Effect of oxytocin on spontaneous electrical and mechanical activities in pregnant human myometrium

Spontaneous intracellular electrical activity and contraction of pregnant human myometrium were recorded by the single sucrose-gap method, and the effects of oxytocin on the muscle were studied. In pregnant human myometrium at term, both plateau and spike types of action potentials were observed. All contractions were well synchronized with each action potential. Oxytocin, 10(-2) U/ml, potentiated spontaneous contractions by enhancing the plateau part of action potentials; spike-type configuration became plateau. When extracellular ionized calcium was removed, spontaneous activities disappeared, while 10(-2) U/ml of oxytocin could evoke action potentials and contractions but these were smaller than those of the controls. Spontaneous activities also disappeared when ionized calcium was increased to 5 mmol/L, but oxytocin evoked plateau potentials and contractions remarkably. Diltiazem (ionized calcium antagonist), 10(-6) gm/ml, suppressed the spontaneous activity, but oxytocin evoked action potentials and contractions in high frequency, the duration of the action potential being short and the contraction being small. In the presence of 10(-4) gm/ml of diltiazem, 10(-2) U/ml of oxytocin could not evoke any action potentials but did evoke small and long contractures, while in a high ionized potassium contracture experiment, oxytocin potentiated the tonic phase. These results suggest that oxytocin can increase spontaneous contractions by enhancing plateau potentials and that this effect requires sufficient extracellular ionized calcium. In this potentiation, the effects on frequency and amplitude of contractions might vary. It is also suggested that oxytocin may evoke a contracture in the absence of an action potential by releasing calcium from intracellular storage sites.     

Accuracy of conventional plus transoral carotid ultrasonography in distinguishing pseudo-occlusion from total occlusion of the internal carotid artery

BACKGROUND: To investigate the accuracy of conventional carotid ultrasonography (CCU) combined with transoral carotid ultrasonography (TOCU) for distinguishing pseudo-occlusion from total occlusion of the internal carotid artery (ICA). METHODS: This study included 95 patients who were suspected of having an occlusion of the ICA on magnetic resonance angiography (MRA) and underwent both CCU and conventional digital subtraction angiography (DSA) in order to confirm the diagnosis. TOCU was also performed to observe the cervical portion of the ICA distal to the stenosis. We compared the ultrasonographic findings with the DSA findings. RESULTS: Twelve of the 95 patients were defined as having an ICA pseudo-occlusion on DSA. On B-mode images with CCU color Doppler, slight residual flow signals in the ICA lumen were shown in 20 patients. Among them, 2 patients had a pulsed Doppler waveform of the distal ICA occlusion pattern. Among the remaining 18 patients, 4 had a pulsed Doppler waveform of the to and fro flow pattern, and 14 had a weak antegrade flow pattern in the ICA lumen. The conventional ultrasonographic method showed 100% sensitivity with 93% specificity for diagnosing an ICA pseudo-occlusion. The addition of TOCU findings increased the specificity to 98%. In 2 patients, who were overdiagnosed as having an ICA pseudo-occlusion even using TOCU, DSA revealed an occlusion of the ICA distal to the ophthalmic artery with a severe stenosis of the proximal ICA. CONCLUSIONS: Using conventional and transoral carotid ultrasonography, an ICA pseudo-occlusion can be diagnosed with higher accuracy.     

Spontaneous rupture of common iliac artery associated with fibromuscular dysplasia presenting with colic pain suggestive of ureteral stone

We report a case of spontaneous rupture of the common iliac artery associated with fibromuscular dysplasia (FMD). A 21-year-old previously healthy male presented with acute onset of colic pain, suspected to be caused by a ureteral stone. Abdominal computed tomography and angiography revealed a retroperitoneal hematoma caused by rupture of the common iliac artery. In spite of an emergency operation initiated quickly, the patient died. A pathological examination demonstrated FMD of the common iliac artery. Although very rare, it is important to bear in mind that the possibility of retroperitoneal hemorrhage exists in patient with sudden lumbago.     

The Impact of Donor Factors on Early Graft Function in Kidney Transplantation From Donation After Cardiac Death

Donation after cardiac death (DCD) has the potential to significantly increase the number of organ donors. In this study, we investigate the influence of several donor parameters on the early graft function in kidney transplantation from DCD donors. We performed 58 kidney transplantations from DCD donors. Recipients were divided into 2 groups according to their graft function: normal graft function (NGF), patients who became be free of hemodialysis within 14 days post-transplantation) and delayed graft function (DGF) group, patients who required hemodialysis for longer than 15 days after transplantation). We compared donor age, sex, cause of death, warm and total ischemic time, duration of anuria (urine volume < 10 mL/h), and low blood pressure (systolic blood pressure < 60 mm Hg), usage of catecholamine and vasopressin, serum creatinine on the day of admission and graft retrieval, serum sodium concentration, and body temperature between 2 groups. The number of recipients in NGF and DGF group was 41 and 17. Univariate analysis revealed that duration of anuria (<24 vs ≥24 hours) and usage of catecholamine significantly influenced graft function. Duration of anuria was an independent risk factor for early graft function by multivariate analysis. In cadaveric kidney transplantation from DCD donors, there was a trend to poorer early graft function with donors who suffered from anuria for longer than 24 hours before kidney retrieval.     

