Tumor endothelial marker 1 is upregulated in heart after cardiac injury and participates in cardiac remodeling.

Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.

Soluble tumor endothelial marker 1 in heart failure with reduced ejection fraction: A pilot study.

Background: Tumor endothelial marker 1 (TEM1/CD248) is a transmembrane protein that expresses in mesenchymal lineage derived cells during embryogenesis and becomes undetectable in normal adults after birth. Re-expression of TEM1 is found in organ fibrosis, wound healing and cardiac remodeling indicating its potential role in heart failure (HF). The purpose of this study is to explore the role of soluble TEM1 (sTEM1) in patients with HF with reduced ejection fraction. Methods: We examined endomyocardial biopsy specimens from three HF patients and blood samples from 48 patients admitted for acute decompensated HF (age 72 years, men 61.7%). The expression of TEM1 in cardiac tissue and concentrations of sTEM1 in plasma were evaluated. Cultured rat cardiomyocytes (H9c2) and human cardiac fibroblasts (HCF) were stimulated with hypoxia or transforming growth factor beta (TGF-ß) to observe the release of sTEM1 into culture media. The conditioned media of hypoxia-stimulated H9c2 cells was harvested and added into cultured cardiac fibroblast to evaluate its biological effect. Results: Immunofluorescence study of biopsy specimens from three HF patients showed TEM1 expression in cardiomyocytes and cardiac fibroblasts. The plasma level of sTEM1 was significantly higher in patients (0.90 ± 0.23 vs. 0.33 ± 0.10 ng/mL, p = 0.032) with LVEF ≤ 35% compared with those with LVEF 36-49%. The sTEM1 levels had correlations with HF biomarkers of cardiac fibrosis, including growth differentiation factor-15 (GDF-15) and galectin-3. There was a significant increase in sTEM1 levels in the cultured media of H9c2 and HCF after being stressed with hypoxia or TGF-ß. The conditioned media derived from hypoxia-stimulated H9c2 cells significantly increased cell proliferation of cardiac fibroblasts. This effect was partially reversed by anti-TEM1 antibody. Conclusion: This pilot study demonstrated that cardiac TEM1 expression was upregulated in HF. The levels of sTEM1 were significantly higher in HF patients with LVEF ≤ 35% and correlated with other biomarkers of cardiac fibrosis. In vitro study proved that functional sTEM1 was released into cultured media after stressing cardiomyocytes and HCF.

The role of vascular smooth muscle cell membrane-bound thrombomodulin in neointima formation.

BACKGROUND AND AIMS: Thrombomodulin (TM) is an endothelial cell membrane-bound anticoagulant protein expressed in normal arteries. After vascular injury, medial and neointimal smooth muscle cells (SMCs) exhibit large amounts of TM. The purpose of this study was to investigate the physiological significance of vascular SMC-bound TM. METHODS: The morphology, expression of phenotype markers and cell behaviors of cultured aortic SMCs after knockdown of TM were observed. Transgenic mice with SMC-specific TM deletion were generated, and carotid neointima formation was induced by carotid ligation. RESULTS: Cultured human aortic SMCs displayed a synthetic phenotype with a rhomboid-shaped morphology and expressed TM. TM knockdown induced a spindle-shaped change in morphology with an increased expression of contractile phenotype marker and decreased expression of synthetic phenotype marker. TM knockdown not only attenuated the proliferation of SMCs but also reduced tumor necrosis factor-α-induced nuclear factor-κB activation and interlukin-6 production. In a carotid artery ligation model, transgenic mice with SMC-specific TM deletion (SM22-cretg/TMflox/flox) had significantly less cellular proliferation in arterial walls compared with wild type mice (SM22-cretg/TM+/+). The neointima area and neointima/media area ratio were smaller in SM22-cretg/TMflox/flox mice at 4 weeks after ligation. CONCLUSIONS: Our results indicate that vascular SMC-bound TM plays a role in changes of the SMC phenotype. It also influences SMC cell behavior and injury-induced neointima formation.

