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Biomedical subjects

J Haas

Publications and source records attributed to J Haas.

At least 19 recordsLinked to original sources

Differential glucocorticoid effects on proliferation and invasion of human trophoblast cell lines.

Several clinical situations require continuous glucocorticoid (GC) treatment during pregnancy. A well-known deleterious side effect of such treatment is the higher incidence of growth-restricted fetuses, for which a too shallow trophoblast invasion is presently hypothesised as the underlying cause. This study investigated whether the synthetic GC triamcinolone acetonide (TA) influences proliferation, invasion and endocrine activity of human trophoblast. BeWo and JEG-3 choriocarcinoma cell lines both express GC receptors (western blotting) and were used as models for human trophoblast. JAR devoid cells of GC receptor were used as negative control. The cells were cultured for 48 h without (control) or with 0.5, 5 and 50 microM TA. In the presence and absence of serum, proliferation was determined by cell counting and measuring the cell cycle regulating protein cyclin B1 (Western blotting); invasion was determined by a conventional Matrigel invasion assay and by measuring the secretion (ELISA) of matrix-metalloproteinases (MMP-2, MMP-9) into the culture medium; endocrine activity was assessed by measuring the levels of human chorionic gonadotropin (ELISA) into the culture medium. TA altered the number of viable and dead cells as well as cyclin B1 levels and, to a lesser extent, invasion of BeWo and JEG-3, with a strong influence of serum. BeWo and JEG-3 cells reacted differently and in most instances reverse. In the cell lines used as models of human trophoblast, TA alter some functions relevant to proliferation and invasion, and suggest that caution should be exercised when treating women with GCs during pregnancy.

Cell Line↗

[Venous leg ulcers: no improvement of wound healing with 685-nm low level laser therapy. Randomised, placebo-controlled, double-blind study].

INTRODUCTION: Venous leg ulcers (ulcera crurum venosa) are frequently seen in elderly patients. It has been suggested that low level laser irradiation has a biostimulative and wound healing effect; however, this has not yet been clinically verified by controlled studies. STUDY DESIGN: The difference in size reduction of leg ulcers with and without low level laser or placebo laser treatment was measured in 44 patients randomised into two treatment groups (685-nm low level laser and placebo laser) or a control group which served to quantify the effect of laser application. All patients received standardized wound care. OBJECTIVE: The aim of the study was to compare the effectiveness of low level laser irradiation with that of a placebo "light source". The size of the ulcers was planimetrically measured at baseline (day 1), at the end of therapy (day 28) and 2 months later (day 90). The difference in wound size was evaluated. RESULTS: There were no statistically significant differences in reduction of wound size between the three groups, thus suggesting that low level laser light does not have any stimulatory effect on wound healing in ulcera crurum venosa.

Adult↗

[MS registry in Germany--design and first results of the pilot phase].

In the summer of 2001, a nationwide epidemiological multiple sclerosis (MS) register was initiated under the auspices of the German MS Society (DMSG). This project aimed at collecting epidemiological data on the number of patients with MS, course of the disease, and their social situation in Germany. During the 2-year pilot phase, five MS centers with various regional differences and treatment methods participated, leading to a representative selection of patients. In December 2003, standardised data sets of 3,458 MS patients were available for evaluation. After examining the quality of the data, 3,223 sets remained for further analysis. The demographics were similar to those obtained from other epidemiological studies: 72% of the patients were female, mean age was 42.9+/-11.2 years, mean disease duration 12.6+/-8.7 years, and 64% suffered from the relapsing-remitting form of the disease. The median EDSS was 3.0, and 69% of patients had an EDSS </=4.0. The great effect of this disorder was underscored by the fact that one third of the patients had prematurely retired due to MS. After successful completion of the pilot phase, the MS register will provide reliable data and thus serve as an important tool to improve the overall situation of MS patients in Germany.

Adult↗

Immunoadsorption patients with multiple sclerosis: an open-label pilot study.

BACKGROUND: Immunoadsorption (IA) is occasionally applied in patients with acute relapses of multiple sclerosis (MS). This pilot study was undertaken to determine whether IA might help in secondary progressive and relapsing-remitting multiple sclerosis. DESIGN: IA was performed at 1-week intervals in 12 patients with secondary progressive or relapsing-remitting MS. These patients had an extended disability status scale (EDSS) score of 4.5-7 and an EDSS increase of 0.5 within 6 months before inclusion in the study despite conventional drug therapy. The change in the EDSS and that in the MS functional composite (MSFC) score, which consisted of quantitative tests of arm function, ambulation, visual acuity and cognition, served as the primary outcome variables, which were measured at baseline and at 3, 6 and 12 months. Changes in quality of life and cerebral lesions by magnetic resonance imaging (MRI) were also assessed at baseline and after the last immunoadsorption (month 3). RESULTS: A significant reduction of the median EDSS change was observed after the treatment period, which reversed 3 months after the immunoadsorptions had been stopped. Ten of 12 patients remained stable during the first year of follow-up with no significant changes of the MSFC scores. No significant changes in magnetic resonance imaging T2-hyperintense brain lesions or in the number of gadolinium-positive lesions and in the patients' quality of life were observed. Western blot analyses demonstrated a reduction of serum myelin-specific antibodies, which were collected in the adsorber eluates. CONCLUSIONS: Removal of immunoglobulins, including myelin-specific antibodies by immunoadsorption, seems to delay disease progression as defined by EDSS, MSFC and MRI, while the patients' quality of life did not deteriorate.

