[Concentration of Hyaluronic Acid in Synovial Fluid as an Indicator of Severity and Degree of Impairment in Patients Suffering from Gonarthrosis]. / Koncentrace kyseliny hyaluronové v synoviální tekutine jako ukazatel závaznosti a stupne postizení u pacientu s gonartrózou.

PURPOSE OF THE STUDY Hyaluronic acid is a major component of synovial fluid and an indicator of joint viscosity and viscoelasticity. Decreased concentrations of hyaluronic acid in the synovial fluid indicate the severity of osteoarthritis. The aim of the study was to determine the concentrations of hyaluronic acid in the synovial fluid and to evaluate the correlation with the severity of osteoarthritis determined based on the radiological criteria (evaluation according to X-ray classification) and the physicochemical criteria (measurement of synovial fluid osmolality). MATERIAL AND METHODS A total of 67 patients with the mean age of 67 years (35 men, mean age = 65 years, and 32 women, mean age = 68 years) with clinically diagnosed osteoarthritis were included in the study. The patients were divided into four groups according to the severity of arthrosis (from Group 1 - the lowest degree of disability to Group 4 - the most severe degree of arthrosis). Samples were taken during knee arthroscopies or total knee replacements. Hyaluronic acid concentrations in synovial fluid were determined using a commercially available kit based on the sandwich ELISA principle (Teco Hyaluronic acid, Switzerland). Osmolality was measured by the cryoscopic method. RESULTS The average concentrations of hyaluronic acid in the synovial fluid in the individual groups were as follows: Group 1: HA = 2302 mg/L, Group 2: HA = 2234 mg/L, Group 3: HA = 2300 mg/L, Group 4: HA = 2446 mg/L. HA concentrations in synovial fluid did not differ from the published reference values in synovial fluid (1500 - 3200 mg/L. HA concentrations do not depend on age, sex, and severity of the disease. The patients who underwent arthroscopy have significantly elevated synovial HA concentration compared to the patients who underwent total knee replacements (2581 mg/l/L vs. 1763 mg/l/L, p = 0.01, Mann-Whitney test). HA positively correlates with the osmotic pressure determined by the examination of osmolality in synovial fluid (r = 0.29, p = 0.015). CONCLUSIONS Hyaluronic acid concentrations in patients with knee osteoarthritis who underwent arthroscopy are significantly increased compared to the group of patients with total knee replacement. Hyaluronic acid concentrations in the synovial fluid correlate with the increased osmotic pressure, and may therefore be an additional indicator of the severity of the disease. Key words: hyaluronic acid, knee arthrosis, total knee replacement, osmolality.

Immunohistochemistry and serum values of S-100B, glial fibrillary acidic protein, and hyperphosphorylated neurofilaments in brain injuries.

INTRODUCTION: Traumatic brain injury (TBI) triggers a series of reactions resulting in cytoskeletal-related changes varying between focal and diffuse injuries. METHODS: The patients (n=38) were divided into group of diffuse axonal injuries (DAI, n=10) and focal (n=28) injuries. Serum hyperphosphorylated neurofilaments (NF-H) and glial fibrillary acidic protein (GFAP) were measured by Biovendor immunoassay, and serum S-100B protein was measured by Cobas e411 (Roche) by immunoassay. Immunohistochemistry was performed with monoclonal antibodies (Chemicon, USA). RESULTS: The median serum S-100B concentration was higher in patients with focal mass lesions (1.72±0.4 µg/l vs. 0.37±0.1 µg/l, p<0,05) compared to patients with DAI during 10 days of hospitalisation. With respect to all patients, the highest peak of serum S-100B values (4.21±1.1 µg/l) and GFAP (8.58±2.4 µg/l) were found in expansive lesions. The median serum NF-H was higher in DAI compared to focal TBI (0.625±0.14 vs 0.139±0.02 ng/l, p<0.05) during all 10 days after admission. Further, immunohistochemical investigation, in deceased patients with DAI , using NF-H antibody proved positive varicose and waving axons, and retraction balls. Time-dependent profile of serum NF-H demonstrated the increase of values within 4th up to 10th day in both groups. Values ranged from 0.263 up to 1.325 ng/l in DAI, and from 0.103 up to 1.108 ng/l in focal injuries. Patients with expansive contusions had similar levels of serum NF-H as patients without expansive lesions. Immunohistochemistry of cytoskeletal proteins presented strong positive staining of vinculin, vimentin in vessels, GFAP, and S-100B in DAI compared to weak staining in expansive lesions. CONCLUSION: The time-profile kinetics of all markers may reflect different types of pathophysiological changes of the BBB or axonal damage in focal and diffuse injuries. KEYWORDS: brain contusions - diffuse axonal injury - S-100B protein - GFAP - hyperphosphorylated neurofilaments.

