Adrenergic Receptor Genotype but Not Perioperative Bisoprolol Therapy May Determine Cardiovascular Outcome in At-risk Patients Undergoing Surgery with Spinal Block: The Swiss Beta Blocker in Spinal Anesthesia (BBSA) Study: A Double-blinded, Placebo-controlled, Multicenter Trial with 1-Year Follow-up

Background: Neuraxial blockade is used as primary anesthetic technique in one third of surgical procedures. The authors tested whether bisoprolol would protect patients at risk for cardiovascular complications undergoing surgery with spinal block.

Methods: The authors performed a double-blinded, placebo-controlled, multicenter trial to compare the effect of bisoprolol with that of placebo on 1-yr composite outcome including cardiovascular mortality, nonfatal myocardial infarction, unstable angina, congestive heart failure, and cerebrovascular insult. Bisoprolol was given orally before and after surgery for a maximum of 10 days. Adrenergic receptor polymorphisms and safety outcome measures of bisoprolol therapy were also determined.

Results: A total of 224 patients were enrolled. Spinal block could not be established in 5 patients. One hundred ten patients were assigned to the bisoprolol group, and 109 patients were assigned to the placebo group. The mean duration of treatment was 4.9 days in the bisoprolol group and 5.1 days in the placebo group. Bisoprolol therapy reduced mean heart rate by 10 beats/min. The primary outcome was identical between treatment groups and occurred in 25 patients (22.7%) in the bisoprolol group and 24 patients (22.0%) in the placebo group during the 1-yr follow-up (hazard ratio, 0.97; 95% confidence interval, 0.55-1.69; P = 0.90). However, carriers of at least one Gly allele of the [beta]1-adrenergic receptor polymorphism Arg389Gly showed a higher number of adverse events than Arg homozygous (32.4% vs. 18.7%; hazard ratio, 1.87; 95% confidence interval, 1.04-3.35; P = 0.04).     

Quantitative Monitoring of Extracellular Matrix Production in Bone Implants by <Superscript>13</Superscript>C and <Superscript>31</Superscript>P Solid-State Nuclear Magnetic Resonance Spectroscopy

We used ³¹P and ¹³C solid-state nuclear magnetic resonance (NMR) spectroscopy to detect and analyze the major organic and inorganic components (collagen type I and bioapatite) in natural rabbit bone and β-tricalcium phosphate implants loaded with osteogenically differentiated mesenchymal stem cells. High-resolution solid-state NMR spectra were obtained using the magic-angle spinning (MAS) technique. The ³¹P NMR spectra of bone specimens showed a single line characteristic of bone calcium phosphate. ¹³C cross-polarization (CP) MAS NMR spectra of bone exhibited the characteristic signatures of collagen type I with good resolution for all major amino acids in collagen. Quantitative measurements of ¹³C-¹H dipolar couplings indicated that the collagen segments are very rigid, undergoing only small amplitude fluctuations with correlation times in the nanosecond range. In contrast, directly polarized ¹³C MAS NMR spectra of rabbit bone were dominated by signals of highly mobile triglycerides. These quantitative investigations of natural bone may provide the basis for a quality control of various osteoinductive bone substitutes. We studied the formation of extracellular bone matrix in artificial mesenchymal stem cell-loaded β-tricalcium phosphate matrices that were implanted into the femoral condyle of rabbits. The NMR spectra of these bone grafts were acquired 3 months after implantation. In the ³¹P NMR spectra, β-tricalcium phosphate and bone calcium phosphate could be distinguished quantitatively, allowing recording of the formation of the natural bone matrix. Further, ¹³C CPMAS allowed detection of collagen type I that had been produced in the implants. Comparison with the spectroscopic data from natural bone allowed assessment of the quality of the bone substitute material. J. S. and M. P. contributed equally to this study     

Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?

BACKGROUND: Fatigue is a major complaint of multiple sclerosis (MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue. METHODS: We compared whole blood stimulatory capacity for pro- (TNFalpha, IFNgamma) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS). RESULTS: Proinflammatory cytokines were significantly higher (TNFalpha: 478.9 v 228.2 pg/ml, p = 0.01; IFNgamma: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNFalpha values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity (as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment. CONCLUSION: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.     

Cognition in the early stage of multiple sclerosis

Objective Cognitive dysfunctions may contribute to limitation of everyday activities of patients with multiple sclerosis (MS). Recent studies have demonstrated that 45 to 65% of MS-patients are cognitively impaired. The profile of MS-related cognitive dysfunctions varies greatly. It includes memory and learning deficits, attention deficits, executive dysfunctions and visuo-spatial deficits. Most studies of cognition in MS examined patients in later stages, often including MS-patients with marked physical disabilities. Studies of cognitive dysfunctions in the early stage of the disease are rare. This study specifically aimed at evaluating and characterizing cognitive impairments in the early stage of MS, and determining specific patterns of cognitive dysfunction. Methods 21 MS patients, experiencing their first neurological symptoms not more than two years previously, and 22 healthy controls were compared. A comprehensive neuropsychological test-battery was used to evaluate MS-related cognition. The battery consisted of memory and learning tests, executive functioning tests and a visuo spatial functioning test. A computerized attention test-battery was also included, which assess accuracy and speed of test responses. In addition depression and intellectual capabilities were assessed. Results Compared with healthy controls, MS-patients in the early stage of the disease performed significantly lower on each neuropsychological assessment, except for verbal short-term memory. In particular, MS-patients showed a lengthened reaction time for simple and focused attention (19–38%), impaired non-verbal memory function (RVDLT recognition: 33%) and a planning deficit (24%). Associations between information processing speed and disease course and the employment situation were additionally found. However, patients did not have clinically relevant depression rates on the ADS-L and visuo spatial abilities remain preserved. Conclusion Our findings revealed discrete cognitive dysfunction in MS-patients within the early stage of the disease. Received in revised form: 18 January 2006     

Predictors of complicated grief among dementia caregivers: a prospective study of bereavement.

