Urological manifestations of the disease related to immunoglobulin G4.

Immunoglobulin G4 related disease (IgG4-RD) is a fibro-inflammatory disease of unknown etiology, characterized by lesions in the form of tumors, elevated serum IgG4 levels, plasma cells with significant IgG4 infiltration, accompanied by phlebitis obliterans and fibrosis. This disease usually has multiorgan disease, including pancreas, biliary tract, salivary glands, peri orbital tissues, kidneys, lungs, lymph nodes and retro peritoneum. IgG4-RD mainly affects men with a predominance of age by young adults until old age. The clinical manifestations of IgG4-RD, depend mainly on the organs affected and the response to steroids. His forecast is not yet clear. Within the affected urogenital organs can be observed kidney, retroperitoneum, ureter, bladder, urachus, testis/epididymis, paratesticular region, prostate and urethra.

La enfermedad relacionada con la inmunoglobulina G4 (ER-IgG4) es una enfermedad fibroinflamatoria de etiología desconocida, la cual se caracteriza por presentar lesiones en forma de tumoraciones, concentraciones séricas aumentadas de IgG4 y células plasmáticas con una infiltración importante de IgG4, junto con flebitis obliterante y fibrosis. Esta enfermedad suele tener afección multiorgánica, incluyendo el páncreas, el tracto biliar, las glándulas salivares, los tejidos periorbitarios, los riñones, los pulmones, los ganglios linfáticos y el retroperitoneo. La ER-IgG4 afecta principalmente a hombres, con un predominio de edad por los adultos jóvenes y hasta la vejez. Las manifestaciones clínicas de la ER-IgG4 dependen principalmente de los órganos afectados y de la respuesta a los esteroides. Su pronóstico aún no es del todo claro. Dentro de los órganos urogenitales afectados pueden incluirse el riñón, el retroperitoneo, el uréter, la vejiga, el uraco, el testículo/epidídimo, la región paratesticular, la próstata y la uretra.

Current Therapeutic Strategies in Clinical Urology.

The field of urology encompasses all benign and malignant disorders of the urinary tract and the male genital tract. Urological disorders convey a huge economic and patient quality-of-life burden. Hospital acquired urinary tract infections, in particular, are under scrutiny as a measure of hospital quality. Given the prevalence of these pathologies, there is much progress still to be made in available therapeutic options in order to minimize side effects and provide effective care. Current drug delivery mechanisms in urological malignancy and the benign urological conditions of overactive bladder (OAB), interstitial cystitis/bladder pain syndrome (IC/BPS), and urinary tract infection (UTI) will be reviewed herein. Both systemic and local therapies will be discussed including sustained release formulations, nanocarriers, hydrogels and other reservoir systems, as well as gene and immunotherapy. The primary focus of this review is on agents which have passed the preclinical stages of development.

Poor immune reconstitution is associated with symptomatic BK polyomavirus viruria in allogeneic stem cell transplant recipients.

BACKGROUND: BK polyomavirus (BKPyV) infections are known indicators of immune suppression in hematopoietic stem cell transplant (HSCT) recipients; they can lead to hemorrhagic cystitis, ureteral stenosis, renal dysfunction, and prolonged hospital stays. In this study, we determined transplant-associated variables and immune parameters that can predict for the risk of BKPyV viruria. We hypothesized that BKPyV infection is a marker of poor immune recovery. METHODS: We analyzed all engrafted patients undergoing first allogeneic HSCT at MD Anderson Cancer Center in Houston between January 2004 and December 2012. We evaluated their immune parameters and their transplant-associated factors. BKPyV positivity was defined as BKPyV detection in urine by polymerase chain reaction testing. Cox proportional hazards model, as well as competing risk analysis method using subdistribution hazard models with death as competing risk, were applied to assess risk of BKPyV viruria. RESULTS: We identified a total of 2477 patients with a median age of 52 years. BKPyV viruria was manifest in 25% (n=629) of the patients. The median time from transplantation to BKPyV viruria development was 42 days among the patients who had BKPyV viruria. On multivariate analysis, tumor type, acute GVHD, chronic GVHD, myeloablative conditioning regimen, cord blood as the graft source, CD3+ , CD4+ , CD8+ , CD56+ , NK counts, and low platelet count were shown to be significantly associated with BKPyV infection. These finding were further confirmed when models incorporating the competing risk of death yielded similar findings. CONCLUSION: In this study, we report significant associations between BKPyV reactivation following allogeneic HSCT and suppressed immune variables. In addition, this study provides valuable information on the immune status of HSCT recipients as a predictor of BKPyV infections that may in turn help us formulate plans for more effective prevention and treatment of this infection.

