WONCA研究论文摘要汇编——基层抑郁症风险患者的连续性服务

背景目前已开展了对重性精神病患者进提供连续性服务的研究。目的探讨基层对有抑郁症风险患者提供连续性服务的水平,并与对心力衰竭患者的服务水平进行对比。方法采用抑郁症风险患者与心力衰竭患者对比的探索性研究。采用患者问卷评估服务的持续性,包含如下内容:(1)联系的服务提供者数(个人连续性);(2)诊所内服务提供者之间的合作(团队连续性)(6个项目,分数1~5分);(3)诊所外全科医师与服务提供者之间的合作(跨界连续性)(4个项目,分数1~5分)。结果大多数抑郁症风险患者在过去1年中寻遍整个服务提供界联系了几个服务提供者,曾遇到过高水平团队连续性服务及低水平跨界连续性服务。在诊所中可接触到的不同服务提供者要明显多于心力衰竭患者服务提供者(P<0.01)。抑郁症风险患者的服务提供者之间的合作更好一些,每项平均得分4.3分,心力衰竭患者得分为4.0分(P=0.03)。然而,跨界连续性服务方面正好相反:抑郁症风险患者每项平均得分3.5分,心力衰竭患者得分为4.0分(P=0.01)。结论抑郁症风险患者与心力衰竭患者之间的探索性对比显示:体验服务连续性方面的差距不大。对此还应行进一步分析。     

Enhanced Dopamine-Dependent Hippocampal Plasticity after Single MK-801 Application

Dopaminergic hyperfunction and N-methyl-D-aspartate receptor (NMDAR) hypofunction have both been implicated in psychosis. Dopamine-releasing drugs and NMDAR antagonists replicate symptoms associated with psychosis in healthy humans and exacerbate symptoms in patients with schizophrenia. Though hippocampal dysfunction contributes to psychosis, the impact of NMDAR hypofunction on hippocampal plasticity remains poorly understood. Here, we used an NMDAR antagonist rodent model of psychosis to investigate hippocampal long-term potentiation (LTP). We found that single systemic NMDAR antagonism results in a region-specific, presynaptic LTP at hippocampal CA1-subiculum synapses that is induced by activation of D1/D5 dopamine receptors and modulated by L-type voltage-gated Ca²⁺ channels. Thereby, our findings may provide a cellular mechanism how NMDAR antagonism can lead to an enhanced hippocampal output causing activation of the hippocampus-ventral tegmental area-loop and overdrive of the dopamine system.     

Discovery and characterization of a selective, nonpeptidyl thrombopoietin receptor agonist

OBJECTIVE: Peptide and other small molecule agonists have been described for several cytokines and growth factors. Hydrazone compounds described here as thrombopoietin receptor agonists were identified as activating STAT proteins in a Tpo responsive cell line. METHODS: STAT activation and analysis of signal transduction pathways in cell lines and normal human platelets was elucidated by Western blot and electrophoretic mobility shift assays. Proliferation assays in cell types responsive to other cytokines determined specificity for Tpo receptor. Flow cytometry quantified differentiation of CD34(+) cells into CD41(+) megakaryocytes and platelet production in vitro. RESULTS: Activation of STAT5, mitogen-activated protein kinase, p38, and early response genes by SB 394725 was similar to that induced by Tpo. SB 394725 induced a reporter gene response under a STAT activation promoter as well as the megakaryocyte-specific gpIIb promoter. The compound induced proliferation of Tpo responsive lines but demonstrated no activity in cell lines responding to other cytokines, i.e., erythropoietin, granulocyte-colony stimulating factor, interleukin-3, interferon-gamma. The response of normal human Tpo receptors was elucidated by measuring growth and differentiation of human bone marrow in vitro. Activation of endogenous Tpo receptors by SB 394725 was demonstrated in human and chimp platelets, but not in platelets of other species including mouse, dog, rabbit, or cynomolgus monkey. CONCLUSIONS: SB 394725, a small molecule with a molecular weight of 452 Da, is capable of activating Tpo-specific signal transduction, proliferation, and differentiation responses similar to the responses and functions of the protein growth factor, Tpo.     

