Alexander Fisher

TOXICITY OF PASSIFLORA INCARNATA L

Background: Herbal medicines may have significant adverse effects which are not suspected or recognized. Case Report: A 34-year-old female developed severe nausea, vomiting, drowsiness, prolonged QTc, and episodes of nonsustained ventricular tachycardia following self-administration of a herbal remedy, Passiflora incarnata L., at therapeutic doses. The possible association of symptoms with passiflora was not recognized for several days. She required hospital admission for cardiac monitoring and intravenous fluid therapy. Conclusions: Passiflora incarnata was associated with significant adverse effects in this patient. It is important to ask specifically about the use of herbal medicines in patients with undiagnosed illnesses.

Acute Myocardial Infarction Associated with Albuterol

OBJECTIVE To report a case of acute myocardial infarction (AMI) following the use of albuterol (salbutamol) in a patient without preexisting coronary artery disease and to review the related literature. CASE SUMMARY An 84-year-old white woman with no history of cardiac disease was treated for an exacerbation of chronic obstructive pulmonary disease with albuterol 5 mg and ipratropium bromide 500 μg nebulized with oxygen; the albuterol was given in the same dose every 2 hours. Her respiratory condition improved, but soon after the sixth dose of albuterol, she developed increasing chest tightness. The electrocardiogram (ECG) showed ST segment elevation in the chest leads (V2,3) and, subsequently, the troponin I concentration and creatine kinase rose. Urgent coronary angiography showed smooth coronary arteries with no obstructive coronary artery disease or thrombosis. Left ventriculography showed anterior hypokinesia consistent with anterior myocardial injury. A subsequent echocardiogram also revealed normal left ventricular size but anterior, anteroseptal, and apical hypokinesia. An objective causality assessment revealed that albuterol had a probable likelihood of causing the AMI in this patient. DISCUSSION A MEDLINE search (1966–February 2004) revealed 6 other case reports of AMI associated with albuterol treatment. The possible pathogenesis of albuterol-induced myocardial necrosis includes activation of cardiac and peripheral β2-adrenoceptors, inducing positive chronotropic and inotropic effects and vasodilation with coronary blood flow redistribution. Albuterol can also cause hypokalemia and other metabolic and electrical changes, including prolonged QT interval. These effects may be especially detrimental in patients with hypoxia, hypercapnea, and preexisting heart diseases. CONCLUSIONS Although myocardial injury is a rare complication following albuterol therapy, clinicians should use high-dose β2 agonists with caution. Close monitoring of ECG and metabolic changes is recommended before early repeated high doses are administered.

Entacapone-Induced Hepatotoxicity and Hepatic Dysfunction†

We describe 2 patients with Parkinsons disease who developed hepatotoxicity associated with the use of entacapone, a novel, mainly peripheral acting inhibitor of catechol‐D‐methyltransferase. Hepatotoxicity resolved rapidly with discontinuation of the drug. Analysis of causality in a further case initially linked to entacapone exposure was confounded by conflicting serial adverse reaction reports.

Citalopram-induced severe hyponatraemia with coma and seizure. Case report with literature and spontaneous reports review.

Numerous case reports of hyponatraemia followed increasing use of selective serotonin re-uptake inhibitors (SSRIs) but this adverse effect was only rarely observed in relation to citalopram. We report a case of severe hyponatraemia associated with deep coma, seizure, atrial fibrillation and muscle damage in a 92-year-old woman after only two doses of citalopram, and review 14 cases previously published in the literature and 28 cases spontaneously reported to Australian Drug Reaction Advisory Committee (ADRAC). The data presented suggest that citalopram, as well as SSRIs may cause hyponatraemia secondary to syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The majority of symptomatic cases occurred in elderly patients (79% were older than 70 years) and in women (74%). Polymedication and concomitant use of another psychotropic drug or thiazide diuretic may precipitate and/or augment the development of hyponatraemia/SIADH. In 84% of cases, the hyponatraemia associated with citalopram was detected during the first month of treatment. High level of suspicion, close and careful monitoring of serum sodium concentration particularly in elderly patients and especially in the first month of therapy with citalopram may reduce the incidence of this serious and likely not rare adverse effect.

