[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Validation of a Multiplexed Gene Signature Assay for Diagnosis of Canine Cancers from Formalin-Fixed Paraffin-Embedded Tissues.

BACKGROUND: Use of molecular-based diagnostics for companion animals is impeded by availability of technology platforms, tissue acquisition requirements, and species-specific reagents. HYPOTHESIS/OBJECTIVES: To validate a quantitative nuclease protection assay (qNPA) to simultaneously measure RNA expression of multiple genes in archived formalin-fixed paraffin-embedded (FFPE) tumors from dogs. ANIMALS: All tumor biopsy samples were collected retrospectively from surgical biopsies and in the care of veterinarians. METHODS: Retrospective case series. A qNPA 96-well ArrayPlate was built using 30 canine-specific genes, 5 housekeeping genes, positive and negative controls with qualified gene-specific oligonucleotides. Pearson's correlation, coefficient of variation (CV), and multivariate analysis were used to determine analytical performance using 40 FFPE dog tumors. Once validated, 70 FFPE dog tumors were analyzed for differences in gene expression using hierarchical clustering and analysis of variance of log transformed data. Immunohistochemistry (IHC) was performed to correlate gene expression and protein expression in a subset of tumors. RESULTS: The assay was linear with decreasing sample input (R2 = 0.978), reproducible within and between 96-well plates (r = 0.988 and 0.95, respectively) and between different laboratories (CV = 0.96). Hierarchical cluster analysis showed grouping of tumors by histogenesis and oncogenes. Significant differences were found between BCl2, E2F transcription factor 1, MDM2, COX-2, MET proto-oncogene receptor kinase, and other biologically relevant gene expression in tumor subtypes. Immunohistochemistry confirmed protein expression. CONCLUSIONS AND CLINICAL IMPLICATIONS: Because this technology works reliably on FFPE specimens, it can help expedite the broad introduction of multiplexed genomic information for improved diagnostics and discovery of new targets for therapies in veterinary oncology.

Alternating Rabacfosadine/Doxorubicin: Efficacy and Tolerability in Naïve Canine Multicentric Lymphoma.

BACKGROUND: Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12-16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX. HYPOTHESIS/OBJECTIVES: Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma. ANIMALS: Fifty-four dogs with previously untreated lymphoma. METHODS: Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days. RESULTS: The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis. CONCLUSIONS AND CLINICAL IMPORTANCE: Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations.

Geographical differences in survival of dogs with non-Hodgkin lymphoma treated with a CHOP based chemotherapy protocol.

BACKGROUND: In humans geographical differences in the incidence and presentation of various cancers have been reported. However, much of this information has not been collected in veterinary oncology. AIM: The purpose of this study was to determine if a geographic difference in progression free survival exists for dogs with lymphoma treated within the US. MATERIALS AND METHODS: Medical records of 775 cases of canine lymphoma from 3 US regions (west, south and north), treated with CHOP chemotherapy, were retrospectively evaluated. Cases were collected from referral institutions and were required to have received at least one doxorubicin treatment and have follow up information regarding time to progression. RESULTS: Significant differences in sex (p = 0.05), weight (p = 0.049), stage (p < 0.001), immunophenotype (p = <0.001), and number of doxorubicin doses (p = 0.001) were seen between regions. Upon univariate analysis, progression free survival (PFS) differed by region (p = 0.006), stage (p = 0.009), sub-stage (p = 0.0005), and immunophenotype (p = 0.001). A multivariable Cox regression model showed that dogs in the western region had a significantly shorter PFS when compared to the south and east. CONCLUSION: PFS was significantly affected by stage, sub-stage and phenotype.

Clinical presentation, treatment and outcome in 31 dogs with presumed primary colorectal lymphoma (2001-2013).

The objective of this multicentre retrospective study was to describe clinical presentation, treatment and outcome and to determine prognostic factors for dogs with presumed primary colorectal lymphoma (PCRL). A total of 31 dogs were included. The predominant features of PCRL were high grade (n = 18) and immunophenotype B (n = 24). Most dogs were substage b (n = 25) with higher prevalence of haematochezia (n = 20). One dog had surgery only. Thirty dogs received chemotherapy; amongst them 13 had surgery or radiotherapy. Progression free survival (PFS) was 1318 days and disease-related median survival time (MST) was 1845 days. Fourteen dogs were alive at the end of the study with a median follow-up time of 684 days (3-4678 days). Younger dogs had longer PFS (P = 0.031) and disease-related MST (P = 0.01). Presence of haematochezia corresponded with longer PFS (P = 0.02). Addition of local treatment to chemotherapy did not significantly improve the outcome (P = 0.584). Canine PCRL has considerably longer PFS and MST than other forms of non-Hodgkin's lymphoma.

