[Female prostate cancer?] / Weibliches Prostatakarzinom?

We present a case of a female patient who had a clinically suspected advanced urothelial carcinoma of the urethra. Histopathological examination surprisingly revealed a malignant tumor with morphological and immunohistochemical features of prostate cancer, leading to the diagnosis of the extremely rare entity of Skene's gland adenocarcinoma.

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts.

Specialized epithelial cells in the respiratory tract such as solitary chemosensory cells and brush cells sense the luminal content and initiate protective reflexes in response to the detection of potentially harmful substances. The majority of these cells are cholinergic and utilize the canonical taste signal transduction cascade to detect "bitter" substances such as bacterial quorum sensing molecules. Utilizing two different mouse strains reporting expression of choline acetyltransferase (ChAT), the synthesizing enzyme of acetylcholine (ACh), we detected cholinergic cells in the submucosal glands of the murine larynx and trachea. These cells were localized in the ciliated glandular ducts and were neither found in the collecting ducts nor in alveolar or tubular segments of the glands. ChAT expression in tracheal gland ducts was confirmed by in situ hybridization. The cholinergic duct cells expressed the brush cell marker proteins, villin and cytokeratin-18, and were immunoreactive for components of the taste signal transduction cascade (Gα-gustducin, transient receptor potential melastatin-like subtype 5 channel = TRPM5, phospholipase C(ß2)), but not for carbonic anhydrase IV. Furthermore, these cells expressed the bitter taste receptor Tas2r131, as demonstrated utilizing an appropriate reporter mouse strain. Our study identified a previously unrecognized presumptive chemosensory cell type in the duct of the airway submucosal glands that likely utilizes ACh for paracrine signaling. We propose that these cells participate in infection-sensing mechanisms and initiate responses assisting bacterial clearance from the lower airways.

Potassium channels and human corporeal smooth muscle cell tone: diabetes and relaxation of human corpus cavernosum smooth muscle by adenosine triphosphate sensitive potassium channel openers.

PURPOSE: Sustained contraction of human corporeal smooth muscle depends on continuous transmembrane calcium flux through voltage gated calcium channels. K channels modulate corporeal smooth muscle membrane potential and, thus, ultimately affect transmembrane calcium flux. Therefore, we characterized relaxation responses elicited by the K channel modulators pinacidil and levcromakalim on isolated human corporeal tissue strips. We also evaluated the possibility that there may be alterations in adenosine triphosphate sensitive K channel pharmacology/function related to the presence of diabetes mellitus. MATERIALS AND METHODS: A total of 215 isolated human corporeal tissue strips obtained from 57 male patients with organic erectile dysfunction were investigated. Cumulative concentration-response curves were constructed at half log increments for steady state relaxation responses elicited by pinacidil and levcromakalim on equivalently phenylephrine pre-contracted (to approximately 75% of maximum) isolated corporeal tissue strips. Potassium currents were measured using the cell attached whole cell patch clamp technique on freshly isolated corporeal smooth muscle cells. RESULTS: A concentration dependent, glibenclamide sensitive relaxation response of phenylephrine pre-contracted corporeal tissue strips was observed for pinacidil and levcromakalim. Consistent with such observations, electrophysiological recordings on freshly isolated myocytes revealed that pinacidil (10 microM.) and levcromakalim (10 microM.) induced whole cell potassium currents that were blocked by glibenclamide (10 microM.). In addition, statistical analysis revealed that phenylephrine pre-contracted corporeal tissue strips from patients without diabetes were more sensitive to relaxation by both compounds than corporeal tissue strips excised from those with diabetes. Furthermore, relaxation responses elicited by pinacidil and levcromakalim were not affected by charybdotoxin or 4-aminopyridine but were completely reversed by KCl or tetraethylammonium chloride. CONCLUSIONS: These data indicate that the adenosine triphosphate sensitive K channel subtype is likely to have an important role in the relaxation of isolated corporeal tissue strips and, moreover, they are the molecular target for the K channel modulators/openers levcromakalim and pinacidil. Such observations are consistent with the supposition that alterations in the structure/function/activity of these potassium channels may underlie at least some aspects of observed diabetes related differences in tissue sensitivity to K channel modulators.

The use of plane-parallel chambers in electron dosimetry without any cross-calibration.

