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Biomedical subjects

G Zimmermann

Publications and source records attributed to G Zimmermann.

At least 19 recordsLinked to original sources

[TGF-beta1 as a pathophysiological factor in fracture healing].

AIM: TGF-beta1 is an important local and systemic regulatory molecule during fracture healing. Various authors have shown differences in the systemic levels of TGF-beta1 over the time taken for bone healing in distraction osteogenesis and osteotomies. Previous studies have shown characteristic differences in the physiological levels of growth factors between normal fracture healing and delayed fracture union. The aim of the present study was to evaluate possible differences in sera levels of patients with normal and delayed union fracture healing. METHODS: Patients with long bone shaft fractures were recruited prospectively. Peripheral blood samples were collected over a period of 1 year using a standardized time schedule. At the end of the individual's investigation period, TGF-beta1 levels were determined. To achieve a homogeneous collective of patients, only those with a maximum of two fractures were included in the study. After matching for four criteria, we compared patients with normal fracture healing to patients with delayed unions. The fact of delayed union was accepted in case of failed consolidation 4 months after trauma. RESULTS: During a prospective study period of 1 year, 15 patients with normal fracture healing could be compared to 15 patients suffering from delayed union. By determining the absolute sera levels we found a typical increase of TGF-beta1 up to 2 weeks after fracture in both groups, with a subsequent decrease up to the sixth week after fracture. However, a decline in serum concentration occurred earlier in patients with delayed union, causing significantly lower TGF-beta1 levels in the non-union group 4 weeks after trauma (P=0.00006). CONCLUSION: Even with a relatively small number of patients, we could show a significant difference in serum concentrations of TGF-beta1 between the investigated groups. If these results can be verified within a larger collective, TGF-beta1 could be used as a predictive cytokine for delayed fracture healing.

Adult↗

[Clinical experience with bone morphogenetic protein 7 (BMP 7) in nonunions of long bones].

BACKGROUND: Nonunions of long bone fractures are considerable therapeutic and economic problems with increasing tendency. Basic surgical options are autogenous cancellous bone grafting, rod dynamization, reamed nailing, plate fixation with compression, and bone transport techniques. If these methods fail to work, alternative treatment options are needed. MATERIAL AND METHODS: Since May 2001 treatment with recombinant human (rh) bone morphogenic protein 7 [BMP-7 or osteogenic protein 1 (OP-1)] in combination with a type one collagen carrier has gained interest. BMP 7 induces the formation of new bone by differentiation of stem cells, thereby initiating the reaction cascade of osteogenesis. Nonunions over 9 months and unsuccessful bone grafting delineate the indication. RESULTS: We report our experience with 21 patients and nonunion of long bone fractures. Between July 2002 and June 2004, 23 units of BMP 7 were implanted. The implantation sites were 7 femora, 12 tibias, 2 humeri, and 2 forearms. In ten cases BMP 7 was combined with a new osteosynthesis and bone grafting and in five patients with bone grafting alone. In contrast in eight patients BMP 7 was applied as a single procedure without any bone grafting or any change of the osteosynthesis. CONCLUSION: There were no peri- or postoperative complications. Follow-up was obtained for a minimum of 6 months. Of 23 implantations, 22 were successful with bony healing revealed by clinical and radiological evaluation. In one patient no bony consolidation of the nonunion has been seen so far. In summary, based on our results we propose BMP 7 as an additional innovative therapy of long bone nonunions.

Adult↗

Systemic regulation of angiogenesis and matrix degradation in bone regeneration--distraction osteogenesis compared to rigid fracture healing.

