Search

Introduction and objective: Community-acquired sepsis is a life-threatening systemic reaction to infection starting 72 hours within hospital admittance. Data concerning kinetics of serum C-reactive protein (CRP) and procalcitonin (PCT) levels during disease progression are sparse. Our aim was to analyze kinetics of CRP and PCT among adults with community-acquired sepsis. Methods: We analyzed data of consecutive patients hospitalized with community-acquired sepsis at our centre during 2016. Sepsis was defined according to ACCP/SCCM criteria, community-acquisition was ascertained by a priori exclusion criteria. CRP and PCT values of days 1–14 were collected. Primary outcomes were in-hospital all-cause mortality, intensive care unit admission, secondary outcomes were septic source and the causative microorganism. Absolute (ΔabsCRP, ΔabsPCT) and relative (Δ%CRP, Δ%PCT) differences were calculated between values at the time of diagnosis and control values within 24 hours of empirical antimicrobial therapy initiation. Results: 193 patients were included. In-hospital all-cause mortality was 13.9%, intensive care unit admittance was 25.9%. Patients who died had significantly smaller median Δ%PCT decrements (–7.7 ± 127.9% vs. –45.7 ± 88.8%, p = 0.01), compared to survivors. During hospital stay, daily absolute values of PCT on days 2–14, while those of CRP on days 5–14 were significantly higher among patients who died. Patients admitted to the intensive care unit also had smaller median Δ%PCT decrements (–19.6 ± 72.5% vs. –49.8 ± 100.8%, p = 0.01), compared to non-admitted patients. Calculated parameters did not show significant correlations with septic focus or causative microorganisms. Discussion, conclusion: Our findings suggest that specific fluctuations of CRP and PCT are observable, and Δ%PCT might be a favourable parameter for outcome prediction among adults with community-acquired sepsis.

The objective of the present pilot study was to determine the force required to break (a) intact canine tibiae, (b) tibiae following the osteotomy of the tibial tuberosity and (c) tibiae following Tibial Tuberosity Advancement- (TTA-) rapid surgery. Six pairs of tibiae of dogs between 15 and 35 kg body weight were used in a cadaver study. Three groups were created with four tibiae in each group; intact (Group 1), osteotomy of the tibial tuberosity and tibial crest (Group 2) and TTA-rapid (Group 3). The tibiae were put under static axial compressive load, applied until failure. The force required to break the tibiae was termed maximal force (F max). The mean of F max was 8193.25 ± 2082.84 N in Group 1, 6868.58 ± 1950.44 N in Group 2 and 7169.71 ± 4450.39 N in Group 3. The sample size was small for a statistical analysis but as a preliminary result, we have determined the force (F max) required to break canine tibiae. Furthermore, we hypothesise that osteotomies result in weakening of the tibial structure.

