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Oral administration of low-dose cyclophosphamide in pets with spontaneously occurring malignant neoplasms has become a common practice in veterinary medicine. The purpose of this retrospective study was to investigate toxicity events in cats with spontaneous malignancies receiving cyclophosphamide as a metronomic therapy for at least 1 month. The number and severity of clinical, haematological and biochemical adverse events were recorded according to the Veterinary Cooperative Oncology Group's Common Terminology Criteria for Adverse Events v1.1 classification scheme. Twenty-four cats were enrolled in the study with a total number of 27 neoplasms: 13 sarcomas, 12 carcinomas, one melanoma and one neuroendocrine tumour. Seventeen cats presented with macroscopic disease, while seven had microscopic disease. Seven cats (29%) had metastasis either to the regional lymph nodes and/or distant sites at the time of study enrolment. Additional medications, administered concurrently, included non-steroidal anti-inflammatory drugs (17), toceranib (4) and thalidomide (7). Four cats showed grade I gastrointestinal toxicity during the first month of treatment, which was controlled with antiemetics. Overall, 2/24 cats (8%) showed grade I haematological toxicities and 1/24 (4%) showed grade I renal toxicity in the first 4 weeks. Median follow-up for all cats was 30 days (range 30-360 days). For the 15 cats with follow-up longer than 1 month the only additional toxicities observed were two grade III and one grade II azotaemia that occurred after 2 months of therapy. Low-dose cyclophosphamide seems to be a well-tolerated option for cats bearing primary or metastatic tumours. Evaluation of toxicity after long-term administration is still needed., (© ISFM and AAFP 2014.)

Food intake increases to a varying extent during pregnancy to provide extra energy for the growing fetus. Measuring the respiratory quotient (RQ) during the course of pregnancy (by quantifying O2 consumption and CO2 production with indirect calorimetry) could be potentially useful since it gives an insight into the evolution of the proportion of carbohydrate vs. fat oxidized during pregnancy and thus allows recommendations on macronutrients for achieving a balanced (or slightly positive) substrate intake. A systematic search of the literature for papers reporting RQ changes during normal pregnancy identified 10 papers reporting original research. The existing evidence supports an increased RQ of varying magnitude in the third trimester of pregnancy, while the discrepant results reported for the first and second trimesters (i.e. no increase in RQ), explained by limited statistical power (small sample size) or fragmentary data, preclude safe conclusions about the evolution of RQ during early pregnancy. From a clinical point of view, measuring RQ during pregnancy requires not only sophisticated and costly indirect calorimeters but appears of limited value outside pure research projects, because of several confounding variables: (1) spontaneous changes in food intake and food composition during the course of pregnancy (which influence RQ); (2) inter-individual differences in weight gain and composition of tissue growth; (3) technical factors, notwithstanding the relatively small contribution of fetal metabolism per se (RQ close to 1.0) to overall metabolism of the pregnant mother., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

In this work we fabricate and characterize field-effect transistors based on the solution-processable semiconducting polymer poly(3-hexylthiophene) (P3HT). Applying two independent gate potentials to the electrolyte-gated organic field-effect transistor (EGOFET), by using a conventional SiO(2) layer as the back-gate dielectric and the electrolyte-gate as the top-gate, allows the measurement of the electrical double layer (EDL) capacitance at the semiconductor-electrolyte interface. We record the transfer curves of the transistor in salt solutions of different concentration by sweeping the bottom gate potential for various constant electrolyte-gate potentials. A change of the electrolyte-gate potential towards more negative voltages shifts the threshold voltage of the bottom-gate channel towards more positive back-gate potentials, which is directly proportional to the capacitive coupling factor. By operating the EGOFET in the dual-gate mode, we can prove the dependency of the EDL capacitance on the molarity of the electrolyte according to the Debye-Hückel theory, and additionally show the difference between a polarizable and non-polarizable electrolyte-gate electrode. With the experimentally obtained values for the EDL capacitance at the semiconductor-electrolyte interface we can model the electrolyte-gate transfer characteristics of the P3HT OTFT.

