Biomedical subjects

Richard Crevenna

Publications and source records attributed to Richard Crevenna.

At least 19 recordsLinked to original sources

PubMed2006

Mcl-1 is a relevant molecular target for antisense oligonucleotide strategies in gastric cancer cells.

Gastric cancer is the second most common cause of death from cancer worldwide and resistant to various chemotherapeutic regimens. In gastric cancer, the anti-apoptotic Mcl-1 protein is expressed in up to 75% of all cases and associated with poor prognosis. The biological relevance of Mcl-1 expression in gastric cancer is unclear. Thus, we investigated the functional significance and potential role of Mcl-1 as a molecular target in gastric cancer by using an antisense strategy. Gastric cancer cell lines (NCI-N87, MKN-28, MKN-45) were treated with Mcl-1 antisense oligonucleotides. Protein expression, cell growth and apoptosis were assessed for single-agent Mcl-1 AS oligonucleotide treatment and for combinations with docetaxel or cisplatin. Treatment by Mcl-1 AS oligonucleotides resulted in approximately 50% reduction in Mcl-1 protein levels in all gastric cancer cell lines examined. Surprisingly, dose-dependent Mcl-1 downregulation produced a significant increase in apoptosis and up to 60% decrease in cell growth. Moreover, combination of Mcl-1 AS oligonucleotide with docetaxel or cisplatin displayed synergistic anti-tumor activity. In conclusion, the impressive single-agent anti-tumor activity and the synergistic effect of Mcl-1 AS oligonucleotides in combination with chemotherapy might qualify Mcl-1 as a promising molecular target for AS oligonucleotide based treatment strategies for gastric cancer in the future.

Antineoplastic Agents↗

PubMed2006

Neuromuscular electrical stimulation for a patient with metastatic lung cancer--a case report.

A 47-year-old female patient suffering from advanced lung cancer with metastatic bone and brain disease participated in a passive exercise program, consisting of neuromuscular electrical stimulation (NMES) five times a week, carried out for 4 weeks. After the training period, the results of the 6-min walk (420 m before and 603 m after the training period) have improved by 44%, which demonstrates the increase of physical performance (mobility, endurance capacity). The results of the "Timed up and go" indicate an improvement of mobility and functional health of skeletal muscles. Furthermore, the quality of life (QOL)-scales (assessed by using the SF-36 health survey) "Physical functioning", "Role-physical", "Mental health", "Role-emotional", "Vitality", "Bodily pain", and "General health" showed improvements after the intervention period. Feasibility, safety, and beneficial effects of the NMES program were proven for the patient in this case study. These findings indicate that NMES, initiated and executed with appropriate care, may serve as a useful supportive means of palliative treatment in some patients with advanced cancer and metastatic disease, especially in cases of metastatic involvement of the brain and of the skeletal system with the risk of seizures and pathological fractures where volitional training is not allowed.

Bone Neoplasms↗

PubMed2006

First clinical experience with an automatic control system for rotary blood pumps during ergometry and right-heart catheterization.

BACKGROUND: At present, most clinically implanted rotary blood pumps are operated at constant speed and adjusted by the physician. It is generally assumed that an adaptation of pump speed to the patient's physiologic requirements would be beneficial. The data provided in this paper, based on hemodynamic and spirometric data during exercise in which a pre-load-sensitive control was used, lend quantitative support to this assumption. METHODS: An automatic speed control was developed and implemented with Matlab on a dSpace controller board. The system uses pump speed, pump power, and pump flow as its only input signals. It was connected to the clinical hardware of the DeBakey VAD System. The control is pre-load-sensitive and uses an expert system to detect excessive unloading and eventual suction. This system was used to quantify the cardiovascular reaction of patients to both automatically controlled and constant pump speed. A sub-group of 5 patients underwent bicycle ergometry with Swan-Ganz catheterization and spiroergometry. RESULTS: The automatic, closed-loop speed control showed robust and stable performance. It provided an increase in pump flow (+0.94 +/- 0.5 liters/min, p < 0.05) compared with constant-speed mode in response to physical activity. Pulmonary arterial (PAP) and capillary wedge pressure (PCWP) clearly decreased (-7.4 +/- 4.1 mm Hg for PAP and -8.3 +/- 4.2 mm Hg for PCWP, p < 0.05), and venous oxygen saturation moderately increased (+5.2%). CONCLUSION: An automatic speed-control system for rotary blood pumps was developed and demonstrated by spiroergometry to be appropriately responsive to physiologic demand.

