Treatment of Alzheimer's disease with a synthetic ACTH 4-9 analog

The synthetic ACTH 4-9 analog, Org 2766, was administered to 77 Alzheimer's patients for 6 months in a double-blind, placebo-controlled study. Although Org 2766 was tolerated well, no significant effect of Org 2766 could be demonstrated in terms of rating scales or cognitive functions.     

Multidetector computed tomography in acute joint fractures

Conventional radiography plays an essential diagnostic role in the primary evaluation of acute joint trauma. In complex fractures, however, computed tomography (CT) is an imaging modality often used second to radiography. As a result of technical breakthroughs in the field, multidetector CT (MDCT) allows faster imaging and better temporal, spatial, and contrast resolution compared with conventional single-slice spiral CT. MDCT with multiplanar reformation is helpful in disclosing fracture patterns, particularly in complex joint fractures, where they reveal occult fractures and show the exact number of fracture components and their degree of displacement.     

Factors associated with nonunion in conservatively-treated type-II fractures of the odontoid process

In type-II fractures of the odontoid process, the treatment is either conservative in a halo vest or primary surgical stabilisation. Since nonunion, requiring prolonged immobilisation or late surgery, is common in patients treated in a halo vest, the identification of those in whom this treatment is likely to fail is important. We reviewed the data of 69 patients with acute type-II fractures of the odontoid process treated in a halo vest. The mean follow-up was 12 months. Conservative treatment was successful, resulting in bony union in 32 (46%) patients. Anterior dislocation, gender and age were unrelated to nonunion. However, nonunion did correlate with a fracture gap (> 1 mm), posterior displacement (> 5 mm), delayed start of treatment (> 4 days) and posterior redisplacement (> 2 mm). We conclude that patients presenting with these risk factors are unlikely to achieve bony union by treatment in a halo vest. They deserve careful attention during the follow-up period and should also be considered as candidates for primary surgical stabilisation.     

Multidetector computed tomography of cervical spine fractures in ankylosing spondylitis

PURPOSE: To analyze multidetector computed tomography (MDCT) cervical spine findings in trauma patients with advanced ankylosing spondylitis (AS). MATERIAL AND METHODS: Using PACS, 2282 cervical spine MDCT examinations requested by emergency room physicians were found during a period of 3 years. Of these patients, 18 (16 M, aged 41-87, mean 57 years) had advanced AS. Primary imaging included radiography in 12 and MRI in 11 patients. RESULTS: MDCT detected one facet joint subluxation and 31 fractures in 17 patients: 14 transverse fractures, 8 spinous process fractures, 2 Jefferson's fractures, 1 type I and 2 type II odontoid process fractures, and 1 each: atlanto-occipital joint fracture and C2 laminar fracture plus isolated transverse process and facet joint fractures. Radiographs detected 48% and MRI 60% of the fractures. MRI detected all transverse and odontoid fractures, demonstrating spinal cord abnormalities in 72%. CONCLUSION: MDCT is superior to plain radiographs or MRI, showing significantly more injuries and yielding more information on fracture morphology. MRI is valuable, however, in evaluating the spinal cord and soft-tissue injuries. Fractures in advanced AS often show an abnormal orientation and are frequently associated with spinal cord injuries. In these patients, for any suspected cervical spine injuries, MDCT is therefore the imaging modality of choice.     

Radicular lower extremity pain as the first symptom of primary hyperparathyroidism

Clinical symptoms of hyperparathyroidism are generally nausea, vomiting, fatigue, constipation, and hypotonicity of the muscles and ligaments; bone pain and tenderness are also seen but are more common in secondary hyperparathyroidism. We report a histologically confirmed case of a 28-year-old man whose sole symptom of primary hyperparathyroidism was lower extremity radicular pain due to a vertebral brown tumor. Magnetic resonance imaging demonstrated brown tumor to be hyperintense on T2-weighted and slightly hypointense on T1-weighted sequences; it showed intense contrast enhancement with gadolinium. Because brown tumors usually contain hemosiderin a short T2 should have been expected, but this was not seen in our case. Healing resulted in decreasing contrast enhancement on T1-weighted sequences and increasingly short T2. To our knowledge, this is the first report of a lumbar vertebral brown tumor associated with primary hyperparathyroidism.     