[Microglial activation and GFAP astroglial immunopositivity in drug abusers]. / Aktivace mikroglie a GFAP imunopozitivita astroglie u toxikomanu

INTRODUCTION: The neurotoxicity brought about by application of toxic and psychotropic substances is accompanied by an activation of astroglial and microglial cells in the brain. MATERIALS AND METHOD: We investigated clinically 42 patients addicted to psychotropic substances (hospitalised in the Motol Teaching Hospital). The NSE, S1OOB, and manganese concentrations in the blood were measured in the patients. In 14 deceased patients with drug evidence in the hair indicating a chronic abuse of addictive substances, the brain tissue glial cells were immunohistochemically labelled with antibody against CD68 and GFAP. RESULTS: In 8 hospitalised patients, there were increased NSE, S100B values in the blood (p < 0.05). Manganese in the blood was increased (3,03±1,9 µg/l, p < 0,05) in all patients. In deceased persons, the CD68 positivity of microglial cells and neurophagy have been proved. GFAP positive astroglial cells have been evidenced in the gray and white matter. CONCLUSION: The CD68 and GFAP positive glial cells in brain tissue can be a pathomorphological correlate of neurotoxicity in chronic abusers. The neurotoxicity can be monitored with NSE and S100B markers of damaged neuronal cells.

Matrix metalloproteinases.

Matrix metalloproteinases (MMPs), also known as matrixins, belong to a group of zinc-dependent proteins, which are thought to play a central role in the breakdown of extracellular matrix. Collagen, elastin, gelatin and casein are major components cleaved by MMPs. The breakdown of these components is essential for many physiological processes such as embryonic development, morphogenesis, reproduction, and tissue resorption and remodelling. MMPs also participate in pathological processes such as arthritis, cancer, cardiovascular and neurological diseases. This review summarizes current knowledge regarding these proteins, their participation in physiological and pathophysiological roles, their involvement in activation and inhibition, and their interactions with other metal-binding proteins including metallothioneins.

Re-evaluation of cord blood arterial and venous reference ranges for pH, pO(2), pCO(2), according to spontaneous or cesarean delivery.

Umbilical cord blood gas analysis (pO(2) and pCO(2)) is now recommended in all high-risk baby deliveries and in some centers it is performed routinely following all deliveries. The aim of this study was to re-evaluate cord blood arterial and venous reference ranges for pH, pO(2), pCO(2) in newborns, delivered by spontaneous vaginal delivery (SVD) and by cesarean section (CS) performed in Faculty Hospital Motol. Two groups of subjects were selected for the study. Group I consisted of 303 newborns with SVD. Group II consisted of 189 newborns delivered by cesarean section. Cord blood samples were analyzed for standard blood gas and pH, using the analytical device Rapid Lab 845 and Rapid Lab 865. We obtained reference values expressed as range (lower and upper reference value expressed as 2.5 and 97.5 percentiles) for cord blood in newborns with SVD: arterial cord blood: pH=7.01-7.39; pCO(2)=4.12-11.45 kPa; pO(2)=1.49-5.06 kPa; venous cord blood: pH=7.06-7.44; pCO(2)=3.33-9.85 kPa; pO(2)=1.80-6.29 kPa. We also obtained reference values for cord blood in newborns delivered by CS: arterial cord blood: pH=7.05-7.39; pCO(2)=5.01-10.60 kPa; pO(2)=1.17-5.94 kPa; venous cord blood: pH=7.10-7.42; pCO(2)=3.88-9.36 kPa; pO(2)=1.98-7.23 kPa. Re-evaluated reference ranges play essential role in monitoring conditions of newborns with spontaneous and caesarean delivery.

