Antileukoproteinase protects against hepatic inflammation, but not apoptosis in the response of D-galactosamine-sensitized mice to lipopolysaccharide.

BACKGROUND AND PURPOSE: There is major evidence for the strong bi-directional interrelation of parenchymal cell apoptosis and leukocyte accumulation and inflammation in acute liver injury. Therefore, the aim of this in vivo study was to investigate the anti-apoptotic and anti-inflammatory potential of antileukoproteinase (ALP) in a murine model of acute liver failure. EXPERIMENTAL APPROACH: C57BL/6J mice were given galactosamine (D-GalN) and E. coli lipopolysaccharide (LPS) followed by administration of saline or ALP. Besides survival rate, hepatic tissue damage and inflammatory response were analyzed by intravital fluorescence microscopy 6 hours after treatment. In addition, immunohistochemical analysis of NFkappaB-p65 and hepatocellular apoptosis, plasma levels of AST/ALT, TNF-alpha and IL-10 were determined. KEY RESULTS: Administration of D-GalN/LPS provoked hepatic damage, including marked leukocyte recruitment and microvascular perfusion failure, as well as hepatocellular apoptosis and enzyme release. NFkappaB-p65 became increasingly detectable in hepatocellular nuclei, accompanied by a rise of TNF-alpha and IL-10 plasma levels. ALP markedly reduced intrahepatic leukocyte accumulation, nuclear translocation of NFkappaB and plasma levels of TNF-alpha and IL-10. Moreover, liver enzyme levels indicated the absence of necrotic parenchymal cell death. In contrast, ALP failed to block both apoptosis and caspase-3 levels and the mortality rate of ALP-treated animals was comparable to that of saline-treated mice. CONCLUSIONS AND IMPLICATIONS: ALP could effectively prevent D-GalN/LPS-associated intrahepatic inflammatory responses by inhibition of NFkappaB activity, but not apoptosis-driven mortality. Thus, a protease-inactivating approach such as application of ALP seems to be inadequate in damaged liver where apoptosis represents the predominant mode of cell death.

IgG and IgM antibodies to human parvovirus B19 in the serum of patients with a clinical diagnosis of infection with the virus and in the general population of Saudi Arabia.

A total of 56 samples of serum from 32 patients with a clinical diagnosis of human parvovirus B19 infection were tested for specific immunoglobulin G (IgG) and M (IgM) antibodies by means of the recently available indirect enzyme-linked immunosorbent assay (ELISA) (Parvoscan-B19, Ferring Diagnostica, Sweden). The assay was also used in order to determine the age-specific prevalence of antibodies to the virus in the general population of Saudi Arabia. Specific IgM antibodies were detected in 94% specimens collected 1 week after the onset of illness and could be detected for up to 2 months. On the other hand, specific IgG antibodies were detected in 85% patients from whom acute- and convalescent-phase serum samples were collected. Saudis begin to be exposed to human parvovirus B19 early in life and prevalence of exposure increases with age in both sexes (overall prevalence 19.0%). The availability of a commercial ELISA makes it possible to diagnose infection with the virus routinely and will help in establishing the extent of exposure to it in various communities.

Dose-response study of fenoterol on uterine activity in labor at term.

Uterine hyperactivity can be treated with uterine relaxants. In order to establish the most satisfactory dosage for Fenoterol, several doses were administered intravenously to pregnant women during birth and the actions on uterine relaxation and on side effects were examined. Saline was injected in a group of patients as control. With doses of 20 and 40 micrograms Fenoterol, submaximal uterine relaxation times of 7.3 and 7.9 min were obtained. Subjective side effects were observed, such as palpitations and restlessness; maternal blood pressure was unchanged. The pulse rate increased significantly only after 40 micrograms. 10 micrograms Fenoterol induced a uterine relaxation time of 5.6 min, was without side effects and was therefore regarded as the most satisfactory dosage. With 5 micrograms Fenoterol a relaxation time of only 3.2 min was observed. In the control group, administration of saline was without any observable effect.

Factor XIII levels in relation to gynaecological operations.

In 25 patients with vaginal hysterectomies and 14 with abdominal hysterectomies, Factor XIII activity in the antiseruminhibition test of Bohn and Haupt was measured in the first 7 postoperative days. Both groups showed a statistically significant reduction in activity (40--50%) which started at 2 h after operation and lasted until the 3rd postoperative day. The route of operation did not significantly affect the results and neither did the phase of the cycle nor the age of the patient.

[Medical procedure in cases of rape (author's transl)]. / Arztliches Vorgehen bei Vergewaltigungen.

