Zinc, iron, copper, selenium, lactoferrin, and ferritin in human pus

BACKGROUND: Restriction of zinc and iron available for microbial growth in tissues are well-recognized host defense mechanisms. The present studies were performed to characterize some constituents of human pus that may affect these important host defenses. METHODS: Zinc, iron, copper, calcium, and magnesium in pus were measured using an atomic absorption spectrophotometer; selenium was measured fluorometrically. Ferritin was measured with a fluorometric enzyme immunoassay, and lactoferrin was measured with a radial diffusion assay. The growth of Escherichia coli at 37 degrees C was measured in pus supernate adjusted to pH 5.5 or 7.4, in boiled supernate, or in supernate adjusted with 1.3 mM iron or 0.9 mM zinc singly or together. RESULTS: Zinc and iron concentrations in pus exceeded normal serum. Calcium and magnesium levels were 2- to 3-fold lower and higher, respectively, than normal serum values. Lactoferrin concentrations of were 880 +/- 48 microg/mL and ferritin levels were 20,726 +/- 2,667 ng/mL. Growth of an E coli strain was inhibited in pus at pH 5.5 but not at pH 7.4, and growth was enhanced by addition of iron or zinc to E coli suspended in pus at pH 6.7. CONCLUSIONS: To our knowledge, this is the first report of the zinc, iron, copper, selenium, lactoferrin, and ferritin levels of human pus. These studies provide additional insight into host defense mechanisms mediated by the restriction of the bioavailability of zinc and iron in suppurative infection.     

Serum enzyme activity in bone tumors and osteomyelitis (LDH, GOT, GPT, CPK, CHE, ALP, AP, PP, ALD).

Enzyme activity of lactate dehydrogenase, glutamate-oxalacetate and glutamate-pyruvate transaminase, creatine phosphokinase, cholinesterase, alkaline, acid and prostatic phosphatase and aldolase has been studied in a total of 213 subjects, of whom 97 were of good health, 63 had bone tumors and 53 suffered from osteomyelitis. The activities of the majority of the enzymes were found to become significantly changed in comparison with the norm. In both patient groups, the more striking differences being noted in that of osteomyelitis. However, enzymatic activity alone does not allow to differentiate the group of bone tumors from that of osteomyelitis, the differences between these two groups not being of significance in any one of the enzymes followed.     

New antiarrhythmic agents: amiodarone, aprindine, disopyramide, ethmozin, mexiletine, tocainide, verapamil.

The present status, clinical experience, side effects, clinical pharmacology and electrophysiologic actions of seven new antiarrhythmic agents are reviewed. The drugs selected for comment are amiodarone, aprindine, disopyramide, ethmozin, mexiletine, tocainide and verapamil. Each drug has been shown to have clinical efficacy in suppressing cardiac arrhythmias.     

Environmental hazards, hot, cold, altitude, and sun

There has been an increase in both recreational and adventure travel to extreme environments. Humans can successfully acclimatize to and perform reasonably well in extreme environments, provided that sufficient time is given for acclimatization (where possible) and that they use appropriate behavior. This is aided by a knowledge of the problems likely to be encountered and their prevention, recognition, and treatment.     

Chronic pancreatitis and diabetes mellitus: plasma and gastroduodenal mucosal profiles of regulatory peptides (gastrin, motilin, secretin, cholecystokinin, gastric inhibitory polypeptide, somatostatin, VIP, substance P, pancreatic polypeptide, glucagon, enteroglucagon, neurotensin)