Subacute thyroiditis confused with dental problem.

Subacute thyroiditis is an inflammatory disease of the thyroid gland, most probably preceded by viral infection. Common symptoms include fever, thyroid tenderness associated pain, and initial hyperthyroidism sometimes followed by a transient period of hypothyroidism with generally favourable outcomes as self-limited entity. It was known that it may be confused with pharyngitis; however search on Medline using key words (dental pain, subacute thyroiditis, and differential diagnosis) in combination recently produced no reports. Herein, we report a case of subacute thyroiditis associated pain, which was initially mistaken and treated as pain of dental origin after otorhinolaryngologic examination revealed no pathology. The aim of this communication is to remind that thyroiditis as part of differential diagnosis should be considered in patients with unexplained dental pain to avoid unnecessary diagnostic procedures, which increase expenses and may delay appropriate therapeutic measures.

Changes of blood count, lymphocyte subpopulations and immunoglobulin levels in nephroblastoma long term survivors.

The aim of this study was to investigate the frequency of blood count, lymphocyte subpopulations, and immunoglobulin levels alterations in a group of healthy nephroblastoma long-term survivors. The group included 122 nephroblastoma longterm survivors who were at least five years post anticancer therapy and free of any sign of recurrence The proportion of lymphocyte subpopulations was analyzed by flow cytometry using antibodies anti CD45 FITC/CD14 PE, anti CD3 FITC/ CD16+CD56 PE, anti CD4 FITC/ CD8 PE and anti CD20 FITC. Immunoglobulin G, A, and M levels were evaluated by immunoturbidimetry. Total blood count was also examined. The occurrence of decreased immunoglobulin levels, leukocytes, lymphocytes, and granulocytes count, proportion of T lymphocytes and their CD4+ subpopulation are not frequent. The most frequently decreased lymphocyte subpopulation was CD8 (15.5%). The most frequent abnormal findings were increased proportion of NK cells (38.5 %), B lymphocytes (38,52 %), decreased number of erythrocytes (25.2 %), hemoglobin levels (41.7 %) and hematocrit (13.9 %). The only significant differences between results of immunological examination and course of the disease were more frequently decreased proportion of CD4+ lymphocytes in recurrent disease survivors and lower IgA levels in survivors after radiotherapy. We found decreased at least one immunological parameter in one fifth of the survivors. The most frequently altered parameter was hemoglobin, which was decreased in 41.7 % of survivors. Decraesed hemoglobin may worsen quality of survivors life. Key words: nephroblastoma long-term survivors, blood count, lymphocyte subpopulations, immunoglobulin G, A, M serum levels.

Correlation of ultrastructural changes of endothelial cells and astrocytes occurring during blood brain barrier damage after traumatic brain injury with biochemical markers of BBB leakage and inflammatory response.