Aim of this study was the investigation of systemic biochemical regulation mechanisms of bone regeneration by angiogenic and matrix-degrading enzymes during distraction osteogenesis compared to rigid osteotomy bone healing. Serum samples of 10 otherwise healthy patients with callus distraction for lower limb-lengthening and 10 osteotomy patients undergoing elective axis correction have been collected prospectively in a standardized time schedule before and up to 6 months after the procedure. At the end of the individual investigation period, concentrations of metalloproteinases (MMP-9, -13), tissue inhibitors of metalloproteinases (TIMP-1, TIMP-2) and the angiogenic factors angiogenin and VEGF have been detected by use of commercially available enzyme immunoassays. Results have been compared to our preliminary study on proMMP-1-3. In distraction osteogenesis, significantly elevated serum concentrations compared to baseline could be detected postoperatively for proMMP-1, MMP-9, TIMP-1, angiogenin and VEGF but not for proMMP-2, proMMP-3 or TIMP-2. In patients with rigid osteotomy healing, MMP-9, TIMP-1, TIMP-2, angiogenin and VEGF were significantly increased respectively. Comparison of both patient collectives revealed significantly higher increases of serum proMMP-1, VEGF and TIMP-1 in distraction patients during the lengthening period and significantly higher serum concentrations of TIMP-2 in late fracture healing period in osteotomy patients. Serum levels of MMP-13 were below the lowest standards, and therefore quantitative analysis was not possible. Bone regeneration in distraction osteogenesis and rigid osteotomy healing is accompanied by systemic increase of matrix-degrading and angiogenic factors in a certain time course and quantity. This might reflect biochemical regulation of local bone healing in the circulation. ProMMP-1, VEGF and TIMP-1 seem to be key regulatory factors during distraction osteogenesis.

Adult↗

The effect of cognitive behavioral treatment on the positive symptoms of schizophrenia spectrum disorders: a meta-analysis.

BACKGROUND: Despite the effectiveness of anti-psychotic pharmacotherapy, residual hallucinations and delusions do not completely resolve in some medicated patients. Additional cognitive behavioral therapy (CBT) seems to improve the management of positive symptoms. Despite promising results, the efficacy of CBT is still unclear. The present study addresses this issue taking into account a number of newly published controlled studies. METHOD: Fourteen studies including 1484 patients, published between 1990 and 2004 were identified and a meta-analysis of their results performed. RESULTS: Compared to other adjunctive measures, CBT showed significant reduction in positive symptoms and there was a higher benefit of CBT for patients suffering an acute psychotic episode versus the chronic condition (effect size of 0.57 vs. 0.27). DISCUSSION: CBT is a promising adjunctive treatment for positive symptoms in schizophrenia spectrum disorders. However, a number of potentially modifying variables have not yet been examined, such as therapeutic alliance and neuropsychological deficits.

Adult↗

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. SETTING: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. PARTICIPANTS: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). MAIN OUTCOME MEASURES: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Adult↗

Molecular mapping of Fusarium head blight resistance in the winter wheat population Dream/Lynx.

Fusarium head blight (FHB), mainly caused by Fusarium graminearum and F. culmorum, can significantly reduce the grain quality of wheat (Triticum aestivum L.) due to mycotoxin contamination. The objective of this study was to identify quantitative trait loci (QTLs) for FHB resistance in a winter wheat population developed by crossing the resistant German cultivar Dream with the susceptible British cultivar Lynx. A total of 145 recombinant inbred lines (RILs) were evaluated following spray inoculation with a F. culmorum suspension in field trials in 2002 in four environments across Germany. Based on amplified fragment length polymorphism and simple sequence repeat marker data, a 1,734 cM linkage map was established assuming that the majority of the polymorphic parts of the genome were covered. The area under disease progress curve (AUDPC) was calculated based on the visually scored FHB symptoms. The population segregated quantitatively for FHB severity. Composite interval mapping analysis for means across the environments identified four FHB resistance QTLs on chromosomes 6AL, 1B, 2BL and 7BS. Individually the QTLs explained 19%, 12%, 11% and 21% of the phenotypic variance, respectively, and together accounted for 41%. The QTL alleles conferring resistance on 6AL, 2BL and 7BS originated from cv. Dream. The resistance QTL on chromosome 6AL partly overlapped with a QTL for plant height. The FHB resistance QTL on 7BS coincided with a QTL for heading date, but the additive effect on heading date was of minor importance. The resistance QTL on chromosome 1B was associated with the T1BL.1RS wheat-rye translocation of Lynx.

Area Under Curve↗

TGF-beta1 as a marker of delayed fracture healing.

