Lege Artis Medicinae

[Halfway on a physician’s life course]

VÁRADI András

FEBRUARY 20, 2010

Lege Artis Medicinae - 2010;20(02)

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Lege Artis Medicinae

[Switching from human basal insulin to once daily insulin detemir in type 2 diabetic patients treated by basal-bolus regimen - Results from the LEONCET2, an observational, prospective, multicenter study]

JEMENDY György

[Insulin analogues have been developed in order to overcome some drawbacks of human insulins. Switching from a human insulin-based basal- bolus regimen to once daily detemir could result in improved metabolism and increased safety of the therapy. We assessed the effects of switching from human NPH-insulin to once daily detemir insulin in patients with type 2 diabetes mellitus treated with a basal-bolus insulin regimen. We evaluated the data of 1,474 patients with diabetes (age: 59.1±9.8 years, body weight 89.6±8.6 kg, BMI 31.6±5.4 kg/m2) in an observational, prospective, 24-week, multicenter study. All patients were treated with a basal-bolus regimen consisting of human NPH as basal insulin and a human or analogue insulin as bolus insulin. After enrollment, patients received once daily detemir insulin instead of NPH-insulin, while treatment with bolus insulin was continued. Patients were examined at weeks 12 and 24. By week 24, the mean HbA1c value, irrespective of BMI-categories, decreased significantly (p<0.0001) from 8.63±1.01% by 0.79±0.63%. Fasting blood glucose level decreased from 8.86±1.78 mmol/l to 7.09±1.31 mmol/l; p<0.0001). The target level of HbA1c (<7.0%) was reached by 194 patients (13.1%). The patients’ body weight decreased significantly by week 12 (-0.69±2.00 kg; p<0.0001) and by week 24 (-1.28±2.80 kg; p<0.0001). The changes were more pronounced in higher than in lower BMI-categories (p for trend <0.0001). The mean daily doses of basal insulin were increased from 0.28 IU/kg to 0.33 IU/kg while those of bolus insulins were not changed. The rate of severe hypoglycaemic events decreased significantly (p=0.048) from 2.95 [daytime 1.02, nocturnal 1.93] to 0.06 [daytime 0.04, nocturnal 0.02] episodes/patient-year. In patients with type 2 diabetes mellitus treated with basal-bolus regimen, switching from human basal insulin to once daily insulin detemir results in a significantly improved metabolism, as well as fewer hypoglycaemic events and decreased body weight. Nevertheless, the low rate of patients reaching the glycaemic target implicates that some factors other than an appropriate basal insulin substitution have a role in achieving an optimal metabolic control.]

Lege Artis Medicinae

[Death as a Challenge A Discussion with Criminalist Mihály Filó]

NAGY Zsuzsanna

Lege Artis Medicinae

[Antiplatelet therapy with acetylsalicylic acid - Cardiovascular indications and haemorrhagic complications]

KISS Nóra, KISS Róbert Gábor

[Acetylsalicylic acid effectively blocks the activation of platelets, and becomes a basic element of antithrombotic therapy of patients with high cardiovascular risk. Decrease of platelet reactivity is due to the irreversible inhibition of COX- 1 isoenzime in platelets during treatment. Choosing the right dose is still not an easy task. Bleeding side effects are frequently seen in patients treated with this drug worldwide. Clinical benefit does not improves with escalated doses (300 mg), however the risk of haemorrhagic events increases. Therefore acetylsalicylic acid dose should be reduced to the effective minimal dose (75-150 mg daily) after the acute phase of atherothrombosis in order to prevent side effects. Effect of acetylsalicylic acid differs individually, it might be important screening out those patients who respond less to the drug. Resistance is still an evolving field, proper methodology is to be determined. Right indications of acetylsalicylic acid needs balance between reaching clinical benefit and avoiding side effects. The Hungarian Cardiovascular Therapeutic Consensus Conference 2009 suggested acetylsalicylic acid in primary prevention for those males only, who have overt cardiovascular risk, and SCORE result is more than 10%, with no gastrointestinal haemorrhage in medical history, and with a well-controlled hypertension. Lifelong aspirin prevention should be used after all diagnosed cardiovascular atherothrombotic event as a cornerstone of secondary prevention with low dose (75-150 mg daily) in both genders.]