The aim of this study was to compare the energy expenditure (EE) estimations of activity-specific prediction equations (ASPE) and of an artificial neural network (ANNEE) based on accelerometry with measured EE. Forty-three children (age: 9.8 ± 2.4 yr) performed eight different activities. They were equipped with one tri-axial accelerometer that collected data in 1-s epochs and a portable gas analyzer. The ASPE and the ANNEE were trained to estimate the EE by including accelerometry, age, gender, and weight of the participants. To provide the activity-specific information, a decision tree was trained to recognize the type of activity through accelerometer data. The ASPE were applied to the activity-type-specific data recognized by the tree (Tree-ASPE). The Tree-ASPE precisely estimated the EE of all activities except cycling [bias: -1.13 ± 1.33 metabolic equivalent (MET)] and walking (bias: 0.29 ± 0.64 MET; P < 0.05). The ANNEE overestimated the EE of stationary activities (bias: 0.31 ± 0.47 MET) and walking (bias: 0.61 ± 0.72 MET) and underestimated the EE of cycling (bias: -0.90 ± 1.18 MET; P < 0.05). Biases of EE in stationary activities (ANNEE: 0.31 ± 0.47 MET, Tree-ASPE: 0.08 ± 0.21 MET) and walking (ANNEE 0.61 ± 0.72 MET, Tree-ASPE: 0.29 ± 0.64 MET) were significantly smaller in the Tree-ASPE than in the ANNEE (P < 0.05). The Tree-ASPE was more precise in estimating the EE than the ANNEE. The use of activity-type-specific information for subsequent EE prediction equations might be a promising approach for future studies.

Purpose: Assess fertility preservation (FP) measures chosen by patients newly diagnosed with malignancy and their outcomes., Methods: Reproductive-age patients referred for FP underwent counseling and elected cryopreservation vs. no treatment. Outcome measures included ovarian stimulation, FP choice, oocytes/zygotes retrieved/cryopreserved and pregnancy outcome., Results: From 2005 to 2012, 136 patients were counseled with 124 electing treatment: 83 oocyte-only, 21 oocyte + zygote and 20 zygote-only cryopreservation. Age, partnership and financial status factored into FP choice. Treatment was completed in 12 ± 2 days with 14 ± 11 metaphase-II oocytes harvested and cryopreserved/cycle. Eight patients returned to attempt pregnancy; three succeeded., Conclusions: Our data demonstrate that oocyte and/or zygote banking are feasible FP options for women with malignancy; given the choice, the majority elected oocyte cryopreservation, highlighting desire for reproductive autonomy. Continued growth and research, combined with interdisciplinary communication, will ensure that appropriate candidates are offered FP and the potential for future parenthood, an important quality-of-life marker for survivors.

Melanoma is the most common oral tumor in dogs, characterized by rapid growth, local invasion, and high metastatic rate. The goal of this study was to evaluate the combination of radiation therapy and DNA tumor vaccine. We hypothesized, that the concurrent use would not increase toxicity. Nine dogs with oral melanoma were treated with 4 fractions of 8 Gray at 7-day intervals. The vaccine was given 4 times every 14 days, beginning at the first radiation fraction. Local acute radiation toxicities were assessed according to the VRTOG toxicity scoring scheme over a time period of 7 weeks. In none of the evaluated dogs, mucositis, dermatitis and conjunctivitis exceeded grade 2. In 3 dogs mild fever, lethargy, and local swelling at the injection site were seen after vaccine application. In conclusion, the concurrent administration of radiation therapy and vaccine was well tolerated in all dogs.

Background: Thrombangiitis obliterans or Buerger's disease is a segmental inflammatory disease affecting small and medium-sized veins and arteries, which most often affects young smokers leading to thrombophlebitis and acral ischaemic syndromes, inducing high amputation rates. Based on positive results of a former pilot study we report on our results of immunoadsorption (IA) in clinical routine care, where IA was offered as a treatment option., Patients and Methods: The uncontrolled course of 12 consecutive TAO-patients treated by IA on a series of 5 consecutive days was observed. Follow-up period was 14.1 (ranging from 1-26) months., Results: Eight patients were treated with one, four patients completed 2 IA-series. In 9 patients an early onset and lasting clinical improvement and an improvement of ischaemia was noted. The intake of pain-relievers (especially opioids) sank drastically. Eight patients returned to work. Retrospectively, in two out of three treatment failures the correct diagnosis of TAO was questionable., Conclusion: IA seems to be a promising treatment option for patients suffering from TAO which should be further evaluated in controlled clinical trials., (Georg Thieme Verlag KG Stuttgart · New York.)

Background: Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO., Methodology/principal Findings: TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group) were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dim)CD34(+) progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dim)CD34(+) progenitor cells co-expressing VEGF receptor-2 (VEGFR2) was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA) of common angiogenic factors (such as VEGF) did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay) and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs). Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients., Conclusion: Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation) on endothelial cells, which may contribute to vascular pathology in this patient population.

