Unusual foreign body in the nasal cavity after craniofacial injury.

A 68-year-old man with severe craniofacial trauma underwent endoscopic surgery for nasal cerebrospinal fluid leak. During the operation, a plastic object in the shape of a spectacle lens was found wedged in the left nasal passage, which we extracted. As subsequently established from the patient's documentation, it was a dislodged acrylic implant originally placed at the base of the orbit which was surgically treated after an injury to the facial skeleton thirty-five years ago. What is also rare about this is the fact that the patient had been examined for many years at the otorhinology department for purulent discharge from the left nasal cavity and impaired ventilation. The patient had also undergone an endoscopic examination of the nasal cavity during which an intranasal tumor was even suspected, but it was not histologically confirmed.

Sinonasal quality of life in patients after an endoscopic endonasal surgery of a sellar tumour.

Endoscopic endonasal approach uses the nasal cavity and paranasal sinuses to access the cranial base and may be a source of post-surgical morbidity in many patients with a sellar tumour. The objective of the presented study was to evaluate sinonasal quality of life and assess the effect of chosen reconstruction of the cranial base on the final condition. 65 patients, 33 male and 32 female who underwent an endoscopic endonasal surgery due to sellar expansion, were included into this prospective study. Sinonasal quality of life was evaluated using the Sinonasal Outcome Test-22 (SNOT-22) questionnaire before the surgery and six months after the surgery. Sinonasal quality of life was evaluated for the total cohort of patients and for patients after reconstruction (fascia lata, muscle) and without reconstruction. The minimum follow-up period was one year. There was no significant difference between the score (SNOT-22) before the surgery (average 14.4 points) and after the surgery (average 17.5 points), p = 0.067 in the whole cohort. Statistically significant differences were found in the following items-the need to blow nose, nasal congestion, loss of smell and taste, and thick discharge from the nose. The comparison of subgroups with and without the reconstruction yielded statistically significant differences in favour of patients with reconstruction in the following items-lack of high-quality sleep and feeling exhaustion. The endoscopic endonasal approach in patients with a sellar tumour is a gentle method with minimal effects on sinonasal quality of life over a period longer than six months. The most common complaints are the need to blow nose, nasal congestion, loss of smell and taste, and thick discharge from the nose. Cranial base reconstruction using the muscle and fascia lata seems to be a potential factor positively influencing sinonasal quality of life.

[Metastatic Pituitary Disorders]. / Metastatické postizení hypofýzy.

BACKGROUND: Pituitary metastases are a rare complication of generalized cancer. Metastases to the pituitary gland occur in only 1% of patients operated on for sellar tumor. The most common presenting symptom in patients with pituitary metastases is diabetes insipidus, whereas this is rare in those with pituitary adenoma. MATERIAL AND METHODS: This publication presents the cases of two patients with pituitary metastases and a systematic review of the literature. English-language publications related to pituitary metastases and published from 1957 to 2016 were identified using the PubMed database. RESULTS: A total of 131 publications containing information about 259 patients (121 female and 138 male; mean age, 57.3 years) were identified. The most often metastasized breast carcinoma (24.6%) and lung carcinoma (23.8%), followed by thyroid carcinoma (11.3%), renal cell carcinoma (7.8%), hepatocellular carcinoma (4.3%), colorectal carcinoma (3.5%), and malignant melanoma (3.5%). The most frequent initial symptoms were manifestations of diabetes insipidus (39.6%), anterior pituitary deficiency (44.9%), perimeter disorders (51.6%), headache (37.6%), cranial nerve palsy (33.5%), and pseudoprolactinemia (16.7%). Radiotherapy (67.8%) and surgical treatment (63.9%) were the most frequently used treatment. CONCLUSION: The average survival time from the onset of metastatic disease was 11.8 months. Surgical therapy alone or in combination with radiation therapy does not prolong survival, but alleviates symptoms and improves quality of life.Key words: pituitary metastasis - diabetes insipidus - hypopituitarism - transsphenoidal surgery The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 13. 1. 2017Accepted: 4. 4. 2017.

Methotrexate efficacy, but not its intolerance, is associated with the dose and route of administration.

