The relationship between sudomotor function and skin microvascular reactivity in individuals with type 1 diabetes of long duration.

AIM: The aim of this study was to assess the relationship between sudomotor function and microvascular perfusion in patients with type 1 diabetes (DM1). METHODS: We evaluated 415 patients (206 women), with DM1, median age of 41 (IQR: 33-53) years, disease duration of 25 (IQR: 20-32) years. We assessed metabolic control of diabetes and the presence of peripheral and cardiac autonomic neuropathy. Sudomotor function was assessed using Sudoscan device by electrochemical skin conductance (ESC). Microvascular function was measured by laser-Doppler flowmetry with basal perfusion, the peak flow after occlusion (PORHpeak) and THmax which is the percentage change between basal perfusion and the peak flow during thermal hyperemia (TH). The accumulation of advanced glycation end products in the skin was assessed by skin autofluorescence (AF) measurement using AGE Reader. We subdivided patients based on the presence of diabetic peripheral neuropathy (DPN), cardiac autonomic neuropathy (CAN) and according to normal value of ESC. RESULTS: Patients with abnormal ESC had higher skin AF [2.5 (2.1-2.9) vs 2.1 (1.9-2.5) AU, p < 0.001], lower eGFR [83 (72-96) vs 98 (86-108) ml/min/1.73 m2, p < 0.001], higher basal perfusion [25 (12-81) vs 14 (7-43) PU, p < 0.001], lower THmax [664 (137-1461) vs 1115 (346-1933) %, p = 0.002], higher PORHpeak [104 (59-167) vs 70 (48-135) PU, p < 0.001] as compared to subjects with normal ESC results. We found negative correlation between THmax and TG level (Rs = -0.14, p < 0.005), AF (Rs = -0.19, p = 0.001), vibration perception threshold - VPT (Rs = -0.24, p < 0.001) and positive correlation with HDL level (Rs = 0.14, p = 0.005), Feet ESC (Rs = 0.21, p < 0.001) and Hands ESC (Rs = 0.14, p = 0.004). We found positive correlation between PORHpeak and TG level (Rs = 0.14, p = 0.003), skin AF (Rs = 0.29, p < 0.001), VPT (0.27, p < 0.001) and negative correlation with eGFR (Rs = -0.2, p < 0.001), HDL (Rs = -0.12, p = 0.01), Feet ESC (Rs = -0.27, p < 0.001) and Hand ESC (Rs = -0.16, p = 0.002). CONCLUSION: Impaired microvascular reactivity is associated with sudomotor dysfunction in patients with type 1 diabetes.

The occurrence of dynamic structural disorders in the pharynx and larynx, at rest and during exercise, in horses diagnosed with mild and moderate Equine Asthma (Inflammatory Airway Disease).

The goal of the present study was to establish the occurrence of structural disorders in the larynx and pharynx during treadmill exercise tests in horses diagnosed with Equine Asthma (EA). Investigation was performed in 29 horses, patients of the Equine Clinic of the Warsaw University of Life Sciences in Poland, admitted with poor exercise performance. Upper and lower airway examinations were performed in all patients revealing both mild to moderate Equine Asthma (13 horses), and no lower airway abnormalities (16 animals). In the group of horses with EA, 11 did not have structural disorders of the pharynx and larynx at rest. During exercise two horses were free of abnormalities, while 11 had structural disorders, eight of them solely in the pharynx, two in the larynx, and one in both the pharynx and larynx. In the non- asthmatic group, 11 horses had no structural disorders during resting endoscopy. Endoscopy performed during exercise revealed disorders of the larynx in 10 horses, of the pharynx in three horses, and in both the larynx and pharynx in the remaining three horses. IN CONCLUSION: horses with diagnosed EA frequently have disorders of the pharynx during treadmill exercise tests, while without EA, often have disorders of the larynx. Endoscopy of upper airways during exercise testing is a valuable tool in the diagnosis of poor performance in horses with lower airway inflammatory disease.

Cytological evaluation of tracheal aspirate and broncho-alveolar lavage fluid in comparison to endoscopic assessment of lower airways in horses with recurrent airways obstruction or inflammatory airway disease.

