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1.
Surg Open Sci ; 10: 168-173, 2022 Oct.
Article in English | MEDLINE | ID: mdl-36211629

ABSTRACT

Background: The COVID-19 pandemic has caused unprecedented health care challenges mandating surgical service reconfiguration. Within our hospital, emergency and elective streams were separated and self-contained Protected Elective Surgical Units were developed to mitigate against infection-related morbidity. Aims of this study were to determine the risk of COVID-19 transmission and mortality and whether the development of Protected Elective Surgical Units can result in significant reduction in risk. Methods: A retrospective observational study of consecutive patients from 18 specialties undergoing elective or emergency surgery under general, spinal, or epidural anaesthetic over a 12-month study period was undertaken. Primary outcome measures were 30-day postoperative COVID-19 transmission rate and mortality. Secondary adjusted analyses were performed to ascertain hospital and Protected Elective Surgical Unit transmission rates. Results: Between 15 March 2020 and 14 March 2021, 9,925 patients underwent surgery: 6,464 (65.1%) elective, 5,116 (51.5%) female, and median age 57 (39-70). A total of 69.5% of all procedures were performed in Protected Elective Surgical Units. Overall, 30-day postoperative COVID-19 transmission was 2.8% (3.4% emergency vs 1.2% elective P < .001). Protected Elective Surgical Unit postoperative transmission was significantly lower than non-Protected Elective Surgical Unit (0.42% vs 3.2% P < .001), with an adjusted likely in-hospital Protected Elective Surgical Unit transmission of 0.04%. The 30-day all-cause mortality was 1.7% and was 14.6% in COVID-19-positive patients. COVID-19 infection, age > 70, male sex, American Society of Anesthesiologists grade > 2, and emergency surgery were all independently associated with mortality. Conclusion: This study has demonstrated that Protected Elective Surgical Units can facilitate high-volume elective surgical services throughout peaks of the COVID-19 pandemic while minimising viral transmission and mortality. However, mortality risk associated with perioperative COVID-19 infection remains high.

2.
BJS Open ; 4(1): 91-100, 2020 02.
Article in English | MEDLINE | ID: mdl-32011808

ABSTRACT

BACKGROUND: Surgeon-level operative mortality is widely seen as a measure of quality after gastric and oesophageal resection. This study aimed to evaluate this alongside a compound-level outcome analysis. METHODS: Consecutive patients who underwent treatment including surgery delivered by a multidisciplinary team, which included seven specialist surgeons, were studied. The primary outcome was death within 30 days of surgery; secondary outcomes were anastomotic leak, Clavien-Dindo morbidity score, lymph node harvest, circumferential resection margin (CRM) status, disease-free (DFS), and overall (OS) survival. RESULTS: The median number of annual resections per surgeon was 10 (range 5-25), compared with 14 (5-25) for joint consultant teams (P = 0·855). The median annual surgeon-level mortality rate was 0 (0-9) per cent versus an overall network annual operative mortality rate of 1·8 (0-3·7) per cent. Joint consultant team procedures were associated with fewer operative deaths (0·5 per cent versus 3·4 per cent at surgeon level; P = 0·027). The median surgeon anastomotic leak rate was 12·4 (range 9-20) per cent (P = 0·625 versus the whole surgical range), overall morbidity 46·5 (31-60) per cent (P = 0·066), lymph node harvest 16 (9-29) (P < 0·001), CRM positivity 32·0 (16-46) per cent (P = 0·003), 5-year DFS rate 44·8 (29-60) per cent and OS rate 46·5 (35-53) per cent. No designated metrics were independently associated with DFS or OS in multivariable analysis. CONCLUSION: Annual surgeon-level metrics demonstrated wide variations (fivefold), but these performance metrics were not associated with survival.


