IgG anti-tetanus toxoid antibody synthesis by human bone marrow. I. Two distinct populations of marrow B cells and functional differences between marrow and peripheral blood B cells

This investigation uses a system for inducing and detecting anti-tetanus toxoid antibody (anti-TT) synthesis to study specific antibody (Ab) synthesis by bone marrow mononuclear cells (MC). We measured the amounts of anti-TT secreted and the number of B cells secreting antibody (Ab). The ELISA plaque detects single B cells secreting specific Ab. The results show that (1) spontaneous anti-TT secretion by MC is higher than spontaneous anti-TT secretion by peripheral blood lymphocytes (PBL) using an ELISA plaque (P<0.01); (2) spontaneous anti-TT production by MC correlated with the serum anti-TT titers as measured by an ELISA (r=0.75,P=0.005); (3) two types of marrow B cells were identified—one that spontaneously secretes anti-TT and another that produces anti-TT after TT-stimulation; (4) the frequency of anti-TT-secreting B cells is higher in MC than in PBL; (5) the amount of Ab secreted per marrow B cell is not different from that secreted by a peripheral B cell; and (6) marrow B cells could be induced to produce anti-TTin vitro up to 10 months without added cytokines. These results show that bone marrow is a major repository for differentiated B cells that spontaneously produce Abs to maintain circulating Abs titers and for memory B cells that can be induced to produce specific Ab.     

Decreased specific antibody synthesis in old adults: decreased potency of antigen-specific B cells with aging

The rise in rates of infection in adults over the age of 60 is accompanied by a decreased ability of older adults to make specific immune responses after immunization with a variety of specific antigens (Ag). This investigation delineates age-related changes in Ag-specific humoral immunity, comparing adults over age 60 to young adults aged 18-40, using tetanus toxoid (TT) as an immunologic probe. A culture system which does not require TT booster immunizations of study subjects was used to induce in vitro specific antibody responses. The amount of anti-TT antibody (Ab) produced in serum and in culture was measured by a TT-specific enzyme-linked immunosorbent assay (ELISA). The numbers of anti-TT Ab-secreting B cells were measured by a TT-specific ELISA-plaque assay. The TT-specific responses of old subjects were significantly less than that seen for young control subjects in the following measures: (1) serum anti-TT Ab titers (mean +/- S.E. log 2 titer = 3.3 +/- 1.1 vs. 9.5 +/- 1.4, P less than 0.01); (2) anti-TT Ab produced by peripheral blood lymphocytes (PBL) in cultures stimulated with TT (6 +/- 2.1 ng/ml vs. 22 +/- 8.4 ng/ml, P less than 0.01); (3) numbers of anti-TT Ab secreting B cells per million cells cultured (6.7 +/- 3.4 vs. 26.6 +/- 7.6, P less than 0.001) and (4) mean ng Ab secreted per anti-TT Ab-secreting B cell (0.6 +/- 0.4 ng vs. 12.7 +/- 7.8 ng, P less than 0.01). This study shows that both decreased numbers of Ag-specific immune B cells and decreased potency on a per cell basis contribute to the impaired immune responses to immunizations in older adults.     

Revisiting the Free Nipple Graft: An Opportunity for Nipple Sparing Mastectomy in Women with Breast Ptosis

Objective

Nipple areolar complex (NAC) sparing mastectomy improves the cosmetic outcome of patients with breast cancer. However, women with significant breast ptosis are not candidates for this technique due toexcessive skin flap length and ensuing risk of NAC ischemia.1 ^– 3 We report a novel technique using free nipple graft during skin sparing mastectomy for patients with significant ptosis while concurrently maintaining oncologic integrity.

Design

Case series.

Setting

Community and tertiary care hospital practices.

Patients

Women with breast cancer desiring NAC preservation who are otherwise candidates for nipple sparing mastectomy, but with significant breast ptosis that precludes NAC viability. All women underwent immediate, autologous breast reconstruction.

Interventions

Bilateral and unilateral free nipple grafts were harvested, placed on ice during skin sparing mastectomy and free flap reconstruction, grafted at the conclusion of the case and secured with a bolster.

Outcome Measures

Full or partial NAC preservation, ischemia time, local wound complications at NAC grafting site, pathologic outcomes.

Results

A total of three patients underwent free nipple grafting at the time of skin sparing mastectomy and free or pedicled flap for breast cancer between March and September 2012. Of five total nipple grafts, one had partial NAC loss but did not require operative debridement. Pathologic review of areolar tissue removed during intraoperative defatting of free nipple graft demonstrated residual duct epithelium.

Conclusions

Women with significant breast ptosis that would preclude them from NAC sparing mastectomy can successfully preserve their NAC using a free nipple graft. Duct epithelium present in defatted tissue during preparation of the free nipple graft suggests that oncologic integrity can also be maintained.     

