Adaptive functioning following traumatic brain injury and orthopedic injury: a controlled study

BACKGROUND: In an effort to intensify osteosarcoma therapy, systemic ifosfamide was added pre- and postoperatively to an already aggressive three-drug regimen. In a subgroup of patients, loco-regional treatment intensification was attempted by using the intraarterial route to give cisplatin. PATIENTS AND METHODS: Patients < or = 40 years at diagnosis of a localised, de novo high-grade central extremity osteosarcoma were eligible for inclusion into study COSS-86 if registered within three weeks from biopsy. Doxorubicin, high-dose methotrexate, and cisplatin were given to all patients. Patients who fulfilled one or more of three defined high-risk criteria received early systemic treatment intensification by adding ifosfamide as the fourth agent. Preoperatively, these high-risk patients received cisplatin either intraarterially or intravenously. RESULTS: 171 eligible patients were entered, of which 128 were stratified into the high-risk group. When all 171 were analysed by intention-to-treat, actuarial overall and event-free survival rates at ten years were 72% and 66%, respectively. No benefit of intraarterial cisplatin application was detected. Cumulative treatment toxicity was considerable. CONCLUSIONS: In a multicenter setting, intensive treatment of osteosarcoma according to protocol COSS-86 led to long-term disease-free survival for two thirds of patients. We saw no benefit of using the intraarterial route to administer cisplatin.     

Patterns of expression for the mRNA corresponding to the four isoforms of phospholipase Cbeta in mouse brain

Ligand binding to neurotransmitter and hormone receptors which couple to the Gq subclass of GTP-binding protein leads to the activation of phospholipase Cbeta (PLCbeta) which hydrolyses phosphatidyl-inositol 4,5-bisphosphate, yielding a pair of second messengers, diacylglycerol and inositol 1,4,5-trisphosphate (IP3). The expression of PLCbeta1-4 mRNAs was comparatively examined by in situ hybridization in the mouse brain. In adults, PLCbeta1 mRNA was expressed predominantly in the telencephalon, including the cerebral cortex, hippocampus, amygdala, lateral septum and olfactory bulb, with little expression in most thalamic nuclei. PLCbeta2 mRNA was distributed in the white matter, suggesting its expression in non-neuronal cells, most likely oligodendrocytes. PLCbeta3 mRNA was specifically expressed in cerebellar Purkinje cells. The highest levels of PLCbeta4 mRNA were detected in Purkinje cells. High levels of PLCbeta4 mRNA were also found in the thalamus and medial septum, whereas weak signals were detected in most telencephalic regions, thus showing an expression pattern almost reciprocal to that of PLCbeta1 mRNA. During development, such characteristic regional expression of PLCbeta1 and PLCbeta4 were observed starting in late foetal stages, while specific expression of PLCbeta2 and PLCbeta3 appeared in early postnatal stages. We conclude that despite the existence of four PLCbeta isoforms, only one or two of them is expressed in individual neurons and glial cells. The distinct expression of PLCbetas provides a molecular basis for analysing the nature of the specific signal transduction pathway leading to the production of diacylglycerol and IP3 in distinct cell types and in different regions of the brain.     

Biodegradation of glutaraldehyde-tanned human umbilical vein grafts

A retrospective analysis of the long-term behavior of 111 glutaraldehyde-tanned human umbilical vein (HUV) grafts implanted between September 1977 and December 1993 was conducted. A total of 81 patients, with a mean age of 68.7 years, received the grafts and were followed up for between 1 and 131 months. The 5-year primary cumulative patency rate for above-knee femoropopliteal bypass was 83.1%, whereas that of other bypasses was 60.9%. An aneurysm of the graft was defined as a physically apparent localized dilatation, with diffuse ectasia being excluded. There were 11 aneurysms found in 9 grafts, 2 of which arose at the factory-made suture lines. The accumulated incidence of aneurysms had reached 21.9% by the 6th year. One aneurysm compressed the graft and resulted in limb-threatening ischemia and another resulted in frank rupture. Moreover, reinforcement of the mesh could not prevent aneurysm development, the repair of which is mandatory due to the risk of rupture and acute thrombosis. The HUV grafts showed an acceptable patency rate in the above-knee location, but the incidence of aneurysm formation after 5 years was abnormally high. Thus, both the risks and benefits of HUV grafts must be taken into account when considering their clinical application.     

