ABSTRACT
PURPOSE: Stimulating muscarinic receptors in pig bladder urothelium causes the release of a diffusable factor that inhibits contractions of the underlying detrusor muscle. We investigated whether the contractions of human detrusor strips elicited by the muscarinic agonist carbachol, electrical field stimulation, KCl or the neurokinin receptor agonist neurokinin A are affected by the urothelium. MATERIALS AND METHODS: Paired intact and urothelium denuded muscle strips were placed in modified gassed Tyrode's solution at 37C. Cumulative concentration-response curves to carbachol or KCl were constructed. In other tissues the strips were stimulated electrically (1 to 40 Hz) with trains of square wave pulses 20 seconds in duration at 5-minute intervals. RESULTS: Cholinergic contractions evoked by electrical field stimulation at 10 and 30 Hz or by carbachol were significantly inhibited in the presence of an intact urothelium. Contractions elicited by KCl and by 10 microM neurokinin A were not modified by the urothelium. The urothelium mediated inhibition of contractions induced by carbachol was not affected by 300 microM L-NG-nitroarginine, 1 microM ODQ (1H-[1,2,4]oxadiazolo[4,3-alpha]quinoxalin-1-one), 1 microM propranolol or 5 microM indomethacin. CONCLUSIONS: Muscarinic agonists stimulate the release of an inhibitory factor from the human urothelium. The factor is distinct from nitric oxide and it persists in the presence beta-adrenoceptor blockade or cyclooxygenase inhibition.
Subject(s)
Carbachol/pharmacology , Muscarinic Agonists/pharmacology , Muscle Contraction/physiology , Muscle Hypertonia/physiopathology , Muscle, Smooth/physiopathology , Tissue Extracts/physiology , Urothelium/physiopathology , Aged , Culture Techniques , Dose-Response Relationship, Drug , Electric Stimulation , Female , Humans , Male , Middle Aged , Muscle Contraction/drug effects , Muscle, Smooth/drug effects , Neurokinin A/pharmacology , Potassium Chloride/pharmacology , Stimulation, Chemical , Urothelium/drug effectsABSTRACT
OBJECTIVE: To determine the risks of inguinal and pelvic lymph node metastasis as well as the prognostic factors in carcinoma of the penis. METHOD: Fifty patients with squamous cell carcinoma of the penis who consecutively underwent immediate bilateral ilioinguinal lymphadenectomy after treatment of the primary tumor. Clinical features were evaluated to determine the risk of inguinal and pelvic lymph node metastasis as well as prognostic factors. RESULTS: Patients with palpable inguinal lymph node had a high risk of inguinal lymph node metastasis compared with patients with a non palpable inguinal lymph node (p = 0.002). Patients with poor differentiated tumors had a high risk of pelvic lymph node metastasis compared with patients with well or moderately differentiated tumors (p = 0.021). Prognostic factors significantly related to survival were the clinical status of the inguinal lymph node, histological grade and the status of lymph node metastasis (N stage). None of the patients with stage N0 and N1 died with the longest follow-up at 85 and 67 months, respectively. Cumulative survivals were 0.6 at follow-up at 36 months for the patients with stage N2 and 0.5 at follow-up at 18 months for patients with stage N3. CONCLUSION: The clinical status of inguinal lymph node was related to the risk of inguinal lymph node metastasis. Histological grade was related to the risk of pelvic lymph node metastasis. The clinical status of the inguinal lymph node, histological grade and pathological N stage were the important factors affecting the prognosis.