[The clinical picture, diagnostic and treatment of the acute iliopsoitis].

The treatment results of the acute iliopsoitis in 29 patients were analyzed. The right side inflammation was observed more frequently (n=17). The most common infectious agent was the Staphylococcus aureus. The source of the inflammation was septic lesions of the lower body, whereas the perdisposal factors were considered to be the diabetes mellitus, drug abuse and immunodeficiency. The cardinal diagnostic sign of the acute iliopsoitis proved to be the psoas-symptom. The main diagnostic instruments were the ultrasound investigation, CT and MRI. 1 patient was successfully treated conservatively, though the rest 28 demanded surgical opening and drainage of m. iliopsoas. The lethality rate was 3,4%. 96,6% of the treated patients were successfully cured.

[Prophylaxis of acute postoperative gastroduodenal ulcers at the patients with colorectal cancer].

Effective method for prophylaxis of acute postoperative gastric ulcers and erosions was developed. The core of this method is ozone therapy in preoperative period. Intensity of blood serum and erythrocytes chemiluminescence and ATPase activity of erythrocytes were studied at 86 patients with colorectal cancer before surgery and at 1st and 4th days of postoperative period. It was demonstrated that preoperative ozone therapy promoted normalization of free radical reactions and ATPase activity at postoperative period.

FLT3 ligand administration inhibits tumor growth in murine melanoma and lymphoma.

Successful treatment of melanoma and lymphoma may result from the induction of specific antitumor immunity. Dendritic cells (DCs) are powerful antigen-presenting cells and show a remarkable capacity to stimulate antigen-specific T-cell responses. Administration of FLT3 ligand (FL) results in a reversible accumulation of functionally active DCs in both lymphoid and nonlymphoid tissues. Therefore, we evaluated the possible antitumor effect of FL in murine melanoma (B16 and CL8-1) and lymphoma (EL-4) models. In all experiments, tumor growth was significantly inhibited by FL administration. Analysis by immunohistochemistry revealed an increase in the DC accumulation within B16 and EL-4 tumors after treatment with FL. No change was observed for CL8-1 melanoma. These data suggest a potential role for FL in the immunotherapy of malignant skin tumors and possible DC involvement in this effect.

[Foreign bodies of appendix and caecum complicated with acute appendicitis].

Twelve patients with exogenous foreign bodies (small chicken and fish bones, portion of wire, nail, cherry stone, piece of glass) of appendix (8) or adjacent zone of caecum (4) were treated. Based on experience of treatment of these patients authors analyze pathogenesis of appendicitis associated with foreign bodies, and other aspects of this problem.

[The activity of adenosinetriphosphatase of erythrocytes in peripheral blood of patients with colorectal cancer].

We studied the activity of whole ATPase, Mg2+ -ATPase and Na+, K+ -ATPase of peripheral blood erythrocytes in 68 patients with colorectal cancer before surgery and immediately after it and found such activity to be reduced. The low activity of Na+, K+ -ATPase of peripheral blood erythrocyte was shown as possible for use in prognosticating acute postoperative erosive-ulcerous lesions of the gastric tunic. Ozone therapy, if undertaken preoperatively, restores the ATPase activity.

Differential regulation of epidermal and dermal dendritic cells by IL-12 and Flt3 ligand.

An abrogation of the decline in epidermal Langerhans cell numbers above melanoma might significantly improve the efficacy of immunotherapy for melanoma treatment. Systemic Flt3 ligand (FL) administration in mice induced a significant increase in mature dendritic cells (DC) within the skin, preferentially in the dermis, whereas IL-12 promoted a significant increase of immature DC preferentially in the epidermis. Both effects were abrogated in IL-12 knockout mice. Thus, IL-12 could promote FL-induced accumulation of skin DC. The involvement of FL and IL-12 in the regulation of DC accumulation within the skin may contribute, at least in part, to the stimulation of antimelanoma immunity by FL- and IL-12-based immunotherapies. Moreover, FL and IL-12 could be used for selective in vivo generation of DC in either epidermis or dermis for experimental and clinical purposes.

A correlation between liver plasma membrane-associated stimulatory activity (PMASA) and experimental cirrhosis formation.

