Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis: results of a six-month, multicenter, randomized, double-blind, controlled, phase IV trial.

OBJECTIVE: To compare the efficacy and safety of subcutaneous (SC) versus oral administration of methotrexate (MTX) in patients with active rheumatoid arthritis (RA). METHODS: MTX-naive patients with active RA (Disease Activity Score in 28 joints >or= 4) were eligible for the study if they had not previously taken biologic agents and had not taken disease-modifying antirheumatic drugs for 2 weeks prior to randomization. Patients were randomly assigned to receive 15 mg/week of MTX either orally (2 7.5-mg tablets plus a dummy prefilled syringe; n=187 patients) or SC (prefilled syringe containing 10 mg/ml plus 2 dummy tablets; n=188 patients) for 24 weeks. At week 16, patients who did not meet the American College of Rheumatology criteria for 20% improvement (ACR20) were switched from 15 mg of oral MTX to 15 mg of SC MTX and from 15 mg of SC MTX to 20 mg of SC MTX for the remaining 8 weeks, still in a blinded manner. The primary outcome was an ACR20 response at 24 weeks. RESULTS: At week 24, significantly more patients treated with SC MTX than with oral MTX showed ACR20 (78% versus 70%) and ACR70 (41% versus 33%) responses. Patients with a disease duration >or= 12 months had even higher ACR20 response rates (89% for SC administration and 63% for oral). In 52 of the ACR20 nonresponders (14%), treatment was switched at week 16. Changing from oral to SC MTX and from 15 mg to 20 mg of SC MTX resulted in 30% and 23% ACR20 response rates, respectively, in these patients. MTX was well tolerated. The rate of adverse events was similar in all groups. CONCLUSION: This 6-month prospective, randomized, controlled trial is the first to examine oral versus SC administration of MTX. We found that SC administration was significantly more effective than oral administration of the same MTX dosage. There was no difference in tolerability.

[Post-operative sclerosing mesenteritis]. / Postoperative sklerosierende Mesenteritis.

For the first time we describe a sclerosing mesenteritis that appeared acutely after abdominal operations. The patient suffered from diffuse abdominal symptoms. There was a hard tumour in the left middle and lower abdomen. Histological analysis revealed fibrosis and bone tissue. Symptoms improved after application of prednisone and high-calorie infusions.

[Ureteral rupture when changing a suprapubic vesical catheter]. / Ureterruptur beim suprapubischen Katheterwechsel.

We describe, for the first time, a rupture of the ureter caused by changing a suprapubic vesical catheter. The guide wire passed into the ostium of the left ureter during the procedure, and the catheter was pushed over the wire into the left ureter blocking it. The lesion was diagnosed by intravenous pyelography. A pigtail stent was placed in the left ureter.

[Retroperitoneal bronchogenic cyst]. / Retroperitoneale bronchogene Zyste.

We describe a 35-year-old female patient who underwent surgery because of a coincidentally occurring cryptic tumour near the left adrenal gland and a right renal carcinoma (pT1, N0, G2, R0). The left-sided tumour was intraoperatively identified as a cystic structure filled with secretion. Histopathological analysis provided the diagnosis of a bronchogenic cyst.

[Villous adenoma of the renal pelvis and ureter]. / Villöses Adenom des Nierenbeckens und Ureters.

Villous adenomas of the urinary tract are extremely rare tumours belonging to the adenoepithelial metaplasias. They can be associated with other neoplasias, especially with carcinomas. We describe the case of an 85-year-old female patient suffering from a villous adenoma of the renal pelvis and ureter.

[Tuberculosis induced by Bacillus Calmette-Guerin immuno-prophylaxis -- case study]. / Durch Bacillus Calmette-Guerin induzierte Tuberkulose.

We describe a case of miliary tuberculosis induced by Bacillus Calmette-Guerin (BCG) as a complication of an infection after BCG-instillation therapy into the bladder because of bladder carcinoma. Bacilli surely entered blood circulation via an urethral lesion because of a difficult catheterisation. The 60 year old patient was administered to the hospital with septic temperature 4 four days after BCG instillation. CT showed a miliary patten and the diagnosis was confirmed by bronchoscopy: transbronchial biopsy showed granulomatous infiltration and an acid-fast rod-bacterium was detected in bronchial slime. Symptoms vanished after a consequent antituberculous triple therapy regime and the patient left hospital in a good general state of health.

Synergistic interaction of two independent genetic loci causes extreme elevation of serum IgA in mice.

