Suspect severe gastroenteritis associated with ingestion of caterpillar setae fragments in a cat.

A 6-month-old male neutered Domestic Shorthair cat was assessed for a 24-h history of anorexia, lethargy, depressed mentation, mild abdominal pain and persistent bradycardia. Abdominal ultrasound revealed marked thickening of the gastric wall, gastric distension, free abdominal fluid, distension and corrugation of the small intestine. Full-thickness histopathological biopsy of the gastric wall demonstrated intralesional chitinous structures whose morphology (size and presence of obvious barbs) supports these structures being urticating hairs (setae). A processionary caterpillar is considered most likely as these are the most common urticating caterpillars in Australia. This is the first case of suspected severe gastroenteritis associated with the ingestion of caterpillar setae fragments in a cat.

Decision Regret among Patients with Early-stage Lung Cancer Undergoing Radiation Therapy or Surgical Resection.

AIMS: Clinical equipoise exists regarding early-stage lung cancer treatment among patients as trials comparing stereotactic body radiation therapy (SBRT) and surgical resection are unavailable. Given the potential differences in treatment effectiveness and side-effects, we sought to determine the associations between treatment type, decision regret and depression. MATERIALS AND METHODS: A multicentre, prospective study of patients with stage IA-IIA non-small cell lung cancer (NSCLC) with planned treatment with SBRT or surgical resection was conducted. Decision regret and depression were measured using the Decision Regret Scale (DRS) and Patient Health Questionnaire-4 (PHQ-4) at 3, 6 and 12 months post-treatment, respectively. Mixed linear regression modelling examined associations between treatment and decision regret adjusting for patient sociodemographics. RESULTS: Among 211 study participants with early-stage lung cancer, 128 (61%) patients received SBRT and 83 (39%) received surgical resection. The mean age was 73 years (standard deviation = 8); 57% were female; 79% were White non-Hispanic. In the entire cohort at 3 months post-treatment, 72 (34%) and 57 (27%) patients had mild and severe decision regret, respectively. Among patients who received SBRT or surgery, 71% and 46% of patients experienced at least mild decision regret at 3 months, respectively. DRS scores increased at 6 months and decreased slightly at 12 months of follow-up in both groups. Higher DRS scores were associated with SBRT treatment (adjusted mean difference = 4.18, 95% confidence interval 0.82 to 7.54) and depression (adjusted mean difference = 3.49, 95% confidence interval 0.52 to 6.47). Neither patient satisfaction with their provider nor decision-making role concordance was associated with DRS scores. CONCLUSIONS: Most early-stage lung cancer patients experienced at least mild decision regret, which was associated with SBRT treatment and depression symptoms. Findings suggest patients with early-stage lung cancer may not be receiving optimal treatment decision-making support. Therefore, opportunities for improved patient-clinician communication probably exist.

Low Protein Intake Irrespective of Source is Associated with Higher Mortality Among Older Community-dwelling Men.

OBJECTIVES: Our aim was to determine the association between protein intake (overall and by source) and all-cause and cause-specific mortality among older men. DESIGN: Prospective cohort study. SETTING: 5790 ambulatory community-dwelling older men from multicenter Osteoporotic Fractures in Men (MrOS) study. MEASUREMENTS: Total energy and protein intake, and protein intake by source (dairy, non-dairy animal, plant) were assessed using a 69-item food frequency questionnaire. We included up to 10-year follow-up with adjudicated cardiovascular, cancer and other mortality outcomes. We used time-to-event analysis with protein exposures, mortality outcome, and adjusted for possible confounders including age, center, education, race, smoking, alcohol use, physical activity, weight, total energy intake (TEI), and comorbidities. Hazard ratios were expressed per each unit=2.9% TEI decrement for all protein intake variables. RESULTS: The mean (SD) baseline age of 5790 men was 73.6 (5.8) y. There were 1611 deaths and 211 drop-outs prior to 10 years, and 3868 men who were alive at the 10-year follow-up. The mean (SD) total protein intake was 64.7 (25.8) g/d, while the mean (SD) intake expressed as percent of total energy intake (%TEI) was 16.1 (2.9) %TEI. Lower protein intake was associated with an increased risk of death, with unadjusted HR=1.11 (95% CI: 1.06, 1.17) and adjusted HR=1.09 (95% CI: 1.04, 1.14) and the associations for protein intake by source were similar. The adjusted HR for cancer mortality was HR=1.13 (95% CI: 1.03, 1.25) while the association for CVD mortality was HR=1.08 (95% CI: 0.99, 1.18). CONCLUSIONS: Low protein intake, irrespective of source, was associated with a modest increase in risk of all-cause and cause-specific mortality among older men. Special consideration should be given to level of protein intake among older adults.