Mitogens of the TGF-beta superfamily have been shown to be crucial local and systemic regulatory molecules involved in fracture healing. However, there exists only little information about systemic regulation of bone regeneration by growth factors and no reports comparing serum levels of bone growth factors between normal and failed fracture healing have been published so far. We hypothesized that quality of fracture healing might be reflected by systemic alterations of key regulatory growth factors involved in bone formation and remodeling. Therefore, the aim of this study was to evaluate possible differences in serum levels of BMP-2, BMP-4, and TGF-beta1 in patients with normal and delayed fracture healing. 103 patients with diaphyseal fractures of long bones were recruited prospectively. Peripheral blood samples were collected over a period of 6 months following a standardized time schedule. At the end of the individual investigation period, growth factor serum levels were measured using commercially available enzyme immunoassays. For the elimination of disturbing influences, patients in both groups were matched by gender, age, fracture type, and localization as well as applied technique of osteosynthesis. During a study period of 1 year, 10 patients with an atrophic type of delayed union could be retrieved and matched to 10 patients with normal fracture healing. The diagnosis of delayed union was assumed in case of failed consolidation 4 months after trauma. We found an increase of TGF-beta1 serum levels up to 2 weeks after fracture in both groups with a following return to the reference value within 6 weeks after trauma. However, decline of serum concentration occurred earlier in patients with delayed fracture healing. At 4 weeks after trauma, serum levels of TGF-beta1 were significantly lower in patients of the delayed union group. Serum levels of BMP-2 and BMP-4 were below detection level in all patients, respectively. These findings support the critical role of TGF-beta1 in fracture healing. Events during the consolidation phase seem to be dependent on sufficient availability of TGF-beta1.

Biomarkers↗

Online process control for directional solidification by ultrasonic pulse echo technique.

A method of controlling the actual growth velocity during directional solidification based on ultrasound has been developed. For this purpose a pulse echo technique is used to measure the actual solidification rate online. This quantity is used to control the furnace velocity. Solidification experiments with metallic alloys and constant furnace velocity often result in non-steady actual solidification rates. Experiments carried out with online process control demonstrate that a really steady-state solidification with a constant solidification rate is achieved.

Journal Article↗

Soil-to-grain transfer of fallout 137Cs for 28 winter wheat cultivars as observed in field experiments.

In order to find wheat cultivars with a minimum soil-to-grain transfer of fallout (137)Cs, 28 winter wheat cultivars were investigated at 3 different sites with different soil types in Bavaria, Germany. Each cultivar was grown on an area of 10 m(2) and harvested in August 1999. The soil-to-grain concentration ratios (C(r)) of (137)Cs varied by a factor of up to 3 from cultivar to cultivar at a given site and from site-to-site for a given cultivar. The mean C(r) values at the three sites, 4.2 x 10(-4), 4.9 x 10(-4) and 7.5 x 10(-4), differed significantly. The fact that no cultivar showed similar C(r) values at the three sites indicates a strong influence of the soil on C(r). The cultivars Flair, Kornett and Previa showed a minor uptake of (137)Cs compared with the mean of all cultivars at each site. Unlike (137)Cs, the (40)K concentrations in the wheat grains varied only within a small range (122-190 Bq kg(-1)) at each site, which is due to the potassium regulation by the plants. For both radionuclides, the differences between the root uptake characteristics of the cultivars may not only be explained by an inter-cultivar variability due to genetic differences between the cultivars, but also by an intra-cultivar variability due to different soil conditions.

Cesium Radioisotopes↗

[Clinical usefulness and perspectives of sentinel node biopsy in the management of breast cancer].

INTRODUCTION: In view of its predictive potential, axillary nodal status plays a particularly important role in breast cancer. The concept of sentinel node biopsy (SNB) revealed an accurate method with low postoperative morbidity for staging the axilla in patients with lymph node-negative breast cancer. The aim of this study was to show that SNB alone must have a place in routine clinical work and is reliable after preoperative chemotherapy (PC) and also in patients with multicentric tumors (MC). PATIENTS AND METHOD: Between April 1997 and March 2002, a total of 300 SNBs were performed in patients with uni- or bilateral breast cancer. Of them, 45 who had completed PC and 13 with multicentric lesions underwent SNB followed by axillary dissection. The sentinel nodes (SN) were labelled with a blue dye and radioactive colloids. Median follow-up was 33.6 months (range 8.2-67.0) (StAw 1.4). RESULTS: The detection rate in the learning phase was 81.8% and later 93.5%, independently of the size of the primary tumor. Overall accuracy and negative predictive value of the first 55 patients, after PC and in those with MC came to 97.8% and 96.7%, 97.6%, 95.8% and 100%, respectively. Through focused pathologic examination, staging was improved in 11.3% of patients. A year after the procedure, one patient developed recurrence. Morbidity after SNB alone was significantly lower than after axillary dissection. CONCLUSION: Our experience shows SNB to be reliable and accurate for axillary staging in breast cancer patients. Morbidity after SNB alone was low. Conclusive data on the local recurrence rate are not yet available. Under certain conditions, SNB appears to have future clinical potential, even in patients with PC and MC, which must be confirmed in further multicentric studies. In the meantime, this method has attained definite value in the surgical therapy of breast cancer patients.

