Lege Artis Medicinae

[What’s behind a pathological liver finding]

GASZTONYI Beáta

NOVEMBER 20, 2007

Lege Artis Medicinae - 2007;17(11)

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Lege Artis Medicinae

[The 17th Congress of the European Respiratory Society]

BALIKÓ Zoltán

Lege Artis Medicinae

[Gastrolienalis fistula caused by acute pancreatitis]

CZAKÓ László, GÉCZI Tibor, LEINDLER László, FARKAS Gyula, TISZLAVICZ László, LONOVICS János

Lege Artis Medicinae

[Surgical aspects of the gastrointestinal diseases]

JAKAB Ferenc

Lege Artis Medicinae

[OUR EXPERIENCE WITH COMBINED ANTIVIRAL TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS C WITH PERSISTENTLY NORMAL ALANINE AMINOTRANSFERASE LEVELS]

HORVÁTH Gábor, TOLVAJ Gyula, HALÁSZ Tünde, STOTZ Gyula

[INTRODUCTION - Persistently normal alanine aminotransferase levels, which occur in a fraction of patients chronically infected with hepatitis C virus, do not rule out the presence of chronic hepatitis C, even of that with advanced inflammation and fibrosis. Here we report our results of the treatment of these patients. PATIENTS AND METHODS - Patients with histologically confirmed chronic hepatitis C received combined antiviral treatment with pegylated interferon (alfa-2a 1×180 μg/week or alfa-2b 1×1.5 μg/kg/week) and ribavirin (800- 1200 mg/day) for 48-52 weeks. The alanineaminotransferase levels of 21 patients (14 females, 7 males, age: 20-54, mean 38 years) did not reach the upper limit of normal (40 U/l) during the period of observation (≥6 months). There were 19 and 2 cases with hepatitis C virus genotype 1b and 3, respectively. The patients' hepatitis activity index was 3.7 1.75, fibrosis score: 0.9 0.64, baseline viral titer: 1.18 1.12×106 IU/ml, alanine-aminotransferase level: 33.51 7.2 U/l. The last 100 unselected patients with elevated alanine-aminotransferase levels enrolled in treatment for chronic hepatitis C and who were followed for at least 6 months served as the control group with the following parameters: 41 females and 59 males (age: 18- 65, mean: 45.65 years), viral genotypes: 98 and 2 cases of type 1 and 3, respectively, hepatitis activity index: 5.44±4.03, stage: 1.29±1.00, baseline viral titer: 4.13±6.25×106 IU/ml. RESULTS - In the study group, all patients were hepatitis C virus RNA negative at the end of the treatment and with one exception remained so by the end of the 6-month follow-up period (20/21), while the sustained virologic response was 36% in the control group. The pretreatment normal alanine aminotransferase level decreased significantly (15.26 4.9 vs 33.51 7.2 U/l, p<0.001) by the end of the treatment, and remained at this level during the follow-up in all except one relapse case. CONCLUSION - The efficacy of the combined antiviral treatment is high in patients with persistently normal alanine aminotransferase levels, possibly due to the relatively younger age, the higher proportion of females, the lower baseline viral titer, and the less advanced liver disease (lower inflammatory activity and less or absent fibrosis) observed in this group. Combined antiviral treatment is recommended for patients with histologically confirmed chronic hepatitis C with normal alanine aminotransferase levels, even with mild inflammatory activity and minimal or absent fibrosis in the liver tissue. The previous suggestions based on published evidence to revise the upper limit of the normal range of alanine aminotransferase level are supported by the results of this study.]