Aeromedical retrieval of trauma patients: Impact of flight path model on estimates of population coverage.

BACKGROUND: The aim of this study was to compare the impact of different flight path models on the calculated population coverage of aeromedical retrieval systems, using the state of Alabama as a case study. METHODS: Geospatial analysis of U.S. Census Bureau population data using helicopter bases and trauma centers as foci of either circular or elliptical coverage areas. RESULTS: Circular isochrone models around helicopter bases or trauma centers suggest that the entire population of Alabama could reach a level I or II trauma center within 60 min. Elliptical isochrones, incorporating outbound and inbound flights, suggest that only 78.8% of the population have ready access to level I or II trauma centers. CONCLUSION: While all three flight path models described have some validity and utility, simplistic circular flight time isochrones around trauma centers and helicopter bases provide overly optimistic estimates of population coverage. The elliptical model provides a more realistic evaluation.

Cerebrospinal fluid opening pressure: The effect of body mass index and body composition.

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is strongly related to obesity. The relationship between intracranial pressure, body mass index (BMI), percentage body fat and distribution of body fat in non-IIH patients remains less clear. The aim of this study was to examine the relationship between intracranial pressure and body type in non-IIH patients. PATIENTS AND METHODS: Lumbar puncture manometry was used to measure cerebrospinal fluid opening pressure (CSFOP). BMI, in addition to neck, waist and hip circumferences were calculated. Air displacement plethysmography (BODPOD) was used to assess body composition. RESULTS: Data was collected from 100 subjects. 11 subjects with conditions known to cause raised intracranial pressure were excluded from analysis. According to Pearson correlation factors displaying a significant relationship with CSFOP included: BMI (R = 0.635, p < 0.0001); waist circumference (R = 0.498, p < 0.0001), hip circumference (R = 0.513, p < 0.0001) and percentage body fat (R = 0.435, p < 0.001). Multivariate analysis indicated that BMI was the only independent factor which predicted CSFOP. Sub-analysis according to gender indicated that BMI was predictive in females and percentage body fat was predictive in males. We did not identify any differences in BMI, percentage body fat or distribution of body fat in 7 IIH patients and 7 wt-matched non-IIH patients. CONCLUSION: BMI and percentage body fat both positively correlated with CSFOP, but BMI was more predictive in women and percentage body fat was more predictive in men. We did not find a relationship between distribution of body fat and CSFOP.

Effects and moderators of exercise on sleep in adults with cancer: Individual patient data and aggregated meta-analyses.

OBJECTIVES: To evaluate the effects of exercise interventions on sleep disturbances and sleep quality in patients with mixed cancer diagnoses, and identify demographic, clinical, and intervention-related moderators of these effects. METHODS: Individual patient data (IPD) and aggregated meta-analyses of randomized controlled trials (RCTs). Using data from the Predicting OptimaL cAncer RehabIlitation and Supportive care project, IPD of 2173 adults (mean age = 54.8) with cancer from 17 RCTs were analyzed. A complementary systematic search was conducted (until November 2018) to study the overall effects and test the representativeness of analyzed IPD. Effect sizes of exercise effects on self-reported sleep outcomes were calculated for all included RCTs. Linear mixed-effect models were used to evaluate the effects of exercise on post-intervention outcome values, adjusting for baseline values. Moderator effects were studied by testing interactions for demographic, clinical and intervention-related characteristics. RESULTS: For all 27 eligible RCTs from the updated search, exercise interventions significantly decreased sleep disturbances in adults with cancer (g = -0.09, 95% CI [-0.16; -0.02]). No significant effect was obtained for sleep quality. RCTs included in IPD analyses constituted a representative sample of the published literature. The intervention effects on sleep disturbances were not significantly moderated by any demographic, clinical, or intervention-related factor, nor by sleep disturbances. CONCLUSIONS: This meta-analysis provides some evidence that, compared to control conditions, exercise interventions may improve sleep disturbances, but not sleep quality, in cancer patients, although this effect is of a small magnitude. Among the investigated variables, none was found to significantly moderate the effect of exercise interventions on sleep disturbances.

