Pregnancy outcomes in women with rheumatic diseases: a real-world observational study in Japan.

OBJECTIVES: We aimed to evaluate the obstetric complications and the risk factors for these events in pregnant women with rheumatic diseases (RDs). METHODS: A single-center retrospective study of women with RDs at Hokkaido University Hospital between 2007 and 2016 was conducted. Clinical features and maternal and fetal outcomes were retrospectively collected. The rate of pregnancy complications was compared with the general obstetric population (GOP) in Japan. RESULTS: Overall, 132 pregnancies in 95 women with RDs were recorded. Underlying RDs were systemic erythematosus (SLE) (n = 57), antiphospholipid syndrome (APS) (n = 35), rheumatoid arthritis (n = 9), and other RDs (n = 31). Antiphospholipid antibodies (aPL) were detected in 44 pregnancies (32%). Glucocorticoid was used in 82 pregnancies (62%), and tacrolimus in 20 pregnancies (15%). There were 24 disease flares (18%), but no RD-related death was documented. We recorded 112 live births, 6 abortions, 8 miscarriages, and 6 stillbirths. Pregnancies with RDs appeared to have frequent, emergency cesarean sections and preterm deliveries compared with GOP (30% vs 15% and 21% vs 14%, respectively). The median [interquartile range] birthweight in SLE and APS was lower than GOP (2591 [2231-2958] g and 2600 [2276-2920] g vs 2950 [2650-3250] g, respectively). In pregnancies with SLE, low complement levels presented the risk of maternal complications (odds ratio [95% CI]; 3.9 [1.0-14.9], p = 0.046) and anti-DNA antibody positivity was significantly correlated with the risk of fetal complications (3.5 [1.1-11.2], p = 0.036). In pregnancies with APS, maternal age over 35 years and duration of disease longer than 9 years (7.4 [1.3-40.8], p = 0.021, and 11.16 [1.1-118.8], p = 0.046, respectively) were significantly correlated with the risk of fetal complications. CONCLUSION: Pregnancies with RDs were at increased risk of having both maternal complications and adverse neonatal outcomes, indicating these pregnancies should be closely monitored.

Thrombotic risk stratification by platelet count in patients with antiphospholipid antibodies: a longitudinal study.

Essentials Thrombotic risk stratification is an unmet need in antiphospholipid antibody carriers. Platelet count and antiphospholipid score (aPL-S) were combined to predict thrombotic events. Patients with high aPL-S are at high thrombotic risk regardless of platelet count. If platelet count is low, patients with low aPL-S are also on high thrombotic risk. SUMMARY: Background Thrombocytopenia is a non-criteria clinical manifestation of antiphospholipid syndrome. However, it remains to be elucidated whether thrombocytopenia increases thrombotic risk in antiphospholipid antibody (aPL) carriers. Objectives To investigate the impact of platelet count in terms of predicting thrombotic events in aPL carriers, and to stratify the thrombotic risk by combining platelet count and antiphospholipid score (aPL-S), which represents a quantification of aPL varieties and titers. Patients/methods A single-center, retrospective, longitudinal study comprising 953 consecutive patients who were suspected of having autoimmune disease between January 2002 and December 2006 was performed. Low platelet count was defined as a count of < 150 × 103 µL-1 at the time of aPL testing. Results A negative correlation was observed between aPL-S and platelet count (r = - 0.2477). Among aPL-positive patients, those with a low platelet count developed thrombosis more frequently than those without (hazard ratio [HR] 2.95, 95% confidence interval [CI] 1.11-7.88). Among aPL-negative patients, no difference was found in the predictive value of thrombosis regardless of platelet count. Patients with aPLs were further divided into two subgroups according to aPL-S. Among low-aPL-S patients, those with low platelet counts developed thrombosis more frequently than those without (HR 3.44, 95% CI 1.05-11.2). In contrast, high-aPL-S patients developed thrombosis frequently regardless of platelet count. Conclusions aPL carriers with low platelet counts are at high risk of developing thrombosis. In particular, 'low-aPL-S carriers' may be stratified by platelet count in terms of predicting future thrombotic events.

Ischemic and reperfusion injury of cyanotic myocardium in chronic hypoxic rat model: changes in cyanotic myocardial antioxidant system.