Lege Artis Medicinae

[Tarnabod – Living on the Edge of Society]

SZALAI László

Lege Artis Medicinae

[Methods of liver support for the treatment of fulminant hepatic failure - therapeutic plasmapheresis, hepatocyte transplantation, methods of biological liver support and new therapeutic approaches: the MARSand the Prometheus treatments]

SCHULLER János

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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

[What happens to vertiginous population after emission from the Emergency Department?]

MAIHOUB Stefani, MOLNÁR András, CSIKÓS András, KANIZSAI Péter, TAMÁS László, SZIRMAI Ágnes

[Background – Dizziness is one of the most frequent complaints when a patient is searching for medical care and resolution. This can be a problematic presentation in the emergency department, both from a diagnostic and a management standpoint. Purpose – The aim of our study is to clarify what happens to patients after leaving the emergency department. Methods – 879 patients were examined at the Semmel­weis University Emergency Department with vertigo and dizziness. We sent a questionnaire to these patients and we had 308 completed papers back (110 male, 198 female patients, mean age 61.8 ± 12.31 SD), which we further analyzed. Results – Based on the emergency department diagnosis we had the following results: central vestibular lesion (n = 71), dizziness or giddiness (n = 64) and BPPV (n = 51) were among the most frequent diagnosis. Clarification of the final post-examination diagnosis took several days (28.8%), and weeks (24.2%). It was also noticed that 24.02% of this population never received a proper diagnosis. Among the population only 80 patients (25.8%) got proper diagnosis of their complaints, which was supported by qualitative statistical analysis (Cohen Kappa test) result (κ = 0.560). Discussion – The correlation between our emergency department diagnosis and final diagnosis given to patients is low, a phenomenon that is also observable in other countries. Therefore, patient follow-up is an important issue, including the importance of neurotology and possibly neurological examination. Conclusion – Emergency diagnosis of vertigo is a great challenge, but despite of difficulties the targeted and quick case history and exact examination can evaluate the central or peripheral cause of the balance disorder. Therefore, to prevent declination of the quality of life the importance of further investigation is high.]

Clinical Neuroscience

[The role of sleep in the relational memory processes ]

CSÁBI Eszter, ZÁMBÓ Ágnes, PROKECZ Lídia

[A growing body of evidence suggests that sleep plays an essential role in the consolidation of different memory systems, but less is known about the beneficial effect of sleep on relational memory processes and the recognition of emotional facial expressions, however, it is a fundamental cognitive skill in human everyday life. Thus, the study aims to investigate the effect of timing of learning and the role of sleep in relational memory processes. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. 84 young adults (average age: 22.36 (SD: 3.22), 21 male/63 female) participated in our study, divided into two groups: evening group and morning group indicating the time of learning. We used the face-name task to measure relational memory and facial expression recognition. There were two sessions for both groups: the immediate testing phase and the delayed retesting phase, separated by 24 hours. Our results suggest that the timing of learning and sleep plays an important role in the stabilizing process of memory representation to resist against forgetting.]

