Myocardial infarction (MI) leads to progressive left ventricular (LV) dilatation and is associated with interstitial fibrosis in the non-infarcted myocardium. The NF-κB signaling pathway plays an important role in ventricular remodeling after MI. Recent studies have indicated that the anti-malarial agent artemisinin can inhibit NF-κB activation, which may attenuate post-infarct myocardial remodeling. In this study, we investigated the effect of artemisinin on post-infarct myocardial remodeling using a rat model of MI. Adult male Sprague Dawley rats were divided into a sham group (n = 10) and MI groups that were treated either with oral gavage of artemisinin (75 mg/kg/day, n = 20) or vehicle (0.5% carboxymethyl cellulose, n = 20) three times a day for 4 weeks. Each treatment was started at 24 hours after ligation of the left anterior descending coronary artery. Four weeks after MI, the artemisinin-treated group showed a significantly improved survival rate compared with that of the vehicle-treated group (65% vs. 40%, P < 0.05). Although infarct size was similar in both groups, echocardiography showed significant improvements in cardiac function and left ventricular dimensions in the artemisinin-treated group. Moreover, the degree of myocardial fibrosis and elevated levels of fibrosis-related factors [transforming growth factor-β1, collagen type I, matrix metalloproteinase (MMP)-2 and MMP-9] in the non-infarcted myocardium were remarkably ameliorated by artemisinin (all P < 0.05). Importantly, artemisinin inhibited the NF-κB pathway by blocking IKBα phosphorylation. In conclusion, artemisinin may attenuate post-infarct myocardial remodeling by down-regulating the NF-κB pathway.
Laparoscopic colectomy has been reported as an alternative for treatment of colorectal cancer. However, its long-term efficacy and safety remain obscure. The purpose here was to review our experience with laparoscopic colectomy in 899 patients between June 2001 and December 2008. Of them, 43 patients were converted to open surgery and 846 accepted laparoscopic colorectomy successfully. Among these 846 patients, 790 patients underwent radical resection and 56 patients underwent palliative resection. Only 1 patient died from perioperative pulmonary infection; thus the mortality was 0.12% (1/846). The morbidity of perioperative complications was 18.20% (154/846): intraoperative complication rate was 4.49% (38/846) and the most common intraoperative complication was subcutaneous emphysema and hypercapnia (1.65%, 14/846); postoperative complication rate was 13.71% (116/846) and the most common postoperative complication was ileus (4.37%, 37/846). The overall followed-up rate was 86.41% (731/846, 680 for radical operations and 51 palliative operations). Postoperative deaths happened to 139 patients, including 112 after radical operation and 27 after palliative resection. Of these 112 patients, 97 deaths were cancer-related (14.26%, 97/680) and 15 deaths were non-cancer-related. There were 10 patients encountered local recurrence (1.47%, 10/680) and 105 for metastasis (15.44%, 105/680) after radical operation. Forty-two patients are still alive with tumor. Overall survival rate was 80.98% (592/731), 3-year disease-free survival (DFS) rate after radical operation was 78.0%, and 3-year DFS rate after radical operation for stage I, stage II, and stage III was 89.0%, 85.0%, and 65.0%, respectively. In conclusion, laparoscopic colorectal resection is a feasible and safe technology for colorectal cancer.
