Myocarditis related to Campylobacter jejuni infection: A case report

BACKGROUND: Myocarditis can develop as a complication of various infections and is most commonly linked to enterovirus infections. Myocarditis is rarely associated with bacterial infections; salmonellosis and shigellosis have been the most frequently reported bacterial cause. We report a case of myocarditis related to Campylobacter jejuni enteritis. CASE PRESENTATION: A 30-year-old previously healthy man presented with a history of prolonged chest pain radiating to the jaw and the left arm. Five days prior to the onset of chest pain, he developed bloody diarrhea, fever and chills. Creatine kinase (CK) and CK-MB were elevated to 289 U/L and 28.7 μg/L. Troponin I was 30.2 μg/L. The electrocardiogram (ECG) showed T wave inversion in the lateral and inferior leads. The chest pain resolved within 24 hours of admission. The patient had a completely normal ECG stress test. The patient was initiated on ciprofloxacin 500 mg po bid when Campylobacter jejuni was isolated from the stool. Diarrhea resolved within 48 hours of initiation of ciprofloxacin. The diagnosis of Campylobacter enteritis and related myocarditis was made based on the clinical and laboratory results and the patient was discharged from the hospital in stable condition. CONCLUSION: Myocarditis can be a rare but severe complication of infectious disease and should be considered as a diagnosis in patients presenting with chest pain and elevated cardiac enzymes in the absence of underlying coronary disease. It can lead to cardiomyopathy and congestive heart failure. There are only a few reported cases of myocarditis associated with Campylobacter infection

Dimethylarginine Dimethylaminohydrolase-1 Transgenic Mice Are Not Protected from Ischemic Stroke

Methylated arginines are endogenous analogues of L-arginine, the substrate for nitric oxide (NO) synthase. Asymmetric dimethylarginine (ADMA) interferes with NO formation, causing endothelial dysfunction. ADMA is a predictor of cardiovascular events and mortality in humans. It is eliminated primarily by enzymatic activity of dimethylarginine dimethylaminohydrolase (DDAH).We investigated whether human DDAH-1 (hDDAH-1) transgenicity protects from ischemic tissue damage in temporary middle cerebral artery occlusion (tMCAO) in mice. Infarct sizes did not significantly differ between hDDAH-1 transgenic (TG) mice and wild-type littermates (WT). As expected, ADMA plasma concentrations were significantly decreased, cerebral hDDAH expression and protein significantly increased in transgenic animals. Interestingly, neither brain tissue DDAH activity nor ADMA concentrations were different between TG and WT mice. In contrast, muscular DDAH activity was generally lower than in brain but significantly increased in TG mice.Our study demonstrates that hDDAH-1 transgenic mice are not protected from ischemic cerebral tissue damage in tMCAO. This lack of protection is due to high basal cerebral DDAH activity, which is not further increasable by transgenic overexpression of DDAH

Alterations in bone turnover markers in patients with noncardio-embolic ischemic stroke.

BackgroundThe major cause of ischemic stroke is unstable or thrombogenic atherosclerotic plaques. Vascular calcification, a process that appears crucial for plaque stability, shares common features with bone formation. Many bone turnover proteins exhibit metabolic properties, but the evidence is conflicting regarding their possible involvement in vascular disease. Antibodies against sclerostin and dickkopf-1 are currently being evaluated as potential therapy for treating bone disorders. It is important to carefully assess the cardiovascular and metabolic effects of these proteins. The aim of the present study was to explore serum levels of bone turnover markers in patients with acute noncardio-embolic ischemic stroke in comparison with healthy controls.MethodsIn a cross-sectional study, we compared 48 patients aged ≥75 years with noncardio-embolic ischemic stroke and 46 healthy controls. Serum levels of dickkopf-1, sclerostin, osteoprotegerin, osteopontin and osteocalcin were determined by Luminex technique.ResultsWe found clearly increased serum levels of osteoprotegerin, sclerostin, dickkopf-1 and osteopontin in patients with stroke compared with healthy controls. No difference was seen in serum levels of osteocalcin between the two groups.ConclusionOur findings strengthen the hypothesis of bone turnover markers being involved in vascular disease. Whether these proteins can be used as candidate markers for increased stroke risk or prognostic biomarkers remains to be further elucidated

Asymmetric dimethylarginine and total homocysteine in plasma after oral methionine loading