Gonorrhoea in the asymptomatic patient: Presentation and the role of contact tracing for heterosexual men and women and for homosexual men

Summary Clinically silent gonorrhoea is the major problem in the control of the disease. Only 12 per cent of infected women reported in 1974 because of symptoms, compared with 97 per cent of infected heterosexual men and only 35 per cent of homosexual men with gonococcal proctitis alone. Homosexual men, compared with heterosexual men, had twice as many subsequent sexual contacts after infection and had a higher incidence of early syphilis. Eighty-four per cent had experienced passive anorectal intercourse. Ninety-seven per cent of men with gonococcal urethritis reported because of symptoms, but occasionally (particularly after unsuccessful treatment) urethral gonorrhoea in men may be clinically silent and even require tests of the overnight urethral secretion for diagnosis. For women, and for homosexual men who have had passive anorectal (or oral) intercourse, the indication for attendance for tests for gonorrhoea should be having run the risk, and not the presence of symptoms. Routine tests of the anorectum for gonorrhoea are essential in cases of women at risk, and for most homosexual men since over 80 per cent of these men will have had passive anorectal intercourse. Because gonococcal infections following treatment-failure are often clinically silent in both women and men, symptoms cannot be relied upon to indicate such failure. Follow-up smears and cultures are always essential.

---

Kasuistik von Patienten mit asymptomatischer Gonorrhöe und die Bedeutung der durch Personen durchgeführten Kontaktermittlung bei heterosexuellen Männern und Frauen sowie bei homosexuellen Männern

Zusammenfassung Die asymptomatische Gonorrhöe ist das Hauptproblem bei der Kontrolle dieser Krankheit. Nur 12 Prozent der erfaßten infizierten Frauen im Jahre 1974 kamen wegen Beschwerden zur Untersuchung im Gegensatz zu 97 Prozent der infizierten heterosexuellen Männer und nur 35 Prozent der homosexuellen Männer mit isolierter gonorrhoischer Proktitis. Im Vergleich mit heterosexuellen Männern hatten homosexuelle Männer zweimal so viel sexuelle Kontakte nach der Infektion und eine höhere Inzidenz einer Syphilis im Frühstadium. 84 Prozent hatten passiven anorektalen Verkehr gehabt. 97 Prozent der Männer mit gonorrhoischer Urethritis meldeten sich wegen Beschwerden, aber gelegentlich (insbesondere nach unzureichender Behandlung) kann die gonorrhoische Urethritis bei Männern klinisch stumm sein und sie kann sogar Untersuchungen der nächtlichen urethralen Sekretion zur Diagnose erfordern. Für Frauen und für homosexuelle Männer, die passiven anorektalen (oder oralen) Verkehr gehabt haben, sollte der Grund ihres Kommens nicht das Vorhandensein von Symptomen sein, sondern ein mögliches eingegangenes Infektionsrisiko. Routine-Untersuchungen der Analgegend auf Gonorrhöe sind bei Frauen nach entsprechendem Geschlechtsverkehr unbedingt erforderlich, gleichfalls bei den meisten homosexuellen Männern, weil über 80 Prozent dieser Männer wohl einen passiven anorektalen Verkehr gehabt haben werden. Da Gonokokken-Infektionen nach Behandlungsversagen bei Männern und Frauen oft asymptomatisch sind, ist das Verschwinden der Symptome keine verläßliche Indikation für eine erfolgreiche Behandlung. Ständige Überwachung in Form von Abstrichen und kulturellen Untersuchungen ist auf alle Fälle erforderlich.

---

---

This paper was presented in part on 27 September 1974 at a meeting of the British Society for Antimicrobial Chemotherapy.     

Identification of altered dipeptidyl-peptidase activities as potential biomarkers for unipolar depression

Background

Changes in circulatory aminopeptidases [dipeptidyl-peptidase-IV (DPP-IV), Prolyl-oligopeptidase (POP) and Leucine aminopeptidase (LAP)] activities have been found to be associated with psychiatric illnesses and inflammatory diseases.

Methods

The discriminatory indices of aminopeptidases activities were assessed by enzymatic assays in plasma samples from 240 unipolar depression (UD) patients and 264 matched controls. In addition the relationship between soluble and cellular DPP-IV activity was determined in plasma and blood cells from healthy subjects.

Results

Greater than 95% of the plasma DPP-IV activity could be blocked by inhibitors, demonstrating the specificity of the assay. Also, DPP-IV protein and activity levels were strongly correlated. In contrast, only 50% of the membrane-bound activity in blood cells was inhibited, which suggested that other similar peptidases may be present in these cells. UD patients had decreased plasma levels of DPP-IV and POP activities compared to healthy controls with a concomitant increase in LAP activity. Finally, testing of the LAP/DPP-IV ratio resulted in good discrimination of UD patients from controls with an area under the curve—receiver operating characteristic of 0.70.

Limitations

Further biological validation studies using different cohorts are warranted.

Conclusions

The finding that plasma DPP-IV activity was decreased and LAP activity was increased in UD patients suggests the potential value for testing the levels of these enzymes for improved classification of patients. In addition, the changes in these enzymes, suggests that the proteolytic maturation of their proneuropeptide and prohormone subtrates may also be affected in UD, resulting in altered production of the associated bioactive peptides.     

MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation

A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1–11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.