Effect of vitamin E on reperfusion injuries during reconstructive vascular operations on lower limbs.

INTRODUCTION: The challenge against reperfusion injury and tissue oxidative stress, especially in vascular surgical interventions has an essential importance to reach the optimal clinical result. Numerous experimental attempts have proved the positive antioxidant effect of vitamin E in both chronic and acute phase models. In our study we monitored the effect of continuous preoperative treatment with vitamin E, on oxidative stress and tissue inflammation reactions developed after reconstructive operations. PATIENTS AND METHODS: 32 patients have been involved in a randomized, prospective study, all suffering from AFS occlusion proved by angiography, and all undergone supragenual reconstruction. Duration of ischemia and amount of tissues under vascular clamping were almost the same in all patients. In the group treated with E-vitamin, we administered 1 x 200 mg of vitamin E p/o from the preoperative day till the 7th post operative day. Patients of the second group did not receive vitamin E. MATERIALS AND METHODS: Peripheral blood samples were collected immediately before operation and at the end of the second reperfusion hour (early reperfusion period). Late reperfusion period has been monitored by analyzing blood samples taken at 24th hour and 7th day next to the operative ischemia. Among oxidative stress parameters, direct measurement of reactive oxygen intermediator (ROI) and determination of antioxidant state (GSH, Total-SH group, SOD) have been performed. Malondialdehyde was chosen as marker for lipidperoxidation. Inflammation reactions were monitored up on expression of adhesion molecules (CD11a and CD18). We also controlled the oscillation of myeloperoxidase (MPO) activity. RESULTS: Our study has proved that preoperative (from the preoperative day till the 7th post operative day) administration of 200 mg vitamin E could reduce the level of oxidative stress developed after ischemic-reperfusion insult (lipidproxidation, antioxidant enzymes). According to our results, the prooxidant-antioxidant imbalance also diminished in the group with E-vitamin treatment. We proved that elective administration of vitamin E could decrease the WBC activity (MPO activity, free radicals production, expression of adhesion molecules) and its consequential local inflammation process, during early reperfusion.

Axillary lymph drainage as a prognostic factor of survival in breast cancer.

Axillary lymph node staging is an important prognostic factor in patients with breast cancer. The long-term survival is poor if the number of metastatic axillary lymph nodes exceeds three. With 1-3 metastatic lymph nodes, survival in 30% of the patients is 20 years. The markedly different outcome of these patients with metastatic axillary lymph nodes suggests that other factors likely play a critical role in breast cancer dissemination. In this study, we examined the association of impaired axillary lymph drainage with breast cancer survival. Fifty patients with breast cancer underwent direct breast lymphography before treatment to evaluate the status of ipsilateral axillary lymph nodes and lymph drainage at time of presentation. Twenty-five patients with signs of metastatic disease and/or impaired lymph drainage were followed for 10 years. Seven of 25 patients survived 10 years; 6 are tumor free; and 1 has distant mestastases. The other 18 patients died during the 10 year period. Seventeen of the 18 died from disseminated breast cancer; 1 died of unrelated disease. In the survivors, direct breast lymphography showed normal breast lymph drainage. All patients with distant metastases had obstructed lymph vessels at the time of original diagnosis. These findings suggest that the chance for survival is determined both by the status of axillary lymph drainage as well as the number of metastatic axillary lymph nodes.

The role of the individual domains in the structure and function of the catalytic region of a modular serine protease, C1r.