Individuals who survive near drowning often suffer from complicated infections, including multi-organ and polymicrobial events. This pattern may be especially pronounced among patients exposed to infectious agents during catastrophic events like that of the Great East Japan Earthquake and the associated tsunami disaster. We report here on a patient who presented with Escherichia coli (E. coli) pneumonia in combination with fungal sinusitis and meningitis. A 73-year-old woman survived the tsunami that engulfed the Sanriku coast. By the time of hospital admission, the patient exhibited high fever, severe cough, and sputum production. Chest X-ray and CT scan showed consolidation in the left upper lobe. Administration of an antibacterial agent improved this pneumonia. However, the patient's consciousness was increasingly impaired. Brain CT showed the low-density lesions and partial high-density spot in the sinus, which suggests the fungal infection. MRI showed the inflammation in the sinus spread into the central nerve system. The examination of the cerebrospinal fluid showed the low glucose level, high mononuclear cell count, and highβ-D glucan level, the findings of which supported the diagnosis of fungal meningitis. Although the patient improved temporarily in response to combination treatment with anti-fungal agents, no further improvement was seen. In conclusion, this patient, who suffered from infections of pneumonia, sinusitis, and meningitis, presented a quite rare clinical progress. We propose that fungal infection should be taken into consideration in individuals who suffered near drowning, a profile expected to be frequent among tsunami survivors.
Severely and multiply disabled children (SMDC) are frequently affected in more than one area of development, resulting in multiple disabilities. The aim of the study was to evaluate the efficacy of music therapy in SMDC using monitoring changes in the autonomic nervous system, by the frequency domain analysis of heart rate variability. We studied six patients with SMDC (3 patients with cerebral palsy, 1 patient with posttraumatic syndrome after head injury, 1 patient with herpes encephalitis sequelae, and 1 patient with Lennox-Gastaut syndrome characterized by frequent seizures, developmental delay and psychological and behavioral problems), aged 18-26 (mean 22.5 ± 3.5). By frequency domain method using electrocardiography, we measured the high frequency (HF; with a frequency ranging from 0.15 to 0.4 Hz), which represents parasympathetic activity, the low frequency/high frequency ratio, which represents sympathetic activity between the sympathetic and parasympathetic activities, and heart rate. A music therapist performed therapy to all patients through the piano playing for 50 min. We monitored each study participant for 150 min before therapy, 50 min during therapy, and 10 min after therapy. Interestingly, four of 6 patients showed significantly lower HF components during music therapy than before therapy, suggesting that these four patients might react to music therapy through the suppression of parasympathetic nervous activities. Thus, music therapy can suppress parasympathetic nervous activities in some patients with SMDC. The monitoring changes in the autonomic nervous activities could be a powerful tool for the objective evaluation of music therapy in patients with SMDC.
A skin flap is a piece of skin that has its own blood supply, which is useful to repair large skin defects and deep wounds in plastic surgery. However, partial skin flap necrosis usually occurred. Bone marrow mesenchymal stem cells (BM MSCs) are effective in improving the ischemic flap survival, but their clinical application is restricted by their limited source. Human umbilical cord matrix stem (HUCMS) cells are easily isolated in a large number, compared to BM MSCs. In this study, we evaluated the therapeutic potential of HUCMS to improve the survival of ischemic skin flap. HUCMS cells were characterized with surface markers, and were labeled with 5-acetylene base-2 'deoxidizing uracil nucleoside (EdU) in vitro. Twenty male immunodeficient BALB/c mice with an epigastric flap were randomly divided into two groups. HUCMS cells or Dulbecco's Modified Eagle Medium (DMEM) were injected into the subcutaneous flap tissues. On the 7th postoperative day, flap survival, capillary density, levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), and EdU-positive cells in the skin flap were examined. Results showed that flap survival rate was higher in the HUCMS cell group (P < 0.05). Capillary density, VEGF level, and bFGF level were higher in the HUCMS cell group (P < 0.05). EdU-labeled HUCMS cells were mainly distributed in the subcutaneous flap tissues. These findings suggest that HUCMS cells can improve the survival of ischemic skin flap by promoting vascularization, which may be attributed to the increased expression of VEGF and bFGF.