Background: Elevation of homocysteine (Hcy) and asymmetric dimethylarginine (ADMA) in plasma are believed to be involved in the pathogenesis of cardiovascular disease (CVD). In humans, oral methionine loading results in acute elevation of plasma Hcy. This is associated with impaired NO-dependent vasodilatation, a mechanism that may explain the relationship between elevated Hcy and risk of CVD. ADMA, an endogenous competitive inhibitor of NO-synthase, may be elevated in plasma of patients with CVD. It was proposed that ADMA is synthesized in a methionine-dependent reaction which also forms Hcy. In this study plasma total homocysteine (tHcy) and ADMA concentrations were measured before and after oral methionine loading of human subjects. Methods: Plasma tHcy and ADMA levels were measured in 12 healthy males (age 32-58 years) before and after oral loading with L-methionine (100 mg/kg body weight in orange juice). Results: At noon, 4 h after methionine loading, tHcy and ADMA levels (35.4 +/- 10.9 and 0.80 +/- 0.13 mumol/L, mean +/-SD) were significantly higher than the corresponding values obtained at noon the day before (15.6 +/- 7.4 and 0.63 +/- 0.10 mumol/L, both p < 0.001). Noon values 4 h after methionine loading were also significantly higher than values obtained immediately before the methionine load (13.7 &PLUSMN; 5.9 and 0.66 &PLUSMN; 0.10 μmol/L, both p < 0.001). Reinvestigation of 8 of 12 subjects showed that at 4 and 8 h after compared with levels immediately before methionine loading there was a significant increase in tHcy (28.4 +/- 10.2 and 33.45 +/- 11.1 vs. 10.8 +/- 3.3 mumol/L, both p < 0.001). However, the corresponding ADMA levels did not increase (0.73 &PLUSMN; 0.17 and 0.76 &PLUSMN; 0.22 vs. 0.70 &PLUSMN; 0.10 μmol/L, both not significant). Conclusions: No clear evidence was found to support the supposition that methionine-induced hyperhomocysteinaemia may be accompanied by elevated levels of ADMA, an endogenous competitive NO-synthase inhibitor that may represent an alternative pathogenic mechanism for homocysteine-associated impairment of endothelial NO-dependent functions

Adherence to risk management guidelines for drugs which cause vitamin D deficiency &ndash; big data from the Swedish health system

Ola Nordqvist,1,2 Ulrika L&ouml;nnbom Svensson,3 Lars Brudin,4,5 P&auml;r Wanby,2,6 Martin Carlsson2,7 1The Pharmaceutical Department, Region Kalmar County, Kalmar, Sweden; 2eHealth Institute, Data Intensive Sciences and Applications (DISA), Department of Medicine and Optometry, Linnaeus University, Kalmar, Sweden; 3Department of Chemistry and Biomedical Sciences, Linnaeus University, Kalmar, Sweden; 4Department of Clinical Physiology, County Hospital of Kalmar, Kalmar, Sweden; 5Department of Medical and Health Sciences, University of Linkoping, Link&ouml;ping, Sweden; 6Section of Endocrinology, Department of Internal Medicine, County Hospital of Kalmar, Kalmar, Sweden; 7Department of Clinical Chemistry, County Hospital of Kalmar, Kalmar, SwedenPurpose: Several medications are known to cause vitamin D deficiency. The aim of this study is to describe vitamin D testing and supplementation in patients using these &ldquo;risk medications&rdquo;, thereby assessing adherence to medical guidelines.Patients and methods: A database with electronic health records for the population in a Swedish County (&asymp;240,000 inhabitants) was screened for patients prescribed the pre-defined &ldquo;risk medications&rdquo; during a 2-year period (2014&ndash;2015). In total, 12,194 patients were prescribed &ldquo;risk medications&rdquo; pertaining to one of the three included pharmaceutical groups. Vitamin D testing and concomitant vitamin D supplementation, including differences between the included pharmaceutical groups, was explored by matching personal identification numbers. Results: Corticosteroids were prescribed to 10,003 of the patients, antiepileptic drugs to 1,101, and drugs mainly reducing vitamin D uptake to 864. Two hundred twenty-six patients were prescribed &gt;1 &ldquo;risk medication&rdquo;. Seven hundred eighty-seven patients (6.5%) had been tested during the 2-year period. There were no differences regarding testing frequency between groups. Concomitant supplements were prescribed to 3,911 patients (32.1%). It was more common to be prescribed supplements when treated with corticosteroids. Vitamin D supplementation was more common among tested patients in all three groups. Women were tested and supplemented to a higher extent. The mean vitamin D level was 69 nmol/L. Vitamin D deficiency was found in 24.1% of tested patients, while 41.3% had optimal levels. It was less common to be deficient and more common to have optimal levels among patients prescribed corticosteroids. Conclusion: Adherence to medical guidelines comprising testing and supplementation of patients prescribed drugs causing vitamin D deficiency needs improvement in Sweden. Keywords: drug-induced vitamin D deficiency, medication risk management, big data, electronic health records, vitamin D, precision medicin

