Prosthetic valve endocarditis: superiority of surgical valve replacement versus medical therapy only

The objective of our study was to assess the long-term outcome of patients with prosthetic valve endocarditis. We used a multicenter, prospective, observational study design. Six university teaching hospitals with high volume cardiothoracic surgery participated. Seventy-four patients with prosthetic valve endocarditis as defined by explicit, objective criteria were selected for participation. All patients were followed up prospectively for 1 year. Thirty-one percent and 69% had development of endocarditis within 60 days of valve insertion ("early") and after 60 days ("late"), respectively. The most common causes were Staphylococcus epidermidis (40%), Staphylococcus aureus (20%), streptococcal species (18%), and aerobic gram-negative bacilli (11%). Physical signs of endocarditis (new or changing murmur, stigmata, emboli) were seen in 58%. At 6 months and 12 months, mortality was 46% and 47%, respectively. Surgical replacement of the infected valve led to significantly lower mortality (23%) as compared with medical therapy alone (56%), as assessed by both univariate and multivariate analyses (p < 0.05). Improved outcome was seen for the surgical group even when controlling for severity of illness at time of diagnosis. From these findings we conclude that accurate assessment of outcome in prosthetic valve endocarditis requires long-term follow-up of at least 6 months following diagnosis. Surgical therapy warrants greater scrutiny; evaluation in controlled clinical trials is appropriate.     

Engineering Gold Nanotubes with Controlled Length and Near‐Infrared Absorption for Theranostic Applications

Important aspects in engineering gold nanoparticles for theranostic applications include the control of size, optical properties, cytotoxicity, biodistribution, and clearance. In this study, gold nanotubes with controlled length and tunable absorption in the near‐infrared (NIR) region have been exploited for applications as photothermal conversion agents and in vivo photoacoustic imaging contrast agents. A length‐controlled synthesis has been developed to fabricate gold nanotubes (NTs) with well‐defined shape (i.e., inner void and open ends), high crystallinity, and tunable NIR surface plasmon resonance. A coating of poly(sodium 4‐styrenesulfonate) (PSS) endows the nanotubes with colloidal stability and low cytotoxicity. The PSS‐coated Au NTs have the following characteristics: i) cellular uptake by colorectal cancer cells and macrophage cells, ii) photothermal ablation of cancer cells using single wavelength pulse laser irradiation, iii) excellent in vivo photoacoustic signal generation capability and accumulation at the tumor site, iv) hepatobiliary clearance within 72 h postintravenous injection. These results demonstrate that these PSS‐coated Au NTs have the ideal attributes to develop their potential as effective and safe in vivo imaging nanoprobes, photothermal conversion agents, and drug delivery vehicles. To the best of knowledge, this is the first in vitro and in vivo study of gold nanotubes.     

Transplacental transfer and biotransformation studies of nicotine in the human placental cotyledon perfused in vitro

Our objective was to study the characteristics of transfer and biotransformation of nicotine in the human term placenta. Nicotine transfer was studied by dually perfusing an isolated cotyledon of the human placenta in vitro. Nicotine metabolism to cotinine was investigated in intact tissue during perfusion and in placental microsomal fractions. Following the addition of nicotine (40 ng/ml) to the maternal side of the placenta, distribution into placental tissue (0.43 +/- 0.13 ng/ml/min) was three times higher than transfer to the fetal side of the placenta (0.15 +/- 0.01 ng/ml/min). The steady-state maternal-to-fetal transfer of nicotine was approximately 90% that of antipyrine (a marker of flow-dependent transfer). There was no evidence of nicotine metabolism to cotinine by intact placental tissue or in microsomal fractions. The observation that nicotine readily crosses the human placenta with no evidence of metabolism suggests that nicotine has the potential to cause adverse affects on the developing fetus.     