Advances in cancer treatment have allowed women to live longer, fuller lives. However, gonadotoxic therapies used to effect cancer 'cures' often significantly impair a woman's reproductive potential. Thus, in accordance with improved survival rates,there is an increase in demand for fertility preservation. Initially, fertility preservation was limited to embryo cryopreservation;therefore, the number of patients enrolling was relatively low. Recently, substantial improvements have increased available options, specifically oocyte cryopreservation, thereby expanding and altering the make-up of the patient population under going treatment for fertility preservation. Patient diversity requires the treating physician(s) to be cognizant of issues specific to cancer type and stage. Furthermore, patients often have comorbidities which must be attended to and addressed. Although not all patients will be candidates for, or will elect to pursue, fertility preservation, all should receive counselling regarding their options. This practice will ensure that the reproductive rights of those patients facing impending sterility are maintained. Here, fertility preservation protocols, practices and special considerations, categorized by most frequently encountered cancer types, are reviewed to guide reproductive endocrinologists in the management of fertility preservation in such patients. The formation of a multidisciplinary patient-structured team will ensure a successful, yet safe, fertility-preservation outcome ., (Copyright © 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: No established therapy is available for patients with thromboangiitis obliterans (TAO) and critical limb ischemia. Since abnormalities of the immune system appear to be involved in the pathogenesis, we investigated in this pilot study the efficiency of Ig immunoadsorption (IA) therapy., Methods: Ten patients with advanced TAO underwent a single IA course over five consecutive days. Before IA angiography was performed. In addition, the following were conducted prior to IA, directly after, as well as 1, 3, and 6 months after IA: clinical examination, pain scale (0-10), treadmill test for evaluation of maximum walking distances, and several angiological methods for evaluation of disease extent: photoplethysmography, ultrasound Doppler, and transcutaneous assessment of partial carbon dioxide (tcPCO(2)) and oxygen (tcPCO(2)) pressure., Results: Immunoadsorption treatment was tolerated without side effects. Pain intensity decreased rapidly from 7.7 ± 0.8 (mean ± SEM) before treatment to 2.0 ± 1.2 at the second day of IA. One month after IA, all patients were without pain. This functional amelioration persisted over the follow-up period of 6 months. Correspondingly, maximum walking distances significantly increased from 301.7 ± 191.4 to 727.0 ± 192.7 m immediately after IA, and further continuously up to 1,811.0 ± 223.7 at 6 months after IA. Healing of ischemic ulcerations was observed in all patients during follow-up. (tcPCO(2)) and (tcPCO(2)) values as well as photopletysmographic data that were severely compromised before IA reflecting reduced tissue oxygenation and perfusion showed rapid amelioration reaching normal values at 1 month., Conclusion: Anti-Ig IA appears to be an effective therapeutic option for patients with advanced TAO.

Purpose: To compare direct magnetic resonance galactography (dMRG) and conventional galactography (CGal)., Materials and Methods: Thirty women underwent CGal and dMRG. Duct localization and the depth of the assumed underlying pathology in CGal and dMRG were analyzed., Results: Comparing CGal and dMRG, there was no significant difference regarding sector localization, but for depth of pathology (P=.023)., Conclusion: Duct localization with dMRG was possible with the same reliability as with CGal. Thus, dMRG may have the potential to become an alternative method to CGal., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A 14-year-old male Siberian tiger (Panthera tigris altaica) was admitted with an ulcerating mass on the right thoracic wall. Radiographic and computed tomographic evaluation indicated 2 isolated cutaneous masses without any signs of metastasis. Histology of a Tru-Cut biopsy revealed an anaplastic sarcoma with giant cells. Both tumors were resected with appropriate normal tissue margins. The size of the defect did not allow primary closure of the wound; therefore, a mesh expansion technique was attempted. Three months later, the tiger had to be euthanized due to extensive metastasis to the lungs. Histomorphological features and immunohistochemical results confirmed the diagnosis of malignant peripheral nerve sheath tumor. In contrast to domestic animal experience, the tumor had spread extensively to the lungs without local reccurrence in a short period of time. Correct diagnosis requires various immunohistochemical evaluations of the tumor tissue.

