Dietary sodium restriction restores nocturnal reduction of blood pressure in patients with primary aldosteronism.

The purpose of this study was to elucidate the effects of dietary sodium restriction on diurnal blood pressure (BP) variation in primary aldosteronism. We studied the diurnal variation in the systemic hemodynamic indices and in baroreflex sensitivity (BRS). In 13 subjects with aldosterone-producing adenomas (2 males; mean age, 39+/-2 years), intra-arterial pressure was monitored telemetrically on a normal salt diet (NaCl 10-12 g/day). Non-dippers were defined as those with a nocturnal reduction in systolic BP (SBP) of less than 10% of daytime SBP. Ten subjects showed a non-dipper pattern. Six of these "non-dippers" underwent repetitive hemodynamic studies on the last day of a 1-week low salt diet regimen (NaCl 2-4 g/day). Stroke volume was determined using Wesseling's pulse contour method, calibrated with indocyanine green dilution. BRS was calculated every 30 min as delta pulse interval/delta SBP on spontaneous variations. Nocturnal reduction of SBP was 4.1% on the normal salt diet. With sodium restriction, urinary sodium excretion decreased from 187+/-8 to 46+/-8 mmol/day, and body weight decreased from 57.9+/-2.1 to 56.6+/-1.9 kg. Night-time BP significantly decreased with dietary modification from 154+/-7/88+/-4 to 140+/-6/78+/-4 mmHg, whereas daytime BP was unaltered. With sodium restriction, cardiac index and stroke index decreased throughout the day. No significant difference was seen in either daytime or nighttime BRS between the two diets. We conclude that the non-dipper pattern is common in patients with an aldosterone-producing adenoma on a normal salt intake, and under such conditions, volume expansion appears to play a major role in the impairment of nocturnal BP reduction.     

Identification of cooperative genes for NUP98-HOXA9 in myeloid leukemogenesis using a mouse model

The chromosomal translocation t(7; 11)(p15;p15), observed in human myeloid leukemia, results in a NUP98 and HOXA9 gene fusion. We generated a transgenic mouse line that specifically expressed the chimeric NUP98-HOXA9 gene in the myeloid lineage. While only 20% of the transgenic mice progressed to leukemia after a latency period, myeloid progenitor cells from nonleukemic transgenic mice still exhibited increased proliferative potential. This suggested that the NUP98-HOXA9 fusion induced a preleukemic phase, and other factors were required for complete leukemogenesis. NUP98-HOXA9 expression promoted the onset of retrovirus-induced BXH2 myeloid leukemia. This phenomenon was used to identify cooperative disease genes as common integration sites (CISs). Meis1, a known HOX cofactor, was identified as a CIS with a higher integration frequency in transgenic than in wild-type BXH2 mice. By the same means we identified further 4 candidate cooperative genes, Dnalc4, Fcgr2b, Fcrl, and Con1. These genes cooperated with NUP98-HOXA9 in transforming NIH 3T3 cells. The system described here is a powerful tool to identify cooperative oncogenes and will assist in the clarification of the multistep process of carcinogenesis.     

Efficacy of combination therapy of interferon-α with ursodeoxycholic acid in chronic hepatitis C: A randomized controlled clinical trial

The efficacy of interferon- therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon- with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon- (group A,n=40) and the other with a combination of interferon- and UDCA (group B,n=40). In both groups, human interferon- (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P=0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significantP=0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P<0.01). Although this combination therapy did not lead to a sufficiently sustained complete response, it could serve as adjuvant antiviral therapy when a suitable dosage and administration period are determined.     

Diagnosis of gallstone ileus by serial computed tomography

An unusual case of choledocholithiasis followed by gallstone ileus documented by serial computed tomography is reported. A 91-year-old woman underwent gastrostomy because she repeatedly developed aspiration pneumonia, and a common bile duct stone was detected. She and her family refused surgery once symptoms resolved. One year later, she presented with increasing, intermittent abdominal pain and nausea. Abdominal computed tomography revealed a common bile duct stone with inflammatory changes, but the patient still refused surgery. Three months later, she was admitted with abdominal pain and vomiting. On admission, plain abdominal radiographs demonstrated proximal small bowel obstruction. A long ileus tube was inserted through the gastric fistula. Two days after admission, gallstone ileus was diagnosed on abdominal computed tomography based on the presence of pneumobilia, disappearance of the common bile duct stone, fluid-filled bowel loops, and the discovery of an impacted stone in the small bowel. Ten and 15 days after admission, repeated computed tomography demonstrated the impacted stone in the terminal ileum. Seventeen days after admission, a laparotomy was performed, and a 5x3-cm gallstone was removed through an ileotomy.     

