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Background End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. Objective Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence. Methods A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. Results Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P99%). Missing data due to technical issues were limited. Conclusions The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

BACKGROUND End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. OBJECTIVE Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence. METHODS A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. RESULTS Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (PP=.84), age (P=.22), or education level (lower education level: P=.58, middle education level: P=.46, versus high education level), while higher anxiety scores were associated with lower adherence (P=.03). Adherence to the online questionnaires was also high (>99%). Missing data due to technical issues were limited. CONCLUSIONS The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

Spatial data are key to fishery management; however, most often the spatial distribution of marine populations and fishing dynamics are poorly documented, especially for recreational fish species. The combination of fisheries-dependent data (FDD) obtained from logbooks, and local ecological knowledge (LEK) gathered from key stakeholders could be a powerful approach to inform data gaps in data-limited fisheries. In this study, we used both FDD from guides’ catch reports and LEK using an online survey and key-informant interviews to reconstruct the spatial changes in bonefish (Albula vulpes) catch and fishing effort throughout South Florida over the past 35–40 years, and better understand the extent and spatial patterns of the bonefish decline described in previous studies. Although anglers perceived a decline of bonefish numbers across all fishing areas (26 to 53% drop across Biscayne Bay, the Florida Keys, and Florida Bay), the start of the bonefish decline in Florida Bay resulted in the highest drop in bonefish number (53%); thus, indicating both regional and localized decline events affecting bonefish abundance. Within Florida Bay, LEK and FDD concurred with an initial drop in bonefish at Inner Bay, followed by a greater magnitude of decline at Outer Bay. Metrics of effort derived from the survey and interviews depicted a shrinkage and aggregation in the spatial distribution of fishing and a shift of fishing activities toward the Lower Keys. In sum, the spatiotemporal patterns of catch and effort obtained from LEK and FDD allowed us to understand where, when and how this data-limited species declined in South Florida.

Capromorelin is a ghrelin receptor agonist that is FDA approved for appetite stimulation in dogs. The objective of this study was to evaluate the safety of daily oral administration of capromorelin to cats over a range of doses and for an extended period. Two randomized, controlled studies were conducted: in Study 1, cats (n = 6 per group) received placebo or capromorelin at a dose of 9, 15, 30 or 60 mg/kg once daily for 14 days; and in Study 2, cats received capromorelin at 6 mg/kg (n = 8) or placebo (n = 4) once daily for 91 days. Cats were evaluated using clinical observations and clinical pathology test results for both studies, with the addition of postmortem examination in Study 1 and measurements of growth hormone and insulin-like growth factor 1 in Study 2. Abnormal clinical observations were limited to emesis, hypersalivation, lethargy/depression, head shaking and lip smacking, which occurred more frequently in the capromorelin-treated groups than in the placebo group. There were no clinically relevant differences in clinical pathology test results between the capromorelin and placebo groups in either study.

Background: End-of-day symptom diaries are recommended by drug regulatory authorities to assess treatment response in patients with irritable bowel syndrome. We developed a smartphone app to measure treatment response. Objective: Because the employment of an app to measure treatment response in irritable bowel syndrome is relatively new, we aimed to explore patients’ adherence to diary use and characteristics associated with adherence. Methods: A smartphone app was developed to serve as a symptom diary. Patients with irritable bowel syndrome (based on Rome IV criteria) were instructed to fill out end-of-day diary questionnaires during an 8-week treatment. Additional online questionnaires assessed demographics, irritable bowel syndrome symptom severity, and psychosocial comorbidities. Adherence rate to the diary was defined as the percentage of days completed out of total days. Adherence to the additional web-based questionnaires was also assessed. Results: Overall, 189 patients were included (age: mean 34.0 years, SD 13.3 years; female: 147/189, 77.8%; male: 42/189, 22.2%). The mean adherence rate was 87.9% (SD 9.4%). However, adherence to the diary decreased over time (P 99%). Missing data due to technical issues were limited. Conclusions: The use of a smartphone app as a symptom diary to assess treatment response resulted in high patient adherence. The data-collection framework described led to standardized data collection with excellent completeness and can be used for future randomized controlled trials. Due to the slight decrease in adherence to diary use throughout the study, this method might be less suitable for longer trials.

