In this review the author collected examples from the literature for the verification of her hypothesis, that myelodysplasia might evolve from an unrevealed deficiency condition that had therefore been left uncorrected for a long time. That time might be long enough for a metabolic slip-out resulting in appropriate circumstances for a more primitive cell line to develop by gaining selection advantage. The author would like to emphasize the importance to diagnose and correct such deficiency conditions in time.
Purpose: Improving the management of cardiovascular disease in Hungary represents an important clinical challenge. This article assesses the achievement of national consensus total cholesterol goals among Hungarian patients of physicians educated about the consensus guidelines and assisted in cardiovascular risk assessment. Methods and results: A total of 320 general practitioners provided data on 15,404 eligible patients. Among these individuals, 14,018 (91%) had documented atherosclerosis and the remaining 9% had ≥ 2 risk factors. Despite this, less than half of all patients received lipid-lowering therapy. Only 12% of high-risk patients attained the consensus total cholesterol target of < 4.5 mmol/L (< 175 mg/dL) and 31% of individuals at low-moderate risk achieved the consensus goal of < 5.0 mmol/L (< 194 mg/dL) at the first visit. Among patients in the high-risk group whose total cholesterol levels were above the consensus goal at the first visit, 54% received no lipid-lowering therapy and 46% received inadequate treatment. Overall, lipid-lowering treatment was considered inadequate in most (77%) patients. Dose adjustments and other regimen changes after the first visit were infrequent. Conclusion: Most Hungarian patients seen in primary-care practices did not achieve consensus cholesterol goals. Improvements in lipid-lowering therapies and strategies, as well as enhanced patient education to promote adherence to lifestyle and medication regimens, may be needed to improve cholesterol goal attainment in Hungary. Potential limitations of the study included selection bias and the use of a convenience sample to recruit physicians.
Ourwanderingfellowcountryman,EdeSzengerwitnestedthehistoricaleventthatforMexicans representstheadventoftheRepublicandforEuropeansisbestknownasthetopicofafamous paintingbytheFrenchpainterEdouardManet,theexecutionin1867oftheMexicanemperor MaximilianII,brotherofFranzJoseph,theHabsburgruleroftheAustro-HungarianMonarchy. Ofnote,ManethimselfdidnotwitnesstheexecutionthoughhevisitedthelandoftheAztecs. Manet’sinspirationcamefrombothGoya’spaintingandhisownaversiontotheforeignpolitics ofNapoleonIII.A picturebyHenriRousseau(alsoknownasleDouanier,thecustomsofficer,a French post-impressionist painter) in a naive or primitive manner, also depicts the execution. StoriesspredbyadmirersthatRousseau’sarmyseviceincludedtheFrenchexpeditionaryforceto Mexicoareunfounded.Hisinspirationcamefromstoriesbythesoldierswhohadsurvivedthe disastrousFrenchexpeditiontoMexicoandwhomhemetduringhisserviceasacustomsofficer. PresentwashoweverattheexecutionEdeSzenger,aHungariandoctorservingintheMedical CorpsofMaximilian’sarmy.Tenyearslater,therepatriatedSzengerpublishedabookentitled “Mexicofelvidekeeleteskortanitekintetben”(TheHighlandofMexicoinrespecttoPhysiology and Pathology) which is not only an interesting travel book but also an early example of Hungarianmedicalgeography. MaximilianwasanunsualHabsburg,apeacefulmanandasupporteroftheartswhodisap proved the absolutist politics of his own brother, Franz Joseph. He married into the Belgian Royal Family that earned him the support of Napoleon III in 1864. Maximilian claimed the throneofMexicowiththehelpoftheFrenchexpeditionaryforceledbyGeneralBazaine.The FrencharmywasfortifiedbyvolunteerscomingfromtheAustro-HungarianMonarchy,includ ingthemilitarysurgeonEdeSzenger.BazainebadlyneededthevolunteersbecausehisFrench army had been decimated by the combination of continuous guerilla warfare and epidemics (mostimportantlymalaria,typhoidfever,andyellowfever).TheAustro-Hungarianlegionaries joined the French expeditionary force in the port city of Vera Cruz and then started their WestwardinvasiontowardstheMexicanCapital.Aftermanyhurdles,Maximilian’sarmyfinally reached the safe haven of Puebla, occupied by Mexicans loyal to him. Szenger made a tour of Mexico City to have his medical diploma recognized where he made friends with the famous ProfessorofMedicine,Jimenez.UponhisreturntoPuebla,Szengerwaspromotedtoheadthe Austrianmilitaryhospital.Themilitarysituation,however,soonturnedtothedisadvantageof
The hypophysiotropic corticotropin-releasing hormone- and thyrotropin-releasing hormone-synthesizing neurons have important role in the regulation of energy homeostasis. The studies of this PhD work, carried out on rats, focused on the innervation and regulation of these neurosecretory neurons by specific neuron populations involved in the processing of metabolic signals.
We analyzed the 15p-15q11.2 region of human chromosome 15 that was tetrasomic in a three-generation family with a chromosome 15-derived small supernumerary marker chromosome (der15, sSMC). This stable, inherited sSMC was present in four family members. The breakpoint that led to the formation of der15 was established by fluorescence in situ hybridization (FISH) using 18 bacterial artificial chromosomes (BACs) mapping to the pericentric region of 15q. The breakpoint was mapped to an 11 kb sequence in the 15q11.2b sub-band, and it resides in a NF1 pseudogene, within the BAC 810K23 clones. FISH mapping verified the localization of the overlapping 18 BAC clones in the 15q11.2 region, and confirmed that large duplications were spanning to 15q13.1 including the PWS/AS critical region. Carriers of the der15 pseudodicentric isochromosome are healthy, and these cases support that inherited tetrasomy of the 19.4 Mb chromosomal segment of the 15p-q11.2b region has no phenotypic consequences.
Aims: In cirrhotic ascitic patients the rate of diuretic induced complications is high. Moreover, 5–10% of patients do not respond to diuretics. Paracentesis is safer. The current recommendation is to administer albumin at 6–8 gm/L of ascitic fluid removed. But some studies show no survival benefit. Our aim is to confirm the safety and effectiveness of large volume paracentesis without albumin on renal function and make it a cost-saving alternative strategy. Methods: The prospective randomized study was done on 30 cirrhotic patients with ascites in the Hepatology Department of Bangabandhu Sheikh Mujib Medical University from July 2003 to June 2004. The patients were admitted 48 hours before the study. The patients were maintained on a salt restricted diet and fluid restriction 1 to 1.5L/day and without diuretics. On the 3rd and 7th days after paracentesis blood and urine samples were collected (investigations: serum creatinine, CCR, serum electrolytes) and correlated with baseline investigations. Results: Among the 30 cirrhotic ascitic patients there were 27 Child’s grade C and 3 Child’s grade B, 23 males and 7 females. Age in year: 44 ± 12 (M ± SD). The test was done by paired t-test. The findings of the tests ( p > .05) are insignificant. There is no significant difference in renal function between pre- and post-paracentesis. Conclusions: The study shows that large volume paracentesis without albumin infusion causes no renal impairment at 48 hours and 7 days after the procedure. Large volume paracentesis is a safe and inexpensive therapeutic procedure. It obviates the need for prolonged hospitalization and diuretic therapy.
Background: The aim of this study was to compare fitness levels of 8–13 years old healthy and asthmatic boys from 1985 and 2004. Subjects and methods: The swimmer asthmatics from 1985 (SA1, n = 40) and from 2004 (SA2, n = 26) participated in the same therapeutic swimming training. Healthy, non-swimmer children (NonSH1 in 1985, n = 41 and NonSH2 in 2004, n = 54) participated in physical education classes. Results: Comparing the fitness outcomes of all boys from 1985 with that obtained in 2004 a significant difference was found ( p < 0.0001, boys from 1985 had better results). Fitness of NonSH1 was significantly better than fitness of NonSH2 ( p < 0.0001), similarly SA1 had better fitness results than SA2 ( p = 0.0003). Conclusion: There was a trend between 1985 and 2004, so that the fitness of healthy and asthmatic children worsened. Further investigations are needed to clarify the medical and social aspects of the results.
Background: Over three hundred million people worldwide were estimated to be become diabetic by year 2025. The rates of both obesity and malnutrition are on the increase worlwide. The goal of this study was to describe the relationship of body mass index (BMI) and diabetic peripheral neuropathy (DPN) in persons with diabetes mellitus. Research design and methods: A cross-sectional analysis of BMI and peripheral neuropathy was conducted among one hundred and twenty diabetic subjects, who were grouped based on presence or absence of DPN. Ninety of the diabetic persons had peripheral neuropathy, while thirty of the diabetic persons had no neuropathy. DPN was determined only by clinical assessment using an aspect of the Michigan Neuropathy Screening Instrument (MNSI). Result: The two groups were not different in BMI, total cholesterol and high density lipoproteins (HDL). The group without peripheral neuropathy had better glycaemic control; HB A1C = 5.9 ± 2.5 (%), shorter mean duration of diabetes = 5.3 ± 3.6 years and younger age. More of those with peripheral neuropathy were underweight (six compared to none ‘0’ of those without neuropathy). Similar result was obtained for morbid obesity ‘class 3’, although BMI had no significant effect on DPN after controlling for age, duration of DM and glycaemic control. Discussion and conclusion: Obesity is an index of insulin resistance which may account for poor glycaemic control and predispose to peripheral neuropathy and other complications. Weight loss depicts severity of type 1 DM which may account for complications. This pattern also depicts the trend in a sub-Saharan African city like ours with uneven distribution of wealth and resources hence the poor result in both the underweight and obese class 3.
Cataractsurgeryhaschangedfundamentallybytheintroductionofphacoemulsification,which hasbecomenowadaysthestandardmethodtoremovecataracts.Theself-sealingwoundissmaller,postoperativeastigmatismisless,andtheopticalrehabilitationissignificantlyquickerduring theprocedurecomparedtomanualextracapsularcataractextraction.Mostlensnucleimustbe divided first, after which they can be safely removed during surgery. Many complications may occurduringstandardphacoemulsificationusingtraditionalultrasound.Oneofthemostimpor tantcomplicationsisdamagingtheendothelium,whichmayleadtocornealdecompensationif thedeteriorationisserious. Asaresultofprogressinophthalmology,thekineticenergyofthefluidhasbecomeusablein cataractsurgery.Inrecentyears,oneofthemostmeaningfultechnicalinnovationswastheintro ductionofAqualase.Duringthisprocedure,shortpulsesofwarmedbalancedsaltsolutionlique fythelensmaterial.Advantagesofthemethodarethatthereisnoultrasoundandheatingeffect during the procedure, the Aqualase handpiece is more capsule-friendly than the ultrasound handpiece,andpolishingtheposteriorcapsuleispossiblewiththepulses.Theonlyreportedlim itationofthefluid-basedsystemisthatitisnotaseffectiveinhardcataractsastheconventional ultrasoundtechnique.Theinvivo effectofAqualaseonthecornealendotheliumwasunknown atthebeginningofourstudy. After removing nucleus and cortex, a foldable posterior chamber intraocular lens (IOL) is implanted to secure optical rehabilitation to the patient. In recent years, monofocal IOLs are commonlyusedallovertheworld,whichusuallyprovideperfectuncorrecteddistancevisualacu ityforthepatients,butnearvisionisrarelysufficientwithoutcorrection.Itisknownthatsome pseudophakicpatientswithmonofocalIOLshavegoodnearvisualacuitywiththeirdistancecor rection.Thisphenomenoniscalledpseudoaccommodationorapparentaccommodation,which
Recurrence of hepatitis C virus (HCV) infection after liver transplantation has been shown to negatively affect graft and patient survival. Combination therapy with pegylated interferon (PEG-IFN) and ribavirin is efficacious, but poorly tolerated. A 57-year-old man with HCV infection and cirrhosis underwent cadaveric liver transplantation in the United States. The HCV genotype was 1b. The immunosuppressive regimen consisted of tacrolimus, mycophenolate mofetil, and prednisolone. Liver function was stable until 4 months after transplantation, but then deteriorated, accompanied by a rapid rise in the serum HCV-RNA level. Liver biopsy revealed the recurrence of HCV infection, and treatment with PEG-IFN alpha-2b plus ribavirin was initiated. The patient responded well to therapy, and liver function improved, but high HCV-RNA levels persisted. On postoperative day 260, the patient had a relapse of hepatitis and received β-interferon 3 MU/day for 2 consecutive weeks. The patient responded well, but only transiently to therapy. Liver function fluctuated in association with high HCV-RNA levels, despite subsequent treatment with PEG-IFN alpha-2b plus ribavirin. Eleven months after transplantation, tacrolimus was switched to cyclosporine. Three months later, liver function became normal, and the HCV-RNA level decreased dramatically. Because a combination of cyclosporine and interferon synergistically suppresses HCV replication in vitro , early switching of tacrolimus to cyclosporine may be a safe and worthwhile option in patients who have recurrent HCV infection after liver transplantation.
The hepatoprotective and antioxidant effect of broccoli “Brassica oleracea L.” (aqueous extract of freeze dried powder) on liver injury induced by carbon tetrachloride (CCl 4 ) was investigated. Wistar albino rats weighing 180–200 g were administered a single dose of CCl 4 , GOT, GPT, ALP, GGT and bilirubin were estimated in serum. Non-protein sulfhydryl (NP-SH) and malondialdehyde (MDA) were also estimated in liver tissue. CCl 4 induced hepatotoxicity in all treated animals was evident by elevated serum GOT, GPT, ALP, GGT and bilirubin levels and simultaneous fall in NP-SH and increased MDA activities in liver tissue. The broccoli extract at the doses of 150 and 300 mg/kg produced significant hepatoprotection by decreasing the activity of serum enzymes, bilirubin, while it significantly increased the levels of NP-SH and decreased MDA of liver tissue. Histopathological observations of the liver also showed the protective effect of broccoli in CCl 4 -induced hepatic injury in rats. The obtained results suggest that broccoli possesses hepatoprotective capacity and may have potential therapeutic value in the treatment of some liver disorders probably by its antioxidative effects on hepatocytes, due to flavonoids and sulfurated compounds.
Introduction: Hepatitis C virus (HCV) is a leading cause of chronic liver disease worldwide including Bangladesh. Approximately 0.84% of our population is infected with HCV. Genotypes of HCV are important in the determination of treatment duration and in predicting the response to treatment in HCV infection. Methodology: 61 consecutive patients who presented to us with chronic hepatitis C (CHC) and who could afford treatment and having no features of decompensation were included in the study. Results: Of the 61 study subjects, 46 were males and 15 females. They were between 12 and 70 years of age. Of them 41% had genotype 3, 31% had mixed genotypes 3 + 4 and 21% had genotype 1. Patients also had genotypes 2, 4, 5 and mixed genotypes 5 + 6, the figure being 1.6% in each case. Conclusion: Genotype 3 is the commonest HCV genotype in Bangladesh, while we also have a high prevalence of mixed HCV genotypes.
According to WHO data more than 180 million people suffer from diabetes mellitus worldwide and this number could double within 15 years. Normal function of the brain is dependent on continuous supply of glucose. In hypoglycemia, production of counterregulatory hormones (glucagon, epinephrine, growth hormone, and cortisol) increases, the sympathetic system becomes stimulated, and features of neuroglycopenia appear in order to save the homeostasis. Hypoglycemia is an alarming, actually life threatening condition, but the exposure to chronic hyperglycemia has a more detrimental effect on the brain than recurrent exposure to severe hypoglycemia. The active neural response to hyperglycemia induces changes in gene expression and function. The first steps against hyperosmolality are initially adaptive, but later hyperactivation of the hypothalamic magnocellular neurosecretory cells leads to their structural damage. Changes in hippocampal gene transcription are partially implicated in the deterioration of declarative memory. Neurologically passive shunting of excess glucose through alternative cellular metabolic pathways induces atherogenic, vascular lesions, free radicals, leukoencephalopathy and atrophy of the brain and thus leading to cognitive deficits. In physiological conditions insulin has neuroprotective effect. However, insulin resistance in the central nervous system correlates with insulin resistance in the periphery. Loss of responsiveness to insulin could render neurons more susceptible to neurotoxic insults, the protective effect of insulin diminishes, and apoptosis, neurodegeneration and the resultant cognitive decline are all increased in insulin-resistant patients. Some unclear relations appear between diabetes mellitus and Alzheimer's disease. Diabetic patients with APOE-4 gene have an increased risk for Alzheimer's disease. Prevalence of depression is higher in patients with diabetes mellitus and in turn, depression is a risk factor for diabetes mellitus. Simultaneous presence of depression and diabetes mellitus tends to worsen the course of both.
Cystic liver metastases from carcinoid tumors are rare. We describe a 46-year-old male who presented with right-sided heart failure with a polycystic liver disease on contrast enhanced computed tomography of abdomen. The fine needle aspiration cytology from the liver lesion showed metastatic neuroendocrine tumor with the primary in the rectum.
The intestinal mucosa must rapidly recognise detrimental pathogenic threats to the lumen to initiate controlled immune responses but maintain hyporesponsiveness to harmless lumenal commensals and food antigens. Exaggerated inflammatory responses in the absence of pathogenic bacteria would be otherwise deleterious. If the balance shifts from tolerogenic to immunogenic responses, several inflammatory and autoimmune disorders may be developed, such as coeliac disease, inflammatory bowel disease and necrotizing enterocolitis. Charles Janeway Jr first suggested that so-called pattern recognition receptors (PRRs) may play an essential role in allowing innate immune cells to discriminate between “self” and microbial “non-self” based on the recognition of broadly conserved molecular patterns (PAMPs). CD14, which is a membrane-associated glycosylphosphatidylinositol-linked protein, was the first described PRR. Toll-like receptors (TLRs) comprise a class of transmembrane PRRs, while nucleotide-binding oligomerization domains (NOD1 and NOD2) are a structurally distinct family of intracellular PRRs. Intestinal epithelial tolerance versus intolerance towards lumenal bacterial ligands are distinctly mediated through TLRs and NOD2. Recognition of PAMPs by these receptors initiates a signaling pathway, which leads to activation of several adaptor proteins and transcription factors and finally production of proinflammatory cytokines-, chemokines-, type I interferonsand antibacterial peptides, as well as induction of angiogenesis and apoptosis. In health, TLR signalling protects the intestinal epithelial barrier and confers commensal tolerance, whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. Aberrant TLR and/or NOD2 signalling induce tissue damage and barrier destruction through
Fibroblast growth factor receptor 2 gene codes for IIIb and IIIc transcript variants, which play pivotal roles in normal wound healing. Tumor necrosis factor α mediates several biological processes including wound healing. We aimed to characterise the expression pattern of IIIb expressed by in vitro cultured keratinocytes and in skin biopsy samples of venous leg ulcer patients, and to identify polymorphisms which may play a role in the pathomechanism of prolonged wound healing in venous leg ulcer patients. Real-time reverse transcription polymerase chain reaction and Western blotting methods were used for expression studies, polymerase chain reaction with TaqMan probes and with restriction fragment length polymorphism method were performed for polymorphism studies. We demonstrated that the expression of IIIb is related to the proliferation states of HaCaT keratinocytes and its expression is down-regulated in the uninvolved epidermis of venous leg ulcer patients ( n = 15) compared to the epidermis of controls ( n = 15). We identified a polymorphism in the 3’ untranslated region (2451A/G) of the fibroblast growth factor receptor 2 gene, which displayed a significant difference in the allelic distribution between leg ulcer patients ( n = 82) and controls ( n = 82; p = 0.0103). We hypothesize that this polymorphism may be a susceptibility factor for venous leg ulcer. In another set of experiment we demonstrated that the A allele of the –308 tumor necrosis factor α polymorphism might be a potential factor for venous leg ulcer susceptibility; however, our data suggest that this association is secondary and the primary association probably exists with obesity.
The development of pharmacological agents able to counteract the mechanisms of multidrug resistance (MDR) in oncology has remained a major goal for the past ten years. Several mechanisms are thought to be involved in drug resistance, including those associated with drug transport, detoxification and apoptosis. The first part of this thesis was focused on the inhibition of MDR through inhibition of the MDR P-glycoprotein (P-gp) in various cell lines. Six groups of compounds were involved in the P-gp efflux pump inhibitory studies: cinnamylidene ketones; 1,4-dihydropyridines derivatives; phenothiazines; HSP90 inhibitor peptide derivatives; Tylosin Betti base derivative and Euphorbia diterpenes. The majority of the tested compounds were able to increase the R123 accumulation in cancer cell lines. Generally, the newly identified MDR modifiers were able to enhance the antiproliferative activity of selected anticancer drugs in a synergistic or additive way in vitro on MDR cells. The in vitro activity of TBN was...
Information about the risk of venous thromboembolism and prophylactic practices around the world is limited. ENDORSE (Epidemiologic International Day for the Evaluation of Patients at Risk for Venous Thromboembolism in the Acute Hospital Care Setting) study is a multinational cross-sectional survey designed to assess the prevalence of venous thromboembolism (VTE) risk in the acute hospital care setting, and to determine the proportion of at-risk patients who receive appropriate prophylaxis. All hospital inpatients aged 40 years or above admitted to a medical ward, or those aged 18 years or above admitted to a surgical ward, in 358 randomly selected hospitals across 32 countries were assessed for risk of VTE on the basis of hospital chart review. The 2004 American College of Chest Physicians evidence-based consensus guidelines were used to assess venous thromboembolism risk and to determine whether patients were receiving recommended prophylaxis. Nine Hungarian centers were included in the international survey, and a total of 1300 patients were assessed for thrombosis risk in Hungary. Of these patients 39.9% (N=519) were judged at risk for VTE, including 58.2% (N=253) surgical and 30.8% (N=266) medical patients. 56.6% (N=294) of the total at-risk patients received ACCP-recommended VTE prophylaxis. Among major surgery patients 86.6% (N=219) received recommended prophylaxis compared with 28.2% (N=75) of medical patients. In Hungary more than two-thirds of at-risk hospitalized medical patients did not receive appropriate prophylaxis. ENDORSE results reinforced that a large proportion of hospitalized surgical and medical patients are at risk for VTE worldwide as well as in Hungary. The rate of at-risk patients receiving appropriate prophylaxis should be urgently increased.
Though pap smear abnormality has been documented in female patients with inflammatory bowel disease (IBD) in the recent past, looking into the interrelation between them has been started nowadays by clinicians. The underlying pathophysiology of abnormal pap smear in IBD is still questionable, but there are evidences for and against the proposed hypothesis on the “effect of immunosuppressive therapy” used in IBD. Hence, there are studies coming up by stressing the need of routine pap smear screening protocol in female patients with inflammatory bowel disease. We had a case of inflammatory bowel disease associated with carcinoma of cervix, to move further towards its possible relation.
Introduction: Chronic myeloid leukaemia is a malignant clonal alteration of the pluripotent haemopoietic stem cell. The genetic hallmarks of the disease are the t(9,22) (Philadelphia chromosome), registered by conventional cytogenetics in more than 90% of all chronic myeloid leukaemia cases and the active tyrosine kinase protein encoded by bcr-abl fusion gene. The constitutively active tyrosine kinase is currently accepted to be the cause of chronic myeloid leukaemia. The introduction of imatinib has considerably changed the treatment of chronic myeloid leukaemia. Prior studies demonstrated high rates of cytogenetic responses in all phases of the disease. Methods: The authors evaluated the cytogenetic and molecular responses of 20 chronic phase chronic myeloid leukaemia patients who were consecutively admitted to their center. 13 of them were primarily treated with imatinib, and the other 7 were heavily pretreated with interferon alfa, cytarabine, all-trans-retinoic acid. Hydroxyurea pretreatment was routinely introduced in all patients until complete haematologic remission. Peripheral blood samples were collected in every 3rd month for quantitative real-time polymerase chain reaction, and bone marrow aspirate in every 6th month for conventional cytogenetics, respectively. Results: Haematologic remission could be achieved with hydroxyurea pretreatment in each patient. Complete cytogenetic remisson at the 6th month and major molecular response at the 12th month were observed in each patient. Conclusions: Imatinib treatment caused complete cytogenetic response and major molecular response in each chronic phase chronic myeloid leukaemia patient in our group. Hydroxyurea might have some effect on the rapid and deep cytogenetic and molecular responses, observed in the primary imatinib treated group.