High prevalence of deep vein thrombosis (DVT) in disaster shelters has been reported in the aftermath of earthquakes in Japan. Calf DVT was examined using sonography in the shelters after the Great East Japan earthquake on March 11, 2011. By the end of July 2011, 701 out of 8,630 evacuees suspected with calf DVT, judged by inspections or medical interviews, were examined in 32 shelters, and 190 evacuees were confirmed to have calf DVT. The prevalence of DVT was 2.20%, which was 200 times higher than the usual incidence in Japan. The DVT prevalence seemed to decrease with time. By the end of May, a significantly higher prevalence of DVT was found in tsunami-flooded shelters (109 of 3,871 evacuees; 2.82%) than in non-flooded shelters (53 of 3,155 evacuees; 1.68%). After June, its prevalence was still higher (18/541; 3.33%) in tsunami-flooded shelters than in non-flooded shelters (10/1063; 0.94%). The cause of the high prevalence of DVT was supposed to be dehydration due to the delay in supplying drinking water, vomiting, and diarrhea experienced by the evacuees because of a shortage of clean water to wash their hands. Dehydration was especially noticed in women because they restricted themselves of water intake to avoid using unsanitary toilet facilities. Moreover, crowded shelters restricted the mobility of elderly people, which would exacerbate the prevalence of DVT. Those deteriorated and crowded shelters were observed in tsunami-flooded areas. Therefore, long-term shelters should not be set up in flooded areas after tsunami.
Our new lessons of nurturing life to make happiness and well-being of geriatric patients suggest comprise several important steps. First, geriatric patient care should not be delegated to specialists who focus on individual organ system. Instead, we should respond to the patient's condition based on comprehensive assessment to identify the single pathogenesis. Second, we should appreciate that the behavioral and psychological symptoms of dementia (BPSD) often reflect the behavioral and psychological symptoms of the caregiver (BPSC), and in particular the caregiver's attitude. Third, pleasant stimulations to the limbic system should receive more emphasis than attempting brain training in atrophied portions of the neocortex. Fourth, we should aim not for “successful aging,” but for “balanced aging.” Fifth, we should rely less on drug-based therapy and utilize more non-pharmacologic approaches to appropriate therapy. Geriatric patients should be cared for based on our new lessons of nurturing life rather than the heavily medicalized treatment modalities that are in wide use today.
The complement system, the major component of the innate immune functions resisting microbial infection, includes the classical complement pathway, the alternate pathway, and the mannose-binding lectin pathway. All of these merge at the level of complement component (C) 3. Complement factor H (CFH), a soluble complement mediator in blood, regulates alternate pathway activation; a conformational change of C3 molecules by C3 convertases leads to an enzyme complex formation resulting in opsonization and cell lysis. Clinical manifestations arising from CFH gene (CFH) abnormalities include hemolytic uremic syndrome and membranoproliferative glomerulonephritis. We encountered a 24-year-old woman initially diagnosed with C3 glomerulonephritis associated with persistently low circulating C3. Definitive diagnosis of C3 glomerulonephritis was made from immunohistologic demonstration of isolated mesangial C3 deposits. The biopsy specimen showed moderately increased mesangial proliferation, without thickening of the glomerular capillary walls. Genetic analysis disclosed a homozygous CFH missense mutation, a G-to-T transversion at nucleotide 3,048 in exon 18, resulting in substitution of Asp for Glu at position 936. A low serum CFH concentration (110 μg/mL) might reflect the consequences of this CFH mutation. C3 glomerulonephritis is associated with a CFH mutation, the mutation of which results in the unexpected activation of alternate pathway complement with clinical laboratory fluctuations, such as varying reduction of serum CFH and C3. The finding of a patient with a CFH mutation associated with C3 glomerulonephritis represents an opportunity to expand the phenotypic spectrum of the CFH mutations.
