Carboxylic ester hydrolase and amylase in ischemic pancreatitis in the guinea pig

OBJECTIVES: To define the clinical, neuropsychological, and radiological features of bilateral parietal lobe atrophy. METHODS: Four patients underwent a comprehensive longitudinal neuropsychological assessment, as well as MRI and HMPAO-SPECT. RESULTS: The consistent findings in the patients were early visuospatial problems, agraphia of a predominantly peripheral (or apraxic) type, and difficulty with bimanual tasks, all of which outweighted deficits in memory and language until later in the course of the illness. As the disease progressed, impairments in the phonological aspects of language and in auditory-verbal short term memory were often striking, perhaps reflecting spread from the parietal lobe to perisylvian language areas. Three patients went on to develop a global dementia and fulfilled the criteria for a clinical diagnosis of probable Alzheimer's disease; the fourth patient has only recently been identified. Neuroimaging disclosed bilateral parietal lobe atrophy (MRI) and hypoperfusion (SPECT), which was out of proportion to that seen elsewhere in the brain. One patient has died and had pathologically confirmed Alzheimer's disease with particular concentration in both superior parietal lobes. CONCLUSIONS: Bilateral biparietal atrophy is a recognisable clinical syndrome which can be the presenting feature of Alzheimer's disease. Although the label "posterior cortical atrophy" has been applied to such cases, review of the medical literature suggests that this broad rubric actually consists of two main clinical syndromes with features reflecting involvement of the occipitotemporal (ventral) and biparietal (dorsal) cortical areas respectively.     

Intensified treatment of acute childhood lymphoblastic leukaemia has improved prognosis, especially in non-high-risk patients: the Nordic experience of 2648 patients diagnosed between 1981 and 1996. Nordic Society of Paediatric Haematology and Oncology (NOPHO)

In a multinational, population-based study from the five Nordic countries (Denmark, Finland, Iceland, Norway and Sweden), 2648 children below 15 y of age were diagnosed with acute lymphoblastic leukaemia (ALL) in the years 1981-1996. The annual incidence was 3.9/100000 children and was stable throughout the study period. The development from regional or national protocols to common Nordic treatment protocols for all risk groups was completed in 1992 through a successive intensification of therapy, based on multidrug chemotherapy including pulses of methotrexate in high doses and avoidance of cranial irradiation in most children. For children with non-B-cell ALL (n=2602), the event-free survival (p-EFS) increased from 0.53+/-0.02 (diagnosed 7/81-6/86) to 0.67+/-0.02 (7/86-12/91) to 0.78+/-0.02 (1/92-12/96). The corresponding p-EFS values at 5 y were 0.57, 0.70 and 0.78, respectively. The main improvements were seen in the group of children with non-high risk leukaemia, with 5-y p-EFS values increasing from 0.60 to 0.76 and 0.85 for the three periods. In high-risk patients, progress has been moderate, especially in children with high white blood cell values at diagnosis. During the last 5-y period, only 10% of the patients received cranial irradiation in first remission while 90% of the patients received high doses of cytostatic infusions (methotrexate isolated or combined with cytarabinoside) and multiple intrathecal injections of methotrexate as CNS-adjusted treatment without any indication of an increased CNS relapse rate.     

Evidence suggesting that gonadal hormones influence benzodiazepine withdrawal-induced weight loss in rats

Long-term potentiation (LTP) of synaptic transmission in the CA1 region of the hippocampus is thought to result from either increased transmitter release, heightened postsynaptic sensitivity, or a combination of the two. We have measured evoked glutamate release from Schaffer collateral/commissural fiber terminals in CA1 by recording synaptically activated glutamate transporter currents in hippocampal astrocytes located in stratum radiatum. Although several manipulations of release probability caused parallel changes in extracellular field potentials and synaptically activated transporter current amplitudes, induction of LTP failed to alter transporter-mediated responses, suggesting that LTP does not alter the amount of glutamate released upon synaptic stimulation.     

