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1.  Acute myocardial infarction as the first presentation of thyrotoxicosis in a 31-year old woman - case report 
Thyroid Research  2010;3:1.
A 31-year old woman, previously fit & well was admitted with pressing retrosternal chest pain and palpitations of sudden onset. Her body weight was normal (BMI 20.5 kg/m2) and there was no significant family history of cardiac disease. She smoked, however, about 15 cigarettes a day and she had been taking combined oral contraceptive pill (Cilest®) for about three years. On admission she appeared sweaty and in pain, blood pressure 130/70 mmHg, heart rate about 110/min, mild lid-lag sign. Heart sounds were normal and chest was clear. ECG revealed 2-3 mm ST segment elevations in II, III, aVF as well as V2 to V5. Troponin I was raised and she was qualified to an emergency coronary angiography. This revealed a massive spasm of left anterior descending (LAD) coronary artery that responded to intracoronary glyceryl trinitrite administration, however, with the presence of critical narrowing of the LAD apical segment with possible superimposed thrombus. Cardiac ultrasound revealed akinesis of 1/2 of apical area consistent with myocardial infarction
Treatment and progress
She was started on Aspirin, Simvastatin, and Diltiazem, but continued to have persistent tachycardia and tremor. Thyroid function tests were ordered and showed thyrotoxicosis [free T4-46.9 pmol/l (ref. range 9-25), free T3-11.9 pmol/l (2-5), TSH - 0.02 mIU/l (0.27-4.2)]. She was referred for an endocrine opinion and started on Thiamazole. Other investigations revealed elevated anti-TPO and anti-TSH receptor antibodies consistent with Graves' disease. Thrombophilia screen was negative. She had remained euthyroid on a "block & replace" regimen (Thiamazole plus L-Thyroxine) that was discontinued after 18 months. She denies any anginal symptoms, but continues to smoke against medical advice.
Our case highlights the possibility of development of an acute myocardial infarction in a young subject with thyrotoxicosis. We speculate that patient's smoking habit combined with subtle thyrotoxicosis-induced prothrombotic state and/or coronary-artery spasm had lead to the above-mentioned acute coronary event.
PMCID: PMC2831875  PMID: 20181115
2.  Evaluation of coronary microvascular function in patients with vasospastic angina 
AIM: To investigate endothelium-dependent and -independent coronary microvascular functions in patients with vasospastic angina (VSA).
METHODS: Thirty-six patients with VSA (30 men and 6 women; mean age, 58 years) were enrolled in this study. VSA was defined as ≥ 90% narrowing of the epicardial coronary arteries on angiography performed during a spasm provocation test, presence of chest pain, and/or ST-segment deviation on an electrocardiogram (ECG). Patients (n = 36) with negative spasm provocation test results and those matched for age and sex were enrolled as a control group (nonVSA group). Low-dose acetylcholine (ACh; 3 μg/min) was infused into the left coronary ostium for 2 min during the spasm provocation test. Following the spasm provocation test, nitroglycerin (0.2 mg) was administered intracoronally. Coronary blood flow (was calculated from quantitative angiography and Doppler flow velocity measurements, and the coronary flow reserve was calculated as the ratio of coronary flow velocity after injection of adenosine triphosphate (20 μg) to the baseline value. Changes in the coronary artery diameter in response to ACh and nitroglycerin infusion were expressed as percentage changes from baseline measurements.
RESULTS: Body mass index was significantly lower in the VSA group than in the nonVSA group. The frequency of conventional coronary risk factors and the rate of statin use were similar between the 2 groups. The left ventricular ejection fraction as evaluated by echocardiography was similar between the 2 groups. The duration of angina was 9 ± 2 mo. The results of blood chemistry analysis were similar between the 2 groups. Low-dose ACh did not cause coronary spasms. The change in coronary artery diameter in response to ACh was lower in the VSA group (-1.4% ± 9.3%) than in the nonVSA group (3.1% ± 6.5%, P < 0.05), whereas nitroglycerin-induced coronary artery dilatation and coronary blood flow increase in response to ACh or coronary flow reserve did not differ significantly between the 2 groups.
CONCLUSION: These findings suggest that microvascular coronary function may be preserved despite endothelial dysfunction of the epicardial coronary arteries in patients with VSA.
PMCID: PMC3565162  PMID: 23390571
Coronary spasm; Endothelial function; Acetylcholine
3.  Transient bilateral abducens neuropathy with post-tetanic facilitation and acute hypokalemia associated with oxaliplatin: a case report 
Oxaliplatin is a cytotoxic platinum compound that is in widespread use in the treatment of gastrointestinal cancers. It has been occasionally associated with acute motor neuropathy, but the precise mechanism is uncertain. To the best of our knowledge, we report the first case of a patient demonstrating post-tetanic facilitation in the setting of transient bilateral abducens neuropathy and hypokalemia, after being infused with oxaliplatin.