Adult↗

Expression of beta hCG and alpha CG mRNA and hCG hormone in human decidual tissue in patients during tubal pregnancy.

We recently showed that endometrial tissue produces hCG during the secretory phase of the menstrual cycle. Based on these findings, we hypothesized that the decidua should also be able to secrete hCG. We examined the decidualized endometrium of patients with extrauterine pregnancies. Decidual specimens were obtained for mRNA extraction and paraffin embedding from 24 patients that were between weeks 6-11 of tubal pregnancy. Tissues were evaluated and classified into one of three groups based on the endometrial differentiation that took place prior to conception: (A) high secretory transformation, (B) diminished transformation with restricted decidualization and (C) inferior endometrial proliferation. Decidual gland hCG secretion was demonstrated immunohistochemically and by Western blotting. Serum hCG levels were higher (P < 0.0001) in patients from group A than group C. mRNA expression of both the beta subunit (beta-hCG) and alpha subunit (alpha-CG) was determined by RT-PCR. Furthermore, the specificity of beta-hCG amplification was confirmed by restriction enzymes. beta-LH amplification was not found. Moreover, the degree of endometrial transformation and the level of decidualization was found to correlate with hCG hormone staining and beta-hCG mRNA expression. hCG protein in the decidua was present in the glands of the compact layer and in the spongy layer, and was more pronounced in previously transformed high secretory endometrium than in inferior endometrium. In conclusion, this study provides the first evidence that hCG is produced in the decidua of patients during extrauterine pregnancies and might play a possible paracrine role.

Chorionic Gonadotropin↗

[Rapid induction of withdrawal with opiate antagonists under anesthesia: an alternative to treatment of opiate dependence?].

Rapid induction of withdrawal by opiate antagonists under anesthesia is an opiate detoxification technique. This technique is useful to reduce intensity and duration of withdrawal. Therefore, this technique represents an alternative strategy in the treatment of opiate addicted patients. This paper attempts to present a brief history of this technique, and a critical review of related issues.

Anesthesia, General↗

Shoulder-arm morbidity following axillary dissection and sentinel node only biopsy for breast cancer.

AIMS: The purpose of this study was to examine the outcome of shoulder-arm morbidity in patients with breast cancer after various axillary staging procedures. We used a new specific summation score to compare conventional axillary node dissection (AD) and sentinel node only biopsy for postoperative shoulder-arm morbidity. METHODS: Eighty-five patients undergoing conventional AD and 66 patients undergoing sentinel node biopsy were evaluated both subjectively (questionnaire) and objectively (clinical examination) for reduced muscle strength, limited range of motion, lymphedema and pain, dysesthesias and loss of sensitivity. The symptoms elicited were rated by their severity with a single summation score describing all symptoms reported. RESULTS: Subjective evaluation of patients undergoing breast conserving surgery showed a highly significant difference in favor of SNB only (P< or =0.002). On clinical examination the outcome of patients with SNB only was also significantly or highly significantly better (difference in arm volume:P =0.007; difference in arm muscle strength: P=0.016; loss of sensitivity: P<0.001). Of a total score of 100 (=no symptoms), the mean for AD patients was 80.2 vs 92.8 for SNB patients (P=0.001). In patients undergoing total mastectomy the difference was only significant for pain sensations and total scores. CONCLUSIONS: SNB appears to reduce morbidity. Summation scores are a suitable and practicable tool for describing the symptoms associated with axillary surgery.

Arm Injuries↗

Is sentinel lymph node biopsy reliable and indicated after preoperative chemotherapy in patients with breast carcinoma?