Use of helicopters for retrieval of trauma patients: A geospatial analysis.

BACKGROUND: Helicopters are widely used to facilitate the transport of trauma patients, from the scene of an incident to the hospital. However, the use of helicopters may not always be appropriate. The aim of this project was to conduct a geospatial analysis of helicopter transport to a Level I trauma center. METHODS: Retrospective geospatial analysis of trauma registry data, 2013 to 2018. We included all adult (≥16) trauma patients brought to the trauma center directly from the scene. Data were geocoded and analyzed using arcGIS. Drive times and flight times were calculated using Google Maps. Flight times included the time required to reach the incident location. RESULTS: Two thousand eight hundred ninety-three patients were identified, and 1,911 had incident locations recorded and were therefore included in the analysis. The median age was 41 years (interquartile range [IQR], 27-58 years). Twenty-four percent of the patients had suffered severe injuries (Injury Severity Score [ISS], 16-25), 17% very severe injuries (ISS > 25), 24% moderately severe injuries, and 36% minor injuries (ISS, 1-8). The overall geographical distribution was centroidal, although with a concentration of case volume in the vicinity, and to the northeast, of the trauma center. Median flight time was 60 minutes (IQR, 52-69 minutes), and median drive time 65 minutes (IQR, 54-86 minutes). In 33% of the patients, the calculated drive time to the trauma center was shorter than the calculated flight time when considering the time for the helicopter to reach the scene. CONCLUSION: The majority of patients taken to our level I trauma center by helicopter are injured in relatively close proximity. One in four patients is severely or very severely injured, but one third of the patients have only minor injuries. Over a quarter of trauma patients might have reached hospital more quickly if they had been taken by road, rather than helicopter. LEVEL OF EVIDENCE: Epidemiological/geographical study, level V.

Assessing Community Cancer care after insurance ExpanSionS (ACCESS) study protocol.

BACKGROUND: Cancer is the second most common cause of mortality in the United States. Cancer screening and prevention services have contributed to improved overall cancer survival rates in the past 40 years. Vulnerable populations (i.e., uninsured, low-income, and racial/ethnic minorities) are disproportionately affected by cancer, receive significantly fewer cancer prevention services, poorer healthcare, and subsequently lower survival rates than insured, white, non-Hispanic populations. The Affordable Care Act (ACA) aims to provide health insurance to all low-income citizens and legal residents, including an expansion of Medicaid eligibility for those earning ≤138% of federal poverty level. As of 2012, Medicaid was expanded in 32 states and the District of Columbia, while 18 states did not expand, creating a 'natural experiment' to assess the impact of Medicaid expansion on cancer prevention and care. METHODS: We will use electronic health record data from up to 990 community health centers available up to 24-months before and at least one year after Medicaid expansion. Primary outcomes include health insurance and coverage status, and type of insurance. Additional outcomes include healthcare delivery, number and types of encounters, and receipt of cancer prevention and screening for all patients and preventive care and screening services for cancer survivors. DISCUSSION: Cancer morbidity and mortality is greatly reduced through screening and prevention, but uninsured patients are much less likely than insured patients to receive these services as recommended. This natural policy experiment will provide valuable information about cancer-related healthcare services as the US tackles the distribution of healthcare resources and future health reform. TRIAL REGISTRATION: Clinicaltrails.gov identifier NCT02936609.

Perpetuating effects of androgen deficiency on insulin resistance.

