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1.
Scand J Med Sci Sports ; 33(12): 2470-2481, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37787091

ABSTRACT

Studies examining the effect of protein (PRO) feeding on post resistance exercise (RE) muscle protein synthesis (MPS) have primarily been performed in men, and little evidence is available regarding the quantity of PRO required to maximally stimulate MPS in trained women following repeated bouts of RE. We therefore quantified acute (4 h and 8 h) and extended (24 h) effects of two bouts of resistance exercise, alongside protein-feeding, in women, and the PRO requirement to maximize MPS. Twenty-four RE trained women (26.6 ± 0.7 years, mean ± SEM) performed two bouts of whole-body RE (3 × 8 repetitions/maneuver at 75% 1-repetition maximum) 4 h apart, with post-exercise ingestion of 15 g, 30 g, or 60 g whey PRO (n = 8/group). Saliva, venous blood, and a vastus lateralis muscle biopsy were taken at 0 h, 4 h, 8 h, and 24 h post-exercise. Plasma leucine and branched chain amino acids were quantified using gas chromatography mass spectrometry (GC-MS) after ingestion of D2 O. Fifteen grams PRO did not alter plasma leucine concentration or myofibrillar synthetic rate (MyoFSR). Thirty and sixty grams PRO increased plasma leucine concentration above baseline (105.5 ± 5.3 µM; 120.2 ± 7.4 µM, respectively) at 4 h (151.5 ± 8.2 µM, p < 0.01; 224.8 ± 16.0 µM, p < 0.001, respectively) and 8 h (176.0 ± 7.3 µM, p < 0.001; 281.7 ± 21.6 µM, p < 0.001, respectively). Ingestion of 30 g PRO increased MyoFSR above baseline (0.068 ± 0.005%/h) from 0 to 4 h (0.140 ± 0.021%/h, p < 0.05), 0 to 8 h (0.121 ± 0.012%/h, p < 0.001), and 0 to 24 h (0.099 ± 0.011%/h, p < 0.01). Ingestion of 60 g PRO increased MyoFSR above baseline (0.063 ± 0.003%/h) from 0 to 4 h (0.109 ± 0.011%/h, p < 0.01), 0 to 8 h (0.093 ± 0.008%/h, p < 0.01), and 0 to 24 h (0.086 ± 0.006%/h, p < 0.01). Post-exercise ingestion of 30 g or 60 g PRO, but not 15 g, acutely increased MyoFSR following two consecutive bouts of RE and extended the anabolic window over 24 h. There was no difference between the 30 g and 60 g responses.


Subject(s)
Resistance Training , Male , Humans , Female , Leucine/metabolism , Leucine/pharmacology , Whey Proteins , Muscle, Skeletal/metabolism , Muscle Proteins/metabolism
2.
BMJ Mil Health ; 169(1): 62-68, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36657827

ABSTRACT

INTRODUCTION: Following the opening of all combat roles to women across the UK Armed Forces, there is a requirement to understand the risk of injury to these female personnel. Women injure at a higher rate than men during basic military training, but fewer data are published from individuals who have passed military training. METHODS: A bespoke survey was designed to investigate differences in injury prevalence and medical downgrading between sexes and career employment groups (ie, job roles) in the UK Armed Forces. RESULTS: Questionnaire data were evaluated from 847 service personnel (87% men) employed in combat roles (Royal Marines, Infantry, Royal Armoured Corps, Royal Air Force Regiment (all men)) and non-combat roles (Royal Regiment of Artillery, Corps of Royal Engineers, Royal Logistic Corps and Combat Service Support Corps who were attached to one of the participating units (men and women)). Women reported more total (OR 1.64 (95% CI: 1.03 to 2.59), p=0.035), lower limb (OR 1.92 (95% CI: 1.23 to 2.98), p=0.004) and hip (OR 2.99 (95% CI: 1.59 to 5.62), p<0.001) musculoskeletal injuries in the previous 12 months than men, but there were no sex differences in the prevalence of current or career medical downgrading due to musculoskeletal injury (both p>0.05). There were no differences in 12-month musculoskeletal injury prevalence between men in combat roles and men in non-combat roles (all p>0.05), but men in non-combat roles were more likely to be currently medically downgraded (OR 1.88 (95% CI: 1.27 to 2.78), p=0.001) and medically downgraded during their career (OR 1.49 (95% CI: 1.11 to 2.00), p=0.008) due to musculoskeletal injury than men in combat roles. More time in service and quicker 1.5-mile run times were associated with increased prevalence of total musculoskeletal injuries, and female sex was a predictor of hip injury. CONCLUSIONS: Although women are at greater risk of injury than men, we have no evidence that combat employment is more injurious than non-combat employment. The prevention of hip injuries should form a specific focus of mitigation efforts for women.