Current dosimetry protocols from AAPM, DIN and IAEA recommend a cross-calibration for plane-parallel chambers against a calibrated thimble chamber for electron dosimetry. The rationale for this is the assumed chamber-to-chamber variation of plane-parallel chambers and the large uncertainty in the wall perturbation factor (p(wall)60Co)pp at 60Co for plane-parallel chambers. We have confirmed the results of other authors that chamber-to-chamber variation of the investigated chambers of types Roos, Markus, Advanced Markus and Farmer is less than 0.3%. Starting with a calibration factor for absorbed dose to water and on the basis of the three dosimetry protocols AAPM TG-51, DIN 6800-2 (slightly modified) and IAEA TRS-398, values for (p(wall)60Co)Roos of 1.024 +/- 0.005, (p(wall)60Co)Markus of 1.016 +/- 0.005 and (p(wall)60Co)Advanced Markus of 1.014 +/- 0.005 have been determined. In future this will permit electron dosimetry with the above-listed plane-parallel chambers having a calibration factor N(D, w)60Co without the necessity for cross-calibration against a thimble chamber.

Bladder injection of "naked" hSlo/pcDNA3 ameliorates detrusor hyperactivity in obstructed rats in vivo.

The goal of these studies was to examine the potential utility of bladder instilled K+ channel gene therapy with hSlo cDNA (i.e., the maxi-K channel) to ameliorate bladder overactivity in a rat model of partial urinary outlet obstruction. Twenty-two female Sprague-Dawley rats were subjected to partial urethral (i.e., outlet) obstruction, with 17 sham-operated control rats run in parallel. After 6 wk of obstruction, suprapubic catheters were surgically placed in the dome of the bladder in all rats. Twelve obstructed rats received bladder instillation of 100 microg of hSlo/pcDNA in 1 ml PBS during catheterization, and another 10 obstructed rats received 1 ml PBS (7 rats) or 1 ml PBS containing pcDNA only (3 rats). Two days after surgery cystometry was performed on all animals to examine the characteristics of the micturition reflex in conscious and unrestrained rats. Obstruction was associated with a three- to fourfold increase in bladder weight and alterations in virtually every micturition parameter estimate. PBS-injected obstructed rats routinely displayed spontaneous bladder contractions between micturitions. In contrast, hSlo injection eliminated the obstruction-associated bladder hyperactivity, without detectably affecting any other cystometric parameter. Presumably, expression of hSlo in rat bladder functionally antagonizes the increased contractility normally observed in obstructed animals and thereby ameliorates bladder overactivity. These initial observations indicate a potential utility of gene therapy for urinary incontinence.

Schistosoma hematobium soluble egg antigens induce proliferation of urothelial and endothelial cells.

Bladder carcinoma accounts for 26% of reported human malignancies in Egypt, and has been strongly associated with urinary schistosomiasis. Nevertheless, the immediate role of schistosomal egg proteins in bladder carcinogenesis is unexplored. We investigated the effects of crude soluble egg antigens (SEA) of Schistosoma hematobium on urothelial cell proliferation. The proliferation of bovine endothelial Endo, human urothelial J82 and smooth muscle SMC cell lines was assessed by low-density growth assays. SEA induced proliferation of both J82 and Endo cells in a dose-dependent fashion, but not SMC. Preboiling or proteinase K treatment of SEA abolished its effect. In addition, SEA enhanced urothelial expression of B-cell translocation protein (BTG1) and human proliferating cell nuclear antigen (PCNA) mRNAs. Given the strong correlation between cell proliferation and carcinogenesis, the findings suggest that crude SEA may play some role in schistosomal bladder carcinogenesis.

Rehabilitation for limb salvage patients: kinesiological parameters and psychological assessment.

Osteosarcoma is the most frequently occurring primary malignant tumor of bone, especially in adolescence. Treatment involves either limb salvage surgery or amputation with neoadjuvant chemotherapy. This review article discusses the current treatment modalities for osteosarcoma and also compares the gait patterns and psychosocial profiles of patients treated with either limb salvage surgery or amputation for osteosarcoma. Contemporary orthopedic literature on therapeutic options for osteosarcoma patients is reviewed. Background information on the basic principles of kinesiology, with emphasis on studies of gait pattern differences among patients treated with limb salvage versus amputation, is presented. Finally, several studies of the psychologic profiles of patients after these two procedures for osteosarcoma are reviewed. Trends in contemporary orthopedic literature suggest that functional outcomes, in terms of kinesiologic parameters, are comparable for patients treated with either limb salvage or amputation. Both sets of patients reported quality-of-life problems, including difficulty retaining health insurance and finding appropriate employment, social isolation, and poor self-esteem. The management of patients with osteosarcoma includes not only an individualized surgical plan for each patient but also includes awareness of the patients' psychologic and social needs after surgery.