OBJECTIVE: Most family caregivers adapt well to the death of their care recipient relative; however, a sizable minority continues to experience postdeath psychiatric morbidity. The purpose of this study was to better understand why some caregivers manifest clinical levels of complicated grief postdeath. This is the first study to prospectively assess predictors of complicated grief among family caregivers of patients with dementia who experience the death of their care recipient. METHOD: The sample of bereaved caregivers is drawn from a larger study of 1,222 family caregivers providing in-home care to their relative with dementia. In-home assessments of caregivers and patients were carried out at baseline and six-month intervals for a total of 18 months. This article is based on the 217 caregivers who experienced the death of their care recipient in the course of the study. Three logistic regression models are tested to identify pre- and postbereavement predictors of complicated grief, including sociodemographic factors, characteristics of the caregiving experience, including participation in a caregiver intervention, other psychiatric morbidities, and medication use. RESULTS: Twenty percent of dementia caregivers evidenced complicated grief along with high levels of depressive symptomatology postdeath. Controlling for sociodemographic factors, caregivers who had high levels of preloss depressive symptoms and burden, reported positive features of the caregiving experience, and were caring for a more cognitively impaired patient were more likely to report clinical levels of complicated grief postloss. In addition, caregivers who were enrolled in a psychosocial caregiver intervention designed to reduce depression and burden reported lower levels of complicated grief. CONCLUSION: This study identifies predictors of complicated grief for which interventions could be developed to not only ease caregiver distress, but also serve as preventive interventions for bereavement. Reducing the burden of active caregiving, treating depression before the death of the loved one and providing supportive psychosocial and skills training caregiver interventions can prevent the emergence of postdeath psychiatric morbidity.     

Macromorphology and histology of intramuscular hemorrhages in cases of drowning

In a prospective autopsy series of 39 cases of fatal drowning, the detailed dissection of the skeletal muscles of the neck, anterior / posterior trunk and the upper extremities in layers revealed intramuscular hemorrhages of different size and shape in 20 cases (51.3 %). Light microscopy examination showed a premortal (vital/agonal) type of muscular alteration in 7 (50 %) out of 14 macroscopical hemorrhage-positive cases. These hemorrhages and histological muscle alterations are attributed to agonal convulsions, hypercontraction and overexertion of the affected muscle groups. As long as no cutaneous or subcutaneous hematomas above the hemorrhages can be found, these autopsy findings (with special reference to histology) can serve as an additional criterion concerning the differentiation of drowning and another cause of death. Received: 31 July 1998 / Received in revised form: 31 August 1998     

Distribution of posterior tibial displacement in knees with posterior cruciate ligament tears

BACKGROUND: While stress radiography has been used to objectively determine the limits of posterior tibial displacement in knees with posterior cruciate ligament tears, the magnitude and distribution of posterior tibial translation has not been defined in a large population of patients with this injury. METHODS: A retrospective diagnostic study of 1041 consecutive patients with posterior cruciate ligament tears was done. Posterior tibial displacement values that were obtained with use of instrumented stress radiography with the knee held in 90 degrees of flexion in the Telos device were evaluated and compared with the values from relevant cadaveric dissection studies. RESULTS: The mean amount of posterior tibial displacement on stress radiographs was -11.58 +/- 4.31 mm (range, -5 to -30 mm). There was a displacement peak in the range of -9 to -12 mm, with 37.9% of patients exhibiting posterior laxity within this range. Traffic-related injuries were associated with significantly greater displacement values than were sports-related injuries (p < 0.001). Grade-I or II instability (12 mm of posterior tibial displacement) occurred in association with 68.7% of the sports-related injuries, compared with 54.1% of the traffic-related injuries (p < 0.001). The mean amount of posterior tibial displacement on the intact side was -1.31 +/- 1.85 mm (range, -6 to 4 mm). CONCLUSIONS: Instrumented stress radiography is a useful testing method for objectively determining the amount of posterior tibial displacement of the knee in adults with a posterior cruciate ligament injury. Absolute posterior tibial displacement in excess of 8 mm is indicative of complete insufficiency of the posterior cruciate ligament. With tibial displacement exceeding 12 mm, additional injury of secondary restraining structures should be considered. We recommend the use of stress radiography to grade and classify posterior knee laxity.     

Surgical management of vertebral column metastatic disease

The spine is the most frequent site of skeletal metastases. Among all spinal malignancies metastatic disease is most frequent and indicative of disseminating tumor disease. Depending on primary tumor entity, estimated survival time, general health status of the patient, presence of spinal instability and neurological deficits an oncological useful and patient-specific therapeutic intervention should be performed. New anterior approaches, resections and reconstruction techniques are making surgery a preferred method over radiation therapy. For differential indication of the multiple surgical treatment modalities prognostic scores are available to assist individual decision making. Indications for surgery include survival prognosis of minimum 3 months, intractable pain, progress of myelon compression and/or neurological deficits under radiochemotherapy, spinal instability and necessity for histological diagnosis. Resulting quality of life depends on efficient decompression of the spinal cord and restoration of spinal stability. To achieve these ultimate goals there are different anterior and posterior approaches, instrumentations and vertebral body replacement implants available. Preoperative embolization should be performed in hypervascular tumors, e.g., renal cell cancer. Vertebro-/Kyphoplasty as a percutaneous intervention should be considered for painful multisegmental disease and symptomatic osteolysis without epidural tumor compression to reach analgesia and stability. A multidisciplinary approach in patient selection, decision making and management is an essential precondition for complication avoidance and acceptable quality of life.