h the difference was not significant. The TALM studied by us showed to be functionally defective and expressing relatively high levels of Fas showing the characteristics to be considered as a target for FasL expressing tumor cells, which in this way may escape immune control.     

Diabetes microvascular complications in prepubertal children

In the light of recent experiences and anticipating an increase in similar requests in the future, it seemed very interesting to a drug safety executives' group from the pharmaceutical industry to propose guidelines for the set-up and follow-up of pharmacoepidemiological studies requested by Health Authorities for the assessment of drug risk. The scope of these guidelines is to establish the responsibility of the teams and structures involved in the study, to define the necessary stages set-up, and to determine the rules in order to ensure its smooth running from the drafting of the protocole to the final use of the data.     

The incidence and Dukes'' staging of colorectal cancer over 3 decades

AIMS: Two previous studies (1966-1971 and 1979-1983) of patients with colorectal cancer (CRC) have been reported from our hospital. A large increase in the incidence of CRC was noted, and an improvement in Dukes' staging of tumours at treatment. We report a series of patients admitted with newly diagnosed CRC to evaluate this trend further. METHODS: A prospective study was made of all patients with newly diagnosed CRC admitted to the John Radcliffe Hospital, Oxford in 1995. Means of diagnosis and Dukes' staging were recorded. RESULTS: In 1 year 177 patients were admitted with newly diagnosed CRC. Previous studies had shown an increase from 52.8 to 103.4 patients per year. The number of patients diagnosed by colonoscopy doubled from 19.4% in 1979-1983 to 41% in 1995. No significant change in the proportion of patients with Dukes' A or B tumours was found. CONCLUSION: The number of patients treated annually with CRC in a stable population has more than trebled in the last 3 decades. A real increase in the incidence of CRC is likely as this rise cannot be explained solely by changing referral patterns or an ageing community. There are no significant changes in presentation patterns despite the availability of colonoscopy since 1975.