A disturbed intraduodenal milieu and pancreatic scarring in advanced chronic pancreatitis (CP) may lead to changes of gut and pancreatic hormones. In the present study, the gastroduodenal mucosal content of several regulatory peptides was determined in 8 patients with severe calcific CP and 8 healthy volunteers. In addition, hormone release into the bloodstream was estimated after intraduodenal acid/glucose stimulation in the control subjects and 8 CP patients each with or without secondary diabetes mellitus (DM), and in 8 patients with juvenile DM, so that disturbed gut hormone release could be attributed either to CP or DM. While VIP release into the circulation was similar in all participants, mucosal levels of VIP and substance P were significantly elevated in the duodenal bulb and descending duodenum of CP patients. The somatostatin content of gastroduodenal mucosa in CP was at least as high as in normals. Gastrin was significantly more abundant only in the duodenal bulb of CP patients, while plasma gastrin was normal. Duodenal CCK concentrations tended to be elevated in the duodenal bulb, but not significantly. The release of secretin seemed to be higher in type-1 diabetics than in CP patients. The mucosal pattern of GIP was nearly identical in CP patients and controls. Compatible with this finding, the GIP release did not show any peculiarities in CP with or without DM or in DM. Basal and stimulated plasma levels of motilin were abnormally high in CP. Pancreatic polypeptide plasma levels were normal in DM, but significantly reduced in CP, especially in CP with DM. Fasting PP and stimulated pancreatic enzyme outputs were linearly related.(ABSTRACT TRUNCATED AT 250 WORDS)     

Digestive Neuroendocrine Neoplasms (NEN): French Intergroup clinical practice guidelines for diagnosis,treatment and follow-up (SNFGE,GTE, RENATEN,TENPATH, FFCD,GERCOR, UNICANCER,SFCD, SFED,SFRO, SFR)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of digestive neuroendocrine neoplasms (NEN) published in February 2020 (www.tncd.org).MethodsAll French medical societies involved in the management of NEN took part in this work. Recommendations were graded into four categories (A, B, C or D), according to the level of evidence found in the literature until May 2019.ResultsThe management of NEN is challenging because of their heterogeneity and the increasing complexity of diagnostic and therapeutic procedures. Pathological analysis is required for their diagnostic and prognostic characterization, which mainly relies on differentiation, grade and stage. The two main emergency situations are functioning syndromes and poorly-differentiated carcinoma. Chromogranin A is the main biochemical marker of NET, although of limited clinical interest. Initial characterization relies on morphological and isotopic imaging. The treatment of localized NET relies on watchful follow-up and local or surgical resection depending on its supposed aggressiveness. Treatment options for metastatic disease include surgery, somatostatin analogues, chemotherapy, targeted therapies, organ-driven locoregional therapies and peptide-receptor radionuclide therapy. As specific predictive factors of treatment efficacy are yet to be identified and head-to-head comparisons have not or only rarely been performed, the therapeutic strategy currently depends on prognostic factors. Cumulative toxicity and the impact of treatment on quality of life must be considered since survival is relatively long in most patients with NET.ConclusionThese guidelines are proposed to achieve the most beneficial therapeutic strategy in clinical practice as the therapeutic landscape of NEN is becoming ever more complex. These recommendations are permanently being reviewed.     

Syphilis, neurosyphilis, penicillin, and AIDS

Early neurosyphilis, characterized by meningitis, cranial nerve abnormalities, and cerebrospinal accidents, was first described in patients with syphilis who received inadequate courses of arsphenamine. Although more effective, penicillin at conventional doses does not yield treponemacidal levels in the central nervous system and probably does not eradicate the infecting organisms, suggesting that it works synergistically with the host's immune response in preventing neurosyphilis. Neurosyphilis after penicillin therapy was almost unheard of in the United States until it began to appear in human immunodeficiency virus (HIV)-infected patients. Numerous cases of syphilitic meningitis, cranial nerve abnormalities, and strokes have been reported in the past decade; about one-half of reported patients had received penicillin therapy, often within the previous 6 months. Thus, more intensive diagnostic evaluation, perhaps including routine cerebrospinal fluid analysis, more intensive therapy, for example with at least three doses of benzathine penicillin, and far more rigorous follow-up are indicated in HIV-infected subjects with syphilis. Since the efficacy of conventional therapy is now uncertain, novel approaches to treatment deserve systematic evaluation.     