BACKGROUND: There is a lack of published evidence on the importance of methotrexate (MTX) dose and route of administration on both its efficacy and adverse events in children with Juvenile Idiopathic Arthritis (JIA). We aimed to document our clinical practice based on the treat-to-target approach in order to support the concept that better therapeutic effect achieved with an optimal dose of parenteral MTX is associated with clinically acceptable adverse effects comparable to those reported for oral treatment. METHODS: Study inclusion criteria were indication of new MTX therapy for active arthritis in confirmed JIA patients younger than 18 years. Eligible patients were evaluated prospectively every 3 months for 1 year using standardized instruments for treatment response (American College of Rheumatology Pediatric (ACRPedi) response, Juvenile Arthritis Disease Activity Score (JADAS) 71, Clinically Inactive Disease (CID)) and adverse events (laboratory monitoring, Methotrexate Intolerance Severity Score (MISS)). MTX responders had to achieve at least ACRPedi 70 response. MTX intolerance was defined by MISS ≥ 6. RESULTS: In 45/55 patients (81.8 %) MTX was started as subcutaneous injection. The initial median weekly dose was 14.4 mg/m(2) in parenteral and 11.7 mg/m(2) in oral administration. MTX therapy was effective in the level of ACRpedi70 and CID in 50.9 % and 30.9 % of patients at month 6 and in 70.9 % and 56.4 % after 12 months of the treatment, respectively. MTX intolerance at 6 and 12 months was noted in 25.5 % and 30.6 %, respectively. Management of intolerance included change in the dose and/or route of administration, education and councelling. Adverse events led to MTX withdrawal in 5 patients (9 %) due to toxicity (n = 3) and intolerance (n = 2). We did not find any significant predictive factors for either MTX therapeutic response or intolerance. CONCLUSION: Subcutaneous MTX weekly dose around 15 mg/m(2) is associated not only with a high response rate within the first 12 months of treatment, but also with a relatively low rate of significant adverse effects that would lead to the treatment termination. It allows early recognition of MTX non-responders and addition of biologic therapy. Sustainability of therapeutic effect and longer-term evolution of adverse events will be addressed by an ongoing extension of the study.

Neither expression of VEGF-C/D nor lymph vessel density supports lymphatic invasion as the mechanism responsible for local spread of recurrent salivary pleomorphic adenoma.

Recent research suggests that multinodular recurrent pleomorphic adenoma (PA) might result from cell migration through lymphatics. Lymphangiogenesis in malignancies is mediated by vascular endothelial growth factors C and D (VEGF-C/D). We studied the expression of VEGF-C/D in PA by immunohistochemistry as well as lymphatic vessel density (LVD). In 6 non-recurrent, 4 primary-to-recur, and 10 recurrent PAs, VEGF-C/D expression was assessed by immunohistochemistry. Staining was scored in terms of staining intensity (0 = absent to 3 = strong), and the percentage of positive tumor cells (scored as 0 (0-19 %), 1 (20-39 %), 2 (40-50 %), and 3 (60-100 %)) and a sum score were calculated. Intra- and peritumoral LVD was assessed by counting of LV after immunostaining, using the D2-40 antibody. All but one sample were VEGF-C negative. The differences in VEGF-D expression between non-recurrent, primary-to-recur, and recurrent PAs were not significant (p>0.05). VEGF-D expression did not correlate with peritumoral LVD (p>0.05). Our study revealed a significant difference between intra- and peritumoral LVD values when comparing individual and all sample groups (p=0.01). The lack of VEGF-C expression and of significant differences in VEGF-D expression and peritumoral LVD between patients with non-recurrent, primary-to-recur, and recurrent PAs does not support the lymphangiogenic local spread hypothesis

Efficacy and safety of erdosteine in the treatment of chronic rhinosinusitis with nasal polyposis - a pilot study.