Lege Artis Medicinae

[PAIN RELIEF IN THE CLINICAL PRACTICE - THE USE OF MAJOR ANALGETICS]

HORVÁTH J. Attila

[The use of opioids to relieve strong, unbearable pain is a method that has been known for thousands of years and is still effective today. In contrast to the earlier view, opioids today are not only given to cancer patients. The application area of morphine derivatives is generally the relief of exceptionally strong pain regardless of the diagnosis, but opiates are undoubtedly most commonly used to treat cancer-related or strong acute pain. Strong pain reducers are used much more in developed countries for the treatment of non-cancer related severe pain refractory to other approaches. Today the use of opiates and their derivatives (fentanyl, oxycodon) for non-cancer related pain relief is recognized by the national health insurance in that it allows general practitioners to prescribe them, upon the recommendation of a neurosurgeon, orthopaedic surgeon, traumatologist or rheumatologist, with a significant 90% subsidy for six months to ensure easy access for patients in severe, refractory pain due to degenerative musculoskelatal diseases (ICD: M47, M48, M16.9, M17.9, M54.4, M51.0, M51.1). The indications of opioid use, however, are not limited to strong nociceptive pain since they are also effective in certain types of peripheral neuropathic pain. In brief, a basic principle of the use of major analgetics is that their indication is primarily based on the intensity of pain and not on the nature of the disease, even though the latter has a major influence on the clinician's strategy of pain relief.]

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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

Neuroscience highlights: Main cell types underlying memory and spatial navigation

KRABOTH Zoltán, KÁLMÁN Bernadette

Interest in the hippocampal formation and its role in navigation and memory arose in the second part of the 20th century, at least in part due to the curious case of Henry G. Molaison, who underwent brain surgery for intractable epilepsy. The temporal association observed between the removal of his entorhinal cortex along with a significant part of hippocampus and the developing severe memory deficit inspired scientists to focus on these regions. The subsequent discovery of the so-called place cells in the hippocampus launched the description of many other functional cell types and neuronal networks throughout the Papez-circuit that has a key role in memory processes and spatial information coding (speed, head direction, border, grid, object-vector etc). Each of these cell types has its own unique characteristics, and together they form the so-called “Brain GPS”. The aim of this short survey is to highlight for practicing neurologists the types of cells and neuronal networks that represent the anatomical substrates and physiological correlates of pathological entities affecting the limbic system, especially in the temporal lobe. For that purpose, we survey early discoveries along with the most relevant neuroscience observations from the recent literature. By this brief survey, we highlight main cell types in the hippocampal formation, and describe their roles in spatial navigation and memory processes. In recent decades, an array of new and functionally unique neuron types has been recognized in the hippocampal formation, but likely more remain to be discovered. For a better understanding of the heterogeneous presentations of neurological disorders affecting this anatomical region, insights into the constantly evolving neuroscience behind may be helpful. The public health consequences of diseases that affect memory and spatial navigation are high, and grow as the population ages, prompting scientist to focus on further exploring this brain region.

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.

Hypertension and nephrology

[Polycystic kidney]

DOLGOS Szilveszter, TÁRNOKI Ádám Domonkos, TÁRNOKI Dávid László

[The most common monogenic nephropathy is a congenital, cystic, bulky process in the kidney that leads to a gradual deterioration in renal function. Renal failure is often associated with cystic liver or pancreatic lesions, cerebral artery aneurysm, or mitral prolapse.]

Clinical Neuroscience

Neuroscience highlights: The mirror inside our brain

KRABÓTH Zoltán, KÁLMÁN Bernadette

Over the second half of the 19th century, numerous theories arose concerning mechanisms involved in understanding of action, imitative learning, language development and theory of mind. These explorations gained new momentum with the discovery of the so called “mirror neurons”. Rizzolatti’s work inspired large groups of scientists seeking explanation in a new and hitherto unexplored area of how we perceive and understand the actions and intentions of others, how we learn through imitation to help our own survival, and what mechanisms have helped us to develop a unique human trait, language. Numerous studies have addressed these questions over the years, gathering information about mirror neurons themselves, their subtypes, the different brain areas involved in the mirror neuron system, their role in the above mentioned mechanisms, and the varying consequences of their dysfunction in human life. In this short review, we summarize the most important theories and discoveries that argue for the existence of the mirror neuron system, and its essential function in normal human life or some pathological conditions.