P2 purinoceptor antagonists inhibit the non-adrenergic, non-cholinergic relaxation of the human colon in vitro.

Neurotransmitters released by myenteric neurons regulate movements of intestinal smooth muscles. There has been little pharmacological evidence for a role of purinergic mechanisms in the non-adrenergic, non-cholinergic (NANC) relaxation of the human large intestine. We used P(2) purinoceptor antagonists to assess whether such receptors are involved in the NANC relaxation of the circular muscle of the human sigmoid colon. It was also investigated whether the guanylate cyclase enzyme mediates the NANC response. Human colonic circular strips were tested in organ bath experiments with isotonic recording. NANC, non-nitrergic relaxations induced by electrical field stimulation (1 and 10 Hz, in the presence of atropine, guanethidine, and 100 microM N(G)-nitro-L-arginine [L-NOARG]) were strongly inhibited by a combination of the P(2) purinoceptor antagonists pyridoxal-phosphate-6-azophenyl-2',4'-sulfonic acid (PPADS) (50 microM) and suramin (100 microM). PPADS plus suramin was ineffective in the absence of L-NOARG. L-NOARG alone significantly reduced the NANC relaxation to electrical stimulation. PPADS plus suramin strongly inhibited the relaxation in response to exogenous alpha,beta-methylene ATP. The guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (3 microM) inhibited the NANC relaxation, but did not add to its reduction by L-NOARG. L-NOARG was still slightly effective in the presence of ODQ. Vasoactive intestinal polypeptide tachyphylaxis failed to influence the non-nitrergic NANC relaxation. It is concluded that nitric oxide (NO) and ATP co-mediate, in a non-additive manner, the NANC relaxation. NO probably acts through the guanylate cyclase, though a small fraction of its effect might be mediated by other mechanisms. Activators of the guanylate cyclase other than NO do not seem to participate in the NANC relaxation.

The hourglass appearance of the neurofibroma on rectal ultrasound. A case report.

Colorectal manifestation of von Recklinghausen's disease is a rare entity. The typical dumbbell shape of the lesion has been described previously, but only from a resected cecal specimen. The authors present the endosonographic appearance of a rectal neurofibroma, which shows a similar hourglass shape, thus facilitating the diagnosis.

A comparison of fluorescamine and naphthalene-2,3-dicarboxaldehyde fluorogenic reagents for microplate-based detection of amino acids.

The use of appropriate fluorometric derivatization procedures is of considerable importance for accurate determination of amino acids in biological samples and in metal-assisted peptide hydrolysis reactions. It is especially critical for the relative fluorescence intensities (RFI) of equal amounts of amino acids to be as similar as possible. While fluorescamine and naphthalene-2,3-dicarboxaldehyde (NDA) have proven to be excellent fluorogenic reagents for amino acid detection, the effects of various factors such as organic solvent, buffer, and pH have never been rigorously evaluated with respect to normalizing the relative fluorescence intensities of individual amino acids. To this end, here we describe optimized fluorescamine and NDA derivatization reactions that enhance the accuracy of microplate-based detection of amino acids. For both fluorescamine and NDA, we have shown that the RFI values of 16 of 19 amino acids are greater than 70%. Although determination of tryptophan is problematic, this difficulty is overcome by the addition of beta-cyclodextrin to the NDA reaction. In principle, the optimized fluorescamine and NDA microplate procedures reported here can be utilized as complementary techniques for the detection of 19 of 20 naturally occurring amino acids.

[Current treatment of anal fissure]. / Az analis fissura modern kezeléséról.

More and more authors believe, that the cause of the chronic anal fissure is the increased anal resting pressure. It maintains a vicious circle causing ischaemia and ulcer on the anoderm. There are many traditional surgical methods treating fissures apart from the conservative ways. However, these are likely to cause significant morbidity. Chemical sphincterotomy seems to be a novel way and its most effective drugs are the nitrates. 75-80% of the patients can be cured with the topical use of these. This treatment has to be accompanied with the normalisation of the stools. If the symptoms persist after 6-8 weeks the procedure of choice is the lateral sphincterotomy. Authors evaluate the different treatments based on a literature overview and own experiences. They also suggest a treatment protocol.