ANTECEDENTES: La mortalidad operatoria relacionada con el nivel del cirujano se contempla ampliamente como una medida de calidad tras la resección esofágica. Este estudio tenía como objetivo evaluar este aspecto junto con un análisis de resultados conjuntos a nivel de procedimientos. MÉTODOS: Se estudiaron los pacientes consecutivos que fueron tratados, incluyendo el tratamiento quirúrgico, efectuado por un equipo multidisciplinar formado por siete cirujanos especialistas. La variable principal de resultados era la mortalidad a durante los primeros 30 días de la cirugía, y las variables secundarias fueron la fuga anastomótica, la gravedad de la puntuación de morbilidad de Clavien-Dindo, el número de ganglios linfáticos obtenidos, el estado del margen circunferencial (circumferential margin, CRM), la supervivencia libre de enfermedad (disease-free survival, DFS) y la supervivencia global (overall survival, OS). RESULTADOS: La mediana del número anual de resecciones por cirujano fue de 10 (rango 5-25, P = 0,855). El nivel de la mediana de mortalidad anual por cirujano fue del 0% (0-9,1) y la mortalidad operatoria anual global del equipo de 1,8% (0-3,7, P = 0,389). Los procedimientos conjuntos del equipo consultor se asociaron con menos muertes operatorias (0,5 versus 3,4%, P = 0,027). La tasa mediana (rango) de fuga anastomótica por cirujano fue del 12% (9-20, P = 0,625), la morbilidad global del 46,7% (31-60, P = 0,003), la DFS a los 5 años del 44,8% (28,6-60,0, P = 0,257) y la OS del 46,5% (35,0-52,5, P = 0,573). Ningún factor mostró una asociación independiente con la DFS o la OS en el análisis multivariable. CONCLUSIÓN: Las medidas anuales a nivel de cirujano demostraron amplias variaciones (9 veces), pero estas medidas de rendimiento no se asociaron con la supervivencia.


Subject(s)
Adenocarcinoma/surgery , Benchmarking/methods , Esophageal Neoplasms/surgery , Esophagectomy/statistics & numerical data , Gastrectomy/statistics & numerical data , Stomach Neoplasms/surgery , Adenocarcinoma/mortality , Adenocarcinoma/therapy , Aged , Esophageal Neoplasms/mortality , Esophageal Neoplasms/therapy , Esophagectomy/standards , Female , Gastrectomy/standards , Humans , Male , Margins of Excision , Middle Aged , Stomach Neoplasms/mortality , Stomach Neoplasms/therapy , Surgeons/standards , Survival Analysis , Treatment Outcome , United Kingdom/epidemiology
3.
Eur J Nucl Med Mol Imaging ; 46(4): 801-809, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30116837

ABSTRACT

PURPOSE: PET/CT is now integral to the staging pathway for potentially curable esophageal cancer (EC), primarily to identify distant metastases undetected by computed tomography. The aim of this study was to analyze the effect of PET/CT introduction on survival and assess patterns of recurrence after esophagectomy. METHODS: A longitudinal cohort of EC patients staged between 1998 and 2016 were considered for inclusion. After co-variate adjustment using propensity scoring, a cohort of 496 patients (273 pre-PET/CT and 223 post-PET/CT) who underwent esophagectomy [median age 63 years (31-80), 395 males, 425 adenocarcinomas, 71 squamous cell carcinomas, 325 neoadjuvant therapy] were included. The primary outcome measure was overall survival (OS) based on intention to treat. RESULTS: Three-year OS pre-PET/CT was 42.5% compared with 57.8% post-PET/CT (Chi2 6.571, df 1, p = 0.004). On multivariable analysis, pT stage (HR 1.496 [95% CI 1.28-1.75], p < 0.0001), pN stage (HR 1.114 [95% CI 1.04-1.19], p = 0.001) and PET/CT staging (HR 0.688 [95% CI 0.53-0.89] p = 0.004) were independently associated with OS. Recurrent cancer was observed in 125 patients (51.4%) pre-PET/CT, compared with 74 patients post-PET/CT (37.8%, p = 0.004), and was less likely to be distant recurrence after PET/CT introduction (39.5 vs. 27.0%, p = 0.006). CONCLUSIONS: Enhanced PET/CT staging is an important modality and independent factor associated with improved survival in patients undergoing esophagectomy for cancer.