OBJECTIVE: The objective was to evaluate the effect of left ventricular function on cyanotic myocardium after ischemia-reperfusion and to determine the effect of cyanosis on the myocardial antioxidant system. METHODS: Cyanotic hearts (cyanotic group) were obtained from rats housed in a hypoxic chamber (10% oxygen) for 2 weeks and control hearts (control group) from rats maintained in ambient air. Isolated, crystalloid perfused working hearts were subjected to 15 minutes of global normothermic ischemia and 20 minutes of reperfusion, and functional recovery was evaluated in the two groups. Myocardial superoxide dismutase, glutathione peroxidase, glutathione reductase activity, and reduced glutathione content were measured separately in the cytoplasm and mitochondria at the end of the preischemic, ischemic, and reperfusion periods. RESULTS: Mean cardiac output/left ventricular weight was not significantly different between the two groups. Percent recovery of cardiac output was significantly lower in the cyanotic group than in the control group (56.1% +/- 5.7% vs 73.0% +/- 3.1%, p = 0.001). Mitochondrial superoxide dismutase, mitochondrial and cytosolic glutathione reductase activity, and cytosolic reduced glutathione were significantly lower in the cyanotic group than in the control group at end-ischemia (superoxide dismutase, 3.7 +/- 1.3 vs 5.9 +/- 1.5 units/mg protein, p = 0.012; mitochondrial glutathione reductase, 43.7 +/- 14.0 vs 71.0 +/- 30.3 munits/mg protein, p = 0.039; cytosolic glutathione reductase, 13.7 +/- 2.0 vs 23.2 +/- 4.2 munits/mg protein, p < 0.001; and reduced glutathione, 0.69 +/- 0.10 vs 0.91 +/- 0.24 microgram/mg protein, p = 0.037). CONCLUSIONS: Cyanosis impairs postischemic functional recovery and depresses myocardial antioxidant reserve during ischemia. Reduced antioxidant reserve at end-ischemia may result in impaired postischemic functional recovery of cyanotic myocardium.

Development of a new experimental model for total exclusion of the right heart without the aid of cardiopulmonary bypass.

A new experimental model for the total exclusion of the right heart was successfully developed in mongrel dogs without the use of cardiopulmonary bypass. A Y-shaped conduit was constructed with tube grafts spirally stented on the exterior (10 mm in diameter), and each upper limb of the conduit was provided with a 30F cannula. The foot of the conduit was anastomosed with the main pulmonary artery in an end-to-side way with a side clamp. After a closed atrioseptostomy was performed with a special knife of our design, the upper limbs of the graft were connected to the superior and inferior venae cavae by a cannulation method. The operative procedure was completed by tightening the occluding snares around the venae cavae and ligating the root of the pulmonary artery and azygos vein. Thus, without any use of the right atrium, venous blood from the venae cavae was totally diverted to the pulmonary circulation via the conduit, and only the coronary venous return was shunted to the left atrium. Five consecutive dogs tolerated the operative procedure. No pressure gradients were observed between the pulmonary arteries and venae cavae. The circulation with this model was able to be sufficiently sustained with mean pulmonary arterial pressures of about 25 mm Hg, and no significant changes were shown in the left ventricular pump function from the preoperative state. However, the decrease in the mean pulmonary artery pressure to 20 mm Hg resulted in severe circulatory failure, and two of the five dogs succumbed to this condition. Our new model will be useful for studying the hemodynamic characteristics of the circulation after operations that result in total exclusion of the right heart.

Efficacy of intra-aortic balloon pumping for failing Fontan circulation.

The Fontan circulation occasionally cannot be sustained by currently available medical treatment. In these circumstances, mechanical assistance to the Fontan circulation should be considered. We have experienced three cases where Fontan circulation was assisted by intra-aortic balloon pumping (IABP). The hemodynamic improvement and weaning from IABP were successfully achieved in all cases. One patient survived the serious postoperative course with the aid of IAPB, and two patients died following multiorgan failure, though the circulation had eventually been re-established. By studying the postoperative hemodynamics assisted by IABP, it is concluded that IABP is a reasonable, efficacious strategy to support and to re-establish the failing Fontan circulation, though the changes in hemodynamic variables will not immediately coincide with IABP application.

Participation of endodermal epithelial cells on the synthesis of plasma LDL and HDL in the chick yolk sac.

