The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I‐MIBG accompanied by ASCT for high‐risk and relapsed neuroblastoma: A pilot study

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant ¹³¹I‐MIBG scintigraphy. Twenty high‐risk patients were enrolled. On day ?30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG‐avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m²), carboplatin (1500 mg/m²), and melphalan (210 mg/m²). Non‐MIBG‐avid subgroup received etoposide (600 mg/m²), carboplatin (1200 mg/m²), and melphalan (150 mg/m²). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17–65) in MIBG‐avid and 38.9 months (range, 18–65) in non‐MIBG‐avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG‐avid patients, the three‐yr OS was 66 ± 21%. In MIBG‐non‐avid subgroup, the three‐yr OS was 53 ± 20%. In MIBG‐avid and non‐MIBG‐avid subgroups, the three‐yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre‐ASCT MIBG scintigraphy in high‐risk neuroblastoma. MIBG‐avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.     

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination

Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating and neurodegenerative disorders. In multiple sclerosis, oligodendrocyte progenitor cells (OPCs) migrate to lesion sites to repair myelin. However, during disease progression, the ability of OPCs to participate in remyelination diminishes coincident with worsening of the symptoms. Remyelination is affected by a broad range of cues from intrinsic programming of OPCs and extrinsic local factors to the immune system and other systemic elements including diet and exercise. Here we review the literature on these diverse inhibitory factors and the challenges they pose to remyelination. Results spanning several disciplines from fundamental preclinical studies to knowledge gained in the clinic will be discussed.     

Prevalence of thyroid dysfunctions in systemic lupus erythematosus

The association of systemic lupus erythematosus (SLE) and thyroid autoimmunity has been reported by several studies in a wide range of variability. However, from a review of the literature, discrepant results have been reported. The aim of the study was to evaluate the prevalence of clinical and subclinical thyroid disorders in patients with SLE vs sex- and age-matched controls. Thyroid hormones and the presence of antithyroid antibodies were tested and thyroid ultrasonography was performed in 213 patients with SLE vs 426 sex- and age-matched controls, from the same geographic area, with a well-defined status of iodine intake. The odds ratio for subclinical hypothyroidism for female patients with SLE with respect to controls was 4.5 (95% confidence interval [CI], 2.5-8.4); for antithyroid peroxidase antibody (AbTPO) positivity, it was 2.6 (95% CI, 1.7-4.1); and for thyroid autoimmunity, it was 2.9 (95% CI, 2.0-4.4). The mean values of thyroid-stimulating hormone and AbTPO were higher in female SLE patients than in controls (P < .01). A significantly (P < .01) higher prevalence of clinical hypothyroidism and Graves disease was observed in female SLE patients than in controls. No significant difference between SLE patients and controls was detected with regard to free triiodothyronine and thyroxine. In our series, 3% of SLE patients had “nonthyroidal illness syndrome” vs 0 control. Thyroid function and AbTPOs should be tested and ultrasonography should be performed as part of the clinical profile in SLE patients. Subjects at high risk (women, positive AbTPOs, hypoechoic, and small thyroid) should have thyroid function follow-up and appropriate treatment in due course.     

GJB2 mutations in Iranians with autosomal recessive non-syndromic sensorineural hearing loss

Hereditary hearing loss (HHL) is an extremely common disorder. About 70% of HHL is non-syndromic, with autosomal recessive forms accounting for approximately 85% of the genetic load. Although very heterogeneous, the most common cause of HHL in many different world populations is mutations of GJB2, a gene that encodes the gap junction protein connexin 26 (Cx26). This study investigates the contribution of GJB2 to the autosomal recessive non-syndromic deafness (ARNSD) load in the Iranian population. One hundred sixty eight persons from 83 families were studied. GJB2-related deafness was diagnosed in 9 families (4, 35delG homozygotes; 3, 35delG compound heterozygotes; 1, W24X homozygote; 1, non-35delG compound heterozygote). The carrier frequency of the 35delG allele in this population was approximately 1% (1/83). Because the relative frequency of Cx26 mutations is much less than in the other populations, it is possible that mutations in other genes play a major role in ARNSD in Iran.     

Survey of sarcocystis infection in slaughtered sheep in Kerman Abattoir, Kerman, Iran

Sarcocystosis caused by different Sarcocystis species and is a zoonotic protozoan infection with worldwide distribution in man and many animal species. In the present study, three techniques — direct inspection, impression smears and digestion method — were used for the diagnosis of Sarcocystis infection in 112 slaughtered sheep in a Kerman abattoir from November 2010 to May 2011. A total of 450 slaughtered sheep were selected randomly during three seasons, and their oesophagus and diaphragm were inspected using naked eye examination. In the second stage, 112 carcasses out of the 450 which had no apparent infection were selected randomly and their meat investigated using two techniques: impression smear with staining and pepsin digestion. The percentage of macroscopic cysts found in the oesophagus and diaphragm muscle was 6% and 2.88%, respectively, and microscopically, infection was found in 100% of the organs. There was no significant difference between different ages or between males and females. Although all of the sheep were found to be infected with Sarcocystis, majority of the cysts were demonstrated microscopically. This suggests that meat should be cooked sufficiently, since a macroscopic inspection may not provide true results.     

Prolonged in vitro exposure to autoantibodies against CD38 impairs the function and survival of human pancreatic islets

Autoantibodies against CD38 (adenosine-5'-diphosphate[ADP]-ribosyl cyclase/cyclic ADP-ribose hydrolase) have been described in 10-12% of patients with type 2 diabetes. In human islets, anti-CD38 autoantibodies (CD38Abs) acutely stimulate insulin release (IR) and increase the cytosolic calcium concentration ([Ca(2+)](i)). Whether CD38Abs affect human islet cell function and survival upon prolonged in vitro exposure is not known. We cultured human islets for up to 7 days in the presence of sera from 10 patients with type 2 diabetes that had neither CD38Ab- nor [Ca(2+)](i)-mobilizing activity (-/-), sera from 6 patients with type 2 diabetes that was CD38Ab-positive and had [Ca(2+)](i)-mobilizing activity (+/+), or no sera (control). At baseline, +/+ sera caused a significant (P < 0.002) acute stimulation of IR (IR at 3.3 mmol/l glucose was 45 +/- 19, 84 +/- 24, and 34 +/- 12 micro U/ml in control, +/+, and -/- sera, respectively; the corresponding IR at 16.7 mmol/l glucose was 72 +/- 25, 204 +/- 56, and 80 +/- 32 micro U/ml). At 3 days, IR at 3.3 mmol/l glucose was 42 +/- 18, 27 +/- 11, and 43 +/- 24 micro U/ml (P = 0.0003) for control, +/+, and -/- sera, respectively, whereas at 16.7 mmol/l glucose, it was 95 +/- 76, 45 +/- 35, and 76 +/- 42 micro U/ml, respectively. After 7 days of exposure, the corresponding IR at 3.3 mmol/l glucose was 40 +/- 11, 28 +/- 12, and 35 +/- 15 micro U/ml, respectively, whereas at 16.7 mmol/l glucose it was 79 +/- 39, 39 +/- 17, and 62 +/- 39 micro U/ml. At both 3 and 7 days, IR still increased when switching from 3.3 to 16.7 mmol/l glucose (P < 0.0003), and incubation with +/+ sera induced a significant decrease in the insulin response (P < 0.002). At 7 days, the number of dead cells (as evaluated by an enzyme-linked immunosorbent assay technique) differed significantly between control (1.2 +/- 0.3 OD units) cells, islets exposed to -/- sera (1.4 +/- 0.1), and islets coincubated with +/+ sera (1.9 +/- 0.4, P < 0.01). We conclude that prolonged exposure of human islets to sera positive for the presence of CD38Abs with [Ca(2+)](i)-mobilizing activity impairs beta-cell function and viability in cultured human pancreatic islets.     

Management of thoracic empyema in children

The effectiveness of fibrinolytic treatment has been shown in cases of thoracic empyema in adults. In pediatric patients experience is, however, very limited. The aim of this study was to determine the success and complication rates of fibrinolytic treatment in thoracic empyema in children. A series of 25 consecutive children who had loculated pleural empyemas that did not respond to tube thoracostomy and antibiotics is presented. Their ages ranged from 1 to 12 years (mean 4.2). There were 19 boys and 6 girls, and all epyemas were postpneumonic. The fibrinolytic agent used was urokinase in 17 and streptokinase in 8. The mean duration of fibrinolytic treatment was 4.3 days (range 2 to 8) and the mean duration of chest-tube drainage was 8.9 days (range 7 to 13). In 20 patients the fluid output from the chest tube increased significantly after instillation of the fibrinolytic agent, and these patients showed almost complete resolution of the effusion on chest radiograph and ultrasound examinations (80%). Only 5 patients developed complications: bronchopleural fistula and pleural thickening in 3, and recurrent effusion, multiloculation, and pleural thickening in other 2 which were managed by surgical intervention (20%). Our study suggests that intrapleural fibrinolytic treatment is an effective and safe adjunctive therapy in children with thoracic empyema and can obviate a thoracotomy in most cases. Accepted: 16 February 2001     

Reactive hyperemia of skin microcirculation in septic neonates

Reactive hyperemia after 1 min of arterial occlusion was studied in back, thigh and heel skin of 40 preterm and full-term neonates using laser Doppler flowmetry. Twelve infants had clinical signs of septicemia, but normal laboratory tests at the time of fluxmetry. However, CRP, leukocyte count and the ratio of immature to total neutrophils increased during the following days and septicemia was confirmed by positive blood cultures (septic group). Seven neonates with clinical signs of septicemia had developed neither positive blood cultures nor laboratory signs (non-septic group). Fifteen were healthy neonates. In the septic neonates, time to reach maximal hyperemia, maximum post-occlusive hyperemia and recovery time of skin perfusion were increased significantly in back and thigh skin and the heal skin temperature was decreased when compared to healthy neonates. Healthy and non-septic neonates showed no significant difference in any of the parameters. We conclude that altered reactive hyperemia in the skin may be an earlier sign of neonatal septicemia than laboratory tests.