Subject(s)
Esophageal Neoplasms/diagnostic imaging , Esophageal Neoplasms/pathology , Fluorodeoxyglucose F18 , Positron Emission Tomography Computed Tomography , Propensity Score , Adult , Aged , Aged, 80 and over , Disease-Free Survival , Esophageal Neoplasms/surgery , Esophagectomy , Female , Humans , Male , Middle Aged , Neoplasm Staging , Recurrence
4.
Obes Res Clin Pract ; 12(6): 528-533, 2018.
Article in English | MEDLINE | ID: mdl-29793864

ABSTRACT

OBJECTIVE: Three dimensional (3D) surface imaging is a viable alternative to traditional body morphology measures, but the feasibility of using this technique with people with obesity has not been fully established. Therefore, the aim of this study was to investigate the validity, repeatability and acceptability of a consumer depth camera 3D surface imaging system in imaging people with obesity. METHODS: The concurrent validity of the depth camera based system was investigated by comparing measures of mid-trunk volume to a gold-standard. The repeatability and acceptability of the depth camera system was assessed in people with obesity at a clinic. RESULTS: There was evidence of a fixed systematic difference between the depth camera system and the gold standard but excellent correlation between volume estimates (r2=0.997), with little evidence of proportional bias. The depth camera system was highly repeatable - low typical error (0.192L), high intraclass correlation coefficient (>0.999) and low technical error of measurement (0.64%). Depth camera based 3D surface imaging was also acceptable to people with obesity. CONCLUSION: It is feasible (valid, repeatable and acceptable) to use a low cost, flexible 3D surface imaging system to monitor the body size and shape of people with obesity in a clinical setting.


Subject(s)
Imaging, Three-Dimensional/methods , Obesity/diagnostic imaging , Feasibility Studies , Humans , Reproducibility of Results
5.
Breast ; 28: 121-9, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27288864

ABSTRACT

Breast volume is a key metric in breast surgery and there are a number of different methods which measure it. However, a lack of knowledge regarding a method's accuracy and comparability has made it difficult to establish a clinical standard. We have performed a systematic review of the literature to examine the various techniques for measurement of breast volume and to assess their accuracy and usefulness in clinical practice. Each of the fifteen studies we identified had more than ten live participants and assessed volume measurement accuracy using a gold-standard based on the volume, or mass, of a mastectomy specimen. Many of the studies from this review report large (>200 ml) uncertainty in breast volume and many fail to assess measurement accuracy using appropriate statistical tools. Of the methods assessed, MRI scanning consistently demonstrated the highest accuracy with three studies reporting errors lower than 10% for small (250 ml), medium (500 ml) and large (1000 ml) breasts. However, as a high-cost, non-routine assessment other methods may be more appropriate.


Subject(s)
Breast/anatomy & histology , Breast/diagnostic imaging , Dimensional Measurement Accuracy , Anthropometry/methods , Breast/surgery , Female , Humans , Imaging, Three-Dimensional , Magnetic Resonance Imaging , Mammography , Organ Size , Tomography, X-Ray Computed
6.
World J Surg ; 40(7): 1645-54, 2016 Jul.
Article in English | MEDLINE | ID: mdl-26956905