We ultrastructually examined the chick yolk sac endodermal epithelium and evaluated our findings in combination with the biochemical analysis of serum and yolk lipoproteins. Twenty-five to 30 nm-sized particles were demonstrated to be a principal element of the extracellular yolk mass and these were determined to be yolk very low density lipoprotein (VLDL). The particles were shown to be taken up by the epithelial cells via coated pits and engulfed by plasma membrane invaginations together with yolk subdroplets, another element of the yolk mass. Through apical vacuoles, the two yolk elements were incorporated into yolk drops, which were identified to be one of the lysosomal structures by a cytochemical procedure using acid phosphatase (AcP)ase activity. During the last week of incubation, which is the final third of the incubation period, the digestion seemed to progress rapidly in the yolk drops, which came to resemble lipolysosomes; lipoprotein production became active as expressed by an enlarged Golgi apparatus. The newly produced lipoprotein particles were electron-lucent and irregular in size (50-120 nm). They were sequestered in secretory vacuoles and secreted from the vascular surface of the epithelial cells. Finally, the particles were thought to be taken into the vitelline circulation as plasma lipoproteins. The major component of lipoprotein in serum was determined to be low density lipoprotein (LDL) and high density lipoprotein (HDL), while cholesterol content was found to increase during incubation. We concluded that endodermal epithelial cells participate the synthesis of plasma LDL and HDL. For this synthesis the cells probably apply lipids and apo-protein generated from yolk VLDL degradation.

Late aneurysm after subclavian flap aortoplasty for coarctation of the aorta.

Late aneurysms are common after repair of coarctation of the aorta by prosthetic patch aortoplasty but are rare after subclavian flap aortoplasty. We present the case of a 14-year-old boy who underwent a grafting procedure for a descending thoracic aortic aneurysm after subclavian flap aortoplasty for coarctation of the aorta when he was 2 years old. This is the fifth report of late aneurysm formation after subclavian flap aortoplasty.

Successful surgical repair of truncus arteriosus with interrupted aortic arch in infancy by an anterior approach.

A 98-day-old infant was successfully operated on for truncus arteriosus (type I) with interrupted aortic arch (type B) using a one-stage anterior approach. The interrupted aortic arch was reconstructed by direct anastomosis between the ascending and descending aorta. The ventricular septal defect was closed, and a 12-mm porcine valved conduit was placed on the right side of the ascending aorta to establish continuity between the right ventricle and pulmonary artery. Surgical procedures for the repair of this malformation are the focus of discussion.

Expanded selection criterion for Fontan's operation based on the size of distal pulmonary arteries.

This study examined pulmonary arterial size to clarify a quantitative selection criterion for Fontan's operation in six cases without pulmonary hypertension. Pulmonary arterial size was angiographically assessed before and after the operation. No enlargement of the artery was observed, even after the procedure, confirming the importance of preoperative pulmonary arterial size. All three cases with preoperative PAa/N-RPAa of more than 0.5 survived the operation, whereas two of the remaining three cases (less than 0.5) died due to low cardiac output. The only survivor in the latter group had previously received Glenn's anastomosis. Hemodynamic study was done simultaneously, and a significant exponential correlation was obtained between preoperative PAa/N-RPAa and perioperative post-repair right atrial pressure (p less than 0.025). It was concluded that the selection criterion based on pulmonary arterial size could be expanded to a PAa/N-RPAa value of 0.5 when no Glenn's anastomosis had previously been done and the rudimentary right ventricle was not to be utilized. The exponential curve is useful for postoperative care in Fontan's operation, since it indicates the central venous pressure necessary to sustain the circulation at a level corresponding to the preoperative pulmonary arterial size.

Protective effects of calmodulin antagonists (trifluoperazine and W-7) on hypothermic ischemic rat hearts.

The cardioprotective effect of calmodulin antagonists, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7) was examined on the isolated rat heart exposed to hypothermic and ischemic conditions by measuring distribution of lysosomal enzymes in myocardial cells, and leakage of creatine kinase (CK) during reperfusion and postischemic recovery in myocardial systolic function. Experimental hearts were infused with 20 degrees C Krebs-Henseleit bicarbonate buffer (KHB) or KHB containing TFP or W-7 for 2min every 30min during hypothermic ischemia. After ischemia for 120min at 20 degrees C, rat hearts were reperfused at 37 degrees C for 30min. TFP and W-7 improved functional recovery and prevented CK release. In TFP treated hearts, leakage of lysosomal enzymes was reduced significantly, whereas stabilization of lysosomes by W-7 did not occur. These results suggest that calcium-calmodulin dependent enzymes may play an important role in the development of cellular damage of the myocardium during hypothermic ischemia, although levels of leakage of lysosomal enzymes may be unreliable predictors of functional recovery after hypothermic ischemia.

