On the role of TRPC1 in control of Ca2+ influx, cell volume, and cell cycle.

Ca(+) signaling plays a crucial role in control of cell cycle progression, but the understanding of the dynamics of Ca(2+) influx and release of Ca(2+) from intracellular stores during the cell cycle is far from complete. The aim of the present study was to investigate the role of the free extracellular Ca(2+) concentration ([Ca(2+)](o)) in cell proliferation, the pattern of changes in the free intracellular Ca(2+) concentration ([Ca(2+)](i)) during cell cycle progression, and the role of the transient receptor potential (TRP)C1 in these changes as well as in cell cycle progression and cell volume regulation. In Ehrlich Lettré Ascites (ELA) cells, [Ca(2+)](i) decreased significantly, and the thapsigargin-releasable Ca(2+) pool in the intracellular stores increased in G(1) as compared with G(0). Store-depletion-operated Ca(2+) entry (SOCE) and TRPC1 protein expression level were both higher in G(1) than in G(0) and S phase, in parallel with a more effective volume regulation after swelling [regulatory volume decrease (RVD)] in G(1) as compared with S phase. Furthermore, reduction of [Ca(2+)](o), as well as two unspecific SOCE inhibitors, 2-APB (2-aminoethyldiphenyl borinate) and SKF96365 (1-(ß-[3-(4-methoxy-phenyl)propoxyl-4-methoxyphenethyl)1H-imidazole-hydrochloride), inhibited ELA cell proliferation. Finally, Madin-Darby canine kidney cells in which TRPC1 was stably silenced [TRPC1 knockdown (TRPC1-KD) MDCK] exhibited reduced SOCE, slower RVD, and reduced cell proliferation compared with mock controls. In conclusion, in ELA cells, SOCE and TRPC1 both seem to be upregulated in G(1) as compared with S phase, concomitant with an increased rate of RVD. Furthermore, TRPC1-KD MDCK cells exhibit decreased SOCE, decreased RVD, and decreased proliferation, suggesting that, at least in certain cell types, TRPC1 is regulated during cell cycle progression and is involved in SOCE, RVD, and cell proliferation.

Canine and human sinoatrial node: differences and similarities in the structure, function, molecular profiles, and arrhythmia.

The sinoatrial node (SAN) is the primary pacemaker in canine and human hearts. The SAN in both species has a unique three-dimensional heterogeneous structure characterized by small pacemaker myocytes enmeshed within fibrotic strands, which partially insulate the cells from aberrant atrial activation. The SAN pacemaker tissue expresses a unique signature of proteins and receptors that mediate SAN automaticity, ion channel currents, and cell-to-cell communication, which are predominantly similar in both species. Recent intramural optical mapping, integrated with structural and molecular studies, has revealed the existence of up to five specialized SAN conduction pathways that preferentially conduct electrical activation to atrial tissues. The intrinsic heart rate, intranodal leading pacemaker shifts, and changes in conduction in response to physiological and pathophysiological stimuli are similar. Structural and/or functional impairments due to cardiac diseases including heart failure cause SAN dysfunctions (SNDs) in both species. These dysfunctions are usually manifested as severe bradycardia, tachy-brady arrhythmias, and conduction abnormalities including exit block and SAN reentry, which could lead to atrial tachycardia and fibrillation, cardiac arrest, and heart failure. Pharmaceutical drugs and implantable pacemakers are only partially successful in managing SNDs, emphasizing a critical need to develop targeted mechanism-based therapies to treat SNDs. Because several structural and functional characteristics are similar between the canine and human SAN, research in these species may be mutually beneficial for developing novel treatment approaches. This review describes structural, functional, and molecular similarities and differences between the canine and human SAN, with special emphasis on arrhythmias and unique causal mechanisms of SND in diseased hearts.

Effective lipid modification by partial ileal bypass reduced long-term coronary heart disease mortality and morbidity: five-year posttrial follow-up report from the POSCH. Program on the Surgical Control of the Hyperlipidemias.