Algorithms↗

PubMed2006

Aerobic capacity, muscle strength and health-related quality of life before and after orthotopic liver transplantation: preliminary data of an Austrian transplantation centre.

OBJECTIVE: Patients before orthotopic liver transplantation usually show a reduced physical performance status, which impacts on their daily life and social participation. This pilot study aimed to evaluate endurance capacity, muscle strength, and quality of life before and after orthotopic liver transplantation in patients in an Austrian transplantation centre. SUBJECTS: Fifteen patients (male/female = 10:5) were included in the pilot study. METHODS: Exercise testing, strength testing of knee extensor muscles and of handgrip, and quality of life (SF-36 health survey) were assessed before and after orthotopic liver transplantation (after 1-2 months). RESULTS: The oxygen uptake at the anaerobic threshold (VO2AT) and isokinetic strength testing of quadriceps femoris muscle did not change significantly from baseline, before transplantation to follow-up after orthotopic liver transplantation. Before orthotopic liver transplantation, quality of life was hampered concerning functional status, emotional role, vitality, and general health perception. Significant improvements of social functioning (p=0.032), vitality (p=0.006), mental health (p=0.004) and general health perception (p=0.002) could be found for this study population after orthotopic liver transplantation. CONCLUSION: The results of this pilot study including a population of an Austrian transplantation centre indicate deficits of physical performance as well as reduced quality of life in patients before and after orthotopic liver transplantation.

Adult↗

PubMed2005

Mcl-1 overexpression in hepatocellular carcinoma: a potential target for antisense therapy.

BACKGROUND/AIMS: Recently, the anti-apoptotic Mcl-1 protein has been reported as a resistance factor in various types of cancer. Here we investigated the presence of Mcl-1 protein in hepatocellular carcinoma (HCC) tissues and its potential role as a molecular drug target for HCC therapy. METHODS: HCC specimens of 149 patients were examined by immunohistochemistry for Mcl-1 expression. Antisense oligonucleotides (ASO) targeting Mcl-1 were evaluated as monotherapy and in combination with cisplatin in the HCC cell lines HepG2 and Snu398. Protein regulation, cell viability, and apoptosis were assessed by western blotting, cell counting, and FACS analysis. RESULTS: Mcl-1 protein is overexpressed in 51% of all cases irrespective of underlying disease. Targeting Mcl-1 by ASO specifically downregulated Mcl-1 protein expression and led to significant dose and time dependent single agent activity in HCC cells characterized by increased apoptosis and decreased cell viability. No significant target regulation or cell death was observed for control oligonucleotide treatment. Upon combination with cisplatin, Mcl-1 ASO revealed a significant chemosensitizing effect. CONCLUSIONS: Mcl-1 is overexpressed in half of HCC-tissues. ASO targeting Mcl-1 revealed a prominent single agent and chemosensitizing activity against HCC in vitro. Targeting Mcl-1 might qualify as a promising novel approach in HCC therapy.

Apoptosis↗

PubMed2004

Extracorporeal shockwave treatment is effective in calcific tendonitis of the shoulder. A randomized controlled trial.

BACKGROUND: Calcific tendonitis of the shoulder is often associated with chronic pain and impairment of function. Extracorporeal shockwave therapy (ESWT) is considered to be a treatment option. We compared the effects of two different ESWT regimens. METHODS: 43 patients (57 shoulders) with symptomatic calcific tendonitis of the shoulder for more than six months were included in a double-blinded study. Thirty-one shoulders were treated at the area of maximum pain with application of 2 x 2000 impulses of 0.28 mJ/mm2 at an interval of two weeks (treatment group) and 26 shoulders with 2 x 2000 impulses of < 0.07 mJ/mm2 at an interval of two weeks (control group), without pretreatment analgesia. Shoulder function (Constant score) and pain (visual analogue scale, VAS) were assessed before treatment and at one week, three months and seven months after treatment. Shoulder X-rays were performed at the 3- and 7-month follow-up visits. RESULTS: Improvement in Constant score was significantly higher in the treatment group at all follow-up visits (p < 0.05). Seven months post-treatment, calcifications dissolved completely in 19% of the treatment group and 8% of the control group, and a > 50% reduction was observed in 19% and 8% respectively. With regard to reduction of pain, there was significant improvement in the treatment group compared with the control group at the 1-week follow-up (p < 0.05). However, at the 3-month and 7-month visits, no significant between-group difference in pain could be detected. CONCLUSION: As applied, ESWT with an energy flux density of 0.28 mJ/mm2 led to a significantly greater improvement in shoulder function and a slightly higher, nonsignificant, rate of > 50% disintegration of calcific deposits compared with the control group. However, this did not result in reduction of pain.

