Increased blood cadmium levels were not associated with increased fracture risk but with increased total mortality in women: the Malmö Diet and Cancer Study.

This study aimed to investigate if high levels of blood cadmium at baseline were associated with increased fracture risk during follow-up in middle-aged women. No increased fracture risk was observed during follow-up, but women with higher levels of cadmium had an increased overall mortality. INTRODUCTION: Exposure to high levels of cadmium has been associated with an increased fracture risk. The aim was to investigate a perceived association between low levels of blood cadmium (B-Cd) at baseline and risk of first incident fracture. METHODS: From the population-based Malmö Diet and Cancer Study Cardiovascular cohort, 2920 middle-aged women with available background questionnaire and B-Cd measurements were included. Women were divided into quartiles (Q) according to their cadmium levels (Cd-Q1 <0.18 µg/L, Cd-Q2 0.18-0.28 µg/L, Cd-Q3 0.28-0.51 µg/L, and Cd-Q4 >0.51 µg/L). National registries were analysed for prospective risk of fractures or death. Associations between B-Cd and fracture risk were assessed by survival analysis (Cox regression analysis). RESULTS: In total, 998 first incident fractures occurred in women during a follow-up lasting 20.2 years (median) (12.5-21.2 years) (25th-75th percentile). Women in Cd-Q4 were more often current smokers than in Cd-Q1 78.4 vs. 3.3% (p < 0.001) and the number of cigarettes smoked per day correlated with B-Cd (r = 0.49; p < 0.001). The risk of fracture was not associated with baseline B-Cd in adjusted models. The hazard ratio (HR) Cd-Q4 vs. Cd-Q1 was 1.06 (95% confidence interval (CI) 0.89-1.27). In the multivariate Cox regression, independent variables for increased fracture risk were history of gastric ulcer and increasing age, whereas increasing body mass index (BMI) lowered fracture risk. Overall mortality was significantly higher for women with high B-Cd, HR 2.06 (95% CI 1.57-2.69). CONCLUSIONS: Higher blood levels of cadmium did not increase fracture risk in middle-aged women but reduced overall survival.

Neutrophilic granulocytes are the predominant cell type infiltrating pancreatic islets in contact with ABO-compatible blood.

The poor outcome of intraportal islet transplantation may be explained by the instant blood-mediated inflammatory reaction (IBMIR), characterized by islet entrapment in blood clots, leucocyte infiltration and disruption of islet morphology. Here we employ a newly developed in vitro system to identify the blood cells involved in this process. Islets were mixed with ABO-compatible blood in heparinized tubes and incubated for various times up to 6 h. Clots were analysed immunohistochemically for detection of platelets (CD41a), leucocytes/lymphocytes (CD11b), granulocytes (CD16, lysozyme), neutrophilic granulocytes (neutrophil elastase), eosinophilic granulocytes (NaCN + H(2)O(2)), macrophages (CD68), dendritic cells (CD209/DC-SIGN), B cells (CD20) and T cells (CD4, CD8). Platelets were rapidly deposited around the islets in contact with the blood, reaching a maximum by 30 min. The first neutrophilic granulocytes appeared in the islets after 15 min, increased at 1 h and peaked at 2 h. Small numbers of macrophages were found infiltrating the islets already after 5 min, with a slight increase over time. However, control stainings of cultured islets and pancreas biopsies identified these cells as being largely of donor origin. No T cells, B cells, dendritic cells or eosinophilic granulocytes were detected during the 6 h observation time. Neutrophilic granulocytes were identified as the main infiltrating blood cell in islets exposed to blood, implying that these cells play a key role in clinical islet transplantation. Because islets are known to be exquisitely susceptible to oxidative stress, development of drugs targeting neutrophilic cytotoxicity could markedly improve the outcome of islet transplantation.

Radionuclide migration in forest ecosystems--results of a model validation study.

The primary objective of the IAEA's BIOMASS Forest Working Group (FWG) was to bring together experimental radioecologists and modellers to facilitate the exchange of information which could be used to improve our ability to understand and forecast radionuclide transfers within forests. This paper describes a blind model validation exercise which was conducted by the FWG to test nine models which members of the group had developed in response to the need to predict the fate of radiocaesium in forests in Europe after the Chernobyl accident. The outcomes and conclusions of this exercise are summarised. It was concluded that, as a group, the models are capable of providing an envelope of predictions which can be expected to enclose experimental data for radiocaesium contamination in forests over the time scale tested. However, the models are subject to varying degrees of conceptual uncertainty which gives rise to a very high degree of divergence between individual model predictions, particularly when forecasting edible mushroom contamination. Furthermore, the forecasting capability of the models over future decades currently remains untested.