BACKGROUND/OBJECTIVES: Androgen deprivation therapy (ADT) is commonly used for treatment of prostate cancer but is associated with side effects, such as sarcopenia and insulin resistance. The role of lifestyle factors such as diet and exercise on insulin sensitivity and body composition in testosterone-deficient males is poorly understood. The aim of the present study was to examine the relationships between androgen status, diet and insulin sensitivity. SUBJECTS/METHODS: Middle-aged (11-12 years old) intact and orchidectomized male rhesus macaques were maintained for 2 months on a standard chow diet and then exposed for 6 months to a Western-style, high-fat/calorie-dense diet (WSD) followed by 4 months of caloric restriction (CR). Body composition, insulin sensitivity, physical activity, serum cytokine levels and adipose biopsies were evaluated before and after each dietary intervention. RESULTS: Both intact and orchidectomized animals gained similar proportions of body fat, developed visceral and subcutaneous adipocyte hypertrophy and became insulin resistant in response to the WSD. CR reduced body fat in both groups but reversed insulin resistance only in intact animals. Orchidectomized animals displayed progressive sarcopenia, which persisted after the switch to CR. Androgen deficiency was associated with increased levels of interleukin-6 and macrophage-derived chemokine (C-C motif chemokine ligand 22), both of which were elevated during CR. Physical activity levels showed a negative correlation with body fat and insulin sensitivity. CONCLUSIONS: Androgen deficiency exacerbated the negative metabolic side effects of the WSD such that CR alone was not sufficient to improve altered insulin sensitivity, suggesting that ADT patients will require additional interventions to reverse insulin resistance and sarcopenia.

Nutrient and plant secondary compound composition and iron-binding capacity in leaves and green stems of commonly used plant browse (Carolina willow; Salix caroliniana) fed to zoo-managed browsing herbivores.

Plant secondary compounds are diverse structurally, and associated biological effects can vary depending on multiple factors including chemical structure and reaction conditions. Phenolic compounds such as tannins can chelate dietary iron, and supplementation of animal species sensitive to iron overload with tannins may prevent/treat iron overload disorder. We assessed the nutrient and phenolic composition and iron-binding capacity of Carolina willow (Salix caroliniana), a plant fed to zoo-managed browsing herbivores. Based on studies in other plant species and the chemical structures of phenolic compounds, we hypothesized that the concentration of condensed tannins in willow would be inversely related to the concentration of phenolic glycosides and directly related to iron-binding capacity. Our results indicated that willow nutrient composition varied by year, season, and plant part, which could be taken into consideration when formulating animal diets. We also found that the predominant plant secondary compounds were condensed tannins with minimal phenolic glycosides. Instead of binding to iron, the willow leaf extracts reduced iron from the ferric to ferrous form, which may have prooxidative effects and increase the bioavailability of iron depending on animal species, gastrointestinal conditions, and whole animal processes. We recommend identifying alternative compounds that effectively chelate iron in vitro and conducting chelation therapy trials in vivo to assess potential effects on iron balance and overall animal health.

Rare human nicotinic acetylcholine receptor α4 subunit (CHRNA4) variants affect expression and function of high-affinity nicotinic acetylcholine receptors.

Nicotine, the primary psychoactive component in tobacco smoke, produces its behavioral effects through interactions with neuronal nicotinic acetylcholine receptors (nAChRs). α4ß2 nAChRs are the most abundant in mammalian brain, and converging evidence shows that this subtype mediates the rewarding and reinforcing effects of nicotine. A number of rare variants in the CHRNA4 gene that encode the α4 nAChR subunit have been identified in human subjects and appear to be underrepresented in a cohort of smokers. We compared three of these variants (α4R336C, α4P451L, and α4R487Q) to the common variant to determine their effects on α4ß2 nAChR pharmacology. We examined [(3)H]epibatidine binding, interacting proteins, and phosphorylation of the α4 nAChR subunit with liquid chromatography and tandem mass spectrometry (LC-MS/MS) in HEK 293 cells and voltage-clamp electrophysiology in Xenopus laevis oocytes. We observed significant effects of the α4 variants on nAChR expression, subcellular distribution, and sensitivity to nicotine-induced receptor upregulation. Proteomic analysis of immunopurified α4ß2 nAChRs incorporating the rare variants identified considerable differences in the intracellular interactomes due to these single amino acid substitutions. Electrophysiological characterization in X. laevis oocytes revealed alterations in the functional parameters of activation by nAChR agonists conferred by these α4 rare variants, as well as shifts in receptor function after incubation with nicotine. Taken together, these experiments suggest that genetic variation at CHRNA4 alters the assembly and expression of human α4ß2 nAChRs, resulting in receptors that are more sensitive to nicotine exposure than those assembled with the common α4 variant. The changes in nAChR pharmacology could contribute to differences in responses to smoked nicotine in individuals harboring these rare variants.

Impact + resistance training improves bone health and body composition in prematurely menopausal breast cancer survivors: a randomized controlled trial.