Activities of Daily Living↗

PubMed2004

[The role of gender medicine in rehabilitation].

This article provides a coherent view of gender differences in rehabilitation medicine from the biological, individual and social perspective. It reports the role of gender in pain, in rehabilitation of the musculosceletal system and in rehabilitation of patients with prostate cancer.

Chronic Disease↗

PubMed2004

Beneficial effects of chronic low-frequency stimulation of thigh muscles in patients with advanced chronic heart failure.

AIMS: Patients with chronic heart failure (CHF) exhibit detrimental changes in skeletal muscle that contribute to their impaired physical performance. This study investigates the possibility of counteracting these changes by chronic low-frequency electrical stimulation (CLFS) of left and right thigh muscles. METHODS AND RESULTS: (mean+/-SD) 32 CHF patients (53+/-10 years) with an LVEF of 22+/-5%, NYHA II-IV, undergoing optimized drug therapy, were randomized in a CLFS group (CLFSG) or a control group (controls). The groups differed in terms of the intensity of stimulation, which elicited strong muscle contractions only in the CLFSG, whereas the controls received current input up to the sensory threshold without muscle contractions. Functional capacity was assessed by peak VO(2), work capacity, and a 6-min-walk (6-MW). Muscle biopsies were analyzed for myosin heavy chain (MHC) isoforms, citrate synthase (CS) and glyceraldehydephosphate dehydrogenase (GAPDH) activities. Peak VO(2)(mlmin(-1)kg -1) increased from 9.6+/-3.5 to 11.6+/-2.8 (P<0.001) in the CLFSG, and decreased from 10.6+/-2.8 to 9.4+/-3.2 (P<0.05) in the controls. The increase in the CLFSG was paralleled by increases in maximal workload (P<0.05) and oxygen uptake at the anaerobic threshold (P<0.01). The corresponding values of the controls were unchanged, as also the 6-MW values, the MHC isoform distribution, and both CS and GAPDH activities. In the CLFSG, the 6-MW values increased (P<0.001), CS activity was elevated (P<0.05), GAPDH activity decreased (P<0.01), and the MHC isoforms were shifted in the slow direction with increases in MHCI at the expense of MHCIId/x (P<0.01). CONCLUSIONS: Our results suggest that CLFS is a suitable treatment to counteract detrimental changes in skeletal muscle and to increase exercise capacity in patients with severe CHF.

Electric Stimulation Therapy↗

PubMed2004

Muscle strength as a predictor of long-term survival in severe congestive heart failure.

AIMS: The objective of the study was to test the relationship between isolated muscle strength and outcome, and its significance in the context of other exercise variables. METHODS AND RESULTS: 122 consecutive patients (LVEF 21+/-7%) were enrolled in the study. Isokinetic strength testing of the knee extensor and flexor muscles were performed. A subset of 51 patients underwent additional upright bicycle testing with gas exchange analysis. The outcome up to 60 months was defined by event-free survival (group A, n=59) or death (group B, n=34). Patients who had been transplanted were excluded from further analysis. The peak strength of the quadriceps muscle was comparable in both groups (N.S.). In contrast, the index (value adjusted for weight) did reveal significant differences (P<0.04), similar to the peak torque of the knee flexor muscle (P<0.04), whose index was even more significant with regard to differences (P<0.01). Multivariate analysis including muscle strength variables, pVO2 and workload into one model show that the flexor strength index is the only independent variable (x2=9 P<0.003). A cut-off point of 68 Nm x 100/kg in the strength index of the flexor muscles was used to establish a significant difference between groups with regard to outcome (P<0.01). Thus, the isokinetic strength of the knee flexor muscles is related to outcome. Moreover, this parameter is superior to variables such as peakVO2 and workload.