Case presentation
A 47-year-old Indian woman with metastatic gastric cancer was receiving an oxaliplatin infusion at the initiation of her third cycle of palliative chemotherapy. She developed acute bilateral abducens neuropathy with post-tetanic facilitation alongside acute laryngopharyngodysesthesia and hypokalemia. Following supportive management, including potassium infusion and warming, her neurological signs and symptoms were spontaneously resolved. This syndrome did not recur in subsequent cycles following prolongation of infusion duration and the addition of supportive calcium and magnesium infusions.
The novel clinical observation of post-tetanic facilitation highlights a possible involvement of voltage-gated channels at the presynaptic terminals in the mechanism of acute oxaliplatin neurotoxicity.
PMCID: PMC2827431  PMID: 20205880
4.  Coronary Balloon Angioplasty in a Severe Takotsubo Syndrome 
Mædica  2013;8(3):265-268.
We reported a patient with Takotsubo syndrome, with severe symptoms, prolonged angina with hemodynamic compromise, in the context of severe coronary artery spasm, without response to full medical treatment, which was successfully managed with coronary balloon angioplasty. A 49-year old woman was admitted with chest pain, ECG changes and elevated myocardial necrosis markers suggestive for acute coronary syndrome. First coronary angiography revealed normal epicardial arteries and typical left ventricular apical ballooning, strongly suggestive for Takotsubo syndrome. Forty-eight hours later, with standard medical treatment, patient developed again severe angina with hemodynamic consequences. Second angiography showed total occlusive spasm of one coronary artery, without response to full medical treatment. Coronary balloon angioplasty was performed with final good result. Two month later, angiography revealed normal coronary arteries and normal ventricular shape. The patient is currently asymptomatic.
As far as we know, no other examples of similar cases were published in medical literature. Therefore, interventional treatment can be taken into consideration for some particular types of patients with Takotsubo syndrome, non-responsive to medical treatment; despite of balloon angioplasty or stenting of coronary vasospasm is not a standard of care.
PMCID: PMC3869116  PMID: 24371496
Takotsubo syndrome; balloon angioplasty; coronary artery spasm
5.  Granulomatous Lung Disease Requiring Mechanical Ventilation Induced by a Single Application of Oxaliplatin-Based Chemotherapy for Colorectal Cancer: A Case Report 
Combined chemotherapeutic regimens in conjunction with oxaliplatin are considered safe and effective treatment options in the clinical management of metastatic colorectal cancer. A 62-year-old male patient with a metastatic rectal carcinoma developed a pulmonary reaction after the first application of the combined standard chemotherapy regimen (5-fluorouracil and sodium folinic acid as a 24 h infusion and oxaliplatin). Following the first dose of chemotherapy, the patient developed acute dyspnoea and fever. A computerised scan of the chest revealed bilateral pulmonary patchy consolidation. Despite high-dose empiric antibiotic and antimycotic treatment, no clinical improvement was seen. The patient's condition deteriorated, and he required invasive mechanical ventilation. Diagnostic thoracoscopic wedge resections were performed for further diagnosis. The histological workup revealed distinct granulomatous inflammation, but no microbial pathogens were to be found. Thereupon, a drug-induced reaction to chemotherapy was suspected and high-dose steroid treatment initiated. Subsequently, the patient's respiratory condition improved and he was extubated. The present case exemplifies the rare course of a bilateral pneumonia-like, drug-induced granulomatous reaction following a single application of oxaliplatin. In addition to the known side effects of oxaliplatin-containing combination chemotherapy, unexpected serious adverse events in the form of pulmonary toxicities should also be taken into account.
PMCID: PMC3638573  PMID: 23691384
6.  A Prehospital Acute Coronary Syndrome in a Cocaine User: An Unstable Clinical Situation 
Journal of Medical Toxicology  2011;8(1):80-82.
Chest pain is a common reason why cocaine-addicted patients call the emergency department, and acute coronary syndromes are difficult to diagnose in these situations. A 30-year-old cocaine-user patient contacts the Emergency Medical Assistance Service with constrictive chest pain. A doctor is sent out to the patient at home. The initial ECG is normal. No other aetiology of chest pain is revealed, except nicotine and cocaine addictions. First, a coronary artery spasm is suggested, caused by the injection of cocaine. During the journey, the patient indicates that the chest pain has returned. A 12-lead ECG shows repolarisation abnormality in the form of a subepicardial ischaemia. Fibrinolysis is not prescribed in view of the patient’s history and of the proximity of the interventional cardiology team. The coronary angiogram enables the diagnosis of myocardial bridging in the middle anterior interventricular artery, and no significant lesion of the coronary arteries is noted. A particular feature of prehospital management in France is that medical care can be given in the early stages by a physician who is called by the patient. This case report discusses the specific care requirements of which the emergency physician needs to be aware in the context of this unstable clinical situation due to the urgency associated with the difficulties of ECG diagnosis of ST-segment elevation in cocaine users.
