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1.
Osteoporos Int ; 32(6): 1221-1226, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33585952

ABSTRACT

We introduced virtual fracture liaison clinics during the COVID-19 pandemic in order to support clinical care while DXA services were down-turned. We observed that virtual FLS clinics are effective in delivering fracture risk assessment, health promotion, and clinical management and are well received by patients with positive patient experience. INTRODUCTION: We examined the impact of virtual FLS telephone clinics, as an alternative to face-to-face clinics during the COVID-19 lockdown. METHODS: Patients presenting with low trauma fracture were recruited according to standard criteria. A structured telephone clinic appointment was offered, which included fracture risk and health promotion assessment and a treatment plan. Risk factors, demographics, fracture type, FRAX scores, and outcomes were analysed. We assessed patient experience with an anonymised patient survey. RESULTS: Clinical outcomes from virtual clinics were assessed (77F/33M; mean age 65.7 years). The mean 10-year observed fracture risk for major osteoporotic fracture was 18.2% and 7.0% for hip fracture. We observed high 'attendance' rates at 79%; however, a significant number were still not available for telephone review (11%) or cancelled their appointment (10%). A recommendation for bisphosphonate treatment was made in 54% of the cohort based on National Osteoporosis Guidelines Group (NOGG) criteria. Follow-up DXA assessment is planned for 64%, according to fracture risk and NOGG guidance. We received 60 responses from the initial patient survey. Ninety percent rated their overall experience of service at 4 or 5 (very good to excellent). Ninety-eight indicated they would recommend the service to others. CONCLUSIONS: Virtual clinics are effective in delivery of fracture risk assessment and clinical management with positive patient experience. While a significant proportion will require DXA follow-up to complete the clinical assessment, virtual clinics have mitigated delays in fracture prevention interventions during the COVID-19 pandemic.


Subject(s)
COVID-19 , Osteoporotic Fractures , Aged , Communicable Disease Control , Humans , Osteoporotic Fractures/epidemiology , Osteoporotic Fractures/prevention & control , Pandemics , Patient Outcome Assessment , SARS-CoV-2 , Secondary Prevention
2.
Arch Osteoporos ; 15(1): 53, 2020 03 21.
Article in English | MEDLINE | ID: mdl-32198547

ABSTRACT

We introduced an electronic triage system into our osteoporosis service to actively manage referral demand in a busy outpatient service. Our study demonstrated the effectiveness of e-triage in supporting alternative management pathways, through use of virtual advice and direct to investigation services, to improve patient access. PURPOSE: Osteoporosis referrals are increasing with awareness of the potential for prevention of fragility fracture and with complex decision making around management with long-term bisphosphonate therapy. We examined whether active triage of referrals might improve referral management processes and patient access to osteoporosis services. METHODS: We implemented electronic triage (e-triage) of referrals to our osteoporosis service using the Northern Ireland electronic health care record. This included the option of 'advice only', direct to investigation with DXA or face-to-face appointments at the consultant-led complex osteoporosis service. We anticipated that there was scope to manage patient flow direct to investigation, or to provide referring clinicians with clinical advice without the need for a face-to-face assessment, at the consultant-led specialist service. RESULTS: We reviewed e-triage outcomes of 809 referrals (692 F; 117 M) to osteoporosis specialist services (mean age 65 ± 16.5 years) over a 12-month period. There was a high degree of agreement for the triage category between the referring clinician and specialist services (741/809). 73.3% attended a face-to-face appointment at the consultant-led clinic, while active triage enabled direct to investigation (18.4%) or discharge (8.3%) in the remainder. The mean time between receipt of an electronic referral and e-triage was 3 days over the 12-month period as compared with 2.1 days (median 1.1 days) when annual leave periods were excluded. CONCLUSION: E-triage supports effective referral management in a busy osteoporosis service. Efficiency is limited by reliance on a sole clinician and 5 day working at present. There is scope to further improve systems access through multidisciplinary team working, virtual clinics and future information technology developments.