Understanding the molecular regulation of immunoglobulin A (IgA) expression is important as it plays an essential role in the first-line defence through mucosal secretions. Using inbred mouse strains, we identified two independent and dominant acting genetic loci that synergistically cause a 40-fold upregulation in serum IgA levels when introduced into the murine strain C57Bl/6J (B6). The first locus on chromosome 12 appears to be mainly responsible for the natural four-fold higher IgA levels in C3HeB/FeJ (C3H) compared to B6 mice. A second independent, chemically induced mutation on chromosome 5 caused a two-fold elevation when transferred from C3H into B6 mice. Both loci in concert effect a 40-fold elevation against the B6 genetic background. We determined the chromosomal localization of the two loci simultaneously by a one-step mapping process. The chemically induced mutation was identified within the immunoglobulin joining chain (IgJ) gene on chromosome 5. The major serum IgA modifier between the C3H and B6 was located on chromosome 12. This modifier region was mapped to a 350 kb region containing several immunoglobulin heavy-chain genes and the Ig alpha germline switch gene. We speculate that by interfering with both IgA expression and distribution, synergistic regulation of IgA is achieved.

Cirrhotic patients with or without hepatocellular carcinoma harbour AFP-specific T-lymphocytes that can be activated in vitro by human alpha-fetoprotein.

BACKGROUND: Alpha-fetoprotein (AFP) is re-expressed in 60%-70% of hepatocellular carcinomas (HCC) and may therefore be a potential target for a prophylactic or therapeutic tumour-specific vaccination. A prerequisite for this approach is the possibility to induce AFP-specific T-lymphocytes in patients with HCC and/or cirrhosis. METHODS: Peripheral blood was examined for the presence of AFP-specific T-lymphocytes using a FACS-based interferon-gamma secretion assay. RESULTS: In a group of healthy volunteers, the presence of AFP-specific CD4- and CD8-lymphocytes was demonstrated. Screening of blood of 14 cirrhotic patients without HCC and 23 cirrhotic patients with HCC showed that patients with liver diseases that represent targets for vaccination also harbour CD4-positive as well as CD8-positive AFP-specific Tlymphocytes. AFP reactivity in patients' lymphocytes was not significantly influenced by soluble serum AFP. The median stimulation factors for CD4-positive T-lymphocytes were significantly higher (P = 0.0365) in cirrhotic patients without HCC (median 2.08, range 0.50-4.40) compared to cirrhotic patients with HCC (median 1.15, range 0.24-8.50). CONCLUSION: AFP-specific T-lymphocytes that may be instrumental in HCC vaccination strategies are present in humans. This study suggests that immunopreventive vaccination of cirrhotic patients rather than immunotherapeutic vaccination of HCC patients may be preferable.

Health and environment of rural families: results of a Community Canvass survey in the Prairie Ecosystem Study (PECOS).

This cross-sectional survey was conducted as Phase I of the Prairie Ecosystem Study (PECOS): Environmental Pesticide Exposure and Human Health. In November of 1995, community volunteers delivered a self-administered household questionnaire to 1185 rural households in southern Saskatchewan, Canada. The survey provided a broad description of the general health and the physical environment of 511 men, 499 women, and 393 children (< 18 years of age) residing in 549 respondent households in the rural study area (population density of about one person/km2). Families in the respondent households resided on a farm, in town or both. Of the 369 households that operated a farm, 25.2% of the households did not list the farm as their primary household. Residents of both farming and non-farming households reported contact with pesticides and fertilizers through home or garden use. History of smoking was greater among men and women from non-farming households. The most commonly reported health problems among the children were a history of bronchitis, asthma, skin allergies, pneumonia, and hay fever. The most frequently reported health problems among the men were a history of high blood pressure, bronchitis, pneumonia, hearing problems, and stress; and among the women were a history of bronchitis, high blood pressure, shortness of breath, and pneumonia. Compared to farming households, more members of non-farming households reported a history of respiratory problems, particularly bronchitis among the women and children. Overall, there were important differences in the smoking history, the occupational use of pesticides and fertilizers, and the general health status between the farming and non-farming households and individuals in this rural population.

[Improved tumor stent for internal palliative urinary diversion]. / Neu entwickelter Tumorstent zur internisierten palliativen Harnableitung.

The disadvantages of high flexible endoureteral stents (DJ) in case of tumorinduced extrinsic ureteral compression are due to an insufficient vertical stability of the used stents leading to stent-compression and consecutive hydro- or pyonephrosis. The new developed tumor-stent used in case of tumor-induced ureteral compression is available from 6 to 8 French in diameter and 24 to 32 cm in length. The corpus consists of a combination of high-stability plastics but is of sufficient elasticity in length. Both ends consist of extremely elastic J-parts guaranteeing an exact fixation. As against common DJ's with the same outside-diameter the new stent has a comparable interior diameter and compared to used "old" tumor stents promises a higher interior flow in case of extrinsic diseases. The application can be undertaken in well-known technique, needs no special instrumentation and no learning-curve. To date 52 stents at our urologic departments were placed without any problems, the latest remaining for 15 months. Tumor-induced compression or a higher rate of encrustation could not be seen. All patients tolerated these stents well. In our opinion the new stabilized endoureteral stent can be seen as a better solution instead of percutaneous nephrostomy or frequent stent changing in patients with tumor induced extrinsic ureteral compression.