Recurrence rates and clinical outcome for dogs with grade II mast cell tumours with a low AgNOR count and Ki67 index treated with surgery alone.

Grade II mast cell tumours (MCT) are tumours with variable biologic behaviour. Multiple factors have been associated with outcome, including proliferation markers. The purpose of this study was to determine if extent of surgical excision affects recurrence rate in dogs with grade II MCT with low proliferation activity, determined by Ki67 and argyrophilic nucleolar organising regions (AgNOR). Eighty-six dogs with cutaneous MCT were evaluated. All dogs had surgical excision of their MCT with a low Ki67 index and combined AgNORxKi67 (Ag67) values. Twenty-three (27%) dogs developed local or distant recurrence during the median follow-up time. Of these dogs, six (7%) had local recurrence, one had complete and five had incomplete histologic margins. This difference in recurrence rates between dogs with complete and incomplete histologic margins was not significant. On the basis of this study, ancillary therapy may not be necessary for patients with incompletely excised grade II MCT with low proliferation activity.

Use of adjuvant carboplatin for treatment of dogs with oral malignant melanoma following surgical excision.

Melanoma is the most common oral malignancy in dogs. This retrospective study evaluated adjuvant carboplatin chemotherapy (with or without radiation therapy) in 17 dogs with malignant oral melanoma following surgical resection. The median dosage and number of doses of carboplatin administered to the 17 dogs was 300 mg m(-2) (range, 150-300 mg m(-2)) and 4 (range, 2-11), respectively. The overall median progression-free survival for all dogs was 259 days [95% confidence interval (CI95), 119-399 days]. The first progression-free survival event was local recurrence in seven dogs (41%) and metastases in seven dogs (41%). The median overall survival for all dogs was 440 days (CI95, 247-633 days). The tumour was the cause of death in 10 dogs (59%). On the basis of this study, systemic therapy with carboplatin may be an appropriate adjunct to local treatment for canine malignant melanoma, although future prospective controlled studies are needed to compare treatment modalities for this aggressive neoplasia.

Prolonged prothrombin time correlates with serum monoclonal protein concentration in patients with plasma cell dyscrasia.

INTRODUCTION: Abnormal screening coagulation tests are frequently observed in asymptomatic patients with multiple myeloma and other plasma cell neoplasms. METHODS: Prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen activity were correlated with clinical history and disease parameters in patients referred to the Myeloma Institute for Research and Therapy. RESULTS: An isolated prolonged PT was the most common abnormal coagulation test (25%). Prolonged PT was more frequently observed in patients with multiple myeloma (n = 157) compared to MGUS patients (n = 34) or other diagnostic categories of plasma cell dyscrasia. There were no differences in age, gender, previous chemotherapy, or immunoglobulin isotype in patients with isolated prolonged PT (n = 62) compared to those with normal screening coagulation tests (n = 173). Fibrinogen activity was significantly lower in patients with prolonged PT; however, there was no correlation between fibrinogen activity and PT. Serum M protein concentrations were significantly greater in patients with prolonged PT and were positively correlated with PT. CONCLUSION: An association between disease severity and prolonged PT is suggested by our finding that patients with multiple myeloma were more likely to have prolonged PT than patients with other plasma cell neoplasms. Of the factors examined, the monoclonal protein level was significantly higher in patients with isolated prolonged PT and correlated with PT.

Feline exocrine pancreatic carcinoma: a retrospective study of 34 cases.

Thirty-four cases were reviewed in this retrospective study for information on clinical presentation, prognostic indicators, survival time and response to various therapies. The most common presenting clinical signs were weight loss, decreased appetite, vomiting, palpable abdominal mass and diarrhoea. Metastatic disease was confirmed in 11 cats. The overall median survival was 97 days. The median survival times for patients who received chemotherapy or had their masses surgically removed was 165 days. Those patients who had an abdominal effusion present at the time of diagnosis survived a median of 30 days. Cats that received non-steroidal anti-inflammatory drug therapy had a median survival of 26 days. This study confirms that exocrine pancreatic carcinoma in cats is an aggressive tumour with a high metastatic rate and poor prognosis, although three patients survived over 1 year. Fifteen percent of the patients were diabetic, which raises the question as to what the link between diabetes and pancreatic cancer in people and cats may be.

Unaltered instrumental learning and attenuated body-weight gain in rats during non-rotating simulated shiftwork.

