Effect of cell concentration on bone marrow and peripheral blood stem cell cryopreservation

The effects of cell concentration during cryopreservation on bone marrow (BM) or peripheral blood (PB)-derived hematopoietic progenitor cells have not been described. The much greater numbers of cells harvested for autologous PB stem cell (PBSC) transplantation requires that the cells be frozen at higher cell concentrations, or in much greater volumes, compared with BM. We cryopreserved 108 PBSC collections from 30 patients at an average (+/- SD) cell concentration of 3.7 +/- 1.9 x 10(8) nucleated cells per mL in 127 +/- 45 mL. The proportion of mononuclear cells was 52.9% +/- 27.2%. The products also contained 2.9 +/- 2.1 x 10(9) platelets/mL and an average red cell proportion of 12.9% +/- 7.2%. The nucleated cell recovery after thawing was 75.4% +/- 13.0%. The nucleated cell concentration during freezing was not predictive for the postthaw recoveries of nucleated cells (P = .38), granulocyte-macrophage colony-forming unit (P = .06) or CD34+ cells (P = .54), or for the viability of mononuclear cells (P = .81). The platelet and red cell concentrations similarly were not predictive for these endpoints. Samples (3 BM, 7 PBSC) from 10 patients were simultaneously cryopreserved at two-fold, and from 5 additional patients (PBSC) at 6- to 24-fold differing cell concentrations. A lower recovery of erythroid burst forming unit was found for samples frozen at higher cell concentrations (P = .04), but no significant differences were found in the other endpoints listed above. The average cell concentration during freezing for each patient's PBSC collections (n = 34 patients) did not predict time to achieve a PB count of > 500 granulocytes/microL (P = .51) or platelet transfusion independence (P = .39). Patients achieved these endpoints of engraftment at medians of 12 and 13 days, respectively. The infusion of these products was generally well tolerated. Similarly, the cell concentration at which BM cells were frozen did not predict for the duration of granulocyte (P = .63) or platelet (P = .36) aplasias for 54 patients undergoing autologous BM transplantation. These data suggest that PBSC or BM cells collected for transplantation may be cryopreserved at very high cell concentrations without loss of engraftment potential or undue infusion-related toxicity.     

Marrow transplantation for chronic myelocytic leukemia: a controlled trial of cyclosporine versus methotrexate for prophylaxis of graft- versus-host disease

Forty-eight patients with chronic myelocytic leukemia, aged 11 to 47, were treated with high-dose cyclophosphamide and fractionated total body irradiation, followed by infusion of marrow from HLA-identical siblings. They were randomized to receive either methotrexate (MTX) (n = 23) or cyclosporine (CSP) (n = 25) as postgrafting prophylaxis for graft-v-host disease (GVHD). All patients had evidence of sustained hematopoietic engraftment. Seventeen of the 25 patients receiving CSP and 17 of the 23 patients receiving MTX are alive between one and almost four (median, 1.7) years, with an actuarial survival rate at three years of 62% and 66%, respectively (P = .60). Also, with respect to most other parameters studied, the two drugs were identical. The probability of acute GVHD was .42 and .46, respectively (P = .70), that of chronic GVHD, .50 and .63 (P = .44), and that of death from transplant-related causes, .30 and .24 (P = .51). There were no differences in the speed of granulocyte and platelet engraftment (P = .82 and .94, respectively), and the duration of hospitalization was comparable (P = .58). Patients receiving MTX required red cell transfusions for a shorter period of time (P = .02), but had a slightly increased morbidity from early oral mucositis. The leukemia recurrence rates were comparable (P = .60). With the regimens used in this study, we conclude that CSP failed to reduce the incidence of GVHD and improve the survival of patients with chronic myelocytic leukemia when compared to results with standard MTX.     

Risks for methicillin‐resistant Staphylococcus aureus colonization or infection among patients with HIV infection*

Background

Risks for methicillin‐resistant Staphylococcus aureus (MRSA) among those with HIV infection have been found to vary, and the epidemiology of USA‐300 community‐acquired (CA) MRSA has not been adequately described.

Methods

We conducted a retrospective review of HIV‐infected out‐patients from January 2002 to December 2007 and employed multivariate logistic regression (MLR) to identify risks for MRSA colonization or infection. Pulsed‐field gel electrophoresis (PFGE) was used to identify USA‐300 strains. Results Seventy‐two (8%) of 900 HIV‐infected patients were colonized or infected with MRSA. MLR identified antibiotic exposure within the past year [odds ratio (OR) 3.4; 95% confidence interval (CI) 1.5–7.7] and nadir CD4 count <200 cells/μL (OR 2.5; 95% CI 1.2–5.3) as risks for MRSA colonization or infection. Receipt of antiretroviral therapy (ART) within the past year was associated with decreased risk (OR 0.16; 95% CI 0.07–0.4). Eighty‐nine percent of available strains were USA‐300. MLR identified skin or soft tissue infection (SSTI) as the only predictor for infection with USA‐300 (OR 5.9; 95% CI 1.4–24.3). Conclusion Significant risks for MRSA among HIV‐infected patients were CD4 count nadir <200 cells/μL and antibiotic exposure. Only the presence of an SSTI was associated with having USA‐300, and thus the use of patient characteristics to predict those with USA‐300 was limited. In addition, ART within the previous year significantly reduced the risk of MRSA colonization or infection.

