Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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Pulmonary Impairment after Respiratory Viral Infections Is Associated with High Mortality in Allogeneic Hematopoietic Cell Transplant Recipients

Pulmonary impairment predicts increased mortality in many settings, and respiratory viral infection (RVI) causes considerable morbidity and mortality in allogeneic hematopoietic cell transplant recipients (allo-HCT). We hypothesized that pulmonary impairment after RVI, defined as a decline of forced expiratory volume in 1 second values by ≥10%, may identify allo-HCT recipients at high risk for mortality. We studied all allo-HCT recipients at our institution who had RVI with respiratory syncytial virus, parainfluenza virus, or influenza from 2004 to 2013 and had pre-RVI and post-RVI pulmonary function tests. We used competing risk regression models to identify risk factors for 2-year nonrelapse mortality (NRM) as the primary outcome after RVI and relapse-related mortality as a competing risk. From 223 eligible patients, pulmonary impairment after RVI was associated with over a 3-fold increase in 2-year NRM (pulmonary impairment, 25.3%; no impairment, 7.4%; univariate subhazard ratio [SHR], 3.9; 95% confidence interval [CI], 1.9 to 8.1; P < .001). After adjusting for age and systemic steroid use, pulmonary impairment after RVI was still associated with increased 2-year NRM (SHR, 3.3 [95% CI, 1.6 to 6.9]; P?=?.002). After adjustment for race and graft-versus-host disease (GVHD) prophylaxis, chronic GVHD at the time of RVI (odds ratio [OR], 2.8 [95% CI, 1.4 to 5.4]; p?=?.003) and lymphopenia (OR, 2.2 [95% CI, 1.1 to 4.2]; P?=?.02) were associated with increased odds of pulmonary impairment, whereas use of nonmyeloablative conditioning was associated with reduced odds of pulmonary impairment (OR, .4 [95% CI, .2 to .8]; P?=?.006). In allo-HCT recipients with RVIs, pulmonary impairment after RVI is associated with high NRM at 2years.     

Sarcomere length behaviour along single frog muscle fibres at different lengths during isometric tetani

Summary A detailed investigation of sarcomere lengthening and shortening during fixed-end tetani has been made along frog muscle fibres stretched over a large range of sarcomere lengths. A variety of sources of error common in such measurements are quantitated and give an uncertainty in sarcomere length of about 53–62 nm. The difference in sarcomere length calculated from the left and right first orders at rest was 21 nm ±16 nm and this is suggested to be a measure of Bragg artefact. The laser diffraction measurements showed that the shortening end regions decrease in size during contraction and that the magnitude of shortening is increased at greater fibre extensions. The average length change and sarcomere length of the central and end regions was 0.10 m (2.85 m) and –0.37 m (2.66 m), respectively. The sarcomere length of the end regions at the end of creep was regularly observed to be <2.1 m. An unexpected finding was the occasional observation of striations in the transition zone between lengthening and shortening regions which remained nearly isometric during a period of tension rise during creep. Measurements of diffraction order linewidth do not suggest increased sarcomere length dispersion in these areas. A smooth transition from shortening to lengthening was always observed. Although our data are in general agreement with the models proposed by Morgan, Mochon and Julian (Biophys. J. 39 (1982) 189–96) and Edman and Reggiani(J. Physiol. (Lond.) 351 (1984) 169–98), specific differences which do exist are discussed.     

Antibody-forming cell induction during an early phase of germinal centre development and its delay with ageing.

The present study was initiated to determine if an early phase of germinal centre (GC) development is associated with the generation of antibody-forming cells (AFC). Germinal centres in draining lymph nodes from immune mice were examined histochemically after secondary immunization for the presence of AFC at both the light and electron microscopic levels. Additionally, peanut agglutinin (PNA) high (Hi) GC B cells were isolated, placed in cell culture and specific antibody production was monitored at successive intervals. Electron microscopy showed that plasma cells in all stages of differentiation were present within GC at 3-5 days and to a lesser extent at 7 days following antigenic challenge. Furthermore, PNAHi GC B cells obtained between Days 3 and 5 spontaneously produced specific IgG when placed in culture. Germinal centre B cells isolated either before or after this period did not produce antibody without the addition of T-cell cytokines. Induction of AFC in GC occurred at the time when GC B cells acquire follicular dendritic cell (FDC)-derived, immune complex-coated bodies (iccosomes) and process and present this antigen to helper T cells. This suggested a causal relationship between iccosome release and AFC induction. Support for this was obtained by examination of AFC induction in aged mice where iccosome release has not been observed. Peanut agglutinin-positive GC B cells isolated from aged mice on Days 3-5 after antigen challenge failed to spontaneously produce specific antibody. Collectively, these data show that GC development 3-5 days after booster immunization results in AFC generation and suggests a role for FDC iccosomes in their induction.     

Variant histology,IgD and CD30 expression in low‐risk pediatric nodular lymphocyte predominant Hodgkin lymphoma: A report from the Children's Oncology Group

1 Background

Histologic prognostic factors have been described for nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). This study examines histologic and immunophenotypic variants in a clinical trial for pediatric NLPHL.

2 Procedure

One hundred sixty‐eight cases of localized NLPHL were examined for histologic variants, CD30 and immunoglobulin D (IgD) expression, and outcome. Histologic types were scored categorically as 0 = 0, 1 ≤ 25%, and 2 > 25% of the sample.