Appendiceal tumors and pseudomyxoma peritonei: French Intergroup Clinical Practice Guidelines for diagnosis,treatments and follow-up (RENAPE,RENAPATH, SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,ACHBT, SFR)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of appendicular epithelial tumors (AT) and pseudomyxoma peritonei (PMP) published in March 2020, available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).MethodsAll French medical societies specialized in the management of AT and PMP collaboratively established these recommendations based on literature until December 2019 and the results of a Delphi vote carried out by the Peritoneal Surface Oncology Group International experts, and graded into 4 categories (A, B, C, Expert Agreement) according to their level of evidence.ResultsAT and PMP are rare but represent a wide range of clinico-pathological entities with several pathological classification systems and different biological behaviors. Their treatment modalities may vary accordingly and range from simple surveillance or laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) and / or systemic chemotherapy. The prognosis of these neoplasms may also largely vary according to their pathological grade and spreading at diagnosis or during the follow-up. Given the rarity of certain situations, the therapeutic strategy adapted to each patient, must be discussed in a specialized multidisciplinary meeting after a specialized pathological and radiological pre-therapeutic assessment and a clinical examination by a surgeon specializing in the management of rare peritoneal malignancies.ConclusionThese recommendations are proposed to achieve the most beneficial strategy in a daily practice as the wide range and the rareness of these entities renders their management challenging. These guidelines are permanently being reviewed.     

Barrett carcinoma--diagnosis, screening, surveillance, endoscopic treatment, prevention

An adenocarcinoma of the distal esophagus may also be designated as Barrett's carcinoma as it evolves from Barrett's esophagus. Barrett's esophagus currently is defined as a columnar metaplasia of the distal esophagus, as identified by endoscopy, that, upon histopathology, is confirmed to contain intestinal metaplasia. A different histological entity of columnar metaplasia of the distal esophagus is cardia-type mucosa which probably precedes intestinal metaplasia, but lacks goblet cells typical for the latter. The conversion rate from Barrett's esophagus to Barrett's carcinoma amounts to 0.5 to 1 % per year. Patients with reflux symptoms should undergo early endoscopy in order to search for Barrett's esophagus (screening). In those cases where Barrett's esophagus is identified, regular endoscopic controls should be scheduled (surveillance). The intervals for this have been defined by recent consented guidelines. The aim is to detect neoplasia early. Neoplasia confined to the epithelium or mucosal layer can mostly be treated by endoscopic resection. The depth of infiltration, as determined by histopathology of the resected specimen, allows one to estimate the risk of lymph node metastasis, and therefore is crucial for the final judgment as to whether the endoscopic intervention may be considered curative. Individually, the risk of metastasis has to be weighed against the risk of morbidity and mortality conferred by the alternative surgical resection. The rapid increase of the incidence of Barrett's carcinoma in Western countries suggests that life style factors, in particular overweight, having a causal role. Data from interventional trials on prevention are, however, pending.     

Trust,benefit, satisfaction,and burden

BACKGROUND: Community-based participatory research (CBPR) approaches that actively engage communities in a study are assumed to lead to relevant findings, trusting relationships, and greater satisfaction with the research process. OBJECTIVE: To examine community members' perceptions of trust, benefit, satisfaction, and burden associated with their participation. DESIGN, SETTING, AND PARTICIPANTS: A randomized controlled trial tested a cancer prevention intervention in members of African-American churches. Data were collected at baseline and 1-year follow-up. MEASUREMENTS: Subscales measured perception of trust in the research project and the project team, benefit from involvement with the project, satisfaction with the project and the team, and perception of burden associated with participation. MAIN RESULTS: Overall, we found high levels of trust, perceived benefit, and satisfaction, and low perceived burden among community members in Partnership to Reach African Americans to Increase Smart Eating. In bivariate analyses, participants in the intervention group reported more perceived benefit and trust (P <.05). Participants in smaller churches reported more benefit, satisfaction and trust, while participants from churches without recent health activities perceived greater benefit, greater satisfaction, and lower burden with the project and the team (P <.05). Participants whose pastors had less educational attainment noted higher benefit and satisfaction; those whose pastors were making personal lifestyle changes noted higher benefit and satisfaction, but also reported higher burden (P <.05). CONCLUSIONS: A randomized clinical trial designed with a CBPR approach was associated with high levels of trust and a perceived benefit of satisfaction with the research process. Understanding variations in responses to a research partnership will be helpful in guiding the design and implementation of future CBPR efforts.     

Strikes, flooding, rats, and leptospirosis in Marseille, France

Objectives

The aim of this study was to examine the mechanisms by which weather conditions, the incidence of Leptospira in reservoir populations, and various socio-ecological factors are driving the emergence of leptospirosis in Marseille, France.