Background Reduced appetite is a common clinical sign in dogs. This study evaluated the effectiveness and safety of capromorelin oral solution, (ENTYCE®, Aratana Therapeutics, Leawood, KS) a new drug that is a ghrelin receptor agonist, for stimulation of appetite in dogs with reduced appetite. Hypothesis/Objectives Capromorelin will increase appetite, as measured by the owner's evaluation, over 4 days. An additional objective was to evaluate the safety of capromorelin at the labeled dose. Animals A total of 244 client‐owned dogs reported by owners to be inappetent for at least 2 days were enrolled, with 177 cases in the effectiveness analysis. Methods In this prospective, randomized, masked, placebo‐controlled study, dogs were treated daily with capromorelin (3 mg/kg) oral solution (n = 121) or placebo oral solution (n = 56). Owners completed an evaluation of appetite at days 0 and 3 ± 1. Success was defined as improvement in appetite at day 3. Safety was evaluated by physical examination, clinical pathology, and monitoring adverse events and owner observations. Results Capromorelin treatment improved appetite compared to placebo (68.6% and 44.6% treatment successes with 95% CI 59.7, 76.3 and 32.2, 57.8, respectively, P = .008). Mean body weight in capromorelin‐treated dogs increased compared to placebo‐treated dogs (1.8% with 95% CI 1.3, 2.3, and 0.1% with 95% CI 0.9, 1.1, respectively, P 5% of either group were diarrhea and vomiting. Conclusions and Clinical Importance Capromorelin oral solution is an effective treatment for stimulation of appetite in dogs and represents the first ghrelin receptor agonist shown to be effective for this indication.

Storm runoff in the steep watersheds in Hawaii leads to sediment and freshwater pulses to coastal waters that quickly affect nearshore water quality. This is particularly true in semi-enclosed embayments, such as Kaneohe Bay, Oahu, where water has a relatively long residence time compared to more open coastal areas of the islands. In this paper the authors discuss water quality and productivity in Kaneohe Bay after back-to-back rain events in late November and early December 2003, following a particularly dry summer. The short-term biogeochemical response of coastal waters and the ecosystem to runoff and physical forcing was evaluated through a combination of continuous in situ measurements and adaptive synoptic sampling carried out on a variety of temporal and spatial scales. Dissolved N:P ratios in Kaneohe Bay, which normally range from 2 to 4, consistent with a previously documented N-limited system, increase to as high as >25 during storm runoff. Order of magnitude increases in nutrients and chlorophyll in the bay shortly after the first storm and subsequent changes in the plankton community structure reflect an evolving biological response stimulated by storm inputs to the bay. Phytoplankton blooms did not draw nutrients down to limiting levels, likely due to grazing pressure by zooplankton, yet phytoplankton were not grazed to limiting levels. As a result, a slow but steady increase of the phytoplankton standing stock was observed over time. Low phosphate levels (

Background Mechanisms linking changes to the environment with changes in physical activity are poorly understood. Insights into mechanisms of interventions can help strengthen causal attribution and improve understanding of divergent response patterns. We examined the causal pathways linking exposure to new transport infrastructure with changes in cycling to work. Methods We used baseline (2009) and follow-up (2012) data (N = 469) from the Commuting and Health in Cambridge natural experimental study (Cambridge, UK). Exposure to new infrastructure in the form of the Cambridgeshire Guided Busway was defined using residential proximity. Mediators studied were changes in perceptions of the route to work, theory of planned behaviour constructs and self-reported use of the new infrastructure. Outcomes were modelled as an increase, decrease or no change in weekly cycle commuting time. We used regression analyses to identify combinations of mediators forming potential pathways between exposure and outcome. We then tested these pathways in a path model and stratified analyses by baseline level of active commuting. Results We identified changes in perceptions of the route to work, and use of the cycle path, as potential mediators. Of these potential mediators, only use of the path significantly explained (85%) the effect of the infrastructure in increasing cycling. Path use also explained a decrease in cycling among more active commuters. Conclusion The findings strengthen the causal argument that changing the environment led to changes in health-related behaviour via use of the new infrastructure, but also show how some commuters may have spent less time cycling as a result., Highlights • Environmental perceptions did not explain effects of new infrastructure on cycling. • Motivational factors did not explain effects of new infrastructure on cycling. • Eighty-five percent of the effect on increasing cycling was explained by use of the infrastructure. • These results strengthen quasi-experimental causal attribution and understanding.