Neonatal intrathymic splenocyte injection yields prolonged cardiac xenograft survival.

Intrathymic (i.t.) injection of allogenic cells without administration of anti-lymphocyte serum (ALS) in neonatal recipients has induced donor-specific tolerance to subsequent cardiac allografts in rats. This study examines whether similar tactics can be successfully applied to a hamster-to-rat cardiac xenotransplantation model. Lewis neonates on their first day of life underwent i.t., subcutaneous (s.c.), intraperitoneal (i.p.), or intravenous (i.v.) injections of 5 x 10(7) Golden Syrian hamster splenocytes. After six weeks, the rats underwent heterotopic cardiac transplantation of hamster hearts. Cyclophosphamide (CyP) was administered on the day before surgery and postoperatively to suppress antibody-mediated graft rejection. Rats given splenocytes with 80 mg/kg of CyP had the following graft survival times: 8 to 12 days for i.t. injection (mean, 9.4 days); 5 to 7 days for s.c. injection (mean, 6.6 days); 4 to 11 days for i.p. injection (mean, 7.4 days); and 4 to 13 days for i.v. injection (mean, 7.9 days). Only the extension of graft survival produced by i.t. injection was statistically significant in comparison with the rats given only CyP treatment (mean, 7.5 days; P < 0.05). Thus, it appears that i.t. injection of xenogenic splenocytes in neonatal recipients with administration of CyP, but without ALS, can prolong xenograft survival. This biological intervention may be most useful in pediatric xenotransplantation when combined with other immunomodulation techniques.

Angiocardiographic quantitative evaluation of double-outlet right ventricle: special reference to the morphology of the common outflow tract.

Geometrical measurements of angiocardiograms of the common outflow tract (COT) of 13 patients were made to determine in which cases internal conduit repair was feasible, and under which conditions a patch enlargement of the COT was indicated. In the pulmonary stenosis (PS) group, the area of the narrowest cross-section of the COT was significantly smaller than that in the pulmonary hypertension (PH) group (p less than 0.025). In the PS group, the area was rarely sufficient to be shared by systemic and pulmonary circulation. Therefore, stenosis in the outflow tract to the pulmonary artery will occur if the intraventricular tunnel technique is applied, without patch enlargement of this portion, to patients with PS. On the contrary, the cross-sectional areas of the COT and pulmonary arteries were significantly larger in the PH group than in the PS group. Accordingly, the intracardiac conduit operation may be possible in such patients without a patch enlargement, even in young patients if other intracardiac conditions allow. Preoperative angiocardiographic evaluation of the COT is helpful in preoperatively selecting the proper operative procedure for this anomaly.

Mid-term results of bilateral internal thoracic artery grafting.

Forty patients underwent coronary revascularization using bilateral internal thoracic artery (ITA) grafts between 1988 and 1992. A total of 111 coronary grafts were performed, or an average of 2.8 grafts per patient. Each patient received bilateral ITA grafts, and in 20 patients an additional 29 grafts were constructed with 18 autologous veins and 11 gastroepiploic arteries. The right ITA was grafted as a free graft in 20 patients. The ITA graft patency rate was 96 per cent (67/70) at the time of hospital discharge. The operative morbidity included 3 reoperations for bleeding, 1 perioperative myocardial infarction, 1 renal failure, 2 postcardiotomy shock, and 1 colon perforation. Two hospital deaths occurred; one due to colon perforation and the other due to postcardiotomy cardiogenic shock. One patient died of cerebral infarction 6 month after the operation. Thirty-four patients were in New York Heart Association functional class I, 2 were in class II and 1 was in class III. Cardiac function evaluated by echocardiography and scintigraphy showed significant improvement postoperatively. These data suggest that the use of bilateral ITA grafts is associated with an acceptable mortality and increases the versatility of arterial grafting.

Use of ventricular assist devices in patients with postcardiotomy shock.

Over the last three years, we have used ventricular assist devices (VAD) in 7 patients. Of these 7, four patients with combined aortic and mitral valvular disease underwent double valve replacement; one patient with annuloaortic ectasia underwent a Cabrol's operation; another had aortic valve replacement; the last patient had triple coronary artery bypass grafts. The only patient who could be weaned from CPB developed cardiogenic shock after the operation. LVADs supported 6 patients for 4 to 8 days and a BVAD supported one patient for 9 days. All patients survived the weaning procedure. Three were discharged from the hospital and survived 7 to 21 months. The 4 other patients died of multiple organ failure. Three of these four suffered from both renal failure and infection, while one patient had arrhythmia and died of ileus. These data suggest that renal failure and major infection can be serious detrimental complications to VAD support.

