Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors

Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.     

Endovascular therapy for critical limb ischemia

AbstractChronic critical limb ischemia (CLI) occurs when arterial perfusion is reduced below a threshold level that results in rest pain and/or tissue breakdown in the lower extremities. Importantly, it is associated with high cardiovascular morbidity and mortality. Without prompt revascularization, CLI may result in loss of a limb (i.e. amputation) and/or life. The goal of endovascular therapy is the re-establishment of pulsatile, straight-line flow to the distal extremity. Percutaneous transluminal angioplasty (PTA) has been shown to be effective and safe in the setting of CLI, with limb salvage rates that compare favorably with surgical procedures. Stents are indicated for failed PTA, while adjunctive therapies such as lasers, thermal angioplasty and atherectomy devices lack data demonstrating improved efficacy compared with conventional lower extremity interventions. In addition to successful revascularization, the institution of lifestyle changes, atherosclerotic risk factor modification, and pharmacologic therapies are indicated to reduce cardiovascular morbidity and mortality.     

Involvement of guanine nucleotide binding proteins in neutrophil activation and priming by GM-CSF

Pre-incubation of human neutrophils with pertussis toxin significantly inhibited the neutrophil-directed biologic actions of granulocyte- macrophage colony-stimulating factor (GM-CSF) in three separate assays: the induction of c-fos mRNA, the enhancement of both platelet- activating factor-induced mobilization of intracellular calcium, and stimulation of leukotriene synthesis by the calcium ionophore A23187. Cholera toxin did not have an effect on the latter two assays. Pre- treatment of human neutrophils with pertussis toxin did not affect the binding of GM-CSF to its surface receptor. These results provide the first evidence that a pertussis toxin substrate plays an important mediatory role in the mechanism of action of GM-CSF.     

Endoscopic ultrasound‐guided fine‐needle aspiration diagnosis of large cell neuroendocrine carcinoma of the gallbladder and common bile duct: Report of a case

Endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) allows a reliable and accurate diagnosis of neoplasms of the gallbladder and bile ducts. We report the cytopathologic findings of a case of large cell neuroendocrine carcinoma (LCNEC) of the gallbladder and extrahepatic bile ducts in a 67‐year‐old woman who presented with progressive abdominal pain and jaundice. EUS‐FNA of the mass involving the common bile duct and of a porta hepatis lymph node showed abundant cellularity with tumor cells arranged singly and occasionally in tight and loose clusters and rosette‐like structures in a background showing extensive necrotic debris. The tumor cells were predominantly plasmacytoid, showed a moderate amount of focally vacuolated cytoplasm and large round to oval hyperchromatic nuclei with prominent nucleoli, numerous mitoses, and apoptotic bodies. The differential diagnosis included poorly differentiated adenocarcinoma, lymphoma, melanoma, and poorly differentiated neuroendocrine carcinoma (NEC), large cell type. The tumor cells were strongly and diffusely positive for cytokeratin AE1/AE3, CD56, synaptophysin, and chromogranin and showed a very high proliferative fraction on Ki67 staining, supporting the diagnosis of a high‐grade NEC. Due to the large size of the neoplastic cells, moderate amounts of cytoplasm and prominent nucleoli, a diagnosis of LCNEC was made on the EUS‐FNA sample. Despite the prompt institution of chemotherapy, the patient died shortly thereafter and the diagnosis was confirmed at autopsy. This is to our knowledge the first case of LCNEC of the gallbladder and bile ducts diagnosed by EUS‐FNA. Diagn. Cytopathol. 2013;41:1091–1095. © 2012 Wiley Periodicals, Inc.     

Human papillomavirus and oral disease – emerging evidence: a review

Human papillomavirus (HPV) infections have received considerable attention in recent years. Of the 120 or so known types of the virus, some cause a variety of benign wart‐like lesions of the skin and genital and oral mucosae, whilst others are aetiologically associated with cervical and anogenital cancers. Recent epidemiologic evidence suggests that HPV may also be an independent risk factor for oropharyngeal cancer. In this context it has been suggested that HPV virus may modulate the process of carcinogenesis in some tobacco and alcohol induced oropharyngeal cancers and act as the primary oncogenic agent for inducing carcinogenesis among non‐smokers. Dental practitioners have a major role in detecting all lesions of the oral mucosa caused, or possibly caused, by HPV. This paper briefly reviews the current state of knowledge of molecular and clinical aspects of HPV infections of the oral mucosa.     

Comparision of blood loss between computer assisted and conventional total knee arthroplasty

Background:

Bleeding during total knee arthroplasty (TKA) can cause significant morbidity and mortality. One proposed benefit of computer assisted TKA is decreased bleeding as the femoral canal is not invaded. This study assessed blood loss between computer assisted surgery (CAS) and conventional TKA.

Materials and Methods:

73 consecutive patients (37 males, 36 females) underwent primary TKA between 2006 and 2009. Thirty eight patients underwent navigated TKA and 35 underwent conventional TKA for symptomatic osteoarthritis of the knee. These patients were matched for age, gender, and body mass index (BMI). Average age was 70.3 years (range 47-91 years). Mean BMI was 30 (range 17-49). Average preoperative hemoglobin was 13.26 g/dL (range 8.7-18.4 g/dL) in the navigated group and 13.47 g/dL (range 9.6-15.8 g/dL) in the conventional group (P = 0.9). Average tourniquet time was 110 min (range 90-150 min) in the navigated group and 96.7 min (range 60-145 min) in the conventional group (P = 0.77).

Results:

Average postoperative hemoglobin in the navigated group was 10.34 g/dL (range 7.5-14.8 g/dL) and in the conventional group was 10.03 g/dL (range 7.5-12.2 g/dL) (P = 0.17). Six patients in both groups required blood transfusions. The mean drain collection was 599 mL (range 150-1370 mL) in the navigated group and 562 mL (range 750-1000 mL) in the conventional group (P = 0.1724). These results suggest that there is no significant reduction in blood loss in CAS TKA.

Conclusion:

These results suggest that there is no significant difference in blood loss in CAS TKA and conventional TKA. This study also highlights the heterogeneity of methods used in studies related to CAS TKA. We believe that there is a need for a large multicenter prospective randomized controlled trial to be performed before a consensus can be reached on the influence of CAS techniques on blood loss during primary TKA.