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Biomedical subjects

C Maier

Publications and source records attributed to C Maier.

At least 19 recordsLinked to original sources

The release of the adipocytokine visfatin is regulated by glucose and insulin.

AIMS/HYPOTHESIS: The novel insulin-mimetic adipocytokine visfatin has been linked to the metabolic syndrome, but its regulation has not been characterised to date. Since insulin-mimetic actions of visfatin may be part of the feedback regulation of glucose homeostasis, we hypothesised that visfatin concentrations are influenced by glucose or insulin blood levels in humans. SUBJECTS, MATERIALS AND METHODS: In this randomised, double-blind, placebo-controlled crossover study, nine healthy male subjects (age 26+/-6 years) attended three different study days. On each day, systemic glucose concentrations of 5.0, 8.3 and 11.1 mmol/l were attained by stepwise increases in i.v. infusions of glucose, representing fasting and postprandial conditions. Visfatin plasma concentrations were studied during concomitant exogenous hyperinsulinaemia, inhibition of endogenous insulin production by somatostatin infusion, and placebo time control. Additionally, human adipocytes were cultured to study visfatin release and mRNA expression in vitro. RESULTS: Glucose concentrations of 8.3 and 11.1 mmol/l increased circulating visfatin from baseline concentrations of 0.5+/-0.0 ng/ml to 0.9+/-0.1 and 2.1+/-0.3 ng/ml, respectively (p<0.01). Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p<0.05). Cultured subcutaneous and visceral adipocytes released an equivalent amount of visfatin upon glucose-concentration- and time-dependent stimulation. Visfatin secretion involved the phosphatidylinositol 3-kinase (PI3-kinase) and protein kinase B (AKT) pathways. The mRNA expression pattern of visfatin was consistent with this altered protein release. CONCLUSIONS/INTERPRETATION: Circulating visfatin concentrations are increased by hyperglycaemia. This effect is suppressed by exogenous hyperinsulinaemia or somatostatin infusion. Glucose signalling for visfatin release in adipocytes involves the PI3-kinase/AKT pathway.

Adipocytes↗

Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): standardized protocol and reference values.

The nationwide multicenter trials of the German Research Network on Neuropathic Pain (DFNS) aim to characterize the somatosensory phenotype of patients with neuropathic pain. For this purpose, we have implemented a standardized quantitative sensory testing (QST) protocol giving a complete profile for one region within 30 min. To judge plus or minus signs in patients we have now established age- and gender-matched absolute and relative QST reference values from 180 healthy subjects, assessed bilaterally over face, hand and foot. We determined thermal detection and pain thresholds including a test for paradoxical heat sensations, mechanical detection thresholds to von Frey filaments and a 64 Hz tuning fork, mechanical pain thresholds to pinprick stimuli and blunt pressure, stimulus/response-functions for pinprick and dynamic mechanical allodynia, and pain summation (wind-up ratio). QST parameters were region specific and age dependent. Pain thresholds were significantly lower in women than men. Detection thresholds were generally independent of gender. Reference data were normalized to the specific group means and variances (region, age, gender) by calculating z-scores. Due to confidence limits close to the respective limits of the possible data range, heat hypoalgesia, cold hypoalgesia, and mechanical hyperesthesia can hardly be diagnosed. Nevertheless, these parameters can be used for group comparisons. Sensitivity is enhanced by side-to-side comparisons by a factor ranging from 1.1 to 2.5. Relative comparisons across body regions do not offer advantages over absolute reference values. Application of this standardized QST protocol in patients and human surrogate models will allow to infer underlying mechanisms from somatosensory phenotypes.

Adolescent↗

[A new parallel drill guide for navigating femoral neck screw placement. Development and evaluation].

