Showing papers by "Gdańsk Medical University published in 2000"

Increases in leptin levels, sympathetic drive, and weight gain in obstructive sleep apnea

Abstract: Patients with obstructive sleep apnea (OSA) are frequently obese and are predisposed to weight gain. They also have heightened sympathetic drive. We reasoned that noradrenergic activation of β3-receptors on adipocytes would inhibit leptin production, predisposing to obesity in sleep apnea. We therefore tested the hypothesis that obesity and predisposition to weight gain in OSA are associated with low levels of plasma leptin. We prospectively studied 32 male patients (43 ± 2 yr) with OSA who were newly diagnosed and never treated and who were free of any other diseases. Control measurements were obtained from 32 similarly obese closely matched male subjects (38 ± 2 yr). Leptin levels were 13.7 ± 1.3 and 9.2 ± 1.2 ng/ml in patients with OSA and controls, respectively (P = 0.02). Weight gain over the year before diagnosis was 5.2 ± 1.7 and 0.5 ± 0.9 kg in sleep apnea patients and similarly obese control subjects, respectively (P = 0.04). Muscle sympathetic activity was 46 ± 4 and 30 ± 4 bursts/min in patient...

Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors. A study of 200 cases.

Abstract: Gastrointestinal stromal tumors (GISTs), the most common mesenchymal tumors of the gastrointestinal tract, typically express the KIT protein. Activating mutations in the juxtamembrane domain (exon 11) of the c-kit gene have been shown in a subset of GISTs. These mutations lead into ligand-independent activation of the tyrosine kinase of c-kit, and have a transforming effect in vitro. Several groups have studied the clinical implication of the c-kit mutation status of exon 11 in GISTs and a possible relationship between c-kit mutations and malignant behavior has been established. Recently, a 1530ins6 mutation in exon 9 and missense mutations, 1945A>G in exon 13 of the c-kit gene were reported. The frequency and clinical importance of these findings are unknown. In this study we evaluated 200 GISTs for the presence of mutations in exons 9 and 13 of c-kit. Six cases revealed 1530ins6 mutation in exon 9 and two cases 1945A>G mutation in exon 13. All tumors with mutations in exon 9 and 13 lacked mutations in exon 11 of c-kit. None of the analyzed tumors had more than one type of c-kit mutation. All but one of the eight tumors with mutations in exon 9 or 13 of the c-kit gene were histologically and clinically malignant. All four of six cases with exon 9 mutation of which location of primary tumor was known, were small intestinal, suggesting that this type of mutation could preferentially occur in small intestinal tumors. Exon 9 and 13 mutations seem to be rare, and they cover only a small portion (8%) of the balance of GISTs that do not have mutations in exon 11 of c-kit. This finding indicates that other genetic alterations may activate c-kit in GISTs, or that KIT is not activated by mutations in all cases.

Effects of Sleep Deprivation on Neural Circulatory Control

Abstract: —Effects of sleep deprivation on neural cardiovascular control may have important clinical implications. We tested the hypothesis that sleep deprivation increases heart rate, blood pressure...

Cytokine (TNF Alpha, LT Alpha and IL-10) Polymorphisms in Inflammatory Bowel Diseases and Normal Controls: Differential Effects on Production and Allele Frequencies