Focal cerebral contusion can be dynamic and expansive. It has been proved that subsequent expansive contusion is caused by brain parenchyma damage, especially BBB damage. We investigated a group of patients with traumatic brain injury. The patients (n=18) were divided into group I (n=7) of patients submitted to neurosurgery due to expansive contusion, and group II (n=11) of patients without surgery. Serum concentrations of NSE and S-100B protein were measured by electrochemiluminescence immunoassay, interleukin-6 (IL-6) was measured by chemiluminescent sequential immunometric assay and matrix metalloproteinases (MMP-9, MMP-2) were measured by immunoassays. Cortical biopsy specimens of brain were investigated by electron microscopy in patients with trauma brain injury submitted to neurosurgery. Biochemical investigation from first day up to third day after traumatic brain injury proved increased values of IL-6 (302.2+/-119.9 vs. 59.6+/-11.9 ng/l, p<0.02) and S-100B protein (3.064+/-1.064 vs. 0.649+/-0.182 microg/l, p<0.05) in patients with expansive lesion compared to patients without expansive contusion. Significantly higher levels of MMP-9 (150.4+/-28.46 vs. 74.11+/-13.16 ng/l, p<0.05) and of MMP-2 (814.5+/-126.3 vs. 523.1+/-25.28 ng/l, p<0.05) were found during first 3 days after admission in group I compared to group II. MMP-9 has also elevated in group II from lower values after admission (74.11+/-13.16 ng/l) up to high levels on the 10th day of hospitalization (225.1+/-49.35 ng/l). Ultrastructural investigation of endothelial cells and surrounded tissue revealed perivascular hemorrhage, increased pinocytic activity of endothelial cells, and cytotoxic edema of astroglial cells. Multivesical bodies were disclosed inside the endothelial cells. Higher levels of serum protein S-100B and IL-6 correlated with ultrastructural changes of endothelial cells, and with inflammatory response following TBI, respectively.

[Formation of the urinary stones in alkaptonuria patients]. / Alkaptonurie a tvorba mocových konkrementu.

Alkaptonuria is an autosomal recessive disease with late complications (arthritis and ochronosis). Excretion of alkapton (homogentisic acid) in the urine is due to congenital lack of the enzyme homogentisate 1,2-dioxygenase, which mediates the essential step in the catabolism of phenylalanine and tyrosine. Urine excretion of homogentisic acid is very high, urine turns dark if allowed to stand or is alkalinized (a result of formation of polymerization products of alkapton). The presence of alkapton in urine has high lithogenic effect. We report 71 years old man suffering from alkaptonuria with present severe late complications. In this man black coloured urinary calculus was extracted from the urethra. This calculus was formed of organic amorphous part and crystallized part analyzed by X-ray diffraction and infrared spectroscopy identifying weddelite and whitlockite (1:1), and trace amounts of carbonate apatite.

[Hypokalaemia in a suicide attempt of an adolescent girl]. / Hypokalémie u suicidálního pokusu dospívající dívky.

In acute theophylline poisoning hypokalaemia, hyperglycaemia, and other electrolyte disturbances may occur. These abnormalities have been attributed to catecholamine excess with intracellular movement of potassium and catecholamine-stimulated gluconeogenesis. Herein we describe a female teenager, who developed metabolic disturbances with significant toxic response to oral theophylline overdose in a suicide attempt. Severe hypokalaemia (1.8 mmol/L) was among the leading pathological findings, at peak theophylline concentration (68 mg/L). There was high plasma glucose (10.2 mmol/L). Creatinine-kinase was evidently abnormal (8.60 microkat/L) several hours post poisoning, while serum myoglobin was markedly elevated (74.8 microg/L) despite the decrease in the drug level. Ventricular arrhythmia with marked extra systoles has been confirmed on electrocardiograph. Finally, the patient recovered through intensive care management with theophylline level (21.1 mg/L) falling close to reference range after 48 hours, but relative hypokalaemia persisted despite potassium supplementations even after the drug level fall below detection limit. In conclusion, timely gastrointestinal decontamination, determination of serum drug levels in intervals, electrocardiography evaluation followed by treatment of arrhythmias, supportive care including balancing of metabolic disturbances, follow-up assessment of serum electrolytes, in particular potassium and creatinine-kinase parallel with myoglobin level assessment even after significant decrease in theophylline level are very important measures.

[Is the assessment of serum creatinine reliable?]. / Je stanovení sérového kreatininu vzdy v rohodné? Uskalí preanalytické fáze.