Supraomohyoid neck dissection in the treatment of T1/T2 squamous cell carcinoma of oral cavity

BACKGROUND: Recent studies in patients with previously untreated T1 and T2 squamous cell carcinoma (SCC) of the tongue and floor of the mouth have shown a relationship between tumor thickness, neck metastasis, and survival. Our study was conducted to determine the indication of elective neck dissection in patients with early oral cavity SCC. PATIENTS AND METHODS: Sixty-seven patients were stratified by stage (T1 and T2 NO), and those in each stage were randomized to receive one of two types of treatment; resection alone (RA) or resection plus elective supraomohyoid neck dissection (RSOND). Fifty-two patients (78%) were men and 15 (22%) were women. The median age was 57 years old (range 34 to 95). RESULTS: Twenty-six (39%) patients had tumor in the floor of the mouth and 41 (61%), in the tongue. Using the criteria of the Union Internationale Contre le Cancer (UICC), 1987, we classified 31 tumors (46%) as T1 lesions and 36 (54%) as T2 lesions. Thirty patients had a tumor thickness < or = 4 mm and 37 had a tumor thickness > 4 mm. Thirty-three (49%) patients were treated with RA, and 34 patients (51%) were treated with RSOND. Seven (21%) patients of the RSOND group had occult cervical metastasis. There were recurrences in 14 (42%) patients of the RA group and 8 (24%) patients of the RSOND group. The disease-free survival rates at 3.5 years for RA and RSOND patients were 49%, and 72%, respectively. The impact of sex, age, site, cancer stage, and tumor thickness was assessed by the Mantel-Haenszel chi-square procedure. Later stage (P = 0.05) and increased tumor thickness (P = 0.005) were significantly associated with treatment failures. CONCLUSION: Neck dissection remains mandatory in the early stage of oral SCC, because of better survival rates compared to RA and the poor salvage rate. In particular, patients with tumor thickness > 4 mm treated with RSOND had significant benefit on disease-free survival.     

Ovarian vein syndrome

SETTING: A voluntary community health worker programme, in the Western Cape, South Africa, utilizing volunteers to administer directly observed therapy to tuberculosis (TB) patients. OBJECTIVE: This study describes the perceptions of health team members regarding the voluntary community health worker project. DESIGN: A qualitative, participatory research study utilizing focus groups. RESULTS: TB was perceived by the health team to be a stigmatized disease causing some patients to be reluctant to be associated with the TB control programme. Despite the project's dedicated approach to case-holding, volunteers expressed the need to develop skills in providing more comprehensive care. The volunteers appear to administer a more personalized service to TB patients and can bridge the gap between TB patients and the health agency. CONCLUSION: Sustained evaluation and support seem to be a vital tool in integrating a volunteer project into a health team approach. Its effectiveness appears to depend to a large degree on the people involved.     

Plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation

Thrombin Activatable Fibrinolysis Inhibitor (TAFI) is a recently identified fibrinolysis inhibitor in plasma, that when converted to an enzyme potently attenuates fibrinolysis. It is activated by relatively high concentrations of thrombin that exceed the thrombin concentration required for fibrin formation. These high concentrations of thrombin are generated by the intrinsic pathway via activation of factor XI by thrombin. The down regulation of fibrinolysis by TAFI can be measured in a clot lysis assay. When the clot lysis times of healthy individuals were determined, large inter-individual differences were observed. To determine if differences in concentration of TAFI explain the variation in clot lysis between individuals, specific assays were developed for the measurement of TAFI antigen and activity in plasma. In normal plasma, there was a dose-dependent relationship between TAFI antigen and TAFI activity. There was also a correlation between clot lysis time and plasma TAFI antigen, indicating that the amount of TAFI that is activated during the clot lysis assay, is dependent on the concentration of TAFI. In the plasmas of 20 healthy individuals, clot lysis times, TAFI antigen and TAFI activity were determined. Both TAFI antigen and TAFI activity showed a significant correlation with the clot lysis time. No correlation between TAFI antigen and clot lysis time was found when the clot lysis time was determined in the presence of an antibody blocking the factor XI feedback loop. These results indicate that plasma TAFI levels influence the clot lysis time in healthy individuals in the presence of an intact intrinsic pathway of coagulation.     