Abstract: The influence of biallelic polymorphisms in the tumour necrosis factor-alpha (TNF alpha), lymphotoxin-alpha (LT alpha) and interleukin-10 (IL-10) genes on stimulated TNF alpha and IL-10 production was studied in ulcerative colitis (UC) patients, Crohn's disease (CD) patients and in healthy controls. A polymerase chain reaction sequence-specific primer (PCR-SSP) system was developed to type nine biallelic polymorphisms, three in each of the TNF alpha, LT alpha and IL-10 genes. Production of the TNF alpha and IL-10 was measured by ELISA in lipopolysaccharide (LPS) stimulated whole blood. Four haplotypes of the TNF alpha gene, three haplotypes of LT alpha and three haplotypes of IL-10 were identified. No significant differences in haplotype frequencies were found between patients and controls overall. On subgroup analysis however, haplotype TNF-2 was more frequent in women with extensive colitis compared to distal colitis (31% vs 12%; P = 0.028). This difference was even greater for the combined TNF-2-LT alpha-2 haplotype (56% vs 21%; P = 0.0007). The TNF-2 and LT alpha-2 haplotypes were associated with higher TNF alpha production in CD patients, and the TNF-4 haplotype was associated with lower TNF alpha production in UC patients. The A allele in the IL-10 promoter region at position -1082 was associated with decreased IL-10 production in CD patients and controls (P = 0.005, P = 0.015 respectively). These data provide evidence that the effect of TNF alpha, LT alpha and IL-10 gene polymorphisms on cytokine production differ in CD, UC patients and controls.

Sympathetic Activation by Sildenafil

Abstract: Background —Sildenafil citrate is an effective and widely prescribed therapy for erectile dysfunction. Little is known about the effects of sildenafil on neural control of the circulation or about the effects of sildenafil on neurocirculatory stress responses. Methods and Results —We studied 14 normal volunteers (age 32±7 years) who were randomized in a double-blind crossover fashion to receive a single oral dose of sildenafil 100 mg or placebo on 2 separate study days. Blood pressure, heart rate, forearm vascular resistance, muscle sympathetic nerve activity, and plasma catecholamines were measured at baseline and at 30 and 60 minutes after sildenafil and after placebo administration. The effects of sildenafil and placebo on neural and circulatory responses to stressful stimuli (sustained handgrip, maximal forearm ischemia, mental stress, and the cold pressor test) were also evaluated. Blood pressure, heart rate, and forearm vascular resistance after sildenafil and placebo were similar. However, muscle sympathetic nerve activity increased strikingly after sildenafil (by 141±26%, mean±SEM) compared with placebo (3±8%) ( P =0.006); plasma norepinephrine levels also increased by 31±5% after sildenafil administration ( P =0.004). Sympathetic nerve traffic during mental, physical, and cold stresses was 2- to 8-fold higher after sildenafil than with placebo ( P Conclusions —Sildenafil causes a marked increase in sympathetic activation, evident both at rest and during stressful stimuli. Sympathetic activation by sildenafil may have implications for understanding cardiovascular events associated with sildenafil use.

Steady-state and time resolved fluorescence of albumins interacting with N-oleylethanolamine, a component of the endogenous N-acylethanolamines.

Abstract: The functions of N-acylethanolamines, minor constituents of mammalian cells, are poorly understood. It was suggested that NAEs might have some pharmacological actions and might serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes or mediated by activation of cannabinoid receptors. Albumins are identified as the major transport proteins in blood plasma for many compounds including fatty acids, hormones, bilirubin, ions, and many drugs. Moreover, albumin has been used as a model protein in many areas, because of its multifunctional binding properties. Bovine (BSA) and human (HSA) serum albumin are similar in sequence and conformation, but differ for the number of tryptophan residues. This difference can be used to monitor unlike protein domains. Our data suggest that NOEA binds with high affinity to both albumins, modifying their conformational features. In both proteins, NOEA molecules are linked with higher affinity to hydrophobic sites near Trp-214 in HSA or Trp-212 in BSA. Moreover, fluorescence data support the hypothesis of the presence of other NOEA binding sites on BSA, likely affecting Trp-134 environment. The presence of similar binding sites is not measurable on HSA, because it lacks of the second Trp residue.

