[Influence of pain perception, morbidity and mood on functional impairment in elderly chronic pain patients]. / Einfluss von Schmerzwahrnehmung, Morbidität und aktueller Stimmung auf funktionelle Beeinträchtigung Alterer mit chronischen Schmerzen.

The purpose of the study was to address the impact of pain perception, morbidity and mood on functional impairment in elderly chronic pain patients. Multimorbid pain patients beyond the age of 65 in two geriatric hospitals (n = 84), a pain clinic (n = 60) and three general practices (n = 117) provided information about pain perception, comorbidity, additional symptoms and mood by means of the "Structured Pain Interview for Geriatric Patients", the "Cumulative Illness Rating Scale" and a list of symptoms. Data analysis relied on stepwise multiple regression with variables of pain perception entered in the first step, of morbidity entered in the second step and of mood entered in the third step. Although patients believe that pain is the main reason for their functional impairment (71.3%), the data do not support this assumption. Increasing morbidity and bad mood have more impact to reduced functional performance than the pain perception. Our results support the recommendation that a multimodal program should be offered to even multimorbid and older people with chronic pain in order to achieve a maximum of functional rehabilitation.

Randomised, controlled outcome study of active mobilisation compared with collar therapy for whiplash injury.

OBJECTIVES: Standard therapy in Germany for acute whiplash injury has traditionally included a soft collar (cervical orthosis), an approach that is passive compared with early exercise and mobilisation. The purpose of this study is to examine the recovery in the first six weeks of groups of acute whiplash injury patients subjected to two different treatment approaches, the traditional approach of a collar compared with active, early mobilisation. METHODS: Between August 1997 and February 2000 a randomised clinical trial with a total of 200 patients was performed. A total of 97 were randomly assigned to a collar therapy group, and 103 to the exercise group, treated by a physiotherapist. Study participants recorded average pain and disability twice (baseline and six week follow up) during a one week period by diary, using numeric visual analogue (VAS) rating scales ranging from 0 to 10. RESULTS: The initial mean VAS pain intensity and VAS disability reported by the collar therapy group and the exercise group showed no statistical difference. The mean VAS pain rating reported by the collar therapy group after six weeks was 1.60 and mean VAS disability rating was 1.56. The mean VAS pain intensity of the exercise group was 1.04 and mean VAS disability was 0.92. These differences between the groups were both significant, as was the reduction in the prevalence of symptoms in the exercise therapy group compared with the collar group at six weeks. CONCLUSIONS: Early exercise therapy is superior to the collar therapy in reducing pain intensity and disability for whiplash injury.

The detection of Chlamydia pneumoniae in aneurysm of abdominal aorta and in normal aortic wall of organ donors.

Sixty patients underwent surgery due to abdominal aortic aneurysms; the group included 30 patients with asymptomatic aneurysm and 30 with ruptured aneurysm. A control group comprised 30 organ donors. Surgical specimens derived from aneurysm or aorta fragments were investigated for Chlamydia pneumoniae DNA using PCR. In asymptomatic aneurysms, DNA was found in 9 cases (29%), and in ruptured aneurysms in 14 cases (49%). In the control group, C. pneumoniae DNA was not detected in an aortic wall. These results suggest that healthy aortic wall is not susceptible to chlamydial infection. A large number of aneurysm infections implies C. pneumoniae role in proteolysis and degradation of the aneurysm wall. The biological effect of this process may cause an enlargement of the aneurysm.

[Diagnosis and therapy of acute complaints after "whiplash injury" in Germany. Results of a representative survey at surgical and trauma departments in Germany]. / Diagnostik und Therapie akuter Beschwerden nach "HWS-Distorsion" in Deutschland. Ergebnisse einer Umfrage an chirurgischen und unfallchirurgischen Kliniken in Deutschland.