[Analgesics-induced chronic renal failure in patients on dialysis therapy in Hungary]. / Analgetikum-nephropathia elófordulása krónikus veseelégtelenség miatt dializált betegekben Magyarországon.

In recent years elaboration of the diagnosis of analgesic-nephropathy (ANP) with the help of imaging techniques significantly increased the possibility of diagnosing the disease. Therefore, evaluating the prevalence of ANP has become more accurate in our country as well. The prevalence of ANP has been investigated in patients who have newly been taken into the dialysis program due to renal disease of unknown aetiology in 22 dialysis centers between December 1994-December 1997. The diagnosis of ANP has been based on revealing chronic drug abuse in the history and positive results of renal imaging (decrease in length of both kidneys combined with either bumpy contours and/or papillary calcification). Among 284 patients dialysed with unknown diagnosis 42 (14.8% of all cases) proved to have ANP. All patients except 2 took analgesic mixtures containing phenacetin/paracetamol, phenason derivatives, acetilsalysilic acid, caffeine and/or codeine. According to their investigations, ANP is a common disease resulting in end-stage renal failure in Hungary as well.

First Hungarian, internet-based prospective, multicenter study: the hernia-project.

In inguinal hernia repair, different laparoscopic and open techniques of tension-free repair using synthetic meshes have been reported to result in better patient comfort and lower recurrence rates compared with conventional procedures like Shouldice's or Bassini's operation. In comparison with the laparoscopic procedure, open tension-free repair can be performed under local anaesthesia and is less expensive. For these reasons, the recent trend in inguinal hernia surgery, has been towards using an open, mesh-based tensionless repair (Lichtenstein technique). To evaluate and support the widespread use of this technique in Hungary a large, prospective multicentre trial was initiated at 15 March 1999. Prospective registration of 1500 hernia operation using Lichtenstein technique is undertaken that is carried out in 15 hospitals. Postoperative outcome, complications and recurrence is recorded through a five years period. The case presentation and data collection is internet based. Each center participating in the study is connected by internet to the coordinating center and all information concerning this study is sent by this way. This system is able to generate actual statistical data in every moment of the study.

Reverse two-stage procedure in the surgical treatment of esophageal cancer.

Authors have performed 266 one-stage resections and 6 reversed two-stage operations for the treatment of esophageal cancer during a 10-year-period. In six cases first a substernal bypass with colon or stomach was carried out while the tumourous esophagus was removed only 3-4 weeks later from a right thoracic approach. All six patients recovered. The reverse two-stage operation for esophageal cancer can be suggested with rare indications (pulmonary abscess, previous abdominal operations, severe malnutrition, etc.) and it is only justified when the advantage gained by increased operability and decreased morbidity and/or mortality is higher than the disadvantage ensuing from oncological, financial and patient demanding considerations.

Validation of a particle enhanced immunoturbidimetric assay for serum beta 2-microglobulin on the Dade aca.

We describe the development and validation of a fully automated homogeneous immunoassay for serum beta 2-microglobulin on the Dade aca clinical analyzer. The assay employs latex enhanced immunoturbidimetry, with an affinity purified polyclonal antibody covalently coupled to a 40 nm latex particle. The assay working range is < 0.5 to 20 mg/l with no evidence of loss of signal due to antigen excess at concentrations up to 120 mg/l. The assay sensitivity is 0.2 mg/l; within run and between run imprecision showed coefficients of variations of < 7%, across the assay range 1-20 mg/l. A method comparison with an established RIA procedure gave a regression equation of (aca) = 1.14 (RIA)-0.26, r = 0.996, n = 109. Good analytical recovery (98-101%), no evidence of a lack of parallelism and no interference from rheumatoid factor (tested up to 1.2 x 10(6) U/l) were observed. The low method to be considered as an effective means of monitoring seroconversion in HIV infected subjects and treatment of patients with myelomatosis.