Subject(s)
Ambulatory Care/methods , Osteoporosis/therapy , Telemedicine/methods , Triage/methods , Aged , Aged, 80 and over , Ambulatory Care Facilities , Delivery of Health Care , Female , Fractures, Bone/prevention & control , Health Services Accessibility , Health Services Research , Humans , Male , Middle Aged , Osteoporosis/complications , Outcome and Process Assessment, Health Care , Referral and Consultation
3.
Med Vet Entomol ; 34(2): 207-214, 2020 06.
Article in English | MEDLINE | ID: mdl-31846089

ABSTRACT

Insects with access to finite energy resources must allocate these between maintenance and reproduction in a way that maximizes fitness. This will be influenced by a range of life-history characteristics and the environment in which any particular insect species lives. In the present study, females of the blowfly Lucilia sericata (Diptera: Calliphoridae) were fed diets differing in protein and carbohydrate (sucrose) content and the allocation of lipid to reproduction was quantified using a spectrophotometric method of analysis. Immediately after adult emergence, total body lipid, scaled for differences in body size, showed an initial decline as it was utilized to meet the metabolic demands of cuticle deposition, muscle maturation and then flight. When flies were denied access to sucrose, stored lipid then continued to decrease until flies died, usually within 4 days of emergence. However, flies given access to sucrose were able to increase body lipid content, demonstrating that carbohydrate is essential for homeostasis and that it can be used to synthesize lipid. Nevertheless, female flies fed sucrose only were unable to synthesize egg yolk. Only flies provided with protein were able to mature eggs. However, the rate of egg maturation and number and size of eggs matured were greater for female flies given liver compared with flies provided with pure whey protein powder. The results demonstrate the importance of different dietary components for different elements of the life-history of L. sericata, namely survival and reproduction.


Subject(s)
Diptera/physiology , Nutritional Requirements , Animal Feed/analysis , Animals , Diet , Dietary Carbohydrates/administration & dosage , Dietary Proteins/administration & dosage , Female , Sucrose/administration & dosage
4.
Ulster Med J ; 88(3): 150-156, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31619848

ABSTRACT

Osteoporosis is a significant global health and economic burden associated with bone fracture, morbidity and mortality. Denosumab, a novel human monoclonal antibody second-line treatment, inhibits osteoclast-mediated bone resorption and increases bone mineral density (BMD). Treatment achieves reductions in vertebral, non-vertebral and hip fracture risk. We undertook a service evaluation to review clinical outcomes of patients treated with denosumab in an osteoporosis department that provides regional services. We identified 529 patients (95% female; mean age 72.8 years; 35-98 years), who had at least one dose of denosumab administered for the treatment of osteoporosis. The mean number of denosumab doses administered was 4.9 (range: 1 to 12). 330/529 patients had completed a baseline and post-treatment bone densitometry scan (DXA). The mean observed BMD change at around 18 months at the lumbar spine was +8.4% and at the hip was +3.5%. While the majority have transitioned to shared care administration of treatment within primary care (53%), 20% continue to attend hospital clinics to receive treatment. During follow-up, there were 66 deaths (12%). 15% switched to an alternative treatment or were discharged. This retrospective cohort study demonstrates the clinical effectiveness of denosumab in improving bone mineral density in a real life setting in an ageing, co-morbid population. There has been recent progress with adoption of shared care administration in primary care. As part of a quality improvement programme we have recently developed a dedicated denosumab database and day-case treatment clinic for those receiving treatment in secondary care.


Subject(s)
Bone Density Conservation Agents/administration & dosage , Denosumab/therapeutic use , Fractures, Spontaneous/prevention & control , Osteoporosis/diagnostic imaging , Osteoporosis/drug therapy , Absorptiometry, Photon/methods , Age Factors , Aged , Aged, 80 and over , Bone Density/drug effects , Cohort Studies , Databases, Factual , Female , Humans , Male , Middle Aged , Northern Ireland , Osteoporosis/diagnosis , Prognosis , Retrospective Studies , Risk Assessment , Severity of Illness Index , Sex Factors , Statistics, Nonparametric , Treatment Outcome
5.
BMC Med Res Methodol ; 18(1): 94, 2018 09 15.
Article in English | MEDLINE | ID: mdl-30219029

