Femoroacetabular Impingement as a Complication of Acetabular Fracture Fixation

Case We present the case of a thirteen-year-old female who sustained a posterior wall acetabular fracture dislocation. She underwent urgent closed reduction and subsequent uncomplicated open reduction and internal fixation. Post reduction computed tomography demonstrated a concentrically reduced hip joint with no evidence of femoroacetabular impingement (FAI). She subsequently healed her fracture and returned to running activities; however, one year later presented with aching pain in her thigh. Radiographs demonstrated the development of a large osseous prominence on her anterolateral femoral neck consistent with femoroacetabular impingement. Based on these findings she was evaluated by a hip preservation specialist. She subsequently underwent successful hip arthroscopy for labral repair and femoral osteochondroplasty. She was eventually able to return to running sports with little pain. Summary We present a case of FAI presenting as a complication of acetabular fracture fixation. This should be discussed with patients presenting with traumatic hip dislocations as a possible complication of surgical fixation or possibly of the injury itself

Children with hyperdiploid but not triple trisomy (+4,+10,+17) acute lymphoblastic leukemia have an increased incidence of extramedullary relapse on current therapies: A single institution experience

To evaluate the outcome of children with high hyperdiploid acute lymphoblastic leukemia (hHDALL) treated at the author's institution. One hundred thirty-five consecutive children with B-precursor ALL were diagnosed between 1991 and 2002: 38 (28.1%) hHDALL and 97 (71.9%) non-hHDALL. In the hHDALL group, 11/38 (28.9%) relapsed at a median interval of 2.8 years (range: 0.8–5.0 years) with 9/11 relapses occurring at the end or after the completion of therapy. Three (27.3%) relapses were isolated hematopoietic (BM), while eight (72.7%) were either isolated extramedullary (EM) relapses ( n = 6; Testis: 4; CNS: 2) or combined hematopoietic and extramedullary relapses ( n = 2; BM + CNS: 1; BM + Testis: 1). For the non-hHDALL group, 29/97 (29.9%) relapsed. Unlike the hHDALL group, the non-hHDALL group experienced hematopoietic relapses (62%; n = 18) more frequently than isolated extramedullary (27.5%; n = 8: Testis: 1; CNS: 7) or combined hematopoietic and extramedullary relapses (10.3%; CNS + BM: 3), with 24/29 (82.8%) of the relapses occurring on therapy. Relapses in hHDALL frequently involved EM sites ( P = 0.053). Presence of triple trisomy of +4,+10,+17 at diagnosis had a protective effect against relapse ( P < 0.05). Five-year EFS for the hHDALL and non-hHDALL patients was similar, 70.5 ± 7.5% and 66.4 ± 4.9%, respectively. Five-year OS for the hHDALL patients was significantly higher than for the non-hHDALL patients, 92 ± 4.5% vs. 74.1 ± 4.5%, P = 0.038. Biologically significant differences exist between relapse patterns of hHDALL and non-hHDALL cases related to relapse sites and time periods when relapses occur. hDALL relapses continue to be chemo-sensitive. Am. J. Hematol., 2008. © 2007 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57520/1/21011_ftp.pd

Defective Erythrocyte Pyruvate Kinase with Impaired Kinetics and Reduced Optimal Activity

A unique mutant form of erythrocyte pyruvate kinase has been found associated with chronic haemolytic anaemia in a child who is apparently doubly heterozygous for the mutant isoenzyme and for pyruvate kinase deficiency of the classical quantitative type. Clinical and laboratory findings conformed closely to those typically observed in homozygous pyruvate kinase deficiency anaemia. Assayed in fresh haemolysates, the isoenzyme exhibited reduced optimal activity ( c 45% of normal) and an increased Michaelis constant for phosphoenolpyruvate (four to five times greater than normal). The kinetic anomaly was only partially corrected by activation with fructose-1,6-disphosphate. Despite some common characteristics, this isoenzyme appears distinct from others reported in the literature and lends support to the polymorphous nature of heritable baemolytic anaemias secondary to defective pyruvate kinase.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73844/1/j.1365-2141.1972.tb05713.x.pd

Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation

We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN

Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes

Purpose of reviewThe purpose of this review is to summarize pathogenic mechanisms and clinical implications of the most illustrative genetic entities of congenital neutropenia syndromes.Recent findingsCongenital neutropenia comprise monogenetic entities with or without additional immunologic and extrahaematopoietic syndromatic features. Continuous careful explorations of known entities such as ELANE, GFI1, HAX1, G6PC3 deficiency and XLN help to define principles controlling differentiation and function of neutrophil granulocytes. Furthermore, the identification of novel genetic defects associated with congenital neutropenia, such as VPS45 deficiency, broadens our understanding of neutrophil biology. Pathogenic mechanisms imply protein and vesicle mistrafficking, endoplasmic reticulum stress, the unfolded protein response, destabilization of the mitochondrial membrane potential, disturbed energy metabolism, dysglycosylation and deregulated actin polymerization.SummaryAdvanced genetic and biochemical techniques have helped to expand our knowledge of congenital neutropenia syndromes. Known and novel genetic entities shed light on fundamental biological processes important for the homeostatis and functioning not only of the neutrophil granulocyte but as well of the entire haematopoietic system. Furthermore, treatment decisions become more tailored and might pave the road towards personalized molecular medicine

Problem of “false positive” conclusions in genetic epidemiology: Lessons from the leukemia cluster near the sellafield nuclear installation

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/38505/1/1370110302_ftp.pd

Species-Specific Therapy of Acute Lymphoid Leukemia

Forty years ago, Farber and associates described temporary remissions of acute leukemia in children produced by folic acid antagonists [13]. This ignited the hope that this most frequent and always fatal childhood cancer might be curable by drugs. Twenty years ago, Aur and as-sociates completed accession of patients to total therapy study V, the first treat-ment protocol to result in 50 % cure of acute lymphoid leukemia (ALL) [3]. Their results stand 20 years later (Fig. 1), and have been reproduced throughout the world in many thousands of children [6]. More important, recent national vital statistics of the United States and the United Kingdom indicate a 50 % reduc-tion in childhood leukemia mortality [4, 29]. Further, the cured children generally enjoy a normal life-style without need for medication. In the past 20 years, efforts have been directed at improving the cure rate of ALL while simplifying curative treat-ment, reducing its side effects, and im-proving its availability and accessibility. In a Stohlman Lecture at Wilsede 10 years ago the following statement was made [32]:- The most significant opportunity for improving the treatment of acute lymphoid leukemia in the past five years has been its biological and clini-cal classification by immunological cell surface markers. This allows spe-cies identification of the leukemia cells, the first step toward developing specific cytocidal or cytostatic therapy