PMCID: PMC3550224  PMID: 21302016
Cocaine; Prehospital care; Coronary vasospasm; Fibrinolytic agents; Interventional cardiology; Delay of care
7.  XELOX vs FOLFOX-4 as first-line therapy for metastatic colorectal cancer: NO16966 updated results 
British Journal of Cancer  2011;105(1):58-64.
We report updated overall survival (OS) data from study NO16966, which compared capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX4) as first-line therapy in metastatic colorectal cancer.
NO16966 was a randomised, two-arm, non-inferiority, phase III comparison of XELOX vs FOLFOX4, which was subsequently amended to a 2 × 2 factorial design with further randomisation to bevacizumab or placebo. A planned follow-up exploratory analysis of OS was performed.
The intent-to-treat (ITT) population comprised 2034 patients (two-arm portion, n=634; 2 × 2 factorial portion, n=1400). For the whole NO16966 study population, median OS was 19.8 months in the pooled XELOX/XELOX-placebo/XELOX-bevacizumab arms vs 19.5 months in the pooled FOLFOX4/FOLFOX4-placebo/FOLFOX4-bevacizumab arms (hazard ratio 0.95 (97.5% CI 0.85–1.06)). In the pooled XELOX/XELOX-placebo arms, median OS was 19.0 vs 18.9 months in the pooled FOLFOX4/FOLFOX4-placebo arms (hazard ratio 0.95 (97.5% CI 0.83–1.09)). FOLFOX4 was associated with more grade 3/4 neutropenia/granulocytopenia and febrile neutropenia than XELOX, and XELOX with more grade 3 diarrhoea and grade 3 hand-foot syndrome than FOLFOX4.
Updated survival data from study NO16966 show that XELOX is similar to FOLFOX4, confirming the primary analysis of progression-free survival. XELOX can be considered as a routine first-line treatment option for patients with metastatic colorectal cancer.
PMCID: PMC3137415  PMID: 21673685
5-fluorouracil/folinic acid; capecitabine; colorectal cancer; overall survival; oxaliplatin
8.  Oral Calcium Ameliorating Oxaliplatin-Induced Peripheral Neuropathy 
The journal of applied research  2004;4(4):576-582.
Oxaliplatin has become an integral part of the standard treatment for advanced colorectal cancer. While oxaliplatin has only mild hematologic and gastrointestinal side effects, its dose-limiting toxicity is a cumulative sensory neurotoxicity. Oxaliplatin causes a unique, but frequent, acute sensory neuropathy that is triggered or aggravated by exposure to cold but is rapidly reversible, without persistent impairment of sensory function. Various strategies have been proposed to prevent or treat oxaliplatin-induced neurotoxicity. One such strategy is the “Stop-and-Go” concept, which uses the reversibility of neurologic symptoms to aim at delivering higher cumulative oxaliplatin doses, as long as the therapy is still effective and the other is the administration of neuromodulatory agents (ie, calcium-magnesium infusions, carbamazepine, gabapentin, amifostine, alpha-lipoic acid, and glutathione) that could limit the neurotoxic effects of oxaliplatin. Among all of the agents, intravenous calcium and magnesium have shown the most promise in prophylaxis and treatment of oxaliplatin-induced neurotoxicity. We report a case of a patient, in which oral calcium supplements not only were successful in treating his neurotoxicity, but we also were able to administer a cumulative dose of 2500 mg/m2 (990 mg/m2 with oral calcium). Although the current recommendations for the management of the acute and cumulative neurotoxicity from oxaliplatin with the use of infusion of Ca/Mg remain valid, our case is the first report demonstrating the role of oral minerals in ameliorating neurotoxicity from oxaliplatin. Future studies to evaluate the role of oral Ca/Mg are warranted, since they could prove to be an effective, less expensive and more convenient way to treat and prevent oxaliplatin-associated toxicity.
PMCID: PMC2758795  PMID: 19816592
oxaliplatin; neuropathy; colon cancer; calcium; magnesium
9.  Dobutamine stress test and beta-agonist - a potential concern for nuclear cardiology testing: a case report 
Cases Journal  2009;2:7466.
Chest pain with ST-segment elevation is a rare clinical problem during dobutamine stress testing. Although beta-agonists treatment prior to dobutamine stress testing has been shown to reduce the duration and amount of dobutamine infusion and atropine requirement, there is insufficient information about potential complications of this pharmacologic combination.