ABSTRACT

BACKGROUND: Conducting prospective epidemiological studies of hospitalized patients with rare diseases like primary subarachnoid hemorrhage (pSAH) are difficult due to time and budgetary constraints. Routinely collected administrative data could remove these barriers. We derived and validated 3 algorithms to identify hospitalized patients with a high probability of pSAH using administrative data. We aim to externally validate their performance in four hospitals across Canada. METHODS: Eligible patients include those ≥18 years of age admitted to these centres from January 1, 2012 to December 31, 2013. We will include patients whose discharge abstracts contain predictive variables identified in the models (ICD-10-CA diagnostic codes I60** (subarachnoid hemorrhage), I61** (intracranial hemorrhage), 162** (other nontrauma intracranial hemorrhage), I67** (other cerebrovascular disease), S06** (intracranial injury), G97 (other postprocedural nervous system disorder) and CCI procedural codes 1JW51 (occlusion of intracranial vessels), 1JE51 (carotid artery inclusion), 3JW10 (intracranial vessel imaging), 3FY20 (CT scan (soft tissue of neck)), and 3OT20 (CT scan (abdominal cavity)). The algorithms will be applied to each patient and the diagnosis confirmed via chart review. We will assess each model's sensitivity, specificity, negative and positive predictive value across the sites. DISCUSSION: Validating the Ottawa SAH Prediction Algorithms will provide a way to accurately identify large SAH cohorts, thereby furthering research and altering care.


Subject(s)
Administrative Claims, Healthcare/statistics & numerical data , Algorithms , Hospitalization/statistics & numerical data , Subarachnoid Hemorrhage/diagnosis , Canada/epidemiology , Cohort Studies , Female , Humans , International Classification of Diseases , Male , Prognosis , Registries/statistics & numerical data , Reproducibility of Results , Sensitivity and Specificity , Subarachnoid Hemorrhage/classification , Subarachnoid Hemorrhage/epidemiology
6.
Biol Lett ; 13(4)2017 04.
Article in English | MEDLINE | ID: mdl-28404820

ABSTRACT

In group-living mammals, the eviction of subordinate females from breeding groups by dominants may serve to reduce feeding competition or to reduce breeding competition. Here, we combined both correlational and experimental approaches to investigate whether increases in food intake by dominant females reduces their tendency to evict subordinate females in wild meerkats (Suricata suricatta). We used 20 years of long-term data to examine the association between foraging success and eviction rate, and provisioned dominant females during the second half of their pregnancy, when they most commonly evict subordinates. We show that rather than reducing the tendency for dominants to evict subordinates, foraging success of dominant females is positively associated with the probability that pregnant dominant females will evict subordinate females and that experimental feeding increased their rates of eviction. Our results suggest that it is unlikely that the eviction of subordinate females serves to reduce feeding competition and that its principal function may be to reduce reproductive competition. The increase in eviction rates following experimental feeding also suggests that rather than feeding competition, energetic constraints may normally constrain eviction rates.


Subject(s)
Behavior, Animal/physiology , Eating/physiology , Herpestidae/physiology , Social Dominance , Animals , Female , Male , Population Dynamics , Pregnancy
7.
Neurocrit Care ; 25(3): 365-370, 2016 12.
Article in English | MEDLINE | ID: mdl-27071924

ABSTRACT

BACKGROUND: To compare the in-hospital mortality and institutional morbidity from medical therapy (MT), external ventricular drainage (EVD) and suboccipital decompressive craniectomy (SDC) following an acute hemorrhagic posterior cranial fossa stroke (PCFH) in patients admitted to the neurosciences critical care unit (NCCU). Retrospective observational single-center cohort study in a tertiary care center. All consecutive patients (n = 104) admitted with PCFH from January 1st 2005-December 31st 2011 were included in the study. METHODS: All patients with a PCFH were identified and confirmed by reviewing computed tomography of the brain reported by a specialist neuroradiologist. Management decisions (MT, EVD, and SDC) were identified from operative notes and electronic patient records. RESULTS: Following a PCFH, 47.8 % (n = 11) patients died after EVD placement without decompression, 45.7 % (n = 16) died following MT alone, and 17.4 % (n = 8) died following SDC. SDC was associated with lower mortality compared to MT with or without EVD (χ 2 test p = 0.006, p = 0.008). Age, ICNARC score, brain stem involvement, and hematoma volume did not differ significantly between the groups. There was a statistically significant increase in hydrocephalus and intraventricular bleeds in patients treated with EVD placement and SDC (χ 2 test p = 0.02). Median admission Glasgow Coma Scale scores for the MT only, MT with EVD, and SDC groups were 8, 6, and 7, respectively (ranges 3-15, 3-11 and 3-13) and did not differ significantly (Friedman test: p = 0.89). SDC resulted in a longer NCCU stay (mean of 17.4 days, standard deviation = 15.4, p < 0.001) and increased incidence of tracheostomy (50 vs. 17.2 %, p = 0.0004) compared to MT with or without EVD. CONCLUSIONS: SDC following PCFH was associated with a reduction in mortality compared to expectant MT with or without EVD insertion. A high-quality multicenter randomized control trial is required to evaluate the superiority of SDC for PCFH.