Optimal nutritional intakes are critical for health- and skill-related physical fitness. This review details the effect of energy restriction and supplementation on physical fitness, discusses the optimal chronic macronutrient intakes for physical fitness in exercising subjects and finally overviews the impact of short-term intakes of carbohydrate and protein, before, during and after exercise, on physical fitness of athletes. The present standings highlight that it is essential that health care givers personalize nutritional advice to meet the specific needs of exercising individuals while applying the described recommendations. It reminds the difficulty of providing straight nutritional recommendations for physical fitness on the basis of evidence-based medicine., (Copyright 2010 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Regular physical activity is associated with improved physiological, metabolic and psychological parameters, and with reduced risk of morbidity and mortality. Current recommendations aimed at improving the health and well-being of nonpregnant subjects advise that an accumulation of > or =30 minutes of moderate physical activity should occur on most, if not all, days of the week. Regardless of the specific physiological changes induced by pregnancy, which are primarily developed to meet the increased metabolic demands of mother and fetus, pregnant women benefit from regular physical activity the same way as nonpregnant subjects. Changes in submaximal oxygen uptake (VO(2)) during pregnancy depend on the type of exercise performed. During maternal rest or submaximal weight-bearing exercise (e.g. walking, stepping, treadmill exercise), absolute maternal VO(2) is significantly increased compared with the nonpregnant state. The magnitude of change is approximately proportional to maternal weight gain. When pregnant women perform submaximal weight-supported exercise on land (e.g. level cycling), the findings are contradictory. Some studies reported significantly increased absolute VO(2), while many others reported unchanged or only slightly increased absolute VO(2) compared with the nonpregnant state. The latter findings may be explained by the fact that the metabolic demand of cycle exercise is largely independent of the maternal body mass, resulting in no absolute VO(2) alteration. Few studies that directly measured changes in maternal maximal VO(2) (VO(2max)) showed no difference in the absolute VO(2max) between pregnant and nonpregnant subjects in cycling, swimming or weight-bearing exercise. Efficiency of work during exercise appears to be unchanged during pregnancy in non-weight-bearing exercise. During weight-bearing exercise, the work efficiency was shown to be improved in athletic women who continue exercising and those who stop exercising during pregnancy. When adjusted for weight gain, the increased efficiency is maintained throughout the pregnancy, with the improvement being greater in exercising women. Regular physical activity has been proven to result in marked benefits for mother and fetus. Maternal benefits include improved cardiovascular function, limited pregnancy weight gain, decreased musculoskeletal discomfort, reduced incidence of muscle cramps and lower limb oedema, mood stability, attenuation of gestational diabetes mellitus and gestational hypertension. Fetal benefits include decreased fat mass, improved stress tolerance, and advanced neurobehavioural maturation. In addition, few studies that have directly examined the effects of physical activity on labour and delivery indicate that, for women with normal pregnancies, physical activity is accompanied with shorter labour and decreased incidence of operative delivery. However, a substantial proportion of women stop exercising after they discover they are pregnant, and only few begin participating in exercise activities during pregnancy. The adoption or continuation of a sedentary lifestyle during pregnancy may contribute to the development of certain disorders such as hypertension, maternal and childhood obesity, gestational diabetes, dyspnoea, and pre-eclampsia. In view of the global epidemic of sedentary behaviour and obesity-related pathology, prenatal physical activity was shown to be useful for the prevention and treatment of these conditions. Further studies with larger sample sizes are required to confirm the association between physical activity and outcomes of labour and delivery.

Objective: We sought to examine the relation between recommended levels of physical activity during pregnancy and pregnancy outcomes., Study Design: We conducted an observational study with energy expenditure, aerobic fitness, and sleeping heart rate measured in 44 healthy women in late pregnancy. Medical records were examined for pregnancy outcome., Results: Active women, who engaged in > or = 30 minutes of moderate physical activity per day, had significantly better fitness and lower sleeping heart rate compared to the inactive. Duration of second stage of labor was 88 and 146 minutes in the active vs inactive women, respectively (P = .05). Crude odds ratio of operative delivery in the inactive vs the active was 3.7 (95% confidence interval, 0.87-16.08). Birthweight, maternal weight gain, and parity adjusted odds ratio was 7.6 (95% confidence interval, 1.23-45.8). Neonatal condition and other obstetric outcomes were similar between groups., Conclusion: Active women have better aerobic fitness as compared to inactive women. The risk for operative delivery is lower in active women compared to inactive, when controlled for birthweight, maternal weight gain, and parity. Further studies with larger sample size are required to confirm the association between physical activity and pregnancy outcomes., (Copyright 2010 Mosby, Inc. All rights reserved.)