Recombinant Thrombomodulin Exerts Anti-autophagic Action in Endothelial Cells and Provides Anti-atherosclerosis Effect in Apolipoprotein E Deficient Mice.

Stress-induced alteration in endothelial cells (ECs) integrity precedes the development of atherosclerosis. Previous studies showed that the soluble recombinant thrombomodulin (rTM) not only increases ECs proliferation but also exerts anti-apoptotic activity in ECs. However, the functional significance of soluble rTM on autophagy-related apoptosis in ECs is still undetermined. Implicating a cytoprotective role for rTM in persistent serum starvation (SS)-induced autophagy in cultured ECs, we found that treatment of rTM decreased the expression of SS-induced autophagy-related proteins, ATG5 and LC3, and the formation of autophagosomes through activation of AKT/mTOR pathway. In addition, treatment of rTM decreased SS-induced EC apoptosis, but this effect of rTM could not be recapitulated by co-treatment with a potent autophagy inducer, rapamycin and in ECs with ATG5 knockdown. In human atherosclerosis specimens, expression of autophagy markers, ATG13 and LC3, were more abundant in aortic intimal ECs with severe atherosclerosis than those without atherosclerosis. Moreover, compared to saline treatment group, administration of rTM reduced LC3 and ATG13 expression, intimal EC apoptosis, and atherosclerotic lesion severity in the aorta of apolipoprotein E deficient mice. In conclusion, treatment with rTM suppressed stress-induced autophagy overactivation in ECs, provided ECs protective effects, and decreased atherosclerosis in apolipoprotein E deficient mice.

Soluble thrombomodulin is a paracrine anti-apoptotic factor for vascular endothelial protection.

BACKGROUND: Thrombomodulin (TM) is an endothelial cell (EC) membrane-bound anticoagulant protein that has novel direct cellular effects. TM is shed from EC and becomes soluble form (sTM) in plasma. Higher sTM levels in healthy subjects are associated with lower cardiovascular risk, suggesting that sTM possesses a protective role. The purpose of the study was to evaluate the effect of sTM on vascular endothelium. METHODS AND RESULTS: Apoptosis of cultured ECs was induced via serum starvation. EC-bound TM was released into the medium after serum starvation. The medium conditioned by serum-starved EC decreased apoptosis in another set of cultured EC. Direct treatment with sTM reduced EC apoptosis and decreased pro-apoptotic protein expression. TM knockdown in EC exacerbated the rate of serum starvation-induced apoptosis. Treatment of sTM activated the phosphatidylinositol 3-kinase (PI3 kinase)-protein kinase B/Akt survival pathway and suppressed the death pathway, c-Jun N-terminal kinase. We found that sTM also increased growth and reduced apoptosis of endothelial progenitor cells. CONCLUSIONS: EC-bound TM is released during stress-induced EC damage and becomes sTM, a paracrine factor that exerts anti-apoptotic activity. Our data indicate that sTM is not only an endothelial injury biomarker but also has cytoprotective effects on vascular endothelium.

Bacteremia caused by extended-spectrum-ß-lactamase-producing Escherichia coli sequence type ST131 and non-ST131 clones: comparison of demographic data, clinical features, and mortality.

Escherichia coli producing the highly virulent, multidrug-resistant, CTX-M-15 extended-spectrum ß-lactamase (ESBL), sequence type 131 (ST131), has emerged on three continents since the late 2000s. We described the molecular epidemiology, clinical features, and outcome of ESBL-producing E. coli bacteremia in Taiwan from 2005 to 2010. This study aims to determine whether the risk factors, clinical features, and outcomes of the ST131 isolate differ from those of non-ST131 isolates. From 2005 to 2010, we collected 122 nonduplicated, consecutive, ESBL-producing E. coli isolates from bloodstream infections in a 1,200-bed hospital in Taiwan. Isolates were characterized using multilocus sequence typing. Demographic data, clinical features, and outcomes were collected from medical chart records. Thirty-six (29.5%) patients with bacteremia with ESBL-producing E. coli ST131 were identified. Patients with clone ST131 were more likely to have secondary bacteremia and noncatheterized urinary tract infections (P < 0.05). Secondary bacteremia (odds ratio [OR], 5.05; 95% confidence interval [CI], 1.08 to 23.56) and urinary catheter nonuse (OR, 3.77; 95% CI, 1.17 to 12.18) were independent risk factors for the ST131 clone after adjustment. Mortality rates at day 28 were similar in ST131 and non-ST131 populations. Independent risk factors predicting mortality at day 28 included malignancy, shock, and hospital-acquired bacteremia. In ESBL-producing E. coli bloodstream infections, the ST131 clone was not associated with health-care-associated risk factors, such as urinary catheter use or antibiotic exposure. Although highly virulent and multidrug resistant, the ST131 clone was not associated with higher mortality than non-ST131 clones.

