Prospective study of transitional cell carcinoma in the prostatic urethra and prostate in the cystoprostatectomy specimen. Incidence, characteristics and preoperative detection

OBJECTIVES: To prospectively evaluate the incidence of transitional cell carcinoma (TCC) in the prostatic urethra and prostate in the cystoprostatectomy specimen, investigate characteristics of bladder tumours in relation to the risk of involvement of the prostatic urethra and prostate and examine the sensitivity of preoperative loop biopsies from the prostatic urethra. MATERIAL AND METHODS: Preoperatively, patients were investigated with cold cup biopsies from the bladder and transurethral loop biopsies from the bladder neck to the verumontanum. The prostate and bladder neck were submitted to sagittal whole-mount pathological analysis. RESULTS: The incidence of TCC in the prostatic urethra and prostate in the cystoprostatectomy specimen was 29% (50/175 patients). Age, previous bacillus Calmette-Guérin treatment, carcinoma in situ (Cis) in the cold cup mapping biopsies and tumour grade were not associated with the risk of TCC in the prostatic urethra/prostate. Cis, multifocal Cis (> or = 2 locations) and tumour location in the trigone were significantly more common in cystectomy specimens with TCC in the prostatic urethra and prostate: 21/50 (42%) vs 32/125 (26%), p=0.045; 20/50 (40%) vs 27/125 (22%), p=0.023; and 20/50 (40%) vs 26/125 (21%), p=0.01, respectively. Preoperative resectional biopsies from the prostatic urethra in the 154 patients analysed identified 31/47 (66%) of patients with TCC in the prostatic urethra/prostate, with a specificity of 89%. The detection of stromal-invasive and non-stromal involvement was similar: 66% and 65%, respectively. CONCLUSIONS: The incidence of TCC in the prostatic urethra and prostate was 29% (50/175) in the cystoprostatectomy specimen. Preoperative biopsies from the prostatic urethra identified 66% of patients with such tumour growth. Our findings suggest that preoperative cold cup mapping biopsies of the bladder for detection of Cis add little extra information with regard to the risk of TCC in the prostatic urethra and prostate.     

Responsiveness to peripherally administered melanocortins in lean and obese mice

To elucidate mechanisms of melanocortin action, we investigated the effects of a melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 microg q.i.d. i.p.) for 24 h results in similar weight loss but a more pronounced decrease of food intake in DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both food intake and body weight is more pronounced in DIO mice than in lean mice. MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.     

Genotype–phenotype correlation in children with autosomal dominant polycystic kidney disease

Adults with autosomal dominant polycystic kidney disease (ADPKD) and PKD1 mutations have a more severe disease than do patients with PKD2 mutations. The aim of this study was to compare phenotypes between children with mutations in the PKD1/PKD2 genes. Fifty PKD1 children and ten PKD2 children were investigated. Their mean age was similar (8.6 ± 5.4 years and 8.9 ± 5.6 years). Renal ultrasound was performed, and office blood pressure (BP), ambulatory BP, creatinine clearance and proteinuria were measured. The PKD1 children had, in comparison with those with PKD2, significantly greater total of renal cysts (13.3 ± 12.5 vs 3.0 ± 2.1, P = 0.004), larger kidneys [right/left kidney length 0.89 ± 1.22 standard deviation score (SDS) vs 0.17 ± 1.03 SDS, P = 0.045, and 1.19 ± 1.42 SDS vs 0.12 ± 1.09 SDS, P = 0.014, successively] and higher ambulatory day-time and night-time systolic BP (day-time/night-time BP index 0.93 ± 0.10 vs 0.86 ± 0.05, P = 0.021 and 0.94 ± 0.07 vs 0.89 ± 0.04, P = 0.037, successively). There were no significant differences in office BP, creatinine clearance or proteinuria. Prenatal renal cysts (14%), hypertension defined by ambulatory BP (27%) and enlarged kidneys (32%) were observed only in the PKD1 children. This is the first study on genotype–phenotype correlation in children with ADPKD. PKD1 children have more and larger renal cysts, larger kidneys and higher ambulatory BP than do PKD2 children. Renal cysts and enlarged kidneys detected prenatally are highly specific for children with PKD1.     