The aim of the present study was to compare the grade of discharge accumulation in the tracheal lumen, area of tracheal bifurcation, main bronchi and the tracheal septum thickness with the cytology of the tracheal aspirate (TA) and broncho-alveolar lavage fluid (BALF) in horses with recurrent airways obstruction and inflammatory airway disease from those horses. This study was conducted on 96 horses with RAO, 139 horses with IAD and 10 control horses. In all the horses, both clinical and endoscopic examinations were performed. During endoscopy, a score of mucus accumulation was estimated in 3/4 lower of the trachea and in the tracheal bifurcation. In addition, thickening of the tracheal septum was also assessed; tracheal aspirates and broncho-alveolar lavage were performed. An estimate of cell percentage was done in TA and BALF samples. In horses suffering from RAO and IAD, there was a positive correlation between the percentage of neutrophils and the accumulation of discharge, and in the IAD group, there was a negative correlation between the percentage of eosinophils and the accumulation of discharge. There was no correlation between tracheal septum thickening and the percentage of neutrophils and/or eosinophils.

Usefulness of the assessment of discharge accumulation in the lower airways and tracheal septum thickening in the differential diagnosis of recurrent airway obstruction (RAO) and inflammatory airway disease (IAD) in the horse.

The aim of the present study was to use endoscopic evaluation to compare the grade of accumulation of discharge in the lower airways of horses with recurrent airway obstruction (RAO) and inflammatory airway disease (IAD), and to estimate the usefulness of endoscopic evaluation in differential diagnosis of these diseases. Endoscopic evaluation consists of: the amount of discharge in the lower part of the trachea and tracheal bifurcation, and the assessment of tracheal septum thickness. This study was performed on 248 horses, 10 were healthy, 97 were diagnosed as RAO, and 141 were diagnosed as IAD. In all animals both a clinical and endoscopic examination were performed. During endoscopy, a score of mucus accumulation was estimated in 3/4 lower of the trachea and in the tracheal bifurcation. In addition to this, thickening of the tracheal septum was also assessed. According to the results of this study, it was estimated that the accumulation of mucus in the lower airways was much more advanced in RAO horses compared to horses with IAD. In horses with RAO there was a marked thickening of the tracheal septum compared to IAD horses. The results indicate the efficacy of scoring the amount of mucus in the tracheal lumen and tracheal bifurcation, as well as the efficacy of the assessment of tracheal septum thickness in the diagnosis of these diseases.

Smoking and other factors associated with short-term partial remission of Type 1 diabetes in adults.

AIMS: The duration of partial remission of Type 1 diabetes is associated with the degree of initial metabolic disturbance and features of insulin resistance. Cigarette smoking decreases insulin sensitivity, but its influence on the length of remission is unknown. Therefore, this study assessed the relationship between cigarette smoking and duration of partial remission in adults with newly diagnosed Type 1 diabetes. METHODS: We recruited 149 patients (48 women and 101 men, aged 16-35 years, median age 25 years), admitted to a teaching hospital with newly diagnosed Type 1 diabetes and followed them for a median period of 1 year and 9 months. We introduced intensive insulin therapy in multiple injections (basal-bolus) in all patients. We defined partial remission as an insulin dose of ≤ 0.3 U/kg body weight/24 h, an HbA(1c) value < 53 mmol/mol (7.0%) and a random serum C-peptide concentration over 0.5 ng/ml. Cigarette smoking was determined by self-report. RESULTS: Of 149 patients, 68 (46%) fulfilled the criteria for partial remission at 1 year after diagnosis of diabetes. Fewer patients who were in partial remission at 1 year smoked (19/68, 28%) than did patients that were not in partial remission (41/81, 51%). In logistic regression analyses, non-smoking was associated with remission at 1 year independent of age, sex, HbA(1c) and presence of diabetic ketoacidosis, all measured at onset of diabetes (OR 3.32, 95% CI 1.42-7.75, P = 0.005). CONCLUSION: Relative to individuals in this study who smoked, those who did not smoke at diagnosis of Type 1 diabetes experienced a longer duration of partial remission.

Evidence of polymorphonuclear neutrophils (PMN) activation in patients with insulin-dependent diabetes mellitus.

Polymorphonuclear neutrophils' chemotaxis, surface charge, superoxide anions generation, NBT (nitro blue tetrazolium) reduction and intracellular lysozyme, and beta-glucuronidase content were estimated in patients with type I diabetes mellitus in a similar state of metabolic control. The chemotaxis of diabetic cells toward bacterial chemotactic factors was similar to controls, whereas migration toward complement-derived chemoattractants was significantly reduced. Polymorphonuclear neutrophils isolated from diabetic patients, when unstimulated, produced significantly greater amounts of superoxide anions and reduced NBT more efficiently. They also revealed reduced surface charge and lower intracellular content of lysozyme, whereas beta-glucuronidase content was similar to controls. The results obtained seem to indicate that neutrophils in patients with insulin-dependent diabetes manifest signs of being in the activated state. The possible mechanisms of such stimulation are discussed.

