Treating depression comorbid with anxiety--results of an open, practice-oriented study with St John's wort WS 5572 and valerian extract in high doses.

Depressive disorders in comorbidity with anxiety disorders represent an frequently diagnostic and therapeutic problem. The studies quoted here prove that the symptoms associated with anxiety that severely afflict patients can be clearly improved more quickly with a combination therapy of St John's wort extract and valerian extract than with St John's wort monotherapy. The combination therapy was well tolerated, no significant side-effects occurred. Further studies are necessary to compare the combination treatment with other forms of therapy (serotonin- and noradrenalin re-uptake inhibitors).

Cost-effectiveness of adjuvant treatment with acamprosate in maintaining abstinence in alcohol dependent patients.

An open prospective cohort study was performed in Germany in order to evaluate the costs of treating alcohol dependence under real-world conditions. Eight hundred and fourteen recently detoxified alcohol-dependent patients were provided with psychosocial rehabilitation support. In addition, 540 alcohol-dependent patients treated with adjuvant acamprosate therapy were compared with 274 patients without pharmacotherapy. Real costs were assessed over a period of one year. Of the patients who were treated with acamprosate, 33.6% remained abstinent compared to only 21.1% in the standard cohort. The mean total costs per patient treated with acamprosate were EUR 1,631.49 per year. In the standard cohort, total costs were EUR 2,068.83. This difference is highly significant (p = 0.012). Direct costs amounted to 76.9% of the total costs, with a 27% difference between the cohorts (p < 0.001). There was no difference in indirect costs between the two groups (p = 0.324). This real-cost study confirms the favourable cost-effectiveness of acamprosate previously suggested by pharmaco-economic modelling studies.

Quality of life in acute exacerbation of chronic bronchitis: results from a German population study.

This study reports on data from a study conducted in the Federal Republic of Germany examining the quality of life (QoL) of patients with chronic bronchitis (CB) and its acute exacerbations (AECB). Data from 320 patients were collected at AECB and subsequently during a stable phase (non-AECB) utilizing the St George's Respiratory Questionnaire (SGRQ) and the Nottingham Health Profile (NHP). As expected, the QoL of CB patients was poor, even at non-AECB, with patients reporting lower scores than patients with other chronic conditions. Patients reported significantly poorer QoL at AECB than at non-AECB. After adjusting for the severity of the underlying condition, poorer QoL at AECB was significantly and independently associated with older age, unemployment, increasing BMI, increasing number of prior AECBs, and Anthonisen AECB grade. While younger subjects reported significantly greater deterioration in QoL at AECB, the factors most consistently and independently associated with relative QoL deterioration at AECB were the number of prior AECBs and exposure to air pollution at home. In conclusion, this study highlights the detrimental effect of CB, and in particular AECB, on QoL. The association between QoL and patient reports of previous AECB number and air pollution are consistent with reports from other studies.

[Adjuvant drug treatment of alcoholism with acamprosate: between sectoral budgets and disease management]. / Die adjuvante Arzneimitteltherapie der Alkoholkrankheit mit Acamprosa--Zwischen sektoraler Budgetierung und Disease Management.

OBJECTIVE: On the basis of several controlled clinical investigations the cost-effectiveness of acamprosate as adjuvant therapy of alcohol-dependent patients has yet been evaluated. These optimal conditions cannot be found in the daily ambulant practice and results in asking which of the alternatives, "standard plus acamprosate" or "standard without acamprosate", is more cost-effective in maintaining abstinence in alcohol dependent patients under realistic conditions. PATIENTS AND METHODS: In an open multi-centre study, medical care, costs and therapeutic outcome was prospectively documented. Prior to enrolling, all patients were obliged to undergo a detoxification procedure. At a mean age of 45 years the patients suffered an average of ten years from alcohol dependence. 521 patients were documented in the acamprosate cohort and 265 patients in the cohort "other therapy" over one year. Two thirds of the participating patients were male. RESULTS: At 33.6 % the rate of abstinence was remarkably higher in the acamprosate cohort in comparison to the cohort "other" at 21.1 % abstinent patients. The mean total costs per patient and year amounted to DM 3191 in the acamprosate-cohort and were significantly lower than in the cohort "other" with DM 4046. Effectiveness-adjusted costs of DM 9500 per successfully treated patient in the acamprosate-cohort were superior to the cohort "other", amounting to DM 19 148 per successfully treated patient. CONCLUSION: The described economic benefits may be utilised under conditions of an adequate disease management.