Effects of lamotrigine and conventional antiepileptic drugs on amygdala- and hippocampal-kindled seizures in rats

A computer aided monitor-data processing system (CAMP-System) was developed in order to get a consistent and comprehensive database which can very precisely reflect intra-operative haemodynamic courses. The goal of the present study was to introduce a new method to scan and to gauge haemodynamic courses and to demonstrate its superiority over the traditional way of data processing based on a handwritten anaesthesia protocol. METHODS: The computerized system was applied to a study which was designed to investigate the influence of ketanserin (K) vs. urapidil (U) on haemodynamic stability during cardiac operations. Twenty male patients scheduled for myocardial revascularization received either 20 mg K or 30 mg U. Heart rate, central venous, arterial and pulmonary artery pressures were measured and on-line recorded every 20 seconds by the computer record system. In the handwritten protocol these variables were registered at eight pre-defined time points. Computerized data processing (including artifact depletion and data condensation) was compared to the results evaluated from the handwritten protocol. RESULTS: While the only significant differences in the handwritten protocol were slightly higher values of pulmonary artery pressures in group K, the computer analysis revealed a number of further differences. Higher maximum and a less stable time course of HR in group K in the pre-bypass phase and lower mean and standard deviation of MAP during cardiopulmonary bypass. CONCLUSION: Computerized data processing including automatic artifact suppression and data condensation was able to reveal differences in the course of haemodynamic variables that cannot be detected in a conventional handwritten protocol.     

Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion

Two patients with polymyositis (PM) or dermatomyositis (DM) complicated with massive pleural effusion are reported here. Both patients presented a high-grade fever, pleural effusion prominent on the right, and good response to steroid therapy. In a 50-year-old woman with PM, combined process of pleural inflammation, cardiomyopathy and coexisting hypothyroidism were considered to be responsible for the accumulation of the massive pleural effusion. However, in a 34-year-old man with DM, pleural inflammation associated with interstitial pneumonia or pleural microvasculopathy in DM was considered to be responsible for the accumulation of the massive pleural effusion.     

Studies on calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate, its metabolites and their enantiomers

The calcium antagonistic and alpha 1-adrenergic receptor blocking activities of monatepil maleate (CAS 103377-41-9, (+/-)-N-(6,11-dihydrodibenzo [b, e] thiepin-11-yl) -4-(4-fluorophenyl)-1-piperazinebutanamide monomaleate, AJ-2615), a novel calcium antagonist, its metabolites and their enantiomers were studied in vitro. Monatepil maleate inhibited calcium-induced contractions of rat thoracic aorta (pA2 = 8.71) and l-phenylephrine-induced contractions of rabbit superior mesenteric artery (IC50 = 56.6 nmol/l). The calcium antagonistic activities of the metabolites of monatepil maleate (AJ-2615-sulfoxide A, AJ-2615-sulfoxide B and AJ-2615-sulfone) were 1/10 of that of monatepil maleate. However, their alpha 1-adrenergic receptor blocking activities were similar to or slightly more potent than that of monatepil maleate. The potencies of the calcium antagonistic activities of monatepil maleate and its enantiomers [(S)-AJ-2615 and (R)-AJ-2615] were in the order of (S)-AJ-2615 > monatepil maleate > (R)-AJ-2615 whereas no difference was observed among them in alpha 1-adrenergic receptor blocking activity. In calcium antagonistic and alpha 1-adrenergic receptor blocking activities, there was no difference between the enantiomers of monatepil maleate metabolites. In conclusion, there was a difference with several times in calcium antagonistic activity between the two enantiomers of monatepil maleate but not in their alpha 1-adrenergic receptor blocking activity.