BACKGROUND: Many studies support the concept and accuracy of sentinel lymph node biopsy (SNB) for staging patients with breast carcinoma, which can be performed with low morbidity in lymph node negative patients. Preoperative chemotherapy (PC) plays an important role in the treatment of patients with operable breast carcinoma and is another approach with which to reduce radical surgery in patients with more advanced disease. It is of interest whether the sentinel lymph node accurately represents the axillary status after PC and, thus, whether the sentinel node concept can be applied to both groups. METHODS: Thirty-three patients underwent SNB after chemotherapy and prior to axillary lymph node dissection. RESULTS: The average greatest tumor dimension before chemotherapy (33 mm +/- 2 mm) was significantly larger (P = 0.000) than after therapy (20 mm +/- 3 mm). Histopathologic complete remission was seen in only three patients. One or two sentinel lymph nodes (average, 1.7 lymph nodes) were identified with certainty in 29 of 33 procedures and accurately predicted axillary lymph node status in all of these patients. Breast-conserving surgery was possible in 21 patients (64%), and axillary lymph nodes were involved in 22 patients (67%). CONCLUSIONS: Even after patients undergo PC, SNB seems to be a reliable method for accurate staging of the axilla in those more advanced breast carcinoma. Thus, axillary dissection may be avoided in certain patients. Lymph node involvement seems to be likely in women with suspicious axillary findings before chemotherapy who have no visible sentinel lymph nodes on preoperative lymphosintigraphy and in patients without recurrent tumors. Further investigation of the SNB concept in this patient group should be evaluated in larger studies.

Adult↗

Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled and antagonize Wnt signaling.

Wnt signals control cell fate decisions and orchestrate cell behavior in metazoan animals. In the fruit fly Drosophila, embryos defective in signaling mediated by the Wnt protein Wingless (Wg) exhibit severe segmentation defects. The Drosophila segment polarity gene naked cuticle (nkd) encodes an EF hand protein that regulates early Wg activity by acting as an inducible antagonist. Nkd antagonizes Wg via a direct interaction with the Wnt signaling component Dishevelled (Dsh). Here we describe two mouse and human proteins, Nkd1 and Nkd2, related to fly Nkd. The most conserved region among the fly and vertebrate proteins, the EFX domain, includes the putative EF hand and flanking sequences. EFX corresponds to a minimal domain required for fly or vertebrate Nkd to interact with the basic/PDZ domains of fly Dsh or vertebrate Dvl proteins in the yeast two-hybrid assay. During mouse development, nkd1 and nkd2 are expressed in multiple tissues in partially overlapping, gradient-like patterns, some of which correlate with known patterns of Wnt activity. Mouse Nkd1 can block Wnt1-mediated, but not beta-catenin-mediated, activation of a Wnt-dependent reporter construct in mammalian cell culture. Misexpression of mouse nkd1 in Drosophila antagonizes Wg function. The data suggest that the vertebrate Nkd-related proteins, similar to their fly counterpart, may act as inducible antagonists of Wnt signals.

Adaptor Proteins, Signal Transducing↗

Heart luxation through a right-sided traumatic pericardial defect.

A traumatic defect of the pericardium is a rarely diagnosed entity. We present a patient with a right-sided luxation of the heart which was incidentally diagnosed during a thoracic CT performed for other reasons. Despite of the threatening strangulation of the great vessels, the patient had a stable circulation until surgical repair of the pericardial defect.

Adult↗

Minimally invasive operation techniques for inguinal hernia: spectrum of indications in Austria.

At the beginning of the 1990s, the introduction of endoscopic surgery led to the surgical treatment of hernias being reconsidered. At present, there are three groups of surgical procedures: conventional procedures (Shouldice, Bassini), open, tension-free mesh procedures (Lichtenstein, Gilbert, Rutkow) and endoscopic procedures, predominantly transabdominal preperitoneal hernioplasty (TAPP) and total extraperitoneal hernioplasty (TEP). The debate about the optimum treatment for hernias provoked by the endoscopic procedures is understandable in view of the large number of hernia operations performed. Numerous studies, some randomised, have demonstrated both advantages and disadvantages for the individual surgical procedures. In addition to the recurrence and complication rates, the cost factor and socio-economic aspects of the operations are playing an increasingly important role in deciding which method should be used. In December 1995, Austrian surgeons concerned with the problems of hernia repair both before and since the introduction of laparoscopic hernia repair came together for a consensus conference. During the meeting, the relevant aspects were summarised and a range of indications were established for surgical interventions. The main recommendation was that conventional open surgery, which can be performed under local anaesthesia, is indicated in unilateral uncomplicated primary hernias. Endoscopic hernioplasty is indicated if the contralateral findings are inconclusive or the hernia is bilateral or recurrent. The Zürser Hernienforum (Zürs Hernia Forum) has now been founded. The function of this forum is to carry out a prospective randomised study of inguinal hernia surgery throughout Austria.

Austria↗