Nonselective cation channels activated by the stimulation of muscarinic receptors in mammalian gastric smooth muscle.

Muscarinic receptors play key roles in the control of gastrointestinal smooth muscle activity. However, specific physiological functions of each subtype remain to be determined. Single cell RT-PCR experiments showed that all five subtypes of muscarinic receptors were present in circular smooth muscle cells of the guinea-pig gastric antrum. Nonselective cation channels (NSCC) activated by ACh or CCh are coupled to pertussis toxin (PTX)-sensitive Go protein through m4 subtype as well as m2 and m3 subtypes in guinea-pig stomach. CCh-activated currents (I(CCh)), especially the steady-state I-V relationship of I(CCh) showed a chracteristic U-shaped curve; reversal potential of around 0 mV and inward rectification at around +15 mV and a negative slope conductance at negative potential range. Under physiological conditions, the measured single channel conductance of NSCC was approximately 25 pS. The single channel conductance was modulated by external monovalent and divalent cations including Na+, Cs+, Li+, and Ca2+ through changing both the open probability and unitary conductance. Through the NSCC, Ca2+ can move into the cell from extracellular solution as well as Na+. Calculated fractional Ca2+ current of I(CCh) (f(Ca)) was around 1% at the 2 mM [Ca2+]o and at the 4 mM [Ca2+]o, f(Ca) was 2.3%. Quinidine blocked I(CCh) potently in a reversible manner; IC50 was 0.25 microM. There were two kinds of I(CCh) modulations through Ca(2+)-dependent pathways in guinea-pig gastric smooth muscle cells; 1) Facilitation of I(CCh) via Ca2+/CaM-dependent MLCK pathway, 2) Desensitization of I(CCh) via Ca(2+)-dependent PKC pathway. In the mouse stomach, all seven types of TRPC mRNA were detected with RT-PCR. On the basis of electrophysiological, pharmacological, and molecular biological experiments, we reported the mTRPC5 as a candidate for the NSCC activated by muscarinic stimulation in mouse stomach.     

Is chronic inflammatory change in the prostate the major cause of rising serum prostate‐specific antigen in patients with clinical suspicion of prostate cancer?

AIM: To evaluate the cause of elevated prostate-specific antigen (PSA) in patients with transrectal needle biopsy negative for prostate cancer. METHODS: Serum PSA concentration, prostate volume, and pathologic findings were examined in 223 patients with negative biopsy for prostate cancer. The degree of prostate inflammation was determined by the extent and degree of inflammation shown by biopsy specimens and is expressed as an inflammation score (range: 0-36). RESULTS: A significant correlation was found between PSA concentration and prostate total volume (P=0.0001). Prostate chronic inflammation showed no correlation with PSA concentration (P=0.485, F=0.488). After allocating patients to normal PSA (4 ng/mL) groups, we found that serum PSA concentrations in both groups were predominantly affected by prostate total volume. CONCLUSIONS: An increase in prostate volume appears to be the major contributor to a high serum PSA concentration in patients with negative biopsy for prostate cancer. However, in contrast to previous reports, there was no correlation between the degree of prostate chronic inflammation and serum PSA concentrations.     

Survival of Patients with the Automatic Implantable Cardioverter Defibrillator

Between May 1982 and May 1988, 37 patients (28 males and 9 females, mean age 57.6, range 16–76 years) of approximately 600 evaluated for sustained ventricular tachycardia and/or fibrillation (VT/VF) were treated with an automatic implantable cardioverter defibrillator (AICD). Twenty-eight of the patients had coronary artery disease, 7 had nonischemic cardiomyopathy, 1 had amyloid hear disease, and 1 had rheumatic heart disease. The mean ejection fraction was 32.2 ± 12.9% (range, 9–64%). Eleven patients have died at a mean of 16.7 months after implantation. The cumulative survival rate was 81% at 1 year, 77% at 2 years. 68% at 3 years, and 53% at 4, 5, and 6 years. Considering only sudden deaths, the survival was 97% at 1 and 2 years, 90% at 3 years, and 80% at 4, 5, and 6 years. Twenty-one of the 37 patients received spontaneous shocks. If the first shock marks the time to death in the absence of an AICD, the cumulative survival rate would have been 56% at 1 year, 42% at 2 years, 29% at 3 years, and 14% at 4, 5, and 6 years. The maximum amount of time to a first appropriate shock was 39.7 months. Thirty-nine devices have been explanted; 28 for battery depletion; 5 for infections; 3 for improper sensing; 2 for electronic failure; and 1 at the time of cardiac transplantation. The average time to failure of the 28 units removed for battery depletion was 19.8 ±6.9 months. We conclude that in this group of patients, short-term survival is increased by AICD implantation, hut long-term survival remains poor. Incidence of sudden death is reduced to 3% at 1 and 2 years, 10% at 3 years, and 20% after 4 years. Other patient selection criteria may be useful in selecting those patients whose survival will be improved by the AICD.     

The use of cadaver kidneys for transplantation in young children

The role of cadaver kidney transplantation in the management of end-stage renal disease in young children is controversial. To assess the current risk-benefit ratio of cadaver first and second kidney transplants in recipients under 6 years of age, we compared the outcome of 19 transplants performed between 1984 and 1989 using a quadruple-drug regimen (Minnesota antilymphocyte globulin, azathioprine, prednisone, cyclosporine) with the outcome of 25 transplants performed prior to 1984 without the use of cyclosporine at a single institution. Twenty-five transplants were in children under the age of 3 years. In the last decade patient survival has significantly improved. One-year patient survival improved from 53% before 1979 to 90% since 1979 (P less than 0.05). The use of the quadruple-drug regimen since 1984 was associated with a significant improvement in one-year cadaver graft function from 40% before 1979 to 78% in recipients under 6 years of age, and from 22% to 82% in recipients under 3 years of age (P less than 0.05). With the quadruple-drug regimen, one-year and four-year graft function rates for children under 6 years of age were 83% for first cadaver transplants and 72% for second cadaver transplants, which were essentially the same results as in older children and adults. Children who received kidneys from donors over 4 years of age achieved the best result, with 87% one-year graft function compared with 50% for kidneys from donors under 4 years old. In 15 children with successful transplants, 8 (53%) showed accelerated growth, 5 (33%) had normal-velocity growth, and only 2 children (14%) with suboptimal renal function had poor growth following transplantation. Therefore, we believe that with a quadruple-drug immunosuppressive protocol, cadaver renal transplantation using kidneys from adults or pediatric donors over 4 years old is an acceptable form of treatment in young children with end-stage renal disease for whom there are no suitable living-related donors.     

徐秀玉:应抓紧建设"平民医院"

3月14日,记者在北京京西宾馆见到了刚刚参加完“两会”闭幕式的全国人大代表、哈尔滨医科大学附属三医院院长徐秀玉,采访从温家宝总理的《政府工作报告》开始。