Aged↗

PubMed2004

Cross-cultural adaption of the Manniche questionnaire for German-speaking low back pain patients.

OBJECTIVE: To develop and validate a cross-cultural version of the Manniche Low Back Pain Rating Scale (MRS) for use in German-speaking low back pain patients. BACKGROUND: Clinical intervention research in back pain would be enormously facilitated if a small number of relevant, patient-centred questionnaires became internationally used. MRS seems to be particularly suitable for cross-cultural adaptation due to its coverage of multidimensional back pain-specific health domains. METHODS: MRS was translated and back-translated, pretested and reviewed by a committee. The German version was tested in 126 patients with low back pain from all countries of German-speaking Europe. Reliability (subsample n = 20), dimensionality and construct validity was assessed. Single-dimensionality, higher correlations of MRS with the physical scales compared with the mental scales of the MOS SF-36, a moderate to good correlation with the Roland Morris Questionnaire and a low correlation with the Finger Floor Distance were hypothesized. RESULTS: Spearman's Rho for test-retest reliability was 0.98 (p < 0.001); Cronbach's alpha 0.95. Factor analysis revealed only 1 factor with an Eigenvalue >1 [3.25]. MRS was strongly correlated with the Roland Morris Questionnaire (r = 0.91), and slightly correlated with the Finger Floor Distance (r = 0.23). Correlations of MRS with domains of the SF-36 "Physical Functioning", "Role Physical" and "Bodily Pain" were higher (r -0.66 to -0.72) than with "Role Emotional", "Mental Health" and "Social Functioning" (r -0.34 to -0.61). CONCLUSION: The German version of the MRS seems to be reliable, uni-dimensional and construct valid for the assessment of functional status in German-speaking low back pain patients.

Adult↗

PubMed2004

Long-term transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study.

Neuromuscular electrical stimulation (NMES) is an option for increasing thigh muscle strength and endurance capacity in patients with chronic heart failure. Electromagnetic interference (EMI) by the signals with sensing of implantable cardioverter defibrillators (ICDs) is possible. The aim of the present pilot safety study was to test the safety of a long-term NMES in patients with ICDs. Six patients with subpectoral ICDs were subjected to long-term NMES of thigh muscles. Four inpatients received NMES to increase muscle strength, and two outpatients performed NMES as a home treatment to increase endurance capacity. During long-term NMES, all patients together received 14 139 799 biphasic electrical pulses and 412 425 on-phases without adverse events. ICD function after the stimulation period revealed no abnormalities in any patient. These results indicate that long-term NMES of thigh muscles seems to be safe in patients with ICDs, providing that an individual risk is excluded before.

Aged↗

PubMed2003

Safety of a combined strength and endurance training using neuromuscular electrical stimulation of thigh muscles in patients with heart failure and bipolar sensing cardiac pacemakers.

Neuromuscular electrical stimulation (NMES) is an effective and non-strenuous therapy to enhance the strength and endurance capacity of the skeletal muscles in patients with severe chronic heart failure. NMES in patients with pacemakers is controversial because potential electromagnetic interference may result in pacemaker malfunction. Therefore, such patients are in general excluded from NMES. The aim of this pilot study was to evaluate the safety of a combined NMES protocol to increase strength and endurance capacity of the skeletal muscles in patients with heart failure and implanted pacemakers. Seven patients with chronic heart failure and implanted cardiac pacemakers with bipolar sensing leads received NMES treatment of thigh muscles, using a combined protocol comprising biphasic, symmetric, rectangular constant current impulses at different frequencies (8-50 Hz), pulse width up to 60 s (8 Hz), 4 s (15 Hz), 4 s (30 Hz), and 6 s (50 Hz), and amplitudes up to +/- 100 mA (all frequencies) applied to both knee extensor and flexor muscles via surface electrodes (8 x 13 cm each). Acute electromagnetic interference during a safety procedure (telemetric monitoring) before therapeutic NMES application was not observed in any of the patients. The 7 patients received during 20 therapeutic NMES sessions a total of 23,380 on-phases, comprising 2194.08 x 10(3) biphasic electrical pulses, without adverse events. Heart rate monitoring during stimulation and pacemaker interrogation revealed no abnormalities. NMES treatment of thigh muscles using a combined NMES protocol to enhance strength and endurance capacity appears to be safe in patients with heart failure and implanted pacemakers with bipolar sensing, as far as the described electrode configuration and parameter range is applied.