Methods

Over the last 30 years our laboratory has surveyed all human cases of leptospirosis in Marseille using clinical, epidemiological, serological, and molecular tools. Data for the weather conditions in Marseille were collected from the official meteorological station, and garbage management strikes were monitored through the local press. Rats were trapped in alleys near to where the patients may have acquired leptospirosis.

Results

Three new cases of autochthonous leptospirosis are reported. The global tendency for rainfall showed a slight increase over the period under analysis. The index case of leptospirosis occurred after a heavy rainfall with flooding. Over the last 10 years Marseille has undergone 82 days of garbage management strikes. Leptospira DNA was detected in two of 11 rats.

Conclusions

The emergence of leptospirosis has become a public health problem in Marseille, and is associated with a combination of heavy rainfall and garbage collection strikes in which garbage is left on the street and thereby contributes to the expansion of the rat population on the surface.     

Electrochemical Recovery and Behaviors of Rare Earth (La,Ce, Pr,Nd, Sm,Eu, Gd,Tb, Dy,Ho, Er,Tm, and Yb) Ions on Ni Sheets

The electrochemical behaviors of rare earth (RE) ions have extensively been studied because of their high potential applications to the reprocessing of used nuclear fuels and RE-containing materials. In the present study, we fully investigated the electrochemical behaviors of RE(III) (La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, and Yb) ions over a Ni sheet electrode in 0.1 M NaClO₄ electrolyte solution by cyclic voltammetry between +0.5 and −1.5 V (vs. Ag/AgCl). Amperometry electrodeposition experiments were performed between −1.2 and −0.9 V to recover RE elements over the Ni sheet. The successfully RE-recovered Ni sheets were fully characterized by scanning electron microscopy, energy dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, and photoluminescence spectroscopy. The newly reported recovery data for RE(III) ions over a metal electrode provide valuable information on the development of the treatment methods of RE elements.     

Infection, inflammation, height, and longevity

Using historical data from cohorts born before the 20th century in four northern European countries, we show that increasing longevity and declining mortality in the elderly occurred among the same birth cohorts that experienced a reduction in mortality at younger ages. Concurrently, these cohorts also experienced increasing adult height. We hypothesize that both the decline in old-age mortality and the increase in height were promoted by the reduced burden of infections and inflammation. Thus, early growth and cardiovascular diseases of old age may share infectious and inflammatory causes rooted in the external environment.     

Pregnancy loss, polycystic ovary syndrome, thrombophilia, hypofibrinolysis, enoxaparin, metformin.

Thrombophilia, hypofibrinolysis, and polycystic ovary syndrome (PCOS) are associated with recurrent pregnancy loss (RPL) and spontaneous abortion (SAB) alone and concurrently. The efficacy and safety of combined enoxaparin-metformin was prospectively assessed in women with PCOS with one or more previous SAB, thrombophilia, and/or hypofibrinolysis. Twenty-four white women with PCOS were studied; 23 with previous pregnancies, seven with RPL of unknown etiology (>/=three consecutive pregnancy losses <20 weeks' gestation), two with two consecutive SABs, 13 with one SAB, and one with one live birth (HELLP syndrome). Prospectively, metformin (1.5 to 2.55 g/day) was administered before and throughout gestation, with concurrent enoxaparin (60 mg/day) throughout gestation. The 24 cases differed from 93 normal white female controls for the factor V Leiden mutation, 17% vs. 2%, Fisher's p [p(f)] = .016, and for the 4G4G mutation of the plasminogen activator inhibitor-1 (PAI-1) gene (46% vs. 24%, Chi-square 4.63, p =. 031). The patients also differed from 44 normal white female controls for high levels (> 21.1 U/mL) of the PAI-1 gene product, plasminogen activator inhibitor activity (PAI-Fx) (33% vs. 8%, p(f) =. 018), and for high factor VIII (>150%) (22% vs. 0%, p(f) = .037). Of the 24 women, 23 had 65 previous pregnancies without metformin or enoxaparin, with 18 live births, 46 SAB (71%), and one elective abortion. On metforminenoxaparin, the same 23 women had 26 current pregnancies (28 fetuses), with 20 live births, two normal pregnancies 13 weeks or longer, and six SAB (21%), 3.4-fold lower than previous gestations (McNemar's S = 33.6, p <. 0001). There were no adverse maternal or fetal therapy effects. Enoxaparin-metformin reduces pregnancy loss in women with PCOS with one or more previous SAB, who also have thrombophilia and/or hypofibrinolysis.     