Whiplash injury of the cervical spine is a relevant medical and socioeconomic problem, which is still the subject of controversy. We performed a survey to evaluate the current status of diagnostics, classification, treatment, and doctors' subjective opinions at surgical and trauma departments in Germany. A total of 1568 hospitals were addressed to answer a standardized questionnaire on their proceedings and opinions concerning whiplash injury. We received 540 (34.44%) completed questionnaires. There was overall agreement concerning the need for physical examination. The radiological assessment included an a.p. and a lateral plain X-ray of the cervical spine in 82.6%. The indication for functional X-rays in flexion/extension was inconsistent. On average they were performed in 39.1% of all patients. In most cases (68.9%) whiplash injury was not classified; 13.2% of doctors used the classification according to the Quebec Task Force and 13.9% according to Erdmann. A cervical collar was prescribed in 85%. While 30% of patients received only a cervical collar, 55.6% underwent additional physiotherapy. Only 8.3% were treated by physiotherapy without immobilization. The doctors' subjective opinions indicated psychological factors to be important for long-lasting problems, but not for the acute period of complaints. There is no homogeneous concept for diagnostics, classification, and treatment of patients who suffered a whiplash injury in Germany. This situation reflects the current problems in management of this condition. Scientific evidence for functional treatment to avoid adverse influence of immobilization by cervical collars has not yet been transferred to our daily routine in Germany.

[Comorbidity, multiple medication, and well-being in elderly patients with chronic pain]. / Komorbidität, Multimedikation und Befinden bei älteren Patienten mit chronischen Schmerzen.

Consecutive patients with a minimum age of 65 years and at least one additional diagnosis participated in a standardized interview during the initial assessments in two geriatric hospitals ( n=86), a multidisciplinary pain center ( n=60), and three primary care practices ( n=117). The average age of the total sample was 76.29 years (SD=7.40); females constituted 73.3% of the sample. The average number of drugs consumed by the patients amounted to 7.31 (SD=2.66) with a maximum number of 19 drugs. Nearly three-quarters of the patients indicated a reduction in their pain by avoiding physical activity. Every second patient often felt depressed and without energy. The most frequent symptoms were a dry mouth, sleep disorders, fatigue, constipation, and dizziness. Patients from the geriatric hospitals were older and better educated, reported fewer painful body regions, indicated lower intensity and duration of pain as well as a lower number of pain medications. On the other hand, they were characterized by a higher intensity of comorbidity and by increased functional impairment. Patients from the pain clinic suffered more frequently from pain in the hip and the pelvis. They took stage I analgesics more often and admitted more frequently to adjusting the drug consumption to changes in well-being and situational factors. They felt the highest amount of impairment in their social activities. Nevertheless, they expressed the highest confidence in future improvement.

[Results of early mobilisation of acute whiplash injuries]. / Ergebnisse der frühfunktionellen krankengymnastischen Ubungsbehandlung nach HWS-Distorsion.

BACKGROUND: Diagnostic evaluation and therapeutic management of acute neck pain after whiplash is a frequent but unsolved clinical problem. Long-lasting symptoms and disability are common. Former studies proposed beneficial effects of physiotherapy in the early management of whiplash injury. The purpose of this study was to assess the effects of early active mobilization versus standard treatment with a soft cervical collar. METHODS: Between August 1997 and February 2000 a prospective randomized clinical trial with a total of 168 patients was performed. Of these patients 81 (31 male, 50 female; average age 28,78 years) were randomly assigned to the standard therapy group, which received a soft cervical collar, and 87 (31 male, 56 female; average age 29,62 years) to the early mobilization group, treated by physiotherapy. Study participants documented pain and disability twice (baseline and six week follow-up) during a one week period by diary, using numeric rating scales ranging from 0 to 10. RESULTS: The initial mean pain intensity (4,75) reported by the standard therapy group was similar to disability (4,76). There were no significant differences to initial pain (4,50) and disability (4,39) reported by the early mobilization group. The mean pain intensity reported by the standard therapy group after 6 weeks was 2,66 and disability was 2,40. The mean pain intensity indicated by physiotherapy group was 1,44 and mean disability was 1,29. The differences between the groups were both significant. CONCLUSIONS: Early mobilization is superior to the standard therapy regarding pain intensity and disability. We conclude that mobilization should be recommended as the new adequate standard-therapy in the acute management of whiplash injury.