The pharmacokinetics after oral application of the fluoroquinolones (FQs), enrofloxacin, difloxacin, marbofloxacin and orbifloxacin were compared in independent crossover studies in Beagle dogs. Commercially available tablet formulations were given at common dosage recommended by the manufacturers which were 2.0 mg/kg body weight (bw) for marbofloxacin, 2.5 mg/kg bw for orbifloxacin and 5.0 mg/kg bw for enrofloxacin and difloxacin. Analysis was performed by an agar diffusion assay. Pharmacokinetic parameters were calculated by noncompartmental methods. All FQs were rapidly absorbed and achieved average peak serum concentrations of 1.41, 1.11, 1.47 and 1.37 μg/ mL for enrofloxacin, difloxacin, marbofloxacin and orbifloxacin, respectively. Enrofloxacin was eliminated at a terminal half-life (t 1 /2) of 4.1 h, difloxacin at 6.9 h, orbifloxacin at 7.1 h and marbofloxacin at 9.1 h. While the area under the serum concentration-time curve of the 24-h dosing interval (AUC 0 - 2 4 ) for marbofloxacin and orbifloxacin were similar (approximately 13 μg . h/mL), enrofloxacin attained an AUC 0 - 2 4 of 8.7 and difloxacin of 9.3 μg . h/mL. Because of its favourable pharmacokinetics combined with excellent in vitro activity, enrofloxacin exhibited superior pharmacodynamic predictors of in vivo antimicrobial activity as C m a x /MIC (maximum serum concentration/minimum inhibitory concentration) and AUC 0 - 2 4 /MIC (area under the 24-h serum concentration-time curve/minimum inhibitory concentration) compared with other FQs.

Prion cell tropism varies significantly among animal species, depending on both the agent strain and host-specific factors. For example, prions show high lymphotropism in scrapie infected sheep and vCJD, but little, if any, in sporadic CJD or BSE. In particular, the BSE strain is associated with significant PrP-res accumulation in tonsils, spleen and appendix in humans, whereas, it is largely confined to the CNS in infected cattle. Given that cellular prion protein (PrPC), is sine qua non for PrP-res formation and the development of TSE, it is well possible that tissue-specific PrPC properties may represent one of the host factors influencing the cell tropism of the infectious agent. We applied a western blot analyses to compare the relative percentage of the di-, mono- and unglycosylated PrPC (i.e. glycoform ratio) as well as the expression of truncated PrPC forms in tissues from the CNS and lymphoid structures (lymphoid follicles, lymphocytes and follicular dendritic cells) of bovine and human. We found that PrPC glycoform ratio is significantly different between cerebellum and medulla in both species. Moreover, the expression of truncated PrPC (i.e. 21 and 18 kDa fragments) was significantly heterogenous according to the brain region investigated. PrPC was highly glycosylated in spleen and lymphoid follicles isolated from bovine tonsils, mesenteric lymph nodes, ileal and jejunal Peyer’s patches. After deglycosylation, a novel PrPC truncated form with a relative molecular mass of about 25 kDa was detected in bovine lymphoid organs beside the 18 and 21 kDa forms. No difference in PrPC profile was seen in human lymphocytes extracted either from spleen or tonsil. Our results highlight variations in the tissue expression profile of PrPC in bovine and human. Such differences may have an implication for PrPC function or may represent critical factors influencing the accumulation of the infectious agent in different tissues.

Although chemoembolization advantageously combines arterial embolization of the vascular supply of a neoplasm with controlled intra-arterial infusion of chemotherapeutic drug(s), its application is limited by the lack of appropriate and reliable embolization materials. Recently, calibrated microspheres of poly( d , l )-lactide have proved to be promising in embolization. Nevertheless, repetitive chemoembolization requires the availability of microspheres degradable within a few days. For this purpose, microspheres consisting of a blend of two polyesters of a very different molecular weight (Mn=65 000 and 3500 in a 16:84 wt. ratio) have been prepared and injected in the renal arteries of rabbits. The in vivo fate of these two component microspheres has been compared by radiology and histology to microspheres prepared from the high molecular weight poly( d , l )-lactide. Furthermore, the in vivo degradation of the polymer has been measured by size exclusion chromatography after quantitative reextraction from the embolized kidney. Degradation kinetics has been compared to data previously reported in vitro. According to the observations performed during the in vivo study, the 50/50 microspheres appear more useful for the chemoembolization of tumors.