A possible role of nitric oxide formation in the vasodilatation of rabbit ear artery induced by a topically applied Capsaicin analogue.

Effects of topical application of a capsaicin analogue, nonylic acid vanillylamide (NVA, 0.032-10.0 mM) on the arterial diameter in the ear skin were examined in conscious rabbits using a precise dial caliper. In addition, the possibility of nitric oxide (NO) participating in a vasodilatation induced by low concentrations of NVA was tested by an NO synthase inhibitor. At the lowest concentration of NVA (0.032 mM), no significant change in the diameter was observed after external application of the NVA ointment. At concentrations of 0.32 mM or more, NVA produced a significant vasodilator response. However, at higher concentrations of 3.2 and 10.0 mM, -NVA induced substantial shrinkage in the arterial diameter and oedema formation, which was not affected by L-NAME (NG-nitro-L-arginine methyl ester, 3 mg/kg, i.v.), suggesting fluid leakage induced by oedema from the vessels might suppress the vasodilatation. Thus, the concentration-response curve for NVA was bell-shaped. NVA (0.32 mM)-induced vasodilatation was not significantly affected by atropine (1 mg/kg, i.v.) or propranolol (80 micrograms/kg, i.v.). However, the NVA-induced vasodilatation was completely suppressed by an NO synthase inhibitor, L-NAME (3 mg/kg, i.v.) which had no influence on the resting diameter, but not by an inactive stereoisomer, D-NAME (3 mg/kg, i.v.). These findings suggest that vanilloid receptor activation results in the release of sensory neuropeptides, which in turn stimulate the synthesis of endothelial NO which is responsible for the vasodilatation.

[A case of aneurysmal bone cyst arising from the left first rib].

A 30 year-old female was admitted to our department because of an abnormal chest radiograph. The chest CT scan revealed a tumor expanding from the left first rib. The tumor was resected through a left posterolateral thoracotomy. Histological findings showed aneurysmal bone cyst. Aneurysmal bone cyst is an uncommon lesion, especially in the rib. The patient's postoperative course was uneventful and there has been no evidence of recurrence during the 15 months since operation.

[A case of congenital atrial flutter associated with atrial septal defect].

We report the case of a 8-month-old boy with atrial septal defect associated with congenital atrial flutter. He was operated on for ASD successfully. Atrial flutter in infants has been reported to be uncommon and to have a poor prognosis when associated with underlying cardiac disease. Therefore, early surgical intervention may improve the prognosis.

[Perioperative insertion of peritoneal dialysis catheter].

Silicon rubber peritoneal dialysis catheter (Tenkoff) was inserted perioperatively in neonates undergoing cardiac surgery and also in those patients in whom right-sided heart failure may occur. This method is easy and safe even in neonates. Post operative excessive fluid retention could be avoided using this method.

[A surgical repair of partial anomalous pulmonary venous drainage to the high superior vena cava].

A 7-year-old boy with partial anomalous pulmonary venous drainage to the high superior vena cava (SVC) underwent surgical repair by Williams procedure. Right upper pulmonary vein was drained to the left atrium via the SVC and the surgically enlarged sinus venosus type ASD. SVC was ligated and divided. SVC was then anastomosed to RA appendage pedicle directly. Autologous pericardium was patched anteriorly to create a new SVC pathway. The postoperative course was uneventful without arrhythmia and cardiac catheterization 1 month postoperation revealed no stenosis of the SVC and right upper pulmonary venous return.

[Surgical treatment of pulmonary aspergillosis].

There is controversy about the optimal treatment for pulmonary aspergillosis. Eight patients with pulmonary aspergilloma underwent surgical treatment. Three patients had tuberculosis, one Sjögren syndrome, one aortitis syndrome, one malignant lymphoma. Lobectomy was performed in five patients, segmentectomy in three patients. All patients are alive and have no recurrence. We have obtained excellent results from surgery and advocate early surgery for localized lesions to prevent life-threatening hemoptysis. This will allow patients to continue with further treatment for the underlying disease. We encountered a granulocytopenic patient with rapidly progressive aspergillus infection resulting in occlusion of main pulmonary artery leading to death. Surgical intervention could not prevent this fatal outcome. The selection of the patients with diffuse lesions should be made carefully.