Long-term minodronic acid (ONO-5920/YM529) treatment suppresses increased bone turnover, plus prevents reduction in bone mass and bone strength in ovariectomized rats with established osteopenia

The present study examined the effect of the highly potent nitrogen-containing bisphosphonate, minodronic acid (ONO-5920/YM529), on bone mineral density (BMD), bone turnover, bone histomorphometry and bone strength in ovariectomized (OVX) rats. Female F344/DuCrj rats, aged 14 weeks, were OVX or sham operated. After 3 months, the OVX rats showed an increase in bone turnover, and a decrease in bone mass and bone strength. Minodronic acid was administered orally once a day for 12 months at doses of 0, 0.006, 0.03 and 0.15 mg/kg from 3 months after OVX. Minodronic acid dose-dependently inhibited the decrease in BMD of lumbar vertebrae and femur. In the femur, treatment with 0.15 mg/kg minodronic acid increased the BMD of distal and mid sites to sham levels. Minodronic acid dose-dependently suppressed OVX-induced increase in urinary deoxypyridinoline, a bone resorption marker, after a month of treatment and these effects were maintained for 12 months of treatment. Minodronic acid also decreased serum osteocalcin, a bone formation marker. In bone histomorphometric analysis after 12 months of treatment, OVX rats showed an increase in bone resorption (Oc.S/BS and N.Oc/BS) and bone formation (MS/BS and BFR/BV) at lumbar vertebral bodies. Minodronic acid suppressed the OVX-induced increase in bone turnover at tissue level. Trabecular bone volume, trabecular thickness and trabecular number of lumbar vertebral bodies were decreased after OVX. Minodronic acid increased these structural indices, indicating that it prevented the deterioration in trabecular architecture. In a mechanical test at 12 months of treatment, ultimate load of lumbar vertebral bodies and mid femur in the OVX-control group was decreased compared to the sham group. Minodronic acid prevented the reduction in bone strength at both sites. In particular, in the mid femur, treatment with 0.03 and 0.15 mg/kg minodronic acid increased bone strength to sham levels or greater. In conclusion, minodronic acid suppressed increased bone turnover, plus prevented the decrease in BMD, deterioration of bone microarchitecture and reduction in bone strength in OVX rats with established osteopenia. These results suggest that minodronic acid may be clinically useful for treatment of osteoporosis.     

Characteristics and Prognosis of Colorectal Cancer Associated With Rheumatic Disease

It is well known that host immunity plays an important role in the defense against colorectal cancer (CRC) progression. The effects of autoimmune diseases, such as rheumatic disease (RD) in which the immune system is deregulated, on this immunity have not been fully investigated. The medical records of 1299 consecutive patients diagnosed with primary colorectal cancer who underwent surgical resection were retrospectively reviewed. The clinicopathologic factors of 28 subjects with RD (RD group) were compared with those of 1271 patients without RD (non-RD group). Compared to the non-RD group, the RD group was typified by a predominance of females (P < 0.01), older age (P < 0.01), and a lower incidence of rectal cancer (P = 0.02). Although no difference was observed between the groups in terms of TNM classification, disease-free and overall survival were significantly poorer in the RD group in both univariate and multivariate analyses. Subjects who had RD for more than 10 years tended to have a higher frequency of lymph node metastasis (P = 0.06) and a significantly higher incidence of synchronous distant metastasis (P = 0.035) at the time of cancer diagnosis. RD was associated with a significantly poorer prognosis of colorectal cancer, suggesting that deregulation of the immune system by autoimmune diseases may adversely affect the host immune defense against colorectal cancer progression.Key words: Colorectal cancer, Rheumatic disease, Host immunity, PrognosisIt is well known that host immunity plays an important role in defenses against the development and progression of cancer. The degree of lymphocyte infiltration into tumors has been reported to correlate with improvements of patient survival.¹ In carcinogen-induced mouse models of cancer, primary tumor susceptibility has been found to be enhanced in immunocompromised mice; conversely, the capacity for such tumors to grow after transplantation into wild-type mice is reduced.^2,3 Although cancer cells originate from autologous normal tissue, the immune system can recognize even minimal cellular alterations, distinguish cancerous from normal cells, and elicit an immune response.In autoimmune diseases represented by rheumatic disease (RD), the immune system loses the ability to distinguish nonself from self, eliciting an immune response against self-antigens; in this process, there is a possibility that immune defenses against non-normal cells are lost or impaired, facilitating the development and progression of cancer. In addition, the development of RD associated with cancer has been reported, and as its development is dependent on the production of substances such as hormones, peptides, autocrine and paracrine mediators, and antibodies or the stimulation of cytotoxic lymphocytes, the condition is known as paraneoplastic rheumatic syndrome. In such cases, RD tends to be less responsive to therapy than its nonparaneoplastic equivalents, and instead, treatment of the underlying cancer usually results in regression of RD.^4,5 Thus, it is postulated that RD and cancer are closely associated. However, only a few reports on the incidence and risk of cancer among patients with RD exist,^6,7 and the characteristics and prognosis of colorectal cancer (CRC) in these patients remain to be elucidated.In the present study, we investigated the development of CRC in the background of an immunologic disorder caused by RD, with the hypothesis that patients with CRC and autoimmune diseases such as RD will have a poorer prognosis than those without RD, as a result of depressed antitumor immunity caused by immune system incompetence. Thus, we aimed to clarify the features and prognosis of CRC-associated RD, and for this purpose, we compared the clinicopathologic features of patients with CRC with or without underlying RD.