Successful rituximab treatment of granulomatous/lymphocytic interstitial lung disease in common variable immunodeficiency.

Successful rituximab treatment of granulomatous/lymphocytic interstitial lung disease in common variable immunodeficiency Common variable immunodeficiency, a heterogeneous group of diseases, represents a clinically relevant form of antibody immunodeficiency. Granulomatous/lymphocytic interstitial lung disease is among the most serious complications. A case report is presented of a young women with granulomatous/lymphocytic interstitial lung disease and splenomegaly accompanied by pancytopenia. Intravenous rituximab treatment in monotherapy (at a weekly dose of 375 mg/m2 for four consecutive weeks, repeated six months later) not only led to a significant improvement in clinical symptoms but also to positive morphological and functional lung changes, mitigation of pancytopenia, considerable reduction of alkaline phosphatase level, and disappearance of splenic granulomas. The treatment was well tolerated without any side effects. The case report presented suggests possible efficacy and safety of rituximab monotherapy in patients with a complicated form of common variable immunodeficiency. KEYWORDS Rituximab - antibody immunodeficiency - lung disease - treatment Epidemiol. Mikrobiol. Imunol., 67, 2018, c. 3, s. 142-148.

Importance of basal fibroblast growth factor levels in patients with ovarian tumor.

OBJECTIVE: Evaluation of importance of serum levels of basic fibroblast growth factor (bFGF) in patients with ovarian cancer, patients with border-line ovarian tumor, patients with benign ovarian cyst and women with normal ovarian tissue. DESIGN: Prospective clinical study. SETTING: Department of Gynecology and Obstetrics, Charles University, Faculty of Medicine in Hradec Kralove and University Hospital Hradec Kralove. METHODS: Measurement of serum levels of bFGF by ELISA using reagents of company R&D Systems prior to treatment in a total of 74 consecutive coming women. RESULTS: Serum level of bFGF from peripheral blood before treatment was significantly higher (p < 0.05) in patients with newly diagnosed ovarian cancer (n = 22), Med = 10.35 pg/ml (1.2-46.2 pg/ml) compared to patients with a border-line ovarian tumor (n = 9), Med = 5.4 pg/ml (1.6-6.8 pg/ml), patients with benign ovarian cyst (n = 24), Med = 5.2 pg/ml (0.1-67.2 pg/ml), and to women with normal ovarian tissue (n = 19) Med = 4.3 pg/ml (0.9-13.4 pg/ml). There isnt strong linear correlation (Spearmans rank correlation coefficient = 0.208791) between the serum level of bFGF and CA125 collected from peripheral blood before primary surgery or neoadjuvant chemotherapy in a group of patients with ovarian cancer (n = 14). We have not found significance correlation between age and serum levels of bFGF in patients with ovarian cancer, with border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue. CONCLUSION: Serum levels of bFGF in patients with ovarian cancer are significantly higher than in patients with a border-line ovarian tumor, with benign ovarian cyst and in women with normal ovarian tissue regardless of age of patients.

Antibodies against Pneumococcal Capsular Polysaccharides and Natural Anti-Galactosyl (Alpha-Gal) in Patients with Humoral Immunodeficiencies.

Humoral deficiencies represent a broad group of disorders. The aim of the study was to compare the levels of antibodies against pneumococcal capsular polysaccharides (anti-PCP) and natural anti-galactosyl (anti-Gal) antibodies in (1) patients with chronic lymphocytic leukaemia (CLL), (2) patients with common variable immunodeficiency (CVID), and (3) a healthy population and to explore their diagnostic and prognostic potential. Serum immunoglobulin levels and levels of anti-Gal IgG, IgA, and IgM and anti-PCP IgG and IgG2 were determined in 59 CLL patients, 30 CVID patients, and 67 healthy controls. Levels of IgG, IgA, IgM, anti-Gal IgA, anti-Gal IgM, and anti-PCP IgA were lower in CLL and CVID patients than in healthy controls (p value for all parameters < 0.0001). Decrease in the levels of IgA, IgM, anti-Gal IgA, and anti-PCP IgA was less pronounced in the CLL group than in the CVID group. IgA decline, anti-Gal IgA, anti-PCP IgA, and anti-PCP IgG2 were negatively correlated with CLL stage. We devise the evaluation of anti-Gal antibodies to be a routine test in humoral immunodeficiency diagnostics, even in cases of immunoglobulin substitution therapy. Significant reductions, mainly in anti-Gal IgA, IgM, and anti-PCP IgA levels, may have prognostic importance in CLL patients.

Artificially low cortical bone mineral density in Turner syndrome is due to the partial volume effect.

