High-dose intravenous gammaglobulin in alloimmunized platelet transfusion recipients

High-dose intravenous gammaglobulin (polyvalent immunoglobulin G) has been shown to be of benefit in some patients with immune thrombocytopenic purpura (ITP), possibly by producing reticuloendothelial system blockade. We studied this approach in patients refractory to random donor platelet transfusion using an IV IgG preparation manufactured by the Swiss Red Cross. Eleven adult patients with acute leukemia received either 0.4 g IgG/kg/d intravenously X five days (four patients) or 0.6 g/kg/d X five days (seven patients). All patients had high levels of lymphocytotoxic antibody and poor responses to random donor platelets. Except for mild headaches in two patients, there were no side effects related to the IgG infusions. All patients had significant elevations of serum IgG on the day after completion of treatment. Either random donor or partially HLA-matched platelet transfusions were administered the day after and, in some cases, during the IgG therapy. No patient had an improvement in one hour posttransfusion platelet count increments. Two additional patients received pooled platelet concentrates incubated for 30 minutes at 37 degrees C with IgG at a final concentration of 3 g% prior to transfusions. These results indicate that high-dose IgG, an extremely expensive treatment, cannot be recommended for alloimmunized adults with leukemia.     

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.     

Three‐dimensional synaptic analyses of mitral cell and external tufted cell dendrites in rat olfactory bulb glomeruli

Recent studies have suggested that the two excitatory cell classes of the mammalian olfactory bulb, the mitral cells (MCs) and tufted cells (TCs), differ markedly in physiological responses. For example, TCs are more sensitive and broadly tuned to odors than MCs and also are much more sensitive to stimulation of olfactory sensory neurons (OSNs) in bulb slices. To examine the morphological bases for these differences, we performed quantitative ultrastructural analyses of glomeruli in rat olfactory bulb under conditions in which specific cells were labeled with biocytin and 3,3′‐diaminobenzidine. Comparisons were made between MCs and external TCs (eTCs), which are a TC subtype in the glomerular layer with large, direct OSN signals and capable of mediating feedforward excitation of MCs. Three‐dimensional analysis of labeled apical dendrites under an electron microscope revealed that MCs and eTCs in fact have similar densities of several chemical synapse types, including OSN inputs. OSN synapses also were distributed similarly, favoring a distal localization on both cells. Analysis of unlabeled putative MC dendrites further revealed gap junctions distributed uniformly along the apical dendrite and, on average, proximally with respect to OSN synapses. Our results suggest that the greater sensitivity of eTCs vs. MCs is due not to OSN synapse number or absolute location but rather to a conductance in the MC dendrite that is well positioned to attenuate excitatory signals passing to the cell soma. Functionally, such a mechanism could allow rapid and dynamic control of OSN‐driven action potential firing in MCs through changes in gap junction properties. J. Comp. Neurol. 525:592–609, 2017. © 2016 Wiley Periodicals, Inc.     

Toxigenic Escherichia coli associated with sudden infant death syndrome

The role of Escherichia coli as a cause of sudden infant death syndrome was investigated prospectively. Strains of E. coli producing the heat labile enterotoxin (LT) or the Vero-cell cytotoxin (VT) were isolated from the intestinal contents of 21/46 infants who died from sudden infant death syndrome (SIDS). None were found in the contemporaneously sampled faeces of 24 normal live infants in the same area. Live infants were used as controls in the absence of dead infants who had not died of SIDS. This high incidence of toxigenic E. coli among the SIDS infants versus the low incidence in controls, together with the general rarity of finding such toxigenic E. coli in the community of a temperate developed country, made us conclude that there may be a causal relationship between toxigenic E. coli and SIDS. The O and H serotypes of the toxigenic E. coli associated with SIDS infants tended not to be those normally considered to be toxigenic. The toxigenicity appeared to be relatively labile. It is suggested that SIDS may be associated with the infant either acquiring these unusual types of E. coli or more likely that its normal resident E. coli acquire the plasmids to produce these toxins.     

Topical corticosteroids in psoriasis: strategies for improving safety

Corticosteroids are a mainstay of topical therapy for psoriasis. While efficacious and relatively safe when used carefully, the potential for side effects, notably skin atrophy and adrenal suppression, have been associated with excesses in potency, prolonged or widespread use. The International Psoriasis Council Working Group on Topical Therapy has reviewed the efficacy and safety of topical corticosteroids and recommends strategies for safe, long‐term use of these agents.     

The Fate of the Remaining Knee(s) or Hip(s) in Osteoarthritic Patients Undergoing a Primary TKA or THA

The purpose of this study was to determine the fate of the remaining hip(s) and knee(s) following an initial total hip or knee arthroplasty in 5352 patients with idiopathic osteoarthritis who were followed for a minimum ten years (mean 17.8 ± 5.7 years). Following an initial primary TKA, 46.0% of patients had a contralateral TKA, 2.3% had an ipsilateral THA and 1.3% had a contralateral THA. Following an initial primary THA, 30.5% of patients had a contralateral THA, 6.8% had an ipsilateral TKA and 2.9% had a contralateral TKA. Cox regression analysis demonstrated that BMI was the sole risk factor for a second THA, but both age less than sixty years and a higher BMI were significant factors for patients requiring an additional primary TKA.     

Numerical study of blood flow in an anatomically realistic aorto-iliac bifurcation generated from MRI data.

Magnetic resonance imaging and computational fluid dynamics (CFD) have been used in combination to simulate flow patterns at the human aorto-iliac bifurcation. Vascular anatomy was reconstructed from stacked two-dimensional (2D) time-of-flight images, and revealed asymmetric, nonplanar geometry with curvature in the abdominal aorta and right iliac artery. The left iliac artery was straight and exhibited a smaller take off angle than the right iliac artery. The anatomical reconstruction was used to generate a computational mesh and obtain CFD predictions of flow and wall shear stress (WSS) within the region of interest. The dynamic boundary conditions necessary were specified by 2D cine phase contrast measurements of velocity profiles in each component vessel. Predicted flow patterns were in good quantitative agreement with experiment and demonstrated major differences in WSS distributions between the iliac arteries. This noninvasive approach has considerable potential to evaluate local geometries and WSS as risk factors for arterial disease in individual subjects.     

Cystic fibrosis and the phenotypic expression of autosomal dominant polycystic kidney disease

Recent experiments in cultured cyst epithelial cells from kidneys of patients with autosomal dominant polycystic kidney disease (ADPKD) have shown that the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) is present in the apical surface of these cells and mediates chloride (Cl-) and fluid secretion in vitro. To determine whether the presence of CF with the expression of mutated CFTR proteins modifies cyst formation in ADPKD, we studied a large family with both inherited diseases. ADPKD in this family is linked to PKD1. The family is composed of 26 members; 11 members with ADPKD, 4 members with CF, and 2 members with both diseases. Renal volumes measured by computerized tomography (CT), calculated creatinine clearances, and other clinical parameters in the family members with ADPKD and CF were compared with those in the family members with ADPKD alone, as well as to a large population of patients with ADPKD. The patients with CF and ADPKD, but not the CF heterozygote carriers with ADPKD, had less severe polycystic kidney and liver disease, as indicated by normal renal function; smaller renal volume, even when corrected for height and body surface area; and the absence of hypertension and liver cysts. These observations suggest that the coexistence of CF may reduce the severity of ADPKD.