Evaluation of the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population

Background  

Bowel cancer is common and is a major cause of death. Meta-analysis of randomised controlled trials estimates that screening for colorectal cancer using faecal occult blood (FOB) test reduces mortality from colorectal cancer by 16%. However, FOB testing has a low positive predictive value, with associated unnecessary cost, risk and anxiety from subsequent investigation, and is unacceptable to a proportion of the target population. Increased levels of an enzyme called matrix metalloproteinase 9 (MMP-9) have been found to be associated with colorectal cancer, and this can be measured from a blood sample. Serum MMP-9 is potentially an accurate, low risk and cost-effective population screening tool. This study aims to evaluate the accuracy of serum MMP-9 as a test for colorectal cancer in a primary care population.     

Successful Results of a Bipolar Active Fixation Lead for Atrial Application: An Interim Analysis

Adequate atrial lead performance consists of stable sensing and pacing properties. To evaluate whether the CPI 4269 bipolar lead, covered with mannitol (Sweet Tip), in the atrial position encounters these properties, we performed a prospective study of this lead. After complete dissolution of the mannitol helix, mapping of the atrium to obtain the highest electrogram and lowest threshold was followed by screw-in into the endocardium. Intraoperative measurements were performed and long-term follow-up was scheduled every 6 to 12 months to measure threshold and perform an intracardial electro-gram. Between February 1993 and December 1996, a total number of 73 leads in the atrial position in a consecutive series of patients was implanted. Implantation was performed in 28 patients receiving an AAIR and 45 patients a DDDR pacemaker. Reason for pacemaker implantation was a third-degree AV block in 37% of patients, type II second-degree AV block in 25%, sick sinus syndrome in 35%, and drug refractory paroxysmal atrial fibrillation following His-bundle ablation in 3%. The intraoperative bipolar atrial electrogram had a mean voltage of 4.25 ± 2.1 mV. The acute atrial bipolar threshold was 0.63 ± 0.43 V, and current was 1.35 ± 0.81 mA at a 1.0-ms pulse duration. The mean acute resistance of the lead was 572 ± 86 Ohm. After a mean follow-up of 18.3 months, the bipolar intracardial electrogram was 3.37 ± 2.00 mV, the mean atrial threshold measured at the last outpatient clinic visit was 0.99 ± 0.74 V and the mean impedance was 640 ±127 Ohm. A sensing problem due to traction of the atrial lead occurred in only one patient. Acute and late dislodgement did not occur. The CPI 4269 (Sweet Tip) lead is manufactured with a dissolvable capsule covering the helix tip electrode, permitting a safe passage through the venous system. This interim analysis shows that this lead in the atrial position has favorable acute and chronic results.     

Intermediate lymphocytic lymphoma: immunophenotypic and cytogenetic findings

A detailed immunohistologic and cytogenetic analysis of 12 cases of intermediate lymphocytic lymphoma was performed. The characteristic immunophenotype of intermediate lymphocytic lymphoma was: surface IgM and IgD+, BA1+, B1+, BA2-, B2-, B4+, Leu 14+, Leu 1+, HLA-DR+, and common acute lymphocytic leukemia associated (CALLA) antigen negative. Clonal chromosome abnormalities were identified in ten cases, with structural or numerical abnormalities of chromosomes 11 or 12 in nine cases. Five cases had structural abnormalities involving the long arm of chromosome 11; three of these had translocations with chromosome 14 at band q32. Three cases had trisomy 12, and one case had a translocation involving the long arm of chromosome 12. The tenth case had a translocation involving the long arms of chromosomes 7 and 9. These characteristic immunophenotypic and cytogenetic findings suggest a close lineage relationship between intermediate lymphocytic lymphoma and small lymphocytic (well differentiated) lymphoma/chronic lymphocytic leukemia. Their differing clinical, cytologic, and architectural features suggest, however, that intermediate lymphocytic lymphoma should be considered a separate category of lymphocytic lymphoma in the International Working Formulation.     

Chromosomal abnormalities in untreated patients with non-Hodgkin's lymphoma: associations with histology, clinical characteristics, and treatment outcome. The Nebraska Lymphoma Study Group

