Sentinel node scintigraphy in breast cancer using a dual tracer technique

AIM: In order to depict the anatomy and improve the localization, sentinel node scintigraphy in breast cancer was combined with intravenous administration of pertechnetate. As this may reduce the detectability of weak 'hot spots', the number of lymph nodes detected at scintigraphy and at surgery in one group of patients was compared with that obtained in another group that had not received pertechnetate. PATIENTS AND METHODS: The number of 'hot spots' at frontal and lateral views in 47 female patients at scintigraphy performed 2-3 h after subcutaneous injection of radiocolloid together with 25 MBq pertechnetate i.v. was compared in retrospect with that of 41 female patients who had not received pertechnetate. The number of lymph nodes detected at surgery using a hand-held gamma probe together with blue dye in the two groups was also compared. The washout kinetics of pertechnetate was studied in 10 patients. RESULTS: There was no difference in the number of detected lymph nodes at any comparison. The kinetics study revealed a decreasing activity with time after correction for physical decay. CONCLUSION: Administration of a 25 MBq pertechnetate i.v. in order to improve the anatomical localization at sentinel node scintigraphy in breast cancer does not reduce the detectability of radioactive lymph nodes.     

Relationship between serum amyloid A level and Tanis/SelS mRNA expression in skeletal muscle and adipose tissue from healthy and type 2 diabetic subjects

Tanis is a recently described protein reported to be a putative receptor for serum amyloid A and found to be dysregulated with diabetes in the Israeli sand rat Psamommys obesus. Tanis has also been identified as a selenoprotein, one of the first two identified membrane selenoproteins. We determined mRNA expression of the human homologue of Tanis, SelS/AD-015, in skeletal muscle and adipose tissue biopsies obtained from 10 type 2 diabetic patients and 11 age- and weight-matched healthy subjects. Expression of Tanis/SelS mRNA in skeletal muscle and adipose tissue biopsies was similar between diabetic and control subjects. A subset of subjects underwent a euglycemic-hyperinsulinemic clamp, and adipose tissue expression of Tanis/SelS was determined after in vivo insulin stimulation. Adipose tissue Tanis/SelS mRNA expression was unchanged after insulin infusion in control subjects, whereas Tanis/SelS mRNA increased in seven of eight subjects following insulin stimulation in diabetic subjects. Skeletal muscle and adipose tissue Tanis/SelS mRNA expression were positively correlated with plasma serum amyloid A. In conclusion, there is a strong trend toward upregulation of Tanis/SelS following insulin infusion in adipose tissue from type 2 diabetic subjects. Moreover, the positive relationship between Tanis mRNA and the acute-phase protein serum amyloid A suggests an interaction between innate immune system responses and Tanis expression in muscle and adipose tissue.     

A longitudinal study on different models of postabortion care in Tanzania

OBJECTIVE: To identify women having unsafe abortions and elucidate whether an acceptable follow-up rate among these women can be retrieved. STUDY POPULATION: One thousand three hundred and fifty-seven women attended Temeke Municipal Hospital, Dar es Salaam with an abortion-related diagnosis. METHODS: Women having unsafe abortions were identified by an empathetic dialogue, offered a contraceptive service and asked to return for follow-up. Three different ways of achieving follow-up information were tested. In phase 1, a combination of hospital-based and home-based interviews was utilized, in phase 2, an additional 1-month control visit was added to the protocol, and in phase 3, the contraceptive counseling and service was provided by technically well-skilled counselors. RESULTS: Seven hundred and eighty-eight women were identified as having had unsafe abortions and 491 women as spontaneous abortions. Women having unsafe abortions were younger, more often single and of higher parity than women having spontaneous abortions. The follow-up rate achieved varied from 47%-72%, being lowest in phase 1 and highest in phase 3. The two most common reasons for loss to follow-up were the interviewer's inability to locate the respondent's house either because of an unspecific or a remote address (58%) and migration (29%). CONCLUSION: If hospital-based and confidential home-based interviews are used combined and if the women having unsafe abortions are counseled by technically well-skilled counselors, it is possible to achieve a reasonable follow-up rate among women having unsafe abortions.     

