Low-factor consumption for major surgery in haemophilia B with long-acting recombinant glycoPEGylated factor IX.

INTRODUCTION: Surgery in patients with haemophilia B carries a high risk of excessive bleeding and requires adequate haemostatic control until wound healing. Nonacog beta pegol, a long-acting recombinant glycoPEGylated factor IX (FIX), was used in the perioperative management of patients undergoing major surgery. AIM: To evaluate the efficacy and safety of nonacog beta pegol in patients with haemophilia B who undergo major surgery. METHODS: This was an open-label, multicentre, non-controlled surgery trial aimed at assessing peri- and postoperative efficacy and safety of nonacog beta pegol in 13 previously treated patients with haemophilia B. All patients received a preoperative nonacog beta pegol bolus injection of 80 IU kg-1 . Postoperatively, the patients received fixed nonacog beta pegol doses of 40 IU kg-1 , repeated at the investigator's discretion. Safety assessments included monitoring of immunogenicity and adverse events. RESULTS: Intraoperative haemostatic effect was rated 'excellent' or 'good' in all 13 cases. Apart from the preoperative injection, none of the patients needed additional doses of nonacog beta pegol on the day of surgery. The median number of postoperative doses of nonacog beta pegol was 2.0 from days 1 to 6 and 1.5 from days 7 to 13. No unexpected intra- or postoperative complications were observed including deaths or thromboembolic events. No patients developed inhibitors. CONCLUSIONS: These results indicated that nonacog beta pegol was safe and effective in the perioperative setting, allowing major surgical interventions in patients with haemophilia B with minimal peri- and postoperative concentrate consumption and infrequent injections as reported with standard FIX products.

CD3G gene defects in familial autoimmune thyroiditis.

The patients with CD3γ deficiency can present with different clinical findings despite having the same homozygous mutation. We report three new CD3gamma-deficient siblings from a consanguineous family with a combined T-B+NK+ immunodeficiency and their variable clinical and cellular phenotypes despite the same homozygous mutation of the CD3G gene (c.80-1G>C). We also re-evaluate a previously reported non-consanguineous family with two CD3gamma-deficient siblings with the same mutation. The median age at diagnosis was 11 years (14 months-20 years). We found all five patients to display autoimmunity: autoimmune thyroiditis (n = 5), autoimmune haemolytic anaemia (n = 2), immune thrombocytopenia (n = 1), autoimmune hepatitis (n = 1), minimal change nephrotic syndrome (n = 1), vitiligo (n = 1) and positive antinuclear antibodies (n = 3) as well as high IgE (n = 2) and atopic eczema (n = 2). While CD3(+) TCRαß+T cell percentages were low in all patients, only one had lymphopenia and 3 had CD3(+) T cell lymphopenia. Strikingly, we report frequent and multiple autoimmunity in tested heterozygous carriers in both families (n = 6; in 67%), and frequent autoimmunity in family members not available for testing (n = 5, in 80%). The results suggest that CD3G should be studied as a candidate gene for autoimmunity and that CD3gamma deficiency should be considered among other primary immunodeficiencies with predominantly autoimmune manifestations.

Successful treatment with interferon alfa in infiltrating angiolipoma: a case presenting with Kasabach-Merritt syndrome.

We report a case of infiltrating angiolipoma who presented with a large mass on the shoulder and the signs of Kasabach-Merritt syndrome. She improved dramatically within one month and the mass completely disappeared after six months of interferon treatment.

Diencephalic tumours presenting as psychosis.

BACKGROUND: Diencephalic tumours are usually presented with the sign and symptoms of increased intracranial pressure, endocrinological changes and visual disturbances. Psychiatric manifestation of such rare tumours is not well known. OBJECTIVE: To investigate the challenges and benefits of psychiatric evaluation on the diagnosis of diencephalic tumours and to emphasize the presence of psychosis as an initial phenomenon. METHODS AND RESULTS: Two cases who presented with the characteristic symptoms of psychosis and diagnosed diencephalic tumour are reported. A detailed radiological examination confirmed such diagnosis in both cases and surgical treatment was done. CONCLUSION: First, all patients who presented with a history of unexplained behaviour change must be evaluated by psychiatrists to exclude an organic pathology. Secondly, until the diagnosis of diencephalic tumour is confirmed, the surgical management must be performed.

Micronucleus incidence and their chromosomal origin related to therapy in acute lymphoblastic leukemia (ALL) patients: detection by micronucleus and FISH techniques.