Clinical Neuroscience

Simultaneous subdural, subarachnoideal and intracerebral haemorrhage after rupture of a peripheral middle cerebral artery aneurysm

BÉRES-MOLNÁR Anna Katalin, FOLYOVICH András, SZLOBODA Péter, SZENDREY-KISS Zsolt, BERECZKI Dániel, BAKOS Mária, VÁRALLYAY György, SZABÓ Huba, NYÁRI István

The cause of intracerebral, subarachnoid and subdural haemorrhage is different, and the simultaneous appearance in the same case is extremely rare. We describe the case of a patient with a ruptured aneurysm on the distal segment of the middle cerebral artery, with a concomitant subdural and intracerebral haemorrhage, and a subsequent secondary brainstem (Duret) haemorrhage. The 59-year-old woman had hypertension and diabetes in her medical history. She experienced anomic aphasia and left-sided headache starting one day before admission. She had no trauma. A few minutes after admission she suddenly became comatose, her breathing became superficial. Non-contrast CT revealed left sided fronto-parietal subdural and subarachnoid and intracerebral haemorrhage, and bleeding was also observed in the right pontine region. The patient had leucocytosis and hyperglycemia but normal hemostasis. After the subdural haemorrhage had been evacuated, the patient was transferred to intensive care unit. Sepsis developed. Echocardiography did not detect endocarditis. Neurological status, vigilance gradually improved. The rehabilitation process was interrupted by epileptic status. Control CT and CT angiography proved an aneurysm in the peripheral part of the left middle cerebral artery, which was later clipped. Histolo­gical examination excluded mycotic etiology of the aneu­rysm and “normal aneurysm wall” was described. The brain stem haemorrhage – Duret bleeding – was presumably caused by a sudden increase in intracranial pressure due to the supratentorial space occupying process and consequential trans-tentorial herniation. This case is a rarity, as the patient not only survived, but lives an active life with some residual symptoms.

Clinical Neuroscience

Life threatening rare lymphomas presenting as longitudinally extensive transverse myelitis: a diagnostic challenge

TOLVAJ Balázs, HAHN Katalin, NAGY Zsuzsanna, VADVÁRI Árpád, CSOMOR Judit, GELPI Ellen, ILLÉS Zsolt, GARZULY Ferenc

Background and aims – Description of two cases of rare intravascular large B-cell lymphoma and secondary T-cell lymphoma diagnosed postmortem, that manifested clinically as longitudinally extensive transverse myelitis (LETM). We discuss causes of diagnostic difficulties, deceptive radiological and histological investigations, and outline diagnostic procedures based on our and previously reported cases. Case reports – Our first case, a 48-year-old female was admitted to the neurological department due to paraparesis. MRI suggested LETM, but the treatments were ineffective. She died after four weeks because of pneumonia and untreatable polyserositis. Pathological examination revealed intravascular large B-cell lymphoma (IVL). Our second case, a 61-year-old man presented with headache and paraparesis. MRI showed small bitemporal lesions and lesions suggesting LETM. Diagnostic investigations were unsuccessful, including tests for possible lymphoma (CSF flow cytometry and muscle biopsy for suspected IVL). Chest CT showed focal inflammation in a small area of the lung, and adrenal adenoma. Brain biopsy sample from the affected temporal area suggested T-cell mediated lymphocytic (paraneoplastic or viral) meningoencephalitis and excluded diffuse large B-cell lymphoma. The symptoms worsened, and the patient died in the sixth week of disease. The pathological examination of the presumed adenoma in the adrenal gland, the pancreatic tail and the lung lesions revealed peripheral T-cell lymphoma, as did the brain and spinal cord lesions. Even at histological examination, the T-cell lymphoma had the misleading appearance of inflammatory condition as did the MRI. Conclusion – Lymphoma can manifest as LETM. In cases of etiologically unclear atypical LETM in patients older than 40 years, a random skin biopsy (with subcutaneous adipose tissue) from the thigh and from the abdomen is strongly recommended as soon as possible. This may detect IVL and provide the possibility of prompt chemotherapy. In case of suspicion of lymphoma, parallel examination of the CSF by flow cytometry is also recommended. If skin biopsy is negative but lymphoma suspicion remains high, biopsy from other sites (bone marrow, lymph nodes or adrenal gland lesion) or from a simultaneously existing cerebral lesion is suggested, to exclude or prove diffuse large B-cell lymphoma, IVL, or a rare T-cell lymphoma.