IgG4-related disease: what urologists should know.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a recent nosological entity defined as a chronic immune-mediated fibro-inflammatory condition characterized by a tendency to form tumefactive, tissue-destructive lesions or by organ failure. Urologic involvement in IgG4-RD has been described in some short series of patients and in isolated case reports. AIM: The aim of the present study was to review urologic involvement in IgG4-RD with the purpose of providing urologists with the proper background necessary for a preliminary assessment of possible urologic localization of this recent clinical entity. Indeed, patients are typically referred for immunologic management, often right after a differential diagnosis of urologic disease. MATERIALS AND METHODS: A systematic search of PubMed® for both original and review articles published up until October 2015 was performed using keywords relating to IgG4 and to single specific urologic organs, structures, or anatomic sites. The search was then extended to Google® using the same search criteria in order to identify articles not indexed in PubMed®. RESULTS: IgG4-RD is a systemic condition potentially involving every urologic site. It can mimic malignancies and is often misdiagnosed due to its rarity. CONCLUSIONS: A multidisciplinary approach to IgG4-RD should be required because it occasionally mimics other urologic diseases, including malignancies. Therefore, urologists should perform preliminary assessments to avoid inappropriate urologic treatments.

Glutamine-enriched enteral nutrition in very low birthweight infants and allergic and infectious diseases at 6 years of age.

In a previous randomised controlled trial, we found that glutamine-enriched enteral nutrition in 102 very low birthweight (VLBW) infants decreased both the incidence of serious infections in the neonatal period and the risk of atopic dermatitis during the first year of life. We hypothesised that glutamine-enriched enteral nutrition in VLBW infants in the neonatal period influences the risk of allergic and infectious disease at 6 years of age. Eighty-eight of the 102 infants were eligible for the follow-up study (13 died, 1 chromosomal abnormality). Doctor-diagnosed allergic and infectious diseases were assessed by means of validated questionnaires. The association between glutamine-enriched enteral nutrition in the neonatal period and allergic and infectious diseases at 6 years of age was based on univariable and multivariable logistic regression analyses. Seventy-six of the 89 (85%) infants participated, 38 in the original glutamine-supplemented group and 38 in the control group. After adjustment, we found a decreased risk of atopic dermatitis in the glutamine-supplemented group: adjusted odds ratio (aOR) 0.23 [95% CI 0.06, 0.95]. No association between glutamine supplementation and hay fever, recurrent wheeze and asthma was found. A decreased risk of gastrointestinal tract infections was found in the glutamine-supplemented group (aOR) 0.10 [95% CI 0.01, 0.93], but there was no association with upper respiratory, lower respiratory or urinary tract infections. We concluded that glutamine-enriched enteral nutrition in the neonatal period in VLBW infants decreased the risk of atopic dermatitis and gastrointestinal tract infections at 6 years of age.