Exposure to shiftwork has been associated with multiple health disorders and cognitive impairments in humans. We tested if we could replicate metabolic and cognitive consequences of shiftwork, as reported in humans, in a rat model comparable to 5 wks of non-rotating night shifts. The following hypotheses were addressed: (i) shiftwork enhances body-weight gain, which would indicate metabolic effects; and (ii) shiftwork negatively affects learning of a simple goal-directed behavior, i.e., the association of lever pressing with food reward (instrumental learning), which would indicate cognitive effects. We used a novel method of forced locomotion to model work during the animals' normal resting period. We first show that Wistar rats, indeed, are active throughout a shiftwork protocol. In contrast with previous findings, the shiftwork protocol attenuated the normal weight gain to 76 ± 8 g in 5 wks as compared to 123 ± 15 g in the control group. The discrepancy with previous work may be explained by the concurrent observation that with our shiftwork protocol rats did not adjust their between-work circadian activity pattern. They maintained a normal level of activity during the "off-work" periods. In the control experiment, rats were kept active during the dark period, normally dominated by activity. This demonstrated that forced activity, per se, did not affect body-weight gain (mean ± SEM: 85 ± 11 g over 5 wks as compared to 84 ± 11 g in the control group). Rats were trained on an instrumental learning paradigm during the fifth week of the protocol. All groups showed equivalent increases in lever pressing from the first (3.8 ± .7) to the sixth (21.3 ± 2.4) session, and needed a similar amount of sessions (5.1 ± .3) to reach a learning criterion (≥ 27 out of 30 lever presses). These results suggest that while on prolonged non-rotating shiftwork, not fully reversing the circadian rhythm might actually be beneficial to prevent body-weight gain and cognitive impairments.

A randomized trial investigating the efficacy and safety of water soluble micellar paclitaxel (Paccal Vet) for treatment of nonresectable grade 2 or 3 mast cell tumors in dogs.

BACKGROUND: Effective treatments for dogs with advanced stage mast cell tumors (MCT) remain a pressing need. A micellar formulation of paclitaxel (paclitaxel [micellar]) has shown promise in early-phase studies. HYPOTHESIS/OBJECTIVES: The objective was to demonstrate greater activity for paclitaxel (micellar) compared with lomustine. The null hypothesis was µ(p) = µ(L) (ie, proportion of responders for the paclitaxel [micellar] and lomustine groups, respectively). ANIMALS: Two hundred and fifty-two dogs with advanced stage nonresectable grade 2 or 3 MCT. METHODS: Prospective multicenter randomized double-blind positive-controlled clinical trial. The primary endpoint was confirmed overall response rate (CORR) at 14 weeks. A secondary endpoint, biologic observed response rate (BORR), also was calculated. Safety was assessed by the characterization and grading of adverse events (AE). RESULTS: Overall CORR (7% versus 1%; P = .048) and BORR (23% versus 10%; P = .012) were greater for paclitaxel (micellar) compared with lomustine. Paclitaxel (micellar)-treated dogs were 6.5 times more likely to have a confirmed response and 3.1 times more likely to experience a biologic observed response. The majority of AE with paclitaxel (micellar) were transient and clinically manageable. Twenty-seven dogs (33%) receiving lomustine were discontinued because of hepatopathy compared with 3 dogs (2%) receiving paclitaxel (micellar) (P < .0001; odds ratio 26.7). CONCLUSIONS AND CLINICAL IMPORTANCE: Paclitaxel (micellar)'s activity and safety profile are superior to lomustine. The addition of an active and novel taxane to the veterinary armamentarium could fill a substantial need and, as its mechanism of action and AE profile do not overlap with currently available TKI, its availability could lead to effective combination protocols.

Single-agent gemcitabine chemotherapy in dogs with hepatocellular carcinomas.

The goal of this study was to determine the efficacy and tolerability of gemcitabine in dogs diagnosed with hepatocellular carcinoma (HCC). Eighteen dogs were examined retrospectively (4 massive HCC, 10 nodular HCC and 4 diffuse HCC). All dogs received gemcitabine at 350-400 mg m(-2) weekly for 5 weeks. Toxicity was graded using VCOG-CTCAE guidelines and response was monitored with serial abdominal ultrasounds. Fifteen dogs completed all five cycles. Toxicity was minimal and consisted of grade I/II vomiting, anorexia and diarrhoea and two episodes of grade III neutropenia. Median survival time for all dogs was 983 days. Median progression free interval was 971 days. Based on the results of this study, surgery remains the best treatment for HCC, despite incomplete resection. There was no improvement in the survival of those diagnosed with nonresectable HCC treated with gemcitabine chemotherapy.

Evaluation of a multidrug chemotherapy protocol with mitoxantrone based maintenance (CHOP-MA) for the treatment of canine lymphoma.

