Lege Artis Medicinae

[“Home Birth should not be Legalized, it is Legal” – An Interview with Ágnes Geréb]

- LAM, ELITMED.HU -

MARCH 20, 2011

Lege Artis Medicinae - 2011;21(03)

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Lege Artis Medicinae

[JAK2 V617F: a new risk factor of stent thrombosis?]

PINCZÉS István, FEKETE Viktória, ZÁMOLYI Károly

[INTRODUCTION - Although the introduction of stents has dramatically improved the efficiency of percutaneous coronary interventions, a new complication, the stent thrombosis has appeared. Owing to intensive research, the incidence of this previously common complication is currently 1%. Because of the high mortality and morbidity, it is important to find more and more predictors, which might help to further reduce the incidence. CASE REPORT - Our elderly male patient presented with acute anterior myocardial infarct. Stent implantation of the left anterior descendent branch was performed using coronarography, with no complications. After five days without any symptoms, ST elevation recurred and subacute stent thrombosis was deteceted. Because of the laboratory results showing thrombocytosis, we performed JAK2 V617F screening, with a positive result. Prolonged heparin therapy, platelet aggegation inhibition at a transiently elevated dose and hydroxyurea treatment because of the myeloproliferativ malignancy were used. At the follow-up visit, the patient did not report any complaints, and cell counts for all three myeloid cell lines were in the normal range. CONCLUSION - The thrombogenic feature of the classic myeloproliferative disorders is well-known, and JAK2 V617F mutations further increase the risk. In our departement, screeing for such genetic alteration was performed in patients with stent thrombosis and a platelet count higher than 450 G/l. Two of the three cases had positive results. Supported by the literature, we think that the hematologic disease lead to the thrombotic complication in our patients. In our opinion, the JAK2 V617F is a potential risk factor of stent thrombosis.]

Lege Artis Medicinae

[Treatment of cardiovascular risk of patients with hypertension: the role of fixed combination amlodipin-atorvastatin therapy in light of recent studies]

ALFÖLDI Sándor

[Risk factors for cardiovascular disease commonly coexist in patients with hypertension: high blood pressure is accompanied by alterations of lipid and glucose metabolism, obesity or smoking in the vast majority (70-80%) of patients. In the presence of multiple risk factors, the increment of relative cardiovascular risk caused by individual risk factors is not additive but multiplied. Since the ASCOT trial was published, statin therapy is recommended to every hypertensive patients with LDL cholesterol >2.5 mmol/L and at least intermediate cardiovascular risk (Euro SCORE>3%). Some studies show, however, that in daily clinical practice, blood pressure and lipid targets are achieved in a small percentage of patients with hypertension and dyslipidaemia. This is partly due to the fact that borderline alterations of serum cholesterol and their risk-increasing effects are often neglected during the planning of the therapy, and therapeutic adherence and persistence of patients are insufficient. According to new studies, both factors can be improved significantly if the antihypertensive and lipid-lowering treatments are initiated simultaneously, using a single pill with dual effect.]

Lege Artis Medicinae

[Succesful endocrine therapy of breast cancer with hepatic metastases]

FARCZÁDI Enikő, BOÉR Katalin

Lege Artis Medicinae

[New treatment option for oral anticoagulation in the prevention of cardiogenic stroke - Focus on the RE-LY trial]

SZAPÁRY László

[Atrial fibrillation (AF) represents the most common cause of cardioembolic stroke. The prevalence of AF increases with age and affects 10% of elderly people. AF-related stroke is usually severe and has a high mortality. The risk of stroke can be estimated on the basis of risk factors accompanying AF and age. Patients with one of the highest risk are those with AF and previous TIA or stroke. Efficient prevention is achieved by chronic anticoagulation therapy. In clinical practice, the use of vitamin K antagonists (VKA) has been the only option. The use of these agents is limited for a number of reasons, and clinicians are especially reluctant to use them in elderly patients at high risk of stroke. Consequently, of the patients with AF for whom anticoagulant therapy is indicated, only about 50-60% receives such therapy, and only half of the treated patients achieves target INR values. More than 50 years after the introduction of warfarin, data of trials with the new direct thrombin inhibitor dabigatran have been published in the past few years. In this paper, we review the results of the phase III, international RE-LY trial, published in 2009, which evaluated the preventive efficacy dabigatran etexilate in patients with AF compared with warfarin at a therapeutic dose. On the basis of the results, dabigatran used at a dose of 2×110mg daily provides the same protection as warfarin, whereas at a dose of 2×150mg it provides a signiificantly more efficient protection from AF-associated stroke and systemic embolism. In addition to its excellent preventive effect, dabigatran tretament results in a significant decrease in the risk of intracranial haemorrhages, and of other major haemorrhages. On the basis of the results, dabigatran will probably change the current treatment paradigm in the stroke prevention in patients with AF, and its introduction can substantially increase the number of patients treated efficiently and safely.]

Lege Artis Medicinae

[Perindopril plus Indapamid CombinAtion blood preSSure reductiOn study (PICASSO)]

FARSANG Csaba

[INTRODUCTION - International and Hungarian (JNC-7, ESH/ESC2007 és 2009, MHT 2009) Guidelines suggest a target blood pressure <140/90 mmHg for hypertensive patients, and <130/80 mmHg for those with high/very high cardiovascular risk (e.g. patients with diabetes mellitus, chronic renal disease). It was proved that for achieving the most efficient antihypertensive effect and reducing side effects, thd use of drug combinations is needed in most patients. In Hungary, ACE-inhibitor plus diuretic combination is one of the most frequently used one in Hungary. The aim of the PICASSO study was to evaluate the efficacy and metabolic effects of the fixed combination of high-dose perindopril plus indapamide (Coverex-AS Komb Forte®) in clinical practice of hypertonologists, cardiologists and general practicioners. PATIENTS AND METHODS - Patients with uncontrolled, grade 1 or 2 primary hypertension, age, >18years were involved in the open, 3-month, multicentre, prospective, observational, non-interventional clinical study if the treating physician indicated a combination treatment with higher dose antihypertensive drugs. Blood pressure (also with ABPM), heart rate, metabolic parameters (plasma lipids, blood sugar, Na, K, creatinine, uric acid, GGT) were measured by routine methods, medical history and quality of life parameters were registered on a validated questionnaire. Changes in the above parameters were also separately evaluated in patients with different risk factors or with concomitant diseases. RESULTS - Data of 9683 patients were evaluated (54% women, 46% men, average age 61.8 years). By the end of the therapy used in the study, blood pressure average decreased from 159/93 to 131/80, by ABPM from 145/83 to 126/74 mmHg (24hr averages, systolic/diastolic blood pressure, respectively), the heart rate from 79 to 73 beats/min (p<0,001). Target blood pressure was achieved in 75,4% of patients with no major concomitant disease, but only in 14% of those with a concomitant disease characterised by lower target blood pressure. The diurnal index by ABPM did not change substantially. Clinically significant decreases were found in the plasma levels of total cholesterol, LDL-cholesterol, triglycerides, fasting glucose and uric acid levels, but there were no major changes in serum levels of HDL-cholesterol, Na, K, and GGT. Quality of life parameters significantly improved by the end of the study. CONCLUSIONS - Combinations of perindopril and indapamide can be successfully and safely used in everyday practice.]

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Alexithymia is associated with cognitive impairment in patients with Parkinson’s disease

SENGUL Yildizhan, KOCAK Müge, CORAKCI Zeynep, SENGUL Serdar Hakan, USTUN Ismet

Cognitive dysfunction (CD) is a common non-motor symptom of Parkinson’s disease (PD). Alexithy­mia is a still poorly understood neuropsychiatric feature of PD. Cognitive impairment (especially visuospatial dysfunction and executive dysfunction) and alexithymia share com­mon pathology of neuroanatomical structures. We hypo­thesized that there must be a correlation between CD and alexithymia levels considering this relationship of neuroanatomy. Objective – The aim of this study was to evaluate the association between alexithymia and neurocognitive function in patients with PD. Thirty-five patients with PD were included in this study. The Toronto Alexithymia Scale–20 (TAS-20), Geriatric Depression Inventory (GDI) and a detailed neuropsychological evaluation were performed. Higher TAS-20 scores were negatively correlated with Wechsler Adult Intelligence Scale (WAIS) similarities test score (r =-0.71, p value 0.02), clock drawing test (CDT) scores (r=-0.72, p=0.02) and verbal fluency (VF) (r=-0.77, p<0.01). Difficulty identifying feelings subscale score was negatively correlated with CDT scores (r=-0.74, p=0.02), VF scores (r=-0.66, p=0.04), visual memory immediate recall (r=-0.74, p=0.01). VF scores were also correlated with difficulty describing feelings (DDF) scores (r=-0.66, p=0.04). There was a reverse relationship bet­ween WAIS similarities and DDF scores (r=-0.70, p=0.02), and externally oriented-thinking (r=-0.77,p<0.01). Executive function Z score was correlated with the mean TAS-20 score (r=-62, p=0.03) and DDF subscale score (r=-0.70, p=0.01) Alexithymia was found to be associated with poorer performance on visuospatial and executive function test results. We also found that alexithymia was significantly correlated with depressive symptoms. Presence of alexithymia should therefore warn the clinicians for co-existing CD.

Clinical Neuroscience

Late simultaneous carcinomatous meningitis, temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting with mono-symptomatic vertigo – a clinico-pathological case reporT

JARABIN András János, KLIVÉNYI Péter, TISZLAVICZ László, MOLNÁR Anna Fiona, GION Katalin, FÖLDESI Imre, KISS Geza Jozsef, ROVÓ László, BELLA Zsolt

Although vertigo is one of the most common complaints, intracranial malignant tumors rarely cause sudden asymmetry between the tone of the vestibular peripheries masquerading as a peripheral-like disorder. Here we report a case of simultaneous temporal bone infiltrating macro-metastasis and disseminated multi-organ micro-metastases presenting as acute unilateral vestibular syndrome, due to the reawakening of a primary gastric signet ring cell carcinoma. Purpose – Our objective was to identify those pathophysiological steps that may explain the complex process of tumor reawakening, dissemination. The possible causes of vestibular asymmetry were also traced. A 56-year-old male patient’s interdisciplinary medical data had been retrospectively analyzed. Original clinical and pathological results have been collected and thoroughly reevaluated, then new histological staining and immunohistochemistry methods have been added to the diagnostic pool. During the autopsy the cerebrum and cerebellum was edematous. The apex of the left petrous bone was infiltrated and destructed by a tumor mass of 2x2 cm in size. Histological reexamination of the original gastric resection specimen slides revealed focal submucosal tumorous infiltration with a vascular invasion. By immunohistochemistry mainly single infiltrating tumor cells were observed with Cytokeratin 7 and Vimentin positivity and partial loss of E-cadherin staining. The subsequent histological examination of necropsy tissue specimens confirmed the disseminated, multi-organ microscopic tumorous invasion. Discussion – It has been recently reported that the expression of Vimentin and the loss of E-cadherin is significantly associated with advanced stage, lymph node metastasis, vascular and neural invasion and undifferentiated type with p<0.05 significance. As our patient was middle aged and had no immune-deficiency, the promoting factor of the reawakening of the primary GC malignant disease after a 9-year-long period of dormancy remained undiscovered. The organ-specific tropism explained by the “seed and soil” theory was unexpected, due to rare occurrence of gastric cancer to metastasize in the meninges given that only a minority of these cells would be capable of crossing the blood brain barrier. Patients with past malignancies and new onset of neurological symptoms should alert the physician to central nervous system involvement, and the appropriate, targeted diagnostic and therapeutic work-up should be established immediately. Targeted staining with specific antibodies is recommended. Recent studies on cell lines indicate that metformin strongly inhibits epithelial-mesenchymal transition of gastric cancer cells. Therefore, further studies need to be performed on cases positive for epithelial-mesenchymal transition.

Clinical Neuroscience

Creutzfeldt-Jakob Disease: A single center experience and systemic analysis of cases in Turkey

USLU Ilgen Ferda, ELIF Gökçal, GÜRSOY Esra Azize, KOLUKISA Mehmet, YILDIZ Babacan Gulsen

We aimed to analyze the clinical, laboratory and neuroimaging findings in patients with sporadic Creutzfeldt-Jakob disease (CJD) in a single center as well as to review other published cases in Turkey. Between January 1st, 2014 and June 31st, 2017, all CJD cases were evaluated based on clinical findings, differential diagnosis, the previous misdiagnosis, electroencephalography (EEG), cerebrospinal fluid and cranial magnetic resonance imaging (MRI) findings in our center. All published cases in Turkey between 2005-2018 were also reviewed. In a total of 13 patients, progressive cognitive decline was the most common presenting symptom. Two patients had a diagnosis of Heidenhain variant, 1 patient had a diagnosis of Oppenheimer-Brownell variant. Seven patients (53.3%) had been misdiagnosed with depression, vascular dementia, normal pressure hydrocephalus or encephalitis. Eleven patients (87%) had typical MRI findings but only 5 of these were present at baseline. Asymmetrical high signal abnormalities on MRI were observed in 4 patients. Five patients (45.4%) had periodic spike wave complexes on EEG, all appeared during the follow-up. There were 74 published cases in Turkey bet­ween 2005 and 2018, with various clinical presentations. CJD has a variety of clinical features in our patient series as well as in cases reported in Turkey. Although progressive cognitive decline is the most common presenting symptom, unusual manifestations in early stages of the disease might cause misdiagnosis. Variant forms should be kept in mind in patients with isolated visual or cerebellar symptoms. MRI and EEG should be repeated during follow-up period if the clinical suspicion still exists.

Clinical Neuroscience

The etiology and age-related properties of patients with delirium in coronary intensive care unit and its effects on inhospital and follow up prognosis

ALTAY Servet, GÜRDOGAN Muhammet, KAYA Caglar, KARDAS Fatih, ZEYBEY Utku, CAKIR Burcu, EBIK Mustafa, DEMIR Melik

Delirium is a syndrome frequently encountered in intensive care and associated with a poor prognosis. Intensive care delirium is mostly based on general and palliative intensive care data in the literature. In this study, we aimed to investigate the incidence of delirium in coronary intensive care unit (CICU), related factors, its relationship with inhospital and follow up prognosis, incidence of age-related delirium and its effect on outcomes. This study was conducted with patients hospitalized in CICU of a tertiary university hospital between 01 August 2017 and 01 August 2018. Files of all patients were examined in details, and demographic, clinic and laboratory parameters were recorded. Patients confirmed with psychiatry consultation were included in the groups of patients who developed delirium. Patients were divided into groups with and without delirium developed, and baseline features, inhospital and follow up prognoses were investigated. In addition, patients were divided into four groups as <65 years old, 65-75 yo, 75-84 yo and> 85 yo, and the incidence of delirium, related factors and prognoses were compared among these groups. A total of 1108 patients (mean age: 64.4 ± 13.9 years; 66% men) who were followed in the intensive care unit with variable indications were included in the study. Of all patients 11.1% developed delirium in the CICU. Patients who developed delirium were older, comorbidities were more frequent, and these patients showed increased inflammation findings, and significant increase in inhospital mortality compared to those who did not develop delirium (p<0.05). At median 9-month follow up period, rehospitalization, reinfarction, cognitive dysfunction, initiation of psychiatric therapy and mortality were significantly higher in the delirium group (p<0.05). When patients who developed delirium were divided into four groups by age and analyzed, incidence of delirium and mortality rate in delirium group were significantly increased by age (p<0.05). Development of delirium in coronary intensive care unit is associated with increased inhospital and follow up morbidity and mortality. Delirium is more commonly seen in geriatric patients and those with comorbidity, and is associated with a poorer prognosis. High-risk patients should be more carefully monitored for the risk of delirium.

Clinical Neuroscience

Autonomic nervous system may be affected after carpal tunnel syndrome surgery: A possible mechanism for persistence of symptoms after surgery

ONDER Burcu, KELES Yavuz Betul

After carpal tunnel surgery, some patients report complaints such as edema, pain, and numbness. Purpose – The aim of this study was to evaluate autonomic nervous system function in patients with a history of carpal tunnel surgery using sympathetic skin response (SSR). Thirty three patients (55 ±10 years old) with a history of unilateral operation for carpal tunnel syndrome were included in the study. The SSR test was performed for both hands. Both upper extremities median and ulnar nerve conduction results were recorded. A reduced amplitude (p=0.006) and delayed latency (p<0.0001) were detected in the SSR test on the operated side compared to contralateral side. There was no correlation between SSR and carpal tunnel syndrome severity. Although complex regional pain syndrome does not develop in patients after carpal tunnel surgery, some of the complaints may be caused by effects on the autonomic nervous system.