BACKGROUND: Trauma navigation applications employ conventional mechanical surgical instruments for the simulation of drilling trajectories. Few complex mechanical targeting instruments, such as guides with fixed angles or with multiple parallel cannulas, have been adapted into trauma navigation systems. We have integrated a complex mechanical tool, the parallel drill guide (PDG) for the minimally invasive treatment of femoral neck fractures, into a trauma navigation module. The combined advantage of a complex yet commonly used mechanical tool with the benefits of fluoroscopic navigation was evaluated. MATERIAL AND METHODS: To adapt the conventional PDG to a fluoroscopic navigation system, the instrument was fitted with a non-detachable reflective marker array. Navigation engineers developed custom software to enable visualization of the navigated PDG. A comparison of conventional versus navigated PDG techniques was performed on plastic bone models and cadavers. No software or mechanical failures occurred with the navigated PDG procedures. RESULTS: While the total operative time was 30% more with navigation compared with conventional techniques, the total radiation time for the navigated group was reduced by more than 60%. This study demonstrates the successful integration of a cannulated parallel drill guide with a fluoroscopic navigation system. CONCLUSION: The continuous display of the complex PDG mechanical instrument, with multiple parallel virtual trajectories, enables safe and accurate parallel screw placement. The integration of complex mechanical instrumentation with navigation for the accurate placement of hardware represents an attractive direction in multiple trauma applications.

Bone Screws↗

[Prospective evaluation of prostate cancer screening in men with a family history of the disease].

BACKGROUND: Family history is one of the strongest risk factors for prostate cancer. In this prospective study we evaluated the results of prostate cancer screening performed in healthy brothers of prostate cancer patients. The detection rate of prostate cancer and the positive predictive value of the examinations were determined. MATERIAL AND METHODS: The study population comprised 513 healthy men who were 38-75 years of age (median 62.0 years). Of these men, 268 having only one affected brother with prostate cancer were assigned to the sporadic group, and 245 probands having 2-10 affected relatives were assigned to the familial group. An abnormal PSA and/or a pathological digital rectal examination (DRE) was noted in 17.5% of familial (43/245) and 15.8% of sporadic probands (35/268). A biopsy of the prostate was performed in 60.5% of familial (26/43) and 71.4% of sporadic (25/35) men with pathological findings. RESULTS: Prostate cancer was found in 15 of 26 familial (57.7%) and 16 of 25 sporadic (64.0%) probands by prostate biopsy. The overall detection rate was 6.0% (31/513). CONCLUSION: Due to an increased prevalence the detection rate of prostate cancer and the positive predictive value of PSA and/or DRE are higher in men with a family history as expected in an unselected population. Our data suggest that in predisposed men prostate cancer screening should be recommended early. Furthermore an early indication for prostate biopsy is necessary. This recommendation should also be applied if only one first-degree relative has prostate cancer.

Adult↗

Effect of a pocket-size tablet-dispensing device on glycaemic control in Type 2 diabetic patients.

AIM: To evaluate whether a pocket-size tablet-dispensing device would improve adherence to therapy as judged by reduction of HbA(1c) levels in a large population of Type 2 diabetic patients. METHODS: The study design was prospective, randomized, open label with two parallel groups. Patients (2296) were recruited from general practitioners and internists and randomized to either receive a tablet dispenser (TD) or no intervention (control group, CO). Patients' characteristics and current oral therapy (including dosage) were recorded at baseline. HbA(1c) was compared between groups at baseline and after 6 months' intervention. RESULTS: Data were available in 2081 patients. Baseline characterisitcs, including age, body mass index (BMI), blood pressure and gender distribution were comparable between the two groups, as was HbA(1c)[7.9 (7.9-8.0), TD vs. 8.0 (7.9-8.0)%, CO, means (95% CI)]. After 6 months, HbA(1c) improved in both groups, but improvement was significantly greater in TD than in controls [-0.74 (0.67-0.80) vs. -0.53 (0.47-0.59)%, P < 0.0001]. Possession of a dispenser remained an independent predictor of improved control in a multiple regression model. In the subgroup analysis, the effect was significantly more pronounced (i) in patients receiving more medications and (ii) more diabetes medications per day (iii) in younger patients. CONCLUSION: In this large study population in a 'realistic' setting, a simple tablet-dispensing device led to a significant and clinically relevant improvement in HbA(1c) levels. Because patients with a more complex therapy regimen benefited more, we suggest that TD might have improved adherence to therapy.