Prevalence of vitamin K and vitamin D deficiency in patients with hepatobiliary and pancreatic disorders

Little is known about the role of fat-soluble vitamins K and D in liver function and bone metabolism in biliary and pancreatic diseases associated with cholestasis and/or fat malabsorption. The aim of this study was to determine vitamin K of bone, vitamin D and parathyroid hormone status in patients with biliary and pancreatic disorders. In 90 consecutive patients (mean +/- SD age, 65.5 +/- 17.7 years; 45 females) undergoing endoscopic retrograde cholangiopancreatography (68 with choledocholithiasis, 14 with other benign condition, and 8 with cholangiopancreatic cancers) fasting concentrations of carboxylated (cOC) and undercarboxylated osteocalcin (ucOC), 25-hydroxyvitamin D, calcium, phosphorus, magnesium, prothrombin time, liver function tests, lipase, and creatinine were measured. Vitamin D deficiency (25-hydroxyvitamin D <50 nmol/L) was found in 45.6% of patients and elevated parathyroid hormone levels in 27.8%. The ratio ucOC/cOC (index of vitamin K deficiency) was above 20% in 50.6% of patients, above 30% in 31%, and above 50% in 18.4%. Hyperbilirubinemia was a significant independent predictor of low cOC (odds ratio [OR], 11.6; 95% confidence interval [CI], 1.9-59.4; P = .07). The ratio ucOC/cOC positively correlated with alanine aminotransferase levels (r = 0.410; P < .001). Elevated gamma-glutamyltransferase (>180 U/L) and international normalized ratio (>1.1) levels were significant independent predictors of ucOC/cOC greater than 30% after adjustment for other covariants (OR, 5.5; 95% CI, 1.2-25.2; P = .027, and OR, 3.1; 95% CI, 1.1-8.8; P = .036, respectively). This study demonstrates that vitamin K and vitamin D deficiencies are common in patients undergoing endoscopic retrograde cholangiopancreatography. Liver dysfunction is associated with and predictive of vitamin K deficiency of bone and decreased production of osteocalcin, indicating the need for appropriate supplementation.

Cardiovascular diseases in older patients with osteoporotic hip fracture: prevalence, disturbances in mineral and bone metabolism, and bidirectional links

Background Considerable controversy exists regarding the contribution of mineral/bone metabolism abnormalities to the association between cardiovascular diseases (CVDs) and osteoporotic fractures. Aims and methods To determine the relationships between mineral/bone metabolism biomarkers and CVD in 746 older patients with hip fracture, clinical data were recorded and serum concentrations of parathyroid hormone (PTH), 25-hydroxyvitamin D, calcium, phosphate, magnesium, troponin I, parameters of bone turnover, and renal, liver, and thyroid functions were measured. Results CVDs were diagnosed in 472 (63.3%) patients. Vitamin D deficiency was similarly prevalent in patients with (78.0%) and without (82.1%) CVD. The CVD group had significantly higher mean PTH concentrations (7.6 vs 6.0 pmol/L, P < 0.001), a higher prevalence of secondary hyperparathyroidism (SPTH) (PTH > 6.8 pmol/L, 43.0% vs 23.3%, P < 0.001), and excess bone resorption (urinary deoxypyridinoline corrected by creatinine [DPD/Cr] > 7.5 nmol/μmol, 87.9% vs 74.8%, P < 0.001). In multivariate regression analysis, SHPT (odds ratio [OR] 2.6, P = 0.007) and high DPD/Cr (OR 2.8, P = 0.016) were independent indictors of CVD. Compared to those with both PTH and DPD/Cr in the normal range, multivariate-adjusted ORs for the presence of CVD were 17.3 (P = 0.004) in subjects with SHPT and 9.7 (P < 0.001) in patients with high DPD/Cr. CVD was an independent predicator of SHPT (OR 2.8, P = 0.007) and excess DPD/Cr (OR 2.5, P = 0.031). CVD was predictive of postoperative myocardial injury, while SHPT was also an independent predictor of prolonged hospital stay and in-hospital death. Conclusion SHPT and excess bone resorption are independent pathophysiological mediators underlying the bidirectional associations between CVD and hip fracture, and therefore are important diagnostic and therapeutic targets.

