Absence of breast cancer cells in a single-day peripheral blood progenitor cell collection after priming with cyclophosphamide and granulocyte-macrophage colony-stimulating factor

The effect of priming on occult tumor cell involvement of peripheral blood (PB) and PB progenitor cell (PBPC) collections is poorly characterized. Using sensitive immunocytochemistry (ICC) and tumor clonogenic assays (TCA) specific for epithelial-derived tumor cells, hematopoietic specimens were analyzed for PBPC and occult tumor cell involvement in 28 patients with chemotherapy-sensitive stage IIIB or IV breast cancer. Before PBPC priming, tumor was detected by ICC in PB of 1 of 23 (4%) patients and in bone marrow (BM) harvests of 4 of 27 (15%) patients. Fifteen days after cyclophosphamide and granulocyte- macrophage colony-stimulating factor (GM-CSF) priming, 2 of 28 (7%) patients had ICC-positive PBPC collections. The median amplification of CD34+ PBPC during this time was over 19-fold (range, < 1 to 199). One patient had pretreatment tumor involvement of both PB and BM. One patient grew tumor colonies in TCA; the PB and BM were ICC- and TCA- positive, but the PBPC collection was ICC-positive and TCA-negative. After cytoreduction with conventional-dose chemotherapy, patients with advanced breast cancer and histologically negative BM biopsy specimens have rare tumor cell involvement of PB and BM. Despite effective PBPC priming with cyclophosphamide and GM-CSF, clonogenic breast cancer cells were not found in the PBPC collection performed on day 15.     

Environmental risk factors for oesophageal cancer in Malawi: A case-control study

Aim

There is a high burden of oesophageal cancer in Malawi with dismal outcomes. It is not known whether environmental factors are associated with oesophageal cancer. Without knowing this critical information, prevention interventions are not possible. The purpose of this analysis was to explore environmental factors associated with oesophageal cancer in the Malawian context.

Methods

A hospital-based case-control study of the association between environmental risk factors and oesophageal cancer was conducted at Kamuzu Central Hospital in Lilongwe, Malawi and Queen Elizabeth Central Hospital in Blantyre, Malawi. Ninety-six persons with squamous cell carcinoma and 180 controls were enrolled and analyzed. These two groups were compared for a range of environmental risk factors, using logistic regression models. Unadjusted and adjusted odds ratios and 95% confidence intervals (CI) were calculated.

Results

Firewood cooking, cigarette smoking, and use of white maize flour all had strong associations with squamous cell carcinoma of the oesophagus, with adjusted odds ratios of 12.6 (95% CI: 4.2–37.7), 5.4 (95% CI: 2.0–15.2) and 6.6 (95% CI: 2.3–19.3), respectively.

Conclusions

Several modifiable risk factors were found to be strongly associated with squamous cell carcinoma. Research is needed to confirm these associations and then determine how to intervene on these modifiable risk factors in the Malawian context.     

Use of oral rehydration therapy in the treatment of childhood diarrhoea in Douala,Cameroon

Introduction

The use of oral rehydration solutions in our context remains limited. This study was conducted to analyze the rate of this use in Douala, Cameroon and thereby determine the factors associated with it.

Method

A cross-sectional survey was administered to parents of children aged five years and younger during a six-month study period. The studied variables focused on the socio-demographic data of the population, data on diarrhoea and its severity, data on oral rehydration salts (ORS), and data related to other interventions for diarrhoea. The chi-square test was used to qualify associations between variables, with the significance level being set at 5%.

Results

Overall, 672 people agreed to participate in the study. Among them, 418 (62.2%) correctly defined diarrhoea. When their children develop diarrhoea, the majority of the parents (348, 51.8%) reported seeking hospital assistance before any intervention, while 225 parents (33.5%) preferred the use of ORS first. Four hundred seventy-five parents (70.7%) had heard of ORS and among them 313 (65.9%) had actually given ORS to their children as treatment during these children''s most recent episodes of diarrhoea. Of the parents who had given their children ORS, 217 (69.3%) knew how to prepare it, and 122 (39.0%) knew how to administer it. One hundred thirty-five parents (20.1%) had administered metronidazole to treat their children''s diarrhoea. The age of the children, the parents'' level of education, and the number of children in the household significantly influenced the use or non-use of ORS (respectively, p < 0.001, p = 0.003 and p < 0.0001). Rehydration was correctly identified by 234 parents (34.8%) as the purpose of administering ORS.

Conclusion

The knowledge and the use of ORS in diarrhoea by the study sample was insufficient. The role of ORS was poorly known. Awareness campaigns can be carried out in order to improve the use of this effective intervention for diarrhoea.     

Implementation of Massachusetts health insurance reform with vulnerable populations in a safety-net setting

This qualitative study examines the experience of racial and ethnic minorities receiving behavioral health care in a safety net setting during the early process of health insurance reform in Massachusetts. Three rounds of interviews were conducted between August 2007 and May 2009, collecting information from patients (n=65) on the experience of health reform and delivery of mental health care. Four categories of enrollees transitioning into health reform emerged over the course of the study that grouped into a typology of experiences with reform: early enrollees, middle enrollees, late enrollees, and multiple switchers. With support, a majority of the sample transitioned smoothly to the new health insurance mechanisms. However, some experienced administrative confusion and disruption in mental health care during the transition. Administrative policies providing special accommodations for individuals with mental health disorders and other vulnerable populations may be important to consider during the transition to health insurance reform.     