Thrombomodulin is upregulated in cardiomyocytes during cardiac hypertrophy and prevents the progression of contractile dysfunction.

BACKGROUND: Cardiac hypertrophy is a common response to pressure overload and leads to left ventricular (LV) dysfunction. Thrombomodulin (TM), an endothelial anticoagulant protein, was found to have direct effects on cellular proliferation and inflammation. We examined the TM expression in cardiomyocytes during cardiac hypertrophy and investigated its physiological significance. METHODS AND RESULTS: TM expression was evaluated in cardiomyocytes from hearts of mice that underwent transverse aortic constriction (TAC). The effects of recombinant TM protein on cardiomyocytes apoptosis and related signaling pathways were examined. Recombinant TM protein was administered continuously in mice that underwent TAC, and serial LV function was determined. There was significant TM expression in cardiomyocytes during cardiac hypertrophy elicited by TAC in mice. TM treatment decreased doxorubicin-induced apoptosis of cardiomyocytes and increased the Bcl-2/Bax ratio. It also increased cardiomyocytes hypertrophy, expression of atrial natriuretic peptide, and significantly activated the extracellular signal-regulated kinase 1/2 (ERK1/2) and the phosphatidylinositol-3-kinase (PI3-K)/protein kinase B (Akt) signaling pathways in cardiomyocytes. Continuous TM supply after TAC prevented the progression of LV contractile dysfunction in mice. CONCLUSIONS: TM treatment decreased cardiomyocyte apoptosis and maintained LV contractile function in response to pressure overload.

Sphingomonas paucimobilis bacteremia in humans: 16 case reports and a literature review.

BACKGROUND/PURPOSE: Sphingomonas paucimobilis is a glucose-nonfermenting Gram-negative bacillus that is widely distributed in both natural environment and hospitals. Various infections in humans have been reported, but most have been limited to sporadic case reports. The aim of this study was to describe the clinical characteristics and manifestations of S. paucimobilis bacteremia. We also reviewed the literature on S. paucimobilis bacteremia. METHODS: Cases of S. paucimobilis bacteremia were identified retrospectively at a university-affiliated hospital in Taiwan. In addition, relevant case reports were identified through PubMed and reviewed. RESULTS: From April 2004 to April 2008, 42 cases of S. paucimobilis bacteremia were identified in this study. Among them, 16 cases were identified from E-Da hospital, Kaohsiung, Taiwan and 26 cases from the literature review. The median age of patients was 48.5 years and 57.1% were male. The most common comorbidities included malignancy (57.1%), immunosuppressant use (40.5%), and diabetic mellitus (11.9%). Hospital-acquired bacteremia accounted for 69.0% of infections. Primary bacteremia and catheter-related bloodstream infection were found in 35.7% and 33.3% respectively. The most effective antibiotics were fluoroquinolones, carbapenems, and beta-lactam/beta-lactamase inhibitor combinations. All 42 patients survived the S. paucimobilis bacteremic episodes, but three patients experienced septic shock. CONCLUSION: S. paucimobilis can cause infections in healthy as well as immunocompromised individuals. Although it is an organism of low clinical virulence, infection caused by S. paucimobilis can lead to septic shock. Further clinical research is required to characterize this infection.

Risk factors of isolated antibody against core antigen of hepatitis B virus: association with HIV infection and age but not hepatitis C virus infection.