Subject(s)
Cerebral Hemorrhage/drug therapy , Cerebral Hemorrhage/mortality , Cerebral Hemorrhage/surgery , Decompressive Craniectomy/methods , Outcome Assessment, Health Care , Ventriculostomy/methods , Adult , Aged , Cranial Fossa, Posterior/drug effects , Cranial Fossa, Posterior/pathology , Cranial Fossa, Posterior/surgery , Female , Glasgow Coma Scale , Hospital Mortality , Humans , Male , Middle Aged , Retrospective Studies
8.
Transplant Proc ; 48(2): 492-6, 2016 Mar.
Article in English | MEDLINE | ID: mdl-27109985

ABSTRACT

BACKGROUND: Cytomegalovirus (CMV) disease is a common and clinically significant complication following intestinal or multivisceral transplantation. CMV disease is more common in cases of serologic mismatch between donor and recipient. Though in some cases it may be asymptomatic, in the immunosuppressed population it often manifests with evidence of systemic infection or end-organ disease. METHODS: We conducted a retrospective review of all patients undergoing intestinal or multivisceral transplantation over 8 years at our institution. RESULTS: Forty-eight transplantations were performed, with 40% of the patients (19/48) having ≥1 episode of CMV viremia, which rose to 90% in the "donor-positive, recipient-negative" (DPRN) serologic mismatch group. The median time to 1st episode following transplantation was 22.3 weeks (range, 1-78) and median duration of each episode was 4.9 weeks (range, 1.6-37.4). Six of the 19 viremic patients (31.6%) developed virologic resistance with 4 of these occurring in the DPRN group. Four of the 6 patients with drug-resistant CMV died with CMV viremia. All patients with drug resistance acquired ganciclovir resistance; these patients were more challenging to manage with second-line toxicity-limited treatments, including foscarnet, cidofovir, and leflunomide. CMV immunoglobulin has been used and we briefly discuss the use of CMV-specific adoptive T-lymphocyte transfer in the management of 1 case. CONCLUSIONS: Post-transplantation CMV disease continues to be challenging to manage, and there is little consensus on optimal management strategies in this patient group, with a significant requirement for novel therapies; these may be pharmacologic or cell based. Extensive multidisciplinary discussion is important for most cases, but particularly for those patients who acquire virologic resistance.


Subject(s)
Cytomegalovirus Infections/epidemiology , Drug Resistance, Viral , Intestines/transplantation , Viremia/epidemiology , Adult , Aged , Antiviral Agents/therapeutic use , Cytomegalovirus Infections/drug therapy , Female , Foscarnet/therapeutic use , Ganciclovir/therapeutic use , Humans , Immunoglobulins/therapeutic use , Immunoglobulins, Intravenous , Immunosuppressive Agents/therapeutic use , Isoxazoles/therapeutic use , Leflunomide , Male , Middle Aged , Retrospective Studies , Viremia/drug therapy
9.
J Evol Biol ; 27(9): 1893-904, 2014 09.
Article in English | MEDLINE | ID: mdl-24962704

ABSTRACT

Individual variation in growth is high in cooperative breeders and may reflect plastic divergence in developmental trajectories leading to breeding vs. helping phenotypes. However, the relative importance of additive genetic variance and developmental plasticity in shaping growth trajectories is largely unknown in cooperative vertebrates. This study exploits weekly sequences of body mass from birth to adulthood to investigate sources of variance in, and covariance between, early and later growth in wild meerkats (Suricata suricatta), a cooperative mongoose. Our results indicate that (i) the correlation between early growth (prior to nutritional independence) and adult mass is positive but weak, and there are frequent changes (compensatory growth) in post-independence growth trajectories; (ii) among parameters describing growth trajectories, those describing growth rate (prior to and at nutritional independence) show undetectable heritability while associated size parameters (mass at nutritional independence and asymptotic mass) are moderately heritable (0.09 ≤ h(2) < 0.3); and (iii) additive genetic effects, rather than early environmental effects, mediate the covariance between early growth and adult mass. These results reveal that meerkat growth trajectories remain plastic throughout development, rather than showing early and irreversible divergence, and that the weak effects of early growth on adult mass, an important determinant of breeding success, are partly genetic. In contrast to most cooperative invertebrates, the acquisition of breeding status is often determined after sexual maturity and strongly impacted by chance in many cooperative vertebrates, who may therefore retain the ability to adjust their morphology to environmental changes and social opportunities arising throughout their development, rather than specializing early.