Case presentation
We present a 67-year-old patient with dobutamine stress testing -induced chest pain and ST elevation who received albuterol for clinical treatment of bronchospastic disease prior to the test. She developed persistent chest pain and ST elevation despite medical management. Urgent cardiac catheterization showed no significant obstructive coronary artery disease. Thus coronary artery spasm was likely responsible for the chest pain and electrocardiogram abnormality in our patient as a result of β-agonist and dobutamine combination.
Beta-agonists pre-treatment with dobutamine stress testing may induce coronary spasm in association with chest pain and ST elevation. Clinicians and nuclear cardiologist should be aware of this potential side effect of β-agonists treatment with dobutamine stress testing, particularly since dobutamine stress testing in nuclear cardiology is done in patient with chronic obstructive lung disease.
PMCID: PMC2740317  PMID: 19829971
10.  Coronary artery spasm induced by carotid sinus massage 
Heart  2000;84(1):e2.
A 60 year old man with a history of frequent episodes of chest pain and dizziness was referred for evaluation of coronary artery disease. He had no significant coronary artery stenosis at baseline coronary angiography. A carotid sinus massage was performed for evaluation of carotid sinus hypersensitivity in the patient. Both heart rate and blood pressure decreased a little, and returned to baseline level immediately after carotid sinus massage. However, 2.5 minutes after carotid sinus massage, ECG showed ST segment elevation in leads II, III, and aVF. Four minutes after carotid sinus massage, he had chest pain with a progressive elevation in the ST segment in the same leads, when he had 99% focal spasm in the right coronary artery. The vasospasm induced by carotid sinus massage was reproducible over several minutes and resolved spontaneously. Coronary artery spasm may be provoked by the enhanced vagal activation due to carotid sinus massage.

Keywords: coronary vasospasm; vasospastic angina; coronary artery spasm; carotid sinus massage
PMCID: PMC1729425  PMID: 10862603
11.  Survey of oxaliplatin-associated neurotoxicity using an interview-based questionnaire in patients with metastatic colorectal cancer 
BMC Cancer  2005;5:116.
New chemotherapy regimens for patients with colorectal cancer have improved survival, but at the cost of clinical toxicity. Oxaliplatin, an agent used in first-line therapy for metastatic colorectal cancer, causes acute and chronic neurotoxicity. This study was performed to carefully assess the incidence, type and duration of oxaliplatin neurotoxicity.
A detailed questionnaire was completed after each chemotherapy cycle for patients with metastatic colorectal cancer enrolled in a phase I trial of oxaliplatin and capecitabine. An oxaliplatin specific neurotoxicity scale was used to grade toxicity.
Eighty-six adult patients with colorectal cancer were evaluated. Acute neuropathy symptoms included voice changes, visual alterations, pharyngo-laryngeal dysesthesia (lack of awareness of breathing); peri-oral or oral numbness, pain and symptoms due to muscle contraction (spasm, cramps, tremors). When the worst neurotoxicity per patient was considered, grade 1/2/3/4 dysesthesias and paresthesias were seen in 71/12/5/0 and 66/20/7/1 percent of patients. By cycles 3, 6, 9, and 12, oxaliplatin dose reduction or discontinuation was needed in 2.7%, 20%, 37.5% and 62.5% of patients.
Oxaliplatin-associated acute neuropathy causes a variety of distressing, but transient, symptoms due to peripheral sensory and motor nerve hyperexcitability. Chronic neuropathy may be debilitating and often necessitates dose reductions or discontinuation of oxaliplatin. Patients should be warned of the possible spectrum of symptoms and re-assured about the transient nature of acute neurotoxicity. Ongoing studies are addressing the treatment and prophylaxis of oxaliplatin neurotoxicity.
PMCID: PMC1266024  PMID: 16168057
12.  Spontaneous Coronary Artery Dissection during Cabergoline Therapy 
Texas Heart Institute Journal  2012;39(1):92-94.
Although spontaneous coronary artery dissection is a rare cause of acute coronary syndrome, it should be considered during the evaluation of patients who have chest pain. Coronary vasospasm can lead to spontaneous dissection. The dopamine agonist cabergoline is known to cause digital vasospasm. Herein, we report a case of spontaneous right coronary artery dissection in a 43-year-old woman who was taking cabergoline as therapy for prolactinoma. To our knowledge, this is the first report of an apparent relationship between cabergoline therapy and spontaneous coronary artery dissection. The possible association of cabergoline with coronary artery spasm and dissection should be considered in patients who present with chest pain while taking this medication.