Subject(s)
Military Personnel , Musculoskeletal Diseases , Male , Humans , Female , Cohort Studies , Musculoskeletal Diseases/epidemiology , Surveys and Questionnaires , Employment
3.
BMJ Mil Health ; 169(1): 78-80, 2023 Feb.
Article in English | MEDLINE | ID: mdl-32665421

ABSTRACT

In October 2018, women became eligible to serve in all roles in the UK Armed Forces. The Israeli Defense Forces (IDF) have employed women in limited ground close combat (GCC) roles since 1995. Integration of women into some IDF combat units has improved our understanding of injury risk for servicewomen. While the research findings from physiological studies on women in IDF GCC roles helped inform the integration of women into UK GCC roles, the applicability of the data is limited by the differences between Israeli and UK approaches to recruitment, training and operational deployability of servicewomen. Women in IDF combat roles do, therefore, not provide a good model on the health and performance implications for women in UK Armed Forces combat roles. Further original research to better understand and develop mitigations against any health risks facing UK servicewomen in GCC roles is warranted.


Subject(s)
Military Personnel , Humans , Female , Israel , United Kingdom
4.
BMJ Mil Health ; 169(1): 23-26, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33461982

ABSTRACT

INTRODUCTION: Thirty four per cent of women use hormonal contraceptives in the UK and the contraceptive pill is the most common method. There are no comparable data in the UK Armed Forces, but servicewomen are often required to complete physically arduous job roles in combat zones and may be more likely to take contraceptives to control or stop menstrual bleeding than the general population. We explored the prevalence of hormonal contraceptive prescriptions in the UK Armed Forces. METHODS: The study used defence medical records (Defence Medical Information Capability Programme) to identify hormonal contraceptive prescriptions for all serving regular UK servicewomen (n=15 738) as of 1 September 2017. RESULTS: Thirty one per cent of servicewomen (Royal Navy, 28%; British Army, 30%; Royal Air Force, 34%) had a current prescription for a hormonal contraceptive. Non-officer ranks were more likely to have a prescription for a hormonal contraceptive (32%) than officers (27%) (p<0.01). The contraceptive pill was more commonly prescribed (68%) than long-acting reversible contraceptive methods (32%) (contraceptive injection, 11%; contraceptive implant, 11%; intrauterine device, 10%). CONCLUSION: Prescription data suggest that the prevalence of hormonal contraceptive use in UK servicewomen is comparable with the general UK population. These findings suggest that military service does not influence prevalence or choice of hormonal contraceptives.


Subject(s)
Contraceptive Agents , Military Personnel , Humans , Female , Contraception/methods , Prescriptions , United Kingdom
5.
BMJ Mil Health ; 169(1): 89-93, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33478981

ABSTRACT

Load carriage and marching 'in-step' are routine military activities associated with lower limb injury risk in service personnel. The fixed pace and stride length of marching typically vary from the preferred walking gait and may result in overstriding. Overstriding increases ground reaction forces and muscle forces. Women are more likely to overstride than men due to their shorter stature. These biomechanical responses to overstriding may be most pronounced when marching close to the preferred walk-to-run transition speed. Load carriage also affects walking gait and increases ground reaction forces, joint moments and the demands on the muscles. Few studies have examined the effects of sex and stature on the biomechanics of marching and load carriage; this evidence is required to inform injury prevention strategies, particularly with the full integration of women in some defence forces. This narrative review explores the effects of sex and stature on the biomechanics of unloaded and loaded marching at a fixed pace and evaluates the implications for injury risk. The knowledge gaps in the literature, and distinct lack of studies on women, are highlighted, and areas that need more research to support evidence-based injury prevention measures, especially for women in arduous military roles, are identified.


