Decreased ecto-5'nucleotidase activity of peripheral blood lymphocytes in human monoclonal gammopathies: correlation with tumor cell kinetics

Ecto-5'nucleotidase (5'NT) activity of peripheral blood (PB) lymphocytes was determined in 31 patients with serum monoclonal gammopathies (MG). Twenty-one patients had a diagnosis of multiple myeloma (MM), and ten patients had monoclonal gammopathy of undetermined significance (MGUS). The proliferative activity of the bone marrow plasma cells (LI%) was investigated in 28 of these MG patients by means of tritiated thymidine uptake evaluated by simultaneous autoradiography and cytoplasmic immunofluorescence. 5'NT activity was significantly lower in MG patients as compared with normal controls. MM patients had lower 5'NT activity than MGUS patients, but the difference was not significant. By contrast, MM had significantly higher LI% than MGUS patients. There was a linear regression of 5'NT on LI% which was statistically significant: the higher the LI%, the lower the 5'NT. Because the LI% is an accurate prognostic and monitoring factor in MG, this correlation indicates that 5'NT may be of assistance in predicting the clinical progress of MG patients. In seven MGs, the PB T and B lymphocytes were studied separately. The T cell subpopulation was 5'NT deficient compared to the normal controls, shown as a significant linear regression of T cell 5'NT on the LI%. This suggests that in MG there may be an alteration of nonneoplastic T lymphocytes correlated with tumor growth. The OKT8+ lymphocytes were mainly responsible for the 5'NT deficiency of unseparated T lymphocytes.     

Association of maternal serum α-fetoprotein with persistent placenta previa

Objective: To evaluate the relationship between maternal serum α-fetoprotein (MSAFP) and the risk of persistent placenta previa.

Methods: We conducted a retrospective cohort study of singleton pregnancies with sonographic evidence of placenta previa at 15?–?20 weeks' gestation, between October 1991 and August 2000. Only pregnancies with MSAFP determination at 15?–?20 weeks' gestation and non-anomalous live-born infants ??24 weeks' gestation were included. Pregnancies in which Cesarean delivery was performed for placenta previa were considered persistent; this was the primary outcome.

Results: Of 275 women with previa at 15?–?20 weeks' gestation, 33 (12%) had previa at delivery. Trend analysis revealed a greater likelihood of persistent previa with increasing MSAFP values (p?=?0.01). Mid-trimester MSAFP <?1 multiple of the median (MoM) was associated with a decreased incidence of persistence of 4%, significantly less than the risk at ??1 MoM (16%; p?=?0.01).

Conclusions: There is an association between increasing MSAFP values and greater likelihood of persistent placenta previa. An MSAFP value <?1 MoM is associated with a reduction in the risk of persistence of previa to delivery.     

Antimicrobial resistance surveillance systems: Are potential biases taken into account?

BACKGROUND:

The validity of surveillance systems has rarely been a topic of investigation.

OBJECTIVE:

To assess potential biases that may influence the validity of contemporary antimicrobial-resistant (AMR) pathogen surveillance systems.

METHODS:

In 2008, reports of laboratory-based AMR surveillance systems were identified by searching Medline. Surveillance systems were appraised for six different types of bias. Scores were assigned as ‘2’ (good), ‘1’ (fair) and ‘0’ (poor) for each bias.

RESULTS:

A total of 22 surveillance systems were included. All studies used appropriate denominator data and case definitions (score of 2). Most (n=18) studies adequately protected against case ascertainment bias (score = 2), with three studies and one study scoring 1 and 0, respectively. Only four studies were deemed to be free of significant sampling bias (score = 2), with 17 studies classified as fair, and one as poor. Eight studies had explicitly removed duplicates (score = 2). Seven studies removed duplicates, but lacked adequate definitions (score = 1). Seven studies did not report duplicate removal (score = 0). Eighteen of the studies were considered to have good laboratory methodology, three had some concerns (score = 1), and one was considered to be poor (score = 0).

