Examining preferences for allocating health care gains

This study is part of a programme to elicit and examine community preferences for health care in different contexts. Data were obtained from a group of predominantly Australian health care decision-makers. A short questionnaire contained six valuation questions and four demographic questions. The six valuation questions posed choices where equal health gains were to be allocated to different population groups based upon: age; sex; current health; socio-economic status; across time; and across different numbers of individuals. The results provide some evidence that respondents were prepared to discriminate between health gains derived in different contexts especially where health gains were to be allocated between groups of different health status and over time. Further research is planned and the possible implications for health policy, and in particular for resource allocation in health care, are briefly discussed.     

Neuroendocrine Evidence for Reduced Dopamine Receptor Sensitivity in Alcoholism

Postsynaptic dopamine (DA) receptor sensitivity was assessed during abstinence in 15 male patients with alcohol dependence. The DA receptor sensitivity was evaluated using growth hormone (GH) responses to the DA receptor agonist apomorphine (0.18-0.24 mg intravenously). The patients were cared for in an alcoholism treatment unit for the 2 months prior to the investigation. They were carefully controlled for sobriety during this period. Thirteen healthy men were used as controls. The maximum GH responses to apomorphine were significantly reduced in patients compared with those in the control group. The patients had a significantly higher proportion of blunted GH responses. The findings suggest reduced postsynaptic DA, possibly D2, receptor sensitivity in abstinent alcoholics. The question whether this abnormal DA receptor status is genetically determined or acquired after long-term alcohol consumption remains to be addressed.     

ADAMTS-4 activity on a proteoglycan vs. a polypeptide is controlled by the ancillary domains

Introduction In combination with the catalytic domain, the ancillary domains of the ADAMTS' are proposed to regulate activity via interactions with sulfated GAGs, the extracellular matrix (ECM) and cell surface. Interactions with both GAGs and the ECM have been attributed to the thrombospondin (TSP) type 1 motifs and spacer region ( Kuno and Matsushima 1998 ; Flannery et al. 2002 ). ADAMTS‐1, ‐4 and ‐5, all undergo cleavage within their respective spacer regions ( Flannery et al. 2002 ; Rodriguez‐Manzaneque et al. 2000 ; Georgiadis et al. 2002 ), an event which has been reported to increase activity towards the interglobular domain of aggrecan and decrease the heparin affinity of ADAMTS‐4 ( Flannery et al. 2002 ; Gao et al. 2002 ). Materials and methods V5‐ and His‐tagged recombinant human ADAMTS‐4 constructs terminating after the catalytic (?DTS), disintegrin‐like (?TS), TSP (?S) or spacer region (Full) were expressed in High‐Five cells. Proteoglycanase activities of the resultant proteins were assayed with solution digests of aggrecan and a polyacrylamide‐entrapped aggrecan particle assay. Proteolytic activity was measured using a novel, nonglycosylated, reporter substrate assay. Results All forms of ADAMTS‐4 were active to varying degrees in the reporter substrate assay. Digestion of aggrecan in solution digests was apparent in all proteins with the exception of the catalytic domain in isolation (?DTS). Activity towards aggrecan decreased with increasing truncation of the protein. Discussion Removal of the cysteine‐rich‐spacer domain and further C‐terminal truncations decrease the activity of ADAMTS‐4 towards aggrecan, whilst the proteolytic activity remains intact. Cleavages releasing the ancillary domains of ADAMTS' may therefore alter the catalytic activity of these enzymes against proteoglycans and also nonglycosylated polypeptides. More information is required about potential substrates for the processed forms of ADAMTS‐4.     

The '2-week rule' for suspected breast carcinoma: a qualitative study of the views of patients and professionals.

BACKGROUND: The '2-week rule' for the referral of patients with potential cancers is an important but controversial development. AIMS: To investigate the 2-week rule for women with breast problems from the perspective of the patients and of healthcare professionals. DESIGN OF STUDY: Qualitative study using semi-structured interviews. SETTING: Patients referred to two breast care units and professionals from primary and secondary care in Teesside and Hartlepool. METHOD: Semi-structured interviews with a purposive sample of 12 patients referred under the 2-week rule and 20 professionals. RESULTS: All women experienced considerable worries in the time leading up to diagnosis. This affected relationships with others, and they used selective telling to help maintain control over their own anxiety and prevent anxiety in others. They were not aware of the 2-week rule as a new initiative, but wanted quick referral to assure them that they did not have cancer. Patients felt they needed more information about breast symptoms and the referral process. Comments about communication with professionals, both good and poor, were frequent in their accounts, which contrasted with the absence of such concerns in the accounts of the professionals. The professionals thought that the 2-week rule was advantageous in reducing anxiety, but thought that disadvantages included longer waits for patients referred outside the rule and increased pressure on hospital services. Cultural changes, including increased patient assertiveness and 'breast awareness', were considered important contextual factors. General practitioners (GPs) were concerned about missing diagnoses in patients statistically unlikely to have carcinomas. CONCLUSION: Differences in emphasis were apparent, with patients wanting to be assured that they did not have cancer, specialists concerned both about increased workload and the impact on patients with cancers, and GPs anxious about missing diagnoses. The 2-week rule compromises professional autonomy, which partially accounts for the anger directed against it. There is a need for patients to have more information, and they place great value on good communication. All patient responders experienced significant distress while waiting to be seen.     

Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test.

BACKGROUND: Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals. METHODS: Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4. RESULTS: One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result. CONCLUSIONS: This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.     

Oxytocin attenuates amygdala responses to emotional faces regardless of valence.

BACKGROUND: Oxytocin is known to reduce anxiety and stress in social interactions as well as to modulate approach behavior. Recent studies suggest that the amygdala might be the primary neuronal basis for these effects. METHODS: In a functional magnetic resonance imaging study using a double-blind, placebo-controlled within-subject design, we measured neural responses to fearful, angry, and happy facial expressions after intranasal application of 24 IU oxytocin compared with placebo. RESULTS: Oxytocin reduced right-sided amygdala responses to all three face categories even when the emotional content of the presented face was not evaluated explicitly. Exploratory whole brain analysis revealed modulatory effects in prefrontal and temporal areas as well as in the brainstem. CONCLUSIONS: Results suggest a modulatory role of oxytocin on amygdala responses to facial expressions irrespective of their valence. Reduction of amygdala activity to positive and negative stimuli might reflect reduced uncertainty about the predictive value of a social stimulus and thereby facilitates social approach behavior.     

Empfehlungen für die Anwendung der Immunapherese bei der Therapie bullöser Autoimmundermatosen

The etiology of epidermolysis bullosa acquisita (EBA) is unknown. EBA may be associated with other autoim‐mune systemic diseases; it also has been described in connection with different malignant tumors, showing complete remission after successful treatment of the tumor.In such cases, EBA may be regarded as a paraneo‐plastic dermatosis. We detected a highly differentiated neuroendocrine pancreatic cancer in a 78‐year‐old woman with EBA. Even thought her tumor was completely removed and the patient has been disease‐free for over seven years, a complete regression of her autoimmune bullous dermatosis could not be induced. By using intravenous immunoglobulins in combination with mycophenolate mofetil, further blister formation could be ameliorated.