A novel frozen brain tissue array technique: immunohistochemical detection of neuronal paraneoplastic autoantibodies

We introduce a modification of the tissue microarray technique in which several frozen brain tissue specimens are collected to a single frozen brain array block. In the present application, we use it for the detection of neuronal paraneoplastic anti-Hu autoantibodies. Representative samples from 15 different brain regions were collected according to a standard neuropathological autopsy protocol. Cryostat sections from each block were cut and conventionally stained. From representative areas, cylinder tissue samples from each specimen were punched and then arrayed into a recipient array block. Using the cryostat sections of this brain array, autoantibodies from seven anti-Hu-positive patient sera (confirmed by immunoblotting) were screened by immunohistochemistry. Neuronal architecture was well preserved and immunohistochemical staining was comparable to that of conventional cryostat sections. Because of the variable staining pattern in different brain areas, two anti-Hu-positive sera could be detected immunohistochemically by the one brain array. With the present array technique, it is possible to characterize the variable staining patterns of neuronal paraneoplastic autoantibodies in different locations of the human brain. The frozen brain array also allows the detection of RNA and DNA targets involved in neurological diseases.     

Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy-induced hypertension or obstetric cholestasis

OBJECTIVES: The present study aims at finding out whether a connection exists between altered serum free beta-hCG and/or alpha-fetoprotein (AFP) levels and the manifestation of specific pregnancy complications [i.e. gestational diabetes mellitus (GDM), pregnancy induced hypertension (PIH) or intrahepatic cholestasis of pregnancy (ICP)]. METHODS: We compared free beta-hCG and AFP multiples of median (MoM) values in singleton pregnancies. The study population consisted of 117 pregnancies with GDM, 107 with PIH and 24 with ICP. The control group consisted of 1148 singleton pregnancies without any pregnancy complications. All were spontaneously conceived. RESULTS: In the group with GDM, both the free beta-hCG (0.72 MoM) and AFP MoM values (0.93) were significantly lower than in controls (beta-hCG 0.97 MoM, p = 0.0063 and AFP 1.01 MoM, p = 0.01). No statistically significant differences in the marker levels were observed between the ICP pregnancies and the control group. CONCLUSIONS: GDM has an impact on maternal midtrimester free beta-hCG and AFP levels and may change the DS screening result.     

Alpha-adrenoceptor-mediated modulation of 5-HT2 receptor agonist induced impulsive responding in a 5-choice serial reaction time task