BACKGROUND: Isolated antibody to hepatitis B core antigen (anti-HBc) is defined as seropositivity for anti-HBc in the absence of hepatitis B surface antigen (HBsAg) and antibody to HBsAg (anti-HBs). It is commonly found in HIV-infected persons or hepatitis C virus (HCV)-infected persons, but the risk factors for isolated anti-HBc remain uncertain, especially in regions that are hyperendemic for hepatitis B virus (HBV) infection. METHODS: This cross-sectional study included a cohort of 955 nonhemophiliac, HIV-infected patients, diagnosed between 1988 and 2009, and 643 HIV-uninfected injection drug users (IDUs) attending the methadone clinic between August 2007 and May 2009, with available HBV serological data. The medical records were reviewed to identify the risk factors associated with seropositivity of isolated anti-HBc. RESULTS: The overall seroprevalence of isolated anti-HBc was 12.1% (193 of 1598), in which occult HBV infection accounted for 1.6% (3 of 185) and the majority (91.2 %, 176 of 193) had low titers of anti-HBs (3.6 +/- 2.9 IU/L). Subjects with isolated anti-HBc were significantly older (40.7 +/- 9.3 versus 36.9 +/- 8.0, respectively, P < 0.0001). There was a significantly increasing trend in the prevalence of isolated anti-HBc with age, from 4.0% in those younger than 30 years to 22.5% after 50 years of age (test for trend, P < 0.0001). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects [14.0% (134 of 955) versus 9.2% (59 of 643), adjusted odds ratio, 1.64; P < 0.01], but not in those with HCV infection (P = 0.18). CONCLUSIONS: Isolated anti-HBc seropositivity was significantly associated with HIV infection, and older age. HCV infection was not associated with isolated anti-HBc in a country hyperendemic with HBV infection, even in populations with a high prevalence of HCV infection. The majority was not attributable to occult HBV infection, but rather, low level of anti-HBs, suggesting that HBV vaccination may not be required.

Endometriosis presenting as bloody ascites and shock.

Endometriosis is defined as the presence of ectopic foci of endometrial tissue outside the uterine cavity. Many patients are asymptomatic, but others present protean symptoms, including headache, cyclic hemoptysis, pleural effusion, and ascites depending on the endometrial implantation sites. Although massive ascites has been reported as a manifestation of endometriosis, hypovolemic shock is unusual. We report a case of endometriosis presenting as shock and bloody ascites to show that endometriosis can result in acute abdomen with shock. A 29-year-old female presented to our Emergency Department (ED) complaining of light-headedness and palpitations. Examination suggested hypovolemic shock. Ultrasonography revealed massive ascites and paracentesis showed bloody ascites. Exploratory laparoscopy showed endometriosis over the left broad ligament. After fluid resuscitation and electrocauterization of the endometriosis, the patient's condition stabilized, and she was discharged 5 days after admission. This case is presented to raise awareness that endometriosis can present with hypovolemic shock.

Epidemiology of acute q Fever, scrub typhus, and murine typhus, and identification of their clinical characteristics compared to patients with acute febrile illness in southern taiwan.