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

Asparaginase and MOPP treatment of dogs with lymphoma.

BACKGROUND: Dogs with multicentric lymphoma are treated with various cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP)-based chemotherapy protocols with variable success. OBJECTIVES: To describe the progression-free survival (PFS) time and overall survival time (OST) of dogs with T-cell lymphoma or hypercalcemic lymphoma treated with L-asparaginase and mechlorethamine, vincristine, prednisone, procarbazine (MOPP). ANIMALS: Fifty dogs with T-cell lymphoma, hypercalcemic lymphoma, or both treated at 3 referral veterinary hospitals. METHODS: Retrospective study. Case were selected based on histologic or cytologic diagnosis of lymphoma; presence of the T-cell phenotype, presence of hypercalcemia or both; and absence of previous chemotherapy. The T-cell phenotype was determined by flow cytometry, immunocytochemistry, immunohistochemistry, or polymerase chain reaction of antigen receptor rearrangement. RESULTS: The overall response rate was 98% (78% complete response, 20% partial response). The median PFS for the entire study population was 189 days with 25% PFS at 939 days. The median OST for the entire study population was 270 days with 25% surviving 939 days. Twenty percent of the dogs required hospitalization for treatment related complications. CONCLUSIONS AND CLINICAL IMPORTANCE: L-Asp/MOPP chemotherapy might result in longer PFS and OST for dogs with multicentric T-cell lymphoma, dogs with hypercalcemic lymphoma or both, than achieved with CHOP.

Building the Tower of Babel: cross-border urgent medical assistance in Belgium, Germany and The Netherlands.

The border area between Germany, Belgium, and The Netherlands includes a substantial number of cooperative forms in the urgent medical assistance sector. Collaboration usually takes place in densely populated areas with cities or villages situated on or in proximity to the border. In some regions, definitive borders are not apparent to the extent that inhabitants often times are unaware of their existence. The border may pass directly through a built-up area with intense cross-border activity due to population residency, place of work, shopping, and recreational pursuits. To obtain a deeper insight into cross-border Urgent Medical Assistance (UMA), the Ministry of the Interior and Kingdom Relations (IKR) and the Ministry for Health, Welfare, and Sports (HWS) in The Netherlands commissioned research into cross-border UMA impediments and solutions at administrative, judicial, and operational level. The following central questions were presented for research: (1) What opportunities and impediments are presented in the area of cross-border, urgent medical assistance at administrative, legal, operational, and equipment employable level?; and (2) Which solutions may be submitted to tackle existing impediments? Two techniques were employed to answer the research questions. First, relevant documents were studied from extensive file and literature searches. File and literature search findings subsequently were tested in practice through interviews with relevant experts. Dutch ambulance services provide support to both their Belgian and German counterparts and vice versa. In the instance of cross-border ambulance deployment, relevant assistance services are subject to due observance of various legislations and regulations. Such regulations may restrict effective and efficient deployment of personnel and equipment at critical moments, because regulation discrepancies may arise over ambulance personnel's authorities, ambulance content, and deployment sequence. Discrepencies also may exist in the area of financial compensation concerning ambulance deployment and hospital admission. Gaining knowledge on their disparate systems and the opportunity to utilize the medical provisions of a neighboring country potentially in closer proximity to those in the victim's own country serves the best interests of the patient. Survival chances of a traumatized patient increase with the expedited arrival of medical assistance and increased speed of transportation to an appropriate hospital.

Acquired amegakaryocytic thrombocytopenia--four cases and a literature review.

Acquired amegakaryocytic thrombocytopenla was diagnosed in four dogs. Initial platelet counts in all four dogs were less than 50,000 x 10(9)/litre and initial bone marrow examinations revealed megakaryocytic hypoplasia with minimal changes in the erythroid and myeloid cell lines. Two dogs had evidence of idiopathic immune-mediated disease and two dogs had evidence of associated infectious disease. One dog had a positive antibody titre to Borrella burgdorferi, and one dog had positive titres to both Ehrlichia canis and B. burgdorferi. Treatment consisted of prednisone and cyclophosphamide for the dogs with presumptive immune-mediated disease, and prednisone and tetracycline for the dogs with positive antibody titres to the Infectious organisms. Both dogs with evidence of associated infectious disease responded to treatment. A postmortem examination did not reveal the underlying aetiology in the two dogs with presumptive idiopathic immune-mediated disease.

Effects of health information in youth and young adulthood on risk factors for chronic diseases--20-year study results from the Amsterdam Growth and Health Longitudinal Study.

