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In 2015, H3N2 canine influenza emerged in dogs in the greater Chicago area. During this time, a 10-year-old German Shepherd dog presented to the referring veterinarian with lethargy and coughing that quickly progressed to death. This report describes the macroscopic and microscopic lesions and the molecular testing performed to identify the novel North American H3N2 strain of canine influenza. The larynx, pharynx, and trachea were covered by a fibrinonecrotic membrane. Bilaterally, the lungs had multifocal subpleural necrosis of the caudal lung lobes with hemorrhage, congestion, and pulmonary edema. Staphylococcus pseudointermedius was isolated from the lung. Mycoplasma cynos was identified by real-time polymerase chain reaction from nasal passages, oropharynx, larynx, trachea, and cranial lung lobes. The neuraminidase gene sequence from the influenza virus isolated obtained from this dog had ≥98% homology to the strain circulating in the Chicago area. [ABSTRACT FROM AUTHOR]

Recently, confirmed occurrences of persistent bovine viral diarrhea virus (BVDV) infection in North American alpacas have raised concerns about the role of persistently infected (PI) alpacas in transmission of virus among herds, yet only limited pathological descriptions of persistent infections in alpacas have been reported. The objective of this study was to characterize BVDV antigen distribution in 10 PI alpacas of varying age and to compare viral antigen distribution and localization in tissues of PI alpacas with 5 PI calves of varying age. Ocular dysplasia was evident in 1 PI alpaca, constituting the first reported congenital ocular lesion in PI alpacas. Viral antigen was widely distributed in alpaca tissues and was prominent in neurons, endothelial cells, and vascular tunica media myocytes but had limited distribution in lymphoid tissues and moderate distribution in epithelium of several organ systems of alpacas. Macrophages in the alpaca gastrointestinal system submucosa and lymph node medullary sinuses often had prominent labeling. In addition, only 1 alpaca had antigen labeling in the bone marrow in contrast to PI cattle. Labeled cells in calf tissues were more widely distributed, occurring prominently in lymphoid and epithelial tissues. Common features of the 2 host species were widespread antigen labeling and absence of lymphoid depletion. [ABSTRACT FROM PUBLISHER]

Intravesical instillation of Bacillus Calmette-Guérin (BCG) is used for the treatment of superficial bladder cancer, both to reduce the recurrence rate of bladder tumour and to diminish the risk of progression. Since its first therapeutic application in 1976, major research efforts have been directed to decipher the exact mechanism of action of the BCG-associated antitumour effect. Bacillus Calmette-Guérin causes an extensive local inflammatory reaction in the bladder wall. Of this, the massive appearance of cytokines in the urine of BCG-treated patients stands out. Activated lymphocytes and macrophages are the most likely sources of these cytokines, but at present other cellular sources such as urothelial tumour cells cannot be ruled out. Bacillus Calmette-Guérin is internalised and processed both by professional antigen-presenting cells and urothelial tumour cells, resulting in an altered gene expression of these cells that accumulates in the presentation of BCG antigens and secretion of particular cytokines. [ABSTRACT FROM AUTHOR]

Clinical evaluation in oncology has typically focused on outcome indicators, while less attention has been paid to how treatment affects quality of life (QOL) of the patient. In this article some general aspects of quality of life are discussed, a short review of published data on QOL in patients with prostate cancer is given and results of a QOL study executed by the authors on patients with lymph node positive prostatic cancer are presented. The purpose of the study was to examine the impact of immediate or delayed treatment (after objective progression) in patients with prostatic carcinoma (T1-3 N1-3 M0) on quality of life parameters. To this end an extended questionnaire was constructed. Fifty-five patients participated. Assessment was performed twice, in 1994 and 1995. The comparison between patients with and patients without treatment showed in 1994 as well as in 1995 significant differences for hormonal treatment side effects such as sexual functioning and hot flushes, all of which were experienced more frequently by treated patients. In 1994 the treated patients experienced more psychological distress while in 1995 they showed worse physical function, less energy and more fatigue when compared to patients under surveillance. The premise that active treatment would improve the psychological quality of life was not sustained. In addition global health status and quality of life were identified as independent factors for progression in untreated patients with lymph node positive prostate cancer. Finally, an increase in prostate-specific antigen (PSA) in hormonally treated patients not only indicated hormonal escape but also a decrease in QOL. [ABSTRACT FROM AUTHOR]