Inmunoterapia para las infecciones recurrentes del tracto urinario: efectos de un extracto de escherichia coli: [revisión] / Immunotherapy for recurrent urinary tract infections: effects of an escherichia coli extract: [review]

La carga de las infecciones del tracto urinario (ITU) es alta en el mundo entero. Debido a que los tratamientos causales de estas infecciones frecuentemente recurrentes tienen límites sustanciales, las medidas preventivas merecen la prioridad. Entre ellas, la inmunoestimulación con extractos bacterianos ha demostrado que previene las ITUs y que es muy segura. Esta revisión enfoca el inmunoestimulante OM-89, un extracto liofilizado de Escherichia coli producido mediante biotecnología, formulado para la administración por vía oral a partir de este germen frecuentemente responsable de las ITU, y cubrirá sus efectos farmacológicos y clínicos con respecto a eficacia y seguridad. Se pondrá énfasis especial en los estudios clínicos realizados en niños, adultos y pacientes especiales así como en un estudio que evaluó el efecto de OM-89 sobre la calidad de vida de los pacientes.

Humoral immune response after kidney transplantation is enhanced by acute rejection and urological obstruction and is down-regulated by mycophenolate mofetil treatment.

The anti-allograft immune response may have a cellular and a humoral component. Lymphocytotoxic antibodies (Ab) and anti-human leucocyte antigen (HLA) Ab present before kidney transplantation carry an enhanced risk of acute rejection. Current immunosuppressive drugs act predominantly upon the cellular immune pathway which may leave unopposed the humoral mechanisms of anti-allograft response. We studied the production of lymphocytotoxic Ab and anti-HLA Ab after kidney transplantation under different drug therapies. Two hundred and sixty-four consecutive kidney transplant recipients treated with different immunosuppressive drugs, either stable and or with previous acute rejection or acute urologic obstruction, entered this study. Lymphocytotoxic Ab and anti-HLA Ab were evaluated by complement-dependent cytotoxicity and by ELISA. Ab donor-specificity was determined by flow cytometry. Both lymphocytotoxic Ab and anti-HLA Ab were significantly increased in acute rejection whatever the immunosuppressive regimen and almost significantly in urologic obstruction treated with azathioprine (AZA) groups. The presence of antidonor-specific Ab was associated with a significantly higher rate of graft loss. Mycophenolate mofetil (MMF) therapy significantly down-regulated Ab synthesis in all patients groups when compared with AZA. The development of humoral antidonor response post-transplantation is associated with a dismal graft prognosis. This is the first report that acute urologic obstruction may be followed by unspecific lymphocytotoxic and anti-HLA Ab synthesis, surmising that a protracted obstruction may promote renal fibrosis through antibody mediation. The significant down-regulation of the humoral response by MMF when compared with AZA may herald a lower risk to mount a chronic rejection process.

[Spectrum of tuberculosis antibodies in patients with tuberculosis and borderline urinary tract diseases]. / Spektr protivotuberkuleznykh antitel u bol'nykh tuberkulezom i pogranichnymi zabolevaniiami mochevydelitel'noi sistemy.

The spectrum of tuberculosis antibodies detectable by indirect hemagglutination test, complement consumption, passive hemaagglutilution test (PHAT), and enzyme-linked immunosorbent assay (EISA) in patients with urinary tract diseases (tuberculosis, nonspecific disorders) was studied. In untreated bacteria-isolating patients in the early phase of disease, antibodies were found in 61.8%, their different types were detectable at different rates so it is more advisable to explore responses by using several serological tests. During treatment there is an increase in antibody detection rates by ELISA. At this time only can PHAT and ELISA be made. High seropositive rates (85-100%) are ensured by PHAT and ELISA in new case in end-stage disease. The antibodies are detected in 75 of the pretreated patients with nephrotuberculosis largely by PHAT and ELISA. Examination of patients with nonspecific disease by ELISA clarifies the clinical status of these patients.

Relationship among age, prostate-specific antigen, and prostate volume in men with lower urinary tract symptoms (LUTS) and in different groups of men with and without benign and malignant prostate diseases.