PMCID: PMC3298899  PMID: 22412238
Acute coronary syndrome/diagnosis/etiology/therapy; cabergoline/adverse effects; coronary vasospasm/chemically induced; dopamine agonists/adverse effects; rupture, spontaneous/diagnosis/etiology; substance-related disorders/complications
13.  Coronary spasm-related acute myocardial infarction in a patient with essential thrombocythemia 
World Journal of Cardiology  2011;3(8):278-280.
We report a case of essential thrombocythemia (ET) in a 30-year-old female who exhibited inferior wall ST-elevation acute myocardial infarction (AMI) without significant obstructive coronary artery disease. Right coronary vasospasm was observed after intra-coronary methylergonovine administration and she received verapamil 120 mg/d
thereafter and hydroxyurea 1500 mg/d for thrombocythemia. After discontinuation of the hydroxyurea for 9 mo based on the impression of coronary spasm-related instead of coronary thrombosis-related AMI, her platelet count rose but no chest pain was observed. It is suggested that coronary spasm potentially plays a role in patients with ET, AMI and no significant coronary artery stenosis.
PMCID: PMC3163243  PMID: 21876778
Coronary spasm; Acute myocardial infarction; Essential thrombocythemia
14.  Facial nerve compression by the posterior inferior cerebellar artery causing facial pain and swelling: a case report 
We report an unusual case of facial pain and swelling caused by compression of the facial and vestibulocochlear cranial nerves due to the tortuous course of a branch of the posterior inferior cerebellar artery. Although anterior inferior cerebellar artery compression has been well documented in the literature, compression caused by the posterior inferior cerebellar artery is rare. This case provided a diagnostic dilemma, requiring expertise from a number of specialties, and proved to be a learning point to clinicians from a variety of backgrounds. We describe the case in detail and discuss the differential diagnoses.
Case presentation
A 57-year-old Caucasian woman with a background of mild connective tissue disease presented to our rheumatologist with intermittent left-sided facial pain and swelling, accompanied by hearing loss in her left ear. An autoimmune screen was negative and a Schirmer’s test was normal. Her erythrocyte sedimentation rate was 6mm/h (normal range: 1 to 20mm/h) and her immunoglobulin G and A levels were mildly elevated. A vascular loop protocol magnetic resonance imaging scan showed a loop of her posterior inferior cerebellar artery taking a long course around the seventh and eighth cranial nerves into the meatus and back, resulting in compression of her seventh and eighth cranial nerves. Our patient underwent microvascular decompression, after which her symptoms completely resolved.
Hemifacial spasm is characterized by unilateral clonic twitching, although our patient presented with more unusual symptoms of pain and swelling. Onset of symptoms is mostly in middle age and women are more commonly affected. Differential diagnoses include trigeminal neuralgia, temporomandibular joint dysfunction, salivary gland pathology and migrainous headache. Botulinum toxin injection is recognized as an effective treatment option for primary hemifacial spasm. Microvascular decompression is a relatively safe procedure with a high success rate. Although a rare pathology, posterior inferior cerebellar artery compression causing facial pain, swelling and hearing loss should be considered as a differential diagnosis in similar cases.
PMCID: PMC4018959  PMID: 24661509
Facial pain; Hemifacial spasm; Facial pain; Vascular compression; Posterior inferior cerebellar artery; Vascular compression
15.  Spontaneous coronary artery dissection causing acute myocardial infarction in a 62-year-old postmenopausal woman without co-morbidities: a case report 
Spontaneous coronary artery dissection is an important yet rare cause of acute coronary syndrome. The available literature shows a higher risk factor for women, notably during pregnancy and puerperium. The incidence in postmenopausal women is exceedingly rare, and is more commonly seen in association with concurrent predisposing factors.
We illustrate an extremely rare case of a 62-year-old post-menopausal woman presenting with an acute myocardial infarction secondary to spontaneous dissection of the left anterior descending artery. Subsequent investigations did not reveal the presence of any co-morbidities.
To the best of our knowledge, our patient is one of the oldest documented cases of spontaneous coronary artery dissection on record, and is notable for having no known underlying risk factors for development of spontaneous coronary artery dissection.
Given the paucity of literature on spontaneous coronary artery dissection, particularly in postmenopausal women, we believe this case will provide further insight into the clinical presentation and management of this rare entity.
Case presentation
A 62-year-old previously healthy postmenopausal Hispanic woman presented with chest pain and was found to have an ST elevation myocardial infarction. Cardiac catheterization revealed a dissection in her left anterior descending artery. Revascularization was deferred; our patient received appropriate medical management and remained asymptomatic. A full panel of tests was done to exclude underlying connective tissue disorders and vasculitis. On subsequent follow-up, our patient continued to do well and all work-up was reported as negative.