BACKGROUND: Erdosteine was originally developed as a mucolytic agent. It is a multimechanism substance with anti-bacterial, anti-oxidant, and most importantly anti-inflammatory effects. Given similar mechanisms of action (suppression of cytokines, including tumor necrosis factor α), it could become a reasonable alternative to currently used treatments with macrolides or steroids. OBJECTIVE: To assess efficacy and safety of erdosteine in the treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP). METHODOLOGY: A prospective non-interventional post-authorisation study comparing patients treated with erdosteine only or the combination of erdosteine and nasal corticosteroid spray for CRSwNP. The end-points were pre- and post-treatment changes in endoscopic score and subjective evaluation of CRSwNP related symptoms using a 22-item Sinonasal Outcome Test questionnaire. Patients underwent nasal endoscopy and filled the questionnaire before and after the treatment. RESULTS: No patient experienced any adverse effect during the study. A comparison of pre- and post-treatment endoscopic findings and questionnaire values revealed significant reduction in both patient groups, with a significantly better response in the erdosteine only group. CONCLUSION: Based on this pilot study, erdosteine seems effective in the treatment of CRSwNP and might become a reasonable alternative to currently used medication. The therapeutical role of erdosteine needs to be further assessed.

Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis.

OBJECTIVE: In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy. METHODS: Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients. RESULTS: Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (s.d. 10.1) vs 49.6 nmol/l (s.d. 12.5) in untreated controls (P=0.55). Mean EMTX was 215.56 nmol/l (s.d. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P=0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P=0.9). CONCLUSIONS: We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.

[Laboratory indicators of endothelial involvement in rheumatic diseases associated with vasculitis in children]. / Laboratorní ukazatele postizení endotelu u revmatických onemocnení provázených vaskulitidou u detí.

BACKGROUND: Endothelial activation is an important etiopathogenetic factor in a group of disorders characterised by primary or secondary vasculitis. The aim of our study was to determine blood concentrations of von Willebrand factor (vWF), vypusteno soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in children with various rheumatic diseases and in paediatric controls and to correlate them with clinical and laboratory variables. METHODS AND RESULTS: Total of 28 healthy children (ZD) and 48 patients were evaluated: 6 with systemic lupus erythematosus (SLE), 7 with other diffuse connective tissue diseases (SSD), 11 with Henoch-Schönlein purpura (HSP), 14 with oligoarticular juvenile idiopathic arthritis (JIA) and 10 febrile controls (FC). Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count were recorded. ICAM-1, E-sel and vWF concentrations were measured by sandwich ELISA kits. In SLE patients' concentrations of vWF and ICAM-1 were significantly higher than in healthy (p < 0.05), but not febrile controls. ICAM-1 was significantly increased also in SSD group when compared to healthy children (p < 0.01). Differences in other groups did not reach statistical significance. Significant negative correlation with age was observed for the group as a whole, E-sel correlated with leukocyte and thrombocyte counts (p < 0.01), both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSIONS: Combined measurement of vWF, ICAM-1 and E-sel as possible markers of endothelial activation in such vypusteno wide spectrum of paediatric patients and controls is unique vypusteno. Our finding of increased concentrations of vWF and/or ICAM-1 in children with systemic autoimmune diseases underlines the importance of endothelial involvement in these disorders, but their predictive value in the disease monitoring needs to be further studied.

[Sodium nitrite poisoning in a neonate]. / Otrava novorozence dusitanem sodným.

Natrium nitrosum intoxication is usually associated with a subsequent methemoglobinemia. Beside it, nitrates can cause also some other pathological states. Treatment with the toluidine blue may have various adverse side effects. Newborn intoxication by natrium nitrosum developing after the intoxication of the bearing mother before the parturition has not been described yet. Our own observation is referred.

[Metformin has a positive effect on disorders of carbohydrate metabolism in long-term care with low doses of prednisone]. / Metformin príznive ovlivnuje poruchy glycidového metabolizmu pri dlouhodobé lécbe nízkými dávkami prednisonu.