Subject(s)
Herpestidae/growth & development , Herpestidae/genetics , Animals , Behavior, Animal , Body Weight/genetics , Environment , Female , Genetic Variation , Male , Models, Genetic , Phenotype , Quantitative Trait, Heritable , Reproduction , South Africa
10.
J Evol Biol ; 27(5): 815-25, 2014 May.
Article in English | MEDLINE | ID: mdl-24666630

ABSTRACT

The social niche specialization hypothesis predicts that group-living animals should specialize in particular social roles to avoid social conflict, resulting in alternative life-history strategies for different roles. Social niche specialization, coupled with role-specific life-history trade-offs, should thus generate between-individual differences in behaviour that persist through time, or distinct personalities, as individuals specialize in particular nonoverlapping social roles. We tested for support for the social niche specialization hypothesis in cooperative personality traits in wild female meerkats (Suricata suricatta) that compete for access to dominant social roles. As cooperation is costly and dominance is acquired by heavier females, we predicted that females that ultimately acquired dominant roles would show noncooperative personality types early in life and before and after role acquisition. Although we found large individual differences in repeatable cooperative behaviours, there was no indication that individuals that ultimately acquired dominance differed from unsuccessful individuals in their cooperative behaviour. Early-life behaviour did not predict social role acquisition later in life, nor was cooperative behaviour before and after role acquisition correlated in the same individuals. We suggest that female meerkats do not show social niche specialization resulting in cooperative personalities, but that they exhibit an adaptive response in personality at role acquisition.


Subject(s)
Cooperative Behavior , Herpestidae/physiology , Models, Biological , Animals , Female , Herpestidae/psychology , Social Dominance
11.
J Evol Biol ; 26(10): 2161-70, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23937440

ABSTRACT

The evolution of adaptive phenotypic plasticity relies on the presence of cues that enable organisms to adjust their phenotype to match local conditions. Although mostly studied with respect to nonsocial cues, it is also possible that parents transmit information about the environment to their offspring. Such 'anticipatory parental effects' or 'adaptive transgenerational plasticity' can have important consequences for the dynamics and adaptive potential of populations in heterogeneous environments. Yet, it remains unknown how widespread this form of plasticity is. Using a meta-analysis of experimental studies with a fully factorial design, we show that there is only weak evidence for higher offspring performance when parental and offspring environments are matched compared with when they are mismatched. Estimates of heterogeneity among studies suggest that effects, when they occur, are subtle. Study features, environmental context, life stage and trait categories all failed to explain significant amounts of variation in effect sizes. We discuss theoretical and methodological reasons for the limited evidence for anticipatory parental effects and suggest ways to improve our understanding of the prevalence of this form of plasticity in nature.


Subject(s)
Adaptation, Physiological , Environment , Plants/genetics , Animals , Biological Evolution , Phenotype , Stress, Physiological
12.
Curr Rev Musculoskelet Med ; 3(1-4): 3-10, 2010 Jun 12.
Article in English | MEDLINE | ID: mdl-21063493

ABSTRACT

Posterior knee pain is a common patient complaint. There are broad differential diagnoses of posterior knee pain ranging from common causes such as injury to the musculotendinous structures to less common causes such as osteochondroma. A precise understanding of knee anatomy, the physical examination, and of the differential diagnosis is needed to accurately evaluate and treat posterior knee pain. This article provides a review of the anatomy and important aspects of the history and physical examination when evaluating posterior knee pain. It concludes by discussing the causes and management of posterior knee pain.