The first enzymatic event in the classical pathway of complement activation is autoactivation of the C1r subcomponent of the C1 complex. Activated C1r then cleaves and activates zymogen C1s. C1r is a multidomain serine protease consisting of N-terminal alpha region interacting with other subcomponents and C-terminal gammaB region mediating proteolytic activity. The gammaB region consists of two complement control protein modules (CCP1, CCP2) and a serine protease domain (SP). To clarify the role of the individual domains in the structural and functional properties of the gammaB region we produced the CCP1-CCP2-SP (gammaB), the CCP2-SP, and the SP fragments in recombinant form in Escherichia coli. We successfully renatured the inclusion body proteins. After renaturation all three fragments were obtained in activated form and showed esterolytic activity on synthetic substrates similar to each other. To study the self-activation process in detail zymogen mutant forms of the three fragments were constructed and expressed. Our major statement is that the ability of autoactivation and C1s cleavage is an inherent property of the SP domain. We observed that the CCP2 module significantly increases proteolytic activity of the SP domain on natural substrate, C1s. Therefore, we propose that CCP2 module provides accessory binding sites. Differential scanning calorimetric measurements demonstrated that CCP2 domain greatly stabilizes the structure of SP domain. Deletion of CCP1 domain from the CCP1-CCP2-SP fragment results in the loss of the dimeric structure. Our experiments also provided evidence that dimerization of C1r is not a prerequisite for autoactivation.

[Common bile duct tumor in a young woman with ulcerative colitis]. / Ductus choledochus-tumor kialakulása fiatal colitis ulcerosás nóbetegben.

Bile duct carcinoma is a rare complication of ulcerative colitis. In most of the cases it tends to occur together with primary sclerosing cholangitis predominantly in older males. The authors report a case of a 25 year old woman presenting with jaundice, 6 years after the diagnosis of colitis was made. The cause of the extreme extra- and intrahepatic bile duct dilation was revealed by endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangiography showing polypoid tumor in the common bile duct. The histological result taken during the surgical exploration proved the diagnosis of adenocarcinoma. Radical pylorus preserving pancreato-duodenectomy was performed. Subsequently adjuvant chemotherapy was instituted according to the PAV protocol. This rare case proves, that a malignant bile duct tumor may develop in a young patient with ulcerative colitis without the presence of primary sclerosing cholangitis. The authors emphasise the connection between ulcerative colitis and bile duct carcinoma and the importance of the close follow-up of every patient with ulcerative colitis.

The cleavage of two C1s subunits by a single active C1r reveals substantial flexibility of the C1s-C1r-C1r-C1s tetramer in the C1 complex.

The activation of the C1s-C1r-C1r-C1s tetramer in the C1 complex, which involves the cleavage of an Arg-Ile bond in the catalytic domains of the subcomponents, is a two-step process. First, the autolytic activation of C1r takes place, then activated C1r cleaves zymogen C1s. The Arg463Gln mutant of C1r (C1rQI) is stabilized in the zymogen form. This mutant was used to form a C1q-(C1s-C1rQI-C1r-C1s) heteropentamer to study the relative position of the C1r and C1s subunits in the C1 complex. After triggering the C1 by IgG-Sepharose, both C1s subunits are cleaved by the single proteolytically active C1r subunit in the C1s-C1rQI-C1r-C1s tetramer. This finding indicates that the tetramer is flexible enough to adopt different conformations within the C1 complex during the activation process, enabling the single active C1r to cleave both C1s, the neighboring and the sequentially distant one.

One active C1r subunit is sufficient for the activity of the complement C1 complex: stabilization of C1r in the zymogen form by point mutations.

The binding of C1 (the first component of complement) to immune complexes leads to the autoactivation of C1r through the cleavage of the Arg463-Ile464 bond in the catalytic domain. Spontaneous activation of C1r (and C1) also occurs in the fluid phase, preventing the characterization of the zymogen form of C1r. To overcome this difficulty, the zymogen form of human C1r was stabilized by mutating the Arg in the Arg463-Ile464 bond to Gln. This mutant was designated as mutant QI. Recombinant C1r (wild type (wt) or mutant) was expressed in insect cells using serum-free medium in functionally pure form; therefore, the cell culture supernatant was suitable to reconstruct C1 for the hemolytic assay. Mutant QI was a stable, nonactivable zymogen and showed no hemolytic activity in reconstituted C1. However, this stable zymogen C1r mutant could form an active mixed dimer with the wt C1r, indicating that one active C1r subunit in the C1 complex is sufficient for the full activity of the entire complex. Our experiments also showed that the exchange of C1r monomers between the C1r dimers is completed in less than 16 h even at pH 7 and 4 degrees C. Two other mutants were also constructed by changing Arg463 to Lys, or Ile464 to Phe, and were designated as mutants KI and RF, respectively. Although these substitutions did increase the stability of the proenzyme in the cell culture supernatant, the mutant proteins retained their ability to autoactivate, and both had a wt-like hemolytic activity.

[Diagnostic and therapeutic problems of sponaneous retroperitoneal hematoma]. / A spontán retroperitonealis vérzések felismerésének és kezelésének problémái.

The authors report four cases of spontaneous retroperitoneal haematomas, which occurred in their department during a half year period. The patients were admitted from different internal medicine departments. They had anaemia, and bleeding with unknown origin and localisation, and were in a bad condition. Three patients could be suitable for operation after general preparation. One of these patients died and another one died without operation. Two of them went home after recovering. The patients were transferred to surgical department on average three days after the symptoms developed. Hypoprothrombinaemia was the reason for bleeding in three cases. One patient got overdosed Syncumar, and two patients suffered from alcoholic cirrhosis who had other serious diseases as well. The authors found that the fourth patient, who had the gluteal arterial rupture with inexplicable origin, also had hypoprothrombinaemia. It is very difficult to diagnose these disease. Bleeding always has to be taken into consideration, if the patients have liver disease, or any type of coagulopathy, or take some anticoagulant medicine. The blood test examinations, ultrasound, CT, MR, angiography, laparoscopy can be helpful in the diagnosis of these cases.

[Rupture of extrauterine pregnancy during simultaneous intrauterine pregnancy]. / Extrauterin terhesség rupturája intrauterin terhesség mellett.

The authors report a case of a simultaneous extrauterine and intrauterine pregnancy which posed a problem of differential diagnosis for both the surgeon and the gynecologist. After surgical treatment of the ruptured ectopic pregnancy the patient was symptom free, and later requested the interruption of her normal intrauterine pregnancy. Diagnosis was confirmed by ultrasonographic examination.

"Medical decision making" for repeated computed tomography in neurosurgical intensive care patients.

Multiple CT investigations in critical ill neurosurgical patients are useful for monitoring the course of the illness and for the early detection of complications. CT's however, are expensive and require transportation of the patient, which is often inconvenient and, in some cases, dangerous. The decision to perform CT scanning should be based on the quantitative knowledge of potential benefits and harms (as well as costs) of the procedure. In a prospective trial, in which 59 such decisions were considered, we found it to be absolutely necessary to order a CT-investigation whenever neurological deterioration occurs. Even in patients not showing changes of neurological symptoms, about 30% of CT findings gave reason for therapeutic intervention. Thus, in critical ill neurosurgical patients, especially in those under sedative medication and artificial ventilation, neurological findings alone are insufficient as sole criteria for the decision to order a CT scan. To optimize this decision more sensitive indicators of deterioration are needed.

[Lymph drainage from the breast to the parasternal lymph nodes]. / Az emlök parasternális nyirokdrenázsa.

Breast lymphography revealed linkage between the axillary and parasternal lymph nodes in three out of 55 patients with breast cancer. In all the cases the efferent lymph vessels outlined laterally and, according to Berg's scheme, lymph node groups I, II and III were filled. Lymph vessel responsible for the filling of the parasternal lymph nodes branched from the area of group I lymph nodes. In two out of the 3 cases axillary metastasis was detected in one case, however, the axillary was found unaffected. The lymph vessel linkage observed doesn't seem to support the widely accepted concept, according to which there are only direct efferent lymph vessels running from the breast to the parasternal lymph nodes. This finding also explains why the incidence of parasternal metastases in the breast is higher in the case of tumorous obstruction of the axillary lymph nodes.

The influence of religious affiliation on surname repetition in marriages in Tiszaszalka, Hungary.

The repeated-pairs of surnames in marriages (RP) approach is applied to the population of Tiszaszalka in north-eastern Hungary. The results indicate that: (1) lineage-like behaviour in mate choice results in population subdivision in both the Catholics and the Protestants of the village; (2) unlike in some other Tiszahat villages, the isonymous and the repeating unions in Tiszaszalka occur in different lineages so, in neither of these subpopulations are isonymous and repeating unions monopolised by a few lineages; (3) religious affilitation influences the mating structure of the population as measured by RP summary scores.

PIP: Matrix methods have been devised to overcome the limitation of the isonomy method with high sampling errors. The repeated pairs (RP) of surnames in marriages approach proposed by Lasker and Kaplan in 1985 measures the effect of lineage in mate choice. Any excess of RP over the random occurrence (RP1) indicates lineage involvement via surnames. The degree of population subdivision from lineage influence on mate choice was estimated, lineage influence on repeating matings and isonomy was analyzed, and the effect of religion on mate choice in repeating and isonymous unions was explored. Marriage records were obtained in 1986 in Tiszaszalka and from the Genealogical Society in Salt Lake City, Utah (from 1806 for Protestants and from 1936 for Catholics). 1271 first marriages were analyzed: 972 Protestants and 299 Catholics. The RP and RP1 were larger among the Protestants than among the Catholics. The chi-square value for unique and nonunique surname pairs for the 2 religions was statistically significant: for total Protestant vs. incomplete Catholic and for partial Protestant vs. incomplete Catholic. The distribution of Isonymous and nonisonymous marriages of both religions was not significant indicating no inbreeding. After excluding isonymous matings the chi-square values for unique and nonunique surname pairs remained significant for both religious groups. The coefficient of isonomy indicated that both groups avoided isonymous unions since 1936, thus inbreeding was insignificant. In both groups lineage like behavior in mate choice resulted in population subdivision; religion influenced mating structure significantly and genetic variability decreased as a result. The incidence of isonomy was also low in several other villages in the region, and the RP approaches focus on husband's and wife's surnames was valuable regarding marriage patterns and genetic variability.

Intra-abdominal desmoids observed after total proctocolectomies.

Two cases of mesenteric desmoids observed after colectomy are reviewed. In one of them the familial polyposis had been known, in the other familial history could not be proved. Fibrous change prevented making of the planned Kock reservoir.

Surname repetition and isonymy in northeastern Hungarian marriages.

The repeated-pair (RP) approach to surnames in married couples is a measure of population subdivision resulting from the influence of lineagelike behavior in mate choice. An excess of RP over random RP implies limitations in mate choice and a reduction of genetic variability. Here we apply the RP method to data from the rural populations of Csaroda, Tiszaadony, and Tiszavid in northeastern Hungary. The results indicate small differences between RP and random RP for Tiszavid and somewhat larger differences for Tiszaadony and Csaroda. The excess of RP over random RP in Tiszavid, however, derives primarily from marriages simultaneously isonymous and repeating in only one lineage. The discrepancy between RP and random RP implies a small reduction in genetic variability.

Expression of hemolytically active human complement component C1r proenzyme in insect cells using a baculovirus vector.

The gene of human C1r has been expressed in a baculovirus-insect-cell system via the pAc373 transplacement vector. The full-length cDNA copy was inserted into the pAc373 vector downstream from the strong polyhedrin promoter of the baculovirus, Autographa californica nuclear polyhedrosis virus (AcNPV). Spodoptera frugiperda cells were cotransfected with the resultant plasmid, pAcC1r, and the wild-type AcNPV DNA. Recombinant viruses, which drove the expression of C1r protein, were selected by plaque morphology and ELISA. Insect cells infected with the recombinant virus produced and secreted human C1r protein, at a level of 1-2 mg/l of medium. The expressed C1r was isolated from the medium by chromatofocusing. On reducing gels only a single Coomassie-staining band was observed, and this band migrated at 80-83 kD characteristic of the unactivated C1r proenzyme. Its identification as C1r was immunologically confirmed on Western blots. C1 reconstituted from purified C1r expressed in insect cells together with human C1q and C1s proved biologically active in a hemolytic assay. Thus, the baculovirus-insect-cell system is capable of expressing and secreting a sophisticated, multifunctional human complement subcomponent in its biologically activatable form.

Brief information on an early phase-II study with deprenyl in demented patients.

Eleven elderly female patients (73-88 yrs) suffering from senile dementia of Alzheimer type (7 cases) and from multi-infarct dementia (4 cases) were treated with (-) deprenyl (Jumex) for 3 and 6 months respectively. Improvement was most frequent in SDAT patients and most pronounced as regards self-care, short-term memory, mental alertness and uncooperativeness.

Altered lymphocyte acetylcholinesterase activity in patients with senile dementia.

Reductions in the acetylcholinesterase (AChE) activity of certain brain areas in patients with senile dementia of Alzheimer type (SDAT) have been found to correlate with the severity of the disease, suggesting a central cholinergic lesion. Since AChE is expressed on the surface of various blood cells too, the AChE activity of lymphocytes and erythrocytes was determined to test the possibility whether the cholinergic lesion is also reflected on these readily available cells. The AChE activity of lymphocytes in SDAT and in alcoholic dementia (AD) were significantly lower as compared to those of the age-matched healthy volunteers. In contrast, there was no significant difference in the activity of lymphocyte AChE between age-matched healthy controls and patients with multi-infarct dementia of vascular origin (MID). No changes could be demonstrated in the erythrocyte AChE activities of the patients studied, and the age-matched healthy individuals, when comparing them to the healthy blood donors. The AChE activity of lymphocytes may thus be a useful marker to follow the alterations in the metabolism of acetylcholine (ACh) in the central nervous system (CNS) of different types of dementia.

A scanning electron-microscopic study of the healing of microvascular anastomoses made by invagination.

Anastomoses were prepared on the superior mesenteric artery of rats with invagination technique. The healing process was monitored by scanning electron microscopy. After the thrombotic and degenerative signs of the first three days, significant endothelial regeneration was observed by the end of the first postoperative week. Consequently, the denuded media surface was covered by endothelium by the 3rd week.

Synthesis of new spiro-steroids, II: steroid-17-spiro-oxazolidinones.

New, potential aldosterone blocking 17-spiro-oxazolidinone derivatives with androstane, estrane and 13 beta-ethyl-gonane ring system were synthesized. 17S-Spiro-oxiranes were used as starting compounds and the oxazolidinone ring was built up in different ways. All compounds but one were devoid of considerable endocrine activities. 3-Oxo-13 beta-ethyl-gona-4,9(10),11-triene-17S-spiro-5'-(2'-oxo-3'-methyl)oxazolidine shows significant antiandrogen activity on s.c., but none on p.o. administration.

Histological and autoradiographic changes in locally irradiated lymph nodes (an experimental study on rabbits).

The authors studied the local effect of 3000 Rxl X-ray irradiation on the popliteal lymph nodes of rabbits. Beside the morpho-histological description autoradiography was performed after injection of H3-thymidine in the afferent lymphatic of the irradiated knee node. The main finding is the appearance of newly-formed germinal centers between the 6-10. days after irradiation.

Study of pancreatic tissue pH in the early stage of experimental acute pancreatitis.

Pancreatic pH was measured electrometrically over a period of 3 h in 34 dogs with acute necrotic pancreatis. The disease had been induced with sunflower oil in 10, with Na-taurocholate in 10 and with hen's egg yolk in 10 animals. Four dogs served as controls. The pH of the pancreatic tissue changed differently in the different groups, in accordance with the different pathomechanisms. Injection of sunflower oil was followed by a protracted acidosis of pancreatic tissue, that of taurocholate by a transitory moderate decline of pH. Egg-yolk produced an evanescent, slight fall in pancreatic pH, followed by complete normalization within a few minutes. The differences between the initial and the 3-h values attain the level of significance only in case of sunflower-oil pancreatitis.