Adult↗

Twenty-four-month comparison of immunomodulatory treatments - a retrospective open label study in 308 RRMS patients treated with beta interferons or glatiramer acetate (Copaxone).

A total of 308 patients with relapsing remitting multiple sclerosis (RRMS) documented in a clinical database have been analysed for comparison of treatment effects of first line immunomodulating therapies. During follow up for 24 months the reduction of relapse rates was evaluated in a retrospective and open-label clinical study by comparing the efficacy of interferon (INF)beta-1a i.m. (Avonex), INFbeta-1b s.c. (Betaferon), INFbeta-1a 22 microg s.c. (Rebif 22) and glatiramer acetate (GA; Copaxone) in patients with RRMS (enhanced disability status score (EDSS) < 3.5) who have been treated for at least 6 months. Compared with baseline, relapse rate was reduced to a comparable extend after 6 month treatment with all regimen. For all drugs the effect on the relapse rate was sustained over 24 months.. There was no superiority of one of the INFbeta preparations concerning reduction of relapse rate after 12 and 24 months, however reduction was significantly higher for patients treated with GA compared with all beta interferons (-0.71, P < 0.001). In addition, the discontinuation rate within 24 months was significantly lower for GA. Despite some limitations of the study design, the results provide helpful clinical information regarding the efficacy of immunomodulatory therapies in early stages of RRMS patients in a clinical setting.

Adult↗

Intravenous immunoglobulins in the treatment of relapsing remitting multiple sclerosis--results of a retrospective multicenter observational study over five years.

Use of intravenous immunoglobulins (IVIG) has been recommended for treatment of RRMS if first line therapy with beta-interferon or glatiramer acetate is not tolerated, or if contraindications exist. This consensus recommendation is based on the demonstration of efficacy and tolerability of IVIG in four randomized controlled trials (RCTs). The impact of non-randomized observational trials on evidence-based recommendations for treatment is still under discussion. In order to evaluate the transferability of study results derived from RCTs into a routine practice setting, we carried out a retrospective data analysis on patients with RRMS who had been treated with IVIG during the last five years. Data sets from 308 out of 1122 screened patients were available for analysis. Treatment with IVIG resulted in a 69% reduction of the mean annual relapse rate (ARR) (calculated over two years) from 1.74+/-1.15 before IVIG treatment to 0.53+/-0.61 after start of IVIG treatment. Mean expanded disability status scale (EDSS) values remained stable throughout the observation period. The results of this observational study were similar to the results of previous RCTs with IVIG.

Adolescent↗

Does the use of low-level laser influence wound healing in chronic venous leg ulcers?

OBJECTIVE: Venous leg ulcer treatment often requires months or years of regular wound care by trained staff. It has been suggested that low-level laser irradiation has a biostimulative and wound healing effect, but this has not been clinically verified by controlled studies. This study aimed to compare the effectiveness of low-level laser irradiation with that of a placebo 'light source'. METHOD: Forty-four patients were assigned to two treatment groups (laser and placebo) or a third group (standardised treatment only) to quantify the effect of the laser therapy. Patients in all three groups received standardised wound care (disinfection, a hydrofibre dressing and compression bandaging). Ulcer size was measured at baseline (day 1), at the end of therapy (day 28) and then two months later (day 90). The relative difference in wound size was evaluated. RESULTS: The difference in the reduction in wound size was not statistically significant in all three groups. A positive effect of using the non-laser device (placebo effect) was demonstrated in some patients. CONCLUSION: These study results suggest that low-level laser does not stimulate wound healing in venous leg ulcers. Further controlled studies are needed to clarify the efficacy of low-level laser treatment as a wound-healing stimulant.

Adult↗

IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS.