At the Mainz electron accelerator MAMI a facility has been set up that allows the measurement of the bunchlength, the energy spread and the averaged and phase resolved polarization of picosecond electron bunches from a source of polarized electrons for MAMI. Electron bunches of typically 10 to 30 ps duration are generated by illuminating a strained layer GaAsP photocathode with femtosecond laser pulses.

Gut and blood samples from 119 finishing pigs derived from 11 farms were collected during routine slaughter at an abattoir. Sections of formalin-fixed, paraffin-embedded tissues were labeled immunohistochemically using genus-specific, mouse monoclonal antibody against chlamydial lipopolysaccharide; goat polyclonal antiserum against the major outer membrane protein of Chlamydia trachomatis; and mouse monoclonal antibody against the ovine abortion subtype of C. psittaci. Gut samples from 33 of 111 (29.7%) individual pigs stained positive with the genus-specific monoclonal antibody, and of these 30 of 32 (93.7%) also reacted with the C. trachomatis-specific antiserum. Labeled inclusions were restricted to mature enterocytes of the large intestine in 33 of 111 cases. Infection of small intestinal enterocytes was noted in only one of 82 ileal samples. The blood samples were tested for antichlamydial antibodies by enzyme-linked immunosorbent assay (ELISA) and complement fixation test (CFT). With ELISA, 95 of the 115 sera tested (82.6%) yielded positive antichlamydial reactions. With CFT, 34 of the 119 sera tested (28.6%) were unequivocally positive (≥ 1: 10, 100% binding), and 10 (7.6%) yielded doubtful positive reactions (1: 10, 50-75% binding). Positive ELISA and CFT titers showed poor agreement ( K = 0.112), whereas the agreement between positive findings by immunohistochemical labeling and CFT was fair ( K = 0.205).

The jejunum, ileum, caecum and colon of 200 piglets were investigated immunohistochemically for the presence of Chlamydia psittaci and C. trachomatis using a vitelline IgY. Positive samples were later labelled using a commercial C. trachomatis polyclonal antiserum. Chlamydia were present in 33 (16.4%) of the animals, and 30 out of 33 were labelled by C. trachomatis polyclonal antiserum. Inclusions occurred predominantly (67%) in the large intestine. The serological results (CFT, ELISA) did not correlate well with immunohistochemical labelling in the gut. The incidence of Chlamydia rose from 6.9% in animals up to 4 weeks, to 41.8% in those over 4 weeks of age. A correlation between chlamydia and enteric disease was not obvious. Besides chlamydia, most of the diseased animals harboured other additional agents. In conclusion, intestinal chlamydiae in piglets, predominantly C. trachomatis, exist in Switzerland, although their pathogenic potential seems to be low.

Orodental pathologies are generally classified into two main groups: caries and parodontopathies. They result from polymicrobial infections based on the dental plaque's theory which has constantly evolved. Therefore, the concept of acquired biological pellicle or biofilm has been described and largely elaborated.A bacterial biofilm is a unit of bacterial microcolonies embedded within an exopolymeric matrix and adherent to an inert or living surface. The aim of this paper is to provide a review of the literature with regard to the formation, and composition of the biofilm, as well as to point out the close link that exists between biofilm and dental medicine.

The use of antimicrobial substances has contributed to the development of multiple antimicrobial resistances (1), challenging the pharmaceutical industry to develop with new, innovative, and effective molecules. Discovered around 1980, molecules called natural antimicrobial peptides (AMPs) appear to hold great potential for the treatment of infections. These cationic peptides are able to stop the bacterial development and to control infections. The purpose of this review is to help improve the understanding of the way AMPs operate in the context of the development of new cures against viruses, bacteria, and mushrooms found in the human body in general and in the oral cavity in particular.