Novel mutations in the SLC12A3 gene causing Gitelman's syndrome in Swedes

Purpose: Gitelman's syndrome (GS) is an inherited autosomal recessive disorder due to loss of function mutations in the SLC12A3 gene encoding the Na-Cl co-transporter (NCCT), the target of thiazide diuretics. The defective function of the NCCT, which normally is expressed in the apical membrane of the distal convolute tubule in the kidney, leads to mild hypotension, hypokalemia, hyperreninemic hyperaldosteronism, mild metabolic alkalosis, hypomagnesemia and hypocalciuria. Up to now, more than 100 mutations of the SLC12A3 gene have been described in GS patients. Methods: We have collected 30 patients from Sweden with a clinical diagnosis of GS and undertaken a mutation screening by SSCP and successive sequencing of the 26 exons and intronic boundaries. Both mutations were identified in most (n = 28, 93%) and at least one mutation was identified in all patients. Results: We found 22 different mutations evenly distributed throughout the gene, 11 of which have not been described previously. The new variants include 8 missense mutations (Glu68Lys, His69Asn, Argl45His, Vall53Met, Gly230Asp, Gly342Ala, Val677Leu and Gly867Ser), 1 insertion (c.834_835insG on exon 6) and 2 splice-site mutations (c.2667 + lT>G substitution in splicing donor site after exon 22, c.1569-1G>A substitution in the splicing acceptor site before exon 13). Conclusion: In Swedish patients with the clinical features of GS, disease-causing mutations in the SLC12A3 gene were identified in most patients. The spectrum of GS mutations is wide making full mutation screening of the SLC12A3 gene necessary to confirm the diagnosis

Subjects heterozygous for genetic loss of function of the thiazide sensitive cotransporter have reduced blood pressure.

Gitelman's syndrome (GS) is an inherited recessive disorder caused by homozygous or compound heterozygous loss of function mutations of the NaCl cotransporter (NCCT) gene encoding the kidney-expressed NCCT, the pharmacological target of thiazide diuretics. An observational study estimated the prevalence of GS to 19/1,000,000, in Sweden, suggesting that approximately 1% of the population carries one mutant NCCT allele. As the phenotype of GS patients, who always carry two mutant alleles, is indistinguishable from that seen in patients treated with high-dose thiazide diuretics, we aimed at investigating whether subjects carrying one mutated NCCT allele have a phenotype resembling that of treatment with low-dose thiazide diuretics. We screened first-degree relatives of 18 of our patients with an established clinical end genetic diagnosis of GS for NCCT loss of function mutations and identified 35 healthy subjects carrying one mutant allele (GS-heterozygotes). Each GS-heterozygote was assigned a healthy control subject matched for age, BMI and sex. GS-heterozygotes had markedly lower blood pressure (systolic 103.3 +/- 16.4 versus 123.2 +/- 19.4 mmHg; diastolic 62.5 +/- 10.5 versus 73.1 +/- 9.4 mmHg; P < 0.001) than controls. There was no significant difference between the groups either in plasma concentration or urinary excretion rate of electrolytes, however, GS-heterozygotes had higher fasting plasma glucose concentration. Similar to patients being treated with low-dose thiazide diuretics, GS-heterozygotes have markedly lower blood pressure and slightly higher fasting plasma glucose compared with control subjects. Our findings suggest that GS-heterozygotes, the prevalence of which can be estimated to 1%, are partially protected from hypertension through partial genetic loss of function of the NCCT. However, as our study had a case-control design, it is important to underline that any potential effects on population blood pressure and risk of future cardiovascular disease need to be examined in prospective and population-based studies