Epidural Epinephrine and Clonidine: Segmental Analgesia and Effects on Different Pain Modalities

Background: It is not known whether epidural epinephrine has an analgesic effect per se. The segmental distribution of clonidine epidural analgesia and its effects on temporal summation and different types of noxious stimuli are unknown. The aim of this study was to clarify these issues.

Methods: Fifteen healthy volunteers received epidurally (L2-L3 or L3-L4) 20 ml of either epinephrine, 100 micro gram, in saline; clonidine, 8 micro gram/kg, in saline; or saline, 0.9%, alone, on three different days in a randomized, double-blind, cross-over fashion. Pain rating after electrical stimulation, pinprick, and cold perception were recorded on the dermatomes S1, L4, L1, T9, T6, T1, and forehead. Pressure pain tolerance threshold was recorded at S1, T6, and ear. Pain thresholds to single and repeated (temporal summation) electrical stimulation of the sural nerve were determined.

Results: Epinephrine significantly reduced sensitivity to pinprick at L1-L4-S1. Clonidine significantly decreased pain rating after electrical stimulation at L1-L4 and sensitivity to pinprick and cold at L1-L4-S1, increased pressure pain tolerance threshold at S1, and increased thresholds after single and repeated stimulation of the sural nerve.     

Alcohol and drug use following traumatic brain injury: A prospective study

Primary objectives: To establish pre-morbid alcohol and drug use in persons with TBI, relative to controls, investigate how patterns of substance use change over time following TBI and identify factors associated with heavy post-injury substance use.

Methods and procedures: The Alcohol Use Disorders Identification test (AUDIT) and Drug Abuse Screening Test (DAST) was completed by 121 hospital inpatients with TBI, documenting pre-injury alcohol and drug use, and 133 demographically similar controls. Participants with TBI completed these measures and the Hospital Anxiety and Depression Scale (HADS) again 1 and 2 years post-injury and 76 also completed them at 3 years.

Results: Participants with TBI showed similar levels of drug and alcohol use to controls pre-injury, with 31.4% of the TBI group and 29.3% of controls drinking at hazardous levels. Alcohol and drug use declined in the first year post-injury, but increased by 2 years post-injury, with only 21.4% of participants with TBI reporting abstinence from alcohol and 25.4% drinking at hazardous levels. Only 9% showed a drug problem, but 24% had returned to some drug use. Those showing heavy alcohol use post-injury were young, male and heavy drinkers pre-injury. Drug and alcohol use was similar at 3 years post-injury.

Conclusions: More active intervention is needed to reduce alcohol and drug use following TBI.     

Histomorphometric analysis of innervation of the anterior cruciate ligament in osteoarthritis

The aim of this study was to determine whether there are quantitative changes in the innervation of the anterior cruciate ligament in osteoarthritis. Eleven whole anterior cruciate ligaments were obtained at autopsy from cadavera of individuals with advanced osteoarthritis; five healthy ligaments were used as controls. The ligaments were transected and stained with hematoxylin and eosin, oil red O for fat, and a modification of Gairn's gold chloride method. The latter stain permits visualization of axons, mechanoreceptors, and free nerve endings that are not apparent on routine stains. The ratio of nerve tissue to periligamentous synovial tissue was determined histomorphometrically by the point-counting method. The nerve tissue was located almost exclusively in the periligamentous synovial tissue. There was a statistically significantly greater area of nerve tissue (as a percentage of the total area) around the anterior cruciate ligaments in the osteoarthritic group than around the ligaments in the control group (p < 0.02). The nerve tissue was distributed evenly throughout the periligamentous synovial tissue in the specimens in both groups. A neurological role has been proposed for the anterior cruciate ligament in osteoarthritis. This study provides morphological evidence for neural pathology of the anterior cruciate ligament in subjects with osteoarthritis.     

Genetic imbalances in pleomorphic xanthoastrocytoma detected by comparative genomic hybridization and literature review.

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade astrocytic tumor found in the central nervous system. Histologically, the tumor is characterized by markedly pleomorphic and lipidized cells. Although most of the patients have a favorable prognosis, a small number of cases undergoing recurrence or progression to anaplastic astrocytoma were reported. Very few genetic studies have been performed on PXA because of its rarity and the pathogenesis of this neoplasm is largely unknown. In order to provide an overview of genetic alterations in PXA, we performed comparative genomic hybridization to identify chromosomal imbalances (DNA gains and losses) in three cases of PXA. Genetic imbalance was detected on at least one chromosome for each case. One case, which revealed multiple genetic alterations, showed a poor prognosis. DNA gain on chromosome 7 and loss on 8p were demonstrated in two of three cases, suggesting that the candidate gene(s) located on these regions may play a role in the development of PXA. Further studies are needed to identify the residing candidate genes that are involved in the tumorigenesis of PXA. In addition, the histopathological features and previous genetic studies on PXA are reviewed.     

