Bone marrow megakaryocytes, soluble P-selectin and thrombopoietic cytokines in multiple myeloma patients.

The expression of adhesion molecules and other cell-surface molecules is substantial in the communication between plasma cells and bone marrow microenvironment, and may lead to increased proliferation of myeloma cells. Many of the cytokines involved in multiple myeloma (MM) pathogenesis, e.g. thrombopoietin (TPO) and interleukin-6 (IL-6), play a pivotal role in different developmental stages of megakaryocytopoiesis and thrombopoiesis. The principal aim of our study was to explore the relationship between thrombopoietic cytokines, megakaryocytes (MKs) and soluble P-selectin (sP-selectin) levels in MM patients before and after anti-angiogenic treatment. Forty-four patients (20 female and 24 male) with a newly diagnosed MM were examined in three groups, following a division based on the International Staging System, ISS. Plasma levels of TPO, IL-6 and soluble P-selectin (human sP-selectin) were measured by means of ELISA. Bone marrow specimens were studied to determine the number of MKs and the so-called "naked nuclei" (NN), as well as the expression of platelet-derived growth factor (PDGF). The comparison revealed a significantly higher concentration of cytokines and sP-selectin in newly diagnosed MM patients compared to healthy volunteers: for TPO, p=0.01, IL-6, p=0.0005 and sP-selectin, p=0.00008, respectively. Marked differences were observed in the concentration of sP-selectin, expression of PDGF and MKs counts between patients with MM stage I and MM stage III. Statistically meaningful correspondences were also found between MKs versus TPO, NN versus TPO, as well as MKs versus MPV, p=0.009, p=0.004 and p=0.0005, respectively. Furthermore, the analysis exhibited some statistically meaningful divergences between initial concentrations of sP-selectin in subgroups with different response after chemotherapy. The initial concentration of sP-selectin in the group of MM patients with complete or partial remission stood at 31.86 ± 6.13 ng/ml. In the remaining patients (stable disease), the concentration of sP-selectin amounted to 35.15 ± 7.23 ng/ml (p=0.048). We found a correlation between sP-selectin and IL-6 (ρ=0.57, p=0.0004), TPO and IL-6 (ρ=0.46, p=0.001) as well as sP-selectin and TPO (ρ=0.36, p=0.043), and sP-selectin and PDGF (ρ=0.36, p=0.03). Our study has eventually demonstrated that sP-selectin, as a marker of platelet activation, could be a useful marker of maximum response to therapy. Its strong association with another marker like PDGF-AB could further lead to the development of new combinational therapeutic strategies of anti-angiogenic therapy in MM patients.

[Endoscopic picture of esophagitis in children with primary and secondary acid gastroesophageal reflux]. / Obraz endoskopowy zapalenia przelyku u dzieci z kwasnym refluksem zoladkowo-przelykowym pierwotnym i wtórnym.

UNLABELLED: THE AIM OF THE STUDY was to assess the esophageal mucous membrane in children with pathological acid gastroesophageal reflux (GER) primary and secondary to cow's milk allergy and (or) food allergy (CMA/FA), dependent on the duration of the disease (prospective study). MATERIAL AND METHODS: 264 children of both sexes suspected of GER were enrolled in the study. The age of examined children was 1.5-102 months (mean age 20.78+/-17.23 moths). Pathological acid GER was confirmed in 138 children (52.3%) with pH-monitoring. Taking into consideration complex differential diagnosis, including elimination of noxious nutrient and oral food challenge test (open or blind study), acid GER was differentiated into primary and secondary. Children were assigned into study groups 1 and 2. Group 1: 76 patients (28.8%) aged 4-102 months (mean age 25.2+/-27.28 months) with primary GER. Group 2: 62 patients (23.5%) aged 4-74 months (mean age 21.53+/-17.79 months) with GER secondary to CMA/FA. Endoscopic examination of the upper gastrointestinal tract was performed in 138 children: preliminary and control examination (after one year and two years of GERD diagnosis. RESULTS: Esophagitis of different intensity (second - fourth degree) in macroscopic assessment was diagnosed in 25 children (32.9%) with group 1 and in 29 children (46.8%) with group 2 in preliminary study. Esophagitis was still present in macroscopic assessment after one year of conservative treatment in 13 children (17.1%) from group 1 and in 12 children (19.4%) from group 2. After two years of clinical observation and periodically administered conservative treatment mild esophagitis still persisted in 3 children (3.9%) from group 1, and in 3 children (4.8%) from group 2. CONCLUSION: Esophagitis of various intensity (second - fourth degree) was diagnosed in preliminary endoscopic examination in about 33% of children with group 1 and 47% of children with group 2.

