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Biomedical subjects

J Hoyer

Publications and source records attributed to J Hoyer.

At least 19 recordsLinked to original sources

[Endothelial ion channels -- novel targets for antihypertensive therapy].

Endothelial cation channel are important regulators of vascular tone by modulating intracellular Ca(2+)-signaling and thus adequate synthesis of vasodilating factors. The overall importance of these ion channels suggests that they may represent novel pharmacotherapeutic targets in addition to the well-known voltage-gated calcium channels in vascular smooth muscle. In this short overview we summarize the current knowledge about endothelial ion channels and their roles for endothelium-dependent vasodilatation. Furthermore, we perspectively discuss the usefulness of specific openers of endothelial Ca(2+)-activated K(+)-channels and TRPV-channels as novel antihypertensive drugs.

Antihypertensive Agents↗

Dent's disease: identification of a novel mutation in the renal chloride channel CLCN5.

Dent's disease is an inherited tubulopathy caused by a mutation in the CLCN5 chloride channel gene. It is characterized by low-molecular weight proteinuria, hypercalciuria, nephrolithiasis or nephrocalcinosis, rickets and eventual-progressive renal failure. Onset of clinical symptoms show a great variability, making a diagnosis at an early stage of the disease often difficult. Given the variably clinical picture, genetic analysis can provide a reliable method to confirm the diagnosis. Here, we report on the case of a patient with progressive renal failure showing signs of a tubular lesion and symptoms of Dent's disease. Although this rare disease was suspected by means of the clinical features, it was genetic analysis that confirmed the diagnosis and revealed a novel mutation in the CLCN5 gene.

Adult↗

[Generalized anxiety disorders in primary medical care].

Based on new empirical findings in a large-scale primary care study, the quality of care for the most chronic and debilitating anxiety problem, generalised anxiety disorder, is examined. Following a brief introduction of this disorder, the core findings of the GAD-P study (generalised anxiety and depression in primary care) with more than 20,000 patients of 558 family doctor practices are summarised and measures to improve the quality of care of patients with generalised anxiety disorder, a disorder which is rarely adequately treated, are discussed. This paper particularly emphasises the standard use of time-efficient diagnostic screening instruments, because improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to increase awareness of this disorder as well as patient education materials to improve compliance and to enhance treatment outcome effects are highlighted.

Adolescent↗

Generalized anxiety disorder and clinical worry episodes in young women.

BACKGROUND: This article presents epidemiological data on the prevalence of DSM-IV generalized anxiety disorder (GAD) and sub-threshold GAD (fulfilling three out of four GAD criteria) in young women together with data on co-morbidity and psychosocial functioning. The prevalence of clinically relevant worry and its predictive validity for the diagnosis of GAD were also examined. METHOD: Young women (N = 2064), aged between 18 and 25, from a representative German community sample were diagnosed with a structured clinical interview (ADIS-L, German research version). An additional interview questioned all the participants about the frequency/intensity and uncontrollability of diverse worry topics. RESULTS: Thirty-seven participants (1.8%) fulfilled the criteria of current GAD (1 week point prevalence) and 56 received a lifetime diagnosis (2.7%); a further 50 participants (2.3%) were diagnosed with sub-threshold GAD. Co-morbidity between GAD and other disorders was high for current (68%) and lifetime GAD (91%). GAD, as well as sub-threshold GAD, showed clearly reduced levels of psychosocial functioning. Whereas worries of low intensity and high controllability were ubiquitous in all subsamples, clinically defined worrying was rarely present in healthy subjects (0.89%) and of adequate predictive accuracy for GAD. CONCLUSIONS: Full GAD and sub-threshold GAD were moderately frequent in young women. Although DSM-IV worry criteria proved to be highly useful, the strictness of the complete GAD-criteria should not lead to absence of attention from subclinical generalized anxiety states in research and practice.

Adolescent↗

Impaired hyperpolarization in regenerated endothelium after balloon catheter injury.