The Terminal Portion of the T Wave: A New Electrocardiographic Marker of Risk of Ventricular Arrhythmias

Abstract: Experimental studies have shown that transmural dispersion of repolarization (DoR), defined as the difference in action potential duration between mid-myocardial M-cells, epicardial, and endocardial cells is reflected in the duration of the terminal portion of the T wave (TpTe) on the surface ECG. Since DoR is an important factor associated with the propensity for reentrant arrhythmias, this study examined if TpTe may serve as a marker of risk of ventricular arrhythmias. Data from 18 patients with coronary artery disease and inducible sustained ventricular tachycardia (VT group) were compared with those of 16 survivors of myocardial infarction without inducible VT (control group). TpTe was automatically measured in each beat of 24-hour ECG recordings, and programmed ventricular stimulation was performed in the antiarrhythmic drug-free state. TpTe was expressed as the absolute interval in milliseconds, and relative to the duration of QTe (TpTe/QTe x 100%). TpTe duration was 74 +/- 14 ms in the VT group versus 63 +/- 16 ms in the control group (P < 0.004). The TpTe interval expressed as a percent of the QT interval was 21 +/- 4% in the VT group versus 17 +/- 3% in the control group (P = 0.02). In patients with coronary artery disease. TpTe was longer in patients with, versus without, inducible VT. The results of this study support the hypothesis that TpTe reflects transmural dispersion of repolarization.

Hyperventilation alters arterial baroreflex control of heart rate and muscle sympathetic nerve activity.

Abstract: Interactions between mechanisms governing ventilation and blood pressure (BP) are not well understood. We studied in 11 resting normal subjects the effects of sustained isocapnic hyperventilation o...

Recurrent endometrial cancer after surgery alone: Results of salvage radiotherapy

Abstract: Purpose: Postoperative irradiation of endometrial cancer patients decreases the risk of local recurrence but is associated with a number of long-term sequelae. In a proportion of patients, no immediate postoperative radiotherapy is applied and this treatment is introduced only at relapse. The aim of our study was to assess the long-term results of salvage radiotherapy in previously nonirradiated endometrial cancer patients who developed local recurrence, and to evaluate the impact of patient- and treatment-related factors on treatment efficacy. Methods and Materials: We performed a detailed retrospective analysis of 73 endometrial cancer patients given radiotherapy for local recurrence after the initial surgery only. The mean age at diagnosis of the recurrence was 63 years (range, 39–78 years). Median time to recurrence was 11 months (range, 1–19 months). All recurrences were staged with the use of Perez modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for primary vaginal carcinoma. There were five (7%) Stage I patients, 43 (59%) Stage II patients, and 25 (34%) Stage III patients. Forty-four patients (60%) received both external beam irradiation (EBRT) and endovaginal brachytherapy (BRT), 17 (23%) received only BRT, and 12 (17%) received only EBRT. The mean total physical radiation dose was 75.9 Gy (range, 8–130 Gy), and the mean normalized total dose (NTD) calculated on the base of the linear-quadratic model was 86.6 Gy (range, 8.5–171.9 Gy). Median follow-up for alive patients was 8.8 years (range, 3–21 years). The impact of patient-, tumor-, and therapy-related factors on the treatment outcome was evaluated with the use of uni- and multivariate analyses. Results: Three- and 5-year overall survival rates were 33% and 25%, respectively. In the univariate analysis, lower stage of recurrent disease ( p p = 0.027), higher total radiation dose ( p = 0.031), and higher NTD ( p = 0.006) were significantly correlated with better survival. In the multivariate analysis, only stage of recurrent disease ( p p = 0.047) were independently correlated with better survival. Lower FIGO stage of recurrence ( p = 0.023) and higher total dose ( p = 0.005) were also independently correlated with longer time to progression, whereas higher radiotherapy dose was the only factor correlated with better local control ( p = 0.029). Conclusions: The efficacy of salvage radiotherapy in endometrial cancer patients with local failure after previous surgery is limited. Factors determining treatment outcome include advancement of the tumor at relapse and radiotherapy dose.

Atrial fibrillation after coronary artery bypass grafting without cardiopulmonary bypass.