We describe the varied presentation and subsequent management of a case of spontaneous coronary artery dissection and highlight the importance of considering spontaneous coronary artery dissection as a differential diagnosis even in older, postmenopausal women.
The consequences of a delay in diagnosis and appropriate management are associated with a high mortality and morbidity; hence we believe that reporting all cases of spontaneous coronary artery dissection, particularly in postmenopausal women, will add invaluable information to the limited literature on this rare condition.
PMCID: PMC3539931  PMID: 23272729
16.  Cardiogenic Shock From Global Myocardial Ischemia Induced by Simultaneous Multivessel Coronary Spasm 
Korean Circulation Journal  2012;42(6):427-430.
Coronary artery spasm is an uncommon, but well recognized, etiology for acute myocardial infarction. However, cardiogenic shock with myocardial infarction resulting from simultaneous multiple coronary artery spasm has been rarely reported, and not in Korea. Recently, we experienced such a case in a 50-year-old Korean man without previous diagnosis of variant angina. The patient, hospitalized for blood sugar control, developed severe chest pain accompanying ST-segment elevation in multiple leads. The patient immediately received cardiac catheterization because of cardiogenic shock. Coronary angiogram revealed the severe and simultaneous spasm of three major epicardial arteries, which was promptly relieved by an intracoronary administration of isosorbide dinitrate. This case highlights the need to rule out the potential mechanism of coronary spasm even in the most severe episodes of acute coronary syndrome.
PMCID: PMC3390430  PMID: 22787475
Shock, cardiogenic; Myocardial infarction; Coronary vasospasm
17.  Should We Establish a New Protocol for the Treatment of Peripartum Myocardial Infarction? 
Texas Heart Institute Journal  2012;39(2):244-248.
Peripartum myocardial infarction is a rare event that is associated with high mortality rates. The differential diagnosis includes coronary artery dissection, coronary artery thrombosis, vascular spasm, and stenosis. Our evaluation of 2 cases over a 5-year time period has led to a hypothesis that peripartum myocardial infarction is an immune-mediated event secondary to coronary endothelial sensitization by fetal antigen. In our patients, we supplemented standard medical therapy with immunotherapy consisting of corticosteroids, plasmapheresis, and intravenous immunoglobulin.
Herein, we present our most recent case—that of a 29-year-old black woman (gravida V, para IV), 2 weeks postpartum with no relevant medical history. She presented with a 1-week history of chest pain. Initial electrocardiographic and cardiac biomarkers were consistent with acute coronary syndrome. Echocardiography revealed reduced systolic function with inferior-wall hypokinesis. Angiography revealed diffuse disease with occlusion of the left anterior descending coronary artery not amenable to revascularization. We were successful in treating the myocardial infarction without the use of catheter-based interventions, by modifying the immunologic abnormalities.
Two cases do not make a protocol. Yet we believe that this case and our earlier case lend credence to the hypothesis that peripartum myocardial infarction arises from sensitization by fetal antigens. This concept and the immune-modifying treatment protocol that we propose might also assist in understanding and treating other inflammatory-disease states such as peripartum cardiomyopathy and standard acute myocardial infarction. All of this warrants further investigation.
PMCID: PMC3384054  PMID: 22740744
Immunotherapy; intravenous immunoglobulin; myocardial infarction, peripartum/etiology/immunology/therapy; plasma exchange; postpartum period; pregnancy complications, cardiovascular/diagnosis/therapy; puerperal disorders/diagnosis/immunology/therapy
18.  Hypersensitivity reaction and acute immune-mediated thrombocytopenia from oxaliplatin: two case reports and a review of the literature 
Oxaliplatin is a platinum compound used in the treatment of gastrointestinal malignancies, including colorectal cancer. The incidence of hypersensitivity reaction in patients receiving oxaliplatin is approximately 15%, with severe reaction (grade 3 and 4) occurring in 2% of patients.
Case presentation
We report two patients with metastatic colorectal cancer who developed de novo hypersensitivity reaction and acute thrombocytopenia after oxaliplatin infusion. Both patients had oxaliplatin treatment several years before and exhibited hypersensitivity on the third dose of oxaliplatin in recent treatment. Oxaliplatin was discontinued when clinical reaction was identified. Both patients were confirmed to have strong oxaliplatin-induced IgG platelet-reactive antibodies. Both patients' thrombocytopenia resolved within two weeks after discontinuation of oxaliplatin. One patient had disease stabilization lasting for three months without chemotherapy. Both patients subsequently received other chemotherapeutic agents without evidence of hypersensitivity reaction or immune-mediated thrombocytopenia.
We recommend vigilant monitoring of complete blood count and signs and symptoms of bleeding after the occurrence of oxaliplatin-induced hypersensitivity to avoid serious complications of immune-mediated thrombocytopenia.