Application of the laryngeal mask for elective percutaneous dilatation tracheotomy

Percutaneous dilatational tracheostomy is an increasingly accepted procedure for bed-side tracheostomy. The exact positioning of the endotracheal tube, the localization of the point for puncturing the trachea and damage to the endotracheal tube and the cuff as well as to the bronchoscope due to the puncturing process are technical problems which can endanger the course of the operation. In a prospective randomized study, we examined whether use of the laryngeal mask airway (LMA) is a real alternative to the endotracheal tube during tracheostomy. Of 48 consecutive patients only 43 fulfilled all criteria for this study: PaO2 > 100 mmHg, PaCO2 < 45 mmHg (in patients with head injury < 35 mmHg) under intermittent positive pressure ventilation (IPPV) with a mean ventilation pressure of < 25 mmHg and an FiO2 of 1.0. Patients with intestinal obstruction, hemorrhages of the mouth and nose and unfavourable anatomic conditions were not included in this study. Three more patients had to be excluded from the study because of technical problems. In 21 patients tracheostomy was performed using an endotracheal tube (ET group) and in 19 patients using a LMA (LM group). After positioning of the endotracheal tube or the LMA, tracheostomy was performed in the usual way. Arterial blood gases (PaO2 and PaCO2) were investigated before positioning of the endotracheal tube or the LMA, five minutes after this procedure and five minutes after the end of tracheostomy. Mean arterial pressure (MAP), heart frequency (HF) and peripheral oxygen saturation (SpO2), endexpiratory CO2 partial pressure (PetCO2) and minute ventilation volume (MVV) were registered every 60 seconds. The ET group and LM group did not differ regarding basic diseases, age and severity of illness. Before the beginning of tracheostomy, there were no differences in MAP, HF, SpO2, PetCO2 and PaCO2 between the two groups. Before tracheostomy, only PaO2 was significantly higher in the LM group than in the ET group. Immediately before the insertion of the tracheal cannula and five minutes after the end of tracheostomy, there were no differences in the measured parameters of the two groups. An increase in PetCO2 and a decrease in minute ventilation volume were observed in both groups. Regarding technical complications, the LMA is a safe alternative to the endotracheal tube. The choice of method should depend on the basic disease and the patient's ventilation requirements at the time of tracheostomy, while there is still a call for safe instruments guaranteeing sufficient sealing of the respiratory tract during the dilatational tracheostomy and simultaneous avoidance of technical problems during puncturing of the trachea and widening of the point of puncturing.     

Channels formed by the transmembrane helix of phospholamban: a simulation study

Phospholamban is a small membrane protein which can form cation selective ion channels in lipid bilayers. Each subunit contains a single, largely hydrophobic transmembrane helix. The helices are thought to assemble as a pentameric and approximately parallel bundle surrounding a central pore. A model of this assembly (PDB code IPSL) has been used as the starting point for molecular dynamics (MD) simulations of a system consisting of the pentameric helix bundle, plus 217 water molecules located within and at either mouth of the pore. Interhelix distance restraints were employed to maintain the integrity of the helix bundle during a 500 ps MD simulation. Water molecules within the pore exhibited reduced diffusional and rotational mobility. Interactions between the alpha-helix dipoles and the water dipoles, the latter aligned anti-parallel to the former, contribute to the stability of the system. Analysis of the potential energy of interaction of a K+ ion as it was moved through the pore suggested that unfavourable interactions of the cation with the aligned helix dipoles at the N-terminal mouth were overcome by favourable ion-water interactions. Comparable analysis for a Cl ion revealed that the ion-(pore + water) interactions were unfavourable along the whole of the pore, increasingly so from the N- to the C-terminal mouth. Overall, the interaction energy profiles were consistent with a pore selective for cations over anions. Pore radius profiles were used to predict a channel conductance of 50 to 70 ps in 0.2 M KCl, which compares well with an experimental value of 100 ps.     

Cytoplasmic tail regulates the intercellular adhesion function of the epithelial cell adhesion molecule