UNLABELLED: We aimed to show that the decrease in the cortical bone mineral density (BMD) in the radius in Turner syndrome (TS) is artificially caused by the partial volume effect. We confirmed that the partial volume effect-corrected cortical BMD is not decreased in TS compared to in the healthy controls. Other factors are responsible for the increased fracture rate in TS. INTRODUCTION: Decreased cortical bone mineral density (BMD) has been reported in Turner syndrome (TS), using peripheral quantitative computerised tomography, and it is perceived as one of the major factors leading to increased fracture risk. We tested the hypothesis that low cortical BMD in the radius is caused artificially by the partial volume effect. METHODS: A cross-sectional study was conducted at the university hospital referral centre between March and October 2013. Thirty-two participants with TS who consented to the study were included (mean age 15.3 ± 3.2 years). We assessed the cortical BMD in the radius as well as the tibia, where the cortex is thicker compared with the radius. RESULTS: Whereas the cortical BMD was decreased in the radius (mean ± SD Z-score -0.6 ± 1.5, p = 0.037), it was increased in the tibia (mean Z-score 0.83 ± 1.0, p < 0.001). After correcting the cortical BMD for the partial volume effect, the mean Z-score was normal in the radius in TS (0.4 ± 1.3, p = 0.064). The corrected cortical BMD values were similar in the radius and tibia (1108 ± 52 vs. 1104 ± 48, group difference p = 0.75). CONCLUSIONS: The cortical BMD is not decreased in TS. The partial volume effect is responsible for previous findings of decreased cortical BMD in the radius. Altered bone geometry or other factors rather than low cortical BMD likely play a role in the increased fracture risk in TS.

Reference data for jumping mechanography in healthy children and adolescents aged 6-18 years.

OBJECTIVES: To present gender-specific pediatric normative data on the main parameters of muscle function assessed using jumping mechanography. METHODS: The study population included 796 non-selected Caucasian children and adolescents (432 girls and 364 boys) aged 6-19 years recruited from 6 primary schools and 3 high schools. Maximum peak power (Pmax) was examined by a single two-legged jump, and maximum force (Fmax) was examined by a multiple one-legged hopping. All measurements were performed using a portable force platform (Leonardo Mechanograph, Novotec). Pmax, Pmax/mass, Fmax and Fmax/body weight were analyzed as the main outcome parameters. LMS method was used to generate age- and weight-specific reference smooth curves. RESULTS: Both Pmax and Fmax were strongly dependent on age and weight in both genders (all p<0.001). In prepubertal children, there was no intergender difference in Pmax or Fmax. Both parameters steadily increased in boys and plateaued in girls aged >13 years. Whereas Pmax/mass was more dependent on anthropometric parameters, Fmax/BW remained nearly constant with respect to age and weight. CONCLUSIONS: These reference data are intended to assist clinicians in the assessment of muscle function by jumping mechanography in pediatric patients.

Prepubertal girls with Turner syndrome and children with isolated SHOX deficiency have similar bone geometry at the radius.

CONTEXT: The low bone mineral density (BMD) and alterations in bone geometry observed in patients with Turner syndrome (TS) are likely caused by hypergonadotropic hypogonadism and/or by haploinsufficiency of the SHOX gene. OBJECTIVE: Our objective was to compare BMD, bone geometry, and strength at the radius between prepubertal girls with TS and children with isolated SHOX deficiency (SHOX-D) to test the hypothesis that the TS radial bone phenotype may be caused by SHOX-D. DESIGN AND SETTING: This comparative cross-sectional study was performed between March 2008 and May 2011 in 5 large centers for pediatric endocrinology. PATIENTS: Twenty-two girls with TS (mean age 10.3 years) and 10 children with SHOX-D (mean age 10.3 years) were assessed using peripheral quantitative computed tomography of the forearm. MAIN OUTCOMES: BMD, bone geometry, and strength at 4% and 65% sites of the radius were evaluated. RESULTS: Trabecular BMD was normal in TS (mean Z-score = -0.2 ± 1.1, P = .5) as well as SHOX-D patients (mean Z-score = 0.5 ± 1.5, P = .3). At the proximal radius, we observed increased total bone area (Z-scores = 0.9 ± 1.5, P = .013, and 1.5 ± 1.4, P = .001, for TS and SHOX-D patients, respectively) and thin cortex (Z-scores = -0.7 ± 1.2, P = 0.013, and -2.0 ± 1.2, P < .001, respectively) in both groups. Bone strength index was normal in TS as well as SHOX-D patients (Z-scores = 0.3 ± 1.0, P = .2, and 0.1 ± 1.3, P = .8, respectively). CONCLUSIONS: The similar bone geometry changes of the radius in TS and SHOX-D patients support the hypothesis that loss of 1 copy of SHOX is responsible for the radial bone phenotype associated with TS.