[Selection of subjects: a problem of clinical trials in traumatology. Selection effects and the problem of representation as exemplified by a prospective randomized trial on whiplash injuries]. / Selektionseffekte--Ein Problem unfallchirurgischer Studien? Stichprobenselektionseffekte und das Problem der Repräsentativität am Beispiel einer prospektiven randomisierten Studie zur HWS-Beschleunigungsverletzung.

INTRODUCTION: The internal and external validity of studies is endangered by many factors, such as selection of subjects for inclusion. Selection bias itself is a major problem, but remains unmentioned and probably unexamined in the majority of published clinical trials in traumatology. AIM OF THE STUDY: The aim of this investigation was to detect effects of subject selection which occurred during our own prospective intervention study. The clinical trial compared subjects with whiplash injury who were either treated by early mobilization or immobilization (soft collar). MATERIAL AND METHODS: Source population, eligible subjects, study participants and final study participants were compared for differences on various items like age, gender and further sociodemographic as well as crash related factors and clinical findings. RESULTS: Between 21.08.1997 and 30.04.1999 a total of 732 patients was examined and treated after whiplash in our trauma department. The options for inclusion were met by 453 patients. While 346 escaped from the study, 107 agreed to participate. Of these another 39 patients dropped out of the study. Selection effects were detected on two different levels, leading to distinct statistical procedures from those proposed in the study protocol. CONCLUSIONS: Uncontrolled selection effects could undermine the interpretability of the results of clinical trials. Awareness of selection effects is mandatory regarding the applicability of these results to subjects, other than those in the group of the final study participants.

Long-term effects of intracoronary beta-radiation in balloon- and stent-injured porcine coronary arteries.

BACKGROUND: The data on the long-term safety and efficacy of intracoronary beta-radiation in animal models are limited. METHODS AND RESULTS: A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by beta-radiation from a centered 32P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n = 2], and 4 months) as a result of layered, occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15 +/- 0.17 versus 1.80 +/- 0.08 mm2, P=0.06) and larger external elastic lamina areas (3.32 +/- 0.21 versus 2.62 +/- 0.10 mm2, P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58 +/- 0.33, 3.16 +/- 0.35, and 8.12 +/- 0.42 mm2 for irradiated vessel segments; these values were not different from those in controls (3.21 +/- 0.15, 2.84 +/- 0.27, and 7.76 +/- 0.28 mm2, respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. CONCLUSION: In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary beta-radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a background of continuous aspirin but relatively brief ticlopidine treatment.

Prevention of restenosis with intravascular beta-radiotherapy.

Beta radiation has been clearly shown, in a specific dose range, to be highly effective in the inhibition of the restenotic process after balloon or stent injury in animal experiments, as well as in randomized, placebo-controlled human trials. The major advantage of beta radiation, in comparison with gamma radiation, is a significantly lower radiation exposure to the personnel and patient, and easier adaptability to existing cardiac catheterization laboratories. Rapidly accumulating evidence indicates that the two major problems, late thrombosis and edge stenosis, may be minimized with prolonged antiplatelet therapy (6 months or more) and broader radiation coverage of the intervention site. Although there may be better, safer, and easier options to reduce restenosis in the years to come, intravascular radiotherapy is the first breakthrough modality that has been shown to significantly reduce restenosis after percutaneous vascular interventions.

Dose-response study of intracoronary beta-radiation with 32P in balloon- and stent-injured coronary arteries in swine.