The polymorphic human TLX-B/CD46/MCP system and its implications in transplantation and reproduction.

TLX antigens have been found on most peripheral blood cells, trophoblasts, seminal vesicle cells and sperms. These antigens seem to be associated with the membrane cofactor protein (MCP) and the CD46 antigen. Alloantibodies to TLX antigens with Fc tau RII-blocking features were obtained by transfusion of leucocytes or platelets. Preliminary population studies revealed that alloantibodies to TLX/CD46/MCP recognize four overlapping specificities. The terminology TLX-B was introduced with specificities TLX-B1, B2, B3, B4 and frequencies obtained in the population were: 38%, 46%, 42% and 26%, respectively. Family studies showed an independent segregation of the TLX and HLA alleles. At the cellular protein on trophoblast, the alloantibody detected a glycoprotein of 66-67 kDa molecular mass, which may correspond to the alpha chain of the TLX/CD46/MCP isotypes. A direct association of the alloantibody with Fc tau RII could be excluded thus its FcR blocking feature is probably based on an indirect functional effect. After transfusion and in pregnancy the induction of TLX alloantibody production depended on the mismatching in the TLX/CD46/MCP phenotypes. Probable associations were revealed in the case of recurrent habitual abortion between the lack of Fc tau R blocking antibody production and the matched TLX specificities of the couples. After transfusion, TLX alloantibody production with Fc tau R and MLR blocking function was induced only when the recipient was lacking the TLX specificities expressed on the donor cells. Suppression of MLR was found only when TLX specificity in sera corresponded to the TLX specificity of the effector cell. The immunopathological importance of these findings in transplantation and reproductive medicine has yet to be clarified.

[Early cancer of the esophagus]. / A nyelöcsö korai rákjáról.

The authors report four cases with the postoperative diagnosis of the early cancer of the esophagus. The histological type of the tumor was squamous cell carcinoma in three cases and adenocarcinoma in the remaining one. The tumors were localized in the lower part of the esophagus. Left sided thoraco-laparotomy was carried out in two cases. They used a right sided thoracotomy with abdominal and neck incisions. Trans-mediastinal esophagectomy was performed in the remaining one case. The continuity of the gastrointestinal tract was restored by substernal colon interposition in a case, by substernal stomach in another one and by oesophago-jejunostomy in the remaining two cases. New diagnostic possibilities and the international results of the treatment of the early esophageal cancer are discussed.

Differences in non-MHC restricted cytotoxic activities of human peripheral blood lymphocytes after transfusion with allogeneic leukocytes or platelets possessing class I and/or class II MHC molecules.

MHC-unrestricted cytotoxic activity of peripheral blood lymphocytes (PBL) from 4-6 healthy donors was investigated before and after transfusion with allogeneic leukocytes or platelets. Natural killer and lectin-dependent cellular cytotoxicity (LDCC) of PBL was tested against K562 and Raji target cells in a 4-h and 16-h 51Cr-release assay, respectively. After allotransfusion with leukocytes, we found increased cytotoxic activity of each donor's PBL against all the three targets on day 3 or 7. The highest non-specific cytotoxic activity was detected against the relatively NK resistant Raji target cells. The increase of cytotoxic activity was lowest against the LDCC target (PHA-treated Raji) cells. On the contrary, no changes in cytotoxic activity against any targets were observed after allotransfusion with platelets (possessing class I HLA antigens but no HLA class II molecules). Our results suggest that HLA class II molecules, presumably by inducing immune responses, are essential for activation/generation of non-specific killing of tumor targets after leukocyte transfusion. Thrombocytes, known to be less immunogenic than leukocytes, are not effective in in vivo enhancing of non-specific cytotoxicity. Cellular activation of PBL following leukocyte allotransfusion was confirmed by detection of elevated serum neopterin and beta-2-microglobulin levels on day 3. This was not the case after platelet allotransfusion. In addition, the expression of ICAM-1 antigen (as a molecule involved directly in MHC-unrestricted cytotoxicity) was also found to be increased in two donors' PBL on day 3 after leukocyte transfusion in contrast to transfusion with platelets.