Bone geometry and volumetric bone density at the radius in patients with isolated SHOX deficiency.

UNLABELLED: The short stature homeobox-containing gene (SHOX) plays an important role in bone development and growth. We aimed to assess bone geometry and volumetric bone mineral density at the radius in patients with isolated SHOX deficiency and to relate these bone parameters to the severity of disproportion between the upper and the lower body segment. 17 patients with isolated SHOX deficiency (median age 12.3 yrs, range 6.7-37.2, 12 children and 5 adults) were examined by peripheral quantitative CT (pQCT) at the non-dominant forearm. Results were expressed as Z-scores using published reference data. Linear regression analyses were performed to describe associations between pQCT parameters and the severity of disproportion expressed as sitting height to standing subischial leg height ratio. Trabecular volumetric bone mineral density (vBMD) at the distal radius was normal, whereas cortical vBMD was decreased (mean Z-scores 0.34±1.5, n.s., and -2.2±2.2, p<0.001, respectively). Total bone cross-sectional area was enlarged at the diaphysis (2.1±1.2, p<0.001), while cortical bone cross-sectional area was normal (-0.51±1.4, n.s.). Consequently, cortical thickness was decreased (-1.2±1.3, p<0.01). The polar strength-strain index as a surrogate of long bone strength was normal (0.40±1.4, n.s.). We found no associations between pQCT parameters and the severity of disproportion. CONCLUSIONS: Patients with isolated SHOX deficiency are characterized by decreased cortical vBMD and cortical thickness and enlarged diaphysis. As similar changes have been described in girls with Turner syndrome, these findings suggest that haploinsufficiency of SHOX could cause characteristic skeletal anomalies at the radius.

Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2.

The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUG(exp) RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUG(exp) foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUG(exp) repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUG(exp) transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.

Boys with haemophilia have low trabecular bone mineral density and sarcopenia, but normal bone strength at the radius.

Although a decreased areal bone mineral density (BMD) has been reported in patients with haemophilia, data are lacking that would reflect the three-dimensional structure of the bone and the muscle-bone relationship. We aimed to assess volumetric BMD, bone geometry and muscle-bone phenotype in boys with haemophilia, and to describe the association between clinical characteristics of haemophilia and bone quality and structure. A cross-sectional study was conducted in 41 boys with haemophilia (mean age 12.4, range 6.6-19.8 years) using peripheral quantitative CT (pQCT) at the nondominant forearm. Results were transformed into Z-scores using previously published reference data. Significant differences were tested by one-sample t-test or sign test. Two-sample t-test and anova were used to compare results between subgroups of patients divided according to the severity of the disease, the fracture history and the number of joint and muscle bleedings. Boys with haemophilia had a decreased trabecular volumetric BMD (mean Z-score -0.5, P < 0.01), while their cortical volumetric BMD was increased (mean Z-score 0.4, P < 0.05). The volumetric bone mineral content and the bone geometry at the radial diaphysis were normal when adjusted for patients' shorter body height. Muscle area was decreased (mean Z-score -1.0, P < 0.001), irrespective of age. No association was observed of bone quality parameters and bone geometry with the disease severity, fracture history or number of bleedings. Bone strength measured at the diaphysis of the radius is not impaired in boys with haemophilia. The finding of the decreased trabecular bone density can be most likely attributed to their sarcopenia.

[Segmental absence of the muscularis propria layer in the colonic wall--a rare cause of colonic perforation during pregnancy]. / Segmentální absence muscularis propria steny tracníku - vzácná prícina perforace tracníku v tehotenství.

Segmental absence of intestinal musculature (SAM) may, rarely, present with symptoms of ileus or intestinal perforation. Most commonly, the disorder presents with signs of intestinal disorders in newborns. Colonic perforations are then rare in adulthood. In this study, the authors present a case of a young female patient, operated for right abdominal pains when she was 30 weeks pregnant. Although no advanced appendicitis was confirmed, appendectomy was performed. Five days later, surgical revision was indicated for signs of septic condition and abdominal pain. Two perforations of the ascending colon and diffuse peritonitis were found. Section and right-sided hemicolectomy were performed. The final identification of the cause was based on histological examination of the resecate. The perforations were located at the sites, where the intestinal muscular layer was absent. This finding has also got forensic consequences. It revealed a rare cause of colonic perforation, which is undetectable on examination and confirmed that no mistakes were made during the first procedure. The authors did not find any literature data on colonic perforations due to the colonic muscle layer absence during pregnancy.