Ep-CAM, an epithelium-specific cell-cell adhesion molecule (CAM) not structurally related to the major families of CAMs, contains a cytoplasmic domain of 26 amino acids. The chemical disruption of the actin microfilaments, but not of the microtubuli or intermediate filaments, affected the localization of Ep-CAM at the cell-cell boundaries, suggesting that the molecule interacts with the actin-based cytoskeleton. Mutated forms of Ep-CAM were generated with the cytoplasmic domain truncated at various lengths. All of the mutants were transported to the cell surface in the transfectants; however, the mutant lacking the complete cytoplasmic domain was not able to localize to the cell-cell boundaries, in contrast to mutants with partial deletions. Both the disruption of the actin microfilaments and a complete truncation of the cytoplasmic tail strongly affected the ability of Ep-CAM to mediate aggregation of L cells. The capability of direct aggregation was reduced for the partially truncated mutants but remained cytochalasin D sensitive. The tail truncation did not affect the ability of the transfectants to adhere to solid-phase-adsorbed Ep-CAM, suggesting that the ability to form stable adhesions and not the ligand specificity of the molecule was affected by the truncation. The formation of intercellular adhesions mediated by Ep-CAM induced a redistribution to the cell-cell boundaries of alpha-actinin, but not of vinculin, talin, filamin, spectrin, or catenins. Coprecipitation demonstrated direct association of Ep-CAM with alpha-actinin. Binding of alpha-actinin to purified mutated and wild-type Ep-CAMs and to peptides representing different domains of the cytoplasmic tail of Ep-CAM demonstrates two binding sites for alpha-actinin at positions 289 to 296 and 304 to 314 of the amino acid sequence. The results demonstrate that the cytoplasmic domain of Ep-CAM regulates the adhesion function of the molecule through interaction with the actin cytoskeleton via alpha-actinin.     

The evolution of hexamerins and the phylogeny of insects

The impact of group discussion on the decision-making effectiveness of medical teams was examined. Three-person teams of physicians diagnosed 2 hypothetical medical cases. Some of the information about each case was given to all team members prior to discussion (shared information), whereas the rest was divided among them (unshared information). Compared with unshared information, shared information was more likely to be pooled during discussion and was pooled earlier. In addition, team leaders were consistently more likely than other members to ask questions and to repeat shared information and, over time, also became more likely than others to repeat unshared information. Finally, pooling unshared (but not shared) information improved the overall accuracy of the team diagnoses, whereas repeating both shared and unshared information affected bias (but not accuracy) in the diagnoses.     

Valproate prophylaxis in a prospective clinical trial of refractory bipolar disorder

OBJECTIVE: The authors studied the efficacy of valproate plus lithium and of triple therapy with lithium, carbamazepine, and valproate in refractory bipolar illness. METHOD: The subjects were 24 bipolar outpatients who had completed an intended 3-year crossover study comparing lithium, carbamazepine, and their combination. Patients entered a 1-year phase of valproate plus lithium because of inadequate response or major side effects, and patients with inadequate responses were offered an additional year of treatment with all three mood-stabilizing drugs. RESULTS: Six (33%) of the 18 evaluable patients had moderate to marked responses to valproate plus lithium; four of these six had not responded to any previous treatment condition. Three of seven patients responded to triple therapy, although only one response was marked. CONCLUSIONS: Some outpatients with bipolar disorder refractory to lithium and carbamazepine received clinically relevant prophylactic benefit from valproate when used with lithium or in triple therapy.     

Illness-specific control issues in patients with vertigo as the main symptom

The study explored the relationship between health locus of control and anxiety in 90 patients with the chief complaint of dizziness/vertigo. The patients were subjected to a neurological examination, including standardised history, physical examination, electronystagmography with caloric testing and posturography, auditory and visually brainstem-evoked responses, masseter reflex, vertebrobasiliar transcranial Doppler, optional: cranial imaging (CCT/MRI), cardial diagnostic, and a psychiatric-psychodynamic examination (including psychometric tests: STAI-G X2, KKG, SBA-S). The whole group of patients (psychogenic and organic dizziness) had a specific pattern of health locus of control: "double health external" (Type IV-Wallston and Wallston 1982). Patients with psychogenic dizziness showed a higher score of external locus of control (chance) compared with the patients with organic dizziness. High anxiety scores were accompanied by high scores of external locus of control (powerful others and chance) above all in the patients with psychogenic dizziness. Implications for therapy are discussed.     

Extensive epidural hemangioma with skin and bone involvement. A case report

STUDY DESIGN: This is a case report. OBJECTIVE: To report and to examine the clinical findings and management of epidural cavernous hemangioma. SUMMARY OF BACKGROUND DATA: Spinal epidural cavernous hemangiomatous malformation is a very rare entity. Only 20 cases of this disease have been reported in the literature. METHODS: The case of a 20-year-old woman with spinal epidural cavernous hemangioma was reviewed. RESULTS: The clinical presentation, diagnosis, and therapy of this disease are discussed. CONCLUSION: The treatment of epidural hemangioma consists of total or subtotal excision of the lesion, depending on the relation of the lesion to the spinal cord.