Administration, Oral↗

Mutation screening and association study of RNASEL as a prostate cancer susceptibility gene.

To date, germline mutations have been found in three candidate genes for hereditary prostate cancer: ELAC2 at 17p11, RNASEL at 1q25 and MSR1 at 8p22. RNASEL, encoding the 2',5'-oligoadenylate-dependant RNase L, seems to have rare mutations in different ethnicities, such as M1I in Afro-Americans, E265X in men of European descent and 471delAAAG in Ashkenazi Jews. In order to evaluate the relevance of RNASEL in the German population, we sequenced its open reading frame to determine the spectrum and frequency of germline mutations. The screen included 303 affected men from 136 Caucasian families, of which 45 met the criteria for hereditary prostate cancer. Variants were analysed using a family-based association test, and genotyped in an additional 227 sporadic prostate cancer patients and 207 controls. We identified only two sib pairs (1.4% of our families) cosegregating conspicuous RNASEL variants with prostate cancer: the nonsense mutation E265X, and a new amino-acid substitution (R400P) of unknown functional relevance. Both alleles were also found at low frequencies (1.4 and 0.5%, respectively) in controls. No significant association of polymorphisms (I97L, R462Q and D541E) was observed, neither in case-control analyses nor by family-based association tests. In contrast to previous reports, our study does not suggest that common variants (i.e. R462Q) modify disease risk. Our results are not consistent with a high penetrance of deleterious RNASEL mutations. Due to the low frequency of germline mutations present in our sample, RNASEL does not have a significant impact on prostate cancer susceptibility in the German population.

Aged↗

[Is the prostate cancer screening behaviour of men with familial predisposition predictable?].

Little is known about the motives of German men to attend or refuse preventive checkups for prostate cancer. The aims of this study were to investigate if in men with familial predisposition screening behaviours are influenced by epidemiological or clinical parameters of prostate cancer of their affected relatives. 476 probands with one and 312 probands with at least two affected relatives were advised in writing to have a PSA-test and DRE done at their local urologists. We evaluated if the response rate was correlated to the proband's age, to the number and the age of onset of their affected relatives and also to the clinical course of their disease. Our data implicate that in men with familial predisposition the acceptance of prostate cancer screening is influenced only by individual characteristics and personal attitude and not by factors within the family. To which extent the awareness of disease risk is modified by familial predisposition remains to be evaluated.

Adult↗

[Neurological complications and loss of efficacy with intrathecal pain therapy].

In a new guideline issued by the German Association for the Study of Pain, intrathecal opioid therapy is described as proven to be effective with relatively few side effects. We reviewed this statement by analysis of the available literature and critical evaluation of the clinical course in a few of our own patients (n=3). In these cases (as well as in a further eight patients), explantation and a switch to oral opioids led to distinctly better alleviation of pain and abatement of the unwanted effects. The problems we discuss do not appear to be rare instances, but by all means complications that are frequently described. The long-term efficacy of intrathecal opioids has not been adequately verified; moreover, their potency is not high. The frequency of undesired events is comparable to that of oral opioid medication, but serious neurological complications are possible. To avoid dose escalations and to recognize neurological complications in time, diligent monitoring by the surgeon or an experienced pain center is essential.

Administration, Oral↗

[German Acupuncture Trials (gerac) address problems of methodology associated with acupuncture studies].