In the course of experimental CCl4-induced cirrhosis, an increase of the membrane-associated factor stimulating 3T3 cells' proliferation in vitro was observed. Gel filtration showed an approximate molecular mass of 150 kDa. Extraction of growth stimulatory activity by liver perfusion in situ demonstrated a peripheral plasma membrane protein localization. The activity increased with an increasing number of CCl4 treatments, reaching a maximum at the tenth intoxication, faster than the proliferation of connective tissues. Cessation of treatment caused a decrease in activity to the level of untreated liver, although the amount of fibroblast-like cells remained large, which is evidence in favour of an hepatocyte origin of the factor.

In vitro propagation and homing of liver-derived dendritic cell progenitors to lymphoid tissues of allogeneic recipients. Implications for the establishment and maintenance of donor cell chimerism following liver transplantation.

Dendritic cell (DC) progenitors were propagated in liquid culture from nonparenchymal cells resident in normal mouse (B10.BR; H-2k, I-E+) liver in response to granulocyte-macrophage colony stimulating factor (GM-CSF). The liver-derived DC progenitors were MHC class II-/dim and did not express counter receptors for CTLA-4, a structural homologue of the T cell activation molecule CD28. Following subcutaneous or intravenous injection, these liver-derived cells migrated to T cell-dependent areas of lymph nodes and spleen of unmodified, allogeneic (B10; H-2b; I-E-) recipients, where they were identified 1-5 days, and 1 and 2 months after injection by their strong surface expression of donor MHC class II (I-Ek) and their dendritic morphology. Maximal numbers of liver-derived DC in the spleen were recorded 5 days after injection. Both clusters of strongly donor MHC class II+ cells--and (more rarely) dividing cells--could also be identified, suggesting cell replication in situ. Using the same techniques employed to generate DC progenitors from normal liver, GM-CSF-stimulated cells were propagated for 10 days from the bone marrow and spleen of nonimmunosuppressed mice sacrificed 14 days after orthotopic liver transplantation (B10;H-2b-->C3H;H-2k). Immunocytochemical staining for recipient and donor MHC class II phenotype revealed the growth both of host cells with DC characteristics, and of cells expressing donor alloantigens (I-Ab). These results are consistent with the growth, in response to GM-CSF, of donor-derived DC from progenitors seeded from the liver allograft to recipient lymphoid tissue. The functional activity of the progenitors of chimeric DC and the possible role of these cells in the establishment and maintenance of donor-specific tolerance following liver transplantation remain to be determined.

Striking augmentation of hematopoietic cell chimerism in noncytoablated allogeneic bone marrow recipients by FLT3 ligand and tacrolimus.

The influence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and the recently identified hematopoietic stem-progenitor cell mobilizing factor flt3 ligand (FL) on donor leukocyte microchimerism in noncytodepleted recipients of allogeneic bone marrow (BM) was compared. B10 mice (H2b) given 50x10(6) allogeneic (B10.BR [H2k]) BM cells also received either GM-CSF (4 microg/day s.c.), FL (10 microg/day i.p.), or no cytokine, with or without concomitant tacrolimus (formerly FK506; 2 mg/kg) from day 0. Chimerism was quantitated in the spleen 7 days after transplantation by both polymerase chain reaction (donor DNA [major histocompatibility complex class II; I-E(k)]) and immunohistochemical (donor [I-E(k)+] cell) analyses. Whereas GM-CSF alone significantly augmented (fivefold) the level of donor DNA in recipients' spleens, FL alone caused a significant (60%) reduction. Donor DNA was increased 10-fold by tacrolimus alone, whereas coadministration of GM-CSF and tacrolimus resulted in a greater than additive effect (28-fold increase). A much more striking effect was observed with FL + tacrolimus (>125-fold increase in donor DNA compared with BM alone). These findings were reflected in the relative numbers of donor major histocompatibility complex class II+ cells (many resembling dendritic cells) detected in spleens, although quantitative differences among the groups were less pronounced. Evaluation of cytotoxic T lymphocyte generation by BM recipients' spleen cells revealed that FL alone augmented antidonor immunity and that this was reversed by tacrolimus. Thus, although FL may potentiate antidonor reactivity in nonimmunosuppressed, allogeneic BM recipients, it exhibits potent chimerism-enhancing activity when coadministered with recipient immunosuppressive therapy.

Interleukin-17 antagonism inhibits acute but not chronic vascular rejection.