Treatment outcomes in acute exacerbations of chronic bronchitis: comparison of macrolides and moxifloxacin from the patient perspective.

Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group.

[Socioeconomic relevance of acute exacerbations of chronic bronchitis in the Federal Republic of Germany. A prospective cost of illness study]. / Zur sozioökonomischen Relevanz akuter Exazerbationen der chronischen Bronchitis in der Bundesrepublik Deutschland. Eine prospektive Krankheitskostenstudie.

BACKGROUND AND OBJECTIVE: Prospectively determined data on costs of chronic bronchitis were not yet available for the Federal Republic of Germany. The purpose of the burden-of-illness-study conducted in the Federal Republic of Germany from October 1996 to March 1998 was to calculate direct and indirect costs of chronic bronchitis as well as its acute exacerbations per patient and year. Furthermore, the health-related quality of life of the patients was determined. PATIENTS AND METHODS: The burden-of-illness-study was conducted as an open, not randomised surveillance study. The evaluation based on 785 patients (55.4% male, 44.2% female, 0.4% unknown; mean age 60 years) who were treated by 147 general practitioners. 755 patients could be included into the cost analysis. RESULTS: Per patient and year direct costs of chronic bronchitis amounted to DM 1112.27, the calculation of indirect costs resulted in DM 959.09. 41.4% of direct costs were due to drug acquisition, hospitalisation costs shared 31.6% and costs for physicians' fee amounted to 20.6%. The severity of chronic bronchitis revealed significantly different results in cost analysis: per patient, mild disease lead to direct costs of DM 387.86, moderate disease to DM 802.62 and severe disease to DM 2224.40. This result was caused by higher costs for drug acquisition and hospitalisation costs due to chronic bronchitis in higher stages of severity. Indirect costs were calculated by applying the human-capital-approach: 45.8% of indirect costs were due to time-off-work, nursing costs amounted to 23.7%. CONCLUSION: The costs of chronic bronchitis have a considerable impact on the total costs of the health care system of Germany.

A field trial of 2 telemedicine camera systems in a family practice.

Previous reports of telemedicine consultations have demonstrated that the technology is effective but inefficient. Little attention has been directed to the use of telemedicine in a primary care practice, especially the use of the medical peripheral devices. We used a functioning primary care practice as a telemedicine test bed, providing unselected patients in the study group. The goal was to study the performance of a new generation of a compact set of medical peripheral devices specifically designed for telemedicine examinations. In a 3-week field trial, 2 second-generation camera systems were used by physician faculty and residents in family practice to examine the skin, ears, and pharynx of 34 patients, ranging in age from 10 months to 78 years. Evaluations by the clinicians and patients were obtained. The average duration of an examination using these systems was 2 minutes. Patients' response was uniformly positive. A "pistol grip" video otoscope obtained an acceptable image, unless canal debris obscured the view. The system that provided pneumatic otoscopy was preferred, with some modifications necessary to obtain an airtight seal. The preferred skin camera was one that provided an image of a size that clinicians were most accustomed to viewing, although stability of this handheld camera was a problem. This camera also worked well to visualize the pharynx, especially in children with symptoms of pharyngitis. Color was deemed important in all 3 anatomical areas, and using auto-white balance and excluding fluorescent lights were preferred. Thus, the second-generation telemedicine peripheral devices were effective for use in a group of unselected primary care patients. These camera systems can be used by nursing personnel and require a minimum of time per examination.

A telemedicine primer. An introduction to the technology and an overview of the literature.

The examination of patients by telemedicine is currently experiencing a resurgence of interest, perhaps spurred by the increase in activity in managed care and major technologic advances. The history and recent publications show rapid change in the areas of interactive video and store-and-forward equipment, available communications media, and medical peripherals. Several existing demonstration projects serve as practical examples of the potential of telemedicine systems. Important research and clinical care issues and opportunities for constituency building await participation by primary care physicians.

Western blot analysis of water-soluble wheat flour (Triticum vulgaris) allergens.