Caveolin-1 null mice are viable but show evidence of hyperproliferative and vascular abnormalities.

Caveolin-1 is the principal structural protein of caveolae membranes in fibroblasts and endothelia. Recently, we have shown that the human CAV-1 gene is localized to a suspected tumor suppressor locus, and mutations in Cav-1 have been implicated in human cancer. Here, we created a caveolin-1 null (CAV-1 -/-) mouse model, using standard homologous recombination techniques, to assess the role of caveolin-1 in caveolae biogenesis, endocytosis, cell proliferation, and endothelial nitric-oxide synthase (eNOS) signaling. Surprisingly, Cav-1 null mice are viable. We show that these mice lack caveolin-1 protein expression and plasmalemmal caveolae. In addition, analysis of cultured fibroblasts from Cav-1 null embryos reveals the following: (i) a loss of caveolin-2 protein expression; (ii) defects in the endocytosis of a known caveolar ligand, i.e. fluorescein isothiocyanate-albumin; and (iii) a hyperproliferative phenotype. Importantly, these phenotypic changes are reversed by recombinant expression of the caveolin-1 cDNA. Furthermore, examination of the lung parenchyma (an endothelial-rich tissue) shows hypercellularity with thickened alveolar septa and an increase in the number of vascular endothelial growth factor receptor (Flk-1)-positive endothelial cells. As predicted, endothelial cells from Cav-1 null mice lack caveolae membranes. Finally, we examined eNOS signaling by measuring the physiological response of aortic rings to various stimuli. Our results indicate that eNOS activity is up-regulated in Cav-1 null animals, and this activity can be blunted by using a specific NOS inhibitor, nitro-l-arginine methyl ester. These findings are in accordance with previous in vitro studies showing that caveolin-1 is an endogenous inhibitor of eNOS. Thus, caveolin-1 expression is required to stabilize the caveolin-2 protein product, to mediate the caveolar endocytosis of specific ligands, to negatively regulate the proliferation of certain cell types, and to provide tonic inhibition of eNOS activity in endothelial cells.

[Identification of high risk patients with severe, but asymptomatic aortic stenosis]. / Identifizierung von Hochrisikopatienten bei schwerer, aber symptomfreier Aortenstenose.

Whether asymptomatic patients with severe aortic stenosis benefit from surgery remains unclear. We report our data recently published in the New England Journal of Medicine on the natural history of this disease and predictors of outcome.

The genetics and immunology of Peyronie's disease.

Peyronie's disease (PD) is a condition characterized by localized and often progressive fibrosis and scarring of the penis. This condition has an unknown etiology although several hypotheses have been proposed. These include traumatic, immunologic and genetic causes. We studied the genetics and immunology of PD using both molecular biologic and molecular genetic techniques. Men (n=283) with PD were identified by retrospective chart review of one physician's office practice. These men were contacted by telephone and asked to submit to an interview and blood test for genetic studies. Simultaneously, tissue and cells collected in the laboratory were examined by Western and Northern blot analysis for examination of protein and RNA for expression of HLA. Of the first 107 men contacted, 24 were available and consented to interview and blood testing. The mean age was 60.3 y with an average duration of PD of 4.9 y. One patient had a family history of PD while no patients had Dupuytren's contracture. Twenty patients were considered to have primary disease while four were secondary. Eleven patients had tissue prepared for Northern blot analysis and nine patients were the subject of Western blot analysis. All tissue, both Peyronie's and control expressed class I MHC while no tissue expressed class II MHC. The expression of mRNA of class I MHC was equal for Peyronie's and control patients while the expression at the protein level was less in the PD patients. We conclude that PD may have multiple etiologic agents. One cannot exclude a class II MHC association but in our population, HLA DQ is not expressed. Class I MHC may be involved as the expression of class I MHC protein is different in Peyronie's patients than in controls. Genetic studies are ongoing. International Journal of Impotence Research (2000) 12, Suppl 4, S127-S132.

Comparative studies of the maxi-K (K(Ca)) channel in freshly isolated myocytes of human and rat corpora.