OBJECTIVE: To investigate if IV immunoglobulins (IVIg) in combination with methylprednisolone make recovery from a relapse faster and more complete than methylprednisolone alone. Design/ METHODS: The authors studied 76 patients with multiple sclerosis (MS) who had an acute relapse with involvement of visual function, upper limb motor function, or gait, and with onset of symptoms between 24 hours and 14 days before. Patients were treated with either IVIg 1 g/kg or placebo (0.1% human albumin), given 24 hours before treatment with IV methylprednisolone 1 g on 3 consecutive days. RESULTS: Both groups improved, but the authors observed no significant difference between IVIg and placebo patients regarding the primary endpoint, the mean change in the Z-score of the individually chosen targeted neurologic deficit (the most affected system) from baseline to 12 weeks (p = 0.89). A slightly better, but not significant remission was seen in the IVIg group in global scores, i.e., Expanded Disability Status Scale (p = 0.23) and Multiple Sclerosis Impairment Scale (p = 0.24), and in time to next relapse (p = 0.22). CONCLUSIONS: The results do not justify routine application of IV immunoglobulins as add-on therapy to IV methylprednisolone in the treatment of acute multiple sclerosis attacks.

Adult↗

[Leptomeningeal tumor cell infiltrations as a first manifestation of an immunocytoma (Waldenstrom's macroglobulinemia)].

Immunocytoma (Waldenstrom's macroglobulinemia) is a rare chronic lymphoproliferative disorder of B-cell origin. It is characterized by the presence of large amounts of circulating monoclonal immunoglobulin M (IgM) and lymphoplasmocytoid bone marrow infiltration. Affection of the peripheral nervous system is common and causes polyneuropathy (5-10%). An isolated leptomeningeal infiltration by neoplastic cells is very rare and has been reported in few cases only. The diagnosis is difficult, in particular if cerebrospinal fluid (CSF) cytology is inconclusive. We present the case of a patient who developed a personality disorder and cognitive impairment. Initial CSF findings were compatible with chronic lymphocytic (aseptic) meningitis. The serologic detection of IgM paraproteinemia and bone marrow cytology suggested immunocytoma. The selective analysis of B-cell clonality in both whole CSF cell lysates and individual CSF cells using polymerase chain reaction (PCR) based amplification of the rearranged CDR3 region of the IgH gene revealed the presence of a monoclonal B-cell population and was diagnostic for leptomeningeal tumor cell infiltration by immunocytoma.

Aged↗

Escalating immunotherapy of multiple sclerosis--new aspects and practical application.

Recent clinical studies in multiple sclerosis (MS) provide new data on the treatment of clinically isolated syndromes, on secondary progression, on direct comparison of immunomodulatory treatments and on dosing issues. All these studies have important implications for the optimized care of MS patients. The multiple sclerosis therapy consensus group (MSTCG) critically evaluated the available data and provides recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence on MRI for subclinical dissemination of disease. Recent trials show that the efficacy of interferon beta treatment is more likely if patients in the secondary progressive phase of the disease still have superimposed bouts or other indicators of inflammatory disease activity than without having them. There are now data available, which suggest a possible dose-effect relation for recombinant beta-interferons. These studies have to be interpreted with caution, as some potentially important issues in the design of these studies (e. g. maintenance of blinding in the clinical part of the study) were not adequately addressed. A meta-analysis of selected interferon trials has been published challenging the value of recombinant IFN beta in MS. The pitfalls of that report are discussed in the present review as are other issues relevant to treatment including the new definition of MS, the problem of treatment failure and the impact of cost-effectiveness analyses. The MSTCG panel recommends that the new diagnostic criteria proposed by McDonald et al. should be applied if immunoprophylactic treatment is being considered. The use of standardized clinical documentation is now generally proposed to facilitate the systematic evaluation of individual patients over time and to allow retrospective evaluations in different patient cohorts. This in turn may help in formulating recommendations for the application of innovative products to patients and to health care providers. Moreover, in long-term treated patients, secondary treatment failure should be identified by pre-planned follow-up examinations, and other treatment options should then be considered.

Clinical Trials as Topic↗

Gender, age and seasonal effects on IgA deficiency: a study of 7293 Caucasians.

BACKGROUND: The frequency of serum IgA deficiency (SIgAD) differs between populations. We examined the prevalence of SIgAD in healthy Caucasians. MATERIALS AND METHODS: Serum immunoglobulin A (SIgA) was measured in 7293 volunteers (2264 women, 5029 men) aged 30 +/- 14.2 years (mean +/- SD; range: 12-66). Serum immunoglobulin A and subnormal SIgA levels were defined by a SIgA level < 0.07 g L(-1), and between 0.07 and 0.7 g L(-1), respectively. Means were compared by analysis of variance (anova) and analysis of covariance (ancova); frequencies by the chi(2) test. RESULTS: Fifteen subjects (0.21%; one woman, 14 men) had SIgAD. Subnormal SIgA levels were found in 155 persons (2.13%): 21 females (0.93% of the females) and 134 males (2.66% of the males; difference: 1.74%; 95% CI: 1.12-2.33%; P < 0.001). Males were more likely to have subnormal SIgA levels or SIgAD (odds ratio 3.09, 95% CI: 1.97-4.85). The prevalence of SIgAD and subnormal SIgA was lowest in winter (chi(2) = 14.8; P = 0.002; 3 d.f.; and chi(2) = 43.2; P < 0.001; 3 d.f., respectively). Serum immunoglobulin A concentrations were significantly higher during winter. Serum immunoglobulin A levels increased with age on average by 0.2 +/- 0.06 g L(-1) per decade of life (P < 0.001). Taking into account the influence of age, SIgA concentration was lower in females as compared with males. CONCLUSION: The prevalence of SIgAD and subnormal SIgA levels is increased in males. There exists a significant influence of gender, age and seasons on SIgA levels.