PURPOSE: A dose-response study was performed in swine to investigate the vascular effects of 32P over a broad range of doses in order to define the therapeutic window of intracoronary radiotherapy (ICR) with 32P. METHODS AND MATERIALS: A total of 131 porcine arteries were subjected to balloon injury or stenting followed by 0-36 Gy of ICR from a centered 32P source wire to 1 mm beyond lumen surface or a sham ICR procedure. Animals were euthanized at 4 weeks, and vessels were harvested for histomorphometry. RESULTS: In the balloon-injured arteries, doses of 7 and 9 Gy did not impact restenosis. At doses of 14-36 Gy, neointima was markedly reduced, with mild dilatation at the highest dose, 36 Gy. In the stent-injured arteries, the lowest dose of 9 Gy failed to reduce neointimal growth, while 14-26 Gy showed the most favorable response. CONCLUSIONS: ICR with 32P features a broad therapeutic window. Doses of 14-26 Gy to 1 mm beyond lumen surface provided an optimal combination of efficacy and safety. Doses of 7 and 9 Gy were generally ineffective, suggesting a minimum threshold for ICR with 32P to effectively inhibit restenosis.

Inhibition of restenosis with beta-emitting radiotherapy: Report of the Proliferation Reduction with Vascular Energy Trial (PREVENT).

BACKGROUND: Intracoronary gamma- and beta-radiation have reduced restenosis in animal models. In the clinical setting, the effectiveness of beta-emitters has not been studied in a broad spectrum of patients, particularly those receiving stents. METHODS AND RESULTS: A prospective, randomized, sham-controlled study of intracoronary radiotherapy with the beta-emitting (32)P source wire, using a centering catheter and automated source delivery unit, was conducted. A total of 105 patients with de novo (70%) or restenotic (30%) lesions who were treated by stenting (61%) or balloon angioplasty (39%) received 0 (control), 16, 20, or 24 Gy to a depth of 1 mm in the artery wall. Angiography at 6 months showed a target site late loss index of 11+/-36% in radiotherapy patients versus 55+/-30% in controls (P:<0.0001). A low late loss index was seen in stented and balloon-treated patients and was similar across the 16, 20, and 24 Gy radiotherapy groups. Restenosis (>/=50%) rates were significantly lower in radiotherapy patients at the target site (8% versus 39%; P:=0.012) and at target site plus adjacent segments (22% versus 50%; P:=0.018). Target lesion revascularization was needed in 5 radiotherapy patients (6%) and 6 controls (24%; P:<0.05). Stenosis adjacent to the target site and late thrombotic events reduced the overall clinical benefit of radiotherapy. CONCLUSIONS: beta-radiotherapy with a centered (32)P source is safe and highly effective in inhibiting restenosis at the target site after stent or balloon angioplasty. However, minimizing edge narrowing and late thrombotic events must be accomplished to maximize the clinical benefit of this modality.

[Efficacy and tolerance of trimetazidine, a metabolic antianginal, in combination with a hemodynamic antianginal in stable exertion angina. TRIMPOL I, a multicenter study]. / Efficacité et tolérance de la trimétazidine, antiangoreux métabolique, en association avec un antiangoreux hémodynamique dans l'angor d'effort stable. TRIMPOL I une étude multicentrique.

OBJECTIVE: Assess the antianginal and anti-ischemic effect of trimetazidine in patients with stable exercise-induced angina insufficiently controlled with conventional antianginal drugs. PATIENTS AND METHODS: The study population included patients with coronarographically documented stable exercise-induced angina and no other serious concomitant condition. For inclusion, patients had to have two comparably positive treadmill exercise tests. Conventional antiangina drugs (long-acting nitrate derivatives, beta-blockers or calcium antagonists) were continued as was any other therapy having no effect on the ECG ST segment. The patients were given a 4-week regimen of trimetazidine (20 mg t.i.d.) after the second positive treadmill test and final inclusion. At the end of this period, a final exercise test was performed. The study population included 700 patients (mean age 54 +/- 8.4 years, range 32-71 years, 615 men, 85 women) who completed the entire treatment protocol. RESULTS: The main findings observed after 4 weeks of treatment with trimetazidine were: significant lengthening of the total duration of exercise (486.6 s versus 443.7 s, p < 0.01)), increase in total work (10.6 METS versus 9.4 METS, p < 0.01), significant lengthening of delay to 1 mm ST depression (389.9 s versus 337.8 s, p < 0.01) and of the delay to onset of angina (450.3 s versus 251.7 s, p < 0.01). The other results were a significant reduction in the number of daily episodes of angina (2.47 versus 3.66, p < 0.01) and a reduction in mean use of complementary trinitrine (1.8 versus 2.94, p < 0.01). CONCLUSIONS: Four weeks of treatment with trimetazidine in combination with conventional antiangina drugs leads to a longer delay to development of 1 mm ST depression (ischemia threshold), significant lengthening of total duration of treadmill exercise, increased total work, and longer delay to angina theshold. Clinically, there was a reduction in the mean number of episodes of angina and a reduction in the use of trinitrine.