Patch clamp techniques in freshly isolated myocytes from human corpora have documented that the large conductance calcium-sensitive K channel (K(Ca)) subtype represents an important convergence point for the modulation of corporal smooth muscle tone, and therefore, erectile capacity. Other recent studies indicate a similar role for the K(Ca) channel in the modulation of smooth muscle tone in the rat penis. Therefore, the explicit aim of this investigation was to evaluate and compare the characteristics of the K(Ca) channel subtype present in freshly isolated myocytes from rat and human corpora. In short, myocytes isolated from rat and human corpora retain their characteristic morphology and contractility in vitro, as evidenced by light microscopic studies of their respective responses to activation of the alpha1-adrenergic receptor subtype by phenylephrine (PE). Large conductance K+ currents commensurate with the presence of the K(Ca) channel were readily apparent in myocytes from both preparations. I-V curves constructed from cell-attached patches utilizing symmetric KCl solutions revealed the presence of a single channel slope conductance of approximately 200 pS for both rat and human myocytes. 1 mM TEA applied in the bath solution reversibly diminished whole cell outward K+ currents by approximately 50%, and also blocked the unitary K(Ca) channel activity observed in the outside-out patch mode. Addition of 2 mM 8-bromo-cAMP elicited a TEA-sensitive (1 mM) approximately 2-3 fold increase in the magnitude of the whole cell outward K+ currents in rat myocytes. Taken together, these data confirm and extend previous observations and provide strong evidence that the rat corporal smooth muscle K(Ca) channel has many similarities to its counterpart in the human penis.

Predictors of outcome in severe, asymptomatic aortic stenosis.

BACKGROUND: Whether to perform valve replacement in patients with asymptomatic but severe aortic stenosis is controversial. Therefore, we studied the natural history of this condition to identify predictors of outcome. METHODS: During 1994, we identified 128 consecutive patients with asymptomatic, severe aortic stenosis (59 women and 69 men; mean [+/-SD] age, 60+/-18 years; aortic-jet velocity, 5.0+/-0.6 m per second). The patients were prospectively followed until 1998. RESULTS: Follow-up information was available for 126 patients (98 percent) for a mean of 22+/-18 months. Event-free survival, with the end point defined as death (8 patients) or valve replacement necessitated by the development of symptoms (59 patients), was 67+/-5 percent at one year, 56+/-5 percent at two years, and 33+/-5 percent at four years. Five of the six deaths from cardiac disease were preceded by symptoms. According to multivariate analysis, only the extent of aortic-valve calcification was an independent predictor of outcome, whereas age, sex, and the presence or absence of coronary artery disease, hypertension, diabetes, and hypercholesterolemia were not. Event-free survival for patients with no or mild valvular calcification was 92+/-5 percent at one year, 84+/-8 percent at two years, and 75+/-9 percent at four years, as compared with 60+/-6 percent, 47+/-6 percent, and 20+/-5 percent, respectively, for those with moderate or severe calcification. The rate of progression of stenosis, as reflected by the aortic-jet velocity, was significantly higher in patients who had cardiac events (0.45+/-0.38 m per second per year) than those who did not have cardiac events (0.14+/-0.18 m per second per year, P<0.001), and the rate of progression of stenosis provided useful prognostic information. Of the patients with moderately or severely calcified aortic valves whose aortic-jet velocity increased by 0.3 m per second or more within one year, 79 percent underwent surgery or died within two years of the observed increase. CONCLUSIONS: In asymptomatic patients with aortic stenosis, it appears to be relatively safe to delay surgery until symptoms develop. However, outcomes vary widely. The presence of moderate or severe valvular calcification, together with a rapid increase in aortic-jet velocity, identifies patients with a very poor prognosis. These patients should be considered for early valve replacement rather than have surgery delayed until symptoms develop.

Impact of development on children's mourning.

PURPOSE: A qualitative approach was used to analyze the impact of development on the grief responses of 157 children from 88 families to the death of a parent from cancer. DESCRIPTION OF STUDY: Children from age 3 to 17 years were divided by developmental characteristics, derived from interview data, into five development-derived age categories. RESULTS: The responses of children in different categories clarified the impact of development on their distinct expressions of grief, attributes of the parent they mourned, and the parent's tasks in enhancing the reconstitution of the child and the family. CLINICAL IMPLICATIONS: This first attempt to find a way to segregate children into developmentally more homogenous subgroups led to the clarification of patterns of mourning behaviors that are clinically useful. The increased precision of findings, such as the way development affects the child's mourning and the related parental support they need, may help clinicians develop more specific interventions to help children cope with the death of a parent and guide parents in understanding their children's differing responses. The pivotal role of the surviving parent and the tasks required of that parent are important for healthcare professionals to understand and support.