Homocysteine, coagulation, platelet function, and thrombosis

Over the last 30 years, a growing body of evidence has documented the role of hyperhomocysteinemia (HHcy) as an independent vascular risk factor. However, the mechanisms through which elevated circulating levels of homocysteine (Hcy) cause vascular injury and promote thrombosis remain elusive. Most findings have been achieved in in vitro studies employing exceedingly high concentrations of Hcy, whereas only a few studies have been carried out in vivo in humans. In homocystinuric patients, homozygotes for mutations of the gene coding for the cystathionine beta-synthase enzyme, abnormalities of coagulation variables reflecting a hypercoagulable state, have been reported. In vitro studies provide a biochemical background for such a state. In homocystinuric patients, an in vivo platelet activation has also been reported. The latter abnormality is not corrected by the bolus infusion of concentrations of hirudin, which determines a long-lasting impairment of the conversion of fibrinogen to fibrin by thrombin; in contrast, it appears at least in part lowered by the administration of the antioxidant drug probucol. During the autooxidation of Hcy in plasma, reactive oxygen species are generated. The latter initiate lipid peroxidation in cell membranes (potentially responsible for endothelial dysfunction) and in circulating lipoproteins. Oxidized low-density lipoproteins (LDL) may trigger platelet activation as well as some of the hemostatic abnormalities reported in such patients. Thus the oxidative stress induced by Hcy may be a key process in the pathogenesis of thrombosis in HHcy. Accumulation of adenosylhomocysteine in cells (a consequence of high circulating levels of homocysteine) inhibits methyltransferase enzymes, in turn preventing repair of aged or damaged cells. This mechanism has been recently documented in patients with renal failure and HHcy and provides an additional direction to be followed to understand the tendency to thrombosis in moderate HHcy.     

Lipoxins,Resolvins, Protectins,Maresins, and Nitrolipids: Connecting Lipids,Inflammation, and Cardiovascular Disease Risk

Essential fatty acids and their metabolites (γ-linolenic acid [GLA], dihomo-GLA, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid; prostaglandin E₁; prostacyclin [PGI₂]; PGI₃; lipoxins; resolvins; protectins; maresins; and nitrolipids) prevent platelet aggregation, produce vascular relaxation, inhibit neutrophil degranulation and superoxide formation, inhibit platelet activation, possess peroxisome proliferator-activated receptor-γ ligand activity, and release nitric oxide. Thus, they lower blood pressure, are anti-arrhythmic and anti-inflammatory in nature, reduce low-density lipoprotein cholesterol, ameliorate the adverse actions of homocysteine, activate telomerase, and have cytoprotective properties—actions that prevent atherosclerosis and cardiovascular disease. Because coronary heart disease (CHD) and atherosclerosis are low-grade systemic inflammatory conditions, it is likely that reduced formation of lipoxins, resolvins, protectins, maresins, and nitrolipids plays a significant role in the pathogenesis of CHD. Hence, development of stable synthetic analogues of lipoxins, resolvins, protectins, and maresins may form a new therapeutic approach to CHD and other low-grade systemic inflammatory conditions.     

Anal cancer: French Intergroup Clinical Practice Guidelines for diagnosis,treatment and follow-up (SNFGE,FFCD, GERCOR,UNICANCER, SFCD,SFED, SFRO,SNFCP)

IntroductionThis document is a summary of the French Intergroup guidelines regarding the management of anal carcinomas, published in November 2016.MethodsIt is a collaborative work produced under the auspices of the majority of the French medical societies involved in the management of anal cancer. It is based on the previous guidelines published in 2010. Recommendations are graded in three categories, according to the amount of evidence found in the literature.ResultsNon-metastatic anal carcinomas can be divided into two risk groups, according to magnetic resonance imaging (MRI) or endorectal-ultrasonograpy. Localized small cancers (T1N0) are mainly treated by exclusive radiation therapy in the case of cancers of the anal canal, or by surgery in the case of cancers of the anal margin. The recommended treatment of locally advanced tumours (T2-T4, N0-N2) is definitive concomitant radio-chemotherapy. Salvage surgery should be reserved for patients with poor response, tumour progression or local relapse after radio-chemotherapy, or in cases of persistent vaginal fistula or total anal incontinence after the cessation of radio-chemotherapy. In the case of metastatic tumours, current therapeutic recommendations are based on less robust evidence; with chemotherapy playing a major role.ConclusionThese recommendations are permanently being reviewed, and each individual case must be discussed inside a multidisciplinary team.     