BACKGROUND: In order to enhance prostate-specific antigen (PSA) as a predictor of prostate cancer, it is necessary to understand the characteristics of this tumor marker in a population of men without evidence of prostate cancer but who are at risk for developing the condition. METHODS: In an age-stratified population of 328 men with lower urinary tract symptoms (LUTS), we analyzed the distribution of PSA levels as a function of age and prostate volume, and we analyzed the percentage of age-related variance in PSA that can be explained by the age-related variance in prostate volume. RESULTS: Classifying the 328 cases with LUTS according to four age groups, a correlation was found between PSA and prostate volume, becoming stronger from the younger (correlation coefficient, -0.1265) to the older group (correlation coefficient, 0.6044). Serum PSA variance per milliliter of prostate volume also increased from the younger (not significant, P > 0.1) to the older age decades (7.3% in men age 70 years or over). Moreover, the results of the regression analysis suggest that 10% of the variance in PSA with age can be accounted for by prostate volume in men under age 50 years, reaching 37% in men age 70 years or more. CONCLUSIONS: These data confirm that the serum PSA concentration increases with advancing age in the absence of clinically evident prostatic malignancy. In younger patients with LUTS, serum PSA variance with age seems to be less dependent upon the age-related variance in prostate volume.

Relationship of lower urinary tract signs to seropositivity for feline immunodeficiency virus in cats.

A group of 41 cats with signs of lower urinary tract disease was compared to a group of 41 cats without any history of disease for prevalence of seropositivity for feline immunodeficiency virus (FIV). The group of healthy cats was similar in age and gender to the group of cats with signs of lower urinary tract disease. Three of the cats with lower urinary tract disease and one control cat were seropositive for FIV. This difference was not statistically significant. The most common cause of lower urinary tract signs was idiopathic. Only 7 cats had urinary tract infection, most associated with perineal urethrostomy or catheterization. Six of the cats with bacterial urinary tract infections were FIV negative.

[The phagocytic test in the assessment of antimicrobial protection in inflammatory urologic diseases]. / Fagotsitarnyi test v otsenke antimikrobnoi zashchity pri vospalitel'nykh urologicheskikh zabolevaniiakh.

As shown in in vitro original modelling of red cell action on phagocytic process in the whole blood of patients with urological inflammation, these patients have increased count of neutrophils involved in phagocytosis, but low specific absorption of these neutrophils due to red cells. In chronic renal insufficiency characterized by a low phagocytic activity of neutrophils only stimulating potential of red cells can be noted.

IgG antibodies to papillomavirus genus-antigens in adult men with cancer of the urinary bladder.

Forty-five sera from men with bladder cancer were examined in a micro solid-phase enzyme-linked immunosorbent assay (ELISA) and in a Western-blotting (WB) assay for the presence of IgG antibodies to papillomavirus (PV) genus-antigens of bovine origin. The ELISA detected PV antibodies in 75.6% of cancer patients. This antibody frequency was significantly higher than that found in both healthy males (22.7%) and patients with urological disorders (24%). A similar correlation among the PV antibody frequencies of the three groups was found with WB assay: 60% of the neoplastic group showed PV antibodies versus 17.3% in healthy males and 32.6% in non-neoplastic patients. Within the same group, 78% to 87% sera showed the same reactivity to both assays. Of these concordant sera, PV positive sera were 55.6% in cancer patients, 13.3% in healthy adults and 19.6% in patients with urological disorders. ELISA PV antibody level in the cancer group was higher than in each of the two control groups. The meaning of the humoral response to PV genus-antigens in men with bladder cancer is discussed.

Determination of soluble interleukin-2 receptor in human seminal plasma.

Following lymphocyte activation a soluble form of TAC antigen is released. This soluble molecule (soluble interleukin-2 receptor, SIL-2R) seems to corresponds to a truncated extracellular part of the membrane-bound TAC antigen, being smaller than its cellular counterpart. SIL-2R was determined and correlated with PMN elastase levels in the seminal plasma of 79 adult men having different concentrations of PMN elastase (0-700 micrograms/L). The normal level of SIL-2R was detected in the seminal plasma of 15 healthy men. The mean +/- SEM was 101 +/- 29 units/mL. The relation between PMN elastase in human seminal plasma as an index for the state of lymphocyte activity and the sperm motility is also investigated.