13.
J Evol Biol ; 23(8): 1597-604, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20492087

ABSTRACT

Although recent models for the evolution of personality, using game theory and life-history theory, predict that individuals should differ consistently in their cooperative behaviour, consistent individual differences in cooperative behaviour have rarely been documented. In this study, we used a long-term data set on wild meerkats to quantify the repeatability of two types of cooperative care (babysitting and provisioning) within individuals and examined how repeatability varied across age, sex and status categories. Contributions to babysitting and provisioning were significantly repeatable and positively correlated within individuals, with provisioning more repeatable than babysitting. While repeatability of provisioning was relatively invariant across categories of individuals, repeatability of babysitting increased with age and was higher for subordinates than dominants. These results provide support for theoretical predictions that life-history trade-offs favour the evolution of consistent individual differences in cooperative behaviour and raise questions about why some individuals consistently help more than others across a suite of cooperative behaviours.


Subject(s)
Behavior, Animal/physiology , Cooperative Behavior , Herpestidae/physiology , Animals , Female , Individuality , Male
14.
Proc Biol Sci ; 273(1604): 2977-84, 2006 Dec 07.
Article in English | MEDLINE | ID: mdl-17015353

ABSTRACT

Animals that live in cooperative societies form hierarchies in which dominant individuals reap disproportionate benefits from group cooperation. The stability of these societies requires subordinates to accept their inferior status rather than engage in escalated conflict with dominants over rank. Applying the logic of animal contests to these cases predicts that escalated conflict is more likely where subordinates are reproductively suppressed, where group productivity is high, relatedness is low, and where subordinates are relatively strong. We tested these four predictions in the field on co-foundress associations of the paper wasp Polistes dominulus by inducing contests over dominance rank experimentally. Subordinates with lower levels of ovarian development, and those in larger, more productive groups, were more likely to escalate in conflict with their dominant, as predicted. Neither genetic relatedness nor relative body size had significant effects on the probability of escalation. The original dominant emerged as the winner in all except one escalated contest. The results provide the first evidence that reproductive suppression of subordinates increases the threat of escalated conflict, and hence that reproductive sharing can promote stability of the dominant-subordinate relationship.


Subject(s)
Behavior, Animal/physiology , Social Dominance , Wasps/physiology , Aggression/physiology , Animals , Body Size , Cooperative Behavior , Female , Helping Behavior , Male , Models, Biological
15.
Acta Radiol ; 43(4): 433-40, 2002 Jul.
Article in English | MEDLINE | ID: mdl-12225490

ABSTRACT

PURPOSE: To test the feasibility of electron paramagnetic resonance imaging (EPRI) to provide non-invasive images of tissue redox status using redox-sensitive paramagnetic contrast agents. MATERIAL AND METHODS: Nitroxide free radicals were used as paramagnetic agents and a custom-built 300 MHz EPR spectrometer/imager was used for all studies. A phantom was constructed consisting of four tubes containing equal concentrations of a nitroxide. Varying concentrations of hypoxanthine/xanthine oxidase were added to each tube and reduction of the nitroxide was monitored by EPR as a function of time. Tumor-bearing mice were intravenously infused with a nitroxide and the corresponding reduction rate was monitored on a pixel-by-pixel basis using 2D EPR of the tumor-bearing leg and normal leg serving as control. For animal studies, nitroxides were injected intravenously (1.25 mmol/kg) and EPR projections were collected every 3 min after injection using a magnetic field gradient of 2.5 G/cm. The reduction rates of signal intensity on a pixel-by-pixel basis were calculated and plotted as a redox map. Redox maps were also collected from the mice treated with diethylmaleate (DEM), which depletes tissue thiols and alters the global redox status. RESULTS: Redox maps obtained from the phantoms were in agreement with the intensity change in each of the tubes where the signals were decreasing as a function of the enzymatic activity, validating the ability of EPRI to accurately access changes in nitroxide reduction. Redox imaging capability of EPR was next evaluated in vivo. EPR images of the nitroxide distribution and reduction rates in tumor-bearing leg of mice exhibited more heterogeneity than in the normal tissue. Reduction rates were found to be significantly decreased in tumors of mice treated with DEM, consistent with the depletion of thiols and the consequent alteration of the redox status. CONCLUSION: Using redox-sensitive paramagnetic contrast agents, EPRI can non-invasively discriminate redox status differences between normal tissue and tumors.


