The applicability of the measurement of urinary thioethers

Summary The excretion of thioethers was measured in the urine of 6 volunteers, who were experimentally exposed to styrene, and 18 styrene workers. In addition, 12 clerks (non-smokers) and 12 sheet-metal workers (smokers) served as control groups. Diet was standardized during the experiments. Thioethers were measured by a spectrophotometric method. The volunteers were exposed to styrene, 210 mg/m³, for 2 h at a 50-W workload. An increase in thioether excretion was observed; the largest was in the urine samples collected between 0.5 and 5 h after the end of the exposure. After 43 h the excretion of thioethers was close to the preexposure level (3.5 mmol/mol creatinine). About 1% of the styrene absorbed was detected as thioethers in urine, which is only about 1/10 of the conversion reported for rats. From excretion rate curves a half-life of about 11 h was calculated for styrene thioethers. The styrene workers were employed at two plants. The average exposure to styrene (time-weighted average 8 h) was estimated to be about 115 mg/m3 (smokers in plant A), 55 mg/m³ (non-smokers in plant A) and 10 mg/m³ (non-smokers in plant B). The excretion of thioethers in exposed workers at plant A was higher by 2–4 mmol/mol creatinine than that in non-exposed controls. In plant B, where exposure was lower, an increase in that amount of thioethers excreted in the urine by exposed workers was less pronounced, and was statistically significant only when post-shift samples were compared with pre-shift samples. The results of the present study indicate that control samples should be collected both from non-exposed groups and from the exposed individuals before work shifts, to improve the likelihood of detecting genotoxic exposure in the work environment.     

Electron microscopy and X-ray microanalyses of uterine epithelium from lead-injected mice in an experimental delay of implantation

Mice in experimental delay of implantation were injected intravenously with 75 g · g^–1 body weight of lead chloride, corresponding to a dose of lead of about 56 g · g^–1 body weight. Delay of implantation was obtained by ovariectomy 3 days after mating followed by a depot dose of progesterone every fifth day. Electron microscopy showed that the uterine lumen, which was closed in control mice, was opened in lead-injected mice. This morphology suggested that lead caused an increase in uterine secretion. X-ray microanalysis of pyroantimonate precipitates in the uterine epithelium of injected mice demonstrated lead in the precipitates, suggesting that lead could have a direct effect on the function of the uterine epithelium and that lead also could be secreted into the uterine lumen and affect the blastocysts.     

Evaluation of micromotion in cemented vs uncemented knee arthroplasty in osteoarthrosis and rheumatoid arthritis. Randomized study using roentgen stereophotogrammetric analysis

Twenty-four patients (25 knees) with osteoarthrosis (OA) and 19 patients (20 knees) with rheumatoid arthritis (RA) were operated with bi-tricompartmental knee arthroplasty. The patients were randomized to cemented or cementless fixation of the tibial component. The fixation of the tibial components was examined with roentgen stereophotogrammetric analysis (RSA) up to 24 months after operation. The following parameters representing tibial component micromotion were measured: (1) maximum migration of the prosthetic edge (maximum total point motion, MTPM); (2) distal migration of the prosthetic center (subsidence); (3) maximum proximal movements of the prosthetic edge ("lift-off"); and (4) prosthetic rotations, corresponding to internal/external rotation, adduction/abduction, and forward/backward tilt of the tibial component. All prostheses displayed significant micromotions, which tended to decrease 3-6 months after the operation. The average migration after 2 years, when measured as maximum single axis rotation, and MTPM were about 0.9 degrees-1.5 degrees and 1.0-1.5 mm, respectively, in all four groups. There were no statistically significant differences between cemented and cementless prostheses in either the OA or the RA group. The fixation in the RA patients did not significantly differ from that of the OA patients, perhaps because the RA patients had lower weight and were living a more sedentary life.     

Mechanistic Insights Into the Heterogeneity of Glucose Response Classes in Youths With Obesity: A Latent Class Trajectory Approach