     

Caries frequency and distribution in an early medieval Avar population from Austria

Objective:  The aim of this study was to determine frequency and distribution of dental caries in an early medieval Avar population from Central Europe, namely Vienna.
Methods:  The evaluation of caries was carried out in an anthropological sample consisting of the remains of 136 individuals and included 2215 permanent teeth. Age and sex estimations were based on dental development and on skeletal ageing methods. The presence of dental caries was determined according to clinical aspects using a dental probe.
Results:  The frequency of ante mortem tooth loss in the sample was 23.8%; the total caries frequency was calculated as 14.9%. The highest caries rate was recorded in the second mandibular molar (34.6%). The most affected tooth surface was found to be the root with 12.7%, followed by the approximal surface with 8.6%, but only 7.7% of the occlusal surfaces were affected by caries.
Conclusion:  This study revealed that Avars suffered from higher caries rates than most other medieval European populations, but experienced a similar dental caries distribution. Attrition of the occlusal surface resulting from a diet containing abrasive particles with accompanying posteruptive tooth movement is considered the major factor causing this premodern caries pattern.     

Three patterns of cytochrome P450 gene expression during liver maturation in mice

The neonatal period of liver development is an often overlooked phase of development. For instance, ontogeny of xenobiotic-metabolizing enzymes can markedly affect biotransformation as the liver matures. To systematically examine the ontogenic gene expression patterns of cytochrome P450 genes (P450) in mice, the gene expression profiles of 19 xenobiotic-metabolizing P450 in Cyp1 to 4 families were determined. The mRNA levels in C57BL/6 mouse livers were quantified using branched DNA technology at the following ages: gestational day 17 (2 days before birth) and postnatal days 0, 1, 3, 5, 10, 15, 20, 30, and 45. Among the 13 P450 genes expressed in mouse livers, three distinct ontogenic expression patterns were identified by cluster analysis. Genes in group 1 (Cyp3a16 as well as 3a41b in male) were expressed in the perinatal period, but they were essentially nondetectable by 30 days of age. Genes in group 2 (Cyp2e1, 3a11, and 4a10 as well as 3a41b in female) quickly increased after birth and reached maximal expression levels by day 5. Genes in group 3 (Cyp1a2, 2a4, 2b10, 2c29, 2d22, 2f2, 3a13, and 3a25) were expressed at low levels until days 10 to 15, but they markedly increased at day 20 to a high and stable level. In conclusion, the developmental expression of P450 in mouse liver can be divided into three patterns, suggesting that different mechanisms are responsible for the expression of P450 during liver maturation.     

PLUNC protein expression in major salivary glands of HIV‐infected patients

Oral Diseases (2011) 17 , 258–264 Objective: To analyse and compare the expression of Palate, Lung, and Nasal Epithelium Clone (PLUNC) proteins in salivary glands from patients with and without AIDS (control group) using autopsy material. Methods: We analysed the expression of PLUNCs using immunohistochemistry in parotid (n = 45), submandibular (n = 47) and sublingual gland (n = 37) samples of AIDS patients [30 with normal histology, 21 with mycobacteriosis, 14 with cytomegalovirus (CMV) infection, 30 with chronic non‐specific sialadenitis, and 30 HIV‐negative controls. In situ hybridization (ISH) for SPLUNC 2 in the HIV‐negative group was performed. Results: SPLUNC 1 expression was detected in the mucous acini of submandibular and sublingual glands, and SPLUNC 2 were seen in the serous cells. LPLUNC 1 expression was only positive in the salivary ducts. There was a higher expression of SPLUNC 2 in AIDS patients with CMV infection and mycobacteriosis when compared with all other groups. The intensity of staining for SPLUNC 2 was greater around the lesions than the peripheral ones. ISH for SPLUNC 2 showed perinuclear positivity in the serous cells in all HIV‐negative cases. Conclusions: SPLUNC 1 and LPLUNC 1 proteins were similarly expressed in the salivary glands of AIDS patients and non‐HIV patients. CMV infection and mycobacteriosis increase SPLUNC 2 expression in serous cells in the salivary gland of AIDS patients.     

Birth equity on the front lines: Impact of a community-based doula program in Brooklyn,NY

Background

We assessed whether participation in Healthy Start Brooklyn's By My Side Birth Support Program—a maternal-health program providing community-based doula support during pregnancy, labor and delivery, and the early postpartum period—was associated with improved birth outcomes. By My Side takes a strength-based approach that aligns with the doula principles of respecting the client's autonomy, providing culturally appropriate care without judgment or conditions, and promoting informed decision making.

Methods

Using a matched cohort design, birth certificate records for By My Side participants from 2010 through 2017 (n = 603) were each matched to three controls who also lived in the program area (n = 1809). Controls were matched on maternal age, race/ethnicity, education level, and trimester of prenatal-care initiation, using the simple random sampling method. The sample was restricted to singleton births. The odds of preterm birth, low birthweight, and cesarean birth were estimated, using conditional logistic regression.

Results

By My Side participants had lower odds of having a preterm birth (5.6% vs 11.9%, P < .0001) or a low-birthweight baby (5.8% vs 9.7%, P = .0031) than controls. There was no statistically significant difference in the odds of cesarean delivery.

Conclusion

Participation in the By My Side Birth Support Program was associated with lower odds of preterm birth and low birthweight for participants, who were predominantly Black and Hispanic. Investing in doula services is an important way to address birth inequities among higher risk populations such as birthing people of color and those living in poverty. It could also help shape a new vision of the maternal-health system, placing the needs and well-being of birthing people at the center.