MR volumetry during acute alcohol withdrawal and abstinence: a descriptive study

AIMS: The brain volume of chronic drinkers is known to partially recover with abstinence from alcohol. To investigate the relative contribution of grey and white brain matter to this process, magnetic resonance imaging and brain tissue segmentation was used to study brain tissue in acute alcohol withdrawal and abstinence in seven alcohol-dependent men. METHODS: The patients were studied on three occasions; within 48 h after the last drink and approximately one month and two and a half months later. Total brain tissue class volumes [grey matter (GM) and white matter (WM) and cerebrospinal fluid (CSF)] were measured. Eleven healthy volunteers were scanned twice to serve as a control group. The alcohol-dependent patients were investigated with regard to drinking variables, neuropsychological performance and blood biochemistry. RESULTS: In the alcohol-dependent patients, intracranial volume and total GM volume did not change between scan occasions, except in a single patient who demonstrated a GM increase of 4.8% (4.2% relative volume) between scans 2 and 3. For all patients, the increase in total WM volume ranged between 1.9 and 22.4% (absolute volumes) and 2.1 and 21.2% (relative volumes). Between scans 2 and 3, the increase in total WM volume ranged between 0.3 and 13.2% (absolute volumes), and between 1.5 and 14.0% (relative volumes). One patient resumed drinking and was investigated a second time during acute withdrawal. In this patient, the measured decrease of 8.1 and 8.5% of absolute and relative WM volumes corresponded to the size of the volume increase between scans 1 and 2. CSF, GM and WM volumes in the healthy subjects were constant over time. CONCLUSIONS: The results demonstrate that changes in brain volume during short-term abstinence in chronic alcohol-dependent patients are confined to the WM. The time limit of WM volume restitution is variable and continues longer than 3 weeks after withdrawal.     

An external fixation method and device to study fracture healing in rats

We wished to establish a reproducible model for fracture fixation to be used in fracture healing research and therefore developed an external fixation construct and surgical procedure adapted to Sprague-Dawley rats. We evaluated the mechanical properties of the construct in brass rods and rat bone, in an Instron test machine with axial and transverse loading, and the in vivo performance. We found that the mechanical properties of the construct in brass rods were predictable and could be repeated in rat femora. In all tests, the axial load was about 10 times the transverse for the same degree of deformation. The stiffness among fixators was uniform. 1 mm pins caused about 50% less stiffness than 1.2 mm pins in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) as well as in transverse loading of brass rods (p < 0.001). Loosening of 1 or 2 screws that lock the pins to the fixator reduced stiffness by about 50% in axial loading of rat bone (p = 0.009) and brass rods (p = 0.05). A change in the distance between the bone surface and the fixator was linearly related to the stiffness in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) and in transverse loading of brass rods (p < 0.001). If the bone ends touched each other, the axial stiffness of the construct increased almost 10 times (265 N/mm), as compared to a fracture gap size of 2 mm (31 N/mm). In vivo experiments had a complication rate of less than 10% when we used 1.2 mm pins, 6 mm offset and rats weighing 350-450 g. Our method and device for experimental external fixation of rat femora are reliable and the findings are reproducible. These can be used in bone repair and fracture healing research.     

Sinus barotrauma--late diagnosis and treatment with computer-aided endoscopic surgery

Sinus barotrauma is usually easy to diagnose, and treatment achieves good results. We present two severe cases where delayed diagnosis caused significant morbidity. The signs and symptoms were atypical and neither the patients themselves, nor the initial examiners recognized that the onset of symptoms coincided with descent in a commercial airliner. CT and MRI scans of the brain were normal, but in both cases showed opafication of the sphenoid sinuses, which lead to the correct diagnosis. Subsequent surgical intervention consisting of endoscopic computer-aided surgery showed blood and petechia in the affected sinuses. This procedure provided immediate relief.     

K(ATP) channels and pancreatic islet blood flow in anesthetized rats: increased blood flow induced by potassium channel openers

K(ATP) channels are important for insulin secretion and depolarization of vascular smooth muscle. In view of the importance of drugs affecting K(ATP) channels in the treatment of diabetes, we investigated the effects of these channels on splanchnic blood perfusion in general and pancreatic islet blood flow in particular. We treated anesthetized Sprague-Dawley rats with the K(ATP) channel openers diazoxide or NNC 55-0118 or the K(ATP) channel closer glipizide. Both diazoxide and NNC 55-0118 dose-dependently increased total pancreatic and islet blood flow in the presence of moderate hyperglycemia, but had no effects on the blood perfusion of other splanchnic organs. Diazoxide markedly lowered the mean arterial blood pressure and thus increased vascular conductance in all organs studied. NNC 55-0118 had much smaller effects on the blood pressure. Glipizide did not affect total pancreatic blood flow, but decreased islet blood flow by 50% in the presence of hypoglycemia. We conclude that K(ATP) channels actively participate in the blood flow regulation of the pancreatic islets and that substances affecting such channels may also influence islet blood flow.     