BACKGROUND/PURPOSE: In Taiwan, acute Q fever, scrub typhus, and murine typhus (QSM diseases) are the most common rickettsioses, but their epidemiology and clinical characteristics have not been clarified. Diagnosis of these three diseases based on clinical manifestations is difficult, and most of their reported characteristics are identified by describing the predominant manifestations, without being compared with other diseases. METHODS: Serological tests for QSM diseases were examined simultaneously in patients suspected of the three diseases, regardless of which one was suspected. Clinical manifestations were recorded retrospectively from their charts. The characteristics of QSM diseases were identified by comparison with patients who had non-QSM diseases. RESULTS: From April 2004 to April 2007, a total of 226 cases of suspected QSM diseases were included. One hundred (44.2%) cases were serologically confirmed as QSM diseases (68 acute Q fever, 23 scrub typhus, and 9 murine typhus), and 126 (55.8%) cases were non-QSM diseases. Only 33 cases (33.0%) of QSM diseases were initially suspected at the time of hospital visit, whereas 54 cases (42.9%) of non-QSM diseases were incorrectly suspected as QSM diseases. Cases of Q fever and scrub typhus were distributed over plain and mountain areas, respectively. By multivariate analysis, relative bradycardia (OR [95% CI], 2.885 [1.3-6.4]; p = 0.009), radiographic hepatomegaly (OR [95% CI], 4.454 [1.6-12.3]; p = 0.004), and elevated serum aminotransferases (OR [95% CI], 5.218 [1.2-23.1]; p = 0.029) were independent characteristics for QSM diseases, and leukocytosis (OR [95% CI], 0.167 [0.052-0.534]; p = 0.003) was negative for the diagnosis of QSM diseases. CONCLUSION: In southern Taiwan, acute Q fever is the most common rickettsiosis. QSM diseases should be suspected in febrile patients who present with relative bradycardia, hepatomegaly, and elevated serum aminotransferases, but without leukocytosis.

Salmonella infection after surgery of small intestine foreign bodies.

OBJECTIVE: To report the first case of Salmonella enterica serotype choleraesuis infection after surgery for small intestine foreign bodies. CLINICAL PRESENTATION AND INTERVENTION: A 52-year-old woman presented to our hospital with the chief complaint of left abdominal pain for 1 day. The plain kidney-ureter-bladder film and abdominal computed tomography scan showed foreign bodies in the peritoneum. Metallic foreign bodies in the jejunum were found during surgery. Following surgery, the patient developed fever, and blood culture yielded Salmonella enterica serotype choleraesuis. The patient recovered smoothly after antibiotic therapy. CONCLUSION: Salmonella enterica serotype choleraesuis is a highly invasive serotype of nontyphodial Salmonella. In addition to gastroenteritis, bacteremia, or extraintestinal localized infections, physicians should know that it could complicate intestinal surgery.

A novel inhibitory effect of Antrodia camphorata extract on vascular smooth muscle cell migration and neointima formation in mice.

Antrodia camphorata (AC) is a well-known traditional Chinese medicine that has been shown to inhibit proliferation and migration of cancer cells. We examined whether AC could inhibit rat aortic smooth muscle cell (RASMC) proliferation and migration and evaluated its effect on neointima formation in mouse carotid artery after injury. In Transwell migration assay and wound scratch assay, RASMCs were treated with AC or saline, and the number of migrated cells was counted or the distance was determined. Both assays showed that AC significantly inhibited platelet-derived growth factor (PDGF)-induced SMC migration. In 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) and 5-bromo-2' deoxyuridine (BrdU) proliferation assays, RASMCs were pretreated with AC or saline and stimulated with PDGF. Both assays showed that AC inhibited PDGF-induced SMC proliferation. The left common carotid arteries of C57BL/6 mice were ligated near the carotid bifurcation. The mice were given water or AC for 4 weeks. The severity of neointima formation was expressed as the neointima/media (N/M) ratio. The AC-treated mice had less neointima formation at 4 weeks after carotid ligation (N/M ratio, water versus 250 versus 1250 mg/kg AC; 1.33 +/- 0.87 versus 0.83 +/- 0.45 versus 0.63 +/- 0.32, P < 0.05).Our data indicate that AC is an effective inhibitor of PDGF-induced RASMC proliferation and migration. AC treatment reduced neointima formation in this mouse carotid ligation model.

The difference in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan.