PMCID: PMC2859393  PMID: 20346128
19.  Oxaliplatin-Related Ocular Toxicity 
Case Reports in Oncology  2010;3(3):423-427.
We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity.
PMCID: PMC2999736  PMID: 21151636
Chemotherapeutic drugs; Electrooculogram; FOLFOX; Optic nerve; Oxaliplatin; Retina; Retinal pigment epithelium
20.  Pseudoinfarction pattern in a patient with hyperkalemia, diabetic ketoacidosis and normal coronary vessels: a case report 
A rare electrocardiographic finding of hyperkalemia is ST segment elevation or the so called 'pseudoinfarction' pattern. It has been suggested that hyperkalemia causes the 'pseudoinfarction' pattern not only through its direct myocardial effects, but also through other mechanisms, such as anoxia, acidosis, and coronary artery spasm.
Case presentation
A 33-year-old Caucasian woman with insulin-treated diabetes presented with continuous epigastric pain of four hours duration. Her coronary heart disease risk factors apart from diabetes included hypercholesterolemia and smoking. Her initial electrocardiogram revealed ST segment elevation in the anteroseptal leads consistent with anterior myocardial infarction. Blood tests revealed hyperglycemia, hyperkalemia, metabolic acidosis and urine ketones, while a bed-side cardiac echocardiogram showed no segmental wall motion abnormality. We provisionally diagnosed diabetic ketoacidosis that was possibly precipitated by acute myocardial infarction, as there were findings in favor of (epigastric pain, electrocardiogram pattern, presence of 3 coronary heart disease risk factors) and against (young age, normal echocardiogram) the diagnosis of acute myocardial infarction. We performed cardiac angiography in order to exclude an anterior acute myocardial infarction, which could lead to myocardial damage and possible severe complications should there be a delay in treatment. Angiography revealed normal coronary arteries. During the procedure, ST segment elevation in the anteroseptal leads was still present in our patient's electrocardiogram results.
ST segment elevation is a rare manifestation of hyperkalemia. In our patient, coronary spasm did not contribute to such an electrocardiography finding.
PMCID: PMC2876172  PMID: 20420664
21.  Significant Response to Lower Acetylcholine Dose Is Associated with Worse Clinical and Angiographic Characteristics in Patients with Vasospastic Angina 
Korean Circulation Journal  2013;43(7):468-473.
Background and Objectives
The intracoronary injection of acetylcholine (Ach) has been shown to induce coronary spasms in patients with variant angina. Clinical significance and angiographic characteristics of patients with a significant response to lower Ach dosages are as-yet non-clarified compared with patients responding to higher Ach doses.
Subjects and Methods
A total of 3034 consecutive patients underwent coronary angiography with Ach provocation tests from January 2004 to August 2010. Ach was injected in incremental doses of 20, 50, 100 µg into the left coronary artery. Significant coronary artery spasm was defined as focal or diffuse severe transient luminal narrowing (>70%) with/without chest pain or ST-T change on the electrocardiogram (ECG). We compared the clinical and angiographic characteristics of patients who responded to a lower Ach dose (20 or 50 µg, n=556) to those that responded to a higher Ach dose (100 µg, n=860).
The baseline clinical and procedural characteristics are well balanced between the two groups, except diabetes was higher in the lower Ach dose group and there were differences in medication history. After adjusting for confounding factors, the lower Ach dose group showed more frequent temporary ST elevation and atrioventricular block on the ECG. Furthermore, the group of patients who responded to the lower Ach dose was associated with a higher incidence of baseline and severe spasm than those who responded to a higher Ach dose.
Patients with a significant response to a lower Ach dose were associated with more frequent ST elevation, baseline spasm, and more severe spasm compared with those who responded to a higher Ach dose, suggesting more intensive medical therapy with close clinical follow-up is required for those patients.
PMCID: PMC3744734  PMID: 23964293
Angina pectoris, variant; Acetylcholine
22.  Retrospective analysis of capecitabine and oxaliplatin (XELOX) plus bevacizumab as a first-line treatment for Japanese patients with metastatic colorectal cancer 
Molecular and Clinical Oncology  2013;2(1):134-138.
