Interaction between free radicals and excitatory amino acids in the formation of ischemic brain edema in rats

Both oxygen free radicals and excitatory amino acids have been implicated as important cellular toxins in ischemic brain. Recent in vitro studies suggest that there may be a mutual interaction between these two mediators. We explored the relation between oxygen free radicals and excitatory amino acids in the development of ischemic brain edema in vivo. Male Sprague-Dawley rats were treated with the free radical scavenger dimethylthiourea 1 hour before ischemia or with the excitotoxin antagonist MK-801 30 minutes before ischemia produced by occlusion of the middle cerebral artery. Groups of seven or eight animals were treated with vehicle, low-dose (375 mg/kg) dimethylthiourea, high-dose (750 mg/kg) dimethylthiourea, low-dose (0.5 mg/kg) MK-801, high-dose (2.0 mg/kg) MK-801, or both high-dose dimethylthiourea and low-dose MK-801. After 4 hours of ischemia, brain water content was determined. In eight vehicle-treated controls, mean +/- SEM water content of tissue in the center of the ischemic zone was 83.29 +/- 0.18%. A significant reduction of brain edema was observed in all drug-treated groups: for example, 50.2% (p less than 0.001) in the high-dose dimethylthiourea group, 53.7% (p less than 0.001) in the low-dose MK-801 group, and 66.4% (p less than 0.001) in the combined dimethylthiourea and MK-801 group. Combined treatment with dimethylthiourea and MK-801 provided no significant additive effect over that resulting from treatment with MK-801 alone.(ABSTRACT TRUNCATED AT 250 WORDS)     

Scoliosis in pediatric spinal cord-injured patients

One hundred thirty children who sustained spinal cord injuries between birth and age 21 years were reviewed to determine the progression rate of paralytic scoliosis and the effects of bracing and surgery. Patients were divided into two groups: those injured before and those injured after the adolescent growth spurt. Scoliosis developed in 97 and 52%, respectively. Bracing was effective in delaying progression in the preadolescent group. The progressive paralytic spinal deformity did not appear to be related to the level of injury. The older patient is at much less risk for paralytic scoliosis, but still requires routine examination.     

Die doppler-sonographische beurteilung der funktionsfähigkeit extra-intracranieller anastomosen

Zusammenfassung Wir berichten fiber die Doppler-sonographischen Ergebnisse bei 33 Patienten mit einer Anastomose zwischen der A. temporalis superficialis and der A. cerebri media. Die Indikation zur Bypass-Operation beinhaltete rezidivierende TIA oder ein kurz zuvor erworbenes leichtes neurologisches Defizit bei angiographischem Nachweis einseitiger oder beidseitiger tiefer Obliterationen der A. carotis interna und hochgradiger Stenosen oder Verschlüsse im distalen Abschnitt der A. carotis interna bzw. im proximalen Abschnitt der A. cerebri media. Die Funktionsfahigkeit der Anastomose wurde überpriift durch die Berechnung der modifizier ten Pourcelot-Indices (relative enddiastolische Strömungsgeschwindigkeit) der A. temporalis superficialis praeauriculär und am Bohrlochrand Bowie durch den EinfluB der intermittierenden Kompression des den Bypass-versorgenden Gefäßes auf den modifizierten Pourcelot-Index der ipsilateralen A. carotis communis. Bei allen Patienten mit funktionsfahigen Anastomosen, definiert durch einen modifizierten Pourcelot-Index von zumindest 0,20 am Bohrlochrand, kam es zu einer Reduktion dieses Parameters um durchschnittlich 0,08 an der A. carotis communis bei kurzfristiger Kompression des den Bypass-versorgenden Astes. Bei den 18 Patienten mit unilateraler Obliteration der A. carotis interna war der Bypass über-wiegend dann funktionsfähig, wenn die summierten modifizierten Pourcelot-Indices der verbliebenen hirnversorgenden Gefäße um zumindest 10% gegenüber einem vergleichbaren Normalkollektiv reduziert waren. Das Vorhandensein bzw. das Fehlen von Ophthalmica-Kollateralen hatte dabei keinen Einfluß auf den Prozentsatz der funktionsfahigen Anastomosen in diesen Untergruppen. Bei den vier Patienten mit bilateraler Obliteration der A. carotis interna war die angelegte Anastomose in jedem Fall funktionsfähig, während die Hälfte der Patienten mit Stenosen and Verschlüssen im distalen Abschnitt der Carotisstrombahn nur eine ungeniigende Bypass-Funktion zeigten. Die zwei Patienten mit einer Mediahauptstammstenose bzw. -obliteration hatten Indices von 0,45 bzw. 0,46 am Bohrlochrand als Hinweis auf die Funktionstüchtigkeit. Wir Bind der Auffassung, daß man mittels Doppler-sonographischer Kriterien die Funktionsfahigkeit einer Temporalis superficialis-Cerebri media-Anastomose überprüfen kann. Der praeoperativ berechnete summierte modifizierte Pourcelot-Index der verbliebenen hirnversorgenden Arterien kann zumindest bei uni- and bilateraler Internaobliteration als zusatzlicher Parameter herangezogen werden, um die Indikation zur Bypass-Operation zu klären.     

