Objective Fibrogenic cytokines, such as transforming growth factor-beta 1 play a central role in the progression of liver fibrosis. Recently, functional gene polymorphisms in these cytokines have been identified, and some reports have validated the presence of associations between these polymorphisms and disease progression. Connective tissue growth factor (CTGF) is a stimulating factor for fibroblast proliferation and matrix production. This study aimed to examine the relationship between CTGF gene polymorphisms and the progression of hepatitis C virus (HCV)-related chronic liver disease, as well as the incidence and prognosis of hepatocellular carcinoma (HCC). Methods A review was conducted among 235 HCV patients (117 patients with chronic hepatitis (CH) and 118 patients with liver cirrhosis (LC)). The CTGF gene polymorphism (rs6918698; -945 G/C) was identified according to the chimeric cycling probe method. The rate of liver fibrosis progression was measured using two liver fibrosis prediction formulas, the Forns index and the FibroIndex. All HCC patients were followed regularly every month. Results The frequency of the -945 C allele was higher among the LC patients than the CH patients. Regarding the rate of liver fibrosis progression over five years, C homozygotes tended to exhibit a faster rate than G carriers, although the difference was not significant. Among the LC patients, the C homozygotes demonstrated lower prothrombin times, higher rates of indocyanine green retention and higher Child-Pugh scores than the G carriers. There were no significant tendencies in the genotype distribution, irrespective of the status of HCC. However, the prognosis of HCC was poorer for the C homozygotes than for the G carriers. Conclusion A CTGF -945 C homozygote status is a significant risk factor for the progression of HCV-related chronic liver disease, including HCC.
Objective The supplementation of oral branched-chain amino acid (BCAA) granules is known to improve energy metabolism in cirrhotic patients, but not those with hepatocellular carcinoma (HCC). We aimed to clarify whether BCAA granules improve energy metabolism in HCC patients after radiofrequency ablation (RFA). Methods We performed a prospective cohort study (UMIN000004624) involving 40 HCC patients who underwent RFA at Kobe University Hospital. Indirect calorimetry and urinary/blood biochemical examinations were performed before and seven days after RFA. Blood biochemical examinations were also conducted three months after RFA. The patients treated with and without BCAA supplementation were compared, and univariate factors were statistically examined. Results The non-protein respiratory quotient (npRQ) and albumin levels before RFA were significantly lower in the BCAA group than in the control group (p=0.024 and 0.005). The npRQ ratio (seven days after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.019). In addition, the albumin ratio (three months after/before RFA) was significantly higher in the BCAA group than in the control group (p=0.018). Conclusion Supplementation with BCAA granules improves energy metabolism in addition to the liver function after RFA. Improvements in the liver function may result in consistently adequate treatment for HCC recurrence after RFA.
Objective Several studies have shown that arterial stiffness and ventricular dysfunction are increased in individuals with type 2 diabetes. Aortic stiffness (AS) reflects the mechanical tension and elasticity of the aorta, and increased aortic stiffness is a risk factor for cardiovascular disease. The aim of this study was to evaluate the degree of aortic stiffness and its relationship with the left ventricular (LV) function in patients with prediabetes and healthy control subjects. Methods The study groups were composed of 50 patients with prediabetes and 47 healthy adults with similar demographic characteristics. The LV systolic and diastolic functions were assessed using standard two dimensional (2D) echocardiography, M-mode echocardiography, pulsed-wave (PW) echocardiography and tissue Doppler echocardiography. The degree of aortic strain and distensibility were calculated based on the aortic diameters measured on M-mode echocardiography at a level 3 cm above the aortic valve and the blood pressure values obtained on sphygmomanometry. Results There were significant differences between the prediabetic and control groups in the degree of aortic strain (4.7±2.8% vs. 14.9±4.5%; respectively, p<0.001) and distensibility (2.0±1.5 vs. 6.8±2.3; 10-3 cm2 dyn-1, respectively, p<0.001). In addition, significant differences were observed between the patient and control groups in the parameters of the LV systolic and diastolic functions. The left atrial diameter was significantly larger in the prediabetics than in the controls (35.9±3.9 vs. 33.7±4.2; respectively, p=0.027). Conclusion AS is increased in patients with prediabetes. In addition, there is a significant relationship between the degree of aortic stiffness and the LV function in this patient population. Therefore, the aortic elasticity parameters calculated on 2D echocardiography are useful for predicting early cardiovascular risks in prediabetics.
