Perfluorochemicals as US contrast agents for tumor imaging and hepatosplenography: preliminary clinical results

In animals, perfluorochemicals (PFCs) are effective ultrasound (US) contrast agents that produce hepatic, splenic, and tumor enhancement. The use of Fluosol-DA 20%, an emulsion of perfluorodecalin and perfluorotripropylamine, was studied in nine non-critically ill patients with cancer who had liver lesions. US studies without Fluosol were compared with studies obtained 24, 48, and 72 hours after Fluosol infusion. Vital signs and extensive laboratory analyses are performed before and after Fluosol infusion. Liver metastases from colonic, pancreatic, and gastric carcinoma exhibited rim or diffuse enhancement after a Fluosol dose of 1.6 g/kg or greater. Fluosol produced echogenic enhancement of the liver and spleen relative to kidney at a dose of 2.4 g/kg, allowing the detection of nonenhancing lesions. In addition, Fluosol at a dose of 1.6 g/kg or greater allowed detection of lesions not seen before contrast medium was administered in three of the seven patients studied. There was a mild increase in the level of serum glutamic oxaloacetic transaminase in two patients, one given 2.4 and the other 3.2 g/kg of Fluosol. Mild and transient allergic reactions without change in vital signs were experienced by two patients.     

New players in old amyloid precursor protein-processing pathways

The amyloid precursor protein (APP) gives rise to beta-amyloid peptides, which are the main constituents of senile plaques in brains of Alzheimer's disease (AD) patients. The generation of beta-amyloid peptides requires the enzymatic activity of the beta-site APP-cleaving enzyme 1 (BACE1). BACE1 is primarily expressed by neurons and increased BACE1 protein concentrations and enzymatic activities have been reported in the brains of AD patients. However, there is accumulating evidence that, in addition to neurons, reactive astrocytes are capable of expressing BACE1 and, therefore, may contribute to beta-amyloid plaque formation. This suggests that conditions accompanied by chronic astrocyte activation may contribute to developing AD. Non-amyloidogenic processing of the APP can be stimulated by phorbol esters (PEs) and by intracellular diacylglycerol (DAG) generation. This led to the hypothesis that classical and novel protein kinase Cs (PKCs), which are activated by DAG/PEs, regulate APP processing. However, in addition to PKCs, there are other DAG/PE receptors present in neurons which may participate in the modulation of APP processing. Munc13-1, a presynaptic protein with an essential role in synaptic vesicle priming, represents such an alternative target of the DAG second messenger pathway. Using Munc13-1 knock-out mice and human neuroblastoma cells transfected with wild-type and mutant Munc13-1 constructs it was demonstrated that Munc13-1 acts independently of and in parallel with PKC to modulate APP metabolism. Therefore, agonists specific for the Munc13-1 C1-domain or small molecules mimicking the function of the endogenous Munc13-1 activator RIM1 may prove useful to shift APP processing towards the non-amyloidogenic pathway.     

Incidence and clinical features of traveler's diarrhea in infants and children

To assess the incidence rate and the characteristics of traveler's diarrhea in small children ages 0 to 2 years, children ages 3 to 14 years, and adolescents ages 15 to 20 years a retrospective survey was conducted. Of the pretravel visitors to the Zurich University Vaccination Center, all those ages 0 to 20 years were selected between October, 1987, and May, 1988. They received a questionnaire within 2 weeks after returning home. Of the 446 young travelers who were recruited, 363 (81.3%) could be evaluated. Within 14 days in the tropics or subtropics, traveler's diarrhea occurred in 8 of 20 (40.0%) small children, in 4 of 47 (8.5%) children ages 3 to 6 years, in 10 of 46 (21.7%) children ages 7 to 14 years and in 90 of 250 (36.0%) adolescents (P = 0.0003). In small children the clinical course tended to be severe and prolonged (average duration, 29.5; median, 17.5 days) when compared with other age groups (3 to 5 days). In 40% of all the children the parents reported that they had consistently practiced dietary preventive measures. For self-treatment oral rehydration solutions were used in 5.0% and loperamide in 33.8%. In conclusion adults should be discouraged from taking small children to developing countries unless necessary. Parents should be instructed about how to prevent traveler's diarrhea and about the mainstay of self-therapy in pediatric patients by oral rehydration solutions.     