Functional and immunogenetic characterization of FcR-blocking antibody.

The characteristics and functional importance of FcR-blocking antibodies and their production were investigated after immunization with whole blood, "buffy coat" and purified platelets. We studied the presence of FcR-blocking antibody in haemodialyzed, transfused patients waiting for kidney transplantation, and we found strong correlation between the blocking effect and better graft survival. We suggest that this blocking antibody does not attack FcR as primary target. Investigation of blocking activity of ten different immune sera on 50 healthy panel cells showed that target antigen has some polymorphic varieties. On basis of family studies it seems that the target antigen is not linked to HLA haplotype. The blocking effect of sera could be removed by absorption of CD8+ cells, B lymphocytes, platelets and granulocytes, but not with erythrocytes, monocytes, CD8- cells and NK cells.

Caretaking environments.

Recent statistics validate the impact of the Human Immunodeficiency Virus (HIV) on women and children in the United States. An increasing number of women of childbearing age are being infected by sharing needles and syringes with HIV-positive individuals and by having sex with partners who are either known or unknown sources of HIV infection. These women subsequently expose their children to the virus during pregnancy and at birth. Frequently, these children are both HIV-positive and addicted to drugs. In response to the increasing needs of these women and their children who are frequently homeless, orphaned, or without adequate care, private, municipal, county, and federal groups and agencies have either redefined their services or developed new programs. The dedication of these groups has resulted in caretaking environments and programs which furnish the infected women and children and their families with medical care, physical, emotional, and financial support.

Dynamism of the development of "Fc receptor-blocking antibodies" after immunization with buffy coat.

Eight healthy male blood donors who had not received transfusion previously, were immunized 5 times at 6-week intervals. The immunization was carried out with "buffy coat" separated from 400 ml freshly obtained donor blood. Donor-recipient pairs showed a mismatching for 1 to 4 HLA antigens. The production of HLA antibodies could be demonstrated in 4 patients during the repeated immunizations. Fc receptor-blocking antibody activity was determined with the erythrocyte antibody inhibition (EAI) method in serum samples for the recipients. An increase in the Fc receptor-blocking antibody serum level could be detected already on the second day after the first immune stimulus. Fc receptor-blocking activity was maximum on the 10th day after immunization. After repeated immune stimuli, the increased non-specific Fc receptor-blocking antibody activity was demonstrated independently of the appearance of specific HLA cytotoxic antibodies.

Comparative study of alloimmune reactions induced by leukocyte and platelet transfusions in humans: characteristic changes of activation markers, gamma interferon, and FcR blocking antibody production.

This study was undertaken to define immune responses induced by leukocyte and platelet transfusions. We offer evidence that activation by alloimmunization with intravenously administered "buffy coat" cells results in immune alterations similar to the early rejection episodes following kidney transplantation. Thus, IL-2 and HLA-DR expression increased on PBL 2 and 3 days after antigen exposure and paralleled elevations of IFN-gamma, neopterin, and beta 2 microglobulin levels. No significant changes were detected in the number of T-cell subpopulations. Alloimmunization by purified platelets alone that express only class I MHC antigens failed to induce the above alteration, even after repeated exposure. Repeated alloimmunization with "buffy coat" cells or isolated platelets stimulated a progressive increase up to 100% blocking activity on EA rosette formation. We conclude that the expression of activation markers on PBL and the production of IFN gamma and neopterin reflect the early phase of alloimmune response induced by leukocytes. This type of alloactivation is not a prerequisite for the development of FcR-blocking antibody, which is produced after pure platelet transfusion as well.