ABSTRACT

INTRODUCTION: The aim of this study was to examine the influence of an enhanced recovery programme (ERP) on outcomes of upper gastrointestinal (UGI) cancer surgery by means of propensity score-matched analysis. METHODS: Three hundred consecutive patients diagnosed with UGI cancer were studied prospectively before and after the introduction of an ERP. Multiple regression models, including propensity scores, were developed to assess confounding variables associated with undergoing surgery, and the risk adjusted association between treatment and length of hospital stay (LOHS). RESULTS: After regression for confounding factors, a cohort of 252 patients was available of whom 160 received ERP [median age 66 years (IQR 58-73), 119 male, 81 oesophageal, 79 gastric cancer] and 92 control [66 years (IQR 58-74), 74 male, 58 oesophageal, 34 gastric cancer]. ERP operative morbidity (Clavien-Dindo ≥3) and mortality were 13.8 and 3.1 % compared with 17.4 (p = 0.449) and 2.2 % (p = 0.658) in controls. Median ERP critical care and total LOS were 1 (IQR 0-1) and 13 (IQR 10-17) days, compared with 1 (IQR 1-2, p = 0.009) and 16 (IQR 13-26, p < 0.001) days. Multivariable analysis revealed ERP (HR 1.477, 95 % CI 1.084-2.013, p = 0.013), tumour location (HR 2.420, 95 % CI 1.624-3.606, p < 0.001), operative procedure (HR 1.143, 95 % CI 1.032-1.265, p = 0.010), and operative morbidity (HR 0.277, 95 % CI 0.179-0.429, p < 0.001) to be associated with LOHS. CONCLUSION: An ERP in UGI cancer surgery was feasible, safe, and effective.


Subject(s)
Esophageal Neoplasms/surgery , Postoperative Care/methods , Stomach Neoplasms/surgery , Aged , Female , Humans , Length of Stay , Male , Middle Aged , Postoperative Complications , Propensity Score , Prospective Studies
7.
Sci Justice ; 56(1): 9-17, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26746821

ABSTRACT

In the search for better or new methods/techniques to visualise fingermarks or to analyse them exploiting their chemical content, fingermarks inter-variability may hinder the assessment of the method effectiveness. Variability is due to changes in the chemical composition of the fingermarks between different donors and within the same donor, as well as to differential contact time, pressure and angle. When validating a method or comparing it with existing ones, it is not always possible to account for this type of variability. One way to compensate for these issues is to employ, in the early stages of the method development, a device generating reproducible fingermarks. Here the authors present their take on such device, as well as quantitatively describing its performance and benefits against the manual production of marks. Finally a short application is illustrated for the use of this device, at the method developmental stages, in an emerging area of fingerprinting research concerning the retrieval of chemical intelligence from fingermarks.


Subject(s)
Dermatoglyphics , Forensic Sciences/instrumentation , Humans , Image Processing, Computer-Assisted , Reproducibility of Results
9.
Med Eng Phys ; 36(6): 732-8, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24507690

ABSTRACT

Three-dimensional surface imaging technologies have been used in the planning and evaluation of breast reconstructive and cosmetic surgery. The aim of this study was to develop a 3D surface imaging system based on the Microsoft Kinect and assess the accuracy and repeatability with which the system could image the breast. A system comprising two Kinects, calibrated to provide a complete 3D image of the mannequin was developed. Digital measurements of Euclidean and surface distances between landmarks showed acceptable agreement with manual measurements. The mean differences for Euclidean and surface distances were 1.9mm and 2.2mm, respectively. The system also demonstrated good intra- and inter-rater reliability (ICCs>0.999). The Kinect-based 3D surface imaging system offers a low-cost, readily accessible alternative to more expensive, commercially available systems, which have had limited clinical use.


Subject(s)
Breast/anatomy & histology , Imaging, Three-Dimensional/instrumentation , Imaging, Three-Dimensional/methods , User-Computer Interface , Breast/surgery , Calibration , Female , Humans , Imaging, Three-Dimensional/economics , Models, Anatomic , Reproducibility of Results
10.
Prog Retin Eye Res ; 29(4): 249-71, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20226873

