Can we define a tolerable level of risk in food allergy? Report from a EuroPrevall/UK Food Standards Agency workshop.

BACKGROUND: There is an emerging consensus that, as with other risks in society, zero risk for food-allergic people is not a realistic or attainable option. Food allergy challenge data and new risk assessment methods offer the opportunity to develop quantitative limits for unintended allergenic ingredients which can be used in risk-based approaches. However, a prerequisite to their application is defining a tolerable level of risk. This requires a value judgement and is ultimately a 'societal' decision that has to involve all relevant stakeholders. OBJECTIVE: The aim of the workshop was to bring together key representatives from the stakeholders (regulators, food industry, clinical researchers and patients), and for the first time ever discuss the definition of a tolerable level of risk with regard to allergic reactions to food. RESULTS: The discussions revealed a consensus that zero risk was not a realistic option and that it is essential to address the current lack of agreed action levels for cross-contamination with allergens if food allergen management practice is to be improved. The discussions also indicated that it was difficult to define and quantify a tolerable level of risk, although both the clinical and the industry groups tried to do so. A consensus emerged that doing nothing was not a viable option, and there was a strong desire to take action to improve the current situation. CONCLUSIONS AND CLINICAL RELEVANCE: Two concrete actions were suggested: (1) Action levels should be derived from the data currently available. Different scenarios should be examined and further developed in an iterative process. On the basis of this work, a tolerable level of risk should be proposed. (2) 'One-dose' clinical trial with a low challenge dose should be performed in multiple centres to provide additional information about the general applicability of dose-distribution models and help validate the threshold levels derived.

Periductal inflammation and cigarette smoke.

BACKGROUND: Cigarette smoking has been implicated in the etiology of periductal mastitis. The mechanism by which it causes inflammation around the mammary ducts is unknown. STUDY DESIGN: Inflammation and dilatation of the mammary ducts were compared in two groups of women with proven histologic diagnoses of periductal mastitis (PDM, n = 133) and intraductal papilloma (IDP, n = 98) over an eight year period. This study was done to determine if the number of cigarettes smoked correlated with the amount of periductal inflammation seen in PDM. Duct dilatation, periductal inflammation, and squamous metaplasia were assessed objectively by two pathologists without knowledge of the clinical parameters. RESULTS: Women with PDM were significantly more likely to be smokers than women with IDP (p < 0.001). Women with severe periductal inflammation were more likely to be younger (p < 0.05) whereas those with duct dilatation were more likely to be older (p < 0.02). Women with PDM who were heavy smokers (more than ten cigarettes per day) had more periductal inflammation (p = 0.0006) and squamous metaplasia of the lactiferous ducts (p < 0.02) compared with light or nonsmokers. Duct dilatation did not correlate with smoking habits. CONCLUSIONS: Cigarette smoking appears to be an important etiologic factor in periductal mastitis and appears to have direct toxic effects on the mammary ducts.

Nonunion of the femoral diaphysis. The influence of reaming and non-steroidal anti-inflammatory drugs.

We assessed factors which may affect union in 32 patients with nonunion of a fracture of the diaphysis of the femur and 67 comparable patients whose fracture had united. These included gender, age, smoking habit, the use of non-steroidal anti-inflammatory drugs (NSAIDs) the type of fracture (AO classification), soft-tissue injury (open or closed), the type of nail, the mode of locking, reaming nu non-reaming, infection, failure of the implant, distraction at the fracture site, and the time to full weight-bearing. Patients with severe head injuries were excluded. Both groups were comparable with regard to gender, Injury Severity Score and soft-tissue injury. There was no relationship between the rate of union and the type of implant, mode of locking, reaming, distraction or smoking. There were fewer cases of nonunion in more comminuted fractures (type C) and in patients who were able to bear weight early. There was a marked association between nonunion and the use of NSAIDs after injury (p = 0.000001) and delayed healing was noted in patients who took NSAIDs and whose fractures had united.

Manifest anxiety and self-concept: further investigation.

Manifest Anxiety Scale (MAS), Actual-Self, Ideal-Self, and Self-Ideal Discrepancy results from 134 first-year female nursing students were studied by the multivariate methods of factor analysis and multiple regression. Ideal-Self was less variant than Actual-Self, and correlated significantly with it. Factorial compositions of the three self-conceptual indices uncovered three overlapping factors: a tension-steadiness-worry factor, a well-being factor, and superficial social assets factor. The correlation of MAS with the discrepancy scores was overwhelmingly due to its relationship to Actual-Self, since it was only scarcely related to Ideal-Self, MAS was mainly associated with traits loading on the tension factor and secondarily with the well-being factor. Traits touching upon intellectual efficiency, physical attractiveness, and methodicalness were unrelated to MAS.

Some technical and theoretical considerations regarding the missed session.

Although Freud (1913b) originally proposed the 'principle of leasing a definite hour', there are many proponents of a more 'lenient' fee policy. The author critically examines some of the arguments put forward by the latter writers and argues that the missed session risks degrading into a 'missing' session if a financial marker does not remain in the patient's vacated place. The conflict mobilized in both partners to the therapeutic relationship by the missed session is best left open for analytic exploration rather than solved by a 'rational' and 'flexible' fee arrangement. The author suggests ways of theorizing, and eventually interpreting, the 'breach' in the relationship in terms of the absent, decentred subject, the Desire of the Other, the inherent contingency of our most primitive identifications, and the ineluctable violence and alienation of human interdependency. The 'rule of indenture' is seen in closer affinity to these basic contradictions than the more gracious 'gentlemen's agreement'.

Should we or shouldn't we? Some aspects of the confidentiality of clinical reporting and dossier access.

