Hypocalcemic cardiomyopathy in a patient with idiopathic hypoparathyroidism.

An idiopathic hypoparathyroidism-induced cardiomyopathy patient had severe long-lasting hypocalcemia. The dramatic improvement of cardiac function with correction of only the serum calcium concentration could be quantitatively demonstrated on both echocardiogram and ventriculogram. The concentration of the extracellular calcium ion was considered to have a direct effect on the strength of the myocardial contraction through excitation-contraction coupling. Furthermore, elevated serum creatine phosphokinase and lactate dehydrogenase levels which were thought to be delivered from skeletal muscle returned to the normal range concomitant with the correction of hypocalcemia. The serum calcium concentration and these enzyme level showed significant inverse correlations.     

Mucinous cystadenoma of appendix concomitant with perityphlic granuloma

We describe a case of mucinous cystadenoma of the appendix with perityphlic granuloma. The patient developed a hard palpable mass in the right lower quadrant and barium enema inducted irregular bowel wall at the cecum. Based on a preoperative diagnosis of carcinoma of the appendix, we performed a laparotomy. On operation, we found a tumor mass in the region of the appendix; the mass adhered strongly to the retroperitoneum and cecum. Right hemicolectomy was carried out on a diagnosis of carcinoma of the appendix. Microscopic examination revealed mucinous cystadenoma of the appendix with perityphlic granuloma. Mucinous cystadenoma in the appendix is a rare tumor. In this patient, the tumor was accompanied by granuloma formation in adjacent tissues because of mucin expelled from the appendix. This case emphasizes that granuloma formation can make of difficult to differentiate mucinous cystadenoma in the appendix from cancer.     

A technique for diagnosis of accessory pathway using the H-H and A-A intervals of the first entrained cycle during ventricular overdrive pacing

Although advancement of succeeding atrial activation by a ventricular extrastimulus (VES) on His refractoriness during supraventricular tachycardia (SVT) has been used as evidence of an accessory pathway (AP), the sensitivity of this method is suboptimal. This study was designed to compare the His-His (H-H) and atrial-atrial (A-A) intervals of the first entrained cycle during ventricular overdrive pacing (VOD) for the diagnosis of AP, in comparison to the conventional VES method. In 55 patients with SVT, a VES was elicited on His refractoriness during SVT. VOD was subsequently performed at cycle lengths 30 to 40 ms shorter than SVT cycle lengths. When the A-A interval became equal to the pacing cycle length after some beats of VOD, the cycle was considered the first entrained cycle and the H-H interval preceding the A-A interval was measured. VES advanced the next atrial activation in 16 patients (52%) with an AP, but in no patient without an AP. The H-H interval of the first entrained cycle was longer than the pacing cycle length by > or =15 ms in all patients with an AP, but was equal to the pacing cycle length in all patients without an AP. The criterion of H-H greater than A-A by > or =15 ms for the first entrained cycle provided higher diagnostic yield for AP compared with the VES method(100% vs 52%, p <0.001). In conclusion, this new criterion reliably diagnoses the presence of an AP in patients with SVT, with higher sensitivity compared with the VES method.     

Combination therapy of exercise and angiotensin-converting enzyme inhibitor markedly improves insulin sensitivities in hypertensive patients with insulin resistance.

The contraction of muscle enhances the release of bradykinin (BK) and improves glucose uptake by the muscle. Angiotensin-converting enzyme inhibitor (ACEI) slows the breakdown of BK, thus the effect of BK is augmented in the presence of ACEI. The present study investigated whether the combination of exercise (increased production of BK) and ACEI (delay in breakdown of BK) might further improve insulin sensitivity in hypertensive patients with insulin resistance (HOMA-R>1.8). Patients were assigned either to increased walking distance (Walking group) or taking 2 mg temocapril, an ACEI, daily (ACEI group) for 8 weeks. Then both interventions were given to all patients for 8 weeks (ACEI+Walking group). Blood concentrations of triglycerides were slightly lower in the ACEI+Walking group than at baseline, although there were no significant differences in total cholesterol or high density lipoprotein-cholesterol among the 2 groups. Blood glucose was not significantly different with each treatment, but blood concentrations of insulin and HOMA-R were significantly lower in the Walking and ACEI groups compared with the Control group. The combination of walking and ACEI further lowered blood concentrations of insulin and HOMA-R, which suggests that this treatment is beneficial for hypertensive patients with insulin resistance.     