OBJECTIVE: Conflicting or ambivalent findings on the effectiveness of body acupuncture in pain treatment are often attributed to flaws in study methodology. The paper describes the methodology used for the German Acupuncture Trials (gerac), which demonstrates that it is possible to design acupuncture studies in accordance with the standards of good clinical practice. METHOD: Approximately 1000 chronic pain sufferers per indication (migraine, tension-type headache, low back pain (cLBP), or gonarthrosis) are randomly allocated to one of three treatment groups (verum acupuncture, sham acupuncture, or established conservative therapy). Patients are blind to the type of acupuncture. All patients receive ten sessions of treatment (two per week) with an option of adding five more treatments in cases of slight but insufficient improvement (number of headache days or von Korff pain score). Participating physicians are in private practice, representing a variety of specialties. All have completed at least a 140-hour training course in acupuncture. Mandatory and optional verum and sham points are predefined. The point selection is individualized according to the criteria of traditional Chinese medicine (TCM). Primary outcome measures are number of headache days per month, von Korff Graded Chronic Pain Scale or Hannover Functional Ability Questionnaire (cLBP), or WOMAC scores (gonarthrosis). Data are assessed by trained telephone interviewers not involved in treatment and blind to types of acupuncture. PRESENT STATUS: Over 500 participating physicians in ten urban areas of Germany. Patient recruitment for cLBP and gonarthrosis was completed in November 2003 and March 2004 respectively. Recruitment for chronic headaches will be completed in autumn 2004. CONCLUSIONS: The gerac trials prove that it is possible to design and carry out acupuncture studies in accordance to stringent standards of methodology and clinical practice. The results will form a basis for the assessment of acupuncture effectiveness in Germany and abroad.

Acupuncture Therapy↗

[Do physicians overestimate effects of acupuncture treatment?].

BACKGROUND: Physicians' ratings about their patients' pain prove to be invalid compared to patients' ratings. This is especially true if pain rating acts as an indicator for therapy outcome. The aim of this study was to compare physicians' and patients' ratings of pain relief following acupuncture and to identify correlations between patient characteristics and potential miscalibrations. PATIENTS AND METHODS: In a cross-sectional study 291 pain patients with gonarthrosis or chronic low back pain and their attending physicians were asked to give their rating of patients' pain relief following acupuncture. Patients were interviewed by telephone, and doctors responded to questionnaires. RESULTS: The proportion of false-positive physicians' ratings was 81% referring to patients without self-reported benefit from acupuncture. Just every fifth patient without pain relief was correctly classified by his physician. There was no correlation between patients' characteristics and false-positive ratings of physicians. CONCLUSIONS: Evaluation of treatment in daily medical routine should be primarily based on information provided by patients.

Acupuncture↗

[Risk factors for substance abuse and dependence in opioid therapy for chronic noncancer-related pain].

Opioids are valuable analgesics, capable of providing pain relief and functional improvement not only in patients with cancer-related pain, but also in chronic noncancer-related pain patients. However, recent data have shown that the increasing prescription of opioids is associated with a rise in aberrant drug-related behaviour. The causes of this behaviour are multifactorial. Some pharmacotherapeutic, but in particular psychosocial risk and etiologic pain factors have been identified. The indication for the prescription of opioids must be very carefully weighed in the presence of any risk factors. In these cases the integration into a multimodal, interdisciplinary therapy programme is mandatory. A contractual agreement on the opioid therapy including goals, side effects, controls including urine drug testing and criteria to finish the opioid therapy are advisable. Assessment of the progress of therapy is based on the following factors: analgesic efficacy, adverse side effects, functional status and aberrant drug-related behaviour. In the absence of a successful opioid therapy, the treatment must be discontinued to avoid iatrogenic damage, substance abuse and illegal diversion. After discontinuation of the therapy, a comprehensive interdisciplinary re-evaluation is required.

Analgesics, Opioid↗

[Long-term efficiency of opioid medication in patients with chronic non-cancer-associated pain. Results of a survey 5 years after onset of medical treatment].