Catastrophic outcomes of noncardiac surgery soon after coronary stenting.

OBJECTIVES: To assess the clinical course of patients who have undergone coronary stent placement less than six weeks before noncardiac surgery. BACKGROUND: Surgical and percutaneous transluminal coronary angioplasty revascularization performed before high-risk noncardiac surgery is expected to reduce perioperative cardiac morbidity and mortality. Perioperative and postoperative complications in patients who have undergone coronary stenting before a noncardiac surgery have not been studied. METHODS: Forty patients who underwent coronary stent placement less than six weeks before noncardiac surgery requiring a general anesthesia were included in the study (1-39 days, average: 13 days). The records were screened for the occurrence of adverse clinical events, including myocardial infarction, stent thrombosis, peri- and postoperative bleeding and death. RESULTS: In 40 consecutive patients meeting the study criteria, there were seven myocardial infarctions (MIs), 11 major bleeding episodes and eight deaths. All deaths and MIs, as well as 8/11 bleeding episodes, occurred in patients subjected to surgery fewer than 14 days from stenting. Four patients expired after undergoing surgery one day after stenting. Based on electrocardiogram, enzymatic and angiographic evidence, stent thrombosis accounted for most of the fatal events. The time between stenting and surgery appeared to be the main determinant of outcome. CONCLUSIONS: Postponing elective noncardiac surgery for two to four weeks after coronary stenting should permit completion of the mandatory antiplatelet regimen, thereby reducing the risk of stent thrombosis and bleeding complications.

Mapping of immunodominant B-cell epitopes and the human serum albumin-binding site in natural hepatitis B virus surface antigen of defined genosubtype.

Twelve MAbs were generated by immunization of BALB/c mice with plasma-derived hepatitis B virus surface spherical antigen particles subtype ayw2 (HBsAg/ayw2 genotype D). Their epitopes were mapped by analysis of reactivity with plasma-derived HBsAg/ayw2 and HBsAg/adw2 (genotype A) in enzyme immunoassays and blots. Mapping was supported by nested sets of truncated preS2 proteins and preS2 peptides. Five antibodies were S domain-specific, seven were preS2-specific and 11 had a preference for genotype D. According to our data, group I of the three known epitope groups of preS2 has to be divided into IA and IB. Three preS2-specific MAbs forming the new group IA reacted with genotype D residues 3-15 which have not yet been described as an epitope region. IA antibodies strongly inhibited the binding of polymerized human serum albumin. Two antibodies (group II) reacted with the glycosylated N-terminal region of preS2 in plasma-derived HBsAg, but not with a preparation from transfected murine cells. One group III antibody was subtype-specific and reacted with the highly variable preS2 sequence 38-48. Only one antibody (group IB) mapped to the region (old group I) which was believed to be immunodominant and genotype-independent. Geno(sub)type-specific epitopes of preS2 are obviously the immunodominant components of natural HBsAg in BALB/c mice, but these epitopes may be masked by serum albumins in humans. The data may explain why it is difficult to detect anti-preS2 antibodies in human recipients of preS2-containing vaccines, in spite of the preS2 immunodominance in mice.

Intracoronary radiotherapy for prevention of restenosis after percutaneous coronary interventions.