BACKGROUND: In 1990, when the Program on the Surgical Control of the Hyperlipidemias (POSCH) reported its in-trial results strongly supporting the conclusion that effective lipid modification reduces progression of atherosclerosis, the differences for the end points of overall mortality and mortality from atherosclerotic coronary heart disease (ACHD) did not reach statistical significance. METHODS: The Program on the Surgical Control of the Hyperlipidemias recruited men and women with a single documented myocardial infarction between the ages of 30 and 64 years who had a plasma cholesterol level higher than 5.69 mmol/L (220 mg/dL) or higher than 5.17 mmol/L (200 mg/dL) if the low-density lipoprotein cholesterol level was in excess of 3.62 mmol/L (140 mg/dL). Between 1975 and 1983, 838 patients were randomized: 417 to the diet control group and 421 to the diet plus partial ileal bypass intervention group. Mean patient follow-up for this 5-year posttrial report was 14.7 years (range, 12.2-20 years). RESULTS: At 5 years after the trial, statistical significance was obtained for differences in overall mortality (P = .049) and mortality from ACHD (P = .03). Other POSCH end points included overall mortality (left ventricular ejection fraction > or =50%) (P = .01), mortality from ACHD (left ventricular ejection fraction > or =50%) (P = .05), mortality from ACHD and confirmed nonfatal myocardial infarction (P<.001), confirmed nonfatal myocardial infarction (P<.001), mortality from ACHD, confirmed and suspected myocardial infarction and unstable angina (P<.001), incidence of coronary artery bypass grafting or percutaneous transluminal coronary angioplasty (P<.001), and onset of clinical peripheral vascular disease (P = .02). There were no statistically significant differences between groups for cerebrovascular events, mortality from non-ACHD, and cancer. All POSCH patients have been available for follow-up. CONCLUSION: At 5 years after the trial, all POSCH mortality and atherosclerosis end points, including overall mortality and mortality from ACHD, demonstrated statistically significant differences between the study groups.

Myocardial infarction and percent arteriographic stenosis of culprit lesion: report from the Program on the Surgical Control of the Hyperlipidemias (POSCH).

The objective of this study was to assess the percent stenosis of the culprit lesion responsible for subsequent myocardial infarction in the Program on the Surgical Control of the Hyperlipidemias (POSCH). It is unknown if the susceptible coronary artery culprit lesion responsible for an acute myocardial infarction is relatively large ( > or = 50% arteriographic stenosis) and hemodynamically significant ( > or = 70% stenosis), or small ( < 50%, stenosis) and asymptomatic. Certain necropsy and arteriography studies support the large progenitor lesion concept, and other arteriography studies support the small lesion hypothesis. We analyzed the coronary arteriogram immediately preceding a Q wave (transmural) myocardial infarction for the degree of stenosis of the suspected culprit lesion, which was selected by visual inspection of the coronary circulation supplying the electrocardiogram-defined area of myocardial infarction. There was no perceptible difference with respect to vessel segment distribution of culprit lesions or time to infarction between the 52 control-group patients and the 27 intervention-group patients. For the two groups combined (n=79), the predominantly involved segments were the middle right coronary artery and the proximal left anterior descending coronary artery. The time interval from the preceding coronary arteriogram closest to the index myocardial infarction ranged from 0 days to 10 years; however, 64.6% of the arteriograms were performed 2 years or less prior to the myocardial infarction. Only 5.1% of the patients in both groups combined had a culprit lesion stenosis < 50%, while 88.6% of the patients in both groups combined had a culprit lesion stenosis > or = 70%. The results strongly favor the large lesion hypothesis of causation for myocardial infarction. It is premature, however, to state that the relative size of the culprit lesion has been indisputably determined. The resolution of this problem has exceedingly important practical implications for the management of patients with known atherosclerotic coronary heart disease and for those asymptomatic individuals with silent atherosclerotic coronary heart disease.

Prostatic-type polyp in the bladder. A case report.

A case of prostatic-type polyp in the wall of the urinary bladder in a 73-year-old male is presented. The literature concerning ectopic prostatic tissue in the urinary tract is reviewed and it is concluded that the lesion is benign. However, recurrence has been reported in two cases. The etiology and pathogenesis is unknown.

Longitudinal cleavage of the penis, a rare catheter complication seen in paraplegic patients.

Two cases of total necrosis of the penile urethra and overlying ventral structures are described in paraplegic male patients treated with indwelling urethral catheters. The lesions were apparently caused by an inexpedient pull on the catheter causing ischaemic necrosis of the urethral wall.

Calculi in female urethral diverticulum.

A case of two calculi found in the same urethral diverticulum in a 41-year-old woman with recurrent urinary tract infections is reported. The diagnostic procedures are discussed.

Transurethral resection of very large prostates. A retrospective study.

Twenty-one patients with benign prostatic hypertrophy (BPH), and a weight of transurethrally resected tissue exceeding 80 g (Group 1), were compared to a control group of 30 patients with a weight of resected tissue less than 80 g (Group 2) with regard to the peri- and postoperative course and the symptomatic and urodynamic results of surgery. All patients were followed 12 months postoperatively. In both groups more than 90% of the patients were satisfied with the results of the operation. However, the obstructive symptoms were better relieved than the irritative symptoms. The group who had large resections performed had a longer operating time and a greater perioperative blood loss than the group of minor resections. No differences were found with regard to other peri- or postoperative complications or subjective results. Transurethral resection is safe and efficient in treating BPH, also with very large prostates.