Aim: The resting metabolic rate (RMR) varies among pregnant women. The factors responsible for this variability are unknown. This study aimed to assess the influence of the prepregnancy body mass index (BMI) on the RMR during late pregnancy., Methods: RMR, height, weight, and total (TEE) and activity (AEE) energy expenditures were measured in 46 healthy women aged 31 ± 5 years (mean ± SD) with low (<19.8), normal (19.8-26.0), and high (>26.0) prepregnancy BMI at 38.2 ± 1.5 weeks of gestation (t(gest)) and 40 ± 7 weeks postpartum (t(post)) (n = 27)., Results: The mean t(gest) RMR for the low-, normal-, and high-BMI groups was 1,373, 1,807, and 2,191 kcal/day, respectively (p = 0.001). The overall mean t(gest) RMR was 316 ± 183 kcal/day (21%), higher than the overall mean t(post) value and this difference was correlated with gestational weight gain (r = 0.78, p < 0.001). The scaled metabolic rate by allometry (RMR/kilograms⁰·⁷³) was similar in the low-, normal-, and high-BMI groups, respectively (p = 0.45). Changes in t(gest) TEE closely paralleled changes in t(gest) RMR (r = 0.84, p < 0.001). AEE was similar among the BMI groups., Conclusion: The RMR is significantly increased in the third trimester of pregnancy. The absolute gestational RMR is higher in women with high prepregnancy BMI due to increased body weight. The scaled metabolic rate (RMR/kilograms⁰·⁷³) is similar among the BMI groups of pregnant women., (Copyright © 2010 S. Karger AG, Basel.)

Objective: To assess the effects of repeated episodes of propofol-associated anesthesia on quality of recovery from anesthesia, clinical status, and erythrocyte physiology in cats., Design: Original study., Animals: 37 cats undergoing short-duration anesthesia for radiotherapy., Procedures: Twice daily on 5 consecutive days, 13 cats with squamous cell carcinoma of the nasal planum (group 1) underwent anesthesia: first via administration of propofol or a midazolam (0.2 mg/kg [0.09 mg/lb])-propofol combination and then via administration of ketamine and midazolam each day (latter data were not analyzed). During a 19-day period, 24 cats with vaccine associated sarcoma (group 2) were anesthetized 12 times with propofol or a midazolam-propofol combination. Anesthesia was maintained with propofol in both groups. Hematologic analysis was performed before, during, and on completion of radiotherapy; changes in Hct and hemoglobin concentration between groups were compared., Results: Mean duration of anesthesia was 8.1 minutes (range, 5 to 20 minutes); no adverse events were detected during recovery. Total dose of propofol administered did not differ between groups 1 (6.34 mg/kg [2.88 mg/lb]) and 2 (4.71 mg/kg [2.14 mg/lb]). Midazolam administration decreased the propofol dose by 26%. Overall decreases from baseline in Hct and hemoglobin concentration were not significantly different between the 2 groups, nor clinically important; however, compared with baseline, values in group 2 were significantly lower after 6 and 12 anesthetic episodes for both protocols. Heinz bodies were identified in low numbers in both groups during radiotherapy., Conclusions and Clinical Relevance: Results indicated that repeated propofol-associated short-duration anesthesia does not lead to clinically relevant hematologic changes in cats undergoing short-duration radiotherapy.

Introduction: There is a lack of validation studies of formulas for estimating resting metabolic rate (RMR) in healthy subjects over 70 years of age. Indirect calorimetry allows measuring RMR (RMRm), but is time consuming and costly and therefore formula are generally used to estimate RMR (RMRe). We assessed the degree of agreement between RMRm and RMRe predicted by five popular equations: Harris-Benedict (HB), Mifflin-St Jeor (MJ), Owen (OW), World Health Organization (WHO/FAO/UNU) and Lührmann (LM) in a cohort of elderly subjects., Methods: In 119 healthy subjects, aged 70-98 yr, RMRm was obtained by indirect calorimetry and RMRe by the HB, MJ, OW, WHO/FAO/UNU and LM equations. Means were compared by paired t-test. The Bland and Altman method was used to assess agreement between RMRm and RMRe. Accuracy was defined as the % of individuals whose RMRe was within +/-10% of RMRm., Results: The HB showed the lowest mean RMRe-RMRm difference (-40.9 kcal/day), followed by LM (+44.8 kcal/day) and WHO/FAO/UNU (+53 kcal/day). The HB performed the best of the five equations, having 72.4% of the cases within+/-10% of RMRm. In 18.7% of male subjects and 20% of female subjects HB underestimated the measured values., Conclusions: Large discrepancies exist between RMRm and RMRe in subjects above 70 years of age. HB performs best, but still tends to underestimate in both sexes. In order to develop more accurate equations to estimate RMR in elderly subjects it would be worthwhile to examine whether additionally specific markers of body composition should be taken into consideration.