3 Results

Fifty‐eight (35.1%) cases showed only typical nodular with or without serpiginous histology (types A and B). The remainder showed mixtures of histologies. The numbers of patients with score 2 are 85 (50.6%) type A, 21 (12.5%) type B, 46 (27.4%) with extranodular large B cells (type C), 3 with T‐cell‐rich nodular pattern (type D), 55 (32.7%) with diffuse T‐cell‐rich (type E) pattern, and 2 (1.2%) with diffuse B‐cell pattern (type F). Higher level of types C (P = 0.048) and D (P = 0.033) resulted in lower event‐free survival (EFS). Cytoplasmic IgD was found in 65 of 130 tested (50%), did not significantly associate with EFS but positively correlated with types C and E histology (P < 0.0001) and negatively correlated with types A (P = 0.0003) and B (P = 0.006). Seventeen (10%) expressed CD30, with no adverse effect.

4 Conclusions

Variant histology is common in pediatric NLPHL, especially types C and E, which are associated with IgD expression. Type C variant histology and possibly type D are associated with decreased EFS, but neither IgD nor CD30 are adverse features. Variant histology may warrant increased surveillance, but did not affect overall survival.     

Histologic studies of human skin test responses to ragweed and compound 48/80: III. Effects of alternate-day steroid therapy

Our previous studies have shown depressed eosinophil responses in skin test reactions to pollen antigens and compound 48/80 in those just completing a 1-wk course of daily steroids. Wheal reactions were unaffected. In this study, 6 ragweed-sensitive atopic subjects were studied before and on the seventh day (“day on”) and day 8 (“day off”) of a course of alternate-day steroids. Blood neutrophil levels rose on day 7 and were similar to baseline on day 8, whereas blood eosinophil levels were significantly reduced on both days 7 and 8. Neutrophil responses in skin test reactions were depressed on day 7 and normal on day 8. In contrast, the tissue eosinophil responses were depressed significantly, and to similar degree, on both days 7 and 8. These findings are of potential significance in evaluating the clinical effects of steroids in allergic diseases.     

Radical combined treatment of locally extensive head and neck cancer in the elderly

PURPOSE: Few studies have described the effects of aggressive combined therapy for locally extensive head and neck cancer in the elderly. Our study evaluated the outcome of this particular cohort of patients after such treatments. METHODS: Survival, failure, morbidity, and complication rates were determined retrospectively in 43 elderly patients with stage III or IV head and neck cancer who underwent curative surgery and postoperative radiotherapy (n = 33) or neoadjuvant, 3-drug chemotherapy plus radiotherapy (n = 10) between the years 1977 and 1992. RESULTS: The crude survival rate at 3 years was 27% in patients managed by surgery plus radiotherapy, and 30% in individuals treated with chemoradiation; the corresponding locoregional failure rates were 23% and 30%; and the distant failure rates were 13% and 0%, respectively. The acute toxicity rate was 12% in the surgery plus radiotherapy group and 30% in the chemoradiation patients; the corresponding late complication rates were 0% and 10%. There were no toxic deaths. CONCLUSION: Radical combined treatments can be performed safely and achieve long-term, disease-free survival in selected elderly patients with locally extensive head and neck cancer.     

Fractures of the orbital floor

The charts of 324 patients treated for 363 orbital floor fractures between 1965 and 1973 were reviewed retrospectively. Of these, 38 (11 percent) were isolated floor fractures, 27 (8 percent) were rim and floor fractures, 168 (46 percent) were trimalar fractures and 130 (35 percent) were associated with complex facial fractures. On initial examination, 31 percent of the patients were found to have diplopia and 4 percent enophthalmos. Orbital prolapse was suspected in 31 percent of the patients. Thirty-seven percent of the patients had demonstrable ocular injury at the time of initial examination. Treatment was surgical in 336 of the fractures and non-surgical in 29. Of the surgical patients 140 had no support placed, 120 had antral support only, 51 had both antral support and orbital implant, and 20 had an orbital implant only. Postpperatively the incidence of diplopia was 8 percent in all patients, and 7 percent had enophthalmos. A smaller group followed for more than five months were found to have diplopia in 17 percent and enophthalmos in 11 percent. Of the 29 patients treated non-surgically, none had persistent diplopia.     

Development and current functioning in adolescents with Asperger syndrome: a comparative study

Adolescents with Asperger syndrome (AS: without delay in speech development, diagnosed according to ICD-10 clinical criteria) were compared with a group with high-functioning autism (HFA: all with delayed speech development), and a group with conduct disorder (CD). Family and genetic studies suggest that Asperger syndrome and autism form part of the same spectrum, whereas the social impairments in conduct disorder are assumed to have different origins. The aims were to explore the relationships between early speech development and other aspects of functioning in autistic disorders, and to compare autistic and nonautistic social impairments. Early and current behaviour and IQ profiles were investigated. The CD group were clearly different from both the AS and HFA groups. The AS group tended to have less severe early behavioural abnormalities than the HFA group, and were unlikely to have speech abnormalities, but other communicative, social, and restricted/ stereotyped behavioural difficulties were largely of a similar pattern to the abnormalities in the HFA group. Eighty per cent of the AS group met criteria for autism on the diagnostic algorithm associated with the Autism Diagnostic Interview-Revised. By adolescence, the AS group were reported to be as abnormal as the HFA group but in structured 1:1 interaction their conversation was better. IQ profile in the AS group showed relative strength on verbal measures, unlike the HFA group, but relatively good performance on the Block Design subtest of the WISC/WAIS was a feature of both the AS and HFA groups. The results indicate closely similar behavioural manifestations may arise by adolescence despite differences in speech development. Follow-up studies and further family investigations will be required to clarify the origins of these and other patterns of autistic development.