Subject(s)
Electron Spin Resonance Spectroscopy , Magnetic Resonance Imaging , Neoplasms, Experimental/diagnosis , Animals , Contrast Media , Feasibility Studies , Female , Humans , Maleates/pharmacology , Mice , Mice, Inbred C3H , Neoplasms, Experimental/metabolism , Nitric Oxide , Oxidation-Reduction , Phantoms, Imaging
16.
Am J Physiol Heart Circ Physiol ; 282(5): H1804-9, 2002 May.
Article in English | MEDLINE | ID: mdl-11959646

ABSTRACT

The importance of cardiac output (CO) to blood pressure level during vasovagal syncope is unknown. We measured thermodilution CO, mean blood pressure (MBP), and leg muscle mean sympathetic nerve activity (MSNA) each minute during 60 degrees head-up tilt in 26 patients with recurrent syncope. Eight patients tolerated tilt (TT) for 45 min (mean age 60 +/- 5 yr) and 15 patients developed syncope during tilt (TS) (mean age 58 +/- 4 yr, mean tilt time 15.4 +/- 2 min). In TT patients, CO decreased during the first minute of tilt (from 3.2 +/- 0.2 to 2.5 +/- 0.3 l x min(-1) x m(-2), P = 0.001) and thereafter remained stable between 2.5 +/- 0.3 (P = 0.001) and 2.4 +/- 0.2 l x min(-1) x m(-2) (P = 0.004) at 5 and 45 min, respectively. In TS patients, CO decreased during the first minute (from 3.3 +/- 0.2 to 2.7 +/- 0.1 l x min(-1) x m(-2), P = 0.02) and was stable until 7 min before syncope, falling to 2.0 +/- 0.2 at syncope (P = 0.001). Regression slopes for CO versus time during tilt were -0.01 min(-1) in TT versus -0.1 l x min(-1) x m(-2) x min(-1) in TS (P = 0.001). However, MBP was more closely correlated to total peripheral resistance (R = 0.56, P = 0.001) and MSNA (R = 0.58, P = 0.001) than CO (R = 0.32, P = 0.001). In vasovagal reactions, a progressive decline in CO may contribute to hypotension some minutes before syncope occurs.


Subject(s)
Cardiac Output , Muscle, Skeletal/innervation , Sympathetic Nervous System/physiopathology , Syncope, Vasovagal/physiopathology , Adult , Aged , Blood Pressure , Electrocardiography , Female , Heart Rate , Humans , Leg , Male , Middle Aged , Oxygen/blood , Oxygen Consumption , Posture , Sex Characteristics
17.
J Biol Chem ; 276(51): 47763-6, 2001 Dec 21.
Article in English | MEDLINE | ID: mdl-11684673

ABSTRACT

In response to growth factor stimulation, many mammalian cells transiently generate reactive oxygen species (ROS) that lead to the elevation of tyrosine-phosphorylated and glutathionylated proteins. While investigating EGF-induced glutathionylation in A431 cells, paradoxically we found deglutathionylation of a major 42-kDa protein identified as actin. Mass spectrometric analysis revealed that the glutathionylation site is Cys-374. Deglutathionylation of the G-actin leads to about a 6-fold increase in the rate of polymerization. In vivo studies revealed a 12% increase in F-actin content 15 min after EGF treatment, and F-actin was found in the cell periphery suggesting that in response to growth factor, actin polymerization in vivo is regulated by a reversible glutathionylation mechanism. Deglutathionylation is most likely catalyzed by glutaredoxin (thioltranferase), because Cd(II), an inhibitor of glutaredoxin, inhibits intracellular actin deglutathionylation at 2 microM comparable with its IC(50) in vitro. Moreover, mass spectral analysis showed efficient transfer of GSH from immobilized S-glutathionylated actin to glutaredoxin. Overall, this study revealed a novel physiological relevance of actin polymerization regulated by reversible glutathionylation of the penultimate cysteine mediated by growth factor stimulation.