Subject(s)
Military Personnel , Male , Humans , Female , Biomechanical Phenomena , Walking/physiology , Gait/physiology
6.
BMJ Mil Health ; 169(1): 9-16, 2023 Feb.
Article in English | MEDLINE | ID: mdl-33722817

ABSTRACT

INTRODUCTION: Hormonal contraceptive use might impair bone health and increase the risk of stress fracture by decreasing endogenous oestrogen production, a central regulator of bone metabolism. This cross-sectional study investigated bone density and biochemical markers of bone metabolism in women taking hormonal contraceptives on entry to basic military training. METHODS: Forty-five female British Army recruits had biochemical markers of bone metabolism, areal bone mineral density (aBMD) and tibial speed of sound (tSOS) measured at the start of basic military training. Participants were compared by their method of hormonal contraception: no hormonal contraception (NONE), combined contraceptive pill (CP) or depot-medroxyprogesterone acetate (DMPA) (20±2.8 years, 1.64±0.63 m, 61.7±6.2 kg). RESULTS: aBMD was not different between groups (p≥0.204), but tSOS was higher in NONE (3%, p=0.014) when compared with DMPA users. Beta C-terminal telopeptide was higher in NONE (45%, p=0.037) and DMPA users (90%, p=0.003) compared with CP users. Procollagen type 1 N-terminal propeptide was higher in DMPA users compared with NONE (43%, p=0.045) and CP users (127%, p=0.001), and higher in NONE compared with CP users (59%, p=0.014). Bone alkaline phosphatase was higher in DMPA users compared with CP users (56%, p=0.044). CONCLUSIONS: DMPA use was associated with increased bone turnover and decreased cortical bone integrity of the tibia. Lower cortical bone integrity in DMPA users was possibly mediated by increased intracortical remodelling, but trabecular bone was not affected by contraceptive use.


Subject(s)
Contraceptive Agents, Female , Military Personnel , Female , Humans , Bone Density , Medroxyprogesterone Acetate/pharmacology , Contraceptive Agents, Female/pharmacology , Cross-Sectional Studies , Biomarkers
7.
Psychoneuroendocrinology ; 110: 104432, 2019 12.
Article in English | MEDLINE | ID: mdl-31536944

ABSTRACT

BACKGROUND: Basic military training (BMT) is a useful model of prolonged exposure to multiple stressors. 8-12 week BMT is associated with perturbations in the hypothalamic-pituitary-adrenal (HPA) axis which could predispose recruits to injury and psychological strain. However, characterisations of HPA axis adaptations during BMT have not been comprehensive and most studies included few if any women. METHODS: We studied women undertaking an arduous, 44-week BMT programme in the UK. Anxiety, depression and resilience questionnaires, average hair cortisol concentration (HCC), morning and evening saliva cortisol and morning plasma cortisol were assessed at regular intervals throughout. A 1-h dynamic cortisol response to 1 µg adrenocorticotrophic hormone-1-24 was performed during weeks 1 and 29. RESULTS: Fifty-three women (aged 24 ± 2.5 years) completed the study. Questionnaires demonstrated increased depression and reduced resilience during training (F 6.93 and F 7.24, respectively, both p < 0.001). HCC increased from 3 months before training to the final 3 months of training (median (IQR) 9.63 (5.38, 16.26) versus 11.56 (6.2, 22.45) pg/mg, p = 0.003). Morning saliva cortisol increased during the first 7 weeks of training (0.44 ± 0.23 versus 0.59 ± 0.24 µg/dl p < 0.001) and decreased thereafter, with no difference between the first and final weeks (0.44 ± 0.23 versus 0.38 ± 0.21 µg/dl, p = 0.2). Evening saliva cortisol did not change. Fasting cortisol decreased during training (beginning, mid and end-training concentrations: 701 ± 134, 671 ± 158 and 561 ± 177 nmol/l, respectively, p < 0.001). Afternoon basal cortisol increased during training while there was a trend towards increased peak stimulated cortisol (177 ± 92 versus 259 ± 13 nmol/l, p = 0.003, and 589 ± 164 versus 656 ± 135, p = 0.058, respectively). DISCUSSION: These results suggest a normal stress response in early training was followed quickly by habituation, despite psychological and physical stress evidenced by questionnaire scores and HCC, respectively. There was no evidence of HPA axis maladaptation. These observations are reassuring for women undertaking arduous employment.