Abstract: Objective Atrial fibrillation is the most common complication after heart surgery. It rarely has a fatal outcome but causes patient instability, prolongs hospital stay, or even is the reason for perioperative infarction. Although conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass has excellent short-term and long-term results, the number of coronary operations on a beating heart without cardiopulmonary bypass is still growing. To reduce surgical trauma, off-pump coronary artery bypass grafting via sternotomy (OPCABG) or minimally invasive direct vision coronary artery bypass grafting (MIDCABG) via small thoracotomy are performed. The aim of this study was to estimate the frequency of atrial fibrillation in patients after myocardial revascularization without cardiopulmonary bypass. Methods A retrospective analysis of 48 patients undergoing myocardial revascularization without cardiopulmonary bypass was performed. Twenty-four patients underwent OPCABG and 24 were operated using the MIDCABG technique. The incidence of cardiac arrhythmias was analyzed since operation to the fourth postoperative day. Each patient had continuous ECG monitoring with option of arrhythmia analysis during ICU stay. After discharge from ICU 24-h ECG monitor studies were carried out. Surface 12-lead ECG was accomplished once a day, and additionally each time symptoms of cardiac arrhythmia occurred. Risk factors of atrial fibrillation were estimated. Results Atrial fibrillation occurred in 25% of patients after MIDCABG, in 29% after OPCABG, and in 18% after CABG with cardiopulmonary bypass. This difference has no statistical significance. Risk factors and incidence of postoperative complications were comparable in all groups. Conclusions Atrial fibrillation is a common complication after procedures of myocardial revascularization, performed with or without cardiopulmonary bypass. The occurrence is not dependent on the type of operation.

Headache in patients with mild to moderate hypertension is generally not associated with simultaneous blood pressure elevation.

Abstract: ObjectiveAlthough headache is regarded a symptom of hypertension, its relation to blood pressure, especially in mild and moderate hypertension, is not clear. Thus, the aim of the study was to investigate whether headache in patients with mild to moderate hypertension may be attributed to simultaneou

Corticotropin releasing hormone and related peptides can act as bioregulatory factors in human keratinocytes

Abstract: Following previous findings in human skin of the functional expression of genes for the corticotropin releasing hormone (CRH) receptor type 1 (CRH-R1) and CRH itself, we searched for local phenotypic effects for peptides related to CRH. We now report that CRH, sauvagine, and urocortin inhibit proliferation of human HaCaT keratinocytes in a dose-dependent manner. The peptides produced variable cyclic adenosine 3':5'-monophosphate stimulation, with CRH having the highest potency. Binding of iodine 125 CRH to intact keratinocytes was inhibited by increasing doses of CRH, sauvagine, or urocortin, all showing equal inhibitory potency. Immunocytochemistry identified CRH-R1 immunoreactivity in HaCaT keratinocytes. In conclusion, CRH (exogenous or produced locally) and the related urocortin and sauvagine peptides can modify human keratinocyte phenotype through a receptor-mediated pathway.

Comparative study of the lipogenic potential of human and rat adipose tissue.

Abstract: The reported low activity of lipogenic enzymes (especially adenosine triphosphate [ATP]-citrate lyase) in human adipose tissue led to the general conclusion that in humans lipogenesis occurs primarily in the liver. However, recent studies indicate that the liver plays a minor role in de novo lipogenesis and suggest that adipose tissue may be the principal lipogenic human tissue. In an attempt to resolve these contradictions we reinvestigated the lipogenic potential of human adipose tissue and compared with adipose tissue of rats fed a high-fat diet for 2 weeks and fasted overnight before death. These conditions mimic the nutritional state of patients at the moment of tissue sampling. We found that overnight fasting of the rats maintained previously for 12 days on a high-fat diet caused a decrease of ATP-citrate lyase of about 7-fold. Thus, in human adipose tissue, the mean activity of ATP-citrate lyase was approximately 8 times lower than in rats fed a high-fat diet and fasted overnight, and about 50 times lower than in rats maintained on normal laboratory diet. Unlike ATP-citrate lyase, fatty acid synthase (FAS) activity was only slightly lower in human adipose tissue than in rats maintained on a normal laboratory diet. Comparable FAS activity was found when rats were fed a high-fat diet and fasted overnight. The average activities of human adipose tissue acetyl-coenzyme A carboxylase, malic enzyme, and glucose-6-phosphate dehydrogenase were approximately 3-, 4-, and 6-fold lower than in adipose tissue from rats fed a high-fat diet and fasted overnight before tissue sampling, while the activity of 6-phosphogluconate dehydrogenase in humans was higher than in rat adipose tissue. No significant differences in lipogenic enzyme activities were found between male and female and between lean and obese patients. The rate of fatty acid synthesis in intact pieces of human adipose tissue was approximately 5 times lower than in adipose tissue pieces of rats fed a high-fat diet and fasted overnight before tissue samples were taken. The comparison of the lipogenic potential of humans and rats (maintained on the diet to mimic the nutritional state of patients at the time of tissue sampling) suggests that human adipose tissue is an important site of fatty acid synthesis.