Ca(2+)-activated K(+) (K(Ca)) channels control endothelial Ca(2+) homeostasis and the formation of vasodilators. After angioplasty, dysfunction of the regenerated endothelium leads to abnormal vasoregulation. In this study, we tested the expression and function of K(Ca) channels in regenerated endothelium at 6 weeks after balloon catheter injury of rat carotid arteries (CAs) by using single-cell reverse transcription-polymerase chain reaction, patch-clamp techniques, and analysis of vasoreactivity. In single regenerated endothelial cells (ECs), the percentage of ECs expressing the K(Ca) genes, rSK3 (12+/-8%) and rIK1 (22+/-9%), was significantly lower compared with the percentage of native ECs expressing these genes (rSK3 58+/-8%, rIK1 64+/-10%). In patch-clamp experiments, K(Ca) currents and acetylcholine-induced hyperpolarization were markedly reduced in regenerated ECs (shift of membrane potential -6+/-3 mV) compared with those in native ECs (shift of membrane potential -21+/-5 mV). In pressure myograph experiments, acetylcholine-induced dilation was impaired in reendothelialized CAs compared with normal CAs. Intraluminal application of the K(Ca) blocker apamin and charybdotoxin inhibited dilation by 30% in normal CAs but was without effect in reendothelialized CAs. Intraluminal application of 1-ethyl-2-benzimidazolinone (100 micromol/L), an opener of K(Ca) channels, evoked dilation by 29% in normal CAs but had no effect in reendothelialized CAs. In conclusion, the impaired expression of K(Ca) channels in regenerated endothelium results in defective hyperpolarization and impaired dilation. Thus, the impaired K(Ca) channel function contributes to functional alterations of regenerated endothelium after angioplasty.

Acetylcholine↗

Characteristics of worry in GAD patients, social phobics, and controls.

Phenomenological features of worry such as thought content, subjective experience of worry, and efforts to control were investigated in the present interview study, as well as retrospective information about possible origins. To examine the clinical specificity of worrying in Generalized Anxiety Disorder (GAD), 36 GAD patients were compared to a normal control group (N = 30) and to a clinical control group (N = 22 social phobics). GAD patients differed from both groups in having higher frequency of worry, higher number of different worry topics, lower subjective controllability, more accompanying bodily symptoms, and more distress during worry. Thus, in general, our data confirm the central and specific role of worrying in GAD. Furthermore, in contrast to other topics, worrying about daily hassles was specific to GAD patients, which represents a lower threshold for starting to worry.

Adult↗

Expression of ryanodine receptor type 3 and TRP channels in endothelial cells: comparison of in situ and cultured human endothelial cells.

OBJECTIVE: Ca(2+) mobilization plays an important role in endothelial function by stimulating Ca(2+)-dependent synthesis of vasodilating factors. In addition to inositol-1,4,5-trisphosphate (InsP(3)) mediated Ca(2+) mobilization, Ca(2+) release from ryanodine-sensitive pools and Ca(2+)-influx through TRP channels have been suggested to be important in endothelial Ca(2+)-signaling. However, the function and molecular identity of TRP channels and ryanodine receptors in human endothelium in situ are still elusive. We hypothesized that expression of ryanodine-receptors (RyR) and TRP channels differs between human endothelium in situ and in cultured cells. METHODS: By combining single-cell RT-PCR and patch-clamp techniques, expression of RyR and TRP channels was determined in situ in endothelial cells of human mesenteric artery (HMAECs) obtained from patients undergoing bowel resection and in the endothelial cell line EA.hy926. RESULTS: At the single cell level, expression of RyR 3 was detected in 25 and 5% of HMAECs and EA.hy926 samples, respectively. Expression of the RyR 1 and 2 was not detected in either HMAECs or EA.hy926. In patch-clamp experiments in HMAECs, applications of caffeine (0.5 mM) induced sustained hyperpolarization mediated by activation of Ca(2+)-activated K channels. In EA.hy926, caffeine-induced hyperpolarization was not detected. Single HMAECs expressed the TRP genes, TRP1 and TRP3, but not TRP 4 and 6. The TRP1 was the predominantly expressed TRP gene in HMAECs in situ whereas TRP3 expression was rarely detected. EA.hy926 expressed only TRP1. In patch clamp experiments in HMAECs, Ca(2+)-store depletion activated non-selective cation currents leading to Ca(2+) entry. CONCLUSIONS: Our findings suggest that, in addition to InsP(3) mediated Ca(2+) release, Ca(2+) release from ryanodine-sensitive stores mediated by RyR3 and Ca(2+) entry through TRP1 might represent important components of endothelial Ca(2+) signaling in situ and thereby of endothelial function in intact human blood vessels.