Founder BRCA1 mutations and two novel germline BRCA2 mutations in breast and/or ovarian cancer families from North-Eastern Poland.

Germline mutations in the BRCA1 and BRCA2 genes account for the majority of high-risk breast/ovarian cancer families, depending on the population studied. Previously, BRCA1 mutations were described in women from Western Poland. To further characterize the spectrum of BRCA1 mutations and the impact of BRCA2 mutations in Poland, we have analyzed 25 high-risk breast and/or ovarian cancer families from North-Eastern Poland for mutations in all coding exons of the BRCA1 and BRCA2 genes, using combined heteroduplex analysis/SSCP followed by direct DNA sequence analysis. Out of 25 probands a total of five (20%) carried three recurrent BRCA1 mutations (300T>G, 3819del5, 5382insC). The 300T>G mutation accounted for 60% (3/5) of BRCA1 mutations and allelotyping suggested a common founder of this mutation. No unique mutations were found. In addition, we identified three BRCA2 (12%) mutations, one recurrent 4075delGT, and two novel frameshift mutations, 7327ins/dupl19 and 9068delA. We conclude that 30% of high-risk families from North-Eastern Poland may be due to recurrent BRCA1 and unique BRCA2 mutations. Intriguingly, the BRCA1 mutation spectrum seems to be different within subregions of Poland.

Possible prognostic value of plasma activity augmenting polymorphonuclear neutrophils (PMN) adherence estimations in untreated patients with chronic myeloid leukemia.

Plasma activity augmenting polymorphonuclear neutrophils adherence was evaluated in 30 untreated patients with chronic myeloid leukemia. The estimations were done by the use of cells isolated from healthy persons. The plasma of some patients with CML induced the intensive adherence of PMN to plastic surface. Further observations suggested, that these patients were characterized by earlier blast crisis occurrence and poorer prognosis.

Polymorphonuclear neutrophils adherence, superoxide anion (O2-) production and HBA1 level in diabetic patients.

It was established that metabolic disturbances accompanying the impairment of diabetes control induced polymorphonuclear neutrophil (PMN) activation. Therefore, we evaluated the influence of diabetes control, measured as HbA1, level on superoxide anions production and neutrophils adherence to foreign surface. Twenty patients with insulin-dependent or non-insulin-dependent diabetes being in different state of metabolic control were studied. It was revealed that PMN from diabetics demonstrated significantly increased unstimulated superoxide anion production (11.07 +/- 1.25 vs. 4.15 +/- 1.24 nmol O2-/10(6) PMN/10 min). Stimulated O2- production did not reach the same levels as controls (21.80 +/- 1.34 vs. 23.67 +/- 4.36 nmol O2-/10(6) PMN/10 min). There were highly significant correlations between unstimulated O2- production and HbA1, levels (r = 0.86). Adherence of diabetic PMN suspended in autologous plasma was significantly increased in comparison to controls (12.76 +/- 1.20 vs. 6.04 +/- 1.99 cells/mm2). However, these data did not correlate with HbA1 level (r = 0.06). In conclusion our results seems to indicate that metabolic control of diabetes influence PMN function.

Impairment of the oxygen-dependent microbicidal mechanisms of polymorphonuclear neutrophils in patients with type 2 diabetes is not associated with increased susceptibility to infection.

Phagocytosis, bactericidal capacity and some selected parameters of oxygen-dependent bactericidal mechanisms were evaluated in 20 patients with type 2 diabetes being in similar (intermediate) state of metabolic control and in 15 healthy individuals. Polymorphonuclear neutrophils (PMNs) from diabetics showed normal ability to phagocytose staphylococci, a decreased Intracellular bacteria killing, the impaired stimulated superoxide anion (O2-) and hydrogen peroxide (H2O2) production and the low intracellular myeloperoxidase activity. The obtained data seem to indicate that the decreased bacterial killing by PMNs isolated from diabetics are partly at least related to an impairment of the oxygen-dependent bactericidal mechanisms. Since none of the diabetic patients suffered from recurrent infection the clinical significance of our finding is still uncertain.