BACKGROUND: Blocking the action of interleukin (IL) 17 with an IL-17 receptor (R):Fc fusion protein inhibits T-cell proliferative responses to alloantigens and prolongs vascularized heart graft survival. In this study, we examined whether IL-17 antagonism could suppress the development of chronic rejection. METHODS: A 0.6-cm section of C57BL10 (H2b) thoracic aorta was transplanted to recipient C3H (H2k) abdominal aorta. IL-17R:Fc or control human immunoglobulin G was administered i.p. (500 microg/day) from days 0 to 6 or from days 0 to 29. Mice were killed on days 7 or 30. Grafts were examined histologically and stained for alpha-smooth muscle actin (alpha-smA). Antidonor mixed leukocyte reaction, cytotoxic T cell, and alloantibody responses were quantified. RESULTS: On day 7, control grafts showed mononuclear cell (MNC) infiltration, pronounced endothelial damage, and apoptosis of intimal and medial cell compartments. By day 30, there was concentric intimal thickening, accumulation of alpha-smA+ cells, and collagen deposition. Patchy destruction of the elastic membranes and loss of alpha-smA expression in media were evident. IL-17R:Fc for 6 days decreased MNC infiltration in the intimal and medial compartments at day 7. The endothelium was preserved (completely or partially) in all grafts. The medial compartment showed normal alpha-smA expression. Irrespective of IL-17R:Fc treatment for either 6 days or continuously, allografts harvested at day 30 showed circumferential intimal thickening, with accumulation of alpha-smA+ cells and collagen deposition. There was no effect on circulating alloantibody levels. CONCLUSIONS: These findings support a role for IL-17 in the immunopathogenesis of acute vascular rejection and demonstrate the potential of IL-17 antagonism for therapy. By contrast, IL-17 antagonism does not appear to prevent ensuing chronic graft vascular disease, in particular neointimal formation.

Comparative analysis of dendritic cell density and total number in commonly transplanted organs: morphometric estimation in normal mice.

Dendritic cells (DC) are considered to be the major cell type responsible for induction of primary immune responses. While they have been shown to play a critical role in eliciting allosensitization via the direct pathway, there is evidence that maturational and/or activational heterogeneity between DC in different donor organs may be crucial to allograft outcome. Despite such an important perceived role for DC, no accurate estimates of their number in commonly transplanted organs have been reported. Therefore, leukocytes and DC were visualized and enumerated in cryostat sections of normal mouse (C57BL/10, B10.BR, C3H) liver, heart, kidney and pancreas by immunohistochemistry (CD45 and MHC class II staining, respectively). Total immunopositive cell number and MHC class II+ cell density (C57BL/10 mice only) were estimated using established morphometric techniques--the fractionator and disector principles, respectively. Liver contained considerably more leukocytes (approximately 5-20 x 10(6)) and DC (approximately 1-3 x 10(6)) than the other organs examined (pancreas: approximately 0.6 x 10(6) and approximately 0.35 x 10(6); heart: approximately 0.8 x 10(6) and approximately 0.4 x 10(6); kidney approximately 1.2 x 10(6) and 0.65 x 10(6), respectively). In liver, DC comprised a lower proportion of all leukocytes (approximately 15-25%) than in the other parenchymal organs examined (approximately 40-60%). Comparatively, DC density in C57BL/10 mice was heart > kidney > pancreas >> liver (approximately 6.6 x 10(6), 5 x 10(6), 4.5 x 10(6) and 1.1 x 10(6) cells/cm3, respectively). When compared to previously published data on allograft survival, the results indicate that the absolute number of MHC class II+ DC present in a donor organ is a poor predictor of graft outcome. Survival of solid organ allografts is more closely related to the density of the donor DC network within the graft.

Impact of Flt-3 ligand on donor-derived antigen presenting cells and alloimmune reactivity in heart graft recipients given adjuvant donor bone marrow.