CONCLUSION:

Contemporary AMR surveillance systems commonly have methodological limitations with respect to sampling and multiple counting and, to a lesser degree, case ascertainment and laboratory practices. The potential for bias should be considered in the interpretation of surveillance data.     

Different sensitivities of rat skeletal muscles and brain to novel anti-cholinesterase agents, alkylammonium derivatives of 6-methyluracil (ADEMS)

BACKGROUND AND PURPOSE

The rat respiratory muscle diaphragm has markedly lower sensitivity than the locomotor muscle extensor digitorum longus (EDL) to the new acetylcholinesterase (AChE) inhibitors, alkylammonium derivatives of 6-methyluracil (ADEMS). This study evaluated several possible reasons for differing sensitivity between the diaphragm and limb muscles and between the muscles and the brain.

EXPERIMENTAL APPROACH

Increased amplitude and prolonged decay time of miniature endplate currents were used to assess anti-cholinesterase activity in muscles. In hippocampal slices, induction of synchronous network activity was used to follow cholinesterase inhibition. The inhibitor sensitivities of purified AChE from the EDL and brain were also estimated.

KEY RESULTS

The intermuscular difference in sensitivity to ADEMS is partly explained caused by a higher level of mRNA and activity of 1,3-bis[5(diethyl-o-nitrobenzylammonium)pentyl]-6-methyluracildibromide (C-547)-resistant BuChE in the diaphragm. Moreover, diaphragm AChE was more than 20 times less sensitive to C-547 than that from the EDL. Sensitivity of the EDL to C-547 dramatically decreased after treadmill exercises that increased the amount of PRiMA AChE(G4), but not ColQ AChE(A12) molecular forms. The A12 form present in muscles appeared more sensitive to C-547. The main form of AChE in brain, PRiMA AChE(G4), was apparently less sensitive because brain cholinesterase activity was almost three orders of magnitude more resistant to C-547 than that of the EDL.

CONCLUSIONS AND IMPLICATIONS

Our findings suggest that ADEMS compounds could be used for the selective inhibition of AChEs and as potential therapeutic tools.     

TB or not TB? Difficulties in the diagnosis of tuberculosis in HIV-negative immigrants to Germany

Background

Immigrants to Germany and their children are at particular risk for tuberculosis (TB).

Methods

35 Patients (10 male/25 female aged 2 - 59 years (median 33 years) originating mostly from high incidence countries in Asia (19 [54.3%]) in Africa (14 [40.0%] and East Europe (2 [5.7%]), attended at the Tropical Medicine unit were analysed.

Results

Primary clinical presentation was most frequently lymphadenitis (13 [37.1%]). other organs involved included bones (7 [20.0%]), central nervous system (5 [14.3%]), urogenital organs (3 [8.6%]), lung (3 [8.6%]), mediastinum, (2 [5.7%]) and abdomen (2 [5.7%]). ESR was abnormal in 21/28 (75.0%), CRP in 20/35 (57.1%), and protein electrophoresis in 22/26 (84.6%) cases. The tuberculin skin test was strongly positive in all 15 cases where the test had been performed. Tuberculosis interferon gamma release assay (TB-IGRA) was positive in all 35 cases (100%). PCR for nucleic acids of Mycobacterium (M.) tuberculosis complex was positive in only 7/20 (35.0%) cases. M. tuberculosis was identified in 32/35 (91.4%), M. bovis in 2 (5.7%) cases. 1 case was diagnosed clinically. All patients were negative for HIV. Typical histopathology was seen in the 29 cases, where biopsies had been taken. Chest-X-ray did not reveal specific pulmonary lesions in the majority of cases (22/35 [62.9%]). Diagnosis of TB was mostly delayed (4 to 299 weeks, [median 8]). The most frequent primary suspicion was a malignancy (17/35 [48.6%]) while TB was initially suspected in 5 cases only. Diagnosis of TB is impeded by its multifaceted presentation especially in immigrants.