UNLABELLED: Our randomized controlled trial in prematurely menopausal breast cancer survivors showed that impact + resistance training prevented increases in percentage of body fat compared with controls and also improved BMD at the hip and prevented BMD loss at the spine among exercise-trained women who were menopausal for >1 year. INTRODUCTION: Cancer treatment-related menopause worsens bone health and body composition in breast cancer survivors (BCS). We investigated whether impact + resistance training could improve bone mineral density (BMD), reduce bone turnover, build muscle, and decrease fat mass in BCS with premature menopause. METHODS: We conducted a randomized controlled trial in 71 BCS (mean age, 46.5 years) within 5 years of treatment-related menopause. Women were randomly assigned to one of two groups: (1) impact + resistance training (prevent osteoporosis with impact + resistance (POWIR)) or (2) exercise placebo (FLEX) 3×/week for 1 year. Outcomes were hip and spine BMD (in grams per square centimeter) and body composition (percent body fat (%BF) and lean and fat mass (in kilograms)) by DXA and bone turnover markers (serum osteocalcin (in nanograms per milliliter) and urinary deoxypryrodinoline (in nanomoles per milliliter). RESULTS: There were no significant group × time interactions for bone outcomes when using an intent-to-treat approach on the full sample. In analyses restricted to BCS who were menopausal for ≥1 year, POWIR increased BMD at the hip and slowed BMD loss at the spine compared with FLEX (femoral neck-POWIR, 0.004 ± 0.093 g/cm(2) vs. FLEX, -0.010 ± 0.089 g/cm(2); p < 0.01; spine-POWIR, -0.003 ± 0.114 g/cm(2) vs. FLEX, -0.020 ± 0.110 g/cm(2); p = 0.03). POWIR prevented increases in %BF (POWIR, 0.01 % vs. FLEX, 1.3 %; p < 0.04). Women with attendance to POWIR at ≥64 % had better improvements in %BF than women attending less often (p < 0.03). CONCLUSION: Impact + resistance training may effectively combat bone loss and worsening body composition from premature menopause in BCS.

Recurrent heterozygous missense mutation, p.Gly573Ser, in the TRPV3 gene in an Indian boy with sporadic Olmsted syndrome.

Olmsted syndrome (OS) is a rare genodermatosis that is often difficult to diagnose because of clinical overlap with other disorders and its uncertain mode of inheritance. The molecular basis of OS was investigated in an Indian boy using comparative exome sequencing and Sanger sequencing data. Sequencing identified a G-to-A transition at position c.573 in the TRPV3 gene, producing the missense mutation p.Gly573Ser in the proband. This mutation was not identified in the mother. This study supports the recent finding of TRPV3 as the gene implicated in OS and suggests that the mutation p.Gly573Ser may be a recurrent abnormality in this genodermatosis.

Long-term survival of concurrent meniscus allograft transplantation and repair of the articular cartilage: a prospective two- to 12-year follow-up report.

We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years (sd 0.4). Cox's proportional hazards model was used to assess the effect of covariates on survival, with age at the time of surgery (p = 0.026) and number of previous operations (p = 0.006) found to be significant. The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial versus lateral allograft transplantation. Patients experienced significant improvements at all periods of follow-up in subjective outcome measures of pain, activity and function (all p-values < 0.05), with the exception of the seven-year Tegner index score (p = 0.076).

Modifiable lifestyle factors affecting bone health using calcaneus quantitative ultrasound in adolescent girls.

UNLABELLED: One hundred and fourteen girls were measured for calcaneus QUS (stiffness index score), calcium intake, weight, and total hours spent in physical activity (moderate to high-impact activities and low to no-impact activities). Multiple regression analysis indicated that hours spent in moderate to high-impact activities, current calcium intake, and weight significantly predicted SI. INTRODUCTION: To determine the influence of modifiable lifestyle factors on adolescent girls' bone health measured by calcaneus quantitative ultrasound (QUS). METHODS: One hundred and fourteen girls, ages 14-18 (15.97 +/- .7), enrolled in high school physical education classes, were measured for calcaneus QUS (stiffness index score), height, weight, current calcium intake from 2-3 day food records, and estimated total hours spent in physical activity from kindergarten to present. Cumulative physical activity hours were separated into two classifications (according to their estimated strain from ground reaction force): moderate to high-impact activities and low to no-impact activities. RESULTS: Pearson correlations between stiffness index (SI) and age, height, weight, current calcium intake, and hours spent in moderate to high-impact versus low to no-impact activities indicated a positive relationships between SI and weight (r = .259, p = .005), current calcium intake (r = .286, p = .002), and hours spent in moderate to high-impact activities (r = .451, p < .001). Multiple regression between SI and the above independent variables indicated that collectively, hours spent in moderate to high-impact activities, current calcium intake, and weight (r (2) = .363, p = <.001) significantly predicted SI. CONCLUSION: Our data indicate that moderate to high-impact activities, current calcium intake, and weight positively influence bone properties of the calcaneus in adolescent girls.