Subject(s)
Adaptation, Physiological/physiology , Hypothalamo-Hypophyseal System/physiology , Military Personnel , Physical Conditioning, Human/physiology , Pituitary-Adrenal System/physiology , Adult , Affect/physiology , Female , Hair/chemistry , Hair/metabolism , Humans , Hydrocortisone/analysis , Hydrocortisone/metabolism , Hypothalamo-Hypophyseal System/metabolism , Military Personnel/psychology , Physical Conditioning, Human/psychology , Pituitary-Adrenal System/metabolism , Resilience, Psychological , Saliva/chemistry , Saliva/metabolism , Stress, Physiological/physiology , Stress, Psychological/metabolism , Stress, Psychological/physiopathology , Stress, Psychological/psychology , United Kingdom , Young Adult
8.
Eur J Appl Physiol ; 119(8): 1701-1709, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31187282

ABSTRACT

PURPOSE: To compare the effects of high-intensity interval training (HIIT) and moderate-intensity training (CONT), matched for total work, on cardiorespiratory coordination and aerobic fitness. METHODS: This is a two-arm parallel group single-blind randomised study. Twenty adults were assigned to 6 weeks of HIIT or volume-matched CONT. Participants completed a progressive maximal cycling test before and after the training period. Principal component (PC) analysis was performed on the series of cardiorespiratory variables to evaluate dimensionality of cardiorespiratory coordination, before and after lactate turnpoint. PC1 eigenvalues were compared. RESULTS: Both HIIT and CONT improved aerobic fitness (main effects of time, p < 0.001, [Formula: see text] ≥ 0.580), with no differences between groups. CONT decreased the number of PCs from two to one at intensities both below and above the lactate turnpoint; PC1 eigenvalues increased after CONT both below (Z = 2.08; p = 0.04; d = 0.94) and above the lactate turnpoint (Z = 2.10; p = 0.04; d = 1.37). HIIT decreased the number of PCs from two to one after the lactate turnpoint only; PC1 eigenvalues increased after HIIT above the lactate turnpoint (Z = 2.31; p = 0.02; d = 0.42). CONCLUSIONS: Although CONT and HIIT improved aerobic fitness to a similar extent, there were different patterns of change for cardiorespiratory coordination. These changes appear training-intensity specific and could be sensitive to investigate the individual response to endurance training.


Subject(s)
Adaptation, Physiological , Anaerobic Threshold , Cardiorespiratory Fitness , High-Intensity Interval Training/methods , Adult , Female , High-Intensity Interval Training/adverse effects , Humans , Lactic Acid/blood , Male
9.
Scand J Med Sci Sports ; 27(12): 1648-1661, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28207951

ABSTRACT

High-intensity exercise induces significant central and peripheral fatigue; however, the effect of endurance training on these mechanisms of fatigue is poorly understood. We compared the effect of cycling endurance training of disparate intensities on high-intensity exercise endurance capacity and the associated limiting central and peripheral fatigue mechanisms. Twenty adults were randomly assigned to 6 weeks of either high-intensity interval training (HIIT, 6-8×5 minutes at halfway between lactate threshold and maximal oxygen uptake [50%Δ]) or volume-matched moderate-intensity continuous training (CONT, ~60-80 minutes at 90% lactate threshold). Two time to exhaustion (TTE) trials at 50%Δ were completed pre- and post-training to assess endurance capacity; the two post-training trials were completed at the pretraining 50%Δ (same absolute intensity) and the "new" post-training 50%Δ (same relative intensity). Pre- and post-exercise responses to femoral nerve and motor cortex stimulation were examined to determine peripheral and central fatigue, respectively. HIIT resulted in greater increases in TTE at the same absolute and relative intensities as pre-training (148% and 43%, respectively) compared with CONT (38% and -4%, respectively) (P≤.019). Compared with pre-training, HIIT increased the level of potentiated quadriceps twitch reduction (-34% vs -43%, respectively, P=.023) and attenuated the level of voluntary activation reduction (-7% vs -3%, respectively, P=.047) following the TTE trial at the same relative intensity. There were no other training effects on neuromuscular fatigue development. This suggests that central fatigue resistance contributes to enhanced high-intensity exercise endurance capacity after HIIT by allowing greater performance to be extruded from the muscle.