Chemical and enzymatic methods are used to measure creatinine in serum and urine. Chemical methods are mostly based on the reaction of creatinine with alkaline picrate (Jaffe reaction). The Jaffe reaction is not specific for creatinine, the same reaction resulting in Jaffe-like chromogens show many interfering substances (ascorbic acid, bilirubin, proteins, ketones, cephalosporins and other drugs). Chemical and enzymatic methods show similar accuracy and day-to-day precision. Chemical methods are cheaper than enzymatic methods. Enzymatic methods require low sample volume and are not affected by the interfering substances as the chemical methods. Presented case report shows an unusual occurrence of drug interference in the enzymatic creatine deaminase procedure. Biological factors (circadian rhythm, pregnancy, hemodialysis, transplantation, stress, exercise), analytical and preanalytical factors (pH, glucose, pyruvate, bilirubin, fatty acids, sample storage and sample collection - gel tubes) and biological variability of creatinine play significant role in the creatinine examination.

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin.

BACKGROUND AND OBJECTIVE: Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient's glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N-acetyl-beta-d glucosaminidase (NAG), creatinine level and creatinine clearance]. METHODS: We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft-Gault formula) and CyC (Grubb's formula). Seventy-one patients (mean age 12 years; range 4-28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U-NAG/U-creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. RESULTS: Significant differences in the rate of U-NAG/U-creatinine were noted before and after treatment with amikacin (P < 0.001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0.001), and CyC clearance showed a significant decrease (P < 0.001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. CONCLUSION: We showed that the rate of U-NAG/U-creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.

[Evaluation of relevance in concussion and damage of health by monitoring of neuron specific enolase and S-100b protein]. / Hodnocení závaznosti otresu mozku a poruchy zdraví pomocí monitorování hladin neuron specifické enolázy a proteinu S-100b v séru.

INTRODUCTION: Proteins released to the circulation from affected glial (neuron specific enolasis, NSE) or ganglial cells (S-100b protein) during traumatic brain injury might be used in diagnosis of traumatic brain injury in cases with negative finding on computer tomography scan (concussion) or in patients where the serious clinical status does not corresponde with mild changes on CT scan (diffuse axonal injury, DAI). Classification of DAI according Gennarelli considered the concussion as lower degree of DAI. MATERIALS AND METHOD: 15 patients were divided into group I of mild conccussion (n=3) with 1-day duration of hospitalisation, group II of serious concussion (n=4) with more days duration of hospitalisation with negative findings on CT scan and group III of patients with diagnosis of DAI (n=8). Blood samples were investigated by immunoanalysis for NSE and protein S-100b (Elecsys 2010, Roche). RESULTS: Values of NSE (16.30 +/- 2.33 vs. 110.48 +/- 34.99 vs. 24.07 +/- 6.29 microg/l), and protein S-100b (0.207 +/- 0.03 vs. 0.945 +/- 0.69 vs. 0.736 +/- 0.36 microg/l) overdrow the reference value in cases of group I, II, and III. We discuss the biomechanics of trauma and the blood brain barrier damage in comparison with values of NSE and S-100b protein. CONCLUSION: [corrected] We proved the significantly higher values of the NSE in group of serious concussion compared to group of DAI. We demonstrated that concussions in some cases lead to serious damage of health.

Endodermal sinus tumor diagnosed in pregnancy: a case report.

Pure endodermal sinus tumor (EST) of the ovary is an uncommon germ cell tumor characterized by rapid growth. Its occurrence during pregnancy is extremely rare. The case of a 34-year-old woman with EST stage IC diagnosed in the 22nd week of gestation is presented. She received four cycles of cisplatin monotherapy during pregnancy. Further, three cycles of combination chemotherapy (cisplatin, bleomycin, and etoposide) were administered. Twenty-eight months posttreatment the patient was in complete remission with good health. A healthy female infant was delivered by cesarean section in the 35th week of pregnancy. The child showed normal laboratory, pediatric, and neurologic examination at the time of discharge from hospital and during the first and second years of her life. We conclude that the prognosis of EST is very good if patient receives adjuvant therapy. Cisplatin monotherapy seems to be effective and safe during pregnancy.

Dynamic changes of orexin A and leptin in obese children during body weight reduction.

