Psychosocial impact of Von Hippel–Lindau disease: levels and sources of distress

Lammens CRM, Bleiker EMA, Verhoef S, Hes FJ, Ausems MGEM, Majoor‐Krakauer D, Sijmons RH, Luijt van der RB, Ouweland van den AMW, Van Os Tam, Hoogerbrugge N, Gomez‐Garcia EB, Dommering CJ, Gundy CM, Aaronson NK. Psychosocial impact of von Hippel–Lindau disease: levels and sources of distress. Von Hippel–Lindau disease (VHL) is a hereditary tumor susceptibility syndrome, characterized by an increased risk of developing multiple benign and malignant tumors at various sites and ages with limited preventive options. This study evaluates the prevalence of distress among VHL family members and factors associated significantly with such distress. Forty‐eight families with a VHL mutation were identified via the nine family cancer clinics in the Netherlands. In total, 171 family members (carriers, 50% at‐risk, non‐carriers) were approached, of whom 123 (72%) completed a self‐report questionnaire. Approximately 40% of the VHL family members reported clinically relevant levels of distress, approaching 50% among the carriers and, possibly even more striking, 36% among the non‐carriers. Having lost a first degree relative due to VHL during adolescence (OR 11.2; 95% CI 1.4–86.9) was related significantly to heightened levels of distress. Approximately, only one‐third of those who reported heightened levels of distress had received professional psychosocial support. A substantial percentage of family members experience clinically relevant levels of distress. We would recommend the introduction of a procedure for screening for distress in this vulnerable population. Special attention should be paid to those individuals who have lost a close relative due to VHL during adolescence.     

Clinical economics review: gastrointestinal disease in primary care.

Gastrointestinal disorders are common in the general population, with annual prevalence figures ranging from 20% for irritable bowel syndrome to over 40% for dyspepsia. Less than one-third of patients consult general practitioners for these problems, and anxiety about serious disease and cancer are as important in the decision to consult as symptom severity. Gastrointestinal disorders have significant socioeconomic effects in the community, and account for 10% of the work of general practitioners in the UK. The health economics implications of management in primary care relate principally to the costs of investigation and therapy, notably antisecretory drugs, endoscopy, radiology and specialist referral. Although guidelines based on evidence and agreed between primary and secondary care physicians offer an attractive approach to rationalizing the use of resources, there is at present little health service research evidence on which to base important decisions. For example, in dyspepsia, the role of Helicobacter pylori identification and eradication in an overall management strategy in primary care has yet to be defined. An exploration of the clinical economics of gastrointestinal disorders in general practice raises a number of research questions, which will require the attention of both generalists and specialists.     

FAILURE OF ADDITION OF LITHIUM TO IMIPRAMINE TO ENHANCE ACTIVITY IN RATS OR MOOD IN NORMAL VOLUNTEERS

Lithium powerfully augments the effects of imipramine in resistant depression. We treated four groups of rats for five weeks with (1) saline alone, (2) saline followed by lithium, (3) imipramine alone, and (4) imipramine followed by lithium. There was no augmentation of activity by lithium. Normal human volunteers took imipramine 75 mg daily for three weeks, followed by imipramine 75 mg daily together with lithium 900 mg daily for another ten days. There was no elevation of mood after the addition of lithium. Lithium augmentation of antidepressants apparently requires a pre-existing neurochemical-behavioral disturbance.     

吲满氨酯的磷光分析

吲满氨酯具有强的磷光,其水液激发波峰304 nm,发射波峰434 nm,磷光寿命为3.87s。在碱液中磷光比在酸液中强。重原子碘对吲满氨酯磷光有增强作用,而寿命变短。金属重原子Cu²⁺,Fe³⁺,Pb²⁺,Tl³⁺,Zn²⁺及钼酸铵等均无增强作用,Cu²⁺,Fe³⁺等反有猝灭作用。比较了9种吲满氨酯类似物的磷光性质,当2位亚甲基氧化为酮基后磷光明显下降。建立了吲满氨酯的磷光分析法,最小检出量为5ng。小鼠腹腔注入药物0.1 mg/kg后10 min其血药浓度为149 ng/ml。     

Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes

The N-hydroxylation of carcinogenic arylamines represents an initial step in their metabolic activation. Animal studies have shown that this reaction is catalyzed by the cytochrome P450 (P450) enzymes P450 1A1 and P450 1A2. In this study, utilizing enzymes expressed in Escherichia coli (and purified) or in human B-lymphoblastoid cells, the catalytic activities of recombinant human P450 1A1, P450 1A2, and P450 3A4 for N- hydroxylation of several carcinogenic arylamines were determined. P450 1A2 from both expression systems catalyzed the N-hydroxylation of 4- aminobiphenyl and the heterocyclic amines, 2-amino-3-methylimidazo[4,5- f/quinoline (IQ), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Rates were similar, with values of 1.1-7.8 nmol/min/nmol P450. In contrast, P450 1A1 catalyzed N-hydroxylation of only PhIP, and no activity was observed with P450 3A4. Further kinetic analysis with purified P450 1A2 showed similar Km and Vmax values for N-hydroxylation of the arylamines. Furafylline and fluvoxamine, inhibitors of P450 1A2 activity in human liver microsomes, were found to be inhibitory of the recombinant P450 1A2 N-hydroxylation activity. Results from this study are supportive of a major role for human P450 1A2 in the metabolic activation of arylamines.