Objective: Significant changes in body composition occur during lifetime. This longitudinal study (8.0 +/- 0.8 yrs) in a cohort of healthy sedentary and physically active men (n = 78) and women (n = 53), aged 20 to 74 yr describes: 1) the longitudinal changes in weight and body composition and 2) their associations with age and physical activity., Method: Fat-free mass (FFM) and body fat (BF) were assessed by bioelectrical impedance analysis (BIA). Subjects who regularly performed >3 hours per week of endurance type physical activity were classified as "Active". Others were classified as "Sedentary". Subjects were also separated by age (<45 yr vs > or =45 yr)., Results: FFM increased by 1.7 +/- 2.8 kg in men <45 yr who gained 4.0 +/- 5.0 kg of body weight and was maintained (0.5 +/- 1.6 kg) in women <45 y who gained 1.6 +/- 3.0 kg of weight. A weight gain of 1.2 +/- 3.3 kg in men > or =45 yr was accompanied by stable FFM (-0.1 +/- 2.3 kg), and of 1.0 +/- 3.2 kg was accompanied by a loss of FFM in women > or =45 yr. In active men > or =45 yr, maintenance of FFM was associated with smaller weight gains than in sedentary; sedentary men > or =45 yr decreased FFM with larger weight gains than active subjects. Sedentary women <45 yr were able to gain FFM; the active women maintained, but did not gain FFM with smaller weight gains than in sedentary women. FFM decreased in >/=45 yr women despite of small weight gains., Conclusion: Weight change is clearly associated with a change in FFM. Weight gain is necessary to offset age-related FFM loss between 20 and 74 yrs. In active men, a FFM increase was associated with less weight gain than sedentary men. Future studies should evaluate the threshold of weight change and the level of physical activity necessary to prevent age-related losses of FFM.

Squamous cell carcinomas of sparsely haired skin are relatively common tumors in cats, and these tumors likely exhibit a rapid growth rate. Thus, we evaluated response and duration of response in relation to the Ki67 proliferative reactivity in such tumors. Seventeen cats with confirmed squamous cell carcinomas and treated with an accelerated, hypofractionated electron beam radiation protocol were included in the study. For all of them histologic grading, Ki67 reactivity, response, and disease-free interval (DFI) were evaluated. Response to therapy was excellent (94% complete response rate) with a median DFI of 414 days. Only moderate acute and few long-term adverse effects were seen. Cats with tumors with a low Ki67 reactivity had markedly shorter DFIs than cats with tumors with high Ki67 reactivity. We concluded that an accelerated, hypofractionated electron beam radiation therapy protocol is well suited for feline squamous cell carcinomas. The protocol appears especially efficacious in tumors with a high Ki67 reactivity.

Purpose: The aim of the present study was to optimize and simplify photodynamic therapy using a new liposomal formulation of the photosensitizer meta-(tetrahydroxyphenyl)chlorin [m-THPC (Foscan); liposomal m-THPC (Fospeg)] and to reduce systemic reactions to the photosensitizer., Experimental Design: To examine the pharmacokinetics of liposomal m-THPC, we determined tissue and plasma variables in feline patients with spontaneous squamous cell carcinoma. In vivo fluorescence intensity measurements of tumor and skin were done with a fiber spectrophotometer after i.v. injection of m-THPC or liposomal m-THPC in 10 cats. Blood samples, drawn at several time points after photosensitizer administration, were analyzed by high-performance liquid chromatography., Results: None of the liposomal m-THPC-treated cats showed side effects during or after drug injection. Fluorescence intensities, fluorescence ratios (tumor fluorescence divided by skin fluorescence), and bioavailability in the tumor were 2 to 4 times higher with liposomal m-THPC compared with m-THPC. Liposomal m-THPC concentration in the tumor increased constantly to reach a maximum at 4 hours after injection. Plasma concentration and bioavailability were approximately 3 times higher with liposomal m-THPC compared with m-THPC measured at the time points of highest plasma concentration. The distribution half-life was shorter with liposomal m-THPC, resulting in maximal tumor accumulation up to 5.5 times earlier. Maximal tumor accumulation and maximal fluorescence ratio with liposomal m-THPC occurred at the same time point, indicating maximal selectivity. In both groups, all cats responded to therapy., Conclusions: Liposomal m-THPC was well tolerated by all cats and seems to have superior pharmacokinetic properties compared with m-THPC. The efficacy of the drug warrants further study.