OBJECTIVE: To identify the differences in clinical characteristics between acute Q fever and scrub typhus in southern Taiwan. METHODS: A prospective observational study was conducted in which serological tests for acute Q fever and scrub typhus were performed simultaneously regardless of which disease was suspected clinically. From April 2004 to December 2007, 80 and 40 cases of serologically confirmed acute Q fever and scrub typhus, respectively, were identified and included in the study for comparison. RESULTS: By univariate analysis, being male (p<0.001) and having an alanine aminotransferase (ALT) >88U/l (p=0.015) were more common in acute Q fever, whereas residence or travel in a mountainous region or offshore island of Taiwan (p<0.001), skin rash (p<0.001), eschar (p<0.001), lymphadenopathy (p=0.04), leukocytosis (p=0.002), and pulmonary involvement on chest X-ray (p=0.003) were more common in scrub typhus. In the multivariate analysis, being male (odds ratio (OR) 10.883, 95% confidence interval (CI) 2.079-56.441, p=0.005) was an independent characteristic of acute Q fever, while residence or travel in a mountainous region or offshore island (OR 0.073, 95% CI 0.019-0.275, p<0.001) and skin rash (OR 0.152, 95% CI 0.024-0.945, p=0.043) were independent characteristics of scrub typhus. The response to doxycycline treatment was not different. CONCLUSIONS: In southern Taiwan, sex, area of residence, travel history, and physical examination are important in the differentiation of acute Q fever from scrub typhus.

Clinical characteristics of acute Q fever, scrub typhus, and murine typhus with delayed defervescence despite doxycycline treatment.

Doxycycline is the recommended antibiotic for acute Q fever, scrub typhus, and murine typhus and defervescence often occurs within 3 days of treatment. Patients with delayed defervescence (> 3 days) are troublesome for clinicians. To investigate the characteristics of such patients, 18 and 88 cases with and without delayed defervescence, respectively, were studied. By univariate analysis, absence of headache (P = 0.004), jaundice (P = 0.030), icteric sclera (P = 0.030), relative bradycardia (P = 0.003), and pulmonary involvement on chest x-ray (P = 0.028) were significant findings in patients with delayed defervescence. By multivariate analysis, absence of headache (odds ratio [OR] = 8.310; 95% confidence interval [CI] = 1.990-34.706, P = 0.004), jaundice (OR = 6.242; 95% CI = 1.374-28.365, P = 0.018), and relative bradycardia (OR = 10.449; 95% CI = 2.137-51.088, P = 0.004) were the independent characteristics of patients with delayed defervescence. In treating acute Q fever, scrub typhus, and murine typhus with doxycycline, clinicians should be aware that delayed defervescence may occur in patients presenting with jaundice, relative bradycardia, and absence of headache.

Non-septicemic melioidosis presenting as cardiac tamponade.

Melioidosis is endemic in Taiwan. It is caused by infection with Burkholderia pseudomallei. A prolonged course of oral eradication therapy to avoid relapse after an intensive intravenous therapy is recommended to treat melioidosis. Melioidosis with cardiac involvement is rare and is often combined with septicemia, for which the mortality rate is 20-60%. The initial clinical presentations of melioidosis mimic Mycobacterium tuberculosis infection, which is the most common etiology of bacterial pericarditis in Taiwan. We present a case of non-septicemic melioidosis that presented as non-suppurative cardiac tamponade and left subcarinal lymphadenopathy. Underlying diseases included hepatitis B-related liver cirrhosis and hepatocellular carcinoma. The patient was successfully treated with 2 weeks of intravenous ceftazidime and 12 weeks of oral doxycycline, trimethoprim-sulfamethoxazole, and amoxicillin/clavulanate. Melioidosis-related pericarditis should be considered in the differential diagnoses of bacterial pericarditis in Taiwan.

Myoclonic jerks due to acute bromovalerylurea intoxication.