The correlation between neuron counts and optical density of NADPH-diaphorase histochemistry in the rat striatum: a quantitative study

NADPH diaphorase (NADPH-d) histochemistry is a useful technique for examining select neuronal populations in both experimental studies and human neuropathology and also provides a simple method to localize nitric oxide synthase in the central nervous system. However, no established method exists for detecting quantitative changes of NADPH-d histochemistry under different experimental conditions. To develop a quantitative procedure, we systematically examined the properties of NADPH-d histochemistry and then investigated the correlation between the number of NADPH-d positive cells and the optical density of NADPH-d histochemistry in the rat striatum. NADPH-d activity was sensitive to specific experimental conditions, such as incubation time, fixation, and high temperature. In the striatum NADPH-d activity of neuropil was more sensitive to these conditions than were the somata. The different staining patterns of NADPH-d between the neuropil of the striatum and white matter, such as the optic tract suggest neuropil staining in the striatum is not just unspecific background staining. Increasing incubation time only increased the optical density of NADPH-d staining, in contrast, the number of NADPH-d positive cells counted was relatively consistent across incubation times. Therefore, little correlation existed between the optical density and cell number. These results indicate that when using NADPH-d histochemistry, the number of NADPH-d positive neurons is independent of the optical density of the staining, and these two parameters should be considered and treated separately when conducting quantitative analysis related to an experimental treatment.     

The use of carbon carriers for the immunoenzyme diagnosis of viral infections

Carbon solid phase for enzyme-linked immunosorbent assay was proposed. This support can be used instead of polysterene plates because the following steps (carbon support incubate with specific and detective reagents) are implemented in arbitrary minimal capacities. The method was tested for detection of the virus antigens (hepatitis B, herpes simplex) and anti-viral (anti-adenovirus, anti-influenza virus) antibodies.     

Antibodies to the food mutagens, 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine and 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline: useful for immunoassay and immunoaffinity chromatography of biological samples

Monoclonal mouse IgG1 and IgG3 antibodies were developed to the food mutagens, 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and 2-amino-3,4,8-trimethylimidazo[4,4-f] quinoxaline (4,8-DiMeIQx) in order to make specific and sensitive detection and purification systems suitable for biological samples. The antibodies were developed with the strategy that cross-reaction with analogues modified in the N2-position was desirable. Competitive enzyme-linked immunosorbent assays (ELISA) with 50% inhibition by 0.4-6 pmol food mutagen were developed. The epitopes recognized by the antibodies have been characterized by ELISA using 52 synthetic analogues and metabolites of PhIP, 4,8-DiMeIQx, and other food mutagens. One of the anti-PhIP antibodies only recognizes PhIP and those PhIP-analogues which have minor modifications in the N2-amino group, whereas the other, 7B7-1, is less stringent and also recognizes several other modified metabolites, including bulky adducts at the N2-amino group e.g. the major guanine and deoxyguanosine adducts isolated from PhIP-modified DNA. The antibodies to DiMeIQx also recognize the food mutagens 2-amino-3,4-dimethylimidazo[4,5-f]quinoxaline (4-MeIQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx), and the corresponding quinolines (4-MeIQ and 8-MeIQ). Two of these antibodies only bind analogues with minor modifications in the free amino group, whereas analogues with major modifications in this position, including a deoxyguanosine adduct, react with the third antibody. Urine samples and faecal extracts from 3H-PhIP or 2-14C-DiMeIQx dosed rats were analysed by these ELISA assays, and high correlations between radioactivity and response in the ELISA assays were observed. Urine samples and faecal extracts from 3H-PhIP-dosed rats were purified on an affinity column containing the less stringent anti-PhIP antibody, 7B7-1. The affinity column was found by high performance liquid chromatography (HPLC) analysis to concentrate exclusively labelled material. This affinity column also bound PhIP-related materials from dilute samples of acid hydrolysed PhIP-DNA with high efficiency. Only approximately 40% of the 4,8-DiMeIQx related materials found in dilute acid hydrolysed samples of 4,8-DiMeIQx-DNA was bound by an affinity column containing the less stringent anti-4,8-DiMeIQx antibody, 2C5-1. We conclude that our anti-PhIP and anti-DiMeIQx antibodies can be used to determine the presence of these food mutagens and some of their activated or conjugated metabolites in complex biological samples.