Összefoglaló. Bevezetés: A krónikus myeloid leukaemia a diagnosztika fejlődésének és a tirozin-kináz-gátlók bevezetésének köszönhetően az elmúlt évtizedekben kiváló prognózisú betegséggé vált. Célkitűzés: A betegséggel kapcsolatos ismereteink nagy része klinikai vizsgálatokból származik, emiatt kiemelt szerepük van a nem szelektált beteganyagon végzett elemzéseknek. Módszer: Retrospektív elemzésünkben a Semmelweis Egyetem Belgyógyászati és Onkológiai Klinikáján 2003 és 2019 között tirozin-kináz-gátló kezelésben részesült betegek adatait tekintettük át. Eredmények: Klinikánkon összesen 88 beteg részesült terápiában, közülük 73 beteg az analízis időpontjában is kezelés alatt állt. A betegek 5 éves össztúlélése 86%, 5 éves progressziómentes túlélése 70% volt. 9 beteg halt meg, közülük 2 betegnél a halál oka a progrediáló alapbetegség volt. 38 betegnél volt szükség az első vonalban terápiaváltásra, a váltás oka akkor elsősorban az elégtelen terápiás válasz volt. A későbbi terápiaváltásokra elsősorban intolerancia miatt került sor. Az első vonalban a betegek több mint fele major molekuláris választ ért el, a jelenlegi kezelés mellett a betegek 85%-ánál major molekuláris választ detektáltunk. Megbeszélés: Adataink alapján az intézményünkben kezelt betegek túlélése és a betegek által elért terápiás válasz megfelel a nemzetközi adatoknak. Következtetés: Mivel nem válogatott beteganyagról van szó, a kapott eredmények pontosabb képet adhatnak a krónikus myeloid leukaemia tirozin-kináz-gátlóval történt kezelésének eredményeiről. Orv Hetil. 2021; 162(32): 1297-1302., Introduction: As a result of advances in diagnostic techniques and the introduction of tyrosine kinase inhibitors, the prognosis of chronic myeloid leukemia has improved over the last decades., Objective: Most of our knowledge about chronic myeloid leukemia results from clinical trials, therefore data derived from non-selected patient population is substantial., Method: Data of chronic myeloid leukemia patients treated with tyrosine kinase inhibitors at the Department of Internal Medicine and Oncology, Semmelweis University, between 2003 and 2019 were analysed retrospectively., Results: 88 patients received treatment, 73 patients were on therapy at the time of the analysis. Overall survival at 5 years was 86%, progression-free survival at 5 years was 70%. 9 patients died, 2 of them due to progressive disease. 38 patients needed 2nd line therapy, the main reason of treatment change was failure of therapy. Subsequent treatment modifications were conducted mostly because of intolerance. More than half of the patients on 1st line treatment reached major molecular response and 85% of the patients on treatment at the end of the analysis are in major molecular response., Discussion: Based on our data, survival and therapeutic response of patients in our center are similar to the international results., Conclusion: This analysis provides real-world data about treatment results of chronic myeloid leukemia in the tyrosine kinase inhibitor era. Orv Hetil. 2021; 162(32): 1297-1302.

Streptococcal toxic shock syndrome (STSS) is a hyperacute, life-threatening illness, a complication of invasive streptococcal (mostly group A, rarely groups B, G or C) infection. There is no portal of entry (skin, vagina, pharynx) in nearly half of the STSS cases. The initial signs and symptoms (fever, flu-like complaints, hypotension) are scarce and aspecific, but because of its rapid progression and poor prognosis, early high level of suspicion is necessary. Management has 3 crucial points: initiation of anti-streptococcal regimen (and intravenous immunoglobulin in some cases), aggressive intensive care support of multi-organ failure, and surgical control of the infective source. In this article, we present a case of a patient succumbing to streptococcal toxic shock syndrome which was preceded by primary S. pyogenes bacteremia, and review the key points of this potentially fatal disease for practising clinicians. Orv Hetil. 2019; 160(48): 1887-1893.

Genetic abnormalities associated with the development, progression and treatment resistance of hematological malignancies are extensively characterized. Rapid, reliable and cost-efficient techniques are needed to screen the clinically relevant aberrations in routine diagnostics. Multiplex ligation-dependent probe amplification is an efficient tool to analyze genomic copy number aberrations at 55-60 different genomic loci. The method allows the profiling of prognostic and predictive markers; thus, it can efficiently be combined with karyotyping and fluorescence in situ hybridization, the most commonly used diagnostic techniques to detect cytogenetic lesions. Furthermore, the method can interrogate methylation status and unravel point mutations at specific sites, providing results in 24 hours. Here, we describe the technical background of multiplex ligation-dependent probe amplification, summarize its advantages and limitations as well as discuss its role in oncohematological diagnostics and research. Finally, future outlook is provided, with emphasis on recent technological advances related to next-generation sequencing. Orv Hetil. 2018; 159(15): 583-592.

Congenital adrenal hyperplasia is a group of genetic diseases due to the disablement of 7 genes; one of them is steroid 21-hydroxylase deficiency. The genes of congenital adrenal hyperplasia encode enzymes taking part in the steroidogenesis of adrenal gland. Steroid 21-hydroxylase deficiency is an autosomal recessive disorder caused by mutations of the steroid 21-hydroxylase gene. The mutations of steroid 21-hydroxylase gene cause 95% of the congenital adrenal hyperplasia cases. Although the non-classic steroid 21-hydroxylase deficiency with mild symptoms is seldom diagnosed, the classic steroid 21-hydroxylase deficiency may lead to life-threatening salt-wasting and adrenal crises due to the insufficient aldosterone and cortisol serum levels. The classic type requires life-long steroid replacement which may result in cushingoid side effects, and typical comorbidities may be also developed. The patients' quality of life is decreased, and their mortality is much higher than that of the population without steroid 21-hydroxylase deficiency. The diagnosis, consequences and the patients' life-long clinical care require a multidisciplinary approach: the specialists in pediatrics, internal medicine, endocrinology, laboratory medicine, genetic diagnostics, surgery, obstetrics-gynecology and psychology need to work together. Orv Hetil. 2018; 159(7): 269-277.

The laparoscopic minimally invasive surgical technique is widely employed on a global scale. However, the efficient and ethical teaching of this technique requires equipment for surgical simulation. These educational devices are present on the market in the form of box trainers and virtual reality simulators, or some combination of those. In this article, we present a systematic overview of commercially available surgical simulators describing the most important features of each product. Our overview elaborates on box trainers and virtual reality simulators, and also touches on surgical robotics simulators, together with operating room workflow simulators, for the sake of completeness. Apart from presenting educational tools, we evaluated the literature of laparoscopic surgical education and simulation, to provide a complete picture of the unfolding trends in this field. Orv Hetil. 2017; 158(40): 1570-1576.

The goal of the study was to find a proper technique to fix tendon grafts into an INSTRON loading machine. From 8 human cadavers, 40 grafts were collected. We removed the bone-patella tendon-bone grafts, the semitendinosus and gracilis tendons, the quadriceps tendon-bone grafts, the Achilles tendons, and the peroneus longus tendons from each lower extremity. We tested the tendon grafts with five different types of fixation devices: surgical thread (Premicron 3), general mounting clamp, wire mesh, cement fixation, and a modified clamp for an INSTRON loading machine. The mean failure load in case of surgical thread fixation was (381N ± 26N). The results with the general clamp were (527N ± 45N). The wire meshes were more promising (750N ± 21N), but did not reach the outcomes we desired. Easy slippages of the ends of the tendons from the cement encasements were observed (253N ± 18N). We then began to use Shi's clamp that could produce 977N ± 416N peak force. We combined Shi's clamp with freezing of the graft and the rupture of the tendon itself demonstrated an average force of 2198 N ± 773N. We determined that our modified frozen clamp fixed the specimens against high tensile forces.

Introduction: Laboratory diagnosis of pheochromocytoma-paraganglioma syndrome has been markedly improved during the past two decades., Aim: Retrospective assessment of diagnostic utility of urinary catecholamines and their metabolites as well as serum chromogranin A in 155 patients diagnosed at the 2nd Department of Medicine, Semmelweis University., Method: Urinary catecholamines and metabolites were measured using high-performance liquid chromatography with electrochemical detection in 155 patients with pheochromocytoma-paraganglioma (of whom 28.4% had hereditary background) and in 170 non-pheochromocytoma patients used as controls. Serum chromogranin A was measured by immunoradiometry., Results: Sensitivity (93.2%) and specificity (87.0%) of urinary fractionated metanephrines were higher than those of urinary catecholamines (90.9% vs. 85.7%, respectively) and serum chromogranin A (88.7% and 77.5%, respectively). Urinary normetanephrine and serum chromogranin A correlated positively with tumor size (r = 0.552, p<0.0001 and r = 0.618, p<0.0001, respectively)., Conclusions: These data confirm the diagnostic utility of urinary catecholamines and their metabolites. Urinary normetanephrine and serum chromogranin A may help to estimate tumour mass and probably tumour progression.

The authors report a case of an ectopic ACTH-syndrome that resulted in severe hypercortisolism, hypokalemia, diabetes mellitus and osteoporosis. The ACTH-secreting tumor tissue was localized in the lung. The tumor was removed by segmentectomy and histological evaluation revealed an ACTH-secreting neuroendocrine tumor. After surgery, however, plasma cortisol and ACTH levels failed to decrease significantly due to subtotal tumor removal. Long-acting somatostatin analogue therapy resulted in a normalization of both plasma cortisol and ACTH levels and the clinical symptoms improved significantly. Residual tumor was removed by repeat surgery and the patient was permanently cured.

The recently introduced pumpless extracorporeal lung assist (PECLA) is a remarkable alternative to the conventional extracorporeal membrane oxygenation in case of severe lung failure. By establishing a shunt between femoral artery and vein using the arterio-venous pressure gradient as a driving force through a low-resistance membrane oxygenator, PECLA provides highly effective gas-exchange by preserved cardiac function. Due to its closed system, reduced priming volume and low heparin demand, the unfavourable effects of extracorporeal membrane oxygenation can be effectively diminished. Hence the small technical, financial and personal input, the PECLA can be ideally used in district hospitals and during transport as well. Our short summary demonstrates the advantages and safety of the system proven over 123 cases.

The differentiation of adrenocorticotropic hormone producing pituitary adenoma (Cushing's disease) from the ectopic ACTH syndrome is always a complex and difficult task, and in rare cases it is not possible to differentiate between the two disorders, even with the use of dynamic endocrine tests and the most advanced imaging techniques. Inferior petrosal sinus sampling (IPSS) with subsequent ACTH measurements became the gold-standard method of the differential diagnostic process. 34 patients with ACTH dependent Cushing's syndrome in whom the source of ACTH secretion couldn't be identified unambiguously with imaging techniques and/or dynamic endocrine tests underwent altogether 41 IPSS between 1999 and 2005. The sensitivity of the method was calculated on the basis of 31 samplings of 25 patients who had definite endocrinological diagnosis confirmed by the recovery from Cushing's syndrome after surgical intervention and/or by histological examinations (22 patients with ACTH-producing pituitary adenoma and 3 patients with ectopic ACTH syndrome). As a result of IPSS, pituitary-dependent Cushing's disease was diagnosed with a baseline central to peripheral ACTH ratio of >2.0 or with a ratio of >3.0 after corticotropin releasing hormone (CRH) administration. IPSS correctly identified ACTH-producing pituitary adenoma in 20 of 28 sampling procedures, with a sensitivity of 71.4%. Three patients had true negative and 8 had false negative results. There was no false positive result. Four of the 8 patients with false negative first sampling had a repeat sampling procedure leading to true positive result in each patient. In patients with Cushing's disease having true positive interventions, the basal and 5 minutes post-CRH ACTH concentrations were diagnostic in 14 and 19 cases, respectively. The sensitivity of IPSS within this series, reported for the first time from Hungary, was lower than it was found in much larger series published in international literature. In addition to technical difficulties, the lower sensitivity can be accounted also for the highly selected nature of the patient group.

Introduction: Primary aldosteronism is the most common form of mineralocorticoid hypertension. The disease has been described by Jerome W. Conn in 1955; since that time there has been a great progress in the knowledge concerning the prevalence, diagnostics and treatment of the disease., Aims: The authors retrospectively analyzed the efficacy of diagnostic procedures and the outcome of treatment by the analysis of data of 187 patients with primary aldosteronism examined between 1958 and 2004 at the 2nd Department of Medicine of Semmelweis University., Methods: The efficacy of different methods used for the diagnosis, the frequency of the different subtypes of primary aldosteronism, as well as the surgical outcomes in patients with surgically treated subtypes of primary aldosteronism were studied., Results: Aldosterone-producing adenoma was detected in more than two thirds of patients (n = 135), whereas idiopathic hyperaldosteronism was found in 46 patients. Other subtypes of primary hyperaldosteronism occurred less frequently (unilateral primary adrenocortical hyperplasia in 5 patients and adrenocortical carcinoma in one patient). For the diagnosis of familial hyperaldosteronism type I, molecular biological studies of the aldosterone-synthase/11beta-hydroxylase gene chimera were carried out in 30 patients but none of them showed the presence of the chimeric gene. When comparing the clinical parameters of patients with aldosterone-producing adenoma and idiopathic hyperaldosteronism, no significant differences were found in the time period between the diagnosis of hypertension and the diagnosis of primary aldosteronism, or in the systolic and diastolic blood pressure values. The mean of the lowest documented serum potassium concentration was slightly lower in patients with aldosterone-producing adenoma (2.8 +/- 0.1 mmol/l) compared to those with idiopathic hyperaldosteronism (3.1 +/- 0.2 mmol/l), but the difference was not significant. Normokalemic primary hyperaldosteronism was found in 7 cases. The ratio of plasma aldosterone concentration (ng/dl) to plasma renin activity (ng/ml/h) was above 20 in all patients with aldosterone-producing adenoma and in all but 5 cases with idiopathic hyperaldosteronism. To confirm the diagnosis and to differentiate the subtypes of primary aldosteronism, the postural test combined with furosemide administration was performed in the majority of patients. When cases showing an elevation of plasma cortisol level during the test were excluded, this test differentiated patients with aldosterone-producing adenoma from those with idiopathic hyperaldosteronism with a sensitivity of 69% and a specificity of 92%. In cases of adrenocortical adenomas not or not clearly detectable by radiological imaging techniques, as well as in cases with bilateral adrenocortical adenomas, selective adrenal vein sampling was performed (n = 55). All but 4 patients with aldosterone-producing adenoma underwent adrenalectomy. Histology and postoperative hormone results confirmed the preoperative diagnosis in all operated patients. After surgery serum potassium concentration returned to normal in all patients showing low serum potassium levels before surgery. Also, the moderate to severe preoperative hypertension disappeared or improved after surgery., Conclusions: These observations are in contrast with the results of international studies which showed a high frequency of normokalemic primary aldosteronism and a more frequent occurrence of idiopathic hyperaldosteronism well treatable with aldosterone-antagonists. Therefore, it can be presumed that a significant number of primary aldosteronism cases that are not accompanied with severe hypokalemia remain undetected in Hungary.

The authors review the historical and epidemiological aspects, as well as the distinguishing clinical features and complications of acromegaly to emphasize the importance of early diagnosis and treatment of patients with this disorder. Acromegaly is a rare disorder with a prevalence of 55-69 cases per million population and an incidence of 3-4 newly detected cases per million per year. Recent estimates indicate, that its slow progression and insidious course leads to a considerable time lag of 7-12 years between the first symptoms and the diagnosis of the disease, although younger patients with more severe disease may be detected earlier. In addition to the disfigurement and disability which develop progressively from the onset of the disease, acromegaly is associated with a number of complications resulting in a two- or three-fold increase of mortality and a decrease of life expectancy by about 10 years. The major causes of death include cardiovascular and cerebrovascular events, respiratory disease and malignancy. Because the duration of the disease before effective therapy may be one of the major predictors of increased mortality, practicing doctors need to be particularly vigilant to recognize undiagnosed cases in order to avoid the serious complications of the disease.

Multiple endocrine neoplasia Type 2 (MEN2) is a hereditary tumour syndrome characterized by the association of medullary thyroid cancer, phaeochromocytoma and hyperparathyroidism. It is inherited as an autosomal dominant trait. During the past few years the cloning of the gene responsible for the syndrome, the ret protooncogene, made the molecular genetic diagnosis of the disease possible. In this study we demonstrate the results of the MEN2 mutation analysis performed in three members of a Hungarian MEN2A family. The mutation analysis was carried out according to the method of Dr. W. Hoppner's Laboratory (Hamburg) that is the main centre for MEN2 genetic diagnosis in Germany. Two Members of the family are affected, one suffered from both medullary thyroid cancer and phaeochromocytoma, the other (the first patient's daughter) had only medullary thyroid cancer. We found a ret exon 11 codon 634 mutation, that resulted in the change of TGC to TAC, a cysteine-tyrosine amino acid exchange. We found no mutation in the youngest member of the family. This result is of great clinical significance, because the carrier status of this individual can thus be excluded and, therefore, there is no need for prophylactic thyroidectomy and further clinical screening tests. As molecular genetic diagnosis of MEN2 becomes possible, the uncertain clinical examinations used for MEN2 diagnosis seems to be less important.

A 40-year-old male patient with a 2 years history of recurring hyperthyroidism is presented with clinical hyperthyroidism and diffuse goiter. Despite thyreostatic treatment and surgical thyroid ablation the hyperthyroidism recurred. The patient had laboratory evidence of hyperthyroidism and his serum TSH was persistently and enormously elevated (T4:214 nmol/l, T3:6.9 nmol/l, TSH:218 mIU/l)> Computed tomography and magnetic resonance imaging confirmed a pituitary mass of 7 cm in a-p diameter, with supra-, parasellar and sphenoidal extension. The pituitary adenoma was partially resected by transsphenoidal surgery, which failed to result in a substantial decrease in the serum thyrotropin level. Pituitary irradiation and a long-term somatostatin analog octreotide treatment (300-600 micrograms/die) combined with bromocriptine therapy resulted in a significant, but still incomplete suppression of thyrotropin secretion (TSH level about 15 mIU/l) and persisting mild hyperthyroidism. The size of the adenoma was unchanged during the two years of highdose octreotide treatment period. According to our best knowledge this is the first reported case of a thyrotropin-secreting pituitary adenoma in Hungary.

Flow cytometric deoxyribonucleic acid measurements were performed on 26 adrenocortical tumours and 9 non-tumours adrenals. All but one tumours were classified both histologically and clinically as benign, however, two thirds of them had abnormal deoxyribonucleic acid stemlines. Proliferative indices of adenomatous tissues were significantly higher than those of non-tumorous adrenals (p < 0.01). When compared to tumors smaller than 5 cm in size, tumours larger than 5 cm displayed significantly higher proliferative indices (p < 0.01). Thus, flow cytometry appears to have only a limited value in distinguishing between benign and malignant adrenocortical tumours, but it may provide additional information about the prognosis of these tumours.

Delicate branching filaments, and cocci or rods, were seen by microscopic examination in the pus of the canaliculus lacrimalis in patients with chronic canaliculitis. Propionibacterium propionicus and different bacteria were cultivated and identified in the pus. After i.p. inoculation of mice with the Propionibacterium strains, the morphological changes characteristic of this microorganism were observed in the peritoneum, in the spleen and in the lung, giving an adequate explanation of the direct microscopic findings in the pus.

The effect of oral Tensiomin treatment, 53.4 mg daily in 29 patients suffering from congestive heart failure associated with acute of chronic forms of ischaemic heart disease, e.g., recent and/or advanced myocardial infarction, aneurysm etc. was studied. The acute and long-term beneficial haemodynamic effects were verified in 4 patients by thermodilution Swan-Ganz catheterization as well. The parameters of ejection function improved moderately, while left ventricular filling pressure (PCW) decreased significantly. The balanced vasodilator effect was not accompanied by an increased myocardial oxygen demand. The "double product" was lowered in response to Tensiomin. During the clinical follow-up (from 6 days to 2 years) there was an improvement in the NYHA functional class by an average of 1.2 however 4 patients died in spite of combined vasodilator and dobutamine treatment. Owing to the improvement of regional blood flow to the brain and the kidney Tensiomin seems to be well-tolerated in patients with low arterial blood pressure. In pts with acute myocardial infarction and angina the critical fall of blood pressure and that of the coronary blood flow should be avoided by giving the drug in approximately titrated. Side effects were observed only with higher doses of Tensiomin in a small number of patients, i.e., transient worsening of renal function in 3 patients and dysgeusia in 2. Our data indicate that Tensiomin treatment is effective and safe in patients suffering from all kinds of congestive heart failure complicating ischaemic heart disease.

The effect of human atrial natriuretic peptide (hANP) on aldosterone, 18-OH-cortisterone, corticosterone, deoxycorticosterone, and cortisol secretion was examined in isolated human aldosteronoma cells from five patients with primary aldosteronism. hANP exerted a nearly identical inhibitory action on basal secretion of each of these steroids and antagonized also the stimulating effects of ACTH, serotonin, metoclopramide and vasoactive intestinal polypeptide. The results suggest that in human aldosteronoma cells hANP may be a non-selective inhibitor of corticosteroid biosynthesis and that the site of inhibition of steroidogenesis may be localized to the early pathway of steroid biosynthesis.

The authors report on a successful medical treatment of a 36-year-old woman who had hypothyroidism and pituitary adenoma. Primary hypothyroidism was evidenced by decreased serum thyroxine (23 nmol/l; 1,77 micrograms/dl) and increased plasma thyroid-stimulating hormone (TSH) levels (108 mU/l). Pituitary mass with suprasellar expansion (1 cm in diameter) was proven by computed tomography (CT). The patient had been treated conventionally with 1-thyroxine and this medication was continued during a 1-year follow-up. Not only did she become symptom-free but control CT scanning revealed a large reduction of tumor size and the disappearance of suprasellar expansion.