Activating mutations of N- and K-ras in multiple myeloma show different clinical associations: analysis of the Eastern Cooperative Oncology Group Phase III Trial

Mutations of members of the ras family are among the most common oncogene mutations found in multiple myeloma (MM). We have examined the mutational status of the N- and K-ras genes at codons 12, 13, and 61 in 160 newly diagnosed MM patients enrolled on the Eastern Cooperative Oncology Group (ECOG) phase III clinical trial E9486. The total incidence of ras mutations was found to be 39% of the samples analyzed. Five patients showed evidence of more than one mutation. We obtained 22 marrow samples from patients at the time of disease progression or relapse, for whom a ras mutation was identified at diagnosis. In all cases, the ras mutation of the disease progression sample was identical to that found at diagnosis. In contrast, three of 25 patients who did not show any ras mutation at diagnosis acquired a ras mutation at the time of disease progression. No significant association was observed between any ras mutation and stage of disease, beta 2-microglobulin levels, labelling index, or protein type. The mean tumor burden and median survival for patients with mutations of N-ras was indistinguishable from patients with no ras mutations. However, patients with K-ras mutations had a significantly higher mean bone marrow tumor burden at diagnosis than patients with no ras mutations (57% v 36%, P < .02); and the median survival of patients with a K-ras mutation was significantly shorter (2.0 v 3.7 years, P < .02). To determine if the status of ras mutations could affect treatment response, we examined patient survival on the three treatment arms of E9486. Although the presence of a ras mutation in the multidrug treatment, VBMCP alone, showed a marginal significance, neither the VBMCP, nor the addition of interferon-alpha showed statistically significant survival differences between mutant and wildtype ras status. Interestingly, there appeared to be a statistically significant difference in survival of patients treated with VBMCP and alternating high doses of cyclophosphamide + prednisone. Patients with ras mutations had a median survival of 2.1 years; patients with wild-type ras had a median survival of 4.0 years (P < .01).     

A new c-kit mutation in a case of aggressive mast cell disease

Systemic mast cell disease (SMCD) is a disorder characterized by a mast cell proliferation in various tissues. Mast cells express the c -kit proto-oncogene. A few cases of c -kit mutations have been described in SMCD. We report an aggressive SMCD in a patient who presented with a bone marrow infiltration by abnormal mast cells. Molecular studies of mast cell DNA and RNA revealed a new c- kit heterozygous mutation (Asp820Gly). This mutation leads to a drastic amino-acid change and is located close to the highly oncogenic Asp816Val. These findings suggest that the Asp820Gly has a potential role in c- kit activation.     

Monoclonal antibodies to the 140,000 mol wt glycoprotein of B lymphocyte membranes (CR2 receptor) initiates proliferation of B cells in vitro

Several mouse monoclonal IgG antibodies (AB1, AB2, AB3, and AB5) were developed that reacted with a 140,000 mol wt glycoprotein on the surface of cultured RAJI B lymphoid cells. The antibodies reacted with purified normal human peripheral blood B cells and CLL Ig+ B cells and showed specific germinal center and mantle zone staining in tissue sections of secondary lymphoid organs. Immunodepletion studies using 125I surface-labeled Raji cell membrane antigens demonstrated that the antigen identified by AB5 is the same 140,000 mol wt glycoprotein detected by anti-B2 that has recently been shown to react with the C3d fragment or CR2 receptor. (Iida et al: J Exp Med 158:1021, 1983). Addition of the AB series and anti-B2 monoclonal antibodies to cultures of purified human peripheral blood B cells resulted in the uptake of 3H- thymidine at two to six times background control levels provided that irradiated autologous T cells were added to the culture. Stimulation was not evoked by other monoclonal antibodies to B cell surface molecules (ie, B1, BA-1, BA-2, and HLA-DR). Pepsin-generated F(ab')2 fragments of anti-CR2 antibodies were essentially as effective as the intact IgG molecule in stimulating B cells. Induction of B cell proliferation by antibody binding to CR2 suggests that the C3d receptor may have an integral role in regulation of humoral immune response.     

Blocking of Protein Pancreatic Secretion by Maximal Secretion Infusion in the Dog

In conscious chronic gastric and pancreatic fistula dogs (Thomas cannula), secretin was perfused for three hours with a submaximal (GIH, 1.0 C.U./kg.) and a maximal dose (GIH, 8.0 C.U./kg.), according to the following schedule: 1. First hour submaximal stimulus; 2. second hour maximal stimulus; 3. third hour submaximal stimulus.
The alkaline and protein components of pancreatic secretion were analyzed in 20-minute sample collections throughout the three hours.
The same protocol was followed in anesthetized dogs subjected to a mid line laparotomy. A biopsy of the pancreatic gland was taken before (control) and at the end of each perfused dose. The secretion showed a significant increase of protein concentration and output when passing from the maximal to the last submaximal secretin perfusion dose. These findings correlate well with the piling up of zymogen and prozymogen granules in the apical zone of the acinar cells during maximal secretin perfusion, with their subsequent discharge into the acinar lumen upon abrupt reversal to the initial secretin submaximal dose.
The study confirms that secretin influences pancreatic protein secretion and indicates in addition, that pharmacologic doses of the hormone, have the capacity to block acinar cell zymogen granule release.