UNLABELLED: A total of 121 patients with at least a 3-year history of opioid use were evaluated by a standardized interview during a clinical visit or telephone call. Assessed items were the present and former drug medication, daily doses, withdrawals, contentment with the treatment, positive/negative treatment effects, average/maximum pain and others. STATISTICS: chi(2), ANCOVA and survival analysis. Of 121 patients (frequency of withdrawal 14.8% mainly due to lack of efficacy) with an average treatment time of 66 months (37-105 months; 80,264 days; 87% more than 5 years), 103 (85%) still took an opioid step II or III according to the WHO analgesic ladder. Patients further treated in the pain clinic stopped significantly less frequently than patients treated by GPs or other non-specialised physicians (5 versus 23%). Patients with long-term opioid intake revealed significantly lower pain intensity and higher contentment with the pain management and achieved improvement (global, quality of life and physical state). Changes of opioid dosages during the 5 years were inconsistent (no change 33%, decrease 16%, slight increase 27%, high increase 19%). However, the number of patients with high dose increased from 6 to 23 due to significant loss of efficacy (proved in the morphine subgroup, p<0.05). The survey demonstrates a very low frequency of withdrawal in patients with long-term opioid medication after initial response without evidence for tolerance development, especially if their treatment is controlled in a pain centre.

Analgesics, Opioid↗

Radiosensitivity detected by the micronucleus test is not generally increased in sporadic prostate cancer patients.

The micronucleus test (MNT) has shown increased micronuclei (MN) frequencies in BRCA associated and sporadic breast cancer patients, Ataxia telangiectasia and Nijmegen Breakage Syndrome patients, demonstrating a common cellular phenotype of increased radiosensitivity. Some genes, causative of these diseases, have also recently been associated with prostate cancer. In order to investigate if prostate cancer exhibits the cellular phenotype of increased radiosensitivity, we performed MNT analysis on 22 sporadic prostate cancer patients and 43 male controls. We determined the baseline MN frequency, in order to see in vivo chromosomal damage without radiation, and induced (after irradiation with 2 Gy) frequency of MN, both in binucleated cells (BNC) obtained from cultured peripheral blood lymphocytes. An automated image analysis system was used to score the MN employing two different classifiers (Classifier A and B) for detection of BNC. The mean baseline frequencies were 48/43 MN/1000 BNC (A/B) for the controls and 42/50 (A/B) for prostate cancer patients. The induced MN frequencies amounted to 107/111 MN/1000 BNC (A/B) for controls and 111/114 MN/1000 BNC (A/B) for prostate cancer patients. The obtained MN frequencies did not result in a statistically significant difference between unselected cases and controls. However, restricting the analysis to young patients (50-60 years, N = 7) and age-matched controls (N = 7) revealed marginally significant higher MN frequencies in patients. We conclude that increased radiosensitivity is not a property of prostate cancer patients in general.

Aged↗

[Pain treatment facilities in Germany. Ambulatory, day care and inpatient facilities for patients with chronic pain].

Specialised pain treatment is available at inpatient, daycare and outpatient units at hospitals in Germany. A total of 579 hospitals in Germany offer at least one of the three pain treatment options. The main treatment involves outpatient care, but inpatient wards and daycare institutions have become more common. The type and number of pain treatment facilities differ regionally. Five of the 16 counties do not officially offer inpatient care at all, although pain treatment sites have been opened on the initiative of the hospitals themselves. Since specialised pain treatment is insufficiently defined by diagnosis (ICD-10) or procedures (OPS) in the German DRG system, it is not possible to recognise its availability when the facilities are not officially named. Pain treatment should be differentiated dependent on whether patients are treated within a single area of expertise or by specialised multi-professional pain facilities. At hospitals, systematic multimodal pain treatment is possible. Inpatient and daycare pain treatment programs are suitable when outpatient treatment has failed. An overview of the pain therapies offered is a prerequisite for their optimal use, the demonstration of their necessity and for their continued development throughout Germany. This study was planned and supervised by the commission for quality assurance of the German IASP chapter and was sponsored by the German IASP chapter.

Chronic Disease↗

[Visual cortex in the Tolosa-Hunt syndrome. Functional imaging for the detection of a psychogenic disorder--a case report].