The expression of cellular prion protein (PrPc) on the surface of peripheral lymphocytes has been previously reported, but little is known about its expression on lymphoid cells from secondary lymph organs. In this report, we compare the surface expression of PrPc on human blood lymphocytes and tonsil lymphocytes.This analysis was performed by cytometry on live lymphocytes isolated from healthy donors or from the tonsils of adults or children.Human peripheral lymphocytes and tonsillar lymphoid cells, but not erythrocytes or granulocytes, express PrPc at their surfaces. Interestingly, we found significantly less PrPc on freshly isolated tonsil lymphocytes, both B and T, than on blood cells. Although tonsil cells bear less PrPc than circulating blood lymphocytes, they are able to express high quantities of PrPc on their surface when placed in culture. However, contrary to previous results, mitogen stimulation does not affect this expression on B- or T-cells.We suggest that the PrPc expression by lymphocytes may be modified by interactions occurring during intratissular migration or during cell-to-cell contacts. Whether PrPc plays a role in intracellular communication at this location, as it does in the nervous system, remains an open question.

Follicular dendritic cells (FDC) are only located in lymph node follicles and particularly developed in the light zones of the germinal centers. FDC differ on important points from the classical dendritic cells presenting antigens to T cells. They are long-lived and derived from local mesenchymal cells. Their complex cytoplasmic extensions, covered with dendrites, are intermingled in a network which surrounds germinal B and T cells. On their surface, receptors fix immune complexes without endocytosis and adhesion molecules ensure close contacts to the lymphoid cells. FDC influence the migration, activation, proliferation, survival and differentiation of B cells into memory cells and probably act also on the germinal center T cells.

Clinical trials in cattle demonstrated that the IBR marker modified live vaccine based on the gE-deleted IBR strain Difivac is immunogenic and safe for bovines of all ages. Potential effects of the vaccine virus have also been tested in swine and sheep and proved safe for these species as well. For evaluation of other environmental aspects, the spread of the vaccine virus after immunisation was investigated. The data indicated that the vaccine virus may be shed by immunised animals but that it has a limited ability to pass from animal to animal. It was also demonstrated that the attenuated Difivac strain does not revert to virulence during calf passage. Preliminary results indicated that the gE-deleted vaccine virus of the IBR marker vaccine cannot be reactivated after dexamethasone treatment, an important advantage for a vaccine strain. Furthermore, immunisation with the Difivac strain reduced the ability of a superinfecting challenge virus to become latent or to be reactivated.

AGM-1470 is a potent angiogenesis inhibitor that is very effective in inhibiting endothelial cell proliferation in both in vitro and in vivo models and that prevents tumor growth in vivo. Although this molecule appears to be a most promising anticancer drug, its mechanism of action has not yet been elucidated. In this study, we examined the effects of AGM-1470 on the cell cycle of normal and transformed endothelial cells. We showed that AGM-1470, at picomolar concentrations, specifically inhibits the proliferation of both bovine aortic endothelial cells and human umbilical vein endothelial cells. AGM-1470 was ineffective in significantly inhibiting the proliferation of Ea.hy926 cells, a hybrid cell line obtained by the fusion of human umbilical vein endothelial cells with a human carcinoma cell line, or cEnd.1 cells, a polyoma middle T oncogene-transformed endothelioma cell line derived from mouse embryo. Using a double labeling technique with anti-Ki67 antibodies and propidium iodide, we demonstrated, with flow cytometry analysis, that AGM-1470 specifically prevents the entry of endothelial cells into the G1 phase of the cell cycle. We also showed that AGM-1470 was ineffective in inhibiting endothelial cell migration toward laminin or capillary-like tube formation inside a type I collagen matrix induced by phorbol esters. Our data strongly suggest that AGM-1470 is a molecule that specifically inhibits a cell cycle control pathway active in normal cells but which could be bypassed or altered in transformed cells.