Radiotherapy is effective for the palliation of pain associated with primary and metastatic bony neoplasia in dogs and humans, but no standard treatment protocol has been established. The goal of this study was to evaluate a 3 x 8 Gy and a 4 x 6 Gy protocol using electrons with a betatron or linear accelerator for the treatment of appendicular osteosarcoma in 54 dogs. Thirty-three dogs received chemotherapy consisting of carboplatin IV concurrently with radiotherapy. Eighty-three % (n = 45) of the dogs experienced pain relief during or following treatment. The median duration of pain relief from treatment start was 53 days. In conclusion, both protocols are effective for palliation of clinical signs of canine appendicular osteosarcoma. The outcome reported here is similar to the results of other studies using Co photons. The use of chemotherapy did not improve the response to radiotherapy.

Purpose of Review: This article will summarize the current findings on the effects of physical activity on human health and well-being., Recent Findings: Physical activity is associated with enhanced health and reduced risk of all-cause mortality such as cardiovascular disease, hypertension, type 2 diabetes, obesity, osteoporosis, sarcopenia, cognitive disorders, and some forms of cancer. Nevertheless, the effects of exercise with respect to potential health consequences are complex. When untrained or previously sedentary persons undertake vigorous exertion suddenly, the undesired side effects of injuries, dehydration or cardiac arrest are amplified., Summary: It is reasonable to conclude that the risk exposure through physical activity is outweighed by its overall benefits, and health authorities strongly encourage participation in moderate intensity physical activity on a daily basis. In the future, the identification and characterization of particularly inactive sub-groups of the population may facilitate and optimize the planning of public health interventions.

Purpose: The purpose is to investigate the clinical relevance of altered patterns of p27 and Skp2 expression in African-American patients with localized prostate cancer. The abundance of p27, an inhibitor of cell proliferation, is controlled by Skp2-dependent proteolysis., Experimental Design: A well-characterized cohort of 162 African-Americans who underwent radical prostatectomy at the Veterans Affairs Medical Center of New York between 1990 and 2000 was studied. We analyzed p27 and Skp2 expression by immunohistochemistry. Altered expression of p27 (defined as <40% tumor cells expressing the protein) and Skp2 (defined as > or ==" BORDER="0">20% tumor cells expressing the protein) were correlated with clinicopathological parameters and time to prostate-specific antigen (PSA) recurrence., Results: Altered expression of p27 and Skp2 was observed in 112 of 162 (69.1%) and 93 of 162 (57.4%) cases, respectively. Inverse patterns of Skp2 and p27 protein expression were seen in 87 of 162 (53.7%) cases. A marginally significant association was found between Skp2 overexpression and extracapsular extension (P = 0.065). Moreover, patients with Skp2 overexpression had a 2.77 years decreased median time to PSA recurrence compared with patients with low Skp2 expression; however, the difference was not statistically significant. In multivariate analysis, only tumor grade and stage independently predicted PSA recurrence in this cohort., Conclusions: Our data suggest a role for Skp2 overexpression in prostate cancer pathogenesis that might not be exclusively related to p27 degradation. More studies are needed to determine the mechanistic role of Skp2 in prostate cancer.

Overexpression of the oncogene HDM2 is observed in a substantial proportion of melanomas, including noninvasive and thin lesions, suggesting that HDM2 overexpression may be an early event in melanocyte transformation. To determine the role of HDM2 in the clinical progression of melanoma, we examined whether its expression was associated with patient survival. From November 1972 through November 1982, 134 patients with melanoma who participated in the New York University Melanoma Cooperative Group were studied, if representative tissues and follow-up were available. HDM2 protein expression was assessed immunohistochemically. Unexpectedly, we observed that HDM2 overexpression was statistically significantly associated with improved disease-free survival (relative risk [RR] = 0.47, 95% confidence interval [CI] = 0.24 to 0.89; two-sided chi(2) P =.021) and overall survival (RR = 0.55, 95% CI = 0.33 to 0.94; two-sided chi(2) P =.027) in multivariable analysis. HDM2 overexpression appears to be an independent predictor of survival for patients with primary melanoma; however, larger prospective studies are required for validation.