Acute Pancreatitis Associated with Angiotensin II Receptor Antagonists

OBJECTIVE: To report a case of acute pancreatitis in a patient receiving a combination formulation of irbesartan and hydrochlorothiazide (HCTZ). CASE SUMMARY: A 33-year-old white woman developed acute pancreatitis 10 days after starting irbesartan 300 mg and hydrochlorothiazide 12.5 mg for treatment of hypertension. Her symptoms disappeared and serum concentrations of lipase and amylase returned to normal 2 days after irbesartan/HCTZ was discontinued. A search of MEDLINE (1990–September 2002) and the Australian Adverse Drug Reaction Advisory Committee database revealed 1 additional case of pancreatitis associated with irbesartan/HCTZ and 3 cases of pancreatitis associated with losartan. DISCUSSION: An objective causality assessment indicates that it is probable that pancreatitis was caused by the angiotensin II receptor antagonist irbesartan (and the same is probably true for losartan). It is less likely that the hydrochlorothiazide in irbesartan/HCTZ caused pancreatitis in our patient since the dose was lower than that usually associated with thiazide-induced pancreatitis. Angiotensin II receptors are thought to be important in regulation of pancreatic secretion and microcirculation, but the mechanism of pancreatitis induced by angiotensin II receptor antagonists remains unclear. CONCLUSIONS: Clinicians should be aware that irbesartan/HCTZ or losartan may cause acute pancreatitis. If abdominal pain develops, the medication should be discontinued and the patient investigated for acute pancreatitis.

Poststroke Hip Fracture: Prevalence, Clinical Characteristics, Mineral-Bone Metabolism, Outcomes, and Gaps in Prevention

Objective. To assess the prevalence, clinical and laboratory characteristics, and short-term outcomes of poststroke hip fracture (HF). Methods. A cross-sectional study of 761 consecutive patients aged ≥60 years (82.3 ± 8.8 years; 75% females) with osteoporotic HF. Results. The prevalence of poststroke HF was 13.1% occurring on average 2.4 years after the stroke. The poststroke group compared to the rest of the cohort had a higher proportion of women, subjects with dementia, history of TIA, hypertension, coronary artery disease, secondary hyperparathyroidism, higher serum vitamin B12 levels (>350 pmol/L), walking aid users, and living in residential care facilities. The majority of poststroke HF patients had vitamin D insufficiency (68%) and excess bone resorption (90%). This group had a 3-fold higher incidence of postoperative myocardial injury and need for institutionalisation. In multivariate analysis, independent indicators of poststroke HF were female sex (OR 3.6), history of TIA (OR 5.2), dementia (OR 4.1), hypertension (OR 3.2), use of walking aid (OR 2.5), and higher vitamin B12 level (OR 2.3). Only 15% of poststroke patients received antiosteoporotic therapy prior to HF. Conclusions. Approximately one in seven HFs occurs in older stroke survivors and are associated with poorer outcomes. Early implementation of fracture prevention strategies is needed.

Should we screen adults with osteoporotic fractures for coeliac disease

In the recently published debate in Gut regarding the utility of mass screening of European and North American populations for coeliac disease (CD), divergent conclusions were presented ( Gut 2003; 52 :168–9 and 170–1). In this context, the increased utility of screening adults for CD in those presenting with concomitant morbidity (for example, metabolic bone disease and fracture) was raised. To support such an hypothesis, evidence of either an increased fracture rate in those with CD or, alternatively, an increased incidence of CD in those presenting with fracture would be required. Thomason and colleagues,1 in a study of 244 patients with CD and 161 age and sex matched controls, addressed the first of these possibilities. They found that patients with …

Interactions between Serum Adipokines and Osteocalcin in Older Patients with Hip Fracture.

Introduction. Experiments on genetically modified animals have discovered a complex cross-regulation between adipokines (leptin, adiponectin) and osteocalcin. The relationships between these molecules in human osteoporosis are still unclear. We evaluated the hypothesis of a bidirectional link between adipokines and osteocalcin. Materials and Methods. In a cross-sectional study of 294 older patients with osteoporotic hip fracture, we estimated serum concentrations of leptin, adiponectin, resistin, osteocalcin, parameters of mineral metabolism, and renal function. Results. After adjustment for multiple potential confounders, serum osteocalcin concentration was inversely associated with resistin and positively with leptin, leptin/resistin ratio, and adiponectin/resistin ratio. In multivariate regression models, osteocalcin was an independent predictor of serum leptin, resistin, leptin/resistin, and adiponectin/resistin ratios. Conclusions. Our data support the bidirectional regulation between osteocalcin and adipokines, but contrary to the genetically modified animal models, in older subjects with osteoporotic hip fracture, serum osteocalcin is positively associated with leptin and inversely with resistin.