Comparison of facemask and mouthpiece interfaces for multiple breath washout measurements

Background

Different interfaces (mouthpiece/nose clip vs. facemask) are used during multiple breath washout (MBW) tests in young children.

A review of cervical spine injury associated with maxillofacial trauma at a UK tertiary referral centre

IntroductionThe aim of this study was to determine the incidence and patterns of cervical spine injury (CSI) associated with maxillofacial fractures at a UK trauma centre.MethodsA retrospective analysis was conducted of 714 maxillofacial fracture patients presenting to a single trauma centre between 2006 and 2012.ResultsOf the 714 maxillofacial fracture patients, 2.2% had associated CSI including a fracture, cord contusion or disc herniation. In comparison, 1.0% of patients without maxillofacial trauma sustained a CSI (odds ratio: 2.2, p=0.01). The majority (88%) of CSI cases of were caused by a road traffic accident (RTA) with the remainder due to falls. While 8.8% of RTA related maxillofacial trauma patients sustained a CSI, only 2.0% of fall related patients did (p=0.03, not significant). Most (70%) of the CSIs occurred at C1/C2 or C6/C7 levels. Overall, 455, 220 and 39 patients suffered non-mandibular, isolated mandibular and mixed mandibular/non-mandibular fractures respectively. Their respective incidences of CSI were 1.5%, 1.8% and 12.8% (p=0.005, significant). Twelve patients with concomitant CSI had their maxillofacial fractures treated within twenty-four hours and all were treated within four days.ConclusionsThe presence of maxillofacial trauma mandates exclusion and prompt management of cervical spine injury, particularly in RTA and trauma cases involving combined facial fracture patterns. This approach will facilitate management of maxillofacial fractures within an optimum time period.     

Improvement in Breast Reconstruction Disparities following Medicaid Expansion under the Affordable Care Act

Background

 Under the Affordable Care Act, Medicaid expansion effective 1 January 2014 aimed to increase access to health care. We sought to determine the association of Medicaid expansion with disparities in utilization of breast reconstruction.

Methods

Non-Hispanic Black (NHB) and White (NHW) breast cancer patients undergoing mastectomy +/? reconstruction between 2010 and 2017 were selected from the National Cancer Database. Annual trends for utilization of breast reconstruction by race, income, and education were evaluated by Medicaid expansion status using difference-in-differences regression analyses. Medicaid expansion was categorized by expansion date as early (2010–2013), 2014 (1/2014), late (after 1/2014), or no expansion.

Results

Of 443,607 patients, 36.3% (n = 161,128) underwent reconstruction, 13.1% (n = 58,249) were NHB, 16.8% (n = 74,430) had median income < $40,227, and 17.1% (n = 75,718) were in the lowest education quartile. In non-expansion states, lower proportions of NHB patients underwent reconstruction than NHW patients in all years, with the smallest disparity (NHB% ? NHW%) (? 6.4%) in 2017. Decreases in disparities between NHB and NHW patients were seen with the smallest difference observed in 2014 (? 2.5%) in early-expansion states, in 2017 (? 0.7%) in 1/2014 expansion states, and in 2017 (? 4.5%) in late-expansion states. Similar findings for convergence of reconstruction utilization rates for the lowest two education levels and lowest two income quartiles were found with Medicaid expansion, with no convergence seen in non-expansion states over the study period.

Conclusions

Some improvement in breast reconstruction disparities followed Medicaid expansion. Failure to improve parity without Medicaid expansion should be a consideration with any modifications to Medicaid access.

     

Drug-induced thrombocytopenia is associated with increased binding of IgG to platelets both in vivo and in vitro

Thrombocytopenia is a common serious adverse effect of drug treatment. A variety of in vitro diagnostic techniques to confirm the diagnosis are available, but the majority lack sufficient sensitivity to detect all cases of drug-induced thrombocytopenia. We studied 19 patients with suspected drug-induced thrombocytopenia and demonstrated that platelet- associated IgG (PAIgG) was elevated in all at the time of thrombocytopenia, and PAIgG returned to normal levels as the thrombocytopenia resolved. In the majority of patients, the platelet count rapidly returned to normal after the drug was discontinued; however, in six patients, the thrombocytopenia persisted well beyond the period of time that the offending drug would be expected to be cleared from the blood. In 13 patients, serum obtained after recovery was used to identify the drug responsible for the thrombocytopenia in an in vitro assay. In all cases, the addition of the drug historically associated with the thrombocytopenic episode was associated with an increased binding of IgG to control platelets. For uncertain reasons, the concentration of drug required to increase the in vitro binding of IgG to test platelets was often more than the concentration usually achieved in vivo. Wider application of these techniques may provide better understanding of the clinical characteristics and mechanisms responsible for drug-induce thrombocytopenia.