The activation of 5-HT2A receptors has been shown to enhance the probability of premature responding, regarded as a form of motor impulsive behaviour. At the behavioural level, the interaction of alpha-adrenoceptors and 5-HT2 receptors has been linked to head twitch behaviour, regarded as an experimental model of compulsive behaviour. The aim was to determine whether the probability of premature responding induced by an excess activation of 5-HT2A receptors can be modulated by the blockade of alpha1- or alpha2- adrenoceptors. In the experiments, the 5-choice serial reaction time task was used to measure attention and response control of the rats. The experiments assessed the effects of (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI) 0.1-0.2 mg/kg subcutaneously, a 5-HT2A/2C agonist, and prazosin, an alpha1-adrenoceptor antagonist, alone or in combination, on the performance of rats. In an additional experiment to examine the possible role of the alpha2-adrenoceptors, a potent, selective and specific alpha2-adrenoceptor antagonist, atipamezole, was given alone or in combination with DOI. Results showed that DOI increased the probability of premature responses, but it did not affect the choice accuracy. Prazosin (0.1 or 0.3 mg/kg, subcutaneously), given on its own had no effects on probability of responding prematurely, but prazosin (0.3 mg/kg.) was able to attenuate the DOI-induced responding. Atipamezole (0.1 mg/kg, s.c.) did not attenuate the effect of DOI on probability of premature responding. When given at lower doses, DOI (0.03 mg/kg) and atipamezole (0.03 mg/kg) synergistically increased the probability of premature responding, whereas a higher dose of atipamezole (0.3 mg/kg) on its own increased the probability of responding prematurely, but this effect was not additive to that of 0.1 mg/kg DOI. These data indicate that 5-HT2 receptor activation enhances impulsive responding and this effect can be diminished by the blockade of alpha1-adrenoceptors. Atipamezole, an alpha2-antagonist, enhances the probability of premature responding and shares the mechanism of action with the 5-HT2 agonist in this respect. These results provide evidence for an interaction between the serotonergic 5-HT2 receptors and alpha-adrenoceptors in the modulation of response control to the motor impulsivity type of behaviour (premature responding) in addition to that of compulsory behaviour (head shakes) found previously.     

Interrelationships between muscle structure,muscle strength,and running economy

PURPOSE: The present study was designed to investigate possible differences in running economy (RE) among elite middle-distance runners by examining muscle structure and maximal isometric force (MVC). METHODS: Ten young male runners ran at six different running speeds. During the running bouts, respiratory gases, and blood lactate were measured. Muscle biopsies were obtained from the vastus lateralis muscle for analyzing fiber type distribution, muscle fiber area, myosin heavy chain (MHC) composition, activities of a number of metabolic enzymes (citrate synthase, lactate dehydrogenase, phosphofruktokinase, and 3-hydroxyacyl-CoA-dehydrogenase), and titin isoforms. RESULTS: Energy expenditure (EE) increased linearly up to the speed of 6.0 m.s. The relative distribution of the MHC isoforms was MHC I: 67.0%, MHC IIA: 31.5%, and MHC IIX: 1.5%. The present results demonstrated that higher the area of Type II fibers, higher the MVC (r = 0.59, P< 0.05). The amount of MHC II correlated inversely with EE when running close to the competition speed (r = -0.61, P< 0.05). Enzyme activities did not correlate significantly with either RE or EE. Titin analysis revealed that a faster-mobility titin band was observed in all subjects, whereas a lower-mobility titin band was observed only in the most economical runner. CONCLUSION: Differences in RE among homogeneous group of middle-distance runners were observed at various running speeds. This may partly be explained by differences in muscle fiber distribution, MHC composition, and titin isoforms.     

Nimodipine affects the microcirculation and modulates the vascular effects of acetylcholinesterase inhibition

The present investigation was undertaken in order to study whether microvascular effects of the calcium antagonist nimodipine induces changes that can explain an increased detoxification of the highly toxic cholinesterase inhibitor soman. Anaesthetised, tracheotomised and artificially ventilated rats were treated intra-peritoneally (ip) with nimodipine, 10 mg kg(-1) or vehicle followed one hour later by the exposure to 45 microg kg(-1) soman (iv). Nimodipine per se induced a vasodilation in the intestine, myocardium and other muscles. In the abdominal skin soman elicited a significant vasoconstriction that was turned into an increased blood flow after nimodipine pre-treatment. A slight vasoconstriction in diaphragm of soman intoxicated rats was turned into a significant vasodilation by nimodipine pre-treatment. In the intestinal parts no effect of soman was detected. However, in nimodipine pretreated animals soman induced a significant vasoconstriction. The capacity of soman detoxifying processes, i.e. enzymatic hydrolysis and covalent binding to different esterases, is unequally distributed throughout the body. Together with the knowledge of the detoxifying processes of cholinesterase inhibition the results support our theory, that nimodipine alters the peripheral blood flow in a beneficial way resulting in improved detoxification ability.