BACKGROUND: The influence of long-term, low doses of prednison administration (< 0.3 mg/kg/day) on glucoregulation and glucose tolerance was studied in 20 female patients (15-20 yrs), including verification of possibility to correct the impairment of glucose tolerance (IGT) by metformin (M). METHODS AND RESULTS: During prednison treatment, we found typical signs of insulin resistance manifestation: HOMAIR 3.55 (5.13), blood insulin/glucose ratio 3.8 (5.84), QUICKI 0.61 (0.124). These were associated with higher Langerhans (L.) islets hormone secretion detected under basal conditions as well as after bolus of 5 g arginine chloride. However, detailed analysis of hormone secretion ratios revealed distinct signs of L. islets function impairment and subcompensation. Specifically, low ratio C peptide/proinsulin and C peptide/glucagon were characteristicaly observed. Six months of M. administration (1000 mg/day) had a beneficial effect on glucose metabolisms deviations as indicated by the following: insulin resistance decreased (HOMAIR 1.96 (1.60), insulin/glucose ratio 2.34 (1.52), QUICKI increased at 0.699 (0.238)). At the same time we found a decrease in the basal levels of insulin, proinsulin, glucagon, C peptide and amyline, and AUC proinsulin and glucagon as well. HOMAsecretion decreased from an initial value of 389 (376) to 207 (119). CONCLUSIONS: Judging by the new hormonal secretion ratios, the L. islets' function following M. treatment substantially improved. From the clinical point of view, it is important to note that M. was tolerated very well. No patient interrupted the follow up because of M. intolerance. IGT in the whole group normalised, in spite of the fact that no accent was put on the regime, diet including. The 90% of lactate values did not exceed 1.7 mmol/l. Based on the results, we may conclude that M. has a beneficial effect on long-term, low doses of glucocorticoid-related (induced) glucose metabolism impairment, and therefore, M. administration could be recommended, particularly in the situations with higher levels of glycosylated hemoglobin.

Soluble adhesion molecules ICAM-1 and E-selectin in juvenile arthritis: clinical and laboratory correlations.

OBJECTIVE: To determine serum and synovial fluid (SF) concentrations of soluble intercellular adhesion molecule-1 (ICAM-1) and E-selectin (E-sel) in patients with active juvenile idiopathic arthritis (JIA) and in paediatric controls and correlate them with clinical and laboratory variables. METHODS: Total of'30 JIA patients were evaluated: 15 with polyarticular disease course (JIA-poly) and 15 with oligoarthritis (JIA-oligo). Paediatric age-matched control groups consisted of 11 Henoch-Schönlein purpura (HSP) and 10 febrile patients (FC) and 28 healthy children (HC). Current medication, the erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and full blood count (FBC) were recorded. Soluble ICAM-1 and E-sel in serum and SF were measured by a sandwich ELISA kit. RESULTS: In the JIA-poly group the concentration of ICAM-1 was significantly higher than in healthy (p < 0.01), but notfebrile controls. Both ICAM-1 and E-selectin correlated with the active joint count (p < 0.01). In 13 JIA patients no correlanon was found between SF ICAM-1 and E-sel levels and the SF leucocyte counts. No significant differences were seen in the disease control and JIA-oligo groups compared to HC. A significant negative correlation with age was observed for the group as a whole (ICAM-1: p < 0.05, E-sel: p < 0.01); E-sel correlated with the leucocyte and thrombocyte counts (p < 0.01), and both molecules with CRP (p < 0.05) and with each other (p < 0.01). CONCLUSION: A high concentration of soluble ICAM-1 in JIA patients with polyarthritis is reported here for the first time. None of the patients showed signs of injection or vasculitis, where generalised endothelial activation could be its main source. Our finding of correlations between both ICAM-1 and E-sel levels and joint counts supports the hypothesis of their synovial origin. ICAM- I and E-sel could serve as a marker of aggressive disease, but their predictive value needs to be further studied.

[Role of the steroids, SHBG, IGF-1, IGF BP-3 and growth hormone in glucose metabolism disorders during long-term treatment with low doses of glucocorticoids]. / Vztah nekterých steroidu, SHBG, IGF-1, IGF BP-3 a rustového hormonu k poruchám glycidového metabolizmu pri dlouhodobé lécbe nízkými dávkami glukokortikoidu.