Synthesis and hypolipidemic and antiplatelet activities of α-asarone isomers in humans (in vitro), mice (in vivo), and rats (in vivo)

Abstract: A series of α-asarone isomers was synthesized and investigated for their hypolipidemic and antiplatelet activity. Considering the hypolipidemic activity in rats at a dose of 80 mg/kg/day, some isom...

Interleukin-10 gene promoter polymorphism in English and Polish healthy controls. Polymerase chain reaction haplotyping using 3' mismatches in forward and reverse primers.

Abstract: A polymerase chain reaction with sequence-specific primers (PCR-SSP) system using primers with mismatches at the 3' ends was developed to determine polymorphisms in IL-10 promoter region. Three previously described biallelic polymorphisms in IL-10 were linked in a 12 reaction PCR-SSP system and the method used to provide genotype data on 233 UK and 166 Polish controls. There are eight possible polymorphic combinations in IL-10 promoter gene but only three were observed in both control groups. Population frequencies of IL-10 genotypes show, in contrast to HLA, that UK and Polish frequencies are remarkably similar.

A Pharmacokinetic Study of Amphotericin B Lipid Complex Injection (Abelcet) in Patients with Definite or Probable Systemic Fungal Infections

Abstract: This study describes a pharmacokinetic evaluation of amphotericin B (AMB) lipid complex injection (ABLC or Abelcet) in 17 patients with systemic fungal infection administered 5 mg/kg of body weight/day by infusion for 10 to 17 days. The results showed that AMB exhibited multiexponential disposition with high clearance, large volume of distribution at steady state, and long apparent elimination half-life but no evidence of accumulation in the blood after multiple daily doses. The results confirm previous observations and further reinforce the suggestion that ABLC may exist as a depot in the tissues from which free AMB is slowly released to limit exposure.

Linear and quadratic relationships between retention and organic modifier content in eluent in Reversed Phase High-Performance Liquid Chromatography: A systematic comparative statistical study

Abstract: Statistical evaluation of linear and quadratic models of chromatographic retention was performed The relationships describing retention were derived for a set of 23 carefully selected test analytes chromatographed on 18 HPLC columns using methanol-water or acetonitrile-water solutions as mobile phase It was ascertained whether the square term in the quadratic model improves the description of chromatographic retention in a statistically significant manner It was also checked whether the retention data extrapolated to a hypothetical neat water eluent (log k w ) obtained with the two models and the two organic modifiers are equivalent or should be considered different The research proved that both models yield similar results and the extrapolated log k w values do not differ statistically significantly in the case of methanol-containing mobile phases In the case of acetonitrile-water systems the log k w values obtained with linear and quadratic models are normally statistically different Correlation analysis for log k w vs log P parameters was performed for data determined on six columns The best correlations were achieved employing log k w data derived with the linear model for methanol/ water systems

Venoocclusive liver disease (VOD) as a complication of Wilms' tumour management in the series of consecutive 206 patients.