Background: The proliferation marker MIB-1, which recognizes the Ki-67 antigen, provides independent prognostic information in several tumor types. Its utility in melanoma has been evaluated mostly in studies of thick primary tumors. Its usefulness in thinner lesions has not been assessed adequately., Methods: A well characterized cohort of 137 patients diagnosed with primary cutaneous melanoma at the New York University School of Medicine between 1972 and 1982 was studied based on the availability of representative tissues and adequate clinical follow-up. Twenty-one tumors were less than or equal to 1.0 mm thick, 94 were between 1.01 and 4.0 mm thick, and 22 were thicker than 4.0 mm. Tumor cell proliferation was assessed by immunohistochemistry using the monoclonal antibody MIB-1. MIB-1 expression was correlated with baseline clinicopathologic parameters, as well as recurrence (RR), disease-free (DFS), and overall survival (OS) rates. Median follow-up among survivors was 6.5 years (range, 5.6-17.5)., Results: High proliferative index, defined as 20% or more of tumor cells showing nuclear immunoreactivity, was observed in 65 of 137 (47.4%) cases. High proliferative index was significantly correlated with increased tumor thickness (P < 0.001) and higher stage (P = 0.03). Trends approaching statistical significance were observed with ulceration of the primary tumor (P = 0.09), male gender (P = 0.06), and shorter DFS (P = 0.12). No significant associations were seen between high proliferative index and RR or OS. In multivariate analyses, tumor thickness was the strongest predictor of clinical outcome., Conclusions: In primary cutaneous melanoma, a high proliferative index is associated with clinicopathologic parameters predictive of worse clinical outcomes. However, it was not an independent predictor of clinical outcome., (Copyright 2002 American Cancer Society.)

Bone cells form a wired network within the extracellular bone matrix. To analyse this complex 3D structure, we employed a confocal fluorescence imaging procedure to visualize live bone cells within their native surrounding. By means of newly developed image processing software, the "Image-Equalizer", we aimed to enhanced the contrast and eliminize artefacts in such a way that cell bodies as well as fine interconnecting processes were visible.

We investigated the role of alterations of HDM2, the human homologue of murine mdm2, in the tumorigenesis and progression of cutaneous melanoma. A well-characterized cohort of 172 cases representing different points in the spectrum of melanocyte transformation (16 dysplastic nevi, 11 melanomas in situ, 107 invasive primaries, and 38 metastatic lesions), as well as 11 human melanoma cell lines were examined by immunohistochemistry and Western blotting for HDM2 protein expression, and by either Southern blotting (SB) or fluorescence in situ hybridization for HDM2 gene amplification. HDM2 overexpression, defined as >20% tumor cells showing nuclear immunoreactivity, was observed in 1 of 16 (6%) dysplastic nevi, 3 of 11 (27%) melanomas in situ, and 81 of 145 (56%) invasive primary and metastatic melanomas. Comparable frequencies of HDM2 overexpression were observed among invasive primary cases with differing tumor thicknesses as well as among the metastatic cases: 21 of 40 (53%) at < or =1.5 mm; 31 of 50 (62%) at 1.6-3.9 mm; 10 of 17 (58%) at >4 mm; and 19 of 38 (50%) metastases. HDM2 amplification was observed in 1 of 88 (1%) primary cases using fluorescence in situ hybridization, and in 0 of 12 (0%) metastatic cases that overexpressed HDM2 using SB. Melanoma cell lines expressed HDM2 protein, but there was no evidence of amplification by SB. Our data suggest that HDM2 protein overexpression is common in invasive and metastatic melanoma. Observing HDM2 overexpression in noninvasive melanoma suggests that expression of this oncogene may play an early role in melanocyte transformation. HDM2 amplification occurs infrequently, and other mechanisms that up-regulate HDM2 expression are under investigation.

Borna disease (BD) is a rare immunopathological disorder of the central nervous system (CNS) caused by infection with Borna disease virus (BDV) and histologically characterized by mononuclear encephalomyelitis. BD primarily affects equines and sheep in well defined endemic areas of central Europe, but BDV infections have also been reported in other host species including humans, as well as in non endemic regions. In this paper recent data on the pathogenesis of BD are reviewed and the current situation in Switzerland and the Principality of Liechtenstein is summarized.