Demographic factors associated with the diet quality of older US men: baseline data from the Osteoporotic Fractures in Men (MrOS) study.

OBJECTIVE: Throughout the world, the proportion of the male population aged 65 years and older is increasing. Yet, we have limited information regarding diet quality and predictors of diet quality in this segment of the population. The objectives of the current analyses are to describe the diet quality of a cohort of men >65 years of age, and identify lifestyle factors associated with poor diet quality. METHODS: We present a cross-sectional analysis of the diet quality of 5928 men, aged 65-100 years, who are participants in the Osteoporotic Fractures in Men (MrOS) cohort study. Dietary intake was determined using a modified Block 98 food-frequency questionnaire. Diet quality was calculated using the previously validated Diet Quality Index-Revised (DQI-R). Univariate and multivariate modelling was used to estimate the variance in diet quality predicted by a number of sociodemographic factors, including age, race/ethnicity, body mass index (BMI), marital status, education, smoking status, physical activity, self-perceived health and nutritional supplement use. RESULTS: Overall, we found that in this geographically diverse group of older men, diet quality was low, with a mean modified DQI-R for the entire study population of 62.5 (standard deviation 13.1) out of an ideal of 100. Further, younger age, very low total calorie intake (< or = 1187 kcal day- 1), higher BMI, residence in a North or Southeast community, being of African-American or Hispanic race, being less educated, not using dietary supplements and smoking were each significant independent predictors of a poorer diet. CONCLUSION: These data may prove useful in both understanding the dietary intake of older US men as it relates to published dietary guidelines, and for targeting future dietary intervention programmes.

Women with hip fracture have a greater rate of decline in bone mineral density than expected: another significant consequence of a common geriatric problem.

INTRODUCTION: Hip fracture is a major public health problem, annually affecting over 350,000 persons in the United States and 1.6 million worldwide. Consequences include decreased survival, loss of independence, and increased risk of subsequent fractures. A substantial decline in bone mineral density (BMD) also occurs, yet the magnitude of the decline specifically attributable to hip fracture has not been documented. METHODS: To determine the amount of BMD decline attributable to hip fracture, the rate of decline in BMD in a cohort of hip fracture patients was compared with that in a cohort of women of similar age and BMD but without hip fracture. All subjects were community dwelling when enrolled. Hip fracture patients in the Baltimore Hip Studies (BHS) came from two hospitals in Baltimore, Maryland, from 1992 through 1995; comparison subjects came from the Study of Osteoporotic Fracture (SOF) enrolled in four areas of the United States during the same period. Eighty-four white, female hip fracture patients 65 years and older from the BHS were compared with 168 SOF participants matched on age, race, and BMD at baseline. BMD of the femoral neck and total hip was measured by dual-energy x-ray absorptiometry. RESULTS: Hip fracture patients had a greater decline in BMD during the 12-month postfracture follow-up than that expected on the basis of the nonfracture cohort: 4.9% vs. 0.4% at the femoral neck and 3.5% vs. 0.7% for the total hip. The decline in BMD in hip fracture patients was 11.8 times the amount expected at the femoral neck (matched on age and baseline BMD and adjusted for between-cohort differences in smoking prevalence) and 4.9 times that expected for the total hip at the end of 1 year after the hip fracture. CONCLUSION: In this sample of older women, bone loss over the year following hip fracture far exceeded that expected and is an important clinical management concern.

Tumor necrosis factor-alpha polymorphism, bone strength phenotypes, and the risk of fracture in older women.