The presence of CD4+, CD57+ T cells in the germinal centers has been reported by several authors. The CD57 antigen is also expressed by natural killer (NK) cells. We purified CD57+ cells from human tonsils and blood by microdissection, rosetting with sheep red blood cells and magnetic cell sorting (MACS) and examined the ultrastructural morphology of these cells. Clear differences were found in cell aspect: blood NK contained large granules which were not found in the tonsillar CD57+ cells. These latter appeared medium-sized and not fully activated. After immunolabeling, the tonsillar CD57+ cells were mainly found in the light zone of the germinal centers.

Zur Überprüfung der von kommerzieller Seite behaupteten diagnostischen Überlegenheit der zur Zeit angebotenen Methoden zur Messung des freien Serum Thyroxins wurde das FT4 von 152 Patienten mit den unterschiedlichsten Diagnosen simultan mit 5 Verfahren (Amerlex; GammaCoat; Immo-Phase; LiquiSol; T4/TBG) gemessen. Eindeutige Hyper- und Hypothyreosen ließen sich mit allen Tests klar von der Euthyreose abgrenzen. Erhebliche Diskrepanzen zwischen den einzelnen Methoden ergaben sich aber bei klinisch euthyreoten Probanden mit den verschiedensten extrathyreoidalen Veränderungen (TBG-Mangel bzw. -Exzeß, Spätgravidität, Schwerkranke, T4-Substitution). In Anbetracht der abweichenden Resultate, deren methodische und physiologische Richtigkeit zur Zeit nicht überprüfbar ist, erscheint es verfrüht, die bewährten Programme in der Schilddrüsendiagnostik durch routinemäßige Bestimmung des FT4 abändern zu wollen.

T4-, T3- and reverse-T3 concentrations were measured in the sera of 365 subjects beyond the age of 65 in order to evaluate if the decrease of serum T3 frequently observed in old age can be attributed to old age per se or to concomitant nonthyroidal disease. The results obtained from a carefully selected healthy group of elderly people show that 1) total and free T3 levels are lower in senescence but well within the range for euthyroidism in younger healty controls;2) the decrease of serum T3 is more pronounced and occurs earlier in healthy old males than in females, so that for subjects over the age of 75, the upper limit for euthyroidism has to be adjusted by 10% in women and by 20% in men; and 3) there is no low T3 syndrome characterized by decreased serum T3 and increased serum reverse T3, solely due to old age. Turnover kinetics have shown the daily production of T4 and T3 in old age to decrease by 20 micrograms and 10 micrograms, respectively, and an increased T3 metabolic clearance not to account for the reduction of serum T3 concentrations. Combined stimulation tests with TSH and TRH showed that the functional reserve of the thyroid gland to produce T3 is maintained in old age. The first step in the sequence of events may be seen in an impairment of TSH secretion leading to an adaptation of the amount of thyroid hormones to a reduced mass of metabolically active body tissue in old age.

An inhibition of peripheral conversion of T4 to T3 is thought to be of benefit in the treatment of thyrotoxicosis. Therefore, propylthiouracil (PTU) has been considered to be more effective in the therapy of hyperthyroidism than methimazole, since the former has the additional peripheral effect of decreasing the conversion of T4 to T3, From in vitro studies PTU is known, however, to inhibit the deiodination at the 5' as well as at the 5 position of the iodothyronine molecule. To study if PTU blocks degradation in T3 in vivo as well, the effect of PTU on thyroid hormone concentrations in serum and liver tissue during a constant and high administration of T4 or T3 to rats was followed. It was shown that PTU clearly inhibits T4 and reverse T3 degradation. Moreover, simultaneous treatment of the rats with T3 and PTU resulted in a significantly higher increase of T3 concentration in liver tissue (11.5 ng/g liver vs 5.6 ng/g liver) and serum (615 ng/di vs 345 ng/dl) than with T3 alone. This effect may be explained by an inhibition of the T3 degradation by PTU in vivo as well. Provided the results obtained from these animal experiments can be applied to the situation in man, the inhibition of peripheral deiodination could have an adverse effect at least in the treatment of T3-thyrotoxicosis.

The Unopette method for the determination of salicylate in blood was evaluated in our laboratory. Excellent correlation was found with the results obtained using Trinder's reagent. The principal advantages of the Unopette procedure are accuracy and the convenience of having all of the test reagents, including the standard, pre-measured. Additional advantages are the short time needed to perform the test, and complete disposability of all of the components of the Unopette kit.