Behavior of different suture materials in the urinary bladder of the rabbit with special reference to wound healing, epithelization and crystallization.

Five urinary bladder incisions were performed in 16 rabbits and the defects closed by plain catgut 4-0, chromic catgut 4-0, polypropylene 4-0, polyglactin 910 4-0 and polyglactin 910 8-0 in the form of an all-layer suture, thereby obtaining a total of 80 suture sites. The running sutures in 8 animals were reviewed by light microscopy after 1, 2, 7 and 15 weeks, and in 8 additional animals after 3 days, 1, 2, 7 and 15 weeks by scanning electron microscopy. Moreover, we analyzed and compared the autopsy findings on gross inspection, the urinary sediments and urinary cultures of the individual animals. Scanning electron-microscopic evaluations showed that epithelization of the intraluminal suture portions can be accomplished after 3 days already. Reduced suture strength and rapid absorption of the suture material prevent later postoperative incrustations. Light-microscopic inspection of the segments of the bladder wall bearing this suture material suggests that a minor inflammatory tissue response around the suture material--with polyglactin 910 8-0 in particular--is more likely to enhance regeneration of the tunica muscularis and to prevent formation of cysts than seen with a long-standing highly inflammatory tissue response around the suture site of catgut threads. In the animal experiment, the polyglactin 910 suture has shown sufficient firmness and proved to be superior to any other suture material as regards the reaction to foreign bodies and inclination to incrustation.(ABSTRACT TRUNCATED AT 250 WORDS)

Women opiate users' perceptions of treatment services in New York City.

This paper focuses on the treatment experiences of women opiate users in New York City. Historically, drug research has used male samples, and drug treatment programs have been based upon the concerns of men. Treatment counselors and administrators are typically male, and female clients are frequently outnumbered by male clients. In addition, unique needs of women are not addressed. Primary among these needs is child care, a provision that is not a standard feature of most programs. Additionally, many women opiate users may be in dysfunctional families and/or have histories of sexual victimization that may require special counselling. Using data from 208 women drug users who had been in an opiate treatment program, this paper examines their perceptions of the extent to which these programs incorporate women's distinctive concerns and the degree to which such provisions are affected by the perceived numbers of women clients in these programs.

A comparative analysis of drug-using women with and without treatment histories in New York City.

Treatment histories of 459 drug-using women in New York City were examined to determine if there were any differences between women who have ever entered a treatment program and those who have not. Both bivariate and regression procedures were employed. The bivariate analysis revealed that the two groups of women differed significantly with regard to age, race, having children, age at which they began their drug-using careers, and the number of lifetime arrests. Controlling for all other variables in the regression analysis, only three variables significantly contribute to the likelihood of entering treatment: age, age at which regular drug use began, and the number of lifetime arrests. Implications of these findings for targeting younger women for treatment intervention are discussed.

[The electromotor unit of the upper urinary tract]. / Zum Problem der elektromotorischen Einheit der oberen Harnwege.

The muscular architecture of the upper urinary tract constitutes a functional but no anatomical syncytium, where the cells are coupled by nexus and crosslinking with low electrical resistance. The action potentials are evoked by spontaneous depolarisation of muscle cells. The sites of peak depolarisation could be termed pace-maker cells. They are localized in the calices. Recent studies have, however, described myofilaments capable of contraction in the proximal tubuli already. Volume and pressure loads on the hollow system have been identified as the regulation mechanism. Modulatory function is directly related to evidence of alpha- and beta-adrenergic receptors, of receptor subtypes, of the adenylate cyclase system, of histamine- and possibly prostaglandin- and serotonin-receptors as well.

Tumour imaging of bladder carcinomas and their metastases with 111indium-labelled monoclonal anti-CEA antibody BW 431/26.

Fifty-one patients with muscle-infiltrating bladder carcinoma (T2-T4, N0-3, M0-1) were studied with a new imaging technique using murine monoclonal antibody directed against the carcinoembryonic antigen (CEA). A total number of 67 investigations were performed. The intact 111indium-labelled antibody (BW 431/26, Behringwerke Marburg) detected 86% of primary tumours, 93% of local and 75% of distant metastases whether there was an elevated CEA level in serum or not. Immunohistologically (avidin-biotin-peroxidase method) positive frozen tissue sections from tumour biopsies stained with the same monoclonal anti-CEA antibody, thus confirming the presence of the CEA antigen in vitro. The method was of much higher sensitivity in detecting even very small metastases than X-ray computed tomography (86% versus less than 30%). The specificity was in the region of 90%. The response to chemotherapy (MVEC regimen) was shown by repeated studies demonstrating reduced uptake (partial remission) or no accumulation (complete remission) in the second immunoscan. We suggest immunoscintigraphy of bladder tumours and their metastases as an additional method in preoperative staging and postoperative care.