[The clinical manifestation of duodeno-gastroesophageal reflux (DGER) in the children and adolescents]. / Objawy kliniczne u dzieci i mlodziezy z refluksem zólciowym.

UNLABELLED: The development of the new techniques and methods enabled to investigate the role of duodenal reflux in the pathogenesis of gastroesophageal reflux disease (GERD) therefore there is a need to establish the most common symptoms occurring in patients with duodenal reflux. THE AIM OF THE STUDY: To determinate the type of manifestation and the prevalence of duodeno-gastroesophageal reflux in children and adolescents confirmed in Bilitec 2000 method. MATERIALS AND METHODS: 59 patients (37 girls, 22 boys) aged 7-17 years (mean 14.7) with the symptoms of GER there were divided into 2 groups: subgroups: A--18 children with confirmed duodeno-gastroesophageal reflux in Bilitec 2000TM method and B--control consisted of 15 children with short stature referred to endoscopy due to celiac disease exclusion. In accordance to the endoscopic finding there were selected 3 subgroups: 20 patients with duodenal reflux, 19 patients with esophagitis and 20 children presenting those both disorders simultaneously. In all patients from group B the endoscopy, Bilitec 2000 and esophagitis pH metric findings haven't showed any abnormality. RESULTS: The most common complain--in 16 (88.89%) patients was recurrent and/or chronic abdominal pain, next- heartburn in 12 (66.67%), vomits and/or regurgitations in 10 (55.56%) children. CONCLUSIONS: The clinical manifestation of duodenal reflux was very much alike as in acid gastroeophageal reflux in the examined group. Therefore the functional gastrointestinal tract examinations have to be included in the diagnostic procedure.

24-hour esophageal pH-monitoring in children suspected of gastroesophageal reflux disease: analysis of intraesophageal pH monitoring values recorded in distal and proximal channel at diagnosis.

AIM: To assess values of 24-h esophageal pH-monitoring parameters with dual-channel probe (distal and proximal channel) in children suspected of gastroesophageal reflux disease (GERD). METHODS: 264 children suspected of gastroesophageal reflux (GER) were enrolled in a study (mean age c=20.78+/-17.23 mo). The outcomes of this study, immunoallerrgological tests and positive result of oral food challenge test with a potentially noxious nutrient, enabled to qualify children into particular study groups. RESULTS: 32 (12.1%) infants (group 1) had physiological GER diagnosed. Pathological acid GER was confirmed in 138 (52.3%) children. Primary GER was diagnosed in 76 (28.8%) children (group 2) and GER secondary to allergy to cow milk protein and/or other food (CMA/FA) in 62 (23.5%) children (group 3). 32 (12.1%) of them had CMA/FA (group 4-reference group), and in remaining 62 (23.5%) children neither GER nor CMA/FA was confirmed (group 5). Mean values of pH monitoring parameters measured in distal and proximal channel were analyzed in individual groups. This analysis showed statistically significant differentiation of mean values in the case of: number of episodes of acid GER, episodes of acid GER lasting >5 min, duration of the longest episode of acid GER in both channels, acid GER index total and supine in proximal channel. Statistically significant differences of mean values among examined groups, especially between group 2 and 3 in the case of total acid GER index (only distal channel) were confirmed. CONCLUSION: 24-h esophageal pH monitoring confirmed pathological acid GER in 52.3% of children with typical and atypical symptoms of GERD. The similar pH-monitoring values obtained in group 2 and 3 confirm the necessity of implementation of differential diagnosis for primary vs secondary cause of GER.

