Effect of macrolide antibiotics on ciliary motility in rabbit airway epithelium in-vitro

Abstract— We have studied ciliary beat frequency (CBF) of rabbit cultured tracheal epithelium by a photoelectric method in-vitro. Addition of erythromycin and roxithromycin increased CBF in a dose-dependent fashion, whereas clarithromycin was without effect. The rank order potency of macrolide was roxithromycin > erythromycin » clarithromycin. The roxithromycin-induced increase in CBF was not altered by propranolol, AA-861, or verapamil, but partially attenuated by indomethacin. Roxithromycin increased intracellular cAMP concentrations. These results suggest that certain macrolides can stimulate airway ciliary motility probably via prostaglandin- and cAMP-dependent regulatory pathways, which may affect mucociliary transport function in the respiratory tract.     

Long-term treatment outcome of tamsulosin for benign prostatic hyperplasia

BACKGROUND: The present study assessed the long-term efficacy (>12 months) of tamsulosin in 123 patients with lower urinary tract symptoms caused by benign prostatic hyperplasia (BPH). METHODS: The patients received a starting dose of tamsulosin of 0.2 mg/day, with a further titration up to 0.4 mg/day until symptom relief. Subjective and objective clinical variables were assessed using the international prostate symptom score (IPSS), IPSS quality of life (QoL) score, BPH impact index score, peak urinary flow rate (Q(max)) and postvoid residual urine volume. RESULTS: Except for Q(max), all clinical variables showed significant sustained improvements from baseline throughout the study period (median follow up, 43 months). Thirty patients (24.4%) withdrew because of surgical interventions. The Cox proportional hazards model showed that a baseline IPSS total score >or=15 (HR [hazard ratio] 2.13; 95% CI 1.04-4.34) was predictive of failure for tamsulosin therapy. Furthermore, during the first 12 months, a lowest IPSS total score >or=13 (HR 2.34; 95% CI 1.12-4.89), a lowest IPSS QoL score >or=3 (HR 4.16; 95% CI 1.26-13.68), and a lowest BPH impact index score >or=4 (HR 3.54; 95% CI 1.62-7.75) were also predictive of failure for tamsulosin therapy. CONCLUSIONS: Tamsulosin treatment of BPH patients for more than 12 months showed a sustained, stable efficacy. Patients without short-term effects were prone to withdraw from tamsulosin therapy, but so did patients with a high baseline IPSS total score, even if therapy was effective for at least 12 months.     

Recurrence of renal cell carcinoma more than 5 years after nephrectomy

OBJECTIVES: We evaluated clinical features and predictive factors for the recurrence of renal cell carcinoma (RCC) developing more than 5 years after nephrectomy. METHODS: We retrospectively reviewed 239 patients with RCC who underwent surgery for the primary lesion. To identify factors that affected recurrence more than 5 years after nephrectomy (delayed recurrence) and its clinical outcomes, we performed a multivariate analysis using Cox's proportional hazards model and a survival study. RESULTS: Recurrence developing within 5 years after nephrectomy (early recurrence) was found in 57 patients and delayed recurrence in 11 patients. The multivariate analysis revealed no clinical and pathologic features influencing delayed recurrence in 114 patients who survived more than 5 years after nephrectomy without having early recurrence. The patients with delayed recurrence showed better clinical outcomes than those with early recurrence when the rate was determined from the time of recurrence. CONCLUSIONS: Although delayed recurrence is not a rare event for patients with RCC, no clinical and pathologic factors at the time of the initial treatment can predict the recurrence. Patients who are free of recurrence for more than 5 years after surgery for a primary lesion should be carefully followed up for delayed recurrence.     

Amino acids and peptides

The Gln-Val-Val-Ala-Gly sequence, which occurs frequently in several natural thiol proteinase inhibitors, and derivatives were synthesized by conventional solution methods and their effect on thiol proteinases were examined. The studies led us to the conclusion that certain of these peptides exhibited a weak inhibitory effect on the thiol proteinase, papain. One of them, Z-Gln-Val-Val-Ala-Gly-OMe, showed a protective effect on papain from natural thiol proteinase inhibitor-induced inactivation. The relationship between structure and activity of these derivatives was studied and certain conclusions were derived on possible mode of action of these inhibitors. From these studies, it was concluded that Z-Gln-Val-Val-OMe was the smallest peptide to exhibit some effect on papain.     

Intraoperative electrical stimulation of cavernous nerves with monitoring of intracorporeal pressure to confirm nerve sparing during radical prostatectomy: Early clinical results

BACKGROUND: We performed intraoperative cavernous nerve stimulation with an intracavernous pressure (ICP) monitoring system to confirm nerve sparing during radical pelvic surgery and assessed the results. METHODS: Nineteen cases of radical prostatectomy and three of radical cystoprostatectomy were examined. Electrical stimulation of the site where the neurovascular bundle (NVB) was determined to run was performed and changes in ICP were measured before and after prostate removal. RESULTS: Of the 22 patients, bilateral NVBs were preserved in six patients while unilateral NVB was preserved in 16. Before dissection, all NVBs examined exhibited positive responses (ICP changes of>5 mmHg) to nerve stimulation. After removal of the prostate, positive responses were observed in 22 (79%) of 28 macroanatomically preserved NVBs. Of 16 sides on which the NVB was not preserved, there were positive responses in five (31%). In these patients, some nerve fibers were macroscopically observed lateral to the original site of NVB. Finally, bilateral or unilateral nerve sparing was confirmed electrophysiologically in 20 (91%) of the 22 patients. CONCLUSION: Intraoperative stimulation of the NVB while monitoring ICP changes is a simple and reliable method of accurately evaluating the preservation of cavernous nerves. This system may provide further insight into the mechanism of postoperative erectile dysfunction.     

The clinical features of Sjögren's syndrome in Japanese children

Sjögren's syndrome (SS) is thought to be uncommon in children. An epidemiological study to describe the clinical features distinguishing SS in Japanese children was performed by sending questionnaires to hospitals. A total of 61 cases of SS were reported from 1290 hospitals. The diagnosis of SS was based on histopathological changes and/or sialographic changes in the salivary glands. Forty-two cases had primary SS and 19 were secondary SS with other autoimmune disorders. Fourteen cases (65%) of secondary SS were associated with systemic lupus erythematosus. In primary SS, the initial symptoms were systemic manifestations (fever, exanthema, arthralgia, etc) except for sicca symptoms. In laboratory studies, antinuclear antibodies, elevated serum IgG, rheumatoid factor, anti-Ro/SS-A antibodies and anti-La/SS-B antibodies were frequently observed.