Characterization of ATP-sensitive potassium channels in human corporal smooth muscle cells.

Potassium (K) channels play a significant role in modulating human corporal smooth muscle tone, and thus, erectile capacity. Recent pharmacological studies indicate that the metabolically-regulated K channel (KATP) may be an important modulator of human penile erection with significant therapeutic potential. The goal of these initial studies, therefore, was to utilize patch clamp techniques to characterize the putative KATP subtype(s) present in cultured and freshly isolated human corporal smooth muscle cells. In the cell-attached patch mode, two distinct unitary K+ currents were identified whose respective conductance values were similar in cultured and freshly isolated smooth muscle cells. In cultured myocytes, the measured conductance values in symmetric KCl (140 mM) solutions were 59.1 +/- 2.7 pS and 18.4 +/- 2.1 pS (n = 5 cells). Under identical experimental conditions in freshly isolated myocytes, corresponding conductance values were 59.2 +/- 3.7 pS and 18.5 +/- 2.4 pS, respectively (n = 4 cells). I-V curves constructed during step depolarization (-60 to +80 mV), revealed a linear I-V relationship for both unitary conductances. Single channel records documented that both conductances were reversibly inhibited by the application of ATP (1-3 mM) to the bath solution in the inside-out attached patch configuration. The unitary activity of both K channel subtypes was significantly increased by the application of pinacidil (10 microM) and levcromakalim (10 microM). Whole cell patch recordings documented a glibenclamide-sensitive, pinacidil- and levcromakalim-induced increase in the whole cell outward K+ current during step depolarization (-70 mV to +130 mV) of 105 +/- 37%, 139 +/- 42%, respectively. These data confirm and extend our previous observations, and provide the first evidence for the presence of KATP channel subtypes in human corporal smooth muscle cells.

Intraoperative electrical stimulation of cavernosal nerves with monitoring of intracorporeal pressure in patients undergoing nerve sparing radical prostatectomy.

OBJECTIVE: To explore the utility of intraoperative cavernosal nerve stimulation in facilitating atraumatic nerve dissection during radical prostatectomy, and thus help predict postoperative erectile function. PATIENTS AND METHODS: Fourteen patients (aged 51-72 years) underwent nerve-sparing radical retropubic prostatectomy (NSRRP); 10 were potent before surgery (group 1), and four had erectile dysfunction (group 2). A multi-acquisition system (MacLab/8e) with a Macintosh computer was used for real-time display and recording of intracavernosal pressure (ICP) during surgery. Nerves were stimulated with a bipolar probe (monophasic rectangular pulses, 10 mA, 20 Hz, 0.22 s) before and after removal of the gland. The follow-up consisted of interviews with patients and their partners' 12-18 months after treatment. RESULTS: The mean (sem) basal ICP of 8. 0 (2.0) cmH2O remained unchanged during nerve dissection. The mean increase in ICP during electrical stimulation was >50 cmH2O in seven potent patients (group 1) and was sustained as long as the nerve was stimulated. Postoperatively, these seven patients reported erections sufficient for sexual intercourse. However, the three remaining patients in group 1 had pressure rises of <30 cmH2O, of whom two reported partial erections and one reported total impotence postoperatively. The recovery time for erectile function was 6-12 months after surgery. Two patients from group 2 had transient increases in ICP to <40 cmH2O; one had an increase to 20 cmH2O and one had no response at all. All four patients remained totally impotent postoperatively. There were no complications. CONCLUSIONS: Intraoperative electrical stimulation of the cavernosal nerves with ICP monitoring before and after NSRRP is a safe and reliable method for documenting nerve continuity and its functional status. Patients who have normal preoperative erectile function and show an adequate rise in ICP upon electrical nerve stimulation during NSRRP will almost certainly be potent after surgery. This tool may be used to facilitate atraumatic nerve dissection during NSRRP.

Evaluation of predictive factors for local tumour control after electron-beam-rotation irradiation of the chest wall in locally advanced breast cancer.

BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects. MATERIAL AND METHODS: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4 x 2.5 Gy/week to 50 Gy total dose (4-12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status. RESULTS: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed. CONCLUSION: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60% for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.

Advancing social work practice in end-of-life care.