The influence of insulin-dependent diabetes mellitus (IDDM) duration on superoxide anion and hydrogen peroxide production by polymorphonuclear neutrophils.

We address the question whether oxygen metabolism of polymorphonuclear neutrophils (PMN) is influenced by disease duration in patients with insulin-dependent diabetes mellitus (IDDM). PMN were isolated from patients with IDDM of various durations and from healthy controls. We measured PMN production of superoxide anions (O2-) by cytochrome c reduction (see Babior, B.M. et al. (1973) J. Clin. Invest. 52, 741-746) and PMN production of hydrogen peroxide (H2O2) by phenol red oxygenation (see Pick, E. (1980) J. Immunol. Methods 38, 161-169) in three groups of IDDM patients subdivided according to disease duration (group A: IDDM less that 10 years; group B: IDDM of 10-15 years; group C: IDDM of more than 15 years) and in control healthy subjects (group H). Unstimulated O2- production in all IDDM patients was not statistically different from control values (A: 4.3 +/- 0.4 nmol/10(6) PMN per 30 min, nmol/10(6) PMN per 30 min; C: 4.9 +/- 0.9 nmol/10(6) PMN per 30 min; and H: 3.5 +/- 0.2 nmol/10(6) PMN per 30 min, respectively). In contrast, stimulated O2- production was significantly lower in both patients with 10-15 years, and patients with more than 15 years, duration of IDDM than in controls (B: 25.7 +/- 2.5 nmol/10(6) PMN per 30 min; C: 21.1 +/- 3.4 nmol/10(6) PMN per 30 min and H: 42.2 +/- 1.1 nmol/10(6) PMN per 30 min, respectively) correlating with disease duration (r = -0.44, P < 0.033). The stimulated O2- production in patients with less than 10 years duration of IDDM (A: 35.7 +/- 1.9 nmol/10(6) PMN per 30 min) was slightly lower than in controls. H2O2 production of unstimulated PMN (A: 4.0 +/- 0.5 nmol/10(6) PMN per 30 min; B: 4.4 +/- 0.8 nmol/10(6) PMN per 30 min and C: 4.4 +/-1.0 nmol/10(6) PMN per 30 min, respectively) was much higher than those in controls. In contrast, stimulated H2O2 production did not differ statistically from the value noticed in healthy subjects. The results obtained might indicate that production of H2O2 by unstimulated cells is increased in diabetic patients while generation of O2- by stimulated neutrophils is markedly impaired, suggesting that toxic oxygen species production might be influenced by disease duration.

Metabolic control quality and free radical activity in diabetic patients.

The role of oxidative/reductive balance derangement in the pathogenesis of diabetic microangiopathy has often been discussed in the last few years. Therefore, we decided to evaluate the influence of intensive insulin therapy on selected indicators of free radical production. The levels of plasma hydrogen peroxide (H2O2) and serum malonyldialdehyde (MDA) were estimated in 15 patients with Type 1 and 15 with Type 2 diabetes before and after 2 weeks of intensive treatment. The initial H2O2 and MDA levels in all cases were significantly higher than in controls. After 2 weeks of treatment, the values for both estimated parameters were significantly lower; however, they were still higher than in the control group. Our results seem to confirm the previous suggestions concerning the relation between metabolic disturbances and oxidative stress in diabetic patients.

Hematological effects of the new immunosuppressive drug 15-deoxyspergualin.

Since systematic hematological studies on blood and bone marrow changes after treatment with 15-Deoxyspergualin (DOS) are lacking, a quantitative assessment was performed fourteen or twenty eight days after intraperitoneal application of DOS to rats. Further observations done 7 and 14 days after discontinuation of DOS administration allowed analysis of bone marrow regeneration. DOS induced lymphocytopenia, granulocytopenia and anemia with a decrease of bone marrow cellularity due to suppression of cell maturation. The effect was dose-dependent and bone marrow as well as blood changes were observed in animals treated with doses from 0.5 to 10.0 mg/kg DOS. Within 14 days after termination of the treatment, rapid recovery with normalization of all hematological parameters was observed. In the light of our data, these hematological side effects may not be a major disadvantage, if DOS is used in doses below 2.5 mg/kg, and for a course of therapy which is limited to 7 to 14 days.

The occurrence of cerebellar hemangioblastoma in numerous first degree relatives with von Hippel-Lindau disease.