Galpha(12/13) mediates alpha(1)-adrenergic receptor-induced cardiac hypertrophy

In neonatal cardiomyocytes, activation of the G(q)-coupled alpha(1)-adrenergic receptor (alpha(1)AR) induces hypertrophy by activating mitogen-activated protein kinases, including c-Jun NH(2)-terminal kinase (JNK). Here, we show that JNK activation is essential for alpha(1)AR-induced hypertrophy, in that alpha(1)AR-induced hypertrophic responses, such as reorganization of the actin cytoskeleton and increased protein synthesis, could be blocked by expressing the JNK-binding domain of JNK-interacting protein-1, a specific inhibitor of JNK. We also identified the classes and subunits of G proteins that mediate alpha(1)AR-induced JNK activation and hypertrophic responses by generating several recombinant adenoviruses that express polypeptides capable of inhibiting the function of specific G-protein subunits. alpha(1)AR-induced JNK activation was inhibited by the expression of carboxyl terminal regions of Galpha(q), Galpha(12), and Galpha(13). JNK activation was also inhibited by the Galpha(q/11)- or Galpha(12/13)-specific regulator of G-protein signaling (RGS) domains and by C3 toxin but was not affected by treatment with pertussis toxin or by expression of the carboxyl terminal region of G protein-coupled receptor kinase 2, a polypeptide that sequesters Gbetagamma. alpha(1)AR-induced hypertrophic responses were inhibited by Galpha(q/11)- and Galpha(12/13)-specific RGS domains, C3 toxin, and the carboxyl terminal region of G protein-coupled receptor kinase 2 but not by pertussis toxin. Activation of Rho was inhibited by carboxyl terminal regions of Galpha(12) and Galpha(13) but not by Galpha(q). Our findings suggest that alpha(1)AR-induced hypertrophic responses are mediated in part by a Galpha(12/13)-Rho-JNK pathway, in part by a G(q/11)-JNK pathway that is Rho independent, and in part by a Gbetagamma pathway that is JNK independent.     

Long-term follow up of re-induction with a new synthetic retinoid, Am-80, for relapse of acute promyelocytic leukemia previously treated with all-trans retinoic acid: results of 7 cases from a single institute

Seven patients experiencing first (n = 5) or second (n = 2) relapse of acute promyelocytic leukemia (APL) were treated with a new synthetic retinoid, Am-80. All 7 patients were previously treated with all-trans retinoic acid (ATRA). Am-80 was orally administered at a dose of 6 mg/m2 daily. Chemotherapy was combined in 3 patients because of leukocytosis. All 7 patients achieved a complete remission (CR) during periods ranging from 36-56 days (median 52 days). Adverse effects such as hyperlipidemia and skin lesions, were tolerable. After achieving CR, 3 patients underwent allogeneic bone marrow transplantation and 4 patients received only consolidation chemotherapy. In 2 of 3 patients who received allogeneic transplantation, relapse free survival has lasted for 9.7 and 28.3 months. Furthermore, in 2 of 4 patients who received only chemotherapy, relapse free survival has lasted for 84.7 and 90.1 months. Am-80 is an active agent for APL patients who have relapsed from ATRA-induced remission.     

Sinomenine and magnoflorine,major constituents of Sinomeni Caulis et Rhizoma,show potent protective effects against membrane damage induced by lysophosphatidylcholine in rat erythrocytes

The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 μM. SCR-WE at 1 ng/mL–100 μg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM–100 μM and 10 nM–100 μM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1–100 μM) but not at lower concentrations (1–100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM–1 μM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

     

Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report

Rationale:Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD.Patient concerns:We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient''s serum and cerebrospinal fluid.Diagnosis:A diagnosis of MOGAD complicated with MPA was made.Interventions:The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy.Outcomes:Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period.Conclusion:To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.