Objectives: Twelve patients with superficial papillary transitional cell carcinoma of the bladder (pTa, pT1) were treated with six consecutive weekly intravesical instillations of Rubratin (in a dose of 1.5, 3.0, or 4.5 mg), a cell wall skeleton preparation of Nocardia rubra (NCW). The main objective of this study was to look for local immunomodulating effects of NCW and in the first four patients the effect on a marker lesion was also investigated. Methods: Local immunostimulation in all 12 patients was determined by (1) measurement of cytokine induction [interleukin 1 β (IL1 β), IL2, IL6, and tumor necrosis factor alpha (TNFα)], (2) leukocyte influx into the urine, and (3) phenotypic analysis of the lymphocyte fraction of these leukocytes. Results: Significantly elevated levels of Rubratin-induced IL1β ( P < 0.001), IL2 ( P < 0.001), IL6 ( P < 0.01), and TNFα ( P < 0.001) were found compared to control pretherapy levels. Rubratin also induced leukocyte influx into the urine. Fluorescence-activated cell sorter (FRCS) analysis of the urinary leukocytes indicated T-cell activation (IL2 receptor and HLA-DR expression), while in two out of five patients the CD4/CD8 ratios were increased. Urinary cytokine induction by Rubratin was comparable with cytokine induction observed in non-responding bacillus Calmette-Guérin (BCG) patients (recurrent tumor within 6 months), but less compared with responding BCG patients (no recurrent tumor within 6 months). Clinical results showed no response on the marker lesion and in five out of eight patients early recurrence was found after complete transurethral resection (TUR) of the bladder tumors. This biological response modifier caused no local or systemic side effects at the doses used. Conclusion: Although local immunostimulation by intravesical Rubratin administration can be induced, the amount of immunocompetent cells attracted to the bladder is not as high as observed in BCG-responding patients, resulting in lower amounts of cytokines produced. This could also explain the lack of clinical efficacy. [ABSTRACT FROM AUTHOR]

In intravesical therapy for superficial bladder carcinoma urothelial cells may, through the production of cytokines, contribute to the bacillus Calmette-Guérin (BCG)-induced local immunological reaction and associated antitumor efficacy. The aim of this study was to investigate such a role for the neutrophil-attracting cytokine interleukin-8 (IL-8). The appearance of IL-8 in patients' urine after BCG therapy was compared with BCG-induced IL-6 and IL-2 and the stability of IL-8 in urine was tested. Compared to IL-6 and IL-2, a rapid induction of IL-8 was observed, occurring after the first BCG instillation. Urinary IL-8 was highly stable, even after 24 h incubation at 37°C. The IL-8 concentration after the first instillation seemed to be associated with subsequent development of an immune response. Consequently, IL-8 seems an attractive candidate for investigation of its prognostic value for a clinical response to BCG therapy. [ABSTRACT FROM AUTHOR]