In this paper, reservations are expressed about two deviations from analytic neutrality: when the analyst seeks the patient's permission for publication or presentation of clinical material and when the analyst allows the patient access to the dossier under access-of-information legislation. In the first case, concern centres mainly on the entanglement of the patient in the therapist's sanctioned version of their work, an entanglement that might inhibit future revisions of the patient's self-understanding. In the second case, the analytic mental space, symbolised by the dossier, is viewed as neither uniquely the analyst's nor the patient's, a complex dialectical chamber the privacy of which must be respected, even by the patient whose discourse contributes to it, in order for it to function effectively. Transparency and accountability in the analytic context reveal a paradox that is not exclusive to it: the possibility of full disclosure runs counter to the expression of subjective truth. In a clinical example, curiosity about the dossier is seen to have been a new version of an earlier thwarted questioning about origins and identity. A specific deficiency in the therapist's understanding may have contributed to the patient's enactment.

Psychotherapy and disclosure: recent court decisions.

OBJECTIVE: To encourage mental health professionals concerned about the practice of psychotherapy to add their voices to the legal debate on disclosure. METHOD: Analysis of recent court decisions, in particular 2 Supreme Court of Canada judgements, R. v. O'Connor and R. v. Carosella, and 1 United States Supreme Court judgement, Jaffee v. Redmond. RESULTS: The lack of a common definition of psychotherapy may, in part, have made it awkward for mental health professionals to mount a concerted defence of psychotherapy dossiers. CONCLUSIONS: Unless mental health professionals develop a more robust justification and delimitation for privilege, in Canadian courts possible relevance of clinical material is likely to override concern for the patient's privacy interest. Future research might evaluate the impact of loss of privilege upon different types of psychotherapy.

Heterotopic ossification: a comparison between reamed and unreamed femoral nailing.

Heterotopic ossification in the abductor region of the hip following reamed intramedullary femoral nailing has an incidence as high as 68 per cent. A definitive triggering factor for heterotopic ossification remains obscure, but it has been suggested that there may be both local and systemic influences. Previous work has only been able to show a statistical correlation with systemic factors. Sixty antegrade femoral nailings were performed in 58 patients, of which 32 were unreamed. There was no significant difference between the two groups for systemic risk factors known to have statistical correlation with the formation of heterotopic bone. The incidence of heterotopic ossification in the reamed nail group was 35.7 per cent and 9.4 per cent in the unreamed nail group (P = 0.01). The difference in the incidence of heterotopic bone formation seems to be due to local factors, in particular the generation of osteogenic reaming debris, which are important in the pathophysiology of heterotopic ossification seen in femoral intramedullary nailing.

The selected use of ultrasound mammography to improve diagnostic accuracy in carcinoma of the breast.

Our initial experience with diagnostic ultrasound mammography (UM) showed it to be of high diagnostic accuracy and improved specificity when compared with x-ray mammography (XRM) in certain categories of patients. To evaluate this modality further, we reviewed our experience with 600 consecutive patients who underwent ultrasound mammography as part of their initial evaluation for breast disease. Five categories of patients were reviewed: I: age 35 or less--129; II: DY or P-2 pattern on XRM--174; III: negative XRM but symptoms requiring additional evaluation--81; IV: high risk remaining breast in patients previously having mastectomy--48; V: refusal of repeat XRM because of pregnancy, lactation, or fear of radiation exposure--168. Fifty-five solid lesions were diagnosed, including 36 carcinomas. Seventeen of these were not diagnosed on x-ray mammography, giving an improved pick-up of carcinoma in this overall group of 2.83%. Of particular interest was that, of the 27 carcinomas that were found in the group having XRM, 8 or 29.6% were missed on that modality alone. Five of these (62.5%) were patients having a DY pattern. All patients have been followed carefully and re-examined at 3-month intervals, with no evidence of a false negative examination. Overall, we feel diagnostic ultrasound mammography is a valuable adjunct to x-ray mammography and recommend its continued use in selected groups of patients where it has a superior diagnostic accuracy over x-ray mammography alone.

Connective tissue activation: stimulation of glucose transport by connective tissue activating peptide III.

Connective tissue activating peptide III (CTAP III), a human platelet derived growth factor, induced marked stimulation of 2-deoxy[14C]glucose (2dG) uptake in cultures of human synovial cells, chondrocytes, and dermal fibroblasts. Cytochalasin B (2 X 10(-5) M) blocked the mediator-induced increase in 2dG uptake; phlorhizin (8 X 10(-4) M) partially inhibited this process. When cells were exposed to CTAP III (4 X 10(-6) M) for 30 min prior to uptake assay, 2dG uptake was stimulated by 30-110%; greater stimulation (400-800%) occurred following 17-40-h preincubation with the mediator. A 17-h exposure to CTAP III similarly stimulated 3-O-methylglucose uptake by over 400%, suggesting that CTAP III stimulated 2dG uptake is mediated via changes in hexose transport. Cycloheximide clearly prevented the 17-h effects of CTAP III on 2dG uptake. Insulin (3 X 10(-6) M) stimulated 2dG uptake 40-70% after 30-min preincubation with hormone; little effect was seen after 17-h preincubation. These data suggest that CTAP III stimulates glucose transport shortly after addition to target cells; the major stimulation observed after a 17-h incubation is consistent with the synthesis of new glucose transport protein.

Renin activity determination using human plasma as a substrate.

A method for human renin activity determination using human plasma as the substrate is described. Angiotensin I is generated by incubating renin with human plasma, which is available along with the commercial radioimmunoassay kit for angiotensin I. The method obviates the need to isolate and purify the substrate, human angiotensinogen, from human plasma. In addition, the assay is highly renin specific, sensitive, and convenient to use for the routine determination of active human renin during its isolation and purification from tissue extracts or from genetically engineered bacterial and nonbacterial expression systems.