Calcium↗

Regulation of pressure-activated channel in intact vascular endothelium of stroke-prone spontaneously hypertensive rats.

The pressure-activated cation channel (PAC), a novel type of mechanosensitive channel, has been suggested to act as a mechanosensor in aortic endothelium. In experimental hypertension, PAC function was up-regulated in the established phase of high blood pressure. This association of altered PAC function and elevated arterial pressure suggests that PAC function is regulated by alterations in blood pressure. In the present study, we electrophysiologically investigated PAC function in intact endothelium of aorta (EA) and mesenteric artery (EMA) from stroke-prone spontaneously hypertensive rats (SHRSP), SHRSP after 4 weeks of treatment with quinaprilat (10 mg/kg/day), and normotensive Wistar-Kyoto (WKY) rats. In untreated SHRSP and WKY rats, systolic blood pressure (SBP) was 201+/-3 mm Hg and 142+/-3 mm Hg, respectively. In quinaprilat-treated SHRSP, SBP was lowered to 135+/-5 mm Hg. Apparent PAC density (percentage of patches with PAC activity) in EA of untreated SHRSP (63.7%+/-7.3%) was 2.4-fold higher than in WKY rats (26.0%+/-5.0%). In contrast, no significant PAC up-regulation was detected in EMA of SHRSP (15.7%+/-4.2%) compared with WKY rats (12.0%+/-3.9%). In EA of quinaprilat-treated normotensive SHRSP, PAC density (27.1%+/-5.2%) was lowered to levels found in normotensive WKY rats. Unitary conductance and pressure sensitivity of PAC were not altered in either hypertensive or normotensive rats. Taken together, hypertension-induced increases of endothelial PAC density can be completely reversed by antihypertensive therapy. The PAC up-regulation in EA was interpreted as a compensatory mechanism to enhance Ca2+-influx and subsequently the synthesis of vasodilatory factors. This mechanism is missing in EMA of SHRSP, which might contribute to high blood pressure in this rat model of severe genetic hypertension.

Angiotensin-Converting Enzyme Inhibitors↗

Laparoscopic treatment of lymphoceles in patients after renal transplantation.

Postoperative lymphoceles after renal transplantation appear in up to 18% of patients, followed by individual indisposition, pain or impaired graft function. Therapeutic options are percutaneous drainage, needle aspiration with sclerosing therapy, or internal surgical drainage by conventional or laparoscopic approach. The laparoscopic procedure offers short hospitalisation time and quick postoperative recovery. From 1993 to 1997, 16 patients underwent laparoscopic fenestration of a post-renal transplant lymphocele, and were presented in a retrospective analysis. Three patients have had previous abdominal surgery. Following preoperative ultrasound and CT scan, 16 patients underwent laparoscopic drainage after drainage and staining of the lymphocele with methylene blue. No conversion was necessary. Mean operation time was 42 min, no intraoperative complications were seen. Oral nutrition and immunosuppression were continued on the day of surgery, and patients were discharged between the 2nd and 5th (median hospital stay 3.3 d) day after surgery. No recurrence was evident in a follow-up time of 15-54 months (median 31.4 months). Renal function remained unchanged in all patients postoperatively.

Drainage↗

Social phobia as a comorbid condition in sex offenders with paraphilia or impulse control disorder.

Studies on the prevalence of social anxiety in sex offenders show mixed results. This may be due to social anxiety being heightened only in diagnostic subgroups of sex offenders, namely in paraphiliacs. In study 1, 72 mentally disordered sexual delinquents and 30 controls were screened for social anxiety with the Social Interaction Anxiety Scale and the Social Phobia Scale by Mattick and Clarke (German versions). In study 2, 55 mentally disordered sexual delinquents were diagnosed with a structured clinical interview. In both studies, sex offenders were categorized as either paraphilic or impulse control disordered (without paraphilia) according to research criteria. Study 1 showed markedly heightened scores for social anxiety in paraphiliacs, particularly for social interaction anxiety. Study 2 found a high lifetime and point prevalence of social phobia in paraphiliacs for which corroborating evidence was again found in questionnaire results. Implications for further research, diagnostic procedures, and therapy are discussed.

