Efficacy of Performing Red-Cell Antibody Elutions in Patients with a Positive Direct Antiglobulin Test

Red blood cell antibody elutions are often routinely performed whenever a positive direct antiglobulin test (DAT) is encountered. To evaluate the efficacy of performing routine red-cell elutions we reviewed our antibody elution data. Of 122 eluates, 83 were negative, 35 were warm panagglutinins, 2 were felt to be transfusion-induced alloantibodies, 1 was passively acquired anti-A, and 1 was inconclusive. One of the eluted alloantibodies was not demonstrable in the serum. Thus, only 1 (0.8%) of the eluates provided important information not readily available through serum testing alone. We conclude that extensive serologic evaluation of a positive DAT should be reserved for those patients who have been recently transfused or are suspected of having immune hemolysis.     

Relationships between independence level of single motor-FIM items and FIM-motor scores in patients with hemiplegia after stroke: an ordinal logistic modelling study.

OBJECTIVE: To assess the relationships between independence levels of single motor-related Functional Independence Measure (FIM) items and summed FIM-motor scores of patients with hemiplegia after stroke. DESIGN: For each patient FIM scores were assessed 4 times during hospitalization. Ordinal logistic analyses were performed on group data. SUBJECTS: Fifty patients with hemiplegia after stroke staying in a long-term rehabilitation facility. RESULTS: Analyses revealed that FIM-motor scores accounted for much of the variability of independence levels for most of the single FIM items, including dressing upper body, and transfers to bed/chair/wheelchair and to toilet. For these items, the independence levels were proportionally associated with FIM-motor scores. For eating, higher FIM-motor scores (>60) were associated with modified independence and lower FIM-motor scores (<40) correlated with attainment of supervision/set-up levels. For dressing lower body, greater independence was apparent when FIM-motor scores were higher (>60). CONCLUSION: For single FIM items, relative difficulty was comparable with results from previous literatures using Rasch analyses. Moreover, our results revealed that relative difficulty for single items varied greatly between independence levels. With regard to disability task targets, probability of independence evaluated from logistic modelling is an aid to efficient rehabilitation scheduling.     

Phenotypic effects of null and haploinsufficiency of acid-labile subunit in a family with two novel IGFALS gene mutations

CONTEXT: IGF-I deficiency may result from impairment of GH secretion or action, or from defects in IGF-I synthesis, transport, or action. Complete deficiency of the acid-labile subunit (ALS), previously described in two male patients, the only known inherited alteration in IGF-I transport, is characterized by severe circulating IGF-I and IGF binding protein (IGFBP)-3 deficiency with only mild growth retardation. OBJECTIVE: Our objective was to study the characterization, at biochemical and molecular levels, of the cause for severe circulating IGF-I and IGFBP-3 deficiency in a male patient with mild growth retardation. PATIENTS: We report an adolescent male with delayed growth and pubertal development (Tanner stage I, -2.00 sd score for height at the age of 15.3 yr), profound circulating IGF-I and IGFBP-3 deficiency, and poor response to GH treatment. RESULTS: The index case, as well as one of his brothers, and his sister were found to be compound heterozygotes for two novel IGFALS gene mutations: C540R, a missense point mutation; and S195_197Rdup, a 9-bp duplication. The parents and youngest brother were found to be carriers for one of these two mutations. The three affected siblings had marked reduction of IGF-I and IGFBP-3 levels, undetectable serum levels of ALS, inability to form ternary complexes, and moderate insulin resistance. All of them attained a normal near-adult height (between -1.0 and -0.5 sd score), which was nonetheless lower than that of their heterozygous brother. The IGF system was only modestly affected in the heterozygous carriers. CONCLUSIONS: This study confirms the critical role of ALS in forming ternary complexes and the maintenance of normal levels of IGF-I and IGFBP-3. Insulin resistance, pubertal delay in male patients, and poor GH responsiveness seem to be frequent findings in ALS deficiency. However, haploinsufficiency of the IGFALS gene has no discernible clinical effects with only modest impact on the IGF system.     