Subject(s)
High-Intensity Interval Training , Muscle Fatigue , Muscle, Skeletal/physiology , Physical Endurance , Adult , Electromyography , Exercise Test , Female , Femoral Nerve/physiology , Humans , Male , Motor Cortex/physiology , Oxygen Consumption , Single-Blind Method , Torque , Young Adult
10.
Scand J Med Sci Sports ; 26(11): 1287-1300, 2016 Nov.
Article in English | MEDLINE | ID: mdl-26606909

ABSTRACT

The development of fatigue after non-exhaustive and exhaustive exercise eliciting differing metabolic demands is poorly understood. Sixteen active males completed five cycling trials. The first trial established the lactate threshold (LT) and maximal oxygen uptake (VO2max ). Two of the remaining trials were completed at a severe intensity (halfway between LT and VO2max , SI) and two at a moderate intensity (90% LT, MI). Each trial involved two non-exhaustive bouts matched for work between intensities before cycling to exhaustion. Responses to stimulation of the femoral nerve and motor cortex were determined after each bout to determine peripheral and central fatigue. Corticospinal excitability, cortical silent period (cSP), short-interval intracortical inhibition (SICI), and intracortical facilitation (ICF) were also assessed. Non-exhaustive cycling induced greater peripheral and central fatigue in the SI compared with the MI (P < 0.05). At exhaustion, there was no difference between intensities; however, peripheral fatigue tended to be greater in the SI vs MI (-31% vs -17%, respectively, P = 0.051). Exhaustive cycling increased SICI (24%, P < 0.001) and reduced the cSP (-14%, P < 0.001) in the SI, whereas ICF was reduced in the MI (-16%, P < 0.001). These findings demonstrate exercise-induced metabolic stress accelerates the development of peripheral and central fatigue, and differentially influences intracortical excitability.


Subject(s)
Bicycling/physiology , Femoral Nerve/physiology , Motor Cortex/physiology , Muscle Fatigue/physiology , Muscle, Skeletal/physiology , Stress, Physiological/physiology , Adult , Humans , Male , Neural Inhibition/physiology , Oxygen Consumption , Young Adult
11.
Biotech Histochem ; 84(5): 217-21, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19886758

ABSTRACT

Abstract Fixation with formaldehyde is the first process to which most biopsy and necropsy specimens are exposed prior to dehydration and embedding in paraffin wax. Tissue specimens that have been fixed in formaldehyde have architectural characteristics that are familiar to virtually every pathologist and these facilitate routine diagnosis. Nevertheless, formaldehyde fixation has some deleterious effects including reduction in immunoreactivity and degradation of nucleic acids. Development of methods to counteract these deleterious effects requires an understanding of the chemical events that occur during tissue fixation and subsequent tissue processing. This short review illustrates some of the chemical consequences of formaldehyde fixation and ethanol dehydration. It also provides some insight into the molecular events accompanying heat-induced antigen retrieval.