[Dual simultaneous esophageal pH monitoring in infants with gastroesophageal reflux]. / Podwójne monitorowanie pH przelyku u niemowlat z objawami refluksu zoladkowo-przelykowego.

The aim of the current study was to analyse selected parameters of pH monitoring in the proximal and distal parts of esophagus. One hundred and twelve infants aged 1.25 to 18 months (mean = 5.6) with symptoms and signs suggesting gastroesophageal reflux (GER) were evaluated. The results are presented of the measurement of reflux index (RI), the number of reflux episodes and the duration of the longest reflux episode in patients classified into the following groups: group I--39 children with vomiting/excessive regurgitation, group II--29 infants with persistent distress/inconsolable crying, group III--16 children with Apparent Life Threatening Events (ALTE), group IV--28 infants with chronic/recurrent respiratory system diseases. No statistically significant difference was noted between the groups in pH parameters at the distal esophageal level, whereas at the proximal level the differences included only the number of reflux episodes. However, we found, that by using the ANOVA test, the incidence was higher in group IV than in group II. As determined by applying Mann-Whitney rank sum test, reflux episodes occurred most frequently in group IV, than in other groups of patients (including controls). None of the reflux parameters recorded at the proximal level among children presenting with ALTE was statistically significantly different than in other groups.

[Bartter syndrome--case report]. / Zespól Barttera--opis przypadku.

The authors present the case of 4-month-old girl, who was admitted to our hospital with hypokalemia, metabolic alkalosis, hyperaldosteronism, hyperreninism with normal blood pressure and high urine concentration of PGE2. All the clinical and biochemical features have led to the diagnosis of Bartter syndrome. Treatment consisted of 15% KCI, spironolacton and indometacin.

[Gastroesophagopharyngeal reflux in infants and children with recurrent symptoms of the upper respiratory tract]. / Refluks zoladkowo-przelykowo-gardlowy u niemowlat i dzieci z nawracajacymi objawami z górnych dróg oddechowych.

Gastroesophageal reflux (GER) plays an important role in pathogenesis of recurrent/chronic disorders of the respiratory tract. Atypical symptoms of GER can be suggested to be cause of the otorhinolaryngological problems. For these last manifestations no cause-effect relationship has yet been proven. There are many therapeutic studies, in which treatment of GERD is examined for its impact on coexisting respiratory disorders. The aim of our study was to confirm the presence of acid reflux by using 24-hour intraesophageal pH monitoring. From the group of 29 patients with recurrent episodes of the pharyngitis, laryngitis and tracheitis, we evaluated 18 children aged 3 months to 8 years (mean, 4.23 +/- 2.85) with coexisting reflux symptoms. The protocol included a parenteral interview, physical examination, roentgenograms of the chest and larynx, laryngoscopy, as well as 24-hour simultaneous proximal and distal esophageal pH monitoring. The most significant differences between examined patients and control subjects was noted in terms of the lowest pH value, number of reflux episodes and index reflux while pH dropped below 4. Every significant drop under pH 6 recorded in proximal esophagus was simultaneous with reflux episode in distal esophagus. We found increased both sensitivity and specificity of the simultaneous pH monitoring in the distal and proximal part of the esophagus comparing to monitoring by the single probe. We confirmed the presence of gastroesophagopharyngeal reflux in patients with recurrent disorders of pharynx, larynx and/or trachea.

[Bartter's syndrome]. / Zespól Barttera.