Insufficient training of health professionals has often been cited as a major barrier to improving the system of care for dying patients and for the bereaved. Although specific problems have been identified for physicians and nurses, the problems of social work in this substantive area have only recently been explored. This study used a practitioner survey, focus groups, and a survey of faculty of schools of social work to broaden the information base. Results suggested that not unlike the professions of medicine and nursing, social work knowledge and skill development in the care of the dying is uneven and not integrated sufficiently with theoretical concepts and research. Social workers felt unprepared for this work by their master's level training and unsupported by continuing education programs. They recognized few social work scholars who could function as role models by providing comprehensive training, knowledge building, innovation, and advocacy. A program for leadership development was created to test new approaches to professional development in the care of the dying and the bereaved.

Transesophageal versus intracoronary Doppler measurements for calculation of coronary flow reserve.

OBJECTIVE: The present study was performed to compare coronary flow reserve by transesophageal Doppler echocardiography and intracoronary Doppler flow wire measurements in patients with LAD disease. METHODS: 17 patients with various degree of LAD stenosis were studied. Intracoronary LAD Doppler measurements were performed at baseline and after intracoronary injection of 18 micrograms adenosine. Transesophageal coronary sinus and LAD Doppler measurements were performed at baseline and after intravenous dipyridamole (0.6 mg/kg/5 min). Coronary flow reserve was calculated as the ratio of hyperemic to baseline average peak velocities. RESULTS: Coronary flow reserve was 2.44 +/- 0.62 and 2.19 +/- 0.76 for proximal and distal intracoronary measurements and was 2.25 +/- 0.64 and 1.74 +/- 0.63 for transesophageal LAD- and coronary sinus measurements. Proximal intracoronary flow reserve significantly correlated with transesophageal coronary sinus (r = 0.73, p < or = 0.001) and LAD (r = 0.70, p < or = 0.005) measurements, whereas distal intracoronary flow reserve only correlated with transesophageal coronary sinus flow reserve (r = 0.56, p < or = 0.02). Receiver operating characteristic curve analysis demonstrated similar diagnostic accuracy of all applied techniques for detection of a significant LAD stenosis. CONCLUSIONS: Coronary flow reserve by both transesophageal techniques correlated with intracoronary Doppler flow wire measurements, however considerable discrepancies may occur in the individual patient.

Reduced connexin 43 expression in high grade, human prostatic adenocarcinoma cells.

Gap junction-mediated communication is required for normal cellular growth and differentiation. As cancer is thought to be a manifestation of the breakdown of cell-cell communication, with the concomitant loss of growth control, it would be expected that alterations in the primary structure, processing, oligomerization or trafficking of connexin (cxn) molecules would have a profound effect on the neoplastic process. Here we a present a preliminary immunohistochemical and molecular analysis of cxn 43 expression in prostatic epithelial cells from resected human tissue. Our data indicate that benign prostatic epithelial cells express cxn 43 protein, but that this expression is diminished in more advanced, anaplastic cancer cells. These data suggest that decreased connexin expression is not involved in the initiation of prostate cancer, but rather occurs during the progression of the disease.

Azelaic acid decreases the fibrinolytic potential of cultured human melanoma cells in vitro.

Azelaic acid (AZA) has been used successfully in the treatment of lentigo maligna melanoma. Since it is generally accepted that the fibrinolytic potential of tumour cells is related to their malignant phenotype, it was the aim of this study to investigate the effect of AZA on the fibrinolytic potential of three different human melanoma cell lines (Bowes, GUBSB and MJZJ). Melanoma cells were incubated with AZA in doses ranging from 10(-2) M to 4 x 10(-2) M for 5, 8 and 24 h. The expression of tissue-type plasminogen activator (t-PA), urokinase-type PA (u-PA) and PA inhibitor-1 (PAI-1) in such treated cells was investigated by specific ELISAs on the protein level and by Northern blotting on the mRNA level. AZA caused a time and dose dependent decrease in the fibrinolytic potential of all three cell lines investigated by decreasing t-PA antigen in Bowes, by decreasing u-PA antigen in GUBSB and by increasing PAI-1 antigen in MJZJ cells, respectively. There was no significant difference between the viability of cells in control cultures and those treated with AZA. The effect of AZA on specific mRNA for t-PA in Bowes cells, u-PA in GUBSB and PAI-1 in MJZJ was consistent with its effect on the secretion of these fibrinolytic proteins by the respective cells. The results show that AZA decreases the fibrinolytic potential of the three human melanoma cell lines in vitro. This decrease may be operative in the mechanism by which AZA has been shown to affect malignant melanoma in vivo.