Water-soluble wheat flour allergens were analyzed using the western blot technique. The sera of 130 bakers (42 with wheat flour allergy, 88 without allergy) were analyzed for IgE, IgG, and IgG4 binding towards wheat flour allergens. Three major allergens with molecular weights of 47, 17, and 15 kD were identified (Tri v Bd 47, Tri v Bd 17, and Tri v Bd 15; IUIS allergen nomenclature) by their ability to bind IgE from approximately 50% of the allergic sera. The specificity of the IgG was mostly directed against three high molecular weight components (134, 122, and 98 kD). In contrast, IgE and IgG4 was found frequently against the major allergens. 40% of healthy donors versus 12% of the asthmatic bakers had no detectable IgG4 against wheat flour extract. The biological activity of the water-soluble wheat flour components has been shown by their ability to induce histamine release from basophil leukocytes obtained from patients with bakers' asthma. The release of histamine from basophil leukocytes significantly correlated with the presence of IgE antibodies against wheat flour components of 47, 17 and 15 kD. A regulatory role of wheat flour specific IgG4 in allergic diseases could not be evaluated by western blot analysis.

Correlation of sCD23 release and immunoglobulin (E, A, G, M) synthesis by peripheral blood lymphocytes of atopic patients.

Peripheral blood lymphocytes of atopic patients were analyzed with regard to spontaneous as well as mitogen-induced CD23 expression, sCD23 release as well as Ig (M, G, A, E) synthesis in vitro. The data were correlated with the results for phenotypically defined peripheral cells (T cells, B cells, monocytes), sCD23 release and amounts of Ig (M, G, A, E). A positive correlation was obtained for serum sCD23 and serum IgE of patients with high and intermediate IgE levels, of sCD23 with the percentage of B cells and sCD23 with serum IgA levels. No correlation was obtained for the mitogen (SAC, PWM) induced amounts of Ig (E, A, M, G) synthesis and, furthermore, sCD23 levels determined in cell culture did not correlate with serum IgE levels. Our data support the role of sCD23 in atopic diseases and in isotype regulation.

Cytokine control of peripheral-blood CD23 expression and sCD23 release: differential regulation by IL-2 and IL-4.

CD23 expression on peripheral-blood lymphocytes (PBL) was studied under the influence of cytokines. It is shown that IL-2 induced CD23 expression on human peripheral-blood B cells. Evidence is presented that the IL-2 induced CD23 expression and release of soluble CD23 (sCD23) are not mediated by IL-4. In comparison to IL-4, the IL-2-induced CD23 expression and sCD23 release revealed kinetic differences and were not inhibited by anti-IL-4. The prestimulation of PBL with Staphylococcus aureus strains Cowan 1 (SAC) led to a pronounced reduction in basal CD23 expression and to a change in the response of cytokines. Subsequent stimulation with IL-4 induced CD23 to the same extent as on unstimulated cells, whereas the IL-2-induced CD23 expression and sCD23 release were greatly reduced. Interferon gamma showed no effects on the IL-4-stimulated CD23 expression of SAC-PBL, whereas the IL-2-induced CD23 expression was suppressed. Furthermore, we demonstrate that the stimulation with IL-2/IL-4 inhibits the effects of the individual cytokine; this inhibition is also seen for immunoglobulin (E, G, M) synthesis.

Cell-cell interactions for CD23 expression and soluble CD23 release from peripheral lymphocytes of atopic donors.

The cell-cell interactions for CD23 expression and soluble (s)CD23 release from peripheral blood lymphocytes (PBL), as well as purified cells (B, T cells, monocytes) of atopic donors, were studied. Cells either stimulated combined and subsequently separated or stimulated after separation were analysed. IL-4, IL-2, phytohaemagglutinin (PHA), interferon-gamma (IFN-gamma) and the combined interaction of IL-4 and IFN-gamma as well as PHA and IFN-gamma were used as stimuli. sCD23 release in the cell supernatant was determined from cells separated before stimulation. CD23 expression induced by IL-4 on cells stimulated and subsequently separated was significantly lower compared with amounts on separated cells which were subsequently stimulated. Major expression of CD23 was obtained on B cells and monocytes. Stimulation with PHA led to an increased expression on T cells compared to the control. When cells were stimulated, combined and separated, the combined stimuli of IL-4 and IFN-gamma showed a reduced CD23 expression for both experimental procedures and an enhanced release of sCD23. The data suggest an important role for cell-cell interactions. These results were supported by experiments in which separated cells were either co-cultured or cultured in Transwells. Co-culture of T cells with B cells and monocytes suggested that T cells are responsible for suppressed CD23 expression. No or only slight enhancement was obtained for sCD23 release. Our data indicate that cell-cell interactions and cytokines regulate CD23 expression, while sCD23 release is apparently solely regulated by soluble mediators (e.g. cytokines).

