Cerebrospinal Fluid Density Influences Extent of Plain Bupivacaine Spinal Anesthesia

Background: The attempts to explain the unpredictability of extent of spinal block provided by plain local anesthetic solutions have resulted in many clinical reports; however, causes of this uncertainty are as yet unknown. Recently, normal values of the human cerebrospinal fluid densities have been studied showing important interindividual variations, especially between females and males. The current study was designed to evaluate as primary endpoint the influence of cerebrospinal fluid density values on the extent of spinal block with plain bupivacaine. The ancillary endpoints were search of factors explaining the interindividual differences in cerebrospinal fluid density values reported and determination of the relation between upper extent and regression of spinal anesthesia.

Methods: Sixty-four consecutive patients undergoing peripheral orthopedic surgery with spinal block were enrolled. Spinal anesthesia was performed in the lateral decubitus position with the operated side upward. Two milliliters of cerebrospinal fluid was sampled before injection of 3 ml plain bupivacaine 0.5%. The patient was immediately turned supine and remained in the horizontal position until the end of the study. Maximal sensory block level and time to sensory regression to L4 were determined for each patient enrolled. Cerebrospinal fluid and bupivacaine densities as well as cerebrospinal proteins, glucose, sodium, and chloride concentrations were measured.

Results: A highly significant correlation between cerebrospinal fluid density and maximal sensory block level was found (P = 0.0004). However, this correlation was poorly predictive (R2 = 0.37). Cerebrospinal fluid density, proteins, and glucose concentrations were significantly higher in men than in women: 1.000567 +/- 0.000091 versus 1.000501 +/- 0.000109 g/ml (P = 0.014), 0.46 +/- 0.18 versus 0.32 +/- 0.13 g/l (P = 0.001), and 3.27 +/- 0.7 versus 2.93 +/- 0.5 mm (P = 0.023), respectively. A highly significant (P = 0.0004) and predictive (R2 = 0.73) inverse correlation was found between maximal upper sensory extent and sensory regression to L4.     

Large French-Canadian family with Lewy body parkinsonism: exclusion of known loci.

The identification of rare, large families with Parkinson's disease (PD) has provided important clues that have contributed to our understanding of this complex disorder. We have identified a large French-Canadian kindred that spans five generations consisting of more than 90 individuals. A total of 65 individuals now have been examined, had venous blood drawn, and DNA extracted. Two-point and multipoint linkage analysis was performed to assess linkage to known PD genes or loci. Within the third and fourth generations of this family there are 10 living, plus 3 deceased members with well-documented levodopa responsive parkinsonism. Autopsy results on 1 member demonstrated the loss of pigmented neurons in the substantia nigra and the presence of alpha-synuclein positive Lewy bodies. Four of the PD patients have prominent postural and kinetic tremors that preceded their parkinsonism by up to 10 years. Two other individuals within the family have prominent isolated postural and kinetic tremors without parkinsonism. The alpha-synuclein(4q21.3-23), Parkin(6q25.2-27), PARK3 (2p13), PARK4, and ubiquitin carboxy terminal hydrolase-L1 (4p14-16.3) and PARK6 and PARK7 (1p35-36) loci were excluded in this kindred using closely linked markers. The clinical and pathological features of this family are consistent with the diagnosis of PD. This family further demonstrates the known genetic heterogeneity in PD and is large enough that a genome-wide screen has been undertaken in an effort to identify a novel PD gene.     

Fibre type characteristics of the lumbar paraspinal muscles in normal healthy subjects and in patients with low back pain

A knowledge of the alteration in the fibre type profile of paraspinal muscle associated with low back pain is essential for the design of successful rehabilitation programmes. In attempting to compare the muscles of patients with low back pain with those of controls, few previous studies have considered factors such as gender, age, and size of the subjects, each of which can potentially confound interpretation of the results. We obtained samples of lumbar paraspinal muscle during spinal surgery from 21 patients with low back pain and, using the percutaneous biopsy technique, from 21 control volunteers matched for gender, age, and body mass. The samples were subject to routine histochemicsl typcal analysis to determine characteristics of muscle fibre type. Compared with controls, the muscle of the patients had a significantly higher proportion of type-IIB (fast-twitch glycolytic) fibres than type- I (slow oxidatve) fibres. The mean size of a given fibre type did not differ between the patients and the controls. Consequently, the relative area of the muscle iccupied by type-IIB fibres was higher and that by type-I fibres Was lower in the patients. The patients had a greater number of muscle samples with more than 1% type-IIC fibres, and abnormalities that could be described as pathological were more marked in the patients than in the controls. In conclusion, the paraspinal muscles of patients who have low back pain display a more glycolytic (faster) profile; this can be expected to render them less resistant to fatigue.     

Breast Cancer Genes

Abstract: The identification of familial breast cancer genes heralds an era of directed breast cancer treatment. Currently, two hereditary breast cancer genes have been identified, BRCA-1 and BRCA-2 . Although accounting for only approximately 5% of all breast cancers, they are being used to identify women with germ-line alterations that are at high risk of developing breast or ovarian cancer. With the identification of such genes comes a need for consideration of the ethical issues associated with testing. These genes are also being examined from a biochemical standpoint encompassing both their biological roles and biochemical pathways in which they reside. Such studies are likely to lead to novel breast cancer therapies.