This study on the increase in albumin in the urine of patients with superficial bladder cancer after intravesical bacillus Calmette-Guérin (BCG) treatment was initiated on the basis of two facts. First, extravasation of serum albumin could be expected as a result of the BCG-induced delayed-type hypersensitivity reaction in the bladder wall. Second, appearance of albumin in the urine was a possibility as cytokines also appear in the urine, although probably after being produced suburothelially by infiltrating leukocytes. Albumin and the cytokines interleukin (IL) 1β, IL2, IL6, and tumor necrosis factor alpha (TNFα) were determined in urine from 20 patients treated with 6 weekly intravesical BCG instillations, collected prior to each instillation and 2, 4, 6, 8, 12, and 24h thereafter. The mean concentration of albumin in pre-therapy specimens was 112±118 (range 2-432) μg albumin/ml urine, approximating 14±14 μg/ μmol creatinine (creat) ( n=15), which was comparable to the mean pre-instillation value of 16±32 μg/μmol creat ( n=96). A significant increase in urinary albumin during the 6 weeks of BCG treatment was observed ( P<0.001). However, a large variation existed between individual patients and in some patients no reaction was seen. Maximum albumin concentrations were observed after instillations 3-6. A significant correlation between albumin and concentration of the cytokines IL1β, IL2, IL6, and TNFα was found ( P<0.01), correlation coefficients ( r) being 0.56, 0.56, 0.67, and 0.71 ( n=418), respectively. During the first 24h after instillation cytokines and albumin peaked in the following order: TNFα→IL2→albumin→IL6→IL1β. TNF peaked most frequently after 2-4h and IL1β after 6h, while IL2, albumin, and IL6 peaked between these time points. In conclusion, the presence of albumin in urine indicates a 'leakiness' of the bladder wall after repeated BCG instillations. Since albumin was shown to be stable in urine and the assay is relatively simple and cheap, it may be performed in most hospitals. This will allow largescale investigations of the correlation between elevation of urinary albumin and (tumor) response on BCG therapy. [ABSTRACT FROM AUTHOR]

The study was initiated as an in vitro approach to the situation existing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a human bladder carcinoma cell line T24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher secretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFα) when compared with T24 cells treated with Escherichia coli, Streptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS). No secretion of IL-1β and IL-2 was detected. Pre-exposing T24 cells to BCG for various periods of time indicated that a minimum exposure time of 0.5-1 h was required to upregulate IL-6 and TNFα production. Extending the BCG pre-exposure time to 2 and 3 h further increased the rate of cytokine production. No significant difference was found, however, between the rate of secretion initiated after a 2-h or 3-h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products possibly secreted by BCG on the upregulation of IL-6 and TNFα. In addition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in the mode of action of BCG. [ABSTRACT FROM AUTHOR]

Transperineal ultrasound-guided 125I implantation was undertaken in 52 patients with localised prostate cancer. After implantation, ultrasound-guided biopsies were taken from the previous malignant areas every 6 months in all patients. The percentage of negative biopsies increased from 22% at 6 months to 50% at 48 months. Implant quality was analysed in 37 patients. The difference between isodose levels encompassing the prostate and the aimed levels of 160 Gy was taken as a measure of implant quality. A good quality implant (< 10% underdosage) was found in 43% of patients, a moderate quality (10-25% underdosage) in 35%, and a poor quality implant (> 25% underdosage) in 22%. A statistically significant correlation was found between the quality of the implant and resulting negative biopsy at the original tumour site. Determination of prostate specific antigen (PSA) was not possible from the beginning of the study but an analysis with biopsy findings, implant quality and prostate volume reduction during follow-up has been performed since 1989. A significant correlation was observed between implant quality and serum PSA, and also between volume reduction and serum PSA. [ABSTRACT FROM AUTHOR]

- Forty-two patients with previously untreated T3/4 N1-4 MO/1 prostatic adenocarcinoma were treated with either cyproterone acetate (n=21; 300 mg intramuscularly per week) or oestradiol undecylate (n=21; 100 mg intramuscularly per month) after extensive staging which included open skeletal biopsy and pelvic lymphadenectomy in some cases. Subjective and objective parameters as well as signs of drug toxicity were recorded regularly. Evaluation after 6 months showed cyproterone acetate to be more effective in the following respects: (1) the significantly different castration effect as judged by plasma testosterone, (2) the objective voiding pattern and tumour response, with regression of palpable and histologically evaluable local tumour in 16 of 21 patients, and (3) side effects and untoward reactions. Thus cyproterone acetate is suggested as a valuable alternative in the treatment of advanced prostatic cancer. [ABSTRACT FROM AUTHOR]

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