Histological and scanning electron microscopic alterations in ileal conduit depending on the time factor.

Five ileal conduit biopsies, taken after 1-7 years, were examined by light microscopy and scanning electron microscopy. The total height of the lamina mucosa decreased from 700 to 275 microns. The height of the villi diminished from 550 to 50 microns; the depth of the crypts increased from 130 to 244 microns and the villus-crypt index changed from 4.2 to 0.2. Signs of chronic inflammation could be observed. Scanning electron microscopy shows that the number of microvilli per cell was markedly reduced. There was a varied picture of different stages of atrophy. After 3 years microvilli could no longer be observed. In view of the prolonged urinary contamination time, it appears to be imperative to check neobladders with regard to possible carcinoma induction.

Actin as a component of cytoskeleton in the collecting tubule system of the mouse kidney.

Actin as a component of the cytoskeleton is familiar as a protein which possibly mediates contraction in nonmuscular cells. In 20 mouse kidneys, the distribution of intracellular actin in the collecting tubule system was investigated by means of the anti-actin PAP method. It could be shown that the positive PAP reaction increases from the proximal to distal up to the collecting tubules in the region of papilla. Stiffening, stabilization and contraction functions are discussed with regard to the biology of the collecting tubule actin.

The Drosophila melanogaster tropomyosin II gene produces multiple proteins by use of alternative tissue-specific promoters and alternative splicing.

The structure of the Drosophila melanogaster tropomyosin II (TmII) gene has been determined by DNA sequencing of cDNA clones and the genomic DNA coding for the gene. Two overlapping transcriptional units produce at least four different tropomyosin isoforms. A combination of developmentally regulated promoters and alternative splicing produces both muscle and cytoskeletal tropomyosin isoforms. One promoter is a muscle-specific promoter and produces three different tropomyosin isoforms by alternative splicing of the last three 3' exons. The second promoter has the characteristics of a housekeeping promoter and produces a cytoskeletal tropomyosin isoform. Several internal exons along with a final 3' exon are alternatively spliced in the cytoskeletal transcript. The intron-exon boundaries of the TmII gene are identical to the intron-exon boundaries of all vertebrate tropomyosin genes reported, but are very different from the intron-exon boundaries of the D. melanogaster tropomyosin I gene. The TmII gene is the only reported tropomyosin gene that has two promoters and a quadruple alternative splice choice for the final exon. Models for the mechanism of D. melanogaster tropomyosin gene evolution are discussed.

Characterization of a Drosophila cDNA clone that encodes a 252-amino acid non-muscle tropomyosin isoform.

We report here the isolation and DNA sequence of a cDNA clone encoding a 252-amino acid non-muscle or cytoskeletal tropomyosin (cTm) isoform from Drosophila. The Drosophila cTm shows considerable homology with vertebrate cTm throughout the middle portion of the molecule. The amino-terminal end of the molecule, however, shows less homology and contains five more amino acids than the equine platelet and human tropomyosins. There is also a proline at position 6 in the Drosophila protein. The carboxyl-terminal 27 amino acids also show little homology with vertebrate non-muscle tropomyosins. This is a region of the molecule that shows considerably diversity among other Drosophila tropomyosins and vertebrate tropomyosins. A comparison of the DNA sequence of the cTm cDNA and a previously reported muscle tropomyosin II cDNA sequence shows regions of identical DNA sequence alternating with regions of nonidentical sequence, suggesting that both mRNAs are produced by alternate splicing of the same gene.

[Specialized and interdisciplinary team work in rheumatology]. / Spezialisierte und interdisziplinäre Arbeit in der Rheumatologie.

The large number of rheumatic diseases demands a clear differentiation between the individual forms of diseases. For this purpose are at first necessary knowledge concerning clinical criteria and in the second place knowledge about serological and radiological examinations. The serological programme shall be relevant to practice, consist of a basis diagnostics and for particular differential-diagnostic problems shall include specialized laboratory investigations. Necessary X-ray pictures must be performed with a special aim and comparison of the sides. For therapy the interdisciplinary team work, consisting in the cooperation of rheumatologists, orthopedic surgeons, specialized surgeons and physiotherapists stood the test. An important prerequisite is also the cooperation of the outpatient and inpatient rheumatological institution. For a complex rehabilitation programme apart from the physicians experienced coworkers for tasks of welfare, ergotherapy and physiotherapy are necessary.