Bartter syndrome is an uncommon tubular disorder inherited as an autosomal recessive entity. It is associated with hypokalemic metabolic alkalosis with high renin and aldosterone plasma concentration with low or normal blood pressure. Recent studies have demonstrated genetic heterogeneity in Bartter syndrome. Mutations of two genes encoding the Na/K/2Cl cotransporter and potassium channel ROMK are responsible for clinical features of neonatal Bartter syndrome. Mutations of gen encoding the chloride channel ClC-Kb is identified as being causative for the classic Bartter syndrome. And dysfunction of Na/Cl cotransporter in the distal convoluted renal tubule is described as Gitelman syndrome.

[Long-term clinical observation of infants with gastroesophageal reflux]. / Dlugotrwala obserwacja kliniczna niemowlat z rozpoznanym refluksem zoladkowo-przelykowym.

The aim of the study was long-term observation of patients with gastroesophageal reflux (GER), diagnosed in their infancy, in aspect of spontaneous resolution of this disorder. 290 symptomatic infants aged 5 weeks to 11 months (mean--5.8 months) underwent 24-hour esophageal pH monitoring. In 243 (83.8%) patients, abnormal reflux score was observed. After one year of conservative therapy, follow-up study by esophageal pH-monitoring has been performed in 136 (46.9%) children and still showed pathological GER in 95 (69.8%) subjects. After 2 years, 45 (15.5%) patients has been investigated--14/45 (31.0%) of them had normal reflux score. At the following five-year clinical observation was available group of 28/290 (9.6%) patients. In the 2-3 year of their life, 13 of them had resolved symptoms and had normal acid reflux parameters, whereas 9 patients still had pathological GER. In the following years, basing of results of 24-hour pH monitoring, pathological GER persisted: in 7 children in age 4, in 5 subjects in age 5 and in 3 children over fifth year of life. Long-term clinical follow-up of these children is necessary because of risk of GER complications.

[Environmental factors as a cause of food allergy in childhood]. / Srodowiskowe uwarunkowania alergii pokarmowej u dzieci i mlodziezy.

There is increasing evidence that both the prevalence and severity of atopic diseases are progressively increasing in developed countries. Similar trends are also observed in rural societies which are in the process of urbanization. If allergy is really malaise of modern society, what are the environmental and societal factors responsible for it's emergence? Authors discuss this problems underlining causative role of both factors in the development of allergic disease including food allergy.

Respiratory response to proton pump inhibitor treatment in children with obstructive sleep apnea syndrome and gastroesophageal reflux disease.

OBJECTIVE: Evaluation of the respiratory response to proton pump inhibitors (PPI) in children with obstructive sleep apnea syndrome (OSAS) and gastroesophageal reflux disease (GERD). METHODS: Of 131 children diagnosed with OSAS (Apnea Hypopnea Index, AHI >1/h), 37 children (6.9 years; 28.24%) with GERD symptoms (>3 times/week) were included. Overnight polysomnography with 24h pH-metry was performed before and after 4-8 weeks of PPI treatment (omeprazole once a day, 1mg/kg). RESULTS: Of 37 children, 21 were diagnosed with acid GERD where pre- and post-treatment reflux indexes were 14.09±1.47 vs. 7.73±1.36; (p<0.001). The number of obstructive apneas and hypopneas decreased after PPI treatment, resulting in an AHI reduction from 13.08±3.11/h to 8.22±2.52/h; (p<0.01). Respiratory response to PPI ranged from complete resolution of OSA (three children with mild OSA; AHI<5/h; 10.31years; 14.29%) to lack of significant AHI change (six children with severe OSA; AHI>10/h; 3.62 years; 28.57%). Post-treatment AHI was predicted by pre-treatment reflux index (adjusted R(2)=0.487; p<0.001). CONCLUSIONS: Reduction of obstructive respiratory events following short-term PPI treatment in children with both GERD and OSAS may suggest a causal relationship between apnea and reflux in some children. Questionnaire screening for GERD in children with OSAS may be of benefit.

The levels of sMUC-1 in patients with multiple myeloma.