Production of tissue factor by pancreatic islet cells as a trigger of detrimental thrombotic reactions in clinical islet transplantation.

BACKGROUND: Intraportal transplantation of pancreatic islets offers improved glycaemic control and insulin independence in type 1 diabetes mellitus, but intraportal thrombosis remains a possible complication. The thrombotic reaction may explain why graft loss occurs and islets from more than one donor are needed, since contact between human islets and ABO-compatible blood in vitro triggers a thrombotic reaction that damages the islets. We investigated the possible mechanism and treatment of such thrombotic reactions. METHODS: Coagulation activation and islet damage were monitored in four patients undergoing clinical islet transplantation according to a modified Edmonton protocol. Expression of tissue factor (TF) in the islet preparations was investigated by immunohistochemistry, immunoprecipitation, electron microscopy, and RT-PCR. To assess TF activity in purified islets, human islets were mixed with non-anticoagulated ABO-compatible blood in tubing loops coated with heparin. FINDINGS: Coagulation activation and subsequent release of insulin were found consistently after clinical islet transplantation, even in the absence of signs of intraportal thrombosis. The endocrine, but not the exocrine, cells of the pancreas were found to synthesise and secrete active TF. The clotting reaction triggered by pancreatic islets in vitro could be abrogated by blocking the active site of TF with specific antibodies or site-inactivated factor VIIa, a candidate drug for inhibition of TF activity in vivo. INTERPRETATION: Blockade of TF represents a new therapeutic approach that might increase the success of islet transplantation in patients with type 1 diabetes, in terms of both the risk of intraportal thrombosis and the need for islets from more than one donor.

Eosinophil cationic protein is stored in, but not produced by, peripheral blood neutrophils.

BACKGROUND: Eosinophil cationic protein (ECP) is an eosinophil-derived protein, which has been shown to be present in circulating neutrophils. OBJECTIVE: To establish whether ECP is produced or internalized by peripheral blood neutrophils. METHODS: This was done using microscopy, flow cytometry, fractionation of cells and RT-PCR techniques. RESULTS: No ECP mRNA was detected after extensive cell purification to eliminate all traces of contaminating eosinophils. Examination of immunostained neutrophils by light, confocal, electron microscopy together with cell fraction experiments, established that ECP is present intracellularly and is mostly associated to cell granules. Uptake studies by flow cytometry and by using both cold and radiolabelled ECP showed that it is internalized by neutrophils and stored in some proportion in their primary granules. Upon stimulation with serum-treated Sephadex particles, the internalized ECP was partially released from cells. CONCLUSION: ECP is not produced but can be internalized by circulating neutrophils, which take it from the environment and partially store it in their primary granules.

Brånemark System and ITI Dental Implant System for treatment of mandibular edentulism. A comparative randomized study: 3-year follow-up.

In a randomized prospective study, two implant systems were compared in forty consecutive patients treated for mandibular edentulism. The patients were randomly allotted for treatment by the Brånemark two-stage (submerged) system (BRS), or the ITI(R) one-stage (non-submerged) system. In all, 102 Brånemark selftapping implants and 106 ITI hollow screw implants were installed and all patients were treated with full bridges. Biological and prosthodontic parameters, complications, success rates, clinical efficacy, patient satisfaction and resource requirements were evaluated. No differences were found in plaque accumulation, bleeding or complications during the follow-up period. The BRS group showed deeper periimplant sulcus, less attached mucosa, larger bridge-mucosa distance and higher Periotest values. Prosthetic complications were not related to the configuration of the implant systems. After 3 years, the cumulative success rates were 97.9% and 96.8% for the Brånemark and ITI systems, respectively (difference not statistically significant). One implant in the BRS group had failed to osseointegrate at the time of abutment connection, and another was lost after 2 years due to progressive breakdown of bone. In the ITI group, three implants showed progressive bone loss after 1-3 years associated with periimplant infection. All 40 bridges were intact and remained stable throughout the study. There was general patient satisfaction, but about half the Brånemark patients reported difficulty in coping with the surgical procedures. Treatment time was similar for the two systems. It is concluded that both systems meet the current requirements for dental implant systems in the treatment of mandibular edentulism.