Decreased cerebrospinal fluid acetylcholinesterase in patients with subcortical ischemic vascular dementia

The main objective was to investigate the acetylcholinesterase E (AChE) activity in the cerebrospinal fluid (CSF) of patients with three common dementia disorders. We also wanted to investigate the influence of apolipoprotein E (ApoE) epsilon4 allele possession and CSF-tau level on the CSF-AChE activity in these patients. The study included 17 consecutive patients with subcortical vascular dementia (SVD), 39 with Alzheimer's disease (AD), 14 with frontotemporal dementia (FTD) and 12 controls. CSF was obtained by lumbar puncture and CSF-AChE activity was measured by an enzyme antigen immunoassay. CSF-AchE activity was significantly decreased compared to controls only in the SVD group (p = 0.010). The CSF-tau level was increased in the AD group compared to the control (p < 0.01) and FTD groups (p < 0.05). No influence of ApoE epsilon4 allele possession on CSF-AChE activity was found. It is suggested that abnormal CSF-AChE activity in patients with SVD reflects a disturbance in the cholinergic system.     

Prostate cancer--prevalence-based healthcare costs

OBJECTIVE: To calculate the total costs of in- and outpatient healthcare for patients with prostate cancer based on an episode-of-care approach. The cost analysis includes costs incurred during the first year of diagnosis, a longitudinal 3-year analysis and the incremental cost of prostate cancer during the first year of diagnosis. MATERIAL AND METHODS: Patients registered with prostate cancer between 1998 and 2000, according to the data files of the Southern Swedish Regional Tumour Registry, were given encrypted identifiers that could also be used in the Patient Administrative System of the Region Sk?ne County Council, making it possible to identify consumption of healthcare on an episode-of-care basis. Itemized costs for resources used by each individual patient were calculated from the complete accounting system of the County Council. RESULTS: Healthcare costs for prostate cancer during the first year varied between 45 000 and 51 000 SEK per patient. The second- and third-year costs were progressively lower, with an estimated total cost of 114 000 SEK over a period of 3 years. The age-standardized incremental cost of prostate cancer corresponded to 33 000 SEK during the first year, compared to the average cost per inhabitant. CONCLUSIONS: The episode-of-care approach, based on encrypted identifiers for the identification of the diagnoses of individual patients and their utilization of healthcare, gives a unique opportunity to estimate the healthcare costs of specific diseases. The incremental healthcare cost per patient with prostate cancer corresponded to 33 000 SEK during the first year.     

Large matrix proteoglycans,versican and perlecan,are expressed and secreted by human leukemic monocytes

THP-1 is a monocytic cell line originally derived from a patient with acute monocytic leukemia. Interactions of THP-1 cells with other cells and their microenvironment are largely determined by proteoglycans (PGs), the identity of which has not been determined. Previous studies on glycosaminoglycan expression by THP-1 cells and peripheral blood mononuclear cells from healthy individuals showed that both cell types secrete mainly chondroitin sulfate PGs to the culture medium, whereas heparan sulfate PGs are mainly retarded at the cell membrane. However, limited data on the type of PGs synthesized by THP-1 is available. In this study, the identification of PG types synthesised by THP-1 cells, which are not differentiated to macrophages, was examined. Analysis at the mRNA level by RT-PCR showed the expression of six cell membrane-associated PGs: syndecan-1, -2 and -4, glypican-1, thrombomodulin and CD44. Cell extraction, ion-exchange chromatography and dot blot analysis of the isolated PG populations with monoclonal antibodies showed the presence of syndecan-1 and thrombomodulin; the other two syndecans were not detected in any of the isolated populations. The synthesis of matrix PGs was also studied. THP-1 monocytes were positive for the mRNA encoding for versican and perlecan, but not for those encoding for decorin, biglycan, betaglycan and fibromodulin. The mRNA encoding for two versican splice variants V0 (351 bp) and V1 (386 bp), but not for V2, were identified. Biochemical analysis showed the presence of perlecan and of two populations of versican in culture medium with protein cores of average molecular sizes similar to those of V0 and V1. The production of these large matrix PGs by THP-1 monocytes is reported for the first time and may be of importance in monocyte malignant transformation and differentiation.     

Determination and clinical verification of dose-response parameters for esophageal stricture from head and neck radiotherapy

The purpose of this work is to determine the parameters and evaluate the predictive strength of the relative seriality model. This is accomplished by associating the calculated complication rates with the clinical follow-up records. The study is based on 82 patients who received radiation treatment for head and neck cancer. For each patient the 3D dose distribution delivered to the esophagus and the clinical treatment outcome were available. Clinical symptoms and radiological findings were used to assess the manifestation of radiation-induced esophageal strictures. These data were introduced into a maximum likelihood fitting to calculate the best estimates of the parameters used by the relative seriality model (D₅₀=68.4 Gy, γ=6.55, s=0.22). The uncertainties of these parameters were also calculated and their individual influence on the dose-response curve was demonstrated. The best estimate of the parameters was applied to 58 patients of the study material and their esophageal stricture induction probabilities were calculated to illustrate the clinical utilization of the calculated parameters. The calculation of the biological effective dose (BED) appeared to be significantly sensitive to the applied fractionation correction for complex treatment plans. The relative seriality model was proved suitable in reproducing the treatment outcome pattern of the patient material studied (probability of finding a worse fit=61.0%, the area under the ROC curve=0.84 and χ² test=0.95). The analysis was carried out for the upper 5 cm of the esophagus (proximal esophagus) where all the strictures are formed. Radiation-induced strictures were found to have a strong volume dependence (low relative seriality). The uncertainties of the parameters appear to have a significant supporting role on the estimated dose-response curve.