Epidemiology and natural course of social fears and social phobia

OBJECTIVE: To summarize epidemiological studies providing data on prevalence, incidence, comorbidity, natural course, risk factors and consequences of social phobia (SP). METHOD: Data from cross-sectional studies and prospective longitudinal studies in particular are considered. RESULTS: These studies portray SP as a frequent mental disorder, which begins typically in early adolescence, and is highly comorbid with other anxiety disorders, as well as secondary depression and substance abuse disorders. Several possible risk factors have already been identified for the onset and unfavorable course of SP; some of them have been tested in prospective longitudinal studies. SP is a chronic disorder when compared with other mental disorders and when subclinical symptomatic levels are considered. Impairment caused by SP is considerable and increases over a patient's life span. The negative impact of SP is not only reflected in subjective well-being and reduced quality of life but also in social role functioning, and it impacts negatively on career progression. CONCLUSION: Prospective longitudinal studies in representative samples drawn from the general population provide information that allows the overall direct and indirect costs of the disorder (treatment costs, disability, social welfare) to be determined, and enables an improvement in long-term care strategies as well as preventive efforts to be established.     

Systemic immune parameters and sleep after ultra-low dose administration of IL-2 in healthy men

A somnogenic function is suspected for various cytokines. Foregoing experiments in humans indicated a selective increase in the production of interleukin-2 (IL-2) during sleep as compared with nocturnal wakefulness. Here, we examined whether conversely, IL-2 exerts a promoting influence on sleep. Also, the effects of IL-2 administered at ultra-low doses on systemic immune and endocrine parameters were assessed. Eighteen healthy men participated in three night sessions, receiving subcutaneously at 19:00 h either placebo or recombinant human IL-2 at doses of 1000 and 10,000 IU/kg bw. Polysomnographical recordings were obtained between 23:00 and 07:00 h. Blood was collected repeatedly to determine (i) white blood cell (WBC) counts including the enumeration of monocytes, natural killer (NK) cells, and lymphocyte subsets, (ii) serum concentrations of IL-2, soluble IL-2 receptor (sIL-2r), IL-4, IL-6, and interferon-gamma (IFN-gamma), and (iii) concentrations of adrenocorticotropin (ACTH), cortisol, thyreotropin (TSH), and growth hormone (GH). Changes after 1000 IU/kg bw IL-2 generally remained non-significant. However, distinct effects occurred after 10,000 IU/kg bw IL-2, inducing serum IL-2 concentrations selectively activating the high affinity IL-2 receptor. At this dose, IL-2 reduced the number of circulating lymphocytes (including all major subtypes) and NK cells, while counts of monocytes and neutrophils were increased. IL-4 release was stimulated and IFN-gamma concentration reduced after IL-2. Also, IL-2 increased the TSH concentration. There were no hints at a sleep promoting effect of IL-2. Immune changes suggest that nocturnal IL-2 administration induces a shift towards Th2 mediated defense.     

Clinical utility of serial serum c-erbB-2 determinations in the follow-up of breast cancer patients

To evaluate the ability of serum c-erbB-2 protein to (1) indicate occult and manifest metastases and (2) reflect response to first-line therapy, serial serum c-erbB-2 measurements were performed in a retrospective series of 52 primary breast cancer patients who had developed metastatic disease during follow-up. The results were compared with CA 15-3. Preoperatively, 31% (16/52) of the primary breast cancer patients had elevated c-erbB-2 concentrations. The CA 15-3 positivity rate was 13% (7/52). After surgery, 10 of the 52 patients showed either stable but highly elevated or rising c-erbB-2 serum levels indicating serum c-erbB-2 producing minimal residual disease. Increasing CA 15-3 concentrations were seen in only three patients. Elevated serum c-erbB-2 levels predicted manifest metastases in 27 and 50% of the patients at 6 and 3 months, respectively, prior to clinical diagnosis. CA 15-3 was less sensitive. Only 16 and 32% of the patients had increased CA 15-3 serum concentrations at 6 and 3 months, respectively, prior to clinical detection. The positivity rates of c-erbB-2 and CA 15-3 were similar when metastases were clinically diagnosed. Elevated c-erbB-2 concentrations were found in 62% (32/52). The sensitivity of CA 15-3 was 56% (29/52). The association between serum profiles and response to first-line therapy was evaluated in detail for 45 patients. Serial c-erbB-2 and CA 15-3 measurements reflected disease course in 24 and 27 patients, respectively. The serum profiles of c-erbB-2 and CA 15-3 were similar in 17 patients. In summary, our results suggest that serial determinations of serum c-erbB-2 are useful to monitor breast cancer patients.     

The international collaborative study of maternal phenylketonuria: status report 1994

Neonatal screening for phenylketonuria (PKU) has created a problem as females with PKU are reaching child-bearing age. Surveys have revealed that maternal phenylalanine blood concentrations greater than 1200 μmol/l are associated with fetal microcephaly, congenital heart defects and intrauterine growth retardation. It is estimated that as many as 3000 hyperphenylalaninemic females may be at risk of producing these fetal abnormalities. To examine this problem, the international maternal PKU collaborative study was developed to evaluate the efficacy of a phenylalanine-restricted diet in reducing fetal morbidity. Preliminary findings have indicated that phenylalanine restriction should begin before conception for females with PKU planning a pregnancy. Dietary control should maintain maternal blood phenylalanine levels between 120 and 360 μmol/l and should provide adequate energy, protein, vitamin and mineral intake. Pregnant hyperphenylalaninemic females who achieved metabolic control after conception or by the 10th week of pregnancy had a better offspring outcome than anticipated. The results of 402 pregnancies are reviewed.     