The Importance of Flaps in Reconstruction of Locoregionally Advanced Lateral Skull-base Cancer Defects: a Tertiary Otorhinolaryngology Referral Centre Experience

BackgroundThe aim of the study was to identify the value of extensive resection and reconstruction with flaps in the treatment of locoregionally advanced lateral skull-base cancer.Patients and methodsThe retrospective case review of patients with lateral skull-base cancer treated surgically with curative intent between 2011 and 2019 at a tertiary otorhinolaryngology referral centre was made.ResultsTwelve patients with locoregionally advanced cancer were analysed. Lateral temporal bone resection was performed in nine (75.0%), partial parotidectomy in six (50.0%), total parotidectomy in one (8.3%), ipsilateral selective neck dissection in eight (66.7%) and ipsilateral modified radical neck dissection in one patient (8.3%). The defect was reconstructed with anterolateral thigh free flap, radial forearm free flap or pectoralis major myocutaneous flap in two patients (17.0%) each. Mean overall survival was 3.1 years (SD = 2.5) and cancer-free survival rate 100%. At the data collection cut-off, 83% of analysed patients and 100% of patients with flap reconstruction were alive.ConclusionsFavourable local control in lateral skull-base cancer, which mainly involves temporal bone is achieved with an extensive locoregional resection followed by free or regional flap reconstruction. Universal cancer registry should be considered in centres treating this rare disease to alleviate analysis and multicentric research.Key words: temporal bone, microsurgery, parotid region, free tissue flaps, neoplasm staging, ear     

An examination of ethical issues raised in the pretreatment of normal volunteer granulocyte donors with granulocyte colony-stimulating factor.

OBJECTIVE: To explore some of the ethical issues surrounding the administration of granulocyte colony-stimulating factor (G-CSF) to healthy individuals for the purpose of retrieval of granulocytes. DESIGN: Review of the historical precedent of drug administration to normal blood donors and review of the literature concerning the side effects of G-CSF administration to healthy individuals, particularly as related to granulocyte collection. We identify and discuss some of the ethical questions regarding this issue. RESULTS: Although the short-term side effects of G-CSF use in normal donors are generally felt to be benign, little is known about the long-term side effects. Ethical questions regarding the administration of this drug to normal donors for the purpose of collecting large numbers of granulocytes include the following: Does the potential benefit to a patient/recipient justify the unknown risks to the medicated granulocyte donor? Who should act as an advocate for donors so that their best interests are protected? What is the role and quality of informed consent for donors undergoing G-CSF administration? Is monetary compensation appropriate for donors administered G-CSF as part of a research protocol? CONCLUSIONS: We recommend the establishment of a donor registry to collect the needed data on the side effects of G-CSF on normal donors. Until adequate data are collected, the use of G-CSF and similar agents in normal donors should be regarded as experimental and subject to review by institutional review boards.     

Growth stimulation of primary B cell precursors by the anti-phosphatase Sbf1

SET binding factor 1 (Sbf1) was originally discovered by virtue of its interaction with a highly conserved motif (the SET domain) of unknown function in the protooncoprotein homolog of Drosophila trithorax, Hrx. Sbf1 shares extensive sequence similarity with myotubularin, a dual specificity phosphatase (dsPTPase) that is mutated in a subset of patients with inherited myopathies. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several evolutionarily conserved amino acid changes in its structurally preserved catalytic pocket. Thus, Sbf1 has features of an anti-phosphatase that could competitively antagonize dsPTPases; however the in vivo role for such factors remains unknown. Given its ability to physically interact with Hrx, a developmental regulator subject to translocation-induced mutations in B cell precursor leukemias, the current studies were undertaken to assess the effects of Sbf1 on lymphopoiesis. After infection with recombinant Sbf1 retroviruses, bone marrow cells were plated under Whitlock-Witte conditions for long-term culture of B lineage cells. Sbf1-expressing cells rapidly dominated the cultures resulting in clonal outgrowths of B cell progenitors that retained a dependence on their primary bone marrow-derived stroma for continuous growth in vitro. Structure/function analyses demonstrated that the SET interaction domain of Sbf1 was necessary and sufficient for growth alterations of B cell progenitors. These observations support a model in which Sbf1 functions as a SET domain-dependent positive regulator of growth-inducing kinase signaling pathways that impinge on SET domain proteins. SET domain-dsPTPase interactions appear to be critically important for regulating the growth properties of B cell progenitors.     

Antibodies against animal growth hormones appearing in patients treated with human growth hormone: their specificities and influence on growth velocity

The appearance of anti-human growth hormone (hGH) and anti-non-hGHs antibodies in 27 patients with idiopathic hypopituitarism, treated for periods of 6-18 months with three different preparations of hGH, was investigated. The preparations induced antibodies to GH in 21 out of the 27 patients: 10 patients produced exclusively an anti-non-hGH response, whereas 11 generated both anti-non-hGH and anti-hGH antibodies. The levels of antibodies against hGH had low correlation with decreased growth velocity, whereas those for the antibodies against non-hGHs did not correlate with decreased growth velocity.