More than 50 different pharmacological and mechanical interventions have been tested to date for prevention of vascular restenosis without success. Intracoronary radiotherapy is the first one showing promise of significantly attenuating neointimal proliferation, causing positive vascular remodelling and thus inhibiting restenosis. This promising modality has moved from animal experiments via safety and feasibility testing into the phase of clinical trials of efficacy in large numbers of patients. While ongoing research continues to search for new sources and delivery techniques, currently available technology is being optimized. The randomized clinical trials conducted to date have shown consistently a reduction of target site restenosis rates by 55-79%. Lower incidence of major adverse cardiac events after radiotherapy has also been demonstrated, primarily as a result of reduction in target site and target vessel revascularization rates. However, experimental and clinical research has identified two major complications of this approach: stenosis at the ends of the radiation zone ('edge effect' or 'candywrapper') as well as late thrombosis (beyond 30 days after intervention) of the angioplasty or stent site. If these two adverse effects can be minimized, intracoronary radiotherapy may prove to be a major breakthrough in percutaneous coronary interventions.

Improving physician-delivered counseling in a primary care setting: lessons from a failed attempt.

BACKGROUND: The high prevalence of behavioral risk factors for cardiovascular diseases demands innovative approaches to achieving behavior change. Primary care physicians are in an ideal position for offering such interventions. PURPOSE: To evaluate whether training of primary care physicians in counseling skills based on the Transtheoretical Model (TTM) leads to motivational and behavioral changes in their patients. METHOD: Seventy-four primary care physicians in Germany were randomly assigned to either an intervention condition (one day of training in TTM-based counseling plus brochures matched to their patients' "stages of change") or a control condition (usual care). Baseline and 12-month follow-up data were collected from 305 of their patients who signed up for a health check-up. OUTCOME MEASURE: Patients' movements across the stages of change for smoking, diet, exercise and stress management. RESULTS: After 12 months, patients of physicians in the intervention group did not show more movement through the stages of change for any of the behaviors than did patients of control physicians. Additionally, there were no differences between groups in counseling frequency, counseling intensity, or patient satisfaction with counseling. CONCLUSIONS: A high dropout rate at follow-up and resulting "power" problems limit the possible conclusions. The high numbers of patients in early stages of change and the minimal improvement over time underline the need for improving motivational counseling skills of primary care physicians in Germany. In our study the dissemination of these strategies failed. We offer lessons we feel can be learned from this outcome. Further studies should focus on ways to enhance the process of educating physicians for implementing counseling strategies in primary care settings.

The antiischemic effects and tolerability of trimetazidine in coronary diabetic patients. A substudy from TRIMPOL-1.

Diabetes mellitus, a disease with a wide prevalence, has major cardiovascular effects, being a risk factor for the development of ischemic heart disease and congestive heart failure. The aim of this open, multicenter study was to assess the antiischemic efficacy and tolerability of trimetazidine, a metabolic agent acting at the myocardial mitochondrial level, in diabetic patients with stable effort angina treated previously with a single conventional antianginal drug. Fifty diabetic patients (mean age 58 years) with proven coronary artery disease, stable effort angina for at least 3 months, and positive, comparable results of two initial treadmill exercise tests separated by a 1-week interval were included in the study. They continued their conventional antianginal monotherapy with a long-acting nitrate, beta-blocker, or calcium channel blocker. After stabilization, 4-week therapy with trimetazidine, three times daily, 20 mg was initiated in combination with previous treatment. The results showed a significant improvement in exercise tolerance (440.2 vs. 383.2 s; P < 0.01), time to 1-mm ST-segment depression (358.3 vs. 301.6 s; P < 0.01), time to onset of anginal pain (400.0 vs. 238.3 s; P < 0.01), and total work (9.39 vs. 8.67 metabolic equivalents, P < 0.01). Maximal ST-segment depression was attenuated compared with baseline (1.82 vs. 1.91 mm). Other findings included a significant decrease in the mean frequency of anginal episodes (3.06 vs. 4.79 per week; P < 0.01) and in mean nitrate consumption (2.29 vs. 4.2 doses/week). These results suggest that trimetazidine may be effective and is well tolerated as combination therapy for diabetic coronary artery disease patients uncontrolled with a single hemodynamic agent.