Mucins have been shown to be aberrantly overexpressed in various diseases including cystic fibrosis, asthma, and cancer. Recent studies have uncovered the roles of these mucins in the pathogenesis of cancer. The presence of MUC-1 has also been detected on the cell surface of multiple myeloma (MM) cells in peripheral blood and showed direct correlation with tumor mass. In this study, we evaluated the levels of soluble MUC-1 (sMUC-1) in 50 new MM patients and correlated this with the levels of sMUC-1 after treatment. High levels of sMUC-1 were found in 20/50 (40%) MM patients, and in 2/50 (4%) healthy individuals (p = 0.001). According to the ISS, we found significant differences of mean sMUC-1 levels between the first stage of the disease (0.63 ± ± 0.26) and the third (0.93 ± 0.24; p = 0.03), but not with the second stage (0.80 ± 0.22; p = 0.08). Our study confirmed the correlation between elevated sMUC-1 and high elevated lactate dehydrogenase (p = 0.03) and the level of IgG in groups of patients with MM IgG at every stage of disease (p = 0.001). We showed for the first time that levels of sMUC-1 after treatment, in a group of patients with initially elevated levels of MUC-1, were statistically lower than in a group of patients with initially lower levels of sMUC-1 (21% vs. 42,6%; p = 0.05). At 37 months median of follow-up, we found a statistically significant difference between patients with normal versus elevated sMUC-1 in terms of progression-free survival (median 12 months vs. 8.1 months; p = 0.03).

Histological evaluation of esophageal mucosa in children with acid gastroesophageal reflux.

AIM: histological evaluation of esophageal mucosa in children, with regard to the duration of primary acid gastroesophageal reflux (GER) and acid GER secondary to cow's milk allergy and/or other food allergy (CMA/FA) (prospective study). MATERIAL AND METHODS: 264 children of both sexes suspected of GER were enrolled in the study. The age of examined children was 1.5-102 months, mean age 20.78+/-17.23 months. Pathological acid GER was confirmed with pH-monitoring in 138 children (52.3%). Taking into consideration complex differential diagnosis, including oral food challenge test with potentially noxious nutrient (open or blind study), children were assigned into study groups 1 and 2 (primary and secondary GER). Group 1: 76 patients (28.8%) aged 4-102 months (x=25.2+/-27.28 months) with primary GER. Group 2: 62 patients (23.5%) aged 4-74 months (x=21.53+/-17.79 months) with GER secondary to CMA/FA. Children with GERD underwent preliminary and control (after 1 year and 2 years of GERD diagnosis) endoscopic examination of the upper gastroinestinal tract. RESULTS: Intensity of esophagitis was assessed initially in 25 children from group 1 (32.9%), in 29 children from group 2 (46.8%), and in 9 children from group 3 - reference group (28.1%). Histological evaluation revealed infiltration of inflammatory cells, mainly neutrophils and intraepithelial lymphocytes, and also eosinophils in 10 children (13.2%) with primary GER. Infiltration of eosinophils and lymphocytes was found in 5 children (8.1%) with secondary GER. In 8 children (25.0%) with food allergy there were only lymphocytes. Infiltration of neutrophils and lymphocytes and basal zone hyperplasia or infiltration of eosinophils and lymphocytes with elongation of lamina propria papillae was found in 10 children (13.1%) with primary GER and in 20 children (32.2%) with secondary GER. Differentiation of particular types of inflammatory cells in mucosal infiltration characterized histological picture in the following way: neutrophils in 21 children (27.6%) with primary GER, eosinophils in 22 children (35.5%) with secondary GER, lymphocytes in 15 children (19.7%) in children with primary GER and in 15 children (24.2%) with secondary GER. Histological examination of esophageal mucosa after 1 and 2 years of clinical observation and periodical conservative treatment in children with primary and secondary GER revealed significant alleviation of inflammatory abnormalities (with regard to the type of abnormalities and the number of particular types of inflammatory cells). CONCLUSIONS: The value of histological findings obtained in own studies comprises the role of food allergy in pathogenesis of GER and is related to GER's contribution, both direct (primary reflux) and indirect (secondary reflux), to triggering off morphological results and clinical outcomes of esophagitis.