BACKGROUND: The relationships between selected steroids, SHBG, growth hormone, IGF-1, IGF BP-3 and indicators of glucose metabolism were studied in the group of 20 female patients (15-20 yrs) on long-term treatment with low prednisone doses (< 0.3 mg/kg/day) (baseline phase) and after adding 1000 mg of metformin per day for following 6 months to improve impaired glucose metabolism (control phase). METHODS AND RESULTS: Lower basal DHEAS and DHEA (DHEA/S) levels were found as compared with reference values. Only DHEAS level returned into the reference range after the treatment with metformin. Decrease of DHEA/S depended on the doses (DHEAS -0.7621, DHEA -0.7685). Positive correlations between DHEA/S and of the results insulin tolerance were found as at the baseline (+0.4452, resp. +0.4455) as well as in the control period after the metformin administration (+0.7549, resp. +0.6073). Testosterone (T) and dihydrotestosterone(DHT) values were within the reference range during the whole study. Due to very low SHBG levels higher free androgen index (FAI) was recorded in more than half of the patients. Significant relationships were revealed between former gonadal androgens and indicators of glucose metabolism deterioration at the control phase: T correlated: with fasting insulin (+0.6005), with HOMAIR (+0.5380), with insulin/glucose (+0.5261), with fasting glucose (+0.9268), with AUC glucose (+0.6792), FAI: with fasting insulin (+0.5560), with HOMAIR (+0.5269), with fasting glucose (+0.9025), with AUC glucose (+0.7143), DHT: with fasting C peptide (+0.7921), with AUC C peptide (+0.7143). SHBG correlated: with fasting glucose (-0.6519), and with AUC glucose (-0.5868). The tendency of GH to lower, and IGF-1, IGF BP-3 to higher values at the baseline changed at the control phase: fasting and AUC value of GH increased (signif.), while were IGF-1 (nonsignif.) and IGF BP-3 (signif.) levels decreased. Surprisingly, no correlation was observed between GH and parameters of glucose metabolism. Contrary to GH, baseline IGFBP-3 values correlated: with HOMAIR (+0.5002), with insulin/glucose (+0.4860). The same relationships were found between AUC IGF BP-3 (+0.5676, +0.5559), IGF-1 (HOMAIR only +0.5412), IGF-1/IGF BP-3 (+0.5059, +0.5716) and parameters of insulin sensitivity (HOMAIR, insulin/glucose) in the control period. For the first time negative correlations between IGF-1, IGF-1 AUC, IGF BP-3, IGF-1/IGF BP-3 and somatostatin blood levels were discovered at the control phase. CONCLUSIONS: The study brought a number of new information about the importance of the "non-classical" glucoregulatory hormones in impairment of glucose metabolism, during long-term administration of low prednisone doses. The results suggest, that without normalisation of low DHEA/S, SHBG and high FAI levels it would not be possible to correct glucose metabolism properly in patients with long-term glucocorticoid therapy.

The Czech version of the Childhood Health Assessment Questionnaire (CHAQ) and the Child Health Questionnaire (CHQ).

We report herein the results of the cross-cultural adaptation and validation into the Czech language of the parent's version of two health related quality of life instruments. The Childhood Health Assessment Questionnaire (CHAQ) is a disease specific health instrument that measures functional ability in daily living activities in children with juvenile idiopathic arthritis (JIA). The Child Health Questionnaire (CHQ) is a generic health instrument designed to capture the physical and psychosocial well-being of children independently from the underlying disease. The Czech CHAQ-CHQ were fully validated with 3 forward and 3 backward translations. A total of 150 subjects were enrolled: 81 patients with JIA (14% systemic onset, 44% polyarticular onset, 10% extended oligoarticular subtype, and 32% persistent oligoarticular subtype) and 69 healthy children. The CHAQ clinically discriminated between healthy subjects and JIA patients, with the systemic, polyarticular and extended oligoarticular subtypes having a higher degree of disability, pain, and a lower overall well-being when compared to their healthy peers. Also the CHQ clinically discriminated between healthy subjects and JIA patients, with the systemic onset, polyarticular onset and extended oligoarticular subtypes having a lower physical and psychosocial well-being when compared to their healthy peers. In conclusion the Czech version of the CHAQ-CHQ is a reliable, and valid tool for the functional, physical and psychosocial assessment of children with JIA.

Immunological investigation in children with juvenile chronic arthritis.