Contribution of the paracellular route to the pH-dependent epithelial permeability to cationic drugs

The aim of this work was to investigate the contribution of the paracellular route to the pH-dependent permeability to cationic drugs in three models expressing different drug permeabilities: hexadecane membranes (HDMs), Caco-2, and 2/4/A1 cell monolayers. The high- and low-permeability drugs alfentanil and cimetidine were used as model drugs. The paracellular permeability was calculated: 1. from the assumption that the ionized form (P(mi)) permeates a cell monolayer only by the paracellular route, and 2. on basis of the pore-restricted diffusion. For both drugs, sigmoidal relationships between membrane permeability and pH were observed in all models. The P(mi) was in excellent agreement with the paracellular permeability of cimetidine in the two cell models, whereas no significant P(mi) of the drugs could be observed in HDM. The results showed that the paracellular route has a significant role in the permeability of small basic hydrophilic drugs, such as cimetidine in leaky, small intestinal-like epithelia such as 2/4/A1. By contrast, in tighter epithelia such as Caco-2 and in artificial membranes such as HDM, the permeability of the ionized forms of the drugs and the paracellular permeability are lower or insignificant, respectively. These findings will have implications in the experimental design and data interpretation of pH-dependent drug transport experiments in cell culture models as well as in artificial membrane models such as HDM and parallel artificial membrane permeability assay (PAMPA).     

Recombinant CD44-HABD is a novel and potent direct angiogenesis inhibitor enforcing endothelial cell-specific growth inhibition independently of hyaluronic acid binding

CD44 is the main cellular receptor for hyaluronic acid (HA). We previously found that overexpression of CD44 inhibited tumor growth of mouse fibrosarcoma cells in mice. Here, we show that soluble recombinant CD44 HA-binding domain (CD44-HABD) acts directly onto endothelial cells by inhibiting endothelial cell proliferation in a cell-specific manner. Consequently, soluble recombinant CD44-HABD also blocked angiogenesis in vivo in chick and mouse, and thereby inhibited tumor growth of various origins at very low doses (0.25 mg/kg x day). The antiangiogenic effect of CD44 is independent of its HA-binding capacity, since mutants deficient in HA binding still maintain their antiangiogenic and antiproliferative properties. Recombinant CD44-HABD represents a novel class of angiogenesis inhibitors based on a cell-surface receptor.     

IL-6 levels in acute and post myocardial infarction: their relation to CRP levels, infarction size, left ventricular systolic function, and heart failure

BACKGROUND: Inflammatory mechanisms in heart disease are of great interest. The proinflammatory cytokine interleukin (IL) 6 has been linked to increased morbidity in unstable angina pectoris and depressed myocardial function in heart failure (HF). METHODS: We studied the relation of IL-6 levels to C-reactive protein (CRP), infarction size, left ventricular function, and HF in acute myocardial infarction (MI) and after hospital discharge in 31 consecutive patients (19 males, mean age 69+/-13 years). Blood sampling for IL-6 was performed on admittance, four times on day 1, twice on day 2, and once daily on days 3-5, and 6 and 12 weeks later. Clinical signs of HF were evaluated daily during hospitalization and after 6 and 12 weeks. Echocardiography was performed on day 3 and at 6 weeks. RESULTS: IL-6 showed a curved time course with elevated levels already on admittance (mean+/-S.D. 19.3+/-26.9 ng/l), thereafter increasing to a peak on days 1 and 2 (maximum 68.5+/-152.9 ng/l), and then declining rapidly to lower, although not normalized, levels during hospitalization and at 6 and 12 weeks. CRP showed a similar time pattern, but with a later peak and a seemingly less rapid decline in levels. Mean levels of IL-6 and CRP on days 1-5 correlated highly (r=0.794, p<0.0001). IL-6 and infarction size did not correlate. HF during hospitalization and at 6 weeks was not related to IL-6; however, patients with HF at 12 weeks had higher IL-6 levels, both at 6 and 12 weeks. Patients on ACE inhibitors or diuretics at discharge had higher IL-6 levels at 6 weeks. IL-6 during hospitalization was not related to LVF; yet, patients with depressed LVF in the hospital and at 6 weeks had higher IL-6 levels at 6 and 12 weeks. CONCLUSIONS: IL-6 in acute MI shows a curved time course and is highly correlated to CRP. It peaks on days 1 and 2 and remains elevated even after 12 weeks. Increased IL-6 levels after hospital discharge are associated with HF and depressed LVF. Whether anti-inflammatory agents will influence left ventricular dysfunction and outcome postacute MI has yet to be determined.     

Association between a functional polymorphism in the progesterone receptor gene and panic disorder in women

Although genetic factors are known to be important risk factors for panic disorder there is as yet no conclusive data regarding specific gene variants. Prompted by evidence supporting progesterone to influence the pathophysiology of panic disorder, polymorphisms in the progesterone receptor gene, a single nucleotide polymorphism (G331A) and an insertion/deletion polymorphism (PROGINS) were investigated in 72 patients with panic disorder and 452 controls. The frequency of the A-allele of the G331A polymorphism was higher in panic disorder patients than in controls (p = 0.01). When male and female patients were analyzed separately, the association was observed in female patients only (p = 0.0009), with an odds ratio of 3.5. No differences between groups were observed for the PROGINS polymorphism. In conclusion, these data suggest that the G331A polymorphism in the progesterone receptor gene may influence the risk for panic disorder in women.