ABSTRACT

The glaucomas are a group of relatively common optic neuropathies, in which the pathological loss of retinal ganglion cells causes a progressive loss of sight and associated alterations in the retinal nerve fiber layer and optic nerve head. The diagnosis and management of glaucoma are often dependent on methods of clinical testing that either, 1) identify and quantify patterns of functional visual abnormality, or 2) quantify structural abnormality in the retinal nerve fiber layer, both of which are caused by loss of retinal ganglion cells. Although it is evident that the abnormalities in structure and function should be correlated, propositions to link losses in structure and function in glaucoma have been formulated only recently. The present report describes an attempt to build a model of these linking propositions using data from investigations of the relationships between losses of visual sensitivity and thinning of retinal nerve fiber layer over progressive stages of glaucoma severity. A foundation for the model was laid through the pointwise relationships between visual sensitivities (behavioral perimetry in monkeys with experimental glaucoma) and histological analyses of retinal ganglion cell densities in corresponding retinal locations. The subsequent blocks of the model were constructed from clinical studies of aging in normal human subjects and of clinical glaucoma in patients to provide a direct comparison of the results from standard clinical perimetry and optical coherence tomography. The final formulation is a nonlinear structure-function model that was evaluated by the accuracy and precision of translating visual sensitivities in a region of the visual field to produce a predicted thickness of the retinal nerve fiber layer in the peripapillary sector that corresponded to the region of reduced visual sensitivity. The model was tested on two independent patient populations, with results that confirmed the predictive relationship between the retinal nerve fiber layer thickness and visual sensitivities from clinical perimetry. Thus, the proposed model for linking structure and function in glaucoma has provided information that is important in understanding the results of standard clinical testing and the neuronal losses caused by glaucoma, which may have clinical application for inter-test comparisons of the stage of disease.


Subject(s)
Glaucoma/complications , Glaucoma/pathology , Models, Biological , Perceptual Disorders/etiology , Visual Fields/physiology , Animals , Humans , Optic Disk/pathology , Predictive Value of Tests , Retinal Ganglion Cells/pathology , Visual Field Tests/methods
11.
J Vet Intern Med ; 22(4): 839-43, 2008.
Article in English | MEDLINE | ID: mdl-18482276

ABSTRACT

BACKGROUND: Early diagnosis and treatment are associated with an improved prognosis in blastomycosis. The diagnosis of blastomycosis may be missed by cytology, histopathology, culture, or serology. An enzyme immunoassay (EIA) for detection of Blastomyces dermatitidis galactomannan antigen in body fluids has been used for rapid diagnosis of blastomycosis in humans. HYPOTHESIS: Measurement of Blastomyces antigen in urine or serum by the MVista Blastomyces antigen EIA is more sensitive than measurement of anti-Blastomyces antibodies for diagnosis of blastomycosis in dogs. METHODS: Serum and urine samples from 46 dogs with confirmed blastomycosis were tested for Blastomyces antigen and serum was tested for anti-Blastomyces antibodies. RESULTS: The sensitivity for the detection of antigen in urine was 93.5% and it was 87.0% in serum. The sensitivity of antibody detection by agar gel immunodiffusion (AGID) was 17.4% and it was 76.1% by EIA. Antigen and antibody decreased during itraconazole treatment. CONCLUSIONS AND CLINICAL IMPORTANCE: Antigen detection is a more sensitive test for diagnosis of blastomycosis than antibody testing by AGID, the only commercially available method. Antigen concentrations decreased with treatment.


Subject(s)
Antibodies, Fungal/immunology , Antigens, Fungal/immunology , Blastomycosis/veterinary , Dog Diseases/immunology , Immunoenzyme Techniques/veterinary , Animals , Antibodies, Fungal/urine , Antifungal Agents/therapeutic use , Antigens, Fungal/urine , Blastomyces/immunology , Blastomycosis/diagnosis , Blastomycosis/drug therapy , Blastomycosis/immunology , Dog Diseases/drug therapy , Dog Diseases/urine , Dogs , Itraconazole/therapeutic use , Sensitivity and Specificity , Time Factors
12.
Br J Sports Med ; 42(2): 93-8, 2008 Feb.
Article in English | MEDLINE | ID: mdl-17984194