(99m)Tc-HMPAO (Ceretec) is stored in and released from the granules of eosinophil granulocytes.

(99m)Tc-HMPAO (Ceretec) labelling of leucocytes is used clinically for the detection of inflammatory processes in the body. This study investigated the mechanisms by which (99m)Tc-HMPAO is taken up by eosinophils and neutrophils. Blood cells were labelled with (99m)Tc-HMPAO and the cells separated by means of their densities in Percoll gradients. For other purposes, eosinophils and neutrophils were purified by means of the MACS system and, after labelling these pure cellular preparations, the cells were ultrasonicated and the organelles separated on sucrose density gradients by means of ultracentrifugation. Organelles were characterized by their morphology on electron microscopy. Granulocytes were stimulated to secrete their granule constituents by means of exposure to complement-coated particles. ECP (eosinophil cationic protein) and MPO (myeloperoxidase) were measured using specific immunoassays. The uptake of (99m)Tc-HMPAO was 15--25-fold higher in eosinophils than in other leucocytes. (99m)Tc-HMPAO was predominantly stored in the secretory granules of eosinophils and released from the eosinophil, upon activation, together with ECP. A second storage compartment was a very light density organelle of unknown nature. These results indicated that, among leucocytes, (99m)Tc-HMPAO is preferentially taken up by eosinophils and stored in the secretory granules, which has to be taken into consideration when evaluating images based on this technique. Our findings suggest that (99m)Tc-HMPAO (Ceretec) may be used as a tool to follow eosinophil turnover and activity in disease.

Resin-bonded bridges by dental undergraduates: three-year follow-up.

This study was conducted to evaluate performance and longevity of resin-bonded bridges in patients treated by undergraduate dental students. A total of 62 bridges had been constructed for 53 patients by the students at the School of Dentistry, Karolinska Institute, between 1989 and 1997. After a mean observation period of 35.3 months retention had been lost in 13.6% of 59 bridges examined (4.6% per year). The debonding rate was greater in the mandible (8.3 %/year) than in the maxilla (2.7 %/year), and greatest in the mandibular anterior region (13.4%). Thirty-nine patients with 46 bridges (27 maxillary and 19 mandibular bridges), underwent more detailed clinical examination. No significant differences in bleeding and pocket depth were found between abutment teeth and controls. Bleeding was more frequent at the approximal than the lingual surfaces of the abutment teeth. A questionnaire revealed high patient satisfaction, the resin-bonded bridges meeting their expectations. The study suggests that resin-bonded bridges are an acceptable alternative to conventional bridges. Successful outcome is dependent on stringent case selection, an abutment preparation designed to establish retention form, and meticulous bonding procedures.

A comparison of three models of 137Cs transfer in forest ecosystems.

The predictions of three models of 137Cs transfer in forest ecosystems (FOA, LOGNAT and FORESTLAND) were compared. The scenario for the model-model comparison consisted of an acute dry deposition of 137Cs over a coniferous forest. The model predictions were subsequently compared (model-data comparison) with values derived from experimental data measured in forests of the Bryansk region in Russia that were contaminated by the Chernobyl accident and that have similar characteristics to the forests described in the scenario. The predictions of radiocaesium levels in the litter-soil layer, berries, needles, wood, whole tree and moose made with the models were in relatively good agreement with each other (within a factor of 1.4-2.9). The best agreement was observed for berries and moose and the worst for wood. There was also good agreement between the model predictions for the same variables and the experimental data (within a factor of 1.2 3.2). In this case, the best agreement was observed for the litter-soil layer and the worst for wood and the whole tree. Overall, at least for the studied scenario and for the first 10 years after deposition, any of the models can be used if the final aim is to estimate average concentrations in different forest components. The agreement between the model predictions worsens with time and there were differences in the form of the time dependencies predicted by the models, especially for wood. This may lead to larger differences between the model predictions and the experimental data for times beyond the period for which data were available for comparison (10 years after the deposition).

Spectrofluorimetric determination of chlorophylls and pheopigments using parallel factor analysis.

