Spectrum and clinical implications of syntaxin 11 gene mutations in familial haemophagocytic lymphohistiocytosis: association with disease-free remissions and haematopoietic malignancies.

OBJECTIVE: To determine the frequency and spectrum of mutations in the gene encoding syntaxin 11 (STX11) in familial haemophagocytic lymphohistiocytosis (FHL), a rare autosomal recessive disorder of immune dysregulation characterised by a defect in natural killer cell function. METHODS: Mutational analysis of STX11 by direct sequencing was done in 28 FHL families that did not harbour perforin mutations, previously identified in some FHL patients. A detailed investigation of clinical features of these patients was also undertaken. RESULTS: Two different STX11 mutations were identified, one nonsense mutation and one deletion, affecting six of 34 children in four of 28 unrelated PRF1 negative families. Both mutations have been reported before. Three patients experienced long periods (> or = 1 year) in remission without specific treatment, which is very uncommon in this disease. Despite the milder phenotype, some children with STX11 mutations developed severe psychomotor retardation. Two of the six patients harbouring STX11 gene defects developed myelodysplastic syndrome (MDS) or acute myelogenous leukaemia (AML). CONCLUSIONS: STX11 gene mutations were found in 14% of the PRF1 negative FHL families included in the present cohort. These results suggest that STX11 gene mutations may be associated with secondary malignancies (MDS/AML), and that there is segregation of specific clinical features in FHL patients with an underlying genotype.

[Foreign body in the urinary bladder after vascular surgery]. / Ein Corpus alienum in der Harnblase nach gefässchirurgischem Eingriff.

INTRODUCTION: We are presenting a rare complication after femorofemoral bypass surgery. CASE REPORT: In a 61-year-old male patient, a femorofemoral crossover bypass graft was inadvertently placed through the urinary bladder. Postoperatively, the patient developed macrohematuria, which cleared spontaneously. The diagnosis of an intravesical graft was made 3 months after surgery by cystoscopy performed because of dysuria. The patient underwent open bladder surgery 7 months later as he refused earlier intervention. The misplaced graft, which was not infected and showed good function and perfusion, was extravesically relocated. At a 16-month follow-up examination, the patient is free of urological symptoms and the bypass functions well. CONCLUSIONS: In case of dysuria or macrohematuria after vascular surgery in the vicinity of the urinary bladder, a misplaced bypass should be excluded.

Serum estradiol as a tumour marker for non-seminomatous germinal cell tumours (NSGCT) of the testis.

Radioimmunoassay (RIA) determinations of serum alphafetoprotein (AFP), beta human chorionic gonadotropin (BHCG) and estradiol (E2) levels have been made at various stages of the disease in 52 patients with testicular carcinoma. In non-seminomatous tumours of the testis, E2 has been found to be a highly specific tumour marker, helping to reduce clinical staging error. Increases in serum E2 levels have been observed in all patients with HCG-secreting tumours, but E2 has indicated tumour recurrence alone in 4 patients with normal AFP and BHCG levels. Gynecomastia, always accompanied by a rise in serum E2 and BHCG levels has been a bad prognostic sign. E2 had no significance as a marker in seminomatous tumours.

Primary carcinoma of the renal pelvis and ureter. A collective review.

During an 18-year period, 17 patients with renal pelvic and 8 with ureteral carcinoma were seen in our clinic. The lesion was transitional cell carcinoma in 23 patients, and epidermoid and anaplastic carcinoma, respectively, in 2 others. Because of frequent tumour recurrence in the lower tract, we recommend total nephroureterectomy including a cuff of the bladder as the treatment of choice for renal pelvic neoplasms. For ureteral tumours, less aggressive and conservative procedures can be considered.

[Fournier's gangrene: report of 6 cases]. / Fournier gangreni: 6 olgu takdimi.

6 patients with Fournier's gangrene a rare but life threatening disease, who were successfully managed are presented. Mortality rates between 17-45 percent have been reported for this disease, but through the use of broad-spectrum antibiotics, aggressive surgical debridement and when possible with multiple drainage incisions to avoid skin defects, the mortality rate has been reduced to 0 percent. We have found an association with diabetes mellitus in 2 cases, which is one of the serious predisposition factors and should not be forgotten.

Homozygous ß-Thalassemia (FCS8-AA) and Hereditary Spherocytosis in the Same Patient.

A three-year old Turkish girl having both homozygous ß-thalassemia and hereditary spherocytosis and her family have been studied. The molecular defect causing thalassemia in the family was of the frame shift codon 8 (-AA) mutation type. The diagnosis of hereditary spherocytosis is based on osmotic fragility test in the patient and the family. However, the examination of erythrocyte membrane proteins has not been possible. ßthalassemia is in the heterozygous form in the mother, the father, and in two sisters. The mother, the father, and one of the sisters also have hereditary spherocytosis in addition to thalassemia. All those family members are asymptomatic. However, the patient who has frame shift codon 8 homozygosity along with hereditary spherocytosis presented with a severe form of hemolytic anemia.

Multiple Cerebral Emboli in a Homozygous b-Thalassaemia Patient Due to Factor V 1299 (His-Arg) 4070 A-G Mutation.

Thromboembolic episodes are quite rare in beta thalassemia major patients although there is a tendency for thrombosis in haemolytic anaemias. We report a patient with cerebral thromboembolic episode triggered by a minor blood group incompatibility in which the underlying defect of factor V 1299 (His-Arg) was detected three years after his death.

Significant loss of hepatitis A Ab after allogeneic hematopoietic SCT in pediatric patients.

Loss of specific immunity after hematopoietic SCT (HSCT) is well documented for polio, measles, mumps and tetanus. There are limited studies reporting the loss of Hepatitis A virus immunity and no reports evaluating the effect of donor immunity on Hepatitis A virus (HAV) immunity loss after HSCT. A total of 49 of the 81 patients who received HSCT at the Ankara University Pediatric HSCT Unit from January 1997 to December 2006 had HAV serology tested before HSCT and were evaluated for seroprevalence, and 30 of 49 patients were evaluated for the loss of Ab and for the effect of donor immunity on the loss of HAV Abs. The seroprevalence before HSCT was 75.5%. Loss of Ab was detected in 43.5% (10/23) of the patients. The median time to loss of Ab was 12 months (12-32 months), and 60% of these patients were seronegative at 12 months after HSCT. After HSCT, 46.7% of the patients were seronegative. Loss of Ab was higher in the seronegative donor group (75 vs 26%). The loss of HAV Ab is high after allogeneic HSCT for pediatric patients. Reimmunization should be considered for the continuation of individual and community immunity. Further studies with larger study groups are warranted to clarify the role of donor immunity on the loss of HAV immunity.

Cytokines as a common components of two different disorders: metabolic syndrome and hemophagocytic lymphohystiositosis.

Increased cytokines secretion occurs in several different disorders. Hemophagocytic lymphohystiositosis (HLH) and metabolic syndrome (MS) are consist two of them. Hemophagocytic lymphohystiositosis results from uncontrolled macrophage activation and huge amounts of cytokine secretion. The metabolic syndrome is a multicomponent condition characterized by insulin resistance, dyslipidemia, abdominal obesity, hypertension, and increased level of proinflammatory cytokines. It was presented a 6.8 years old girl, diagnosed as HLH. Because she was morbid obese, endocrinological investigation had been done and metabolic syndrome, thyroid hormone dysfunction, and hypercortisolemia with disturbances of diurnal rhythm were detected. During follow-up of patient, metabolic syndrome components disappear gradually while haemophagocytosis was recovered. Endocrine system can be affect during HLH attack, and MS can be developed. Cytokines seems to act central role of pathological changes for both diseases.

Immune thrombocytopenia and hemolytic anemia as a presenting manifestation of Hodgkin disease.

A very unusual clinical presentation of Hodgkin disease with immune thrombocytopenia and autoimmune hemolytic anemia is reported. A 6.5-year-old boy presented with thrombocytopenia, Coombs' positive hemolytic anemia, and multiple small posterior cervical lymph nodes. After a course of high-dose methylprednisolone therapy with a diagnosis of Evans syndrome, complete response for thrombocytopenia and partial response for anemia was achieved. Six weeks later there was a sudden increase in the size of left posterior cervical lymph nodes and a biopsy was compatible with Hodgkin disease, mixed cellularity type. The child was successfully treated with chemotherapy and radiation therapy. He has been off therapy for 28 months and has no clinical or laboratory evidence of autoimmune cytopenia. A combination of immune thrombocytopenia and autoimmune hemolytic anemia may be associated with Hodgkin disease. The recognition of this clinical picture as a complication of Hodgkin disease has important implications. This complication appeares to be managed best by the definitive treatment of Hodgkin disease.

A case of severe thrombocytopenia due to parvovirus B19 virus.

A 9-year-old girl admitted with generalized skin, mucosa, and genitourinary system bleeding had anemia and thrombocytopenia. Her bone marrow was normocellular. Parvovirus B19 IgM and IgG were positive. An absence of reticulocytopenia suggested that the virus affected only the megakaryocytic cell line and the anemia was due to generalized bleeding resulting from thrombocytopenia. Intravenous immunoglobulin treatment was instituted. On the tenth day of hospitalization the patient recovered from anemia and thrombocytopenia. IgM antibodies disappeared.

GM-CSF in the treatment of Fanconi's anaemia.

We have used recombinant human (rh) GM-CSF in two 12-year-old Fanconi's aplastic anaemia patients. They had not received any previous therapy except blood transfusions. Each patient was given three 21 d courses of rh-GM-CSF, the first two at a dose of 3.5 micrograms/kg/d and the third at 7 micrograms/kg/d s.c. There were significant increases in WBC and absolute neutrophil counts after the first week of rh-GM-CSF which lasted as long as the treatment was continued. Following the cessation of treatment, WBC and ANC dropped rapidly. We conclude that rh-GM-CSF can be used in FAA, especially in severely neutropenic cases.

Desferrioxamine and urinary zinc excretion in beta-thalassemia major.

This study has been undertaken to find out whether urinary zinc excretion, which is already increased in patients with thalassemia, is further increased by usual and high doses of desferrioxamine (DF). A total of 11 beta-thalassemia major patients were included. DF infusions have been performed with doses, either 50 mg/kg or 150 mg/kg. Nine age and sex matched normal children were taken as the control group. The mean basal-Zn excretion of the patients was significantly higher than the mean Zn excretion observed in controls. No significant difference is observed between the mean Zn excretion obtained on different doses of DF. However, they are both significantly higher than the mean basal-Zn levels of the controls.

Hereditary multiple exostoses and acute myeloid leukemia: an unusual association.

Hereditary multiple exostoses (HME) is an autosomal dominant disorder characterized by the presence of multiple exostoses. Three genetic loci have been identified, of which two (EXT1 and EXT2) have tumor suppressor activity. HME greatly increases the risk to develop sarcoma in the dysplastic tissue. The authors report an 8-year-old girl with HME who developed acute myeloblastic leukemia.

Recombinant human growth hormone treatment in children with thalassemia major.

BACKGROUND: To evaluate the growth hormone reserve and the growth hormone response to recombinant human growth hormone (GH) in prepubertal thalassemic children with growth retardation. METHODS: Twenty thalassemic patients with short stature and delayed bone age were studied. Patients were randomized into GH-treated (n = 10) and non-GH treated (control; n = 10) groups. The GH-treated group received recombinant human (rh)-GH (Genotropin) at the dose of 0.7 IU/kg per week for 12 months. RESULTS: There was a significant discordance between GH response to pharmacologic stimuli and physiological secretion of GH/GHRH testing. Following the administration of rhGH, growth velocity increased from 2.47 +/- 0.48 cm/year to 6.27 +/- 0.76 cm/year (P = 0.005), whereas there was not a similar change in the non-GH-treated group. The height velocities of the two groups during the 1 year follow-up period were significantly different (6.27 +/- 0.76 vs 3.99 +/- 0.34 cm/year; P = 0.025). There were significant differences between the height velocity improvements and height velocity standard deviation scores of the two groups as well. CONCLUSION: The present study has demonstrated that rhGH is a safe and efficacious mode of treatment in thalassemic children.