In this study, we describe changes of plasma levels of the hypothalamic neuropeptide orexin A in obese children during the reduction of body weight and its relationship to other biochemical and anthropometrical parameters. We measured orexin A fasting plasma levels by the RIA method in 58 obese children--33 girls and 25 boys; mean age 13.1+/-0.38 years (range 7-18.5) before and after 5 weeks of weight-reduction therapy. Leptin, IGF-1, and IGFBP-3 levels were measured in all the subjects and were compared to orexin A levels and anthropometrical data. Average weight in subjects before weight-reduction was 74.2+/-2.79 kg and after weight-loss 67.4+/-2.60 kg (p<0.0001). Orexin A levels before the therapy were 33.3+/-1.97 pg/ml and after the therapy 51.7+/-3.07 pg/ml (p<0.0001). Levels of orexin A were not significantly different between girls and boys (p=0.7842). We found negative correlation between orexin A and age (r = -0.5395; p<0.0001), body height (r = -0.4751; p=0.0002), body weight (r = -0.4030; p=0.0017) and BMI (r = -0.2607; p=0.0481). No correlation was found between orexin A and IGF-1, IGFBP-3 or leptin. Orexin A plasma levels increased during body weight loss, whereas the reverse was true for leptin levels. These findings support the hypothesis that orexin A may be involved in regulation of nutritional status in children.

[Biochemical and immunohistochemical markers of brain injury]. / Biochemické a imunohistochemické markery poskození mozku.

Proteins released to circulation from affected tissues during primary or secondary trauma brain injury might be used as serum markers of glial or ganglial cells damage (neuron specific enolasis and S100 B protein). Other markers of trauma can be proved as relatively specific of diffuse axonal injury by immunohistochemical detectoin (amyloid prekurzor protein, neuron specific enolasis, glial fibrilar acidic protein and superficial antigen receptor CD 68). Some markers are associated with blood brain barrier damage (matrix metaloproteinases (MMP-2, MMP-9) and synthase of nitric oxide (iNOS)). We aimed in our short communication on biomechanics of developed of trauma, primary or secondary kinds of trauma brain injury and use of trauma brain injury markers for clinical diagnostics and management of patients.

Lymphocyte subpopulations and immunoglobulin levels in Hodgkin's disease survivors.

We investigated the frequency of lymphocyte populations (CD3+ /T lymphocytes/, CD4+ /helpers/, CD8+ /suppressor and cytotoxic/, CD3- CD16+ /NK cells/, CD3+ HLA-DR+ /activated T lymphocytes/, and CD20+ /B lymphocytes/) and immunoglobulin G, A, M, and E levels in a group of two hundred twenty nine Hodgkins disease long term survivors. The most frequent pathological findings were increased IgE levels, decreased CD3+ and CD4+ proportions, an increased CD20+ proportion and especially a low CD4/CD8 proportion. Decreased CD3+ and CD4+ and increased CD20+ proportions were more frequently found in the group with recurrent infections. IgM and IgA levels were positively correlated with plasmatic cholesterol and triacylglycerols levels. We suppose that immunological defects (increase of IgE levels, decreased T and helper lymphocytes) in Hodgkins disease survivors are inherent and are not related to atopy. Examination of lymphocyte subpopulations may be helpful in the prediction of an increased risk of recurrent infections.

[Evaluation of three dosage regimens of amikacin using pharmacokinetic models in patients with cystic fibrosis]. / Vyhodnocení trí dávkových rezimu amikacinu farmakokinetickým modelováním u pacientu s cystickou fibrózou.