ABSTRACT

OBJECTIVES: To systematically review published articles investigating the association between structural foot characteristics and tibial stress injuries, and to suggest possible future avenues of research in this area. METHODS: Literature was identified, selected and appraised in accordance with the methods of a systematic review. Articles potentially relevant to the research question were identified by searching the following electronic databases: Amed, Cinahl, Index to UK theses, Medline, PubMed, Scopus, Sports discus and Web of science. Duplicates were removed and, based on the title and abstract, the full text of relevant studies were retrieved. Two reviewers independently assessed papers; this formed the basis for the inclusion of the most appropriate trials. RESULTS: From the 479 articles originally identified, nine were deemed appropriate for inclusion in the review. In general, specific data relating to this relationship was limited. Outcomes of the nine investigations were difficult to compare due to differing methods used across studies. Results have proved conflicting, with limited evidence found to implicate any specific foot type as a potential risk factor for tibial stress injuries. CONCLUSIONS: No definitive conclusions can be drawn relating foot structure or function to an increased risk of tibial stress injuries. Extremes of foot types are likely to pose an increased risk of tibial stress injuries compared to normal arched feet.


Subject(s)
Foot/anatomy & histology , Fractures, Stress/etiology , Tibial Fractures/etiology , Adult , Female , Foot/physiopathology , Humans , Male , Risk Factors
13.
J Sports Sci ; 25(7): 749-55, 2007 May.
Article in English | MEDLINE | ID: mdl-17454543

ABSTRACT

Transverse plane rotations of the upper body are often estimated during the golf swing. The aim of this study was to determine the agreement between upper body alignments measured using markers attached to the thorax and markers on the acromion process during the golf drive. Three-dimensional coordinate data from nine markers were collected (300 Hz) during eight golf drives for 10 participants. The transverse plane alignment of the upper body was calculated using three techniques: inter-acromion vector, thorax vector, and Cardan angles. Agreement between the methods was then assessed using intra-class correlation and 95% limits of agreement. Our results suggested that the thorax vector can be used to provide an accurate estimation of thorax alignment at all stages of the golf swing (R > or = 0.97, systematic difference < 1.0 degrees , random difference < 3.8 degrees ). The inter-acromion vector gave an accurate estimation of thorax alignment at address (R = 0.90, systematic difference = 0.0 degrees , random difference = 4.3 degrees ) but it should not be used to estimate thorax alignment at the top of the backswing (R = 0.32, systematic difference = -16.0 degrees , random difference = 8.7 degrees ) or impact (R = 0.90, systematic difference = -5.1 degrees , random difference = 8.3 degrees ) during the golf drive.


Subject(s)
Ergonomics , Golf , Movement/physiology , Upper Extremity , Adult , Humans , Male , Sports Equipment , United States
14.
J Med Virol ; 70(2): 183-6, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12696103

ABSTRACT

Dendritic cells hold promise as adjuvant for immunotherapy for cancer and infectious diseases. We demonstrate that a significant number of cryopreserved peripheral blood CD34(+) cells from HIV-infected subjects can be transduced with a replication-incompetent lentiviral vector expressing HIV antigens. In addition, untransduced and transduced CD34(+) cells from HIV-infected individuals were able to differentiate into dendritic cells with strong T-cell stimulatory capacity. Thus, cryopreserved CD34(+) cells from HIV-infected subjects may prove useful for immunotherapy for HIV/AIDS.


Subject(s)
Antigens, CD34/metabolism , Dendritic Cells/cytology , Genetic Vectors , HIV Antigens/genetics , Lentivirus/genetics , Transduction, Genetic , Cell Differentiation , Dendritic Cells/immunology , Dendritic Cells/virology , HIV Antigens/immunology , HIV Infections/immunology , Hematopoietic Stem Cells/virology , Humans
15.
Environ Pollut ; 122(2): 169-75, 2003.
Article in English | MEDLINE | ID: mdl-12531304

ABSTRACT

An automated water-renewal toxicity test system is described for exposing benthic invertebrates to whole sediments. The system will intermittently deliver laboratory or on-site water for overlying water replacement in sediment exposures. A range of cycle rates can be used to produce different volume additions of overlying water per day to exposure chambers. The system can be used with six different treatments and eight replicates per treatment producing 48 exposure chambers. Three formulated sediments with variable organic carbon (1.5%, 7.5%) and sand (14%, 63%) content were prepared to test the system exposing amphipods, Hyalella azteca and midges, Chironomus tentans in 10 day whole sediment tests. Intermittent water flow was used with a 90 min cycle time to create two volume additions of laboratory water per 24 h in exposure chambers (180 ml sediment, 320 ml water). Overlying water quality conditions, and survival and growth of both species were consistent and within acceptable limits for the testing requirements of the U.S. EPA guidelines for sediments with freshwater invertebrates.


Subject(s)
Environmental Monitoring/instrumentation , Geologic Sediments , Plankton , Toxicity Tests/instrumentation , Animals , Automation , Environmental Monitoring/methods , Fresh Water , Toxicity Tests/methods
16.
J Biol Chem ; 276(51): 47840-3, 2001 Dec 21.
Article in English | MEDLINE | ID: mdl-11602580

ABSTRACT

Recent findings show that human immunodeficiency virus (HIV)-1 protease inhibitors designed to specifically inhibit the aspartic protease of HIV-1 nonetheless exert various effects on immune cell function in vitro and in vivo. Dendritic cells (DC), central players of the immune system, express several aspartic proteases that are important for DC function. In the present study, we demonstrate that all of the HIV-1 protease inhibitors tested affect DC maturation. In addition, saquinavir had a strong inhibitory effect on the T-cell stimulatory capacity of mature DC. In contrast, indinavir had only a slight effect on DC induced T-cell proliferation and allowed efficient transduction of DC with a replication-incompetent HIV-1 vector designed for DC-based immunotherapy. HIV-1 protease inhibitors that have little or no effect on DC function may be preferable for combination with immunotherapy for HIV/AIDS.


Subject(s)
Dendritic Cells/drug effects , HIV Protease Inhibitors/pharmacology , Indinavir/pharmacology , Cell Division/drug effects , Defective Viruses/physiology , Dendritic Cells/immunology , Genetic Vectors , HIV-1/physiology , Humans , Immunophenotyping , T-Lymphocytes/cytology , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
17.
Neuroreport ; 12(11): 2483-6, 2001 Aug 08.
Article in English | MEDLINE | ID: mdl-11496134

ABSTRACT

Functional imaging studies of the cerebellum have mostly investigated motor performance or have been limited to the anterior lobe and therefore the somatosensory representations in the human cerebellum have not been fully demonstrated. We used fMRI of the entire cerebellum during tactile stimulation of the hand and foot in six normal subjects. Our results demonstrate that the tactile projections to the cerebellum in humans are represented in both the anterior and posterior lobes. in agreement with previous functional imaging studies, our results show a large-scale, between-limb somatotopy comparable to that shown in early animal studies.


Subject(s)
Brain Mapping , Cerebellum/physiology , Touch/physiology , Adult , Hand , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Physical Stimulation , Somatosensory Cortex/physiology
18.
Environ Toxicol Chem ; 20(9): 1968-78, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11521823

ABSTRACT

The sheepshead minnow (Cyprinodon variegatus Lacépède), an estuarine fish species, was exposed to 17alpha-ethynylestradiol (EE2) at nominal test concentrations of 0.2, 2, 20, 200, 400, 800, 1,600, and 3,200 ng/L. Fish were exposed for up to 59 d, from subadult stages to sexual maturity, under flow-through conditions. The exposure period was followed by an evaluation of reproductive success and survival of progeny. The reproductive success of exposed sheepshead minnows, as determined from data on egg production from two subsequent spawning trials, was reduced in fish exposed to 200 ng/L EE2 and, in one spawning trial, in the 20-ng/L treatment. Hatching success was reduced in the progeny of fish exposed to 200 ng/L EE2, but survival was good among fry that successfully hatched. Histological examination indicated generalized edema, damage to gill epithelia, hepatic toxicity, fibrosis of the testis, and evidence of sex reversal, including testes-ova and spermatagonia-like cells in ovaries. The maximum acceptable toxicant concentration (MATC) for gonadal development in males was within the normal range of EE2 concentrations in sewage treatment plant effluents. The exposure regimen and choice of test organism, combined with histological examination, allowed independent evaluation of ecologically significant acute, reproductive and estrogenic endpoints. Estrogen receptor-mediated effects occurred at concentrations where reproductive effects were measurable under standard reproduction assays. The sheepshead minnow appears to be a sensitive in vivo model for partial life-cycle testing of compounds that have the potential to disrupt the endocrine system as well as reproduction in estuarine and coastal marine fish species.