Directions are given concerning the medical procedure in cases of rape. Besides emergency treatment for serious injury the patient should have her legal rights explained as well as the procedure for the forthcoming examination. A case history with special attention to the present case of rape is obtained. During the examination special attention is paid to the obtaining of evidence which wll stand up in a court of law. The taking of suitable samples is explained. The available methods for tracing sperm sources are described. Finally the treatment of after effects of rape is discussed.

Platelet function, coagulation and fibrinolysis during termination of missed abortion and missed labor by PGF2 alpha and oxytocin.

In cases of missed abortion and missed labor, labor was induced by PGF2 alpha i.a., i.v. and by oxytocin infusion. Platelet function (methods of Born and Breddin), the coagulation system and fibrinolysis have been studied within the three groups. Using PGF 2 alpha i.v., the initially increased platelet aggregation showed a tendency to become normal. There was no manifestation of activation of the coagulation system. Fibrinolytic activity showed a slight increase during PGF2 alpha i.v. No essential changes in platelet function, coagulation and fibrinolytic system were found after i.a. injection of PGF2 alpha. When inducing labor by oxytocin i.v., both the coagulation and the fibrinolytic system were slightly activated and platelet aggregation increased. The results and their clinical importance for hemostasis as well as therapeutic consequences are discussed.

[Platelet function during long term inhibition of labour by fenoterol/verapamil (author's transl)]. / Die Thrombozytenfunktion bei intravenöser Langzeittokolyse mit Fenoterol/Verapamil.

Platelet function has been studied in 22 patients (methods according to Born and Breddin) during tocolysis with long term administration of intravenous Fenoterol/Verapamil. The extend and speed of platelet aggregation, according to the Born test, were constant in the following 12 days except for a small increase on the second day. The phase of disaggregation remained unchanged. The reaction time to collagen was prolonged up to the 3rd-4th day. Spontaneous platelet aggregation showed a tendency to decrease up to day 3--4; thereafter, there was a return to the original values. The present data show that a hemostatic action in platelet function cannot be expected during long term tocolysis. Thus, there is no evidence that Fenoterol acts as an inhibitor of platelet aggregation in pregnancy.

[Influence on haemostasis exercised by Prostaglandin F2alpha in missed abortion (author's transl)]. / Beeinflussung der Hämostase bei Missed abortion durch Prostaglandin F2alpha.

The changes in the coagulation and the fibrinolytic system which may be related to the dead fetus syndrome indicate an interference of the activation of both coagulation and fibrinolysis. During termination of missed abortion and missed labour disorders of the haemostasis may occur acutely. In 16 patients with intrauterine death coagulation studies were performed inducing labour with PgF2alpha intraamniotically or i.v. No essentiel changes in the plasmatic system of coagulation and fibrinolysis were found. After i.a. application of PgF2alpha, the ADP- and collagen-induced as well as the spontaneous platelet aggregation didn't change. Using PgF2alpha i.v. a diminuation of the initially increased platelet aggregation was found in all parameters, whereas desaggregation was increased. These changes may influence an already existing latent consumption of coagulation factors in a favourable way. A further advantage of prostaglandins consists in the fact that smaller traumata occur, compared with curettage, so the possibility of liberation of thrombo-plastic material is reduced.

Studies on platelet function during different modes of administration of PgF2alpha in obstetrics and gynecology.

Platelet function has been studied during intravenous, intraamniotic, and extraamniotic administration of prostaglandin F2alpha (PgF2alpha) for termination of missed abortion and missed labor, for therapeutic abortion, and for induction of term labor. The controls received oxytocin i.v. (missed labor and term labor). Our investigations have shown that there was a normalization of the increased spontaneous platelet aggregation and a significant reduction of ADP- and collagen-induced platelet aggregation in the groups given PgF2alpha i.v. The desaggregation in these groups was increased. The other groups given PgF2alpha showed no significant changes in platelet function. Inducing labor by oxytocin we found a tendency to increased platelet aggregation and decreased desaggregation. The clinical importance of these findings and the consequences for hemostasis are discussed.

[Changes of platelet function, coagulation and fibrinolysis during induction of labour at term by prostaglandin F2alpha and oxytocin (author's transl)]. / Veränderungen von Thrombozytenfunktion, Gerinnung und Fibrinolyse bei Geburtseinleitung mit PgF2alpha und oxytocin.