A feasibility study to investigate the use of thin-plate splines to account for prostate deformation

Image registration is an important step in the radiotherapy treatment planning process. It provides a method of fusing different types of diagnostic imaging information. One such application is to combine magnetic resonance spectroscopic images (MRSI) of the prostate with anatomical MRI and/or computed tomography images that are routinely used in the radiation treatment planning of prostate cancer. MRSI provides in vivo information related to the underlying metabolic activity of tissues, and can be related to the presence of cancer. However, the inflated endorectal coil required during MRS imaging poses a potential problem by deforming the prostate when it is filled with approximately 100 cm3 of air during image acquisition. This pushes the prostate superiorly/anteriorly, deforming the prostate and consequently the spectroscopic imaging data in a nonlinear manner. In this application, the coil-deformed MRS images are warped back to a non-deformed state, using a single data set. A nonlinear warping algorithm is presented to achieve this. Results indicate that the algorithm attains an accuracy of 97% (4 cm3 difference) when reproducing the total prostate volume compared to a Radiation Oncologist defined prostate volume. This difference is slightly smaller than the measured intra-operator variance of +/-1.5 cm3 (deflated coil) and the measured algorithm variance of +/-1.0 cm3. Additionally, intraprostatic nodules were used to assess the accuracy of the warping algorithm in regions inside the prostate. While choosing anatomical tie points along the external prostate surface, analysis of the nodules revealed the algorithm accuracy reduced to 63-93%.     

The significance of angiogenesis in malignant pheochromocytomas

The purpose of this study was to investigate tumor angiogenesis in a series of benign and malignant pheochromocytomas and to determine whether there is a correlation between angiogenesis and the presence of distant metastases. In this study, the CD31 monoclonal antibody was selected to measure intratumoral microvessel density. Nineteen patients with malignant pheochromocytomas and nineteen patients with benign pheochromocytomas who underwent operation were studied. In order to quantify intratumoral microvessel density, the total number of pixels of CD31-positive reactivity was assessed and expressed as a percentage of the total tissue area in the analyzed field. Analysis of variance revealed a statistically significant correlation between malignancy and intratumoral microvessel density (p=0.0009). Although there was a considerable variability in the intratumoral microvessel density from tumor to tumor within both the benign and the malignant group, a percentage of more than 28.5% anti-CD31 stained area was found only in malignant tumors. In conclusion, this study shows that the mean intratumoral microvessel density in malignant pheochromocytomas is increased approximately two-fold as compared with benign tumors. However, the clinical significance of this prognostic marker is rather weak, because only 4 of the 19 malignant pheochromocytomas had microvesel density higher than this threshold of 28.5%.     

In vitro controllability of the MagScrew total artificial heart system

The purpose of this study was to evaluate the in vitro responses to preload and afterload of our total artificial heart (TAH), the MagScrew TAH. The TAH consists of two blood pumps and a control logic, developed at the Cleveland Clinic, OH, and the MagScrew actuator and its electronic control system, developed by Foster-Miller Technologies, Inc., Albany, NY. Tests were performed on a mock circulatory loop, using water as a test fluid. Preload sensitivity of the Mag-Screw TAH demonstrated a Frank-Starling response to preload in automatic mode. A peak flow of 10 L/min was obtained, with a left atrial pressure of 13 mm Hg. The relationship between right atrial pressure and left atrial pressure was well balanced when tested with a left bronchial shunt flow of 5% and a range of pulmonary artery and aortic pressures. With respect to afterload response, the left pump showed a relatively low sensitivity, which allowed the pump to maintain perfusion over a wide range of aortic pressures. The right pump, on the other hand, was much more sensitive to pulmonary artery pressure, which provided a measure of protection against pulmonary congestion. The very effective physiologic response of the MagScrew TAH is believed to result from employment of a left master, alternating ejection control logic, high inherent sensitivity of the blood pumps to atrial pressure, a lower effective stroke volume for the right pump, and a scaling of right side motor ejection voltage to 80% of that used for the left side ejection.