Effect of anticoagulation on renal function and protein excretion in experimental acute ischemic renal failure.

Female Sprague-Dawley rats underwent right nephrectomy and 40 min left renal artery occlusion (RAO). After 15 min of reflow, polyethylene glycol 1000 (PEG1000) was infused to induce osmotic diuresis and to enable glomerular filtration rate (GFR) measurements. Urine was collected during a 90 min period, and the concentrations of PEG1000, albumin, IgG, IgM and fibrin(ogen)/degradation products (FIB) were assessed both in plasma and urine by radial immuno diffusion technique Groups of rats were subjected to saline + RAO, warfarin + RAO or sham-operation. GFR as measured by PEG1000 clearance averaged 0.61, 0.036 and 0.094 mL/min/100g BW/kidney in sham-operated, saline + RAO and warfarin + RAO rats, respectively. Urinary excretion of albumin and IgG increased substantially in both ischemic groups. IgM was not detected in any of the urine samples. FIB excretion was lowest in the saline + RAO group, possibly due to retention of FIB-containing obstructions in the tubules. Rats subjected to warfarin + RAO had significantly higher excretion of FIB. This result suggests that warfarin does not prevent the glomerular sieving of macromolecules in the glomerular filter, but reduces tubular obstruction by preventing fibrin formation, which may explain its positive effect on GFR.

Effect of anticoagulation upon nephron obstruction in experimental acute ischaemic renal failure. A morphological study.

Ischaemic-reperfusion injury as a model of acute renal failure (ARF) results in increased macromolecular permeability, tubular obstruction, and renal oedema. To investigate the role for coagulation in this model, anticoagulated and saline-pretreated rats were subjected to 60 min unilateral renal artery occlusion (RAO). After 15 min of reflow, specimens were collected for electron and light microscopic examination. Morphometry was employed to study podocyte changes and Bowman's space dilatation as measures of increased permeability and tubular obstruction, respectively. After 15 min of reflow, Bowman's space increased significantly and the podocytes were markedly widened and flattened. Rats pretreated with heparin or warfarin showed less widening of Bowman's space than saline-treated rats, whereas no significant difference was seen regarding the podocyte changes. In saline-treated rats, fibrin-positive material was seen in the tubules but not in the urine sediments collected after 90 min of reflow, either due to fibrinolysis or poor urinary elimination. The results suggest that anticoagulation does not preclude the glomerular sieving of macromolecules, but seems to reduce tubular obstruction, probably by preventing conversion of filtered fibrinogen into fibrin.

[Shortcomings in the coverage of death occurring outside hospitals]. / Brister i handläggningen av dödsfall utanför sjukhus.

The article consists in a report of physicians' observance of legislative requirements concerning the documentation and investigation of deaths outside hospital, as studied in a series of 973 cases of death occurring in four medium-sized Swedish communities during 1993. The results showed manifest shortcomings in the performance of post-mortem investigations: long delays in submitting the death certificate, negligence in reporting unnatural and unexpected deaths to the police, and inadequate notes in the patients' journals concerning death certification, which relatives had been informed, the circumstances of death, and whether post-mortem examination had been performed. A special checklist would be of value in the documentation adn investigation of deaths occurring outside hospital.

Protective effect on postischemic renal edema by anticoagulation.

The effect of anticoagulation upon renal edema and plasma protein accumulation in acute ischemic renal damage was studied. Rats were subjected to unilateral renal artery occlusion for 60 min and 15 min of reflow. The kidney weight and the content of 125-I-fibrinogen and 131-I-albumin, injected 24 h priorly, were measured and the renal morphology studied. Groups of rats were pretreated with a heparin analogue with low anticoagulant effect, standard heparin, warfarin or saline. A marked increase in fibrinogen and albumin content and of the weight of the damaged kidney was noted. Heparin and warfarin both significantly attenuated these changes, whereas the heparin analogue did not. Microscopically, fibrin-positive material was seen in the peritubular capillaries, vasa recta and in the tubules of rats pretreated with saline or the heparin analogue, but not in rats pretreated with heparin or warfarin. The results support the hypothesis that fibrin deposition in the kidney is of importance for the development of renal edema in this model of ischemic renal damage.

Intra- and extrafamilial child homicide in Sweden 1971-1980.

Over the 10-year period studied, a total of 96 children under 15 years of age were killed in Sweden. This number constituted an average annual rate of 0.6 per 100,000 children. The violence, most frequently involving strangulation, shooting, and stabbing, was largely directed at young children. The pattern of child homicide was mainly characterized by intrafamilial violence, especially in connection with the suicide of a parent-perpetrator. Extrafamilial homicides were rare and only committed by male perpetrators. Cases of child abuse by a parent and cases of sexual abuse were infrequent. By psychiatric examination after the crime, only 10 perpetrators out of 47 examined were found not mentally ill.

[Regulations for autopsy and organ removal in Sweden]. / Regeln für die Obduktion und die Organentnahme in Schweden.

In Sweden clinical autopsies are controlled by the autopsy law, which prescribes information to the relatives about the planned autopsy. Permission by the patient before death or by the relatives after information is mandatory. The performance of the autopsy is not regulated. For forensic autopsies no information or permission is prescribed. The performance and the documentation of the autopsy is strictly regulated and no partial autopsies are permitted. Forensic autopsies must be performed by forensic pathologists. A comparison is made of the legislation in the scandinavian countries and the Federal Republik of Germany.

The role of hydrogen cyanide and carbon monoxide in fire casualties: a prospective study.

Determinations of blood cyanide and carboxyhemoglobin concentrations were performed in 18 victims found dead in buildings after fires during a 2-year period. The results indicated that 50% of the victims had been exposed to toxic levels of hydrogen cyanide and 90% to toxic levels of carbon monoxide. Lethal concentrations of carbon monoxide were found in 83% of the victims. In one case a lethal blood cyanide but a non-toxic blood carboxyhemoglobin value was found. It is concluded that carbon monoxide appears to be more important than hydrogen cyanide as a toxic agent in the fire atmosphere, but cyanide poisoning without carbon monoxide poisoning may, under certain circumstances, be the cause of death in fire victims.

Reduction of renal edema by heparin in postischemic renal damage.

Rats were subjected to unilateral renal artery clamping for 60 min and contralateral nephrectomy. 125I-labelled fibrinogen and 131I-labelled albumin were injected intravenously 24 h before the experiment. A significant increase in the fibrinogen and albumin content and weight was found already 5 and 15 min after reflow. Rats given heparin (2,000 IU/kg body weight) 5 min before clamping and killed 15 min after reflow showed significantly smaller increases in these values than rats given saline. Morphological studies showed fibrin deposition in Bowman's space, tubules and peritubular capillaries. The results indicate that fibrin deposition occurs and is of importance in the development of renal edema in this type of renal damage.

Fibrin deposition in the kidney in post-ischaemic renal damage.

To investigate whether fibrin deposition in the kidney occurs in ischaemic acute renal failure, rats were subjected to a left renal artery occlusion (RAO) for 1 h and contralateral nephrectomy. The animals were killed 0, 5, 15 and 60 min after re-establishment of the circulation. Kidney tissue was snap-frozen for immunofluorescence microscopy and scanning electron microscopy, and immersion-fixed for light microscopy and transmission electron microscopy. Immunofluorescence studies showed small amounts of immune reactive fibrinogen/fibrin deposits in the peritubular capillaries. Substantial amounts of fibrinogen/fibrin positive material was observed in Bowman's space and in the tubular lumina. Scanning electron microscopy of freeze-dried tissue disclosed granular and fibrillar material in Bowman's space. A temporary enlargement of Bowman's space was noted; it may have been caused by tubular obstruction. No deposits were found in the control (right) kidneys and in kidneys of heparinized rats subjected to RAO. The results indicate that fibrin deposition occurs in the ischaemic model of acute renal failure in rat, both intravascularly and in the urinary space. Its importance for the development of renal functional impairment remains to be studied.

Fatal intoxication by dextromethorphan: a report on two cases.

A report is given of two young people who died after intake of dextromethorphan, one by suicide and the other for uncertain reasons. To our knowledge this is the first reported fatal intoxications with this drug.

Effects of phospholipase C, a tissue thromboplastin inhibitor, on pulmonary microembolism after missile injury of the limb.

Tissue thromboplastin probably plays an important role in the development of post-traumatic pulmonary microembolism. Infusion of purified human tissue thromboplastin in animals resulted in an intravascular coagulation and respiratory insufficiency. This could be inhibited by previous infusion of phospholipase C (PLC) from Bacillus cereus. We have studied the effects of PLC infusion on the course of post-traumatic pulmonary microembolism, induced by a high-energy (c. 700 J) missile trauma to the hind legs of pigs. The trauma resulted in a major muscular injury and an indirect femoral fracture. Untreated pigs developed intrapulmonary microemboli. The degree of microembolism in the lungs was measured quantitatively by external detection over the right lung of radiolabeled platelets and fibrin. Infusion of 80 micrograms PLC/kg/hour resulted in an accumulation of blood PLC associated with toxic reaction leading to increasing tachycardia and circulatory collapse after 10 hours. PLC infusion of 20 micrograms/kg/hour did not inhibit the pulmonary microembolism. A PLC-dose in between, viz. 40-50 micrograms/kg/hour, proved to efficiently inhibit most of the microembolism during the infusion period. Cessation of PLC infusion after 24 hours was accompanied by a later increase in pulmonary trapping of platelets and fibrin and decreases in paO2. Concomitantly there were opacities seen on chest X-rays. The results show that tissue thromboplastin is an important etiologic factor in post-traumatic pulmonary microembolism and that inhibition with phospholipase C can be of value in the prophylaxis of the syndrome.

Pulmonary trapping of platelets and fibrin after musculoskeletal trauma: an experimental model.

A new experimental model is described in which pulmonary changes identical with the adult respiratory distress syndrome (ARDS) can be induced by reproducible musculoskeletal trauma in anesthetized pigs. The pigs were studied in maintained anesthesia for 3 days after the trauma under standardized conditions. The intrapulmonary aggregation of platelets and fibrin was monitored by external detection of radioactivity arising from pretrauma intravenous injection of 51Cr-labeled platelets and 125I-labeled fibrinogen. Pulmonary trapping of platelets and fibrin was significantly greater in the traumatized pigs than in nontraumatized but otherwise identically handled controls. Radiologic and morphologic changes corresponding to ARDS developed in the traumatized animals, but not in the controls. The experimental model offers new possibilities for study of factors influencing the occurrence and development of ARDS. After further experimental evaluation, the procedure for registering pulmonary microembolism by external detection may be useful in the clinical management of ARDS.

Experimental posttraumatic pulmonary microembolism. Effects of methylprednisolone on its development.

The effects of methylprednisolone sodium succinate on the course of posttraumatic pulmonary microembolism were studied in pigs submitted to a reproducible high-energy trauma of the limb and then observed under long-term anesthesia. Methylprednisolone sodium succinate (30 mg/kg of body weight) was given one hour after trauma and thereafter every eighth hour during a 72-hour observation period. Intrapulmonary microembolism was quantitatively measured by repeated external detection of chromium 51-labeled platelets and iodine 125-labeled fibrinogen, sequential chest roentgenograms, and morphologic examination of the lungs post mortem. Methylprednisolone delayed the onset of pulmonary roentgenogram changes and modulated Pao2 and platelet count reductions, but, at the end of the observation period, the signs of microembolism changes were as pronounced as in the nontreated traumatized pigs. Methylprednisolone thus did not prevent posttraumatic pulmonary microembolism in this experimental situation.

Posttraumatic respiratory distress syndrome and high-dose corticosteroids.

Many authors have advocated glucocorticoids for prophylaxis against or treatment of Adult Respiratory Distress Syndrome (ARDS) or post-traumatic pulmonary microembolism. One of the theories underlying this advocacy is that the activation of the complement system possibly is preventable by pharmacologic doses of corticosteroids. Studies on traumatized patients are difficult to standardize, and clinical observations are correspondingly difficult to evaluate. Animal models for study of the microembolism syndrome have often comprised too short a time and most have greatly differed from the clinical situation. We have earlier evolved an experimental model by means of which changes identical to the microembolism syndrome can be induced from a reproducible musculo-skeletal trauma in pigs observed under long-term anesthesia under standardized conditions. In this study, early and long-term effects of corticosteroids on the course of post-traumatic microembolism was evaluated by following the pulmonary function and X-ray appearance, pulmonary trapping of platelets and fibrin and histologic changes in pigs, using this standardized trauma model. Methylprednisolone sodium succinate (30 mg/kg bw) was given to 9 pigs one hour after trauma and thereafter every 8th hour during a 72 hour observation period. Two other groups of animals were used for comparison, 13 traumatized, non-treated and 15 non-traumatized, non-treated pigs. Intrapulmonary microembolism was measured quantitatively by repeated external detection of labelled platelets (51Cr) and fibrinogen (125I), sequential chest X-rays and morphologic examination of the lungs post mortem.(ABSTRACT TRUNCATED AT 250 WORDS)