Subject(s)
Epitopes/analysis , Epitopes/chemistry , Ethanol/pharmacology , Fixatives/chemistry , Formaldehyde/pharmacology , Hot Temperature , Humans , Immunohistochemistry/methods , Tissue Fixation/methods
12.
Histopathology ; 39(1): 1-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11454038

ABSTRACT

Mitotic counting in surgical pathology: sampling bias, heterogeneity and statistical uncertainty Although several articles on the methodological aspects of mitotic counting have been published, the effects of macroscopic sampling and tumour heterogeneity have not been discussed in any detail. In this review the essential elements for a standardized mitotic counting protocol are described, including microscopic calibration, specific morphological criteria, macroscopic selection, counting procedure, effect of biological variation, threshold, and the setting of an area of uncertainty ('grey area'). We propose that the use of a standard area for mitotic quantification and of a grey area in mitotic counting protocols will facilitate the application of mitotic counting in diagnostic and prognostic pathology.


Subject(s)
Mitotic Index/methods , Pathology, Surgical , Data Interpretation, Statistical , Genetic Heterogeneity , Humans , Mitosis , Mitotic Index/standards , Mitotic Index/statistics & numerical data , Neoplasms/genetics , Neoplasms/pathology , Selection Bias
13.
Mol Diagn ; 6(2): 109-15, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11468695

ABSTRACT

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is an aggressive epithelial neoplasm composed of giant and/or spindle tumor cells and associated with short survival. Most patients are cigarette smokers. The tumor susceptibility gene P-450 1A1 (CYP1A1) is involved in the activation of polycyclic aromatic hydrocarbons, including benzo[a]pyrene, producing DNA-damaging epoxides that lead to G:C-->T:A point mutations. Isoleucine (Ile)-valine (Val) and Val-Val genotypes of the CYP1A1 exon 7 polymorphism are associated with an increased risk for lung cancer in certain populations. METHODS AND RESULTS: We sought to determine whether 25 archival, formalin-fixed, paraffin-embedded PC samples had a modified CYP1A1 gene profile at exon 7 using allele-specific PCR amplification. KRAS mutation status was available for all samples. Previous investigations have shown 0.88 Ile-Ile, 0.12 Ile-Val, and rarely, Val-Val as normal baseline population frequencies. Conversely, the markedly different PC CYP1A1 population frequencies were more likely to have the heterozygote variant alleles: 0.24 (six cases, Ile-Ile) and 0.76 (19 cases, Ile-Val; P <.001). CYP1A1 genotypes were found to be similar in both tumor and nontumor samples in a given case. All KRAS-mutated cases were Ile-Val heterozygotes. CONCLUSION: The increased propensity for the variant CYP1A1 allele may be the contributing factor to PC pathogenesis and may also result from KRAS mutations in these tumors.


Subject(s)
Carcinoma, Giant Cell/genetics , Carcinoma/genetics , Cytochrome P-450 CYP1A1/genetics , Lung Neoplasms/genetics , Alleles , Benzo(a)pyrene , Carcinogens , Exons , Genotype , Heterozygote , Humans , Models, Chemical , Mutation , Phenotype , Polymerase Chain Reaction , Polymorphism, Genetic , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins p21(ras) , Smoking , ras Proteins
14.
Hum Pathol ; 32(6): 578-82, 2001 Jun.
Article in English | MEDLINE | ID: mdl-11431711

ABSTRACT

Gastrointestinal stromal tumor (GIST) has emerged in the past year as a prototypical neoplasm that responds to therapy directed against a single target molecule-the KIT receptor tyrosine kinase protein. Although GIST seldom responds to conventional chemotherapeutic agents, early experience with the tyrosine kinase inhibitor, STI-571 (Gleevec; Novartis, Basel, Switzerland), has been extremely encouraging. Early results have appeared in a recent case report in the New England Journal of Medicine (April 5, 2001),(1) and in early clinical trials from the United States and Europe that were reported at the plenary session of the American Society of Clinical Oncology in San Francisco on May 14, 2001. STI-571 is one of the earliest examples of a nontoxic chemotherapeutic agent (an agent whose anti-cancer activity is not predicated on a cytotoxic mechanism). STI-571 has already shown clinical value in BCR-ABL-positive leukemias. Early clinical results in GIST are so encouraging that oncologists may soon be wrestling with the opportunity of referring every patient with malignant GIST into clinical trials with STI-571. To ensure appropriate treatment, pathologists need to understand the biology and treatment of this tumor and to have standard methods and criteria for providing diagnosis (GIST or not GIST) and consistent prognostic classification (high risk of metastasis or low risk of metastasis).