Subject(s)
Cyprinidae , Estradiol Congeners/adverse effects , Ethinyl Estradiol/adverse effects , Receptors, Estrogen/drug effects , Reproduction/drug effects , Water Pollutants, Chemical/adverse effects , Animals , Biological Assay , Biomarkers/analysis , Dose-Response Relationship, Drug , Environmental Monitoring/methods , Female , Gills/pathology , Gonads/growth & development , Gonads/pathology , Liver/pathology , Male , Receptors, Estrogen/physiology , Survival Analysis
19.
Lancet ; 356(9246): 2013, 2000 Dec 09.
Article in English | MEDLINE | ID: mdl-11130551
20.
Antimicrob Agents Chemother ; 44(6): 1624-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10817719

ABSTRACT

Nikkomycin Z was tested both in vitro and in vivo for efficacy against Histoplasma capsulatum. Twenty clinical isolates were tested for susceptibility to nikkomycin Z in comparison to amphotericin B and itraconazole. The median MIC was 8 microg/ml with a range of 4 to 64 microg/ml for nikkomycin Z, 0.56 microg/ml with a range of 0.5 to 1.0 microg/ml for amphotericin B, and < or =0.019 microg/ml for itraconazole. Primary studies were carried out by using a clinical isolate of H. capsulatum for which the MIC of nikkomycin Z was greater than or equal to 64 microg/ml. In survival experiments, mice treated with amphotericin B at 2.0 mg/kg/dose every other day (QOD) itraconazole at 75 mg/kg/dose twice daily (BID), and nikkomycin Z at 100 mg/kg/dose BID survived to day 14, while 70% of mice receiving nikkomycin Z at 20 mg/kg/dose BID and none of the mice receiving nikkomycin Z at 5 mg/kg/dose BID survived to day 14. All vehicle control mice died by day 12. Fungal burden was assessed on survivors. Mice treated with nikkomycin Z at 20 and 100 mg/kg/dose BID had significantly higher CFUs per gram of organ weight in quantitative cultures and higher levels of Histoplasma antigen in lung and spleen homogenates than mice treated with amphotericin B at 2.0 mg/kg/dose QOD or itraconazole at 75 mg/kg/dose BID. Studies also were carried out with a clinical isolate for which the MIC of nikkomycin Z was 4 microg/ml. All mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID survived until the end of the study at day 17 postinfection, while 30% of the untreated vehicle control mice survived. Fungal burden assessed on survivors showed similar levels of Histoplasma antigen in lung and spleen homogenates of mice treated with amphotericin B at 2.0 mg/kg/dose QOD; itraconazole at 75 mg/kg/dose BID; and nikkomycin Z at 100, 20, and 5 mg/kg/dose BID. The three surviving vehicle control mice had significantly higher antigen levels in lung and spleen than other groups (P<0.05). The efficacy of nikkomycin Z at preventing mortality and reducing fungal burden correlates with in vitro susceptibility.


Subject(s)
Aminoglycosides , Amphotericin B/therapeutic use , Anti-Bacterial Agents/therapeutic use , Antifungal Agents/therapeutic use , Histoplasmosis/drug therapy , Itraconazole/therapeutic use , Amphotericin B/pharmacology , Animals , Anti-Bacterial Agents/pharmacology , Antifungal Agents/pharmacology , Cells, Cultured , Disease Models, Animal , Itraconazole/pharmacology , Mice
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