Adult↗

PubMed2003

Quality of life in patients with non-metastatic differentiated thyroid cancer under thyroxine supplementation therapy.

GOALS: When thyroid and other cancers are "cured" it is often assumed that the patients are able to resume their normal lives. This was a cross-sectional study to evaluate health-related quality of life (HRQOL) and to identify rehabilitation needs of patients with non-metastatic thyroid cancer under thyroxine supplementation therapy. PATIENTS AND METHODS: Included in the study were 150 consecutive patients with differentiated thyroid cancer (age 52 +/- 14 years, range 25-83 years; male/female 39/111). All patients had a history of total thyroidectomy followed by radioiodine ablation, were free of metastatic disease and under levothyroxine treatment. The mean period since the diagnosis of thyroid cancer was 5.5 +/- 6 years (range 0-23 years). Health-related quality of life was evaluated using the SF-36 Health Survey. The findings were compared with sex- and age-matched reference values. RESULTS: "Role-emotional" and "Vitality" were significantly lower ( P<0.001 and P<0.005, respectively) in the group as a whole ( n = 150). In the subgroup of patients with a recent (less than 1 year) diagnosis of thyroid cancer ( n = 51), however, the following subscales were significantly lower: "Mental Health" ( P<0.01), "Role-emotional" ( P<0.001), "Role-physical" ( P<0.005), "Social functioning" ( P<0.005) and "Vitality" ( P<0.001). Multiple regression analysis identified a significant positive correlation between "Mental Health", "Physical functioning", "Vitality", "Role-emotional" and "Social functioning" with the time since initial diagnosis, and there was also a positive correlation between "Physical functioning", "Bodily pain" and "Role-emotional" with male gender. CONCLUSIONS: These findings indicate that "Vitality", "Role-physical", "Mental Health", "Role-emotional" and "Social functioning" are significantly impaired during the first year after diagnosis. Thereafter, quality of life improves correlating with the time since initial diagnosis. However, "Vitality" and "Role-emotional" remain permanently impaired in thyroid cancer patients. A multidisciplinary rehabilitation concept should include psychological support and an early start to exercise to improve physical performance of these patients leading to better HRQOL and to help them fulfill their social role earlier.

Adult↗

PubMed2003

Appointments at a thyroid outpatient clinic and the lunar cycle.

INTRODUCTION: Several variables of health-related human behaviour have been analysed with regard to a possible association with lunar phases. The aim of this study was to evaluate a possible relation between the lunar cycle and the number of requests for appointments at an outpatient clinic. This variable has not been studied hitherto. METHODS: We analysed a total number of 11,413 requests for appointments at our thyroid outpatient clinic during one year. Access to this clinic is not restricted, and all patients with known or suspected thyroid disease living in the area of Vienna may ask for an appointment. During the study period, 8,852 patients requested a follow-up appointment, and 2561 patients asked for a new appointment. We analysed a possible cyclic pattern in these requests using a nonlinear regression model based on both groups of patients. RESULTS: A cosinus curve with a period of 29.531 days (the mean length of a lunar cycle) was significantly associated with the number of requests for both follow-up appointments (p = 0.007) and new appointments (p = 0.001). Requests for follow-up appointments had their highest peaks three days after the full moon, whereas requests for new appointments were most frequent five days afterwards. CONCLUSION: Our findings suggest that lunar phases may affect patients' requests for appointments at a thyroid outpatient clinic. To the best of our knowledge, this is the first study reporting a possible association between health-related behaviour and lunar phases using requests for appointments as a relevant variable. There is a need for more research into the mechanism underpinning this behaviour.

Appointments and Schedules↗

PubMed2003

Functional and biochemical properties of chronically stimulated human skeletal muscle.