Subject(s)
Actins/metabolism , Biopolymers/metabolism , Glutathione/metabolism , Amino Acid Sequence , Cell Line , Cytoskeleton/metabolism , Epidermal Growth Factor/pharmacology , Humans , Molecular Sequence Data
18.
J Urol ; 163(6): 1771-4, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10799179

ABSTRACT

PURPOSE: Salvage prostatectomy after full dose radiation therapy is associated with a high risk of urinary incontinence. We evaluated the complications of salvage prostatectomy with continent catheterizable reconstruction and its impact on urinary incontinence. MATERIALS AND METHODS: Between August 1995 and February 1999, 13 patients with biopsy proved, locally recurrent prostate cancer after radiation therapy underwent salvage prostatectomy with complete bladder neck closure and reconstruction with an appendicovesicostomy to the native bladder in 9 and ileovesicostomy in 4. RESULTS: There were no intraoperative complications. Four patients had serious complications necessitating reoperation, including a vesicourethral fistula requiring delayed cystectomy, wound dehiscence with disruption of the appendicovesical anastomosis, leakage from the small bowel anastomosis that resulted in sepsis and death, and stomal stenosis requiring delayed stomal revision in 1 each. Of 12 patients 2 (17%) used pads for incontinence, while 10 were dry during the day and night with a catheterization interval of 2 to 6 hours. CONCLUSIONS: Salvage prostatectomy with continent catheterizable reconstruction is a technically challenging operation with the potential for serious complications. The postoperative continence rate is excellent and appears superior to those in the literature for salvage prostatectomy and vesicourethral anastomosis.


Subject(s)
Neoplasm Recurrence, Local/surgery , Prostatectomy/methods , Prostatic Neoplasms/surgery , Salvage Therapy , Urinary Reservoirs, Continent , Humans , Male , Prostatectomy/adverse effects , Prostatic Neoplasms/radiotherapy , Plastic Surgery Procedures , Treatment Outcome , Urinary Catheterization , Urinary Incontinence/etiology
19.
Article in English | MEDLINE | ID: mdl-10378225

ABSTRACT

1. Dementia patients who retain musical and game-playing skills exhibit impaired performance on explicit memory tests of knowledge about their retained skill. 2. Dementia patients who retain skill at playing dominoes can answer complex questions about the play of the game almost as well as normal elderly domino players when the questions are presented with real dominoes. 3. The aim of this study was to determine if skilled dementia patients could answer questions about domino play when the stimuli were two-dimensional drawings of dominoes. 4. Seventeen dementia patients and eight normal elderly domino players were tested on two forms of the Domino Quiz: first with real dominoes, then with two-dimensional drawings; other neuropsychological tests were given at the same time. 5. Fourteen of the 17 patients and all of the controls showed no decline in answering questions about domino play when two-dimensional drawings were used. These patients showed retained symbolic processing of information about dominoes despite declines in overall mental status, generation of words from specific semantic categories, and recognition memory for domino terminology. 6. Because the 14 patients with retained domino skill performed as accurately as controls on both administrations of a letter cancellation task, the ability to process familiar symbols may be important to their game-playing skill.


Subject(s)
Cognition , Dementia/psychology , Memory , Aged , Aged, 80 and over , Female , Humans , Male , Play and Playthings , Visual Perception
20.
J Urol ; 161(6): 1871-4, 1999 Jun.
Article in English | MEDLINE | ID: mdl-10332456

ABSTRACT

PURPOSE: We determined whether urinary symptomatology correlates with video urodynamic findings. MATERIALS AND METHODS: A total of 115 women with complaints of urinary incontinence completed a 27-item questionnaire. Pelvic examination and video urodynamic study were performed. Subjective findings were scored from 0 to 5, with 5 representing the most severe symptomatology. Patients were divided into 5 subgroups based on etiology of incontinence, and analyzed by Student's t test with p < 0.05 considered statistically significant. RESULTS: Among the 115 patients 11% had normal studies, 38% proximal urethral hypermobility with stress urinary incontinence, 33% intrinsic sphincter deficiency, 11% significant pelvic prolapse and stress urinary incontinence, and 10% detrusor instability. Subjective complaints, such as incontinence during physical activity, were prominent in both stress urinary incontinence groups as well as the prolapse group with stress urinary incontinence. Questions about nocturia, frequency, urgency, urge incontinence, number of pads, number of vaginal deliveries and incomplete emptying were not statistically significant for any group. CONCLUSIONS: Subjective complaints were not helpful in differentiating the etiology of incontinence. Few questions were helpful in predicting which patients would have a normal video urodynamic study.


Subject(s)
Surveys and Questionnaires , Urinary Incontinence/physiopathology , Urodynamics , Adult , Aged , Female , Humans , Middle Aged
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