Patients with renal failure undergoing hemodialysis often have muscle cramps during and after the dialysis therapy. Muscle cramps are defined as the sudden onset of a prolonged involuntary muscle contraction accompanied with severe pain, resulting in early termination of a HD session and inadequate dialysis. The etiology of the cramps is unknown and effective anti-cramp medicine is not available. We have hypothesized that water-soluble vitamins are deficient in HD patients. Accordingly, we administrated biotin to 14 patients who had frequent muscle cramps during HD sessions. Oral administration of 1 mg/day biotin promptly reduced the onset and the severity of cramps in 12 patients both during and after HD. Then, the plasma biotin levels were measured by an enzyme-linked immunosorbent assay method (ELISA) in HD patients, including 14 patients with cramps and 13 patients without cramps, and 11 healthy volunteers. Plasma biotin levels were elevated in 27 HD patients at baseline compared with healthy volunteers [451 (377 - 649) vs. 224 (148 - 308) ng/l, median (lower-upper quartiles); p < 0.0001]. Unexpectedly, among the 14 cramp patients, the biotin levels were significantly higher in biotin-ineffective 7 patients than biotin-effective 7 patients [1,064 (710 - 1,187) vs. 445 (359 - 476) ng/l; p < 0.001]. Thus, the biotins measured by ELISA may consist of not only intact biotin but also its metabolites that do not function as a vitamin. In conclusion, biotin administration is one choice to relieve HD patients from muscle cramps regardless of their elevated plasma biotin levels.
Myocarditis is an inflammatory disease of the heart and a major cause of dilated cardiomyopathy that can lead to heart failure and sudden death in young adults. Giant cell myocarditis is a severe heart disease of unknown causes and is defined histopathologically as diffuse myocardial necrosis with multinucleated giant cells in the absence of sarcoid-like granulomata. Giant cell myocarditis is often studied using a model of experimental autoimmune myocarditis (EAM) in rats. Emodin is an important component of traditional Chinese herb rhubarb, and has well-documented anti-inflammatory effect. The current study determined the potential efficacy of emodin using a rat model of EAM. Male Lewis rats (6 weeks of age) were immunized on days 0 and 7 with a porcine cardiac myosin at both footpads to induce EAM. Simultaneously with the immunization, rats received emodin (50 mg/kg/day) or distilled water by intragastric administration for 3 weeks (8 animals/group). Likewise, eight animals were immunized with adjuvant alone and treated with distilled water. The immunization significantly enlarged the hearts due to inflammatory lesions. Emodin treatment significantly improved left ventricular (LV) function and reduced the severity of myocarditis, as reflected by echocardiographic and histopathological examination. Emodin treatment decreased the serum levels of proinflammatory cytokines tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Nuclear factor-κBp65 (NF-κBp65), a rapid-response transcription factor that regulates proinflammatory cytokines, in the myocardial tissue was also suppressed in the treated rats. In conclusion, emodin could ameliorate EAM, at least in part, by decreasing the production of proinflammatory cytokines TNF-α and IL-1β.
Rosai-Dorfman disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare non-neoplastic disease that is characterized by a proliferation of histiocytes mostly in lymph nodes. However, the etiological mechanism of RDD still remains unclear. Intrathoracic manifestations of RDD are only observed in 2% of patients with RDD. Spontaneous remission was reported in about 20% of patients with RDD; however, there are no reports of an intrathoracic manifestation of RDD that showed a spontaneous remission within a short period of time. A 64-year-old Japanese female with dry cough and left chest pain was introduced to our hospital, and computed tomography revealed a pulmonary nodular lesion and enlarged mediastinal lymph nodes. The bronchial specimen obtained from the abnormal mucosal lesion showed massive infiltration of histiocytes underneath the bronchial epithelium and emperipolesis, a typical pathological finding in RDD, which is characterized by the presence of histiocyte-like cells engulfing intact lymphocytes. These histiocytes were positive for S-100 (one of the known positive markers of RDD) and for CD68 (a marker for various cells of the macrophage lineage). All these findings are consistent with the diagnosis of RDD. These radiological and endoscopic findings spontaneously resolved within four months without any treatment. In conclusion, clinicians should be aware of this disease as one of differential diagnoses of pulmonary nodules in combination with mediastinal lymph node enlargements, especially in order to differentiate it from primary lung cancer.