Smoking, calcium, calcium antagonists, and aging

Aging is characterized, besides other changes, by a progressive increase in calcium content in the arterial wall, which is enhanced by diabetes mellitus, osteoporosis, arterial hypertension, and tabagism. As to tabagism, experiments in animals have shown that nicotine can increase calcium content of the arterial wall, and clinical studies have demonstrated that cigarette smoking induces peripheral vasoconstriction, with consequent increase in blood pressure levels. In order to study the role of calcium ions in the pathogenesis of the vasoconstrictive lesions caused by "acute" smoking, the author has studied the peripheral vascular effects of the calcium-channel antagonist nifedipine, a dihydropyridine derivative, and calcitonin, a hypocalcemizing hormone which possess vasoactive actions on 12 elderly regular smokers (mean age 65.8 years). The results demonstrated that both nifedipine (10 mg sublingually 20 min before smoking) and salmon calcitonin (100 MRC U/daily intramuscularly for three days) are able to prevent peripheral vasoconstriction evaluated by Doppler velocimetry, as well as the increase of blood pressure induced by smoking. On the basis of our results, the author proposes that cigarette smoking-induced vasoconstriction is a calcium-mediated process, which can be hindered by drugs with calcium antagonist action.     

Food, livestock production, energy, climate change, and health

Food provides energy and nutrients, but its acquisition requires energy expenditure. In post-hunter-gatherer societies, extra-somatic energy has greatly expanded and intensified the catching, gathering, and production of food. Modern relations between energy, food, and health are very complex, raising serious, high-level policy challenges. Together with persistent widespread under-nutrition, over-nutrition (and sedentarism) is causing obesity and associated serious health consequences. Worldwide, agricultural activity, especially livestock production, accounts for about a fifth of total greenhouse-gas emissions, thus contributing to climate change and its adverse health consequences, including the threat to food yields in many regions. Particular policy attention should be paid to the health risks posed by the rapid worldwide growth in meat consumption, both by exacerbating climate change and by directly contributing to certain diseases. To prevent increased greenhouse-gas emissions from this production sector, both the average worldwide consumption level of animal products and the intensity of emissions from livestock production must be reduced. An international contraction and convergence strategy offers a feasible route to such a goal. The current global average meat consumption is 100 g per person per day, with about a ten-fold variation between high-consuming and low-consuming populations. 90 g per day is proposed as a working global target, shared more evenly, with not more than 50 g per day coming from red meat from ruminants (ie, cattle, sheep, goats, and other digastric grazers).     

Vitamins, supplements, herbal medicines, and arrhythmias

Nutritional and herbal supplements may have harmful or beneficial effects on arrhythmias. Potential supplements that may have antiarrhythmic activity include omega-3 polyunsaturated fatty acids (N-3 PUFA), coenzyme Q10, and carnitine. Clinical studies show that N-3 PUFA or fish oil supplementation appears to reduce mortality and sudden death. Coenzyme Q10, used in treatment of heart failure, and carnitine and its derivatives may have beneficial effects on arrhythmias, although clinical studies have been limited. Antioxidant supplements may be beneficial, but large studies with vitamin E have been disappointing in that it does not reduce mortality. Correction of electrolyte disturbances has been long advised and magnesium supplementation has been beneficial in the treatment of torsades de pointes and in some studies after cardiac surgery. However, routine electrolyte supplementation with empiric potassium or magnesium in non-deficient patients has not been convincingly beneficial. Several herbal supplements have also been promoted to have antiarrhythmic activity. However, clinical studies are lacking to support routine use of these herbal medications. In addition, some herbal supplements may cause serious proarrhythmia, and many supplements significantly interact with warfarin and digoxin.