Subject(s)
Gastrointestinal Neoplasms , Stromal Cells , Benzamides , Cytogenetic Analysis , Enzyme Inhibitors/therapeutic use , Gastrointestinal Neoplasms/diagnosis , Gastrointestinal Neoplasms/drug therapy , Gastrointestinal Neoplasms/genetics , Gastrointestinal Neoplasms/pathology , Humans , Imatinib Mesylate , Piperazines/therapeutic use , Prognosis , Protein-Tyrosine Kinases/antagonists & inhibitors , Proto-Oncogene Proteins c-kit/analysis , Pyrimidines/therapeutic use
16.
Appl Immunohistochem Mol Morphol ; 9(1): 19-23, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11277409

ABSTRACT

The authors investigated the relations between outcome and apoptosis, immunohistochemical demonstration of bcl-2 protein, and immunohistochemical staining for p53 protein in patients with gastrointestinal stromal/smooth muscle tumors (GIST). Patients whose tumors demonstrated cellular apoptosis using the terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling (TUNEL) assay had an improved survival over those whose tumors did not improve. In contrast, patients whose tumors demonstrated staining for bcl-2 protein had a decreased survival compared with those whose tumors did not demonstrate bcl-2. There was no relation between p53 immunoreactivity and survival. These results suggest that inhibition of apoptosis may be associated with malignant behavior in patients with gastrointestinal stromal/smooth muscle tumors.


Subject(s)
Apoptosis , Gastrointestinal Neoplasms/metabolism , Gastrointestinal Neoplasms/pathology , Neoplasms, Muscle Tissue/metabolism , Neoplasms, Muscle Tissue/pathology , Proto-Oncogene Proteins c-bcl-2/metabolism , Tumor Suppressor Protein p53/metabolism , Humans , Immunohistochemistry , In Situ Nick-End Labeling , Leiomyoma/metabolism , Leiomyoma/pathology , Leiomyosarcoma/metabolism , Leiomyosarcoma/pathology , Mitotic Index , Neoplasms, Connective Tissue/metabolism , Neoplasms, Connective Tissue/pathology
17.
Appl Immunohistochem Mol Morphol ; 9(1): 3-8, 2001 Mar.
Article in English | MEDLINE | ID: mdl-11277412

ABSTRACT

Over the last few years, the role of immunohistochemical analysis has been changing from that of an ancillary diagnostic technique to that of a stand-alone diagnostic method, the results of which determine treatment approach. With this change comes a need for increasing standardization of both preanalytical and analytical methods, so that results emanating from different laboratories are directly comparable. These efforts have been aided to some degree by the development of automated staining systems and by the increased use of test kits, but interlaboratory reproducibility for immunohistochemical methods is still far lower than that of most clinical analytical measurements. In this article, the author presents some approaches to further reduce intra- and interlaboratory variation in the performance of immunohistochemical assays, focusing attention on guidelines recently published by NCCLS.


Subject(s)
Immunohistochemistry/standards , Animals , Antibodies, Monoclonal/therapeutic use , Antibodies, Monoclonal, Humanized , Antigens/metabolism , Guidelines as Topic , Humans , Immunohistochemistry/statistics & numerical data , Immunohistochemistry/trends , Quality Control , Reference Standards , Reproducibility of Results , Tissue Fixation , Trastuzumab
18.
Acta Cytol ; 45(1): 9-17, 2001.
Article in English | MEDLINE | ID: mdl-11213513