Bolus or continuous hydrocortisone – that is the question

Constantly evolving treatment guidelines based on a growing body of randomized controlled trials are helping us to improve outcomes in sepsis. However, it must be borne in mind that proven benefit from individual sepsis treatments does not guarantee synergistic beneficial effects when new treatments are added to sepsis management. Indeed, unexpected harmful interactions are also possible. A good example of this is the conflict between intensive insulin therapy and 'low dose' hydrocortisone in septic shock. The goal of tight glycaemic control is made more complicated by steroid-induced hyperglycaemia. In their recent study, Loisa and coworkers demonstrate a measure that reduces the risk for this interaction. They found continuous infusion of hydrocortisone to be associated with fewer hyperglycaemic episodes and reduced staff workload compared with bolus application.     

Coralline hydroxyapatite bone graft substitutes: preliminary report of radiographic evaluation

A new bone graft substitute made by conversion of the calcium carbonate exoskeleton of reef-building sea coral into hydroxyapatite has recently become clinically available. The normal radiographic appearance of two forms of this material is described. In the immediate postoperative period, the exoskeletal architecture of these implants is readily appreciated. With graft incorporation over the ensuing months, their intrinsic structure is gradually lost in association with poor marginal definition. Evolving radiographic findings reflect the biocompatible nature of these implants, which provides the potential for ingrowth of native bone with preservation of the coralline scaffold, resulting in enhanced biomechanical properties.     

Cerebrospinal fluidCHOLINESTERASES—MARKERS for loss ofcholinergic basal forebrain neurons?

The present study was conducted to test the hypothesis that cholinergic basalforebrain neurons are a major source of cerebrospinal fluid (CSF) cholinesterases. To address thisquestion enzyme activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inboth CSF and parietal cortex were assayed following selective lesion of basal forebrain cholinergicneurons by a single intracerebroventricular application of the cholinergic immunotoxin192IgG-saporin. Cholinergic immunolesions led to a dramatic decrease in total AChE activity inparietal cortex, which was due to the specific loss of the G4 molecular form while the activity ofthe G1 form was increased as compared to nonlesioned animals. In contrast, the total enzymeactivity of BChE and its molecular forms were not affected by cholinergic lesion in both parietalcortex and CSF. The data suggest, that cholinergic basal forebrain neurons are seemingly not amajor source of cholinesterases in the CSF, and do not provide any evidence for using CSFcholinesterases as a diagnostic marker of basal forebrain cholinergic cell loss in humans.     

Local tissue properties in bone healing: Influence of size and stability of the osteotomy gap

To characterize the site-specific mechanical and histological properties in fracture repair and to relate these properties to the initial mechanical situation, an experimental fracture model was used in the metatarsus of 42 sheep. the mechanical situation of a transverse osteotomy was described by three gap sizes (1,2, or 6 mm) and two amounts of strain (7 or 31 %). An external fixator that allowed a defined axial movement provided control of these settings. Nine weeks following surgery, the healing area was dissected and tensile and compressive properties were measured in subregions of the fracture gap and the periosteal callus. The central, sagittal section was used for quantitative histology. We found the quality of the tissue along the osteotomy line to be most important for regaining mechanical stability. Increasing the size of osteotomy gaps resulted in poorer mechanical and histological qualities, and the repair process was less complete. Interfragmentary strain did not significantly influence the repair process. The smaller strain levels had already stimulated the secondary repair process, and this stimulatory effect could not be further enhanced by increasing the amount of strain. Our finding that large gaps between bone segments were not as well healed as were smaller gaps suggests that it is advantageous to avoid large gaps in fracture treatment.