In the Amsterdam Growth and Health Longitudinal Study (AGAHLS) biological risk factors for chronic diseases were measured on eight separate occasions over a period of 20 years in a group of apparently healthy males and females (n = 164). Data were first collected from participants at 13 years of age. At each of the eight measurements, a medical checkup was performed and participants were given information about their current health status based on their personal biological risk factor profile (cholesterol, blood pressure, body composition, and physical fitness). A comparable group (n = 113) was measured on two occasions only: at age 13 and again at age 33. It was hypothesized that the group with eight measurements would present a more favorable 20-year development of the risk factors than the group with only two measurements. In the present article the six additional measurements with personal feedback of one's health status were perceived as an "intervention," even though the AGAHLS never intended to improve the lifestyle or health of its subjects. The intervention appeared to have had a positive effect on body fat distribution and, in men, on systolic blood pressure. However, it was expected that these significant results were not true effects of the intervention, but that they were type-I errors. For the other variables, total cholesterol, high-density lipoprotein cholesterol, and the ratio between these two, for the sum of four skinfolds, diastolic blood pressure, neuromotor fitness, and for maximal oxygen uptake, the 20-year development did not differ between the two groups. Thus, the effects of a 20-year health measurement and information intervention begun in youth on biologic risk factors for chronic diseases were limited. The absence of clear significant findings may be due to the low contrast between the two groups, as only six intervention measurements were conducted over a period of 20 years. Another reason may be that the young and relatively healthy population under study here was not amenable to changing their fitness and health.

Effects of health information in youth on adult physical activity: 20-year study results from the Amsterdam growth and health longitudinal study.

In the Amsterdam Growth and Health Longitudinal Study (AGAHLS), a group of apparently healthy males and females (n = 200) were interviewed about their physical activities on eight separate occasions over a period of 20 years between 13 and 33 years of age (multi-measured group: MM). Information about their health was given based on their personally measured lifestyle (activity, diet, smoking) and biological risk characteristics for chronic diseases (medical check-ups). A comparable group of boys and girls (n = 200) was only measured on two occasions (bi-measured group: BM): at 13 and 33 years. Physical activity was estimated with a structured interview. Total physical activity and sports activity were estimated in three intensity levels (light, moderate, and heavy). It was hypothesized that the eight repeated medical check-ups with health information in the MM group would result in a healthier lifestyle with respect to the determinants and levels of habitual physical activity compared to the BM group. Contrary to the hypothesis, males and females in the BM group showed a significantly higher increase or a lower decrease in physical activities compared to the MM group. This negative effect on the physical activity pattern at 33 years in the MM group may have been caused by more underreporting of physical activities than in the BM group. In conclusion, there does not appear to be a significant effect of long-term (multi-measured) health information with medical check-ups during adolescence and young adulthood on level of physical activity in males and females at 33 years of age.

Effects of health measurements and health information in youth and young adulthood in dietary intake--20-y study results from the Amsterdam Growth and Health Longitudinal Study.

BACKGROUND: The Amsterdam Growth and Health Longitudinal Study (AGAHLS) is a 20 y observational study concerning biological, psychological and lifestyle risk factors for cardiovascular disease and osteoporosis. In the AGAHLS two cohorts can be distinguished: the so-called Multi-Measurement Group (MMG), which received eight repeated measurements, and a Bi-Measurement Group (BMG), which received two measurements, one at the beginning and one at the end of the 20 y period. OBJECTIVE: In health-related longitudinal research, the outcomes of the study may be influenced by the measurements themselves and the health information provided. It was hypothesized that the repeated measurements and the health information given to the MMG would result in a more healthy dietary intake in comparison to the BMG. DESIGN: The MMG consisted of 164 subjects and the BMG consisted of 90 subjects. At the start of the study, subjects were teenagers of 13-y-old. The hypothesis was tested with use of regression analysis, analysing group differences in mean individual change scores. RESULTS: Only the MMG showed a significantly larger decrease in the intake of mono- and disaccharides compared to the BMG. CONCLUSIONS: The effect of the repeated measurements and the health information provided on dietary intake was relatively small, since it was only one out of the 14 nutrients that differed between the MMG and the BMG.

Clinicopathologic and electron microscopic study of cutaneous neuroendocrine (Merkel cell) carcinoma in a cat with comparisons to human and canine tumors.

Malignant neuroendocrine carcinoma of the skin (Merkel cell tumor) was diagnosed in an 18-year-old spayed female Maine Coon Cat. The diagnosis was made on the basis of morphologic and electron microscopic findings. The cat was euthanatized 321 days after surgical excision of the tumor. The tumor's malignancy contrasted with the benign nature of Merkel cell tumors reported in dogs and was consistent with the malignancy of Merkel cell tumors reported in humans.