ABSTRACT

OBJECTIVE: Gastrointestinal stromal tumors (GISTs) are uncommon mesenchymal tumors of the gastrointestinal tract. Fine needle aspiration (FNA) is one option for diagnosing GISTs before surgery. This study was designed to evaluate the clinical utility of FNA in the diagnosis of GISTs. STUDY DESIGN: FNAs from 19 GISTs originating in the stomach, small bowel and colon obtained from 1988 to 1998 were studied. Immunocytochemistry was performed on 12 cases. The GISTs were classified as benign, borderline and malignant, according to location, size, mitotic activity and clinical outcome. RESULTS: Benign (three) and borderline (five) GISTs were all spindle cell type; malignant GISTs included five spindle cell type and six epithelioid type. Most smears contained abundant cellular material. Benign and borderline GISTs of spindle cell type tended to have cells arranged in tightly cohesive clusters, while malignant GISTs were more likely to exhibit loosely cohesive groups with many single cells, occasional nuclear pleomorphism, hyperchromasia and irregular nuclear contours. Epithelioid-type GISTs mimicked adenocarcinoma. Mitoses were seldom observed in either type. CD117 (KIT protein product) was demonstrated by immunocytochemistry in 9 cases, CD34 in 11, desmin in 3, S-100 protein in 2 and smooth muscle actin in 6 cases. CONCLUSION: FNA can be used to diagnose GISTs as spindle cell and epithelioid types, but cytomorphology alone cannot be used to assess malignant potential. Immunocytochemical staining for CD117 is helpful in confirming the diagnosis. Care must be taken to differentiate epithelioid-type GISTs from adenocarcinoma.


Subject(s)
Biopsy, Needle , Gastrointestinal Neoplasms/pathology , Neoplasms, Connective Tissue/pathology , Adenocarcinoma/diagnosis , Aged , Antigens, CD34/analysis , Antigens, CD34/immunology , Biomarkers, Tumor/analysis , Biomarkers, Tumor/immunology , Diagnosis, Differential , Female , Gastrointestinal Neoplasms/classification , Gastrointestinal Neoplasms/diagnosis , Humans , Immunohistochemistry , Male , Middle Aged , Neoplasms, Connective Tissue/classification , Neoplasms, Connective Tissue/diagnosis , Proto-Oncogene Proteins c-kit/analysis , Proto-Oncogene Proteins c-kit/immunology , Retrospective Studies
19.
Hum Pathol ; 32(12): 1309-17, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11774162

ABSTRACT

Telepathology is the use of telecommunications technology as a means to facilitate transfer of image-rich pathology data between remote locations for the purposes of diagnosis, education, and research. Although varying levels of technology exist to accomplish this task, static image--based systems are currently the most widely used around the world. Field selection and image quality have often been identified as major impediments to the successful use of static images for diagnostic telepathology. Between November 1994 and July 1999, the Armed Forces Institute of Pathology (AFIP) performed electronic consultation on over 1,250 static image--based cases, recording a clinically significant concordance rate of 97.3% between telepathology and final diagnosis (in cases in which follow-up material was available). For the same subset of cases, an absolute concordance rate of 73.7% was attained. A review of the case flow and construction of the AFIP telepathology system is presented, as well as factors that have an impact on the diagnostic accuracy of static image-based telepathology sytems in general.


Subject(s)
Diagnostic Services , International Cooperation , Military Medicine , Remote Consultation/methods , Telepathology/methods , Diagnostic Errors , Humans , Reproducibility of Results , United States
20.
Hum Pathol ; 32(12): 1323-6, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11774164

ABSTRACT

Although numerous reports describe the application of remote video microscopy to pathologic diagnosis (telepathology), only a few address some of the special issues surrounding remote cytologic diagnosis (telecytology). These studies have generally suggested a high correlation between telecytologic diagnoses and those arising from direct examination of the glass slides, but factors affecting the clinical utility of routine cytologic diagnosis have not been examined. In this report, we describe our experience in telecytologic consultation on 99 cases seen at the Armed Forces Institute of Pathology between October 1995 and November 1999. The mean time between receipt of the telecytologic images and the contributor receipt of the faxed report was 9.9 hours (median, 5.13 hours). Using stringent criteria for agreement, we find fair to good (48%) concordance between the contributor's impression and the consultant's opinion. The concordance between the consultant's telecytologic diagnosis and the subsequent glass slide diagnosis is imperfect; in 8 (31%) of 26 cases in which the glass slide was sent after the telecytology consultation, a minor discrepancy between these diagnoses was found. No major discrepancies were found between the consultant's telecytologic and glass slide diagnoses.


Subject(s)
Cytodiagnosis/methods , Diagnostