Protection of killer antiidiotypic antibodies against early invasive aspergillosis in a murine model of allogeneic T-cell-depleted bone marrow transplantation

Antiidiotypic monoclonal antibodies (MAbs) representing the internal image of a yeast killer toxin (KT) have therapeutic potential against several fungal infections. The efficacy of KT MAbs against Aspergillus fumigatus was investigated in a mouse model of T-cell-depleted allogeneic bone marrow transplantation (BMT) with invasive pulmonary aspergillosis. Mice were highly susceptible to infection at 3 days post-BMT, when profound neutropenia was observed both in the periphery and in the lungs. Treatment with KT MAbs protected the mice from infection, as judged by the long-term survival and decreased pathology associated with inhibition of fungal growth and hyphal development in the lungs. In vitro, similar to polymorphonuclear neutrophils, KT MAbs significantly inhibited the hyphal development and metabolic activity of germinated Aspergillus conidia. These results indicate that mimicking the action of neutrophils could be a strategy through which KT MAbs exert therapeutic efficacy in A. fumigatus infections.     

Homozygosity for human leucocyte antigen-C ligands of KIR2DL1 is associated with increased risk of relapse after human leucocyte antigen-C-matched unrelated donor haematopoietic stem cell transplantation

Human leucocyte antigen (HLA)-C molecules regulate the function of natural killer cells and may be subdivided into two groups, C(1) and C(2), based on their specificity for inhibitory killer immunoglobulin-like receptors. We analysed the impact of the HLA-C genotype on outcome of HLA-C-matched unrelated donor haematopoietic stem cell transplantation (URD-HSCT) recipients. HLA-C(2) homozygous patients (n = 18) had lower probability of overall survival (P = 0.01) and disease-free survival (P = 0.02), resulting from increased relapse rate (P = 0.02) when compared with both HLA-C(1) homozygous (n = 43) and HLA-C(1),C(2) heterozygous (n = 50) subgroups. Patients lacking HLA-C(1) should, therefore, be considered at increased risk of relapse following HLA-C-matched URD-HSCT.     

Gallstone prevalence and gallbladder volume in children and adolescents: an epidemiological ultrasonographic survey and relationship to body mass index

To assess the prevalence of gallstone disease and the behavior of gallbladder (GB) volume in childhood and adolescence, an ultrasonographic survey was carried out on 1570 subjects (age range 6-19 yr). Entered in the study were 750 males and 752 females (attendance rate, 95.7%). Gallstones were detected in two females aged 13 and 18 yr, respectively. None of the subjects in the study population had undergone cholecystectomy. The overall prevalence of gallstone disease was equal to 0.13% (0.27% in the female sex). A positive family history for biliary calculous disease was present in one of the two lithiasic girls. A progressive increase of GB volume with age was observed in both sexes, and figures were greater in males, than in age-matched females. A positive and statistically significant relationship was found between GB volume and body mass index (BMI) in both sexes. Obesity was recognized in 188 males (25.3%) and 167 females (25.0%). Obese subjects exhibited larger GB volumes than the nonobese age- and sex-matched controls. The study supports the view of a very low prevalence of gallstone disease in people younger than 20. It also provides information on GB size in relation to age, sex, and BMI.     

The EBMT activity survey: 1990-2010

A total of 654 centers from 48 countries were contacted for the 2010 survey. In all, 634 centers reported a total of 33?362 hematopoietic SCT (HSCT) with 30?012 patients receiving their first transplant (12?276 allogeneic (41%) and 17?736 autologous (59%)). Main indications were leukemias: 9355 (31%; 93% allogeneic), lymphoid neoplasias specifically Non Hodgkin's lymphoma, Hodgkin's lymphoma and plasma cell disorders: 17?362 (58%; 12% allogeneic), solid tumors: 1585 (5%; 6% allogeneic) and non-malignant disorders: 1609 (6%; 88% allogeneic). There were more unrelated donors than HLA-identical sibling donors (53% versus 41%); the proportion of peripheral blood as stem cell source was 99% for autologous and 71% for allogeneic HSCT. Cord blood was primarily used in allogeneic transplants (6% of total) with three autologous cord blood HSCT being reported. The number of transplants has increased by 19% since 2005 (allogeneic 37% and autologous 9%) and continued to increase by about 1100 HSCT per year since 2000. Patterns of increase were distinct and different. The data show the development of transplantation in Europe since 1990, with the number of patients receiving a HSCT increasing from 4200 to over 30?000 annually. The most impressive trend seen is the steady increase of unrelated donor transplantation, in parallel to the availability of unrelated donors through donor registries.     

Postgrafting administration of granulocyte colony-stimulating factor impairs functional immune recovery in recipients of human leukocyte antigen haplotype-mismatched hematopoietic transplants

In human leukocyte antigen haplotype-mismatched transplantation, extensive T-cell depletion prevents graft-versus-host disease (GVHD) but delays immune recovery. Granulocyte colony-stimulating factor (G-CSF) is given to donors to mobilize stem cells and to recipients to ensure engraftment. Studies have shown that G-CSF promotes T-helper (Th)-2 immune deviation which, unlike Th1 responses, does not protect against intracellular pathogens and fungi. The effect of administration of G-CSF to recipients of mismatched hematopoietic transplants with respect to transplantation outcome and functional immune recovery was investigated. In 43 patients with acute leukemia who received G-CSF after transplantation, the engraftment rate was 95%. However, the patients had a long-lasting type 2 immune reactivity, ie, Th2-inducing dendritic cells not producing interleukin 12 (IL-12) and high frequencies of IL-4- and IL-10-producing CD4(+) cells not expressing the IL-12 receptor beta(2) chain. Similar immune reactivity patterns were observed on exposure of donor cells to G-CSF. Elimination of postgrafting administration of G-CSF in a subsequent series of 36 patients with acute leukemia, while not adversely affecting engraftment rate (93%), resulted in the anticipated appearance of IL-12-producing dendritic cells (1-3 months after transplantation versus > 12 months in transplant recipients given G-CSF), of CD4(+) cells of a mixed Th0/Th1 phenotype, and of antifungal T-cell reactivity in vitro. Moreover, CD4(+) cell counts increased in significantly less time. Finally, elimination of G-CSF-mediated immune suppression did not significantly increase the incidence of GVHD (< 15%). Thus, this study found that administration of G-CSF to recipients of T-cell-depleted hematopoietic transplants was associated with abnormal antigen-presenting cell functions and T-cell reactivity. Elimination of postgrafting administration of G-CSF prevented immune dysregulation and accelerated functional immune recovery.     

Communicating hydrocephalus induced by mechanically increased amplitude of the intraventricular cerebrospinal fluid pulse pressure: rationale and method

To elucidate some of the brain stem mechanisms involved in tongue motility, extracellular microelectrode recordings were made from single neurons in the region of the hypoglossal nucleus in 10 decerebrate and 23 anesthetized (chloralose) adult cats. The antidromic response characteristics and the synaptically evoked responses of 71 motoneurons that supplied tongue protrusive (P) or retrusive (R) muscles were documented. Protrusive motoneurons could be synaptically excited by temporomandibular joint (TMJ), glossopharyngeal (IX), and/or superior laryngeal (SLN) nerve stimuli, whereas R motoneurons could be activated by lingual and/or IX nerve stimulation. Conditioning effects revealed that the inhibition of the antidromic responses was shorter in duration than the inhibitory effects noted when synaptically evoked responses were conditioned. Conditioning stimuli delivered to the lingual, TMJ, IX, and SLN nerves were most effective in inhibiting the synaptically evoked responses of P and R motoneurons for conditioning-test intervals of as much as 400 ms. Those conditioning stimuli which also could synaptically activate a motoneuron tended to facilitate the cell's synaptically evoked responses at conditioning-test intervals of about 10 ms, whereas conditioning stimuli which did not synaptically activate the cell resulted in only the long-lasting inhibition.     

Metopic craniosynostosis. Surgical results in 35 surgically treated cases under 1 year of age

The clinical features, the diagnostic findings and the surgical results obtained on 35 children, under 1 year of age, operated on because of an early synostosis of the metopic suture are presented. In 79% of cases, the diagnosis was obvious at birth. A M/F ratio of 2.0 was observed in this series. Associated malformations were recorded in eleven patients (30.5%). The surgical procedure consisted of bilateral frontal craniectomy, opening of the roof of the orbit, advancement of the superior orbital margin, and repositioning of the frontal flaps after 180 degrees rotation. The cosmetical correction was satisfactory even in the immediate postoperative period. No mortality was recorded. The surgical correction was followed by a normal psychomotor development in 33 cases; delayed milestones were recorded in 2 children in whom the metopic synostosis was part of a complex malformative syndrome. On the grounds of our results, the young age of the patients at the operation should not be regarded as an obstacle to the immediate surgical correction; in our advice, the early correction results also in better functional and cosmetic long-term outcomes.     

The value of CSF flow studies in infants with communicating hydrocephalus

The authors describe their technique of dynamic CSF scanning utilizing the radionucleide material Tc-99m diethylentriamine-pentacetic acid (DTPA). Thirty-four infants with macrocephaly and enlarged intracranial CSF spaces were investigated with this technique. The resulting studies were graded according to severity. The grading scheme was of value in determining which patients would benefit from a CSF diversionary shunt.