Experimental and Numerical Investigation of an Axial Rotary Blood Pump

Left ventricular assist devices (LVADs) have become a standard therapy for patients with severe heart failure. As low blood trauma in LVADs is important for a good clinical outcome, the assessment of the fluid loads inside the pump is critical. More specifically, the flow features on the surfaces where the interaction between blood and artificial material happens is of great importance. Therefore, experimental data for the near‐wall flows in an axial rotary blood pump were collected and directly compared to computational fluid dynamic results. For this, the flow fields based on unsteady Reynolds‐averaged Navier–Stokes simulations‐computational fluid dynamics (URANS‐CFD) of an axial rotary blood pump were calculated and compared with experimental flow data at one typical state of operation in an enlarged model of the pump. The focus was set on the assessment of wall shear stresses (WSS) at the housing wall and rotor gap region by means of the wall‐particle image velocimetry technique, and the visualization of near‐wall flow structures on the inner pump surfaces by a paint erosion method. Additionally, maximum WSS and tip leakage volume flows were measured for 13 different states of operation. Good agreement between CFD and experimental data was found, which includes the location, magnitude, and direction of the maximum and minimum WSS and the presence of recirculation zones on the pump stators. The maximum WSS increased linearly with pressure head. They occurred at the upstream third of the impeller blades and exceeded the critical values with respect to hemolysis. Regions of very high shear stresses and recirculation zones could be identified and were in good agreement with simulations. URANS‐CFD, which is often used for pump performance and blood damage prediction, seems to be, therefore, a valid tool for the assessment of flow fields in axial rotary blood pumps. The magnitude of maximum WSS could be confirmed and were in the order of several hundred Pascal.     

Penetration and haptenation of p‐phenylenediamine

Although p‐phenylenediamine (PPD) has been recognized as an extreme sensitizer for many years, the exact mechanism of sensitization has not been elucidated yet. Penetration and the ability to bind to proteins are the first two hurdles that an allergen has to overcome to be able to sensitize. This review is an overview of studies regarding PPD penetration through skin (analogues) and studies on the amino acids that are targeted by PPD. To complete this review, the auto‐oxidation and N‐acetylation steps involved in PPD metabolism are described. In summary, under normal hair dyeing exposure conditions, <1% of the applied PPD dose penetrates the skin. The majority (>80%) of PPD that penetrates will be converted into the detoxification products monoacetyl‐PPD and diacetyl‐PPD by the N‐acetyltransferase enzymes. The small amount of PPD that does not become N‐acetylated is susceptible to auto‐oxidation reactions, yielding protein‐reactive PPD derivatives. These derivatives may bind to specific amino acids, and some of the formed adducts might be the complexes responsible for sensitization. However, true in vivo evidence is lacking, and further research to unravel the definite mechanism of sensitization is needed.     

Cutaneous manifestations of Takayasu arteritis. A retrospective study of 80 cases

The aim of this retrospective study is to delineate in Europe the frequency and type of cutaneous manifestations associated with Takayasu arteritis (TA). Eighty patients with TA were analyzed. Symptoms suggestive of Raynaud's syndrome were noted in 11 patients (14%) and could be directly related to large vessel involvement. Other skin lesions were observed in 10 patients (12.5%). Five had acute tender erythematous nodules on the legs with a clinical diagnosis of erythema nodosum; 2 had subacute ulcerated nodules of the legs; 1 had pyoderma-gangrenosum-like ulcerations of the four limbs which resulted from the breakdown of subcutaneous nodules; 1 had lupus-like malar flush, and the last one had urticarial lesions with livedo reticularis. Skin samples were obtained from 4 patients. Three of them agreed that reiterated biopsies be done on recurrent lesions. A granulomatous vasculitis was observed in 2 cases involving hypodermal arterioles in one case and veins in the other. The other pathological findings were septal and lobular panniculitis which can be associated with granulomatous vasculitis. Different histological findings on reiterated biopsies were frequently found. The absence of any other etiology and chronological arguments suggested a relationship between these skin lesions and TA. Tuberculosis was probable in 1 case but apparently was not related to the skin lesions.     

Location of androgen receptor in human skin.

The distribution of androgen receptor (AR) in human skin was studied by an immunohistochemical method using a polyclonal antibody against the human AR. Skin samples of preputial skin and male and female nongenital skin were examined. The possible correlation of AR location to acne was studied in skin biopsies from skin areas affected or unaffected by acne. In preputial skin, AR was expressed in epidermal cells as well as in fibroblasts, smooth muscle cells, and endothelial cells of blood vessels in the dermal area. AR was found located also in the flat fibroblast-like cells of Pacinian corpuscles. In nongenital skin, AR was also expressed in the basal cells and glandular cells of sebaceous glands, in the outer root sheath of hair follicles, and in eccrine sweat glands. The presence of AR in different cell types in the skin reflects the numerous direct effects androgens may have on this target tissue. The distribution of AR was similar in male and female skin.