BACKGROUND: Immunological investigation is a part of the complex view on a child with juvenile chronic arthritis (JCA). We analyzed the data of a cohort of children with JCA in order to determine the real contribution of this investigation to their diagnosis and therapy. MATERIAL AND METHODS: We included the investigation of humoral immunity and autoantibodies of 78 children with JCA. 18 children completed investigation of both humoral and cellular immunity of paired peripheral blood (PB) and synovial fluid (SF). Humoral immunity consisted from immunoglobulins, complement, circulating immune complexes, rheumatoid factors, soluble HLA I. molecules and antinuclear and antineutrophil cytoplasmic antibodies. Cellular immunity included cytometric studies of CD3, CD4, CD8, CD16/CD56, CD19, CD20, 23, CD3 HLA DR+, CD45 RA, CD45 RO, alpha/beta and gamma/delta T cells. To observe the status of Th1/Th2 balance in children with JCA, the cytokines IL-4, IFN gamma, TNF alpha and IL-6 were measured in the tissue culture of the synovial cells. RESULTS: The parameters of humoral immunity in serum showed wide variability. We could not confirm particular changes specific for the forms or stage of the disease. ANCA were positive in 21 out of 78 children with JCA, 3 times both in PB and SF. More typical pattern could be followed in the comparison of PB and SF, with immunoglobulins and complement always found lower in SF than in PB. The cellular immunity was represented by the activation of lymphocytes mainly in SF, reverse ratio of CD45 RA and RO cells in PB and SF with marked predominance of memory T cells in the joint. High levels of sHLA in SF are the nonspecific marker of activation, the same is true for high levels of TNF alpha and IL 6 in SF cell culture supernatant. CONCLUSION: The described changes in immunological parameters of humoral and cellular immunity are not specific for JCA. In the individual cases they can contribute to the diagnosis and monitoring of the disease. The investigation of sHLA molecules and cytokine profile should be restricted only for research.

[Lactate acidosis in childhood]. / Laktátová acidóza v detském veku.

BACKGROUND: Secondary lactate acidosis is found in children with hypoxaemia, with impaired tissue perfusion, in hepatic and renal failure or in intoxications. Primary lactate acidosis is usually caused by hereditary metabolic disorders. The objective of the trial was to analyze the causes which lead in childhood to the development of primary hyperlactacidaemia. METHODS AND RESULTS: The authors examined during 1995-1996 the lactate and pyruvate concentration in 479 children referred by paediatric and neurological departments with a suspect hereditary metabolic disturbances. A raised lactate in blood or cerebrospinal fluid > 2.3 mmol/l was found in 230 children incl. 49 where a metabolic disorder was detected. Ten children had impaired cytochrome c oxidase, two children had a combined deficience of NADH dehydrogenase and cytochrome c oxidase, three children had a deficience of the pyruvate dehydrogenase (PDH) complex, one child had a deficience of ATP synthase and seven children suffered from impaired beta-oxidation. Glycogenosis type I, III or IX was found in 13 children. In three children organic aciduria was found, two children had an impaired urea cycle and three children impaired fructose metabolism. In five children a low level of free and total carnitene was found as a result of valproate treatment. A significant increase of the lactate level by more than 1 mmol/l during an oral glucose load was found in 11 of 16 children with impairment of the respiratory chain or PDH complex. In 58 children concurrently lactate in blood and cerebrospinal fluid assessed but no correlation of lactate levels was found. CONCLUSIONS: In patients with suspect hereditary metabolic disorders examination of lactate, pyruvate and alanine levels can be considered a screening test for detection of mitochondrial disorders. It remains difficult to reveal the cause of hyperlactacidaemia in a sick child even if a wide range of laboratory methods are used which contribute to the diagnosis of hereditary metabolic disorders.

[Enzyme therapy in children with severe forms of Gaucher's disease]. / Enzymová terapie u detí s tezkou formou Gaucherovy nemoci.

The enzyme therapy with Ceredase in patients with Gaucher's disease is at present probably the most expensive treatment in the whole world. One-year treatment of an adult patient with Gaucher's disease costs more than 7 million crowns. Indications for treatment in individual patients as well as financial provisions are so far problematic in the Czech Republic. From a total of 28 patients of varying age with Gaucher's disease diagnosed by the authors Ceredase was administered to two boys with a severe course of the disease. Within one year of treatment the health status of both children improved, growth became normal, the spleen diminished in size by 20-35%, haematological manifestations of hypersplenism are receding, there was a 32-46% decline of the activity of serum chitotriosidase and biochemical parameters of the disease improved.