Clinical value of abnormal findings on brain magnetic resonance imaging in patients with intravascular large B-cell lymphoma

To investigate the prevalence and clinical value of abnormal findings detected via brain magnetic resonance imaging (MRI) in patients with intravascular large B-cell lymphoma (IVLBCL), we identified 33 patients with IVLBCL pathologically diagnosed and evaluated with pretreatment brain MRI. Abnormal findings on brain MRI were categorized into four patterns: (1) hyperintense lesion in the pons on T2-weighted imaging (T2WI), (2) nonspecific white matter lesions, (3) infarct-like lesions, and (4) meningeal thickening and/or enhancement. Abnormal cerebral findings were detected in 29 patients (87.9%). Hyperintense lesion in the pons was the most common finding (n?=?19 (57.6%) patients), followed by nonspecific white matter lesions (n?=?14 (42.4%) patients), infarct-like lesions (n?=?8 (24.2%) patients), and meningeal thickening and/or enhancement (n?=?4 (12.1%) patients). Impaired consciousness was seen in most of the patients with infarct-like lesions (87.5%) but less frequently in patients with hyperintense lesion in the pons (47.4%). We reviewed brain MRI findings in 39 patients with diffuse large B cell lymphoma with central nervous system (CNS) involvement and/or high-risk extranodal lesions for CNS involvement as a control group. In contrast to the patients with IVLBCL, no patient had hyperintense lesion in the pons in the control group (P?<?0.001). Follow-up brain MRI revealed improvement of abnormal findings in most of the patients who responded to chemotherapy. This study highlighted the diagnostic implication of hyperintense lesion in the pons on T2WI and the clinical usefulness of pretreatment brain MRI in IVLBCL even in patients without impaired consciousness.     

Demographic characteristics of 3,659 Japanese patients with obstructive sleep apnea–hypopnea syndrome diagnosed by full polysomnography: associations with apnea–hypopnea index

Information on obstructive sleep apnea-hypopnea syndrome (OSAHS) in Japan has been limited. The purposes of this clinical study were to evaluate the demographic characteristics of Japanese OSAHS patients and to assess how demographic factors are associated with OSAHS severity. We analyzed 3,659 OSAHS patients who underwent polysomnographic evaluation between January 2000 and December 2004 at 11 hospitals in Niigata Prefecture, Japan. Data consisted of apnea-hypopnea index (AHI) and demographic characteristics, including sex, age, and body-mass index, for statistical analysis. Levels of obesity were classified according to the WHO criteria. The male-to-female patient ratio for OSAHS was 4.6, and male patients presented more severe OSAHS than female patients. High AHI and a high proportion of moderate to serious OSAHS (AHI > or = 15) were found among the patients in their 30s, as well as female patients in their 70s and male patients in their 80s. The AHI and the proportion of moderate-to-serious OSAHS (AHI > or = 15) were greater in patients classified as underweight than in normal weight patients. In conclusion, there is a higher male predominance in the prevalence of OSAHS, and in both sexes, the results suggest different pathophysiological mechanisms of deteriorating OSAHS between adults under age 55 and adults 55 years or over. In addition, underweight patients exhibit more severe OSAHS than normal weight patients.     

The relationship between initial clinical manifestation and long-term prognosis of patients with systemic lupus erythematosus

The relationship between clinical manifestations and prognosis was examined and evaluated among systemic lupus erythematosus (SLE) patients. A total of 542 patients with SLE were selected and divided into nine groups according to their main clinical manifestation at the time of initial diagnosis. The relationship between these clinical manifestations and long-term prognosis was evaluated in respect to the survival, remission, relapse rates, the development of a new clinical manifestation, and/or damage index. Patients with neuropsychiatric SLE (NPSLE), accompanied with acute confusional state/seizure disorder, cerebral vascular disease, or pneumonitis had poor survival rates with cause of death related to their major organ involvement. Patients with nephropathy or leukopenia had lower remission rates, and an increase in relapse rates was frequently recognized in patients with pneumonitis. Body damage (damage index) was higher in patients with lupus psychosis, pneumonitis, and/or arthritis. The translation of the main manifestations after diagnosis was confirmed in 64 patients (11.8%), and often observed in patients with autoimmune hemolytic anemia and arthritis. The majority of these manifestations were nephropathy, NPSLE, thrombocytopenia, and pneumonitis, and the prognosis of patients with nephropathy and thrombocytopenia as a new main manifestation had a poor outcome. The results of long-term prognosis in SLE greatly differed with respect to the initial clinical manifestation at the time of diagnosis.     

Cough reflex by ventricular premature contractions

A 72-year-old man was referred for further assessment of a chronic cough. He noticed an association between the episodes of coughing and palpitations. Electrocardiography (ECG) revealed normal sinus rhythm and sporadic unifocal ventricular premature contractions (VPCs). Each cough was preceded by a premature beat. Continuous wave Doppler echocardiography revealed a VPC-induced transient increase in the pulmonary artery blood flow. He was successfully treated for VPCs with oral disopyramide, resulting in subsidence of both the coughing and palpitations. We suspect that the VPC-induced hemodynamic changes in the pulmonary circulation might be responsible for coughing in our patient. Premature contractions should be considered as a possible cause of chronic dry cough in the clinical setting.     

The effect of body position on a free-floating ball thrombus as observed by transesophageal echocardiography

Two cases of free-floating left atrial ball thrombi (FLABT) in association with mitral stenosis were observed by transesophageal echocardiography (TEE). Our report describes the relation between body position and thrombi kinetics. Both cases demonstrated similar kinetics. In the supine and right lateral decubitus positions, the thrombi recoiled from and sometimes became entrapped within the mitral valve. In the sitting and left lateral decubitus positions, the thrombi appeared to be nearly fixed and did not contact with the mitral valve. Our results indicate that the latter two positions prevent thrombi disintegration and incarceration into the mitral valve. Finally, TEE is an extremely useful tool for assessing the safest position for individuals with FLABT.