[Urinary retention in connection with postoperative pain treatment with epidural opioids]. / Urinretention ved postoperativ smertebehandling med epidurale opioider.

The incidence of retention of urine in cases of postoperative epidural opioid analgesia varies from 15% to 90%. The extent to which this phenomenon depends upon the dosage employed has not been elucidated. The cause of postoperative retention of urine (PU) is probably a combination of the central and peripheral effect of the opiate involving altered autonomic activity. Increased sympathetic activity resulting from surgery may, similarly, be a pathogenetic factor. The current methods of treatment are prophylactic or symptomatic alpha-receptor blockade, naloxon in refractory doses or catheterization. Inhibition of per- and postoperatively increased sympathetic activity may possibly prevent PU. Carbacholine is not effective in the treatment of postoperative retention of urine. In animal experimental studies, kappa-receptor agonists have an analgesic effect without urodynamic side-effects but no clinical trials on man have hitherto been undertaken. When postoperative retention of urine occurs after epidural opioid treatment, clean intermittent catheterization or introduction of a thin suprapubic catheter are recommended.

[Giant fecaloma]. / Gigantisk faekalom.

A case of a giant faecaloma of the sigmoid colon secondary to surgery is reported. The predisposing factors, the diagnostic and therapeutic approaches are discussed.

[Erective dysfunction. Therapeutic consequences of a basal program of investigation]. / Erektiv dysfunktion. Terapeutiske konsekvenser af et basalt undersøgelsesprogram.

During a period of nine months, 50 men aged 21-75 years were investigated on account of erective dysfunction by means of a simple outpatient programme of investigation. Five patients could be discharged after the primary contact with history-taking and information about further investigation and treatment. Forty-five patients were submitted to the programme of investigation which consisted of measurement of penile blood pressure, Doppler investigation of the penile arteries and the papaverine test. After this, ten patients (20%) could be referred for sexological advice while five were discharged as they did not desire further treatment. Sixteen patients (32%) were taught self injection. Out of the six patients (12%) in whom arterial insufficiency was demonstrated, penile prostheses were introduced operatively in four. Venous leakage from the corpus cavernosum was demonstrated in seven patients (14%) by means of cavernosometry and cavernosography. Venous ligature was performed in five with good effect in two. Thus, specific treatment could be offered to 35 men (70%) with satisfactory therapeutic results in 22 (44%).

[Validation of the patient-administered Danish Prostate Symptom Score Schedule]. / Validering af det patientadministrerede Danske Prostate Symptom Scoringsskema.

The DAN-PSS-1 system, a self-administered quality-of-life questionnaire comprising 12 questions related to voiding problems and the perceived bother of each individual symptom, was compared to other extensively used score systems and furthermore included in different clinical situations so as to validate the system. The system was internally consistent (alpha cr = 0.73), the median test-retest reliability of answers to each question was 83.5% (range 0-99.7%). A high degree of construct validity demonstrated in the correlation with the Madsen-Iversen score system (rs = 0.51) and with the patients' answers to questions about how bothersome their symptoms were (rs = 0.71). The discriminant validity of the DAN-PSS-1 was excellent with an area under the ROC curve of 0.94. Finally, the DAN-PSS-1 was sensitive to changes following intervention, with scores decreasing 100% after transurethral prostatectomy and 65% after four months of treatment with an alpha-blocker. The DAN-PSS-1 is reliable, valid and responsive, and therefore can be recommended for assessing the severity of symptoms among patients presenting with lower urinary tract complaints suggestive of BPH and during follow-up.

Alfuzosin in the treatment of benign prostatic hyperplasia: effects on symptom scores, urinary flow rates and residual volume. A multicentre, double-blind, placebo-controlled trial. ALFECH Study Group.

In order to assess the efficacy and safety of alfuzosin, a selective alpha-1 receptor antagonist, 205 patients with Benign Prostatic Hyperplasia (BPH) were randomly assigned in a double-blind, placebo-controlled manner, to receive either alfuzosin 2.5 mg TID or placebo TID during 12 weeks. After 12 weeks symptom scores-assessed according to the Madsen-Iversen scale were significantly reduced in the alfuzosin group and peak flow rate significantly increased compared to the placebo group. There were no significant differences concerning adverse events or withdrawals. Alfuzosin proved to have a beneficial effect in patients with symptomatic BPH with few and minor adverse events.