Event-related brain potentials and working memory function in healthy humans after single-dose and prolonged intranasal administration of adrenocorticotropin 4-10 and desacetyl-alpha-melanocyte stimulating hormone

Neuropeptides of the adrenocorticotropin/melanocorticotropin (ACTH/MSH) family are most potent modulators of cognitive function. Their neurobehavioral activity is principally encoded in the 4-10 fragment of the ACTH/MSH molecule; in humans, it has been shown to pertain primarily to functions of attentive stimulus/response processing. The aims of this study were (1) to examine the effects of ACTH 4-10 on event-related brain potentials (ERPs) and behavioral indicators of stimulus encoding within the working memory; (2) to compare the effects after a single dose and after prolonged treatment with ACTH 4-10; and (3) to compare the effects of ACTH 4-10 with those of desacetyl-alpha-MSH (i.e., ACTH 1-13 amide), which, like ACTH 4-10, binds to the known brain melanocortin receptors (MC-Rs) but with distinctly higher affinity. Double-blind, placebo-controlled experiments were performed in 60 healthy control subjects. The authors monitored ERPs and reaction times while these subjects performed an auditory vigilance task ("oddball"). Recall was tested on a verbal short-term memory task including different word categories (neutral, rare, food, sex). After a single (1 mg) as well as prolonged intranasal administration (1 mg/day over a period of 6 weeks), ACTH 4-10 enhanced the positive slow wave in ERPs to target stimuli of the vigilance task (p < 0.05), but left classic P3 unaffected. Moreover, single-dose and prolonged administration of ACTH 4-10 increased the rate of false responses during vigilance (p < 0.01). In the short term, ACTH 4-10 also impaired recall of neutral words (p < 0.05). Equimolar doses of desacetyl-alpha-MSH did not influence ERPs, neither after a single dose nor after prolonged treatment. Similar to ACTH 4-10, desacetyl-alpha-MSH increased the error rate during vigilance and acutely impaired the recall of neutral words. The increase in ERP slow-wave positivity, in conjunction with behavioral impairments after treatment with ACTH 4-10, complemented previous results of inferior focusing of attention and a less concise structure of thought after administration of ACTH 4-10. The changes indicated an impairment in differential processing of relevant versus irrelevant contents within the working memory, and, in this regard, might mimic aspects of psychopathologic disturbances of attention and thought processes. Their persistence after prolonged treatment with ACTH 4-10 suggests an activation of mechanisms subserving the consolidation of the peptide's effects. The poor efficacy of desacetyl-alpha-MSH suggests that the known MC-Rs may be irrelevant for mediating cognitive effects of this neuropeptide family.     

Controversies in transfusion medicine. Perioperative hemodilution: pro

Hemodilution can obviate the need for allogeneic transfusion in some patients. However, it is only one component of a comprehensive blood conservation program and should be combined with other techniques whenever possible. While most often employed in teenagers and healthy young adults, ANH has been used in small children, the elderly, and patients of all ages who are undergoing cardiac surgery. Extreme caution should be exercised if ANH is used in patients with coronary artery disease or aortic stenosis who are undergoing noncardiac surgery, because their normal compensatory mechanisms are impaired. What usually is a safe and relatively simple procedure can become a disaster if employed in inappropriately selected patients. Careful hemodynamic monitoring and maintenance of normovolemia are critical.     

抗真菌药物的研究II.C-端含氧代赖氨酸二肽的合成及抗白念珠菌活性

引用违法传递概念设计合成了11个C-末端含氧代赖氨酸二肽,进行抗深部致病菌-白念珠菌活性试验,体外实验结果显示极强的抑菌活性,MIC在12.5～0.8μg/disk之间,较母体氧化赖氨酸大50～135倍(克分子比。     

Insulin Infusion Normalizes Cardiovascular Responses and Plasma Noradrenaline after Oral Glucose in Type 1 (Insulin-dependent) Diabetes

ABSTRACT. We examined whether the abnormal regulation of the cardiovascular system and plasma noradrenaline observed after oral glucose in insulin-dependent diabetic patients could be normalized by intravenous infusion of insulin. Eight patients with type 1 (insulin-dependent) diabetes were examined after an oral glucose load with and without simultaneous infusion of insulin. Insulin infusion increased plasma insulin from 0.07 to 0.31 nmol/1. In the control experiment (glucose only), mean heart rate and mean arterial systolic blood pressure remained unchanged and plasma noradrenaline (NA) decreased (p < 0.05). After oral glucose plus intravenous insulin, mean heart rate increased by 11 % and mean systolic blood pressure by 5 % (p < 0.05, p < 0.01), whereas plasma NA did not change significantly. The present study indicates that physiologic increments in plasma insulin concentration are of importance in the regulation of the cardiovascular system and plasma NA following an oral glucose load.