Eosinophilic fasciitis in an adolescent girl with lymphadenopathy and vitiligo-like and linear scleroderma-like changes. A case report.

The patient, a 14-year-old girl, suffered from arthralgias which occurred after tonsillitis. Two months later she developed edema of the left lower extremity, finger flexion contractures and induration of the skin of the left leg, associated with hypergammaglobulinemia, peripheral hypereosinophilia, elevated ESR and a positivity of ANA and anti ds-DNA antibodies. A biopsy of the inguinal lymph node, performed because of left inguinal and retroperitoneal lymphadenopathy, showed only slight inflammatory activation and a granulomatous reaction after lymphography. A few days after the lymphography linear erythema evolving later into hyperpigmentation and corresponding to the superficial lymphatics developed on the left side of the body, very probably as a reaction to the patent-blue dye. Deep en-block skin biopsy confirmed the diagnosis of eosinophilic fasciitis (EF). After two years of therapy with prednisone and d-penicillamine the patient felt well, and her flexion contractures resolved, ANA were positive, while anti ds-DNA were negative. Linear hyperpigmentation persisted, and linear scleroderma-like changes developed on the left lower limb. A vitiligo-like lesion on the right foot which occurred after one year of therapy persisted. The possible risk of developing systemic connective tissue disease necessitates the long term follow up of this patient.

Subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14 in early onset pauciarticular juvenile chronic arthritis (EOPA) with and without iridocyclitis.

A set of 200 patients with early onset pauciarticular juvenile chronic arthritis (EOPA-JCA) from Munich (165) and Prague (35) was investigated for the subtypes of HLA-DRB1*03, *08, *11, *12, *13 and *14. In addition, the relationship of DRB1, DQA1, DQB1 and DPB1 alleles with iridocyclitis in patients with EOPA-JCA was investigated. Subtyping for DRB1*03 was not informative, as all DR3 positive patients and all except one of the controls possessed DRB1*0301. Thus, the role of DRB1*0302 could not be assessed. The subtypes for DRB1*12, *13, and *14 did not reveal any statistically significant difference between patients and controls. In contrast, the subtype DRB1*1104 was the one most strongly associated with EOPA-JCA (chi 2 31.2, p value < 10(-6)). It appears that the subtype DRB1*1103 may also be associated with EOPA-JCA. The association of EOPA-JCA with DR8 is almost exclusively due to the subtype *0801. For the other alleles *0802, *0803, and *0804 there is no evidence for or against involvement in JCA. The analysis of iridocyclitis in EOPA-JCA revealed that DRB1*1104 is not more frequent in patients with eye disease than in patients without eye disease. The presence of DRB1*01 appears to convey some protective effect against the occurrence of iridiocylitis in EOPA-JCA, as had been previously observed by Melin-Aldana et al.

The effect of long-term glucocorticoid therapy on glucocorticoid receptor content and on steroid response to ACTH.

The effect of long-term glucocorticoid therapy for systemic diseases on glucocorticoid receptor (GR) content and on basal and ACTH-stimulated levels of plasma and salivary cortisol 17 alpha-hydroxy-progesterone, androstenedione, 11 beta-hydroxyandrostenedione, DHEA, its sulfate and sex hormone-binding globulin (SHBG), as well as on basal levels of aldosterone, was investigated in a group of 24 children treated with prednisone for at least 8 months. The therapy was interrupted 24 h before the ACTH test and before plasma and saliva sampling. The control group consisted of 21 healthy children of corresponding age and sex. The patients were divided into two subgroups with normal and subnormal basal cortisolemia, they also differed in their response to ACTH. The GR levels in patient groups were indistinguishable from those found in controls. No correlation was found between GR content and basal levels of the above steroids or their response to ACTH. The best markers, apart from basal cortisolemia, for evaluation of the degree of suppression of adrenal function appeared to be the response of salivary (but not of plasma) cortisol and 17 alpha-hydroxy-progesterone to ACTH. Surprisingly, significantly lower levels of SHBG levels, which rose markedly after ACTH, were found in all the patients.