Besides painful ophthalmoplegia, patients suffering from Tolosa-Hunt syndrome often present increasing loss of visual perception. The impairment of the optic nerve leads to a delay of the VEP (visual evoked potentials) responses. Using the method of magnetic resonance imaging (MRI), some patients present unspecific alterations in the vicinity of the optic nerve. However, both methods (VEP and MRI) are unsuitable to assess the effect of an impaired optic nerve function on neuronal processing in the visual cortex. We report one patient suffering from Tolosa-Hunt syndrome affecting the optic nerve. We used fMRI (functional magnetic resonance imaging) to show how this impairment of the optic nerve alters cortical processing of visual information. The activity of the unaffected visual cortex was bilaterally reduced when compared to healthy volunteers but greater that obtained from patients suffering from bilateral occipital infarction. Our results offer new opportunities to assess the efficiency of therapy in patients with increasing loss of visual perception due to the Tolosa-Hunt syndrome. Further studies are necessary to investigate, whether fMRI also provides the possibility to assess the efficiency of drug therapy on optic nerve function.

Humans↗

Acute exercise has no effect on ghrelin plasma concentrations.

Exercise is a potent, dose-dependent stimulus of growth hormone (GH) secretion. The hypothalamic peptides, GH-releasing hormone (GHRH) and somatostatin are regarded as major regulators of this stimulation. The role of the stomach-derived peptide ghrelin, which has been shown to exert strong GH releasing effects, has not been fully characterized yet. We therefore studied GH and ghrelin plasma concentrations in response to graded levels of exercise in eight healthy young volunteers. After determination of their individual maximal exercise capacity, all individuals underwent a treadmill exercise at 50 %, 70 %, and 90 % of maximum oxygen consumption (VO (2)max) on different days. Maximal GH response to exercise was observed after 40 minutes at 50 % VO (2)max and after 20 minutes at 70 and 90 % VO (2max). GH serum concentrations increased significantly at all three exercise intensities (GH peak concentrations were 5.8 +/- 2.3 ng/ml, 12.0 +/- 3.2 ng/ml, and 9.8 +/- 4.7 ng/ml, respectively). In contrast, ghrelin plasma concentrations remained unchanged at all three workloads. Assuming that the sensitivity of the GH neuroendocrine/metabolic regulation of GH is unaltered, ghrelin does not participate in the regulation of the GH response to exercise in healthy males.

Adult↗

Impact of laparoscopic adjustable gastric banding on plasma ghrelin, eating behaviour and body weight.

BACKGROUND: Plasma ghrelin, an orexigenic peptide derived from the stomach and duodenum, increases following weight loss and might contribute to weight regain. The aim of the present study was to evaluate the effect of laparoscopic adjustable gastric banding (LAGB) on body weight and body composition as well as plasma ghrelin in relation to eating behaviour in morbidly obese patients. MATERIALS AND METHODS: This study was performed in 23 morbidly obese subjects who underwent standardized LAGB. Fasting plasma ghrelin was measured before and 6 months after surgery and was correlated with body weight, body composition, and eating behaviour. RESULTS: Six months after LAGB, body weight decreased significantly by -15.7 +/- 1.4 kg (mean +/- SEM, P = 0.0001) which was accompanied by an increased cognitive restraint of eating (P = 0.001), and by a decreased disinhibition of eating and susceptibility to hunger (P = 0.0001). Plasma ghrelin increased (P = 0.016) by 27.2% from 100.39 +/- 12.90 to 127.22 +/- 13.15 fmol mL(-1). The change in plasma ghrelin correlated with changes in body weight (r = -0.49, P = 0.02), BMI (r = -0.42, P = 0.048) and fat mass (r = -0.519, P = 0.013), but not with changes of fat-free mass and of the three dimensions of eating behaviour. CONCLUSION: Weight loss following LAGB leads to an increase in fasting plasma ghrelin and is accompanied by a decrease in hunger, disinhibition of eating and an increase in cognitive restraint. Thus, changes in eating behaviour, which promote reduction of food intake and not fasting ghrelin, determines weight loss achieved by LAGB.

Adolescent↗