Adolescent↗

Prognostic significance of preoperative DNA flow cytometry in surgically-treated cervical cancer.

OBJECTIVE: To evaluate the prognostic significance of preoperative DNA flow cytometry compared with other clinical and histologic variables in cervical carcinoma. STUDY DESIGN: Sixty-four patients with FIGO Stage Ib-II cervical cancer treated with radical abdominal hysterectomy and systematic pelvic lymphadenectomy were analyzed. The mean follow-up was 3.4 (range 0.3-9.8) years. DNA flow cytometry was performed with fresh tumor tissue. Four biopsies were recut from the surgical specimen within 30 minutes of the operation. The ectocervix was divided into four quadrants and a specimen obtained from each. DNA-low-grade tumors (diploid, near-diploid, tetraploid and near-tetraploid) were distinguished from DNA-high-grade tumors (aneuploid and hypoploid). Carcinomas with more than one non-diploid stem line were considered heterogeneous. An S phase fraction >7% was classified as low, 7% - < 14% as moderate, and > or = 14 as high. DNA ploidy, DNA heterogeneity, S phase fraction and various clinical and histological variables were related to disease-free survival. RESULTS: In the univariate analysis patients with DNA-low-grade carcinomas had significantly better disease-free survival than patients with DNA-high-grade tumors (82% vs 45%, p = 0.021). Carcinomas with an S-phase fraction < 7% were associated with better disease-free survival (0.8) than those with an S-phase fraction 7% - > 14% (0.62) and those with > or = 14% (0.64), but this was not statistically significant. Cox stepwise regression analysis showed DNA-heterogeneity, age, grade, parametrial involvement and extrapelvic metastasis to be independent prognostic factors. CONCLUSION: DNA ploidy and DNA heterogeneity are of prognostic importance in cervical cancer. DNA flow cytometry may be used preoperatively to identify low-risk and high-risk patients within a given stage.

Adult↗

[Value of intensive thyroid assessment in male infertility].

In infertile men thyroid hormone and antibody testing was performed and correlated with the results of semen analyses. Evaluation included semen analyses, physical examination, evaluation of sex steroid hormones, thyroid hormones (bTSH, fT4, fT3) and thyroid antibody testing (TGA, TPO-Ab, TRAK). Furthermore 45 men with normal thyroid function were scheduled for TRH testing. No one was diagnosed as having manifest hypo- or hyperthyroidism. Latent thyroid dysfunction had no effect on semen parameters. Elevated TPO-Ab were significantly correlated with reduction in motility of spermatozoa. The routine assessment of thyroid hormones and antibodies in infertile men is not recommended. Subclinical hypothyroidism as a result of TRH testing is a rare finding in infertile men.

Gonadal Steroid Hormones↗

Serum-dependent effects of IGF-I and insulin on proliferation and invasion of human first trimester trophoblast cell models.

Extravillous cytotrophoblasts are specialised epithelial cells of the placenta that proliferate or invade the maternal decidua. Little is known about the mechanisms that regulate these processes. Here the effects of several insulin and insulin-like growth factor-I (IGF-I) doses, either singly or in synergy with serum, on human chorionic gonadotropin-beta (hCG-beta) secretion (RIA), proliferation (cell counting, cyclin B(1) levels) and invasion [Matrigel invasion assay, secretion of matrix metalloproteinases (MMP) 2 and 9] were investigated. The choriocarcinoma cell lines BeWo, JAR and JEG-3 served as models for first trimester human trophoblasts. Both growth factors altered hCG-beta secretion and proliferation dependent on the cell line. Insulin stimulated proliferation in JAR cells and, to a lesser extent, in JEG-3 cells, and when cultured in serum-free medium, BeWo was not affected. Invasion was not affected although proMMP-2 levels in culture medium were altered under some conditions. A strong synergistic effect with serum was noted. In the presence of serum both growth factors reduced proliferation and invasion in a similar fashion. Since the cell models differ by their degree of differentiation, the data demonstrate that the effects of insulin and IGF-I strongly depend on serum and the degree of differentiation. It can be speculated that IGF-I can take on tasks of insulin in the regulation of trophoblast functions under conditions of insulinopenia.

Animals↗