BACKGROUND: Bromides are still sold as sedatives, antitussives, and anticonvulsants in many countries. Bromovalerylurea is a bromide-containing sedative-hypnotic that is occasionally combined with non-steroidal anti-inflammatory drugs in over-the-counter products. Chronic intake of excessive bromovalerylurea can produce bromide intoxication, but acute bromovalerylurea intoxication presenting with myoclonic jerks has never been described. CASE REPORT: A 23-year-old woman was brought to our emergency department with unusual drowsiness. Her physical examination was normal except for frequent myoclonic jerks in all extremities that could be triggered by moving the patient or by noxious stimuli. Initial blood tests results were normal; the serum bromide concentration was 81.0 mg/L (reference <10 mg/L). Treatment with intravenous normal saline and furosemide resulted in gradual improvement in her drowsiness and myoclonic jerks. By the second hospital day, she was normal. A brain magnetic resonance imaging (MRI) was normal. At a 2-month follow-up visit, the patient had no neurological sequelae. DISCUSSION: Chronic bromide intoxication caused by long-term abuse of bromovalerylurea may present as psychiatric or neurologic abnormalities. Our case of acute bromovalerylurea intoxication presented with severe myoclonic jerks and lethargy. The serum bromide concentration was similar to the reported concentrations in acute bromide intoxications. Treatment with normal saline and diuretics results in increased clearance of bromide and an improvement in clinical effects. CONCLUSION: Myoclonic jerks may be one of the major presentations of acute bromovalerylurea intoxication. Physicians should consider bromide intoxication in the differential diagnosis of the causes of myoclonic jerks.

Extremely high prevalence and genetic diversity of hepatitis C virus infection among HIV-infected injection drug users in Taiwan.

BACKGROUND: An outbreak of human immunodeficiency virus (HIV) type 1 infection among injection drug users (IDUs) occurred in Taiwan, and thereafter, injection drug use became the most frequent risk factor for HIV infection in Taiwan. We sought to study the prevalence of and genotypes causing hepatitis C virus (HCV) infection among HIV-infected IDUs in Taiwan. METHODS: A multicenter, longitudinal cohort study of 990 HIV-infected IDUs was conducted from 1993 through 2006. Blood samples were collected and analyzed for the presence of antibody to HCV and to determine the genotype of HCV. RESULTS: The overall prevalence of HCV infection among HIV-infected IDUs was 96.6%. The annual prevalence increased from 65.5% before 2002 to 98.6% in 2006. The main circulating HCV genotypes were 1a (accounting for 29.2% of samples), 6a (23.5%), and 3a (20.2%), whereas 1b, the most predominant genotype circulating in the general population in Taiwan, accounted for only 13.2% of samples. Genotypes 2b (accounting for 6.6% of samples), 6k (2.9%), 2a (1.6%), 6g (1.6%), and 3b (1.2%) were present in only a few IDUs. Multivariate logistic regression analysis revealed that duration of injection drug use and a travel history to China or Southeast Asia were significantly associated with infection due to HCV genotypes 1a, 3, and 6. CONCLUSIONS: Our study demonstrated a high prevalence of HCV infection among HIV-infected IDUs in Taiwan, with a predominance of infection due to genotypes 1a, 6a, and 3a, as a result of the impact of IDUs' behavior and their drug trafficking route. Our study revealed that HCV infection in IDUs originated from a geographically large transmission network that was mainly distinct from that associated with other HCV-infected individuals; this transmission network has also been documented in association with HIV infection in IDUs.

Acute Q fever: an emerging and endemic disease in southern Taiwan.

Acute Q fever is a worldwide zoonosis caused by Coxiella burnetii infection. In Taiwan, cases of acute Q fever increased during 3 y of observation, especially at Kaohsiung County and City in southern Taiwan. From 15 April 2004 to 15 April 2007, a total of 67 cases of acute Q fever were identified at E-Da hospital located at Kaohsiung County. 19 (28.4%) patients had a history of travel in rural areas and only 1 had been outside southern Taiwan. 21 (31.3%) patients had a history of animal contact. 20 (30.8%) of the 65 examined patients had underlying chronic hepatitis B or hepatitis C virus infection. Fever (98.5%), chills (79.1%), headache (79.1%), relative bradycardia (44.8%), elevated aminotransferases (100%), and thrombocytopenia (74.6%) were common manifestations. 12 (19.0%) cases had abnormal findings on chest X-ray. Fatty liver (50.0%) and hepatomegaly and/or splenomegaly (41.9%) were found by abdominal image examinations. 42 (76.4%) of 55 cases had defervescence within 3 d after treatment, whereas 4 (7.3%) had spontaneous remission. Acute Q fever is an endemic infectious disease with hepatitis rather than pneumonia as the major presentation in southern Taiwan and the emergence of Q fever is due to increased alertness for the disease by physicians.