TNFalpha is a proinflammatory cytokine that promotes osteoclastic bone resorption. We evaluated the association between a G-308A polymorphism (rs1800629) at the TNFA locus and osteoporosis phenotypes in 4306 older women participating in the Study of Osteoporotic Fractures. Femoral neck bone mineral density (BMD) and structural geometry were measured using dual-energy x-ray absorptiometry and hip structural analysis. Incident fractures were confirmed by physician adjudication of radiology reports. Despite similar femoral neck BMD, women with the A/A genotype had greater subperiosteal width (P = 0.01) and endocortical diameter (P = 0.03) than those with the G/G genotype. The net result of these structural differences was that there was a greater distribution of bone mass away from the neutral axis of the femoral neck in women with the A/A genotype, resulting in greater indices of bone bending strength (cross-sectional moment of inertia: P = 0.004; section modulus: P = 0.003). Among 376 incident hip fractures during 12.1 yr of follow-up, a 22% decrease in the risk of hip fracture was seen per copy of the A allele (relative risk 0.78; 95% confidence interval 0.63, 0.96), which was not influenced by adjustments for potential confounding factors, BMD, or bone strength indices. The G-308A polymorphism was not associated with a reduced risk of other fractures. These results suggest a potential role of genetic variation in TNFalpha in the etiology of osteoporosis.

[11C]Choline as a PET biomarker for assessment of prostate cancer tumor models.

[(11)C]Choline has been evaluated as a positron emission tomography (PET) biomarker for assessment of established human prostate cancer tumor models. [(11)C]Choline was prepared by the reaction of [(11)C]methyl triflate with 2-dimethylaminoethanol (DMAE) and isolated and purified by solid-phase extraction (SPE) method in 60-85% yield based on [(11)C]CO(2), 15-20 min overall synthesis time from end of bombardment (EOB), 95-99% radiochemical purity and specific activity >0.8 Ci/micromol at end of synthesis (EOS). The biodistribution of [(11)C]choline was determined at 30 min post iv injection in prostate cancer tumor models C4-2, PC-3, CWR22rv, and LNCaP tumor-bearing athymic mice. The results showed the accumulation of [(11)C]choline in these tumors was 1.0% dose/g in C4-2 mouse, 0.4% dose/g in PC-3 mice, 3.2% dose/g in CWR22rv mice, and 1.4% dose/g in LNCaP mice; the ratios of tumor/muscle (T/M) and tumor/blood (T/B) were 2.3 (T/M, C4-2), 1.4 (T/M, PC-3), 2.5 (T/M, CWR22rv), 1.2 (T/M, LNCaP) and 2.6 (T/B, C4-2), 2.6 (T/B, PC-3), 7.8 (T/B, CWR22rv), 3.2 (T/B, LNCaP), respectively. The micro-PET imaging of [(11)C]choline in prostate cancer tumor models was acquired from a C4-2, PC-3, CWR22rv, or LNCaP implanted mouse at 30 min post iv injection of 1 mCi of the tracer using a dedicated high resolution (<3 mm full-width at half-maximum) small FOV (field-of-view) PET imaging system, IndyPET-II scanner, developed in our laboratory, which showed the accumulation of [(11)C]choline in C4-2, PC-3, CWR22rv, or LNCaP tumor implanted in a nude athymic mouse. The initial dynamic micro-PET imaging data indicated the average T/M ratios were approximately 3.0 (C4-2), 2.1 (PC-3), 3.5 (CWR22rv), and 3.3 (LNCaP), respectively, which showed the tumor accumulation of [(11)C]choline in all four tumor models is high. These results suggest that there are significant differences in [(11)C]choline accumulation between these different tumor types, and these differences might offer some useful measure of tumor biological process.

Synthesis, biodistribution and micro-PET imaging of radiolabeled antimitotic agent T138067 analogues.

Radiolabeled antimitotic agents [11C]T138067 and [18F]T138067 have been synthesized for evaluation as new potential positron emission tomography (PET) biomarkers for cancer imaging. In vivo biodistribution and micro-PET imaging of [11C]T138067 were performed in breast cancer animal models MCF-7 transfected with IL-1alpha implanted athymic mice and MDA-MB-435 implanted athymic mice. The results suggest that the uptakes of [11C]T138067 in both MCF-7 transfected with IL-1alpha tumor and MDA-MB-435 tumor are non-specific binding.