In this study, parallel factor analysis (PARAFAC) was applied to fluorescence excitation emission matrices (EEM) of chlorophylls and pheopigments dissolved in acetone:water (9:1). The excitation wavelength range was from 350 to 500 nm and the emission was recorded from 600 to 730 nm. Nine standards, comprising mixtures of six analytes, were decomposed into a six-component PARAFAC model. Each component resembled the corresponding EEM of the pure analyte, demonstrating the uniqueness properties of PARAFAC. The score matrix obtained from the model was used for calibration and prediction of an independent set of standards and for eleven samples collected in the Baltic proper. The results obtained by the proposed method were compared to classical least squares (CLS) and to predictions by reference methods (HPLC and visible spectroscopy). For the independent set of standards the proposed method and CLS performed equal well in terms of predictive ability. But for the samples the proposed method yielded results that were in good agreement to the reference methods, whereas CLS failed. Also the so-called "second-order advantage" was examined, showing that not all constituents must be included in the calibration set. The concentration range was for chlorophyll a varied between 10 and 75 mug l(-1), and similar for the other analytes.

Evaluation of single-tooth restorations on ITI dental implants. A prospective study of 29 patients.

From January 1992 to March 1997, a total of 30 ITI hollow cylinder implants were installed to replace lost single maxillary incisor teeth. Conical abutments with cemented all-ceramic crowns were used in 10 cases and the Octa-abutment with screw-retained metallo-ceramic crowns in 19 cases. One implant failed due to postoperative infection, and was extracted a month after installation. After a mean observation time of 3.4 years, the cumulative success rate is 96.7%. Only minor bone loss has occurred around the implants, and there have been no other complications to date. The implant system fulfills the requirements for good function and esthetics.

Dental implant installation without antibiotic prophylaxis.

The objective of this study was to retrospectively compare the outcomes of dental implant treatment with and without antibiotic prophylaxis. Two groups of patients with edentulous or partially edentulous maxillas or mandibles (or both) were treated with dental implants. One group, consisting of 147 patients (790 implants), was given prophylaxis with oral phenoxymethylpenicillin; 1 g of antibiotic was administered 1 hour preoperatively, and 1 g was administered every 8 hours for 10 days postoperatively. The other group, consisting of 132 patients (664 implants) was not given any antibiotics preoperatively or postoperatively. There were no significant differences with respect to early and late postoperative infections or with respect to implant survival between the two groups. It appears that antibiotic prophylaxis for routine dental implant surgery offers no advantage for the patient.

Pronounced anti-HIV-1 activity of foscarnet in patients without cytomegalovirus infection.

Combined therapy using reverse transcriptase (RT) and protease inhibitors is the current established treatment for HIV-1 infection. Foscarnet is an RT inhibitor that is a product analogue, in contrast to the widely used nucleoside analogues. In this study, the anti-HIV-1 effect of foscarnet, 50 mg three times per day administered intravenously for 4 weeks, was evaluated in 10 patients with minor or no symptoms. Serious adverse events developed in 2 patients, although most patients experienced some side effects. The levels of HIV-1 RNA decreased from a median value of 4.7 to 2.6 10log copies/ml. The effect was sustained through 4 weeks. One week after cessation of treatment, HIV-1 RNA levels increased to baseline. In contrast, no increase in the number of CD4+ cells was observed. The anti-HIV-1 effect was considered to be a direct effect on HIV-1 replication because no patient had concomitant cytomegalovirus (CMV) infection.

Reconstruction of the resorbed edentulous maxilla using autogenous rib grafts and osseointegrated implants.

14 patients with severely resorbed edentulous maxillae underwent reconstruction by the use of autogenous rib graft on-lays and osseointegrated Brånemark System implants in a one-stage procedure. 75 implants were installed. 16 (21.3%) failed to osseointegrate at the abutment connection. After a mean observation period of 5.2 years, 55 (73.3%) of the original implants were osseointegrated. 10 supplementary implants were inserted in 3 patients. At the end of the observation periods, 2 patients had overdentures and 12 had fixed prostheses. The mean marginal bone loss was 2.13 mm (SD 0.47 mm) the 1st year after grafting, and 2.92 mm (SD 1.27 mm) at the end of the follow-up periods. Long-term follow-up did not show any persistent donor site discomfort. The results indicate that this technique is a conceivable alternative for patients with severe maxillary resorption.