Platelet function (induced and spontaneous aggregability according to Born and Breddin respectively) and some parameters of coagulation and fibrinolysis have been investiagted during induction of term labour by PgF2alpha i.v. (n = 9) and oxytocin i.v. (n = 9). During infusion of PgF2alpha there was a slight decrease of platelet aggregation with both methods. Desaggregation in the Born-test was increased. On the contrary there was no change of platelet function except a small increase of the speed of aggregation if one applicates oxytocin. The parameters of the plasmatic coagulation system remained almost unchanged in both groups and hint only at a slight increase of the fibrinolytic activity in the oxytocin group. The clinical importance of the results is discussed.

[Thrombocyte aggregation after vaginal hysterectomy with combined prevention of thromboembolism with macrodex 6% and sintrom]. / Die Thrombozytenaggregation nach vaginaler Hysterektomie unter kombinierter Thromboembolieprophylaxe mit Macrodex 6% und Sintrom.

The ADP- and collagen-induced thrombocyte aggregation has been investigated and statistically evaluated in 25 women. These patients had undergone vaginal hysterectomy and colporrhaphy due to descensus vaginae et uteri and received 500 ml Macrodex 6% during the operation and Sintrom from the 1st post-operative day as prophylactic treatment for early and late thromboembolism. After administration of dextran 60, the ability of the thrombocytes to aggregate was reduced by half, 2 hours post-operatively, independent of the concentration and type of agent added in the aggregation test, and remained at this level during the 1st post-operative day. The original values were once again attained on the 4th post-operative day. The speed and force of deaggregation showed reverse behaviour. There was no influence apparent due to age of the patient or phase of the cycle (proliferation, secretion and post-menopausal). By carrying out this combined prophylactic treatment for thromboembolism, satisfactory protection is provided in the dangerous phases during the operation and post-operatively.

[Thrombocyte aggregation after abdominal hysterectomy with combined prevention of thromboembolism using 6% macrodex and sintrom]. / Die Thrombozytenaggregation nach abdominaler Hysterektomie unter kombinierter Thromboembolieprophylaxe mit Macrodex 6% und Sintrom.

Thrombocyte aggregation was investigated, according to Born, in 14 patients who underwent abdominal hysterectomy due to benign illness. The patients received dextran 60 and 4-hydroxycoumarin as prophylactic therapy for early and late thromboembolism. The following results were obtained: 1. The ability of the thrombocytes to aggregate was reduced by half, 2 hours postoperatively, after administration of dextran 60, and remained at this level during the first postoperative day. This action was independent of the concentration and type of agent used in the aggregation test. The original values were attained again on the 4th postoperative day. The speed and force of desaggregation showed reverse behaviour. 2. Results bore no relationships to the age of the patient. 3. This combined prophylactic therapy with macrodex (500 ml intraoperatively) and sintrom (from the 1st postoperative day) seems to give adequate protection in both the intra- and postoperative risk phases.

[Problems in paediatric gynaecology (author's transl)]. / Probleme der Kindergynäkologie. Eine Ubersicht.

The present survey deals with the physiological development and pathological disturbances of the female genital organs in childhood. The different phases in development of the female genitals are discussed under sections on the newborn phase, the resting phase and the maturing time. Then follows a description of the most important illnesses met with in practice including various types of vulvovaginitis, tumours, genital bleeding and accidental injuries. This review could not be extended to include a description of congenital malformations and endocrinological disturbances.

[Coagulation-physiological studies on the prevention of thromboembolism with dextran 60. II. Changes in coagulation and fibrinolysis]. / Gerinnungsphysiologische Untersuchungen zur Thromboembolieprophylaxe mit Dextran 60 II. Mitteilung: Veränderungen von Gerinnung und Fibrinolyse.

The postoperative behavior of different parameters of coagulation and fibrinolysis have been studied in three groups of 20 patients each. Group A got only 4-hydroxycumarin, group B 500 ml Dextran 60 intraoperatively in addition to that, group C 500 ml Dextran 60 during surgery and on the 1., 2., 4., 7. and 10. postoperative day. The results show that the hypercoagulability which occurs immediately after surgery can be prevented by infusion of Dextran 60. On the other hand there is no evidence that Dextran 60 may cause a consumptive coagulability. There is only little influence on fibrinolysis, so that no defect of haemostasis can be expected. So it is possible to use Dextran 60 both for bridging over the phase of early embolism after surgery until the change to other anticoagulants and as a substance which can be applicated for a longer period of time in prophylaxis of thromboembolism. It is referred to the additional properties of Dextran 60 in prevention of thrombosis due to reduction of blood viscosity and improvement of microcirculation.