Objective The goal of this study was to clarify the clinical manifestation of hypercalcemia due to hypoadrenalism in hemodialysis (HD) patients. Methods We retrospectively analyzed the clinical characteristics of five HD patients who had presented with hypercalcemia due to adrenal insufficiency (age: 69±7 [58-75] years old, time on HD: 13±11 [2-32] years). We conducted corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) stimulation tests. We also examined serum bone turnover markers before and after glucocorticoid replacement. Results All patients had critical illnesses at the onset of hypercalcemia. They had at least one symptom, such as eosinophilia, hypoglycemia, or fever. The prevalence of hypercalcemia due to adrenal insufficiency was 1.3% in maintenance HD patients on admission. The causes of adrenal insufficiency were isolated ACTH deficiency, pituitary apoplexy, pituitary atrophy, glucocorticoid withdrawal syndrome, and unilateral adrenalectomy. Serum calcium (Ca) levels corrected by serum albumin were maximally increased to 12.9 to 14.3 mg/dL in four anuric HD patients and mildly elevated to 10.4 mg/dL in a patient with residual diuresis. Their basal serum cortisol levels ranged from <1.0 to 15.4 μg/dL. Single CRH injections failed to increase serum cortisol in any of the patients. Glucocorticoid replacement acutely normalized serum Ca and decreased levels of carboxy-terminal telopeptide of type I collagen, a marker of bone resorption. Conclusion Adrenal insufficiency could therefore be an occult cause of hypercalcemia in anuric HD patients who are critically ill.
Objective The Japan Diabetes Society (JDS) has recommended target levels of glycemic control based on guidelines for the management of diabetes mellitus (DM). The Japan Society of Ningen Dock created a database of subjects receiving annual health examinations nationwide. Using this database, we evaluated the efficacy of current treatment for patients with DM based on the JDS recommendations. Methods This multicenter, retrospective study was conducted using data obtained from 21 institutions across Japan. In order to assess the level of glycemic control in the Japanese population, we analyzed previously obtained measurements of HbA1c in 7,180 patients 20 to 79 years of age (mean age: 57.9±8.7 years, 6,007 men and 1,173 women) taking DM medications. Results According to the JDS guidelines, 44.7% of the patients fell into the good glycemic control group, with an HbA1c level of <7.0% while 22.4% were classified into the poor glycemic control group, with an HbA1c level of ≥8.0%. The control of other arteriosclerosis risk factors deteriorated as the glycemic control deteriorated. Lifestyle factors were strongly found to be associated with glycemic control in the patients receiving DM treatment. Conclusion Aggressive lifestyle modification is needed to improve glycemic control in patients with DM.
Objective Sepsis is one of the leading causes of mortality in critically ill patients, and providing a timely diagnosis and early intervention is necessary for successful treatment. Procalcitonin (PCT) may be a better marker of sepsis than conventional inflammatory markers. The aim of this study was to evaluate the clinical utility of the PCT level as a marker of sepsis. Methods Forty-five patients with sepsis, 24 patients with pneumonia who did not meet the SIRS criteria (PN) and 56 controls were enrolled in this study. The levels of PCT and other serum markers were measured, and their utility as markers of sepsis was assessed. Results The serum PCT levels exhibited statistically significant differences between the three groups (p<0.0001). The PCT levels in the sepsis group (29.3±85.3 ng/mL) were significantly higher (p<0.001) than those observed in the PN group (0.34±8.6 ng/mL) and the control group (0.74±2.1 ng/mL), according to a post hoc analysis. There were no differences in the white blood cell (WBC) counts or C-reactive protein (CRP) levels between the three groups. Fourteen of the 45 patients with sepsis had positive microbiological blood cultures (Gram-positive cocci [GPC] in seven patients, Gram-negative rods [GNR] in six patients, other types of bacteria in one patient). The 13 patients with GNR or GPC were categorized into the GNR group or GPC group according to the identified pathogens. The serum PCT levels were significantly higher in the GNR group (149.8±199.7 ng/mL) than in the GPC group (19.1±41.8 ng/mL) (p<0.05), although there were no differences in the WBC counts or CRP levels between these groups. When the cut-off value for the PCT level was set at 16.9 ng/mL, the sensitivity and specificity for the detection of GNR infection were 85.7% and 83.3%, respectively. Conclusion The PCT level is a potentially useful marker of the type of causative pathogen in patients with sepsis whose measurement may facilitate the selection of appropriate empiric antibiotic treatment.
Intramural hematomas of the colon are rare. Intramural hematomas of the gastrointestinal tract often result from blunt trauma, although they may also occur spontaneously in patients taking anticoagulants or those with blood dyscrasia. Affected patients present with abdominal pain and lower gastrointestinal bleeding, as well as occasional signs of intestinal obstruction. The diagnosis is made using colonoscopy and abdominal CT. Resection of the involved bowel segment is accepted as the standard therapy; however, experience with conservative treatment has also been reported. We herein report the case of a 62-year-old woman taking warfarin who was diagnosed with a colonic intramural hematoma and completely recovered with conservative management.
We herein present a rare case of acute appendicitis with intestinal malrotation. Coronal images of contrast-enhanced computed tomography (CT) revealed the small intestine on the right side and the large intestine on the left side, thus indicating intestinal malrotation (non-rotation type). In addition, an enhanced, tubular, fluid-filled structure was detected attached to the cecum, which was located superior to the urinary bladder, suggesting acute appendicitis. The present study shows that coronal CT images provide important information for the diagnosis and treatment of acute appendicitis in patients with intestinal malrotation.
Whether recombinant tissue-type plasminogen activator (rt-PA) therapy can be administered in acute stroke patients treated with dabigatran remains controversial. We administered rt-PA (0.6 mg/kg) in an acute stroke patient treated with dabigatran (110 mg bid) whose activated partial thromboplastin time (APTT) was 37.1 seconds 113 minutes after onset, 10 hours after the last dose of dabigatran. His symptoms improved from the National Institute of Health Stroke Scale score of 10 to 1 after treatment without hemorrhagic complications. The administration of rt-PA therapy is feasible in acute stroke patients on dabigatran when taking into account the APTT and time from the last dose.
Congenitally corrected transposition of the great vessels (CTGV) is a rare congenital cardiac and great vessel abnormality. The anomalous inversion of the ventricles and great vessels makes performing catheter ablation difficult. We herein report a successful case of atrioventricular node reentrant tachycardia ablation in a patient with coexistent CTGV and situs inversus.
We herein describe two patients with Brugada syndrome in whom J-waves were successfully modified by drugs. Case 1 was a 54-year-old man who presented with repeated ventricular fibrillations (VF) and J-point elevation in the right precordial and lateral leads. After administration of cilostazol (200 mg/d), J-waves disappeared and coved-type ST-segment elevation changed to a saddleback-type for 25 months. Case 2 was a 31-year-old man who presented with a VF storm and J-point elevation in the lateral leads. After administration of quinidine (300 mg/d), J-waves and coved-type ST-segment elevation disappeared for 20 months. J-wave disappearance and coved-type ST-segment elevation were followed by VF suppression, probably due to transient outward potassium current (Ito) suppression.
A 14-year-old patient was diagnosed with hypertrophic cardiomyopathy associated with Wolff-Parkinson-White syndrome. The two-dimensional speckle tracking strain method showed normal left ventricular local contraction, but the peak systolic longitudinal strain of the right ventricular (RV) anterior wall was earlier than that of the septal wall. As expected, the location of the accessory pathway was at the RV anterior wall. The patient's RV local contraction was normalized by successful radiofrequency application.
Acetaminophen overdose can lead to severe liver and kidney failure; however, the risk of therapeutic doses in healthy individuals causing acute kidney injury (AKI) is less clear. We herein describe the cases of two young adults with renal biopsy-proven acute tubular necrosis under a therapeutic dose of acetaminophen. The first patient exhibited mild reversible renal insufficiency, whereas, in the second case, the patient demonstrated a slightly increased serum creatinine level and enlarged kidneys and the administration of contrast media and antibiotics may have worsened the renal dysfunction, leading to the need for temporal hemodialysis. Physicians should be aware of the risk of acetaminophen causing AKI and avoid administering other nephrotoxic agents in such cases.
A 67-year-old woman who was followed as a patient with bronchial asthma for 1.5 years visited our hospital with progressive dyspnea. Although the chest radiography findings were normal, a chest computed tomography scan revealed a mass obliterating the intrathoracic tracheal lumen. The patient's symptoms disappeared immediately after tumor excision, and no recurrence was observed during a 1.5-year follow-up period. Microscopically, the tumor was composed of densely packed polygonal-, oval- and spindle-shaped cells that were positive for pan-cytokeratin, α-smooth muscle actin and p63. These pathological findings confirmed the diagnosis of benign myoepithelioma. Chest physicians should recognize that benign myoepithelioma can develop in the trachea, although it is very rare.
A 67-year-old woman was admitted to our hospital due to dyspnea on exertion with lung abnormal shadows. A transbronchial lung biopsy specimen demonstrated eosinophilic pneumonia (EP). The patient also exhibited heliotrope eyelids without muscle weakness, which led to a diagnosis of amyopathic dermatomyositis (ADM). As we were unable to find any other causes of EP, we diagnosed her as having EP associated with ADM. Dermatomyositis (DM) has been reported to be associated with various interstitial lung diseases; however, only one case of EP associated with DM has been reported. We herein report the first case of EP complicated with ADM.
Presently, 6 cases of IgG4-related pleuritis have been reported. We encountered a patient who developed chylothorax due to IgG4-related disease. To our knowledge, such patients have not been reported. This patient developed right-sided chylothorax and left-sided non-chylothorax lymphocyte-predominant pleuritis. Elevated serum and pleural IgG4 concentrations and histopathological analysis of pleural biopsy confirmed the diagnosis of IgG4-related pleuritis. Left-sided pleuritis improved with corticosteroid therapy, but right-sided chylothorax persists. IgG4-related disease can be one cause of chylothorax.
We herein report a 74-year-old woman who presented with autoimmune hemolytic anemia (AIHA) associated with pleural solitary fibrous tumor (SFT). Her AIHA was initially treated with 1 mg/kg daily of oral prednisolone (PSL) for 2 months, which had a limited effect. However, after surgical tumor resection, the patient showed remarkable improvement of AIHA with normalizations of serum lactate dehydrogenase and bilirubin levels, and we were able to rapidly reduce the PSL dosage. This is the first description of a case of AIHA caused by SFT.
A 74-year-old right-handed woman without cognitive impairment suddenly developed nonfluent aphasia. Brain MRI showed acute infarction in the right frontal lobe and insula without involvement of the corpus callosum. A neurological examination demonstrated not only transcortical motor aphasia, but also ideomotor apraxia and right hand predominant constructional apraxia (CA). To date, right hand predominant CA has only been reported in patients with corpus callosum lesions. The right hand predominant CA observed in our patient may be associated with the failure to transfer information on the spatial structure from the right hemisphere to the motor cortex of the left hemisphere.
A 57-year-old woman was admitted with recurrent episodes of right frontal headache. Head magnetic resonance imaging (MRI) revealed extensive thickening and enhancement of the right frontal dura, muscle and fascia, as well as abnormal signal intensity and enhancement of bone marrow at the lesions. Synovitis-acne-pustulosis-hyperostosis osteomyelitis (SAPHO) syndrome was diagnosed based on the patient's 8-year history of treatment of palmoplantar pustulosis and abnormal accumulations in the right temporal, sternum, and left medial clavicula on bone scintigraphy. SAPHO syndrome may be associated with skull lesions, which can contribute to the onset of repeated headache or dural thickening, thus these symptoms should be recognized as manifestations of this syndrome.
Emery-Dreifuss muscular dystrophy (EDMD) is caused by mutations in the EMD gene on the X chromosome, which codes for emerin, an inner nuclear membrane protein. Monoclonal antibodies against the N-terminus of emerin protein are used to screen for emerin deficiency in clinical practice. However, these tests may not accurately reflect the disease in some cases. We herein describe the identification of a splice site mutation in the EMD gene in a Japanese patient who suffered from complete atrioventricular conduction block, mild muscle weakness and joint contracture, and a persistently elevated serum creatine kinase level. We used multiple antibodies to confirm the presence of a novel truncating mutation in emerin without the transmembrane region and C-terminus in the skeletal muscle.
A 67-year-old man was admitted due to weakness, coughing, shortness of breath and fever. He had decreased breath sounds in the left lung and muscle weakness in the lower and upper extremities. Chest imaging showed a mass in the left lung, and a biopsy revealed small cell lung cancer. The nerve conduction velocity was decreased, and anti-GM1 IgG antibodies were positive. The patient showed a temporary neurologic recovery following the administration of cancer chemotherapy, although he eventually died of progression of lung cancer. As a result of the almost simultaneous symptomatic development of lung cancer and Guillain-Barré syndrome, this case may be considered to involve a paraneoplastic neurologic syndrome.
A 33-year-old homosexual Japanese man who admitted to having sex with men presented with a two-week history of dyspnea and fever. Chest imaging showed diffuse pulmonary frosted-glass-like shadows. A blood test revealed positive HIV antibodies with a CD4 cell count of 66/μL. Bronchoalveolar lavage identified pneumocystis. Although the patient exhibited a transient response to anti-pneumocystis treatment and mega-dose steroid pulse therapy, he eventually died from respiratory failure. An autopsy suggested massive cytomegalovirus and pneumocystis pneumonitis. The pulmonary co-infection with cytomegalovirus may have been worsened by the use of mega-dose steroids, and such therapy should be avoided in patients with a high HIV viral load and low CD4 count.