XELOX plus bevacizumab is an effective treatment strategy and has a manageable tolerability profile when administered to Japanese patients with metastatic colorectal cancer (mCRC). In this study, we retrospectively reviewed cases in which XELOX plus bevacizumab were administered in order to evaluate its efficacy and safety in clinical practice. In total, 40 patients with mCRC who presented at Fuchu Hospital received XELOX plus bevacizumab as a first-line treatment between September, 2009 and April, 2012. Eligible patients had histologically confirmed mCRC. XELOX consisted of a 2-h intravenous infusion of oxaliplatin 130 mg/m2 on day 1 plus oral capecitabine 1,000 mg/m2 twice daily for 2 weeks of a 3-week cycle. Overall survival (OS) and survival benefit were analyzed when patients continued with XELOX plus bevacizumab beyond disease progression. The median progression-free survival (PFS) was 290 days [95% confidence interval (CI): 222–409 days] and the median OS was 816 days (95% CI: 490 days-not calculated). The response rate (RR; complete plus partial response) was 67.5%, and the disease control rate (RR plus stable disease) was 90%. The most common adverse events observed following administration of XELOX plus bevacizumab were neurosensory toxicity (82.5%), anorexia (50%), hypertension (45%) and a decrease in the platelet count (40%). The most common grade 3/4 adverse events were neurosensory toxicity (15%) and fatigue (15%). In conclusion, XELOX plus bevacizumab may be considered a routine first-line treatment option for patients with mCRC. Notably, the combination of capecitabine and bevacizumab was safe with an acceptable toxicity profile and induced a significant rate of disease control.
PMCID: PMC3915698  PMID: 24649322
capecitabine; oxaliplatin; bevacizumab; colorectal cancer
23.  A Randomized, Phase II Trial of Standard Triweekly Compared with Dose-Dense Biweekly Capecitabine Plus Oxaliplatin Plus Bevacizumab as First-Line Treatment for Metastatic Colorectal Cancer: XELOX-A-DVS (Dense Versus Standard) 
The Oncologist  2012;17(7):937-946.
The results of a trial of metastatic colorectal cancer patients randomized to capecitabine plus oxaliplatin plus bevacizumab as a standard triweekly cycle or a dose-dense biweekly cycle schedule are reported. The biweekly combination at the doses studied cannot be recommended.
Capecitabine administered for 7 days biweekly with oxaliplatin (XELOX) biweekly has been reported to have activity and safety profiles similar to those of standard capecitabine given for 14 days triweekly. Multiple studies have shown that the addition of bevacizumab to 5-fluorouracil–based chemotherapy is active and well tolerated.
Patients with metastatic colorectal cancer (mCRC) were randomized to XELOX plus bevacizumab using a standard triweekly cycle (Q3W) or a dose-dense biweekly cycle (Q2W) schedule. The primary endpoint was the progression-free survival (PFS) interval. This trial is registered on (identifier, NCT00159432).
In total, 435 U.S. patients were randomized. The median PFS intervals were 9.6 months in the Q3W group and 9.1 months in the Q2W group. The median overall survival times were 28.4 months and 22.1 months and the median times to treatment failure were 5.5 months and 3.4 months, respectively. Overall, gastrointestinal disorders were the most common (93%) adverse event (AE). Grade 3 or 4 AEs occurred in 75% and 81% of patients in the Q3W and Q2W groups, respectively. Treatment discontinuation as a result of diarrhea (5% versus 10%) and hand–foot syndrome (2% versus 9%) was less common in the Q3W group than in the Q2W group, respectively.
Based on these results, the first-line treatment of U.S. patients with mCRC using a biweekly combination of XELOX and bevacizumab at the doses studied cannot be recommended. XELOX Q3W remains the preferred schedule for the management of mCRC.
PMCID: PMC3399650  PMID: 22622147
Capecitabine; Clinical trial; Bevacizumab; Progression-free survival; Metastatic colorectal cancer; Toxicity; XELOX
24.  Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report) 
We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient’s performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.
PMCID: PMC3751809  PMID: 23957924
Hepatic arterial infusion chemotherapy; Resistance to systemic chemotherapy; Unresectable colon cancer
25.  Intravenous Atropine Relieves Coronary Arterial Spasm and Hemodynamic Decompensation during Recovery after Exercise 
Texas Heart Institute Journal  2000;27(2):212-214.
A 66-year-old man developed right coronary arterial spasm and hemodynamic decompensation during the early recovery phase of a treadmill exercise test. The unstable condition was corrected immediately after intravenous administration of atropine. A subsequent coronary angiographic study revealed insignificant right coronary artery stenosis. The pathophysiology of this response may be related to rapid alterations in autonomic balance during recovery after exercise. To our knowledge, this is the 1st reported case in which atropine effected immediate reversal of coronary arterial spasm and hemodynamic decompensation that were induced by exercise, rather than by pharmacologic agents. Atropine might be an effective treatment in patients who experience exercise-induced coronary arterial spasm and hemodynamic decompensation, but further investigation is warranted.
PMCID: PMC101059  PMID: 10928512
Atropine/administration and dosage; atropine/therapeutic use; coronary vasospasm/diagnosis; coronary vessels/physiopathology; exercise test

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