Adult↗

Generalized anxiety disorder: nature and course.

Generalized anxiety disorder (GAD) is a chronic and highly prevalent disorder in the adult population, yet it remains a relatively poorly understood condition. Clinicians may be familiar with the symptoms of enduring excessive worrying, anxiety, and hypervigilance that are characteristic of GAD, but may not necessarily recognize that these are usually symptoms of a distinct psychiatric disorder. Despite changes in diagnostic criteria, estimates of prevalence for GAD are remarkably consistent across epidemiologic studies. Lifetime prevalence in the general population is estimated at 5% (DSM-III and/or DSM-III-R criteria), with rates as high as 10% among women aged 40 years and above, and cross-sectional rates among primary care attenders are about 8%, making GAD the most prevalent anxiety disorder in primary care. The age at onset of GAD differs from that of other anxiety disorders: prevalence rates are low in adolescents and young adults but increase substantially with age. Females are at greater risk than males, and the disorder is correlated with being unemployed or a housewife or having a chronic medical illness. GAD is frequently associated with comorbid depression and other anxiety and somatoform disorders. Significant GAD-specific disability occurs even when comorbidity is not present.

Adolescent↗

[Prevalence and correlates of generalized anxiety disorders in primary care].

AIM: The investigators evaluated the (target-day) point prevalence and correlates of generalized anxiety and depression in German primary care practices. METHOD: The study used a representative national sample of more than 500 primary care practices. On a target day, all primary care patients were examined by questionnaires (GAS-Q and DSQ). RESULTS: Conservatively estimated, 5.3% of all primary care patients met criteria for generalized anxiety disorder (GAD). Similar prevalence estimations were found for Major Depression. Only 30% of all GAD patients met criteria for depression cross-sectionally. Patients with GAD (whether comorbid with depression or not) were more frequently female, reported an onset of GAD mostly between ages of 25 and 45 years, had increased rates of disability and impairment in major social roles and high utilization rates of all health care resources. They also revealed a predominantly chronic course of illness over a period of several years and an increased suicide rate. The presence of physical illness increased rates of handicap/impairment days in the past month. Associated negative outcomes were found to be similar to those observed in depressive disorders. Patients with GAD reported significantly more frequently sleep, anxiety and depressive problems as primary reasons for contact. CONCLUSION: The GAD-P study highlights the significance of GAD in primary care as a condition that occurs at about the same frequency as major depression. Further, the relatively high proportion of pure GAD suggests that the frequency of depression-comorbidity of GAD has previously been overestimated.

Adolescent↗

[Family physician's interventions and prescribing practice. Results of the GAD-P study].

More than two thirds of all GAD patients are recognized as cases with mental disorders, only one third is correctly diagnosed. The paper shows that this has significant implications. 36%--as compared to 23% of those with major depression--receive no intervention. Of those recognized at least as a case the majority is treated by the GP, 9% are only referred to specialists, in addition to another 20% that are treated by the GP and referred as well. Almost all patients receive medication, however, only few medications that match scientific guidelines for GAD-specific treatments, namely SNRI, behavioural psychotherapy or SSRI. Also the high degree of comedication as well as high prescription rates for sedatives and phytotonics needs highlightening. The findings overall reveal an unsatisfactory picture of current treatment strategies for GAD patients in primary--especially if compared to depression. Treatments of first choice, SNRI (Venlafaxine SR) and behavioural psychotherapy are prescribed to only the minority of GAD sufferers.

Antidepressive Agents, Second-Generation↗

[Problems and deficiencies in family physician's management of generalized anxiety disorders. Results of the GAD-P study and priorities for an improved care].

The core findings of the GAD-P study (Generalized anxiety and depression in primary care) are summarized and measures to improve the quality of care of patients with generalized anxiety disorders are discussed. In addition to the identification of core research deficits the paper emphasizes the standard use of time-efficient diagnostic screening instruments, because urgently needed improved recognition and diagnosis is the prerequisite for appropriate treatment. Further the role of the media to combat stigma processes, as well as patient education materials to improve compliance and to enhance treatment outcome effects for this neglected disorder that frequently runs a chronic course are highlighted.

Adolescent↗