Effect of cytokines on spontaneous and allergen-induced CD23 expression, sCD23 release and Ig(E,G) synthesis from peripheral blood lymphocytes.

We studied the expression of the CD23 antigen as well as the release of soluble CD23 from peripheral blood lymphocytes (PBL) of atopic donors. PBL were stimulated with allergen (Dermatophagoides pteronyssinus; Der.p.), cytokines (interleukin-4, interferon-gamma; IL-4, IFN-gamma) or combinations of stimuli. CD23 levels were enhanced after the addition of allergen or IL-4 (10 U/ml) up to 10-fold compared to spontaneous expression. Soluble CD23 (sCD23) release was enhanced in a dose-dependent manner by allergen or IL-4. The combined addition of IL-4 and allergen resulted in an expression of CD23 as well as sCD23 release from PBL that was higher compared to the effects obtained with a single component. The production of Ig(E,G) increased in the presence of IL-4 (10 U/ml). This effect was enhanced after the addition of allergen. In contrast, the addition of allergen alone did not modulate IgE synthesis but revealed an enhanced IgG synthesis. Spontaneous as well as allergen- or IL-4-induced CD23 expression was significantly reduced in the presence of IFN-gamma, whereas the concomitant sCD23 release was enhanced in a dose-dependent fashion. IgE synthesis (spontaneous, IL-4 induced) was suppressed in the presence of IFN-gamma. IFN-gamma also reduced the IL-4-enhanced IgG secretion, whereas the spontaneous IgG production was not affected.

Expression of low-affinity receptor for IgE (Fc epsilon RII, CD23) and IgE-BF (soluble CD23) release by lymphoblastoid B-cell line RPMI-8866 and human peripheral lymphocytes of normal and atopic donors.

The low-affinity receptor for IgE (CD23) as well as the soluble IgE-binding factors (IgE-BF, sCD23) are important factors in IgE antibody regulation. The CD23 expression and the concomitant release of CD23 were analysed from the lymphoblastoid B-cell line RPMI-8866 and from peripheral blood lymphocytes (PBL) of healthy volunteers as well as atopic patients. CD23 expression and sCD23 release of RPMI-8866 cells were dependent on the stage of culture. While CD23 expression decreased with increasing time of culture (Day 1-3), the sCD23 release was enhanced during the culture period. Cytokines such as IL-4, IL-2, TNF alpha and IFN-gamma exerted various effects on the target cells depending on the culture period. CD23 expression on normal lymphocytes was lower compared with the expression on atopic cells. Lymphokines (IL-2, IL-4) as well as mitogens (PHA, Con A) enhanced CD23 expression and IgE-BF (sCD23) release. The degree of enhancement was always higher with atopic cells compared with the results obtained with cells of normal donors.

Detection and characterization of IgE-binding factors (IgE-BF) within supernatants of the cell line RPMI-8866, normal human sera and sera from atopic patients.

IgE-binding factors (IgE-BF) have been shown to be important regulatory factors for IgE induction and suppression. The analysis of IgE-binding factor activity by a modified inhibition radioimmunoassay (RIA), as well as by monoclonal antibodies (mAb) was carried out in the supernatant of the Fc epsilon RII+ cell line RPMI-8866 as well as in human sera. Kinetics of IgE-BF showed optimal release from RPMI-8866 cells after 3-4 days. Gel filtration of the supernatant indicated binding activity at less than 100,000, 45,000 and 25,000 MW. Within normal human sera two peaks of IgE-BF activity were obtained at 45,000 and 25,000 MW. In sera with high IgE levels (atopic dermatitis) a peak at less than 100,000 was MW detected. Within this peak endogenous IgE was present. Addition of sodium dodecylsulphate induced a release of IgE-BF with a MW of 60,000.