Prospective strategies for cholinergic interventions in Alzheimer's disease

The cholinergic hypothesis of memory dysfunction has guided most of the recent proposals for treating the primary symptoms of AD. The efficacy of these treatments has been severely limited. This review examines two major lines of evidence which suggest that the cholinergic hypothesis may have to be expanded and revised. The cholinergic hypothesis focuses on pre-synaptic defects. It assumes cholinoceptive neurons would function normally with adequate stimulation. Evidence is not sufficient to support this assumption. In addition, dissociations have been demonstrated between muscarinic receptor number and functional response of cholinoceptive neurons. Various measures are proposed to investigate the functional integrity of muscarinic receptors in AD patients. AD often has been characterized as a disorder produced by generalized cholinergic hypoactivity. Evidence for cortisol hypersecretion, abnormal dexamethasone suppression, and the occurrence of depressive symptoms, motoric dysfunction and sleep abnormalities in AD patients is more consistent with regional cholinergic hyperactivity than generalized hypoactivity. Resolution of these discrepancies could shed new light on the pathophysiology and treatment strategies for AD. Cholinoceptive neurons could be hypersensitive, subsensitive or have unaltered responsivity. These options would have very different treatment implications. New developments in outcome assessment which are capable of discriminating varieties of differential response to treatment can spur treatment development and improve quality of care for patients with complex disorders such as AD.     

Specific binding of the mononuclear phagocyte colony-stimulating factor CSF-1 to the product of the v-fms oncogene.

Cells transformed by the McDonough strain of feline sarcoma virus (SM-FeSV) express a v-fms-encoded glycoprotein whose expression at the cell surface correlates with the transformed phenotype. The mouse mononuclear phagocyte growth factor CSF-1 specifically binds to SM-FeSV-transformed cells at high-affinity sites indistinguishable from those detected on normal feline macrophages. A monoclonal antibody to a v-fms-encoded epitope competed for CSF-1 binding to SM-FeSV-transformed cells, and chemical crosslinking demonstrated that murine CSF-1 bound to the v-fms gene product at the cell surface. Although SM-FeSV-transformed fibroblast lines were found to secrete CSF-1, the growth of transformed cells was not affected by antibodies to the v-fms gene product or to the growth factor. Tyrosine phosphorylation of the v-fms products in membranes was observed in the absence of CSF-1 and was not enhanced by addition of the murine growth factor. The data support the hypothesis that the c-fms protooncogene product is related, and possibly identical, to the CSF-1 receptor and suggest that the v-fms-encoded kinase functions in the absence of an exogenous growth factor.     

Academic Achievement of Children with Epilepsy

The academic achievement scores of 122 children with epilepsy were examined in relation to demographic and clinical seizure variables. As a group, these children were making less academic progress than expected for their age and IQ level. Academic deficiencies were greatest in arithmetic, followed by spelling, reading, comprehension, and word recognition. Results of the multiple regression analyses indicated a modest combined predictive significance of the demographic and clinical seizure variables for academic performance. In addition, the magnitude of these relationships varied by academic area. Among the individual variables examined the strongest correlates of academic performance were age of the child, age of seizure onset, lifetime total seizure frequency, and presence of multiple seizures (absence and tonic-clonic). These results are discussed in relation to developing an understanding of the factors which underlie academic vulnerability in children with epilepsy.     

Multiple Implants for First Molar Prosthodontics

Problems that can occur when single implants are utilized to restore first molar teeth include the frequent loosening of screws, as well as screws and/or implant breakage. These may result from torquing and rotational movements of the prosthesis during masticatory and parafunctional mandibular movements. When sufficient bone and mesio-distal restorative space is present, the placement of two implants should be considered.     

The use of a priori knowledge to quantify short echo in vivo 1h mr spectra

In vivo ¹H MR spectra of the prefrontal cortex acquired with the stimulated echo acquisition mode (STEAM) TE = 20 ms sequence were quantified to determine relative levels of cerebral metabolites. A priori knowledge of spectra from individual metabolites in aqueous solution was incorporated into a frequency domain quantification technique. The accuracy and precision of modeling these metabolites were investigated with simulated spectra of varying signal-to-noise ratios (SNRs) and relative metabolite levels. The efficacy of modeling in vivo data was tested by quantifying 10 repeated measures of two consecutively acquired in vivo spectra (an 8?cm³ volume of interest (VOI) and a 4?cm³ VOI positioned within the 8?cm³ VOI) on the same normal subject. The differences in levels of glutamate (Glu), phosphocreatine plus creatine (PCr+Cr) and choline-containing compounds (Cho₁ between spectra from the 8? and 4?cm³ VOIs corresponded with the expected differences observed in the proportions of gray matter within the VOIs (estimated from ¹H images). Correcting for the T₁ and T₂ relaxation, the estimated concentrations of N-acetylaspartate, PCr+Cr, Cho₁, Glu, and glutamine were consistent with previous in vivo and in vitro reports.     

Intestinal plethora: An early sign of acute posttraumatic hepatic artery-portal vein arteriovenous fistula

Traumatic communications between the hepatic artery or its branches and the portal vein or its tributaries usually are clinically occult until the late sequelae of portal hypertension, such as esophageal and mesenteric varices, ascites, or congestive heart failure, become manifest. The authors describe the early diagnosis of such a lesion by computed tomography. The CT findings included a hepatic hematoma and, more significantly, diffuse thickening of the small and large bowel wall. This thickening represents vascular congestion of the bowel caused by acute portal hypertension prior to the development of decompressing portal collateral circuits. When this CT finding is not associated with other signs of intestinal ischemia or infarction, it should suggest portal hypertension and lead to arteriography for diagnosis and therapy of arterioportal fistula.     

Progress in the treatment of thoracic aortic aneurysms

Progress in the management of thoracic aortic aneurysm includes the following aspects:

1. the concepts of the disease itself, which is frequently generalized so that the second most common cause of late death is rupture of another aneurysm;
2. the diagnostic techniques used: computed tomographic scanning as well as aortography;
3. the medical treatment: with beta blockade and antihypertensive drugs in stable aortic injury in the patient with multiple critical injuries;
4. that hypothermic circulatory arrest with cardiopulmonary bypass and brain temperatures down to 16–20°C has increased successful aortic arch replacement from 50–75% to over 90%;
5. that rapid autologous transfusion by means of a modified Hemonetics machine can collect and process a unit of shed blood in 2–3 minutes and has reduced transfusion requirements by more than half;
6. the vigorous treatment of both consumptive and dilutional coagulopathies;
7. the new reconstructive techniques: involving composite valve graft replacement of the aortic valve, root, and arch as well as coronary artery reattachment;
8. that the use of viable tissue flaps in the treatment of infected aortic grafts as well as intravenous and local irrigation with antibiotics was successful in 8 of 9 of our cases;
9. that graft replacement with intensive antibiotic therapy was effective in 19 of 22 of our patients with mycotic thoracic aortic aneurysm.