OBJECTIVEIn a large, multiethnic cohort of youths with obesity, we analyzed pathophysiological and genetic mechanisms underlying variations in plasma glucose responses to a 180 min oral glucose tolerance test (OGTT).RESEARCH DESIGN AND METHODSLatent class trajectory analysis was used to identify various glucose response profiles to a nine-point OGTT in 2,378 participants in the Yale Pathogenesis of Youth-Onset T2D study, of whom 1,190 had available TCF7L2 genotyping and 358 had multiple OGTTs over a 5 year follow-up. Insulin sensitivity, clearance, and β-cell function were estimated by glucose, insulin, and C-peptide modeling.RESULTSFour latent classes (1 to 4) were identified based on increasing areas under the curve for glucose. Participants in class 3 and 4 had the worst metabolic and genetic risk profiles, featuring impaired insulin sensitivity, clearance, and β-cell function. Model-predicted probability to be classified as class 1 and 4 increased across ages, while insulin sensitivity and clearance showed transient reductions and β-cell function progressively declined. Insulin sensitivity was the strongest determinant of class assignment at enrollment and of the longitudinal change from class 1 and 2 to higher classes. Transitions between classes 3 and 4 were explained only by changes in β-cell glucose sensitivity.CONCLUSIONSWe identified four glucose response classes in youths with obesity with different genetic risk profiles and progressive impairment in insulin kinetics and action. Insulin sensitivity was the main determinant in the transition between lower and higher glucose classes across ages. In contrast, transitions between the two worst glucose classes were driven only by β-cell glucose sensitivity.     

Combination anti-CD137 and anti-CD40 antibody therapy in murine myc-driven hematological cancers

In order to stimulate antigen presentation and T cell activity against cancer, we treated three different tumor models in mice with the monoclonal antibodies anti-CD40 plus anti-CD137 (BiMab). In a subcutaneous transplantable MC38 colon cancer model, there was significant enhancement in the survival of mice following BiMab treatment. Anti-CD40 has shown considerable success against lymphoma in previous studies by other investigators, and we also showed in this study that, in a model of Eμ-Myc lymphoma, there was a statistically significant enhancement of survival of mice following BiMab treatment. Following the success of the BiMab treatment in the previous two models, we wished to determine if it would be successful in a mouse model of multiple myeloma. Firstly, we tested a transplantable model of disease in which multiple myeloma cells derived from Vk*MYC mice were injected intravenously. A minor proportion of anti-CD137 and BiMab treated mice experienced prolongation of life beyond 250 days. Then we tested the therapy in a spontaneously occurring multiple myeloma model, in Vk*MYC transgenic mice. The majority of mice treated survived longer than control mice, although statistical significance was not demonstrated.     

Lactate dehydrogenase isoenzymes of the human periodontal ligament

The isoenzymes of lactate dehydrogenase (E. C. 1. 1. 1. 27.) from the periodontal ligament on the root surface of extracted erupted permanent human teeth have been separated and quantitated by means of cellulose acetate membrane electrophoresis.
LDH-3 and LDH-4 were the predominating isoenzymes. and smaller amounts of LDH-2 and LDH-5 were also present. Only traces of LDH-1 could be seen. The results indicate the presence of both aerobic and anaerobic metabolic pathways in the human periodontal ligament.
These pathways bring about an efficient, economical energy production under normal circumstances, and make the survival of this tissue possible under hypoxic conditions, when the blood supply is briefly interrupted. The results further show that determinations of the survival time of the periodontal ligament on a tooth outside its alveolus have to be made by activity measurements of both aerobic and anaerobic enzymes.     

Extramedullary fixation of 569 unstable intertrochanteric fractures: A randomized multicenter trial of the Medoff sliding plate versus three other screw-plate systems

We compared the efficacy of the Medoff sliding plate (MSP) with 3 other screw-plate systems for fixation of unstable intertrochanteric fractures in a randomized multicenter trial of 569 elderly patients. The MSP has biaxial dynamic capacity along both the neck and the shaft of the femur unlike the other systems, which lack dynamic capacity along the shaft. 268 fractures were operated on with the MSP, and 301 with the dynamic hip screw (DHS), with or without a trochanteric stabilizing plate (DHS/TSP) or with the dynamic condylar screw (DCS). The MSP had recently been shown to the surgeons.The patients in the groups were similar as regards age, domestic situation, preinjury walking ability and type of fracture. We followed the patients clinically and radiographically for at least 1 year. There was no significant difference in walking ability at follow-up or rate of return to home. Fixation failure occurred in 18/268 fractures operated on with the MSP, in 8/238 with the DHS, in 3/49 with the DHS/TSP and in 1/14 with the DCS. The difference in the rate of fixation failure was not statistically significant when the MSP group was compared to the 3 other groups. In 14 of the 18 fixation failures in the MSP group, the biaxial dynamic capacity of the MSP had not been used due to technical errors by surgeons, unfamiliar with the new method. No selection bias was found regarding fracture types in the 2 subgroups of patients with correct or inadequate biaxial dynamization. Extramedullary fixation of unstable intertrochanteric fractures with these implants showed a low failure rate. When using the MSP, biaxial dynamization must be correctly performed.