The present study was undertaken to investigate in a randomized controlled trial the effects of chronic (10 weeks, 4 h per day, 7 days per week) low-frequency (15 Hz) stimulation (CLFS) of the knee extensor and hamstring muscles of both legs in healthy volunteers via surface electrodes. A control group (n=10) underwent the same treatment (sham stimulation) as the CLFS-treated group (n=10), except that stimulation intensity was kept at a level which did not evoke contractions. Biopsy samples were taken before the onset and after cessation of stimulation from the right vastus lateralis muscle of all subjects. The biopsy samples were analyzed for changes in myosin heavy chain (MHC) isoforms and activities of citrate synthase (CS) and glyceraldehyde phosphate dehydrogenase (GAPDH) as markers of aerobic-oxidative and anaerobic pathways of energy metabolism, respectively. In addition, functional properties, i.e., oxygen consumption (VO(2)) and work capacity, were assessed. Sham stimulation did not affect the functional properties and had no detectable effect on MHC isoform and enzyme activity patterns. Conversely, CLFS induced changes in the MHC isoform pattern in the fast-to-slow direction with an approximately 20% decrease in the relative concentration of MHCIId/x (from 28% to 22%) and an approximately 10% increase in the relative concentration of MHCI (from 30% to 34%). In addition, CLFS led to a approximately 9% increase in the activity of CS concomitant with an approximatley 7% decrease in the activity of GAPDH. This increase in aerobic-oxidative capacity was accompanied by improved work capacity and VO(2) at the anaerobic threshold by 26% and 20%, respectively.

Adult↗

PubMed2003

Electromagnetic interference by transcutaneous neuromuscular electrical stimulation in patients with bipolar sensing implantable cardioverter defibrillators: a pilot safety study.

Neuromuscular electrical stimulation (NMES) is a frequently applied therapy for the treatment of pain and a therapeutic option to increase thigh muscle strength and endurance capacity in patients with heart failure. Electromagnetic interference (EMI) by the signals with sensing of ICDs is possible. Eight patients with subpectoral ICD systems and different transvenous bipolar sensing leads were subjected to electrical stimulation of the neck and shoulder and of the thighs using different stimulation algorithms. EMI with ventricular sensing was detectable in three of eight subjects. EMI occurred during stimulation of the neck (n = 2) and thigh (n = 2). EMI by NMES with atrial sensing was seen in two of four subjects with dual chamber ICDs. The safety of peripheral NMES has to be individually tested as EMI can also occur in ICD patients with bipolar sensing.

Adult↗

PubMed2003

[Therapy of head injuries caused by animal slaughter guns].

Slaughterer's guns ("humane killers") are powder-activated cattle skull impacting tools. Today mechanical stunning is typical for country like regions, because in the municipal slaughter-houses electrical stunning of pigs and ruminants is preferred. In rare cases these weapons are used for suicide. They then cause penetrating brain lesions and if the victim survives the brain-damage, an encephalitis caused by the impacted material results. The neurosurgical treatment is to revise the gunshot canal and to remove impacted fragments of bone and contaminated skin (imprimat) under antibiotic cover. A psychiatric treatment of the mostly underlying depression and a rehabilitative treatment should complete therapy. So treatment of slaughterer's gun injury should have a multidisciplinary approach.

Abattoirs↗

PubMed2003

[Aerobic endurance training for cancer patients].

With the increase in the number of patients who survive cancer, there is a growing need to attend to the physical and emotional effects of cancer and oncological treatment. Reduced physical performance, fatigue, nausea, weight gain, psychological distress, changes in body image, dependency, and reduced quality of life are some of the short- and long-term sequelae of cancer. We describe data from the literature about firstly the effects of aerobic exercise as an additive treatment for cancer patients, and about the feasibility of aerobic exercise secondly during oncological treatment, and thirdly in patients suffering from terminal cancer. The data from the literature support that exercise as an additive treatment may help to attenuate the physical limitations caused by cancer and oncological treatment and there by contribute to rehabilitation and quality of life of cancer patients. Feasibility of aerobic exercise has been demonstrated also for patients suffering from advanced cancer. Aerobic exercise has been shown to provide benefits to cancer patients. It enables these patients to recover their physical function and to return to an active lifestyle. Aerobic exercise seems to be an effective possibility to reduce sequelae of cancer and to increase quality of life.

Exercise↗