Micronucleus assay and dual color-fluorescence in situ hybridization (DC-FISH), using centromere-specific and whole chromosome-specific painting probes, are considered a useful screening test to determine the incidence of micronucleus, their origin and contents. The patients with acute lymphoblastic leukemia (ALL), who had undergone chemotherapy, were analysed before and after treatment with vincristine, methotrexate, daunomycin, prednisone, and asparaginase. The incidence of micronuclei after the antileukemic agent treatment was significantly higher than before the treatment. Application of DC-FISH using a combination of whole chromosome-specific painting probes and the same chromosome-specific alpha-satellite centromeric probe showed that there were no significant differences in the micronucleus incidence for any specific chromosome (chromosomes 7, 8, 11, 17, X, and Y). There were no significant differences between the incidence of centromere-positive micronuclei and the incidence of centromere-negative micronucleus. We concluded that antileukemic agents induced the somatic genetic damage but this damage is not related to any specific chromosome studied.

Platelet functions in patients with protein-energy malnutrition.

Protein-energy malnutrition (PEM) has been known to cause several organ damages or dysfunctions. In this study, using optic method, platelet aggregation (PA) analyses were performed in patients with PEM. Adenosine diphosphate (ADP)- and collagen-induced PA were significantly decreased in the patients with PEM. The low values reached normal when the patients caught up the optimal growing curve for their age. PA with ristocetin and epinephrine were not significantly altered in the patients. Conversely, mean platelet count was increased at the beginning compared to those of after therapy and to the control. These results indicate that some platelet functions (ADP- and collagen-induced platelet aggregations), as well as other body functions, have been decreased in PEM.

Hyperdiploid karyotype in a childhood MDS patient.

We present a rare case of a paediatric myelodysplastic syndrome (MDS) with congenital anomalies (frontal bossing and premature closure of anterior fontanelle). The case showed the clinical and biological features of a refractory anaemia excess blasts (RAEB). Bone marrow (BM) cytogenetics demonstrated a hyperdiploid karyotype, with several numerical abnormalities and unidentified rearrangements. Fluorescence in situ hybridization (FISH) using chromosome specific alpha-satellite and whole chromosome-specific painting probes verified the hyperdiploid karyotype, and confirmed the origin of the unknown markers and rearrangements more reliably than would be possible using conventional cytogenetic techniques.

A case of osteopetrosis with pelvic ectopic spleen: an unusual association.

A three-month-old girl was admitted to the hospital with a history of pallor. On physical examination, the liver was enlarged and a solid mass was palpated in the left abdomen. Laboratory evaluation revealed anemia and thrombocytopenia. Bone marrow was hypocellular with reduced number of megakaryocytes. Radiographic findings and scintigraphic study of the long bones were consistant with osteopetrosis. In the imaging studies, including ultrasonography, computerized tomography, magnetic resonance imaging and scintigraphic study, an ectopic spleen expanded into the bony pelvis was observed. We report here unique case of infantile osteopetrosis associated with pelvic ectopic spleen.

Investigation of platelet aggregation by impedance and optic methods in children with iron deficiency anaemia.

Although it is known that platelet count is altered in iron deficiency anaemia (IDA), the qualitative extent of this interference is not well documented. In the present study we investigated platelet aggregation (PA) by impedance and optic methods in IDA. Forty-seven patients (plasma group: 16 boys, 9 girls and whole blood group: 11 boys, 11 girls) with IDA and thirty-one healthy children (plasma group: 6 boys, 10 girls and whole blood group: 6 boys, 9 girls) were enrolled into the study. Template bleeding times were measured by the Ivy method in all children. In the control group whole blood count, serum iron levels, bleeding time and PA were determined. After basal PA was determined in the patients and controls, ferrous sulphate was orally administered to the patients at a dose of 6 mg/kg/24 h for three months. Then, PA tests were performed again in the IDA (test group) patients. Ristocetin-induced PA was suppressed in both plasma and whole blood groups. Inhibition by both collagen (p < 0.05) and ristocetin (p < 0.001)-induced PA was determined by the optic method. Similarly in PA measured by the impedance method a suppression to adenosine diphosphate (p < 0.001) and to ristocetin (p < 0.01) was found. However, no significant alteration was observed in the bleeding time. All defective responses were reversed by the iron supplementation therapy. In addition, a significant correlation was found between some parameters of PA and several haematological values. In conclusion, although defective PA responses cannot be clinically demonstrated in patients with IDA, this suppression of PA may be detected by laboratory examination. Therefore, it is advised that care should be taken when using anti-aggregant agents in IDA.

Effect of laparoscopic cholecystectomy on platelet aggregation.

The purpose of this study was to investigate the effect of laparoscopic cholecystectomy on platelet function. We operated on 40 women with symptomatic gallbladder stone, 20 of whom (study group) underwent laparoscopic cholecystectomy and 20 of whom (control group) open cholecystectomy. Patients with a history of bleeding, abnormal platelet count, or systemic disorders and those who were on salicylates, heparin, or oral anticoagulants were excluded. Blood parameters were checked at the beginning and the end of the operation, including platelet aggregation using adenosine 5'-diphosphate (ADP), collagen, and ristocetin in a whole-blood aggregometer. Platelet aggregation was evaluated by percent aggregation. Platelet aggregation due to collagen and ristocetin increased significantly at the end of the operation in the study group (p < 0.001). Aggregation due to ADP did not differ significantly from the start to the end of the operation. Control group results did not show any differences. Although the clinical findings of aggregated platelet are not frequently observed in practice, we suggest that laparoscopy increases platelet aggregation.

Diminished platelet aggregation in patients with iron deficiency anemia.

To evaluate platelet function in iron deficiency anemia, using impedance (in whole blood) and optic (in platelet-rich plasma methods, platelet aggregation analyses were performed in 42 children with iron deficiency anemia at the time of diagnosis and after iron therapy. Collagen-induced platelet aggregation was decreased in patients before therapy compared to after therapy and control levels as indicated by the two methods while adenosine diphosphate (ADP)-induced platelet aggregation was decreased only by the whole blood method. Platelet aggregation with epinephrine, performed only by the optic method, was not altered in patients with iron deficiency anemia. Platelet counts were found to be increased in patients with iron deficiency anemia, and decreased with therapy. These results indicate that some platelet functions are decreased in patients with iron deficiency anemia. These decreased functions may be compensated by increased platelet numbers.

Paediatric myelodysplastic syndrome (MDS) and juvenile chronic myelogenous leukaemia (JCML) detected by cytogenetic and FISH techniques.

This report presents two rare cases, one of paediatric myelodysplastic syndrome (MDS) and the other juvenile chronic myeloid leukaemia (jCML). In the first case, there were clinical and biological features of MDS-refractory anaemia with excess blasts (RAEB). The bone marrow (BM) karyotype demonstrated a monosomy 7 which was confirmed by fluorescence in situ hybridization (FISH). In addition, FISH analysis showed that an alpha-satellite DNA sequence had been transferred from chromosomes 13/21 to one homologue of chromosomes 22. The BCR-ABL rearrangement was negative. In the second case, at diagnosis, the karyotype was 46,XX. FISH analysis with the simultaneous and individual application of abl and bcr probes for chromosome 9 and 22, respectively, revealed the presence of the BCR-ABL rearrangement in addition to an extra ABL sequence locating chromosome 20. A clone that was BCR-ABL gene rearrangement negative but with an extra ABL DNA sequence on chromsome 20, and another clone that was BCR-ABL gene rearrangement negative were detected by DC-FISH and uni-colour (UC-) FISH analysis. No monosomy 7 was detected by conventional cytogenetic or FISH analyses.

Conn syndrome in a child, caused by adrenal adenoma.

Hyperaldosteronism owing to aldosterone-producing adenoma (Conn syndrome) is a rare but potentially curable form of pediatric hypertension. The authors report on a 5-year-old girl who had symptoms of polyuria, polydipsia, and fatigue, and for whom the diagnosis of hyperaldosteronemia was suggested by a low serum potassium level and persistent hypertension. The diagnosis was confirmed by increased levels of plasma aldosterone and decreased levels of plasma renin. The tumor was localized with ultrasonography and computed tomography, which showed a 2-cm mass in the left adrenal gland. The left adrenal gland was excised, and pathological assessment showed an adenoma. Only 14 other pediatric cases (< 16 years of age) have been reported in the English-language literature.

Effects of verapamil, papaverine, sodium nitrite, and hydralazine on ethyl alcohol-induced contraction of the isolated human umbilical artery.

In this in vitro study, the vasodilator effects of certain drugs such as verapamil, papaverine, sodium nitrite and hydralazine on ethyl alcohol-induced contractions were investigated in the isolated human umbilical artery. Ethyl alcohol caused dose dependent contractions in this tissue. Papaverine, sodium nitrite and hydralazine were found to be effective.