We describe the chromosomal abnormalities found in 104 previously untreated patients with non-Hodgkin's lymphoma (NHL) and the correlations of these abnormalities with disease characteristics. The cytogenetic method used was a 24- to 48-hour culture, followed by G- banding. Several significant associations were discovered. A trisomy 3 was correlated with high-grade NHL. In the patients with an immunoblastic NHL, an abnormal chromosome no. 3 or 6 was found significantly more frequently. As previously described, a t(14;18) was significantly correlated with a follicular growth pattern. Abnormalities on chromosome no. 17 were correlated with a diffuse histology and a shorter survival. A shorter survival was also correlated with a +5, +6, +18, all abnormalities on chromosome no. 5, or involvement of breakpoint 14q11-12. In a multivariate analysis, these chromosomal abnormalities appeared to be independent prognostic factors and correlated with survival more strongly than any traditional prognostic variable. Patients with a t(11;14)(q13;q32) had an elevated lactate dehydrogenase (LDH). Skin infiltration was correlated with abnormalities on 2p. Abnormalities involving breakpoints 6q11-16 were correlated with B symptoms. Patients with abnormalities involving breakpoints 3q21-25 and 13q21-24 had more frequent bulky disease. The correlations of certain clinical findings with specific chromosomal abnormalities might help unveil the pathogenetic mechanisms of NHL and tailor treatment regimens.     

The Bioload and Aflatoxin Content of Herbal Medicines from Selected States in Nigeria

Background

There is increased reliance on traditional herbal medicines by several millions of people worldwide, especially in West Africa and Nigeria in particular. This is due to escalating cost of good quality drugs and consequent proliferation of faked cheaper drugs. However, non standardization of production and handling methods have resulted in herbal medicines with varying quality and safety indices, thus resulting in possible public health concerns. This work investigated the microbial load and aflatoxin levels in herbal medicines from selected states in Nigeria.

Materials and Methods

A total of 210 samples obtained from various renowned herbal medicine practitioners from some selected states in Nigeria, based on their medicinal uses, were analyzed to determine the microbial load by the plate count method and aflatoxin contamination levels using thin layer chromatography with aflatoxin standards.

Results

At least six bacterial genera (Bacillus, Pseudomonas, Salmonella, EPEC, EHEC, Streptococcus and other coliforms) and 6 fungal genera (Aspergillus, Penicillium, Rhizopus, Cladosporium, Geotricum and Candida) were isolated. Aflatoxin B1, B2 and G1 were detected in varying concentrations in the samples analyzed, with an average occurrence of 18.6%. Some of these herbal concoctions were found to contain unacceptably high bioload, according to WHO standards.

Conclusion

Microbial contamination and the presence of aflatoxins in herbal medicines appear to be an endemic problem in Nigeria, as observed in this work, probably due to poor observation of basic hygiene during preparations and poor storage conditions. The findings in this work may serve in developing and instituting public health standards for the production and safety of herbal remedies in Nigeria.     

Changes in insulin receptor signaling underlie neoadjuvant metformin administration in breast cancer: a prospective window of opportunity neoadjuvant study

Introduction

The antidiabetic drug metformin exhibits potential anticancer properties that are believed to involve both direct (insulin-independent) and indirect (insulin-dependent) actions. Direct effects are linked to activation of AMP-activated protein kinase (AMPK) and an inhibition of mammalian target of rapamycin mTOR signaling, and indirect effects are mediated by reductions in circulating insulin, leading to reduced insulin receptor (IR)-mediated signaling. However, the in vivo impact of metformin on cancer cell signaling and the factors governing sensitivity in patients remain unknown.

Methods

We conducted a neoadjuvant, single-arm, “window of opportunity” trial to examine the clinical and biological effects of metformin on patients with breast cancer. Women with untreated breast cancer who did not have diabetes were given 500 mg of metformin three times daily for ≥2 weeks after diagnostic biopsy until surgery. Fasting blood and tumor samples were collected at diagnosis and surgery. Blood glucose and insulin were assayed to assess the physiologic effects of metformin, and immunohistochemical analysis of tumors was used to characterize cellular markers before and after treatment.

Results

Levels of IR expression decreased significantly in tumors (P = 0.04), as did the phosphorylation status of protein kinase B (PKB)/Akt (S473), extracellular signal-regulated kinase 1/2 (ERK1/2, T202/Y204), AMPK (T172) and acetyl coenzyme A carboxylase (S79) (P = 0.0001, P < 0.0001, P < 0.005 and P = 0.02, respectively). All tumors expressed organic cation transporter 1, with 90% (35 of 39) exhibiting an Allred score of 5 or higher.

Conclusions

Reduced PKB/Akt and ERK1/2 phosphorylation, coupled with decreased insulin and IR levels, suggest insulin-dependent effects are important in the clinical setting. These results are consistent with beneficial anticancer effects of metformin and highlight key factors involved in sensitivity, which could be used to identify patients with breast cancer who may be responsive to metformin-based therapies.

Trial registration

ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00897884","term_id":"NCT00897884"}}NCT00897884. Registered 8 May 2009.

Electronic supplementary material

The online version of this article (doi:10.1186/s13058-015-0540-0) contains supplementary material, which is available to authorized users.