Von Hippel-Lindau disease is an autosomal dominant disorder caused by a mutation of VHL gene. The incidence of the disease is one in 36,000 and its clinical manifestation is a familial occurrence of hemangioblastoma of the central nervous system and retina, renal cell cancer and pheochromocytoma. Cerebellar hemangioblastoma is the most frequent or sometimes the only abnormality observed in this syndrome. We present a family with von Hippel-Lindau disease in which four first degree relatives had a cerebellar hemangioblastoma. This neoplasm caused the death of two brothers aged 27 and 24 years old, respectively and their mother aged 62. The third son of this family was affected ten years ago, at the age of 30. The healthy family members are counselled in Oncological Genetic Outpatient Unit in Gdansk.

Association of Klinefelter syndrome and abdominal teratoma: a case report.

Extragonadal germ cell tumors are rare. The association with Klinefelter syndrome has become observed recently. A case of an 11-month-old infant with Klinefelter syndrome and a retroperitoneal mature teratoma is presented. In the tumor and lymphocytes, a 47,XXY karyotype was found. The association of Klinefelter syndrome with germ cell tumors and its possible explanations are discussed.

Intravascular degranulation of polymorphonuclear neutrophils during hemodialysis. The effects of pretreatment with colchicine.

Polymorphonuclear neutrophil (PMN) counts, plasma activity inducing PMN aggregation, augmenting PMN adherence and chemotactic activity were estimated during hemodialysis (HD) with cuprophane membranes. All these plasma activities are accepted as related to the presence of activated complement (C). The same estimations were made for hemodialyzed patients pretreated with colchicine. The results, especially comparison of plasma activities in blood entering and leaving the dialyzer, indicate that significant amounts of activated C components are generated within the patients vascular bed. The PMN entrapped in the pulmonary microcirculation that undergo subsequent degranulation are most probably the source of these C components. This concept was confirmed by the results for patients pretreated with colchicine, who had significantly less of the activities generated in the patients own circulation.

Cardiopulmonary bypass-induced complement activation. Evidence for C5a participation.

Plasma activity inducing polymorphonuclear neutrophils (PMN) aggregation, augmenting PMN adherence, plasma chemotactic activity as well as peripheral PMN count were estimated in patients during cardiopulmonary bypass. In the course of the surgical procedure the chemotactic activity and the activity inducing PMN aggregation were detected in plasma. The top of these two activities was always followed by the significant fall of the peripheral PMN count. The increase of the activity augmenting PMN adherence was observed in a part of cases, but when noticed, always preceded the maximum of the remaining evaluated activities.

[The correlation between clinical and histological features and complexity of chromosomal changes in primary ovarian cancer]. / Ocena zaleznosci pomiedzy zlozonoscia aberracji chromosomowych guzów pierwotnych a czynnikami klinicznymi i histopatologicznymi raka jajnika.

The aim of the study was to determine the correlation between the complexity of chromosome aberrations in ovarian cancer and its clinical stage and histological grade. 38 primary ovarian cancer tumors were analysed cytogenetically. The chromosomes were obtained from primary cell cultures in vitro and were stained using GTW technique. Advanced clinical stage correlated with complex chromosomal rearrangements. Similarly, histologically poorly differentiated tumors more often displayed complex chromosomal rearrangements (p = 0.004). Simple chromosome aberrations or normal karyotype were more frequently detected in well-differentiated tumors. The analysis of the results revealed that the increase in histological grade and clinical stage correlates with the increase in the number and complexity of chromosomal rearrangements.

[The role of cytogenetic studies in prognosis of treatment results in patients with ovarian cancer]. / Rola badan cytogenetycznych w prognozowaniu wyników leczenia chorych na raka jajnika.

UNLABELLED: The aim of this study was to determine the correlation between chromosome aberrations complexity in carcinomatous cells and survival in 38 patients with ovarian cancer. The material of cytogenic studies were 38 specimens taken from primary neoplastic ovarian tumors, which were than crumbled enzymatically. The suspension of neoplastic cells was used to set up primary cell culture in vitro. Only numerical aberrations or one of structural aberrations were assumed to be simple aberrations. More than one of numerical aberrations or structural aberrations were thought to form complex aberrations. The curve of survival in patients were determined using nonparametrical method of Kaplan and Meier and the differences between the curves were compared using logrank test. CONCLUSIONS: 1. The existence of complex chromosome aberrations in ovarian cancer cells is unfavourable prognostic factor. 2. The cytogenic analysis of neoplastic ovarian tumors together with numerous clinical and histological factors is an important prognostic factor.