Temporal sequence of morphological alterations in artery walls during experimental atherogenesis — occurrence of leukocytes

In rabbit carotid arteries arteriosclerotic lesions were induced by repeated local transmural electrical stimulations. The sequence of early morphological alterations in the vessel wall and especially the kinetics of leukocytes were examined by transmission electron microscopy. After a stimulation period of only 1 day monocytes and heterophilic granulocytes adhered to the endothelial surface. In the subendothelium mainly beneath the anode, focal amorphous insudates were present together with mononuclear and granulocytic cells. Thereby, the endothelium was maintained as a continuous lining as shown by surface staining with silver nitrate. However, both pattern and size of the endothelial cells were altered in comparison to the controls. Some of the endothelial cells displayed a heavy cytoplasmic silver salt deposition. After 2 days of the electrical stimulation schedule, the first myocytes occurred in the subendothelial space. The mediamyocytes sending pseudopods through the internal elastic lamina still appeared to be in a contractile phenotype. In the 7-day-old proliferative lesion modulated smooth muscle cells were the predominant cell type; only 10%-20% of the subendothelial cells were identified as macrophages and heterophils. This proportion decreased further, and after a stimulation period of 28 days the granulocytes disappeared completely. At this stage of plaque development, the intimal myocyte population mainly consisted of contractile smooth muscle cells and intermediary states between the contractile and modulated phenotype. The insudation, immigration of white blood cells, and subsequent migration and proliferation of myocytes reinforces the view that the initial phases of arteriosclerotic lesions may represent a special form of an inflammatory response.     

Decision making and results in subtotal and total lower leg amputations: Reconstruction versus amputation

As a result of modern therapeutic and technological advances, the surgeon has the ability to salvage even the most severely injured lower limbs. However, the success of replantation nowadays is no longer measured simply on the basis of restoration of viability but also on functional outcome compared with primary amputation with early prosthetic fitting, the risk to the patient during and after replantation and the overall time of treatment which should not exceed 2 years. Although every major limb replantation has to be considered individually, the decision-making process for reconstruction (replantation/revascularisation) versus amputation with subsequent early prosthetic fitting should be determined by objective criteria. Based on personal experience and an extensive literature search, an algorithm for treatment of amputation or amputation-like injuries to the lower leg has been developed and tested in a clinical study. A 100% viability success rate was achieved. There was not only a significant increase in the percentage of “functional extremities” but also a doubling in grade I results. Moreover, there was a 50% reduction in patients presenting a “non-functional extremity”, and no patient required a secondary re-amputation. The replantation risk (e.g., risk of severe systemic disturbance during and/or after replantation) was about 16.6% (2/12) in our study. There was a significant decrease in the postoperative complication rate and no patient died during or after replantation. Based on our experience, if reconstruction in subtotal or total lower leg amputation is done for a well-selected patient group, good functional results with a reasonable replantation risk and a reasonable time for social re-integration can be achieved. © 1995 Wiley-Liss, Inc.     

Proximal femoral focal deficiency: radiologic analysis of 49 cases

Proximal femoral focal deficiency, an uncommon congenital anomaly, necessitates early radiologic classification for surgical planning and treatment. Objective radiographic criteria, including femoral length index, acetabular depth index, acetabular angle index, and shape of the proximal femur were determined in 49 patients before cartilaginous ossification of the femoral capital epiphysis; final classification was based on follow-up radiographs or findings at arthrography or surgery. These parameters were analyzed to determine the accuracy and contributions of each in classification. Correct classification into one of three groups was possible in 86% of cases with use of three of the parameters: femoral length index, acetabular depth index, and shape of the proximal femur. The acetabular angle was found to contribute insignificantly to classification. Magnetic resonance imaging, used in only one case, depicted the nonossified cartilaginous femoral capital epiphysis, thus obviating the need for invasive diagnostic procedures and facilitating early classification.     

Blood to brain sodium transport and interstitial fluid potassium concentration during early focal ischemia in the rat.

During partial ischemia, sodium and potassium ions exchange across the blood-brain barrier, resulting in a net increase in cations and brain edema. Since this exchange is likely mediated by specific transporters such as Na,K-ATPase in the capillary endothelium and because brain capillary Na,K-ATPase activity is stimulated by increased extracellular potassium in vitro, this study was designed to determine if the rate of blood to brain sodium transport is increased in ischemic tissue having an elevated interstitial fluid potassium concentration ([K]ISF) in vivo. Sprague-Dawley rats were studied between 2-3 h after occlusion of the right middle cerebral artery. To identify where cortical tissue with an elevated [K]ISF could be sampled for transport studies, the regional pattern of cerebral blood flow and [K]ISF was obtained in a group of 17 rats using hydrogen clearance and potassium-selective microelectrode techniques. We observed severely elevated [K]ISF (greater than 10 mM) when CBF was less than 20 ml 100 g-1 min-1 and mildly elevated levels at CBF between 20-45 ml 100 g-1 min-1. In a second group of seven rats, permeability-surface area products (PS products) for 22Na and [3H]alpha-aminoisobutyric acid ([3H]AIB) were determined in ischemic cortex with elevated [K]ISF and in nonischemic cortex. The PS products for AIB were similar in both tissues (2.2 +/- 0.7 and 2.1 +/- 0.4 microliters/g/min) while the PS products for sodium was significantly increased in the ischemic tissue (1.5 +/- 0.2 and 2.4 +/- 1.1 microliters/g/min).(ABSTRACT TRUNCATED AT 250 WORDS)     

Thromboxane B2 synthesis in human platelets induced by the late complement components C5b-9

Sublytic doses of purified C5b6, C7, C8 and C9 induce the release of thromboxane B2 (TXB2) in human platelets. In the present study, we attempted to analyze the signal by which C5b-9 triggers the prostanoid synthesis in platelets. TXB2 release was accompanied by liberation of Ca++ from intracellular stores. Influx of Ca++ was not observed, indicating that C5b-9 did not form a channel large enough to permit passage of Ca++ ions. Therefore, channel formation is apparently not required for cell stimulation.