BACKGROUND: Once-daily administration of aminoglykosides is routinely used, but comparative efficacy data for patients with cystic fibrosis are not available. METHODS AND RESULTS: The aim of the this study was to compare the predicted pharmacodynamic (PD) activity of amikacin at 28 mg/kg/den administered every 24 hod.(q24h), q12h, and q8h. Pharmacokinetic (PK) data were derived from analysis of the amikacin serum concentration from 42 CF children patients. Individual pharmacokinetics values were used to construct serum concentration--versus time curves and to determine various indices (c peak/MIC ratio and time during the concentration was less than the MIC--T < MIC) for all three dose regimens described above. MIC (minimal inhibitory concentration) for Pseudomonas aeruginosa was 4 mg/l. Significantly lower c peak/MIC but shorter T < MIC were noted when regimens of q8h versus q12h (p < 0.001), q8h vs. q24h (p < 0.001) and q12h vs. q24h (p < 0.001) were compared. This analysis suggests that the potential advantage of achieving a greater c peak/MIC with once-daily aminoglycoside administration may be neutralized by the significantly greater T < MIC in CF patients compared with that achieved with multiple-daily-dosing regimens. CONCLUSIONS: Routine use of once daily amikacin administration could not be recommended until the clinical data confirming efficiency of this dose modality are available.

Amylin fasting plasma levels are decreased in patients with osteoporosis.

Amylin is a polypeptide hormone produced in pancreatic beta-cells that belongs to the family of calcitonin gene-related peptides. There is a 20% sequence homology between amylin and calcitonin and 44% homology with calcitonin gene-related peptide. Amylin and its fragments stimulate the proliferation of osteoblasts, inhibit bone resorption, and increase bone density and the amount of bone mass. We measured amylin total and unreduced amylin fasting plasma levels in patients with osteoporosis ( n=28; 3 men, 25 women; mean age 65 years), type 2 diabetes mellitus ( n=10; 5 men, 5 women; 64 years), and in the control group ( n=24; 11 men, 13 women; 53 years) using an ELISA kit with immunofluorescent detection (Linco). Amylin total plasma levels in patients with osteoporosis were 3.33+/-0.46 pmol/l (mean+/-SEM), in patients with type 2 diabetes 6.29+/-1.47 pmol/l (mean+/-SEM), and in the control group 8.48+/-3.12 pmol/l (mean+/-SEM). Mean plasma levels were lower in patients with osteoporosis than in patients with type 2 diabetes and in the control group. Unreduced amylin plasma levels in patients with osteoporosis ( n=28) were 2.51+/-0.87 pmol/l (mean+/-SEM), in patients with type 2 diabetes ( n=10) 4.15+/-0.95 pmol/l (mean+/-SEM) and in the control group ( n=5) 13.50+/-3.94 pmol/l (mean+/-SEM). Plasma levels were significantly lower in patients with osteoporosis than in patients with type 2 diabetes ( P<0.01) and in the control group ( P<0.001). Amylin plasma levels are decreased in patients with osteoporosis. Amylin deficiency in these patients may contribute to the development of osteoporosis. Amylin should be investigated in relation to the pharmacological treatment of osteoporosis.

[Activated factor XII in patients with hyperglycaemia and dyslipidaemia]. / Aktivovaný koagulacní faktor XII u pacientu s hyperglykémií a dyslipoproteinémií.

BACKGROUND: Increased plasma levels of activated factor FXII (FXIIa) are associated with increased risk of atherosclerosis and coronary heart disease. There are increased levels of FXIIa in patients with dyslipidaemia and also elevated levels of FXIIa have been reported in patients with diabetes mellitus. No studies were reported whether FXIIa correlates rather with plasma glucose levels or with other metabolic markers like hypertriacylglycerolemia. METHODS: We measured plasma FXIIa levels, triacylglycerols, uric acid and glucose in a group of 158 hyperglycaemic patients with P-glucose more than 8 mmol/l and variable serum lipid parameters [cholesterol, triacylglycerols, HDL-cholesterol, LDL-cholesterol, lipoprotein (a), apolipoprotein AI, apolipoprotein B] in a group of 55 patients of lipid clinic on hypolipidaemic treatment (statins, fibrates). RESULTS AND CONCLUSION: The comparison of FXIIa with the age in the group of hyperglycaemic patients has shown that the number of patients with FXIIa more than 2.5 microg/l is growing with increasing age. Low concentration of FXIIa was observed in the youngest age group (10-30 years), where all values are within the reference ranges. We proved positive correlation between plasma FXIIa levels and age, triacylglycerols, uric acid. No correlation was found between plasma FXIIa and glucose in both groups.