Abstract: Depuis 4 ans (1993-1996) 206 patients presentant un nephroblastome ont ete traites Tous ces patients ont ete traites selon le protocole SIOP 93-01 La survie globale est de 92% Dans 27 cas des accidents hepato-toxiques sont survenus Dans 10 cas une maladie veino-occlusive (VOD) a ete diagnostiquee VOD est un syndrome qui associe hepatomegalie, augmentation de poids ou ascite et jaunisse Ceci est la consequence d'alterations de l'endothelium des veinules hepatiques et d'une necrose centrale des hepatocytes avec pour consequences une proliferation de tissu fibreux et une occlusion des veines hepatiques La Dactinomycine est l'une des drogues consideree comme responsable de son developpement L'âge moyen des patients avec maladie veino-occlusive etait de 4 ans; quoique 3 d'entre eux etaient d'un âge inferieur a 1 an Dans tous les cas la VOD survient durant la chimiotherapie postoperatoire (en moyenne a 16 semaines de traitement) Tous les patients recevaient Dactinomycine et Vincristine Cinq patients avec des tumeurs du rein droit subirent une irradiation postoperatoire Les principaux syndromes de la maladie veino-occlusive etaient l'hepatomegalie et l'ascite (80%), une augmentation des transaminases associee a un epaissement de la paroi de la vesicule biliaire et/ou un epanchement intra-abdominal etaient observes La duree moyenne de la maladie veino-occlusive etait de 27 jours et son evolution etait generalement temporaire et se limitait par elle-meme Neanmoins dans 2 cas des episodes recurrents de maladie veino-occlusive etaient notes Tous les patients recevaient un traitement symptomatique seulement Dans 6 cas, la maladie veino-occlusive entrainait un retard dans la chimiotherapie ou une diminution des drogues Neanmoins dans 4 autres, la chimiotherapie etait d'emblee complete Ceci n'entraine pas de modification du devenir des patients La survie globale dans la maladie veino-occlusive est de 90% Conclusion: 5% de VOD est une frequence similaire a celle des autres publications Les nourissons et les enfants recevant une irradiation abdominale semblent particulierement a risque de developper une maladie veino-occlusive

Correlation between plasma carnitine, muscle carnitine and glycogen levels in maintenance hemodialysis patients.

Abstract: Chronic hemodialysis (HD) may lead to losses of carnitine from plasma and muscle. Plasma carnitine does not reflect the body content of carnitine. The purpose of this study was the evaluation of total and free plasma and muscle carnitine concentrations (TPC, FPC, TMC, FMC), muscle glycogen and the relationship between plasma and tissue carnitine content and the basic indices of lipid metabolism in HD patients. The studies were conducted in two groups: the first one consisted of 37 HD patients (19 F, 18 M), the second one served as the control and was composed of 29 (10 F, 19 M) patients with healthy kidneys. Tissue specimens in HD patients were taken during surgery on arterio-venous fistula from brachioradial muscle. Carnitine and glycogen measurements were performed using enzymatic methods according to Cederblad and Huijng respectively. Total cholesterol (CH), HDL-CH, and triglycerides were assayed by enzymatic commercial test system (Boehringer-Mannheim, Germany). To summarise, we found the following phenomena in our HD patients in comparison with the controls: 1) In plasma: similar TPC but decreased FPC levels and FPC/TPC ratio which may suggest free carnitine deficiency. 2) In muscle: significantly lower TMC and FMC levels but normal FMC/ITMC ratio. 3) Negative correlation between TMC and FMC levels and duration of dialysis treatment. 4) No correlation between plasma and muscle camitine concentration. 5) Significantly higher concentration of muscle glycogen which could be explained by the changes in the structure of muscle fibres in HD patients and/or lower physical activity. 6) A positive correlation between FPC/APC or FPC/TPC ratio and HDL-CH in HD patients which may suggest that an appropriate proportion between free and acylcarnitines may influence HDL-CH levels in that population.