[The use of plasmapheresis in treating urology patients]. / Ispol'zovanie plazmafereza v lechenii urologicheskikh bol'nykh.

The paper presents the results of plasmapheresis inclusion into a combined therapy of pyelonephritis. Out of 79 patients treated, 42 had urosepsis, 25 developed pyelonephritis in pregnancy, 12 had complicating chronic renal failure. Uroseptic patients were examined for hemostasis, the rest for immune status. There were symptoms of DIC syndrome in the former and immunity suppression in the latter. After the combined therapy with plasmapheresis, latent hypercoagulation and intoxication disappeared, uroseptic manifestations reduced. The above treatment of pregnancy pyelonephritis stopped inflammation, promoted activation of the immune system. In patients with chronic renal failure adjuvant plasmapheresis enhanced cellular and humoral immunity, neutrophil function, the number of middle-size molecules in the blood diminished. The latter improved renal function in decreasing uremia.

[A clinical study of bacteremia in urology].

We investigated 32 patients with bacteremia that occurred in the Department of Urology, School of Medicine, Kanazawa University between April, 1983 and March, 1989. This incidence represented 1.9% of the total number of inpatients. The study group comprised 29 males and 3 females, and their age varied from 25 to 82 years with a mean age of 61.7 years. Twenty-two (75%) of the 32 patients had urologic malignancies. The majority of patients were compromised hosts who had one or more (average, 3.8) factors that promoted bacteremia. Urinary tract infections existed in 26 (86.0%) patients before the bacteremic episode and urine cultures revealed a species identical to that simultaneously isolated from the blood in 19 (73.1%) of the 26 patients. Out of the 26 patients, there were 22 (84.6%) with complicated pyelonephritis and 22 (84.6%) with an indwelling urinary tract catheter. In blood cultures, the most common isolate was Staphylococcus epidermidis and gram-positive cocci were cultured at a rate of 43.9% which was higher than that (39.0%) of gram-negative rods. In contrast, in urine cultures, gram-negative rods were isolated predominantly. S. epidermidis and Corynebacterium spp. isolated less frequently in blood than in urine, indicated contaminants. However, Enterococcus spp. and Candida albicans were recognized as causative organisms of bacteremia via the urinary tract, because the urine culture demonstrated a species identical to that obtained from blood in these bacteremic patients. Antibiotic sensitivity tests demonstrated that isolates from blood tended to show tolerance to beta-lactam antibiotics, but had good sensitivity to aminoglycosides.(ABSTRACT TRUNCATED AT 250 WORDS)

Increase in murine monoclonal-antibody-defined urinary antigens in patients with bladder cancer and benign urogenital disease.

Monoclonal antibodies (MAbs) were obtained from hybridoma clones established by cell fusion between P3X63Ag8.653 mouse myeloma cells and spleen cells of mice or rats hyperimmunized against human bladder cancer tissue or BC47 rat bladder cancer cells. RBS-31 and RBS-85 mouse MAbs and RBA-1 rat MAb were raised against BC47 cells and HBP-1 MAb was raised against human bladder cancer tissues. Urinary antigens detected by these MAbs were quantitatively assayed by means of ELISA using 50 microliters of 1:2 diluted urine samples. The cut-off value of the assay was set up as the mean + 4 X SD of the mean using data from the healthy individual urine samples. The reactivity of all healthy control urine samples were under the cut-off value (negative). By contrast, urine from bladder cancer patients reacted positively with the RBS-31 MAb at 72%, with the RBS-85 MAb at 63%, with the RBA-1 MAb at 51% and with the HBP-1 MAb at 35%. The urine samples from some patients with renal calculi, acute cystitis or complicated urinary tract infections showed only a weak reactivity with our MAbs. As for extra-bladder cancers, some patients with renal, renal pelvis, prostate or ureter cancer, but no patients with esophageal, gastric, colon or liver cancer or leukemia, had reactive urinary antigens.