An eleven year follow-up of delayed-type hypersensitivity testing for the identification of HIV-1 infected patients at increased risk of developing AIDS.

The objective of this study was to investigate whether testing of delayed-type hypersensitivity (DTH) to recall antigens could be used to identify HIV-1 infected patients at increased risk of death or developing AIDS. Eighty-five HIV-1 infected Swedish homosexual men were tested for DTH using a commercially available kit with 7 recall antigens (Multitest, Mérieux). The patients were followed prospectively for 11 years or until death. The 11-year actuarial progression rate to AIDS was 69% and to death 60%. Older age was identified as a factor predisposing to rapid progression independent of cell-mediated immunity measured by DTH. Patients with a subnormal DTH had a significantly more rapid progression to AIDS and death than did patients with normal DTH, and the time between AIDS diagnosis and death was shorter. For patients with a multiscore (MS) < 10 mm, the median time to AIDS was 59 months, the median time to death 88 months, and the median time from AIDS diagnosis to death 11 months, compared to 106, 139, and 25 months, respectively, for patients with MS > or = 10 mm. Of the individual antigens, only a negative reaction to tuberculin was independently predictive of progression to all 3 endpoints, while a negative reaction to tetanus was independently predictive of progression to death. Thus, determination of DTH improves the early recognition of patients at increased risk of progressive disease.

A sensitive double-antibody enzyme-linked immunosorbant assay for bovine myeloperoxidase and its application to serum and neutrophil extracts.

The heme enzyme myeloperoxidase (MPO), with a spectral A430/A280 ratio > 0.78, was purified from isolated bovine neutrophils. Using highly specific anti-MPO monoclonal and anti-MPO polyclonal antibodies raised against MPO, a specific and sensitive double-antibody enzyme-linked immunosorbant assay (ELISA) was developed to measure bovine MPO in serum and neutrophil extracts. The ELISA shows good precision and accuracy, with intra- and interassay coefficients of variation of < 10% for MPO concentrations ranging from 0.5 to 50 ng/ml. The accuracy of the ELISA for measuring MPO in bovine serum was further confirmed by the similarity between the standard curve and curves obtained with successive dilutions of MPO-rich serum samples. The mean analytical recovery of MPO from serum was approximately 90%. Long delays between blood sampling and serum preparation were found to affect the level of MPO in the serum. Mean MPO values in the serum of healthy adult cows were 6.5 ng/ml, with a range of 3.5-15.3 ng/ml. In dairy cows with acute mastitis, mean serum MPO values were approximately 30 ng/ml, with a range of 6.0-59.6 ng/ml, and the elevation was markedly higher than the normal values (P = 0.0001). In isolated neutrophils from healthy cattle, MPO concentrations were found to be 7 x 10(-4) ng, with a range of 6.5-8.3 x 10(-4) ng/neutrophil. The ELISA was used to study the distribution of MPO in the bovine neutrophil granules; it was found to be localized to one distinct compartment.

Evaluation of three silicoating methods for resin-bonded prostheses.

Three different methods of increasing the bond strength of resin to metal were tested: the original Silicoater technique, the Silicoater MD technique, and the Rocatec system. Metals used for the resin-bonded prostheses were gold, a cobalt-chromium (Co-Cr) alloy, and titanium. Silicoating increased the bond strength to sandblasted specimens. The original Silicoater technique produced the highest bond strengths, especially when used with the Co-Cr alloy and titanium. The Silicoater MD technique showed the lowest bond strengths for all of the test metals. Storage for 7 days with protective film on the silicoated surface did not affect the bond strength, as compared with specimens bonded immediately. The retention of the resin to the gold specimens (Rocatec system) decreased after thermocycling, but retention to the Co-Cr alloy and titanium was not affected. Various resin cements were tested and showed the same retention with the exception of Microfill Pontic, which gave a weaker bond. Scanning electron microscope (SEM) and energy-dispersive X-ray analysis (EDAX) of the specimens before and after the measurements gave no clear explanation of the differences in bond strengths between the test metals. However, it was concluded that silicoating of the metal surfaces contributed to the retention of the resin by chemical action, as no differences in adaptation of the resin to the metal were seen between specimens pretreated by sandblasting and those which were also silicoated.