The influence of the haematopoietic growth factor Flt-3 ligand (FL) on the incidence and function of donor major histocompatibility complex (MHC) class II+ cells in the lymphoid tissues of noncytoablated recipients of heart allografts and donor bone marrow (BM) cells was investigated. C3H (H2k) mice received a nonvascularized B10 (H2b) heart allograft in the dorsal ear pinna, followed by an i.v. infusion of 50 x 10(6) donor BM cells. They were given FL (10 microg/day i.p., x7 days), tacrolimus (2mg/kg/day i.p., x13 days) or both agents immediately following heart transplantation (HTx) and were killed 10 or 21 days later. Their BM cells were propagated in vitro in granulocyte macrophage colony stimulating factor (GM-CSF) and IL-4 for 5 days to promote the growth of dendritic cells (DC). Donor DC were identified by immunocytochemical staining. Spleens were harvested, and donor (IAb+) cells enumerated by immunohistochemical analysis. Donor MHC class II DNA was detected in spleens and cultured BM-derived cells by reverse transcriptase-polymerase chain reaction (RT-PCR). A striking increase in donor MHC class II+ cells was noted in both the spleen and BM of the BM + tacrolimus-treated group compared to either the BM alone, or BM + FL-treated groups. Addition of FL treatment to BM + tacrolimus led to a further increase in donor cells in spleen (three-fold at 10 days, and two-fold at 21 days). The increase in donor cells at 10 days was almost 140-fold compared to that with donor BM alone. PCR analysis at this time revealed enhanced donor DNA in the BM + FL + tacrolimus group compared to that in the BM + tacrolimus group. FL treatment augmented mixed leucocyte reactions (MLR) and cytotoxic T lymphocyte (CTL) activity of host spleen cells against donor alloantigens. These effects were reversed by tacrolimus administration. Histopathology of heart grafts from tacrolimus-treated animals at 10 and 21 days showed absence or substantial reduction in cellular infiltration, and the preservation of viable myocardium. By contrast, in untreated mice, or animals given BM or BM + FL alone, there was marked cellular infiltration, and features of accelerated rejection. Donor-derived DC could be propagated in vitro from the BM of heart transplant recipients given donor BM, especially from mice that also received tacrolimus +/- FL. At day 21, donor-derived cells could only be propagated from the BM + FL + tacrolimus-treated group. These findings show that numbers of donor antigen presenting cells (APC) or their progenitors can be markedly increased in conventionally immunosuppressed organ allograft recipients given donor BM + a potent haematopoietic and DC-growth promoting cytokine. Although withdrawal of systemic immunosuppression appears to allow exhibition of the potential allostimulatory activity of these donor APC leading to rejection, the model provides a useful basis for further evaluation of the persistence and manipulation of donor haematopoietic cells and in particular, donor-derived APC, on the outcome of organ transplantation.

Increased hepatic endothelin-1 levels and endothelin receptor density in cirrhotic rats.

Endothelin-1 (ET-1), the most powerful agent to cause constriction of the hepatic vasculature, is synthesized in the liver by sinusoidal endothelial cells. Circulating ET-1 levels have been shown to increase in liver cirrhosis. As liver could be a major source of increased plasma ET-1 as well as a target for its pathologic actions, this study was designed to determine hepatic ET-1 and ET receptor(s) in experimental liver cirrhosis. Cirrhosis was induced in rats by intraperitoneal administration of carbon tetrachloride for 8 weeks. Hepatic ET-1 was measured by radioimmunoassay and ET receptors were determined by radioligand competition binding procedure. A four fold increase in ET-1 concentration accompanied by a 65% increase in ET-receptor density was observed in the cirrhotic liver. There was no change in the ET receptor affinity. The capacity of the liver to metabolize ET-1 was reduced significantly in cirrhosis. Interestingly, transforming growth factor-beta, hepatic levels of which increase in cirrhosis, stimulated ET-1 synthesis in cultured Ito cells. It has been shown that ET-1 is a potent constrictor of Ito cells that proliferate and transform into highly contractile myofibroblasts in liver cirrhosis. Thus, interactions between ET-1 and Ito cells may have significant implications in the pathogenesis and complications of liver cirrhosis.

[Interaction of the plasma membranes of the cells of tumors metastasizing to the lungs with the target organ]. / Vzaimodeistvie plazmaticheskikh membran kletok opukholei, metastaziruiushchikh v legkie, s organom-mishen'iu.

Cells of lines of mice transplantable tumours metastasizing into the lung have been used: lung adenocarcinoma (AL), Lewis lung carcinoma (LL), melanoma B-16 (B-16), mammary tumour MMT-1 (MMT-1), malignant subline of L-cells (LS). Hybrid vesicles were obtained for each tumour. They contain fragments of cell plasmatic membranes (PM). It has been shown that AL-, LL-, LS- and B-16-liposomes were accumulated in lung, the trapping of AL- and LL-liposomes being higher than that of the other hybrid vesicles. Despite the similar dynamics and frequency of metastatic spreading into the lung for all tumours studied, no trapping of MMT-1-vesicles in the target-organ was observed. The role of specific interaction of tumour cells PM with the endothelium of the lung capillaries in the process of organotropic metastatic spreading is discussed.

[Ultrasonic diagnosis of benign focal lesions of the liver]. / Ul'trazvukovaia diagnostika dobrokachestvennykh ochagovykh porazhenii pecheni.

Proceeding from a study of an ultrasound picture of liver focal changes of benign nature in 60 patients a conclusion was made that nonparasitic cysts could be verified on the basis of a typical ultrasound picture and its stability over time. The presence of daughter cysts and septal membranes was indicative of unilocular hydatid disease. Additional laboratory investigations were necessary for the recognition of alveolar hydatid disease. It was desirable that the diagnosis of liver abscess and hematoma should be confirmed by fine needle spot puncture. By their ultrasound picture benign liver tumors did not differ significantly from malignant ones. To exclude the latter fine needle spot puncture was necessary. Hemangioma should be verified by angiography, the rest of benign tumors--by histology.

[Surgical policy in gastrointestinal tract foreign bodies]. / Khirurgicheskaia taktika pri inorodnikh telakh zheludochno-kishechnogo trakta.

66 patients (45 males and 21 females) who have swallowed 157 foreign bodies (fragments of wire, nails, needles, hafts of spoons, et were treated). If the objects were located in the stomach and the duodenum in the absence of complications endoscopic method of treatment was preferable, with the help of which 31 objects were successfully removed and the terms of treatment were significantly decreased. Conservative treatment (diet rich in fiber and protective substances, barium sulfate administration) resulted in elimination of 58 objects by vias naturals, 53 from which were not more that 8 cm long. Evacuation of the foreign bodies was carried out only during the first 3 weeks after the swallowing. Operative treatment was carried out in 21 patients, in whom 68 foreign bodies were extracted. An urgent operation in the first 6 hours in complications due to foreign bodies (perforation, incarceration, gastrointestinal bleeding) was carried out in 13 patients. An urgent operation in terms from 6 to 24 hours of hospitalization was carried out in 6 patients with large (more that 8 cm) swallowed objects, conglomerates and bunches of foreign bodies. Early removal of these objects prevented development of complications. Elective operation was carried out in failure of conservative treatment as was in 2 patients. No lethality was registered.

[The reasons for leaving foreign bodies in the abdominal cavity and the prevention of this complication]. / Prichiny ostavleniia inorodnykh tel v briushnoi polosti i profilaktika étogo oslozhneniia.

An investigation performed in 38 surgical and obstetrics-gynecology departments has established that during 20 years foreign bodies were forgotten in the abdominal cavity of 46 patients which makes up 0.03% of all laparotomies. In 30 patients they were forgotten in emergency operations and in 16 patients in elective operations. Among the victims there were 31 women. The textile foreign bodies such as gauze pads, tampons, towels were left most often (35 things), forgotten surgical instruments and other things were less frequent. The foreign bodies stayed in the abdominal cavity during the period from 6 hours till 15 years and in 26.1% of the patients they resulted in lethal outcomes. The main causes of accidental leaving the foreign bodies in the abdominal cavity during operative interventions are analyzed in detail. Means of prevention of such neglect of surgeons are proposed.

[Odontogenic mediastinitis]. / Odontogennyi mediastinit.

An experience with the surgical treatment of 28 patients with odontogenous mediastinitis is generalized, 12 of them died. The clinical picture is described in detail. Active surgical tactics is given the decisive role in the improvement of results of the treatment.

[Surgical interventions in abdomino-mediastinal lipomas]. / Khirurgicheskie vmeshatel'stva po povodu abdominomediastinal'nykh lipom.

The leading role in the recognition of abdomino-mediastinal lipomas is given to roentgenological examinations. Great significance is attached to thoracoscopy. Operations are fulfilled by the transpleural or transrectal accesses. The latter is the method of choice and must be accompanied by active drainage of the bed of the removed tissues during a day.

[Heart injuries in isolated and multiple trauma]. / Povrezhdeniia serdtsa pri izolirovannykh i sochetannykh raneniiakh.

Under investigation were specific features of the clinical picture in 34 patients with associated wounds of the heart and pericardium. Four dissimilar clinical groups were established. A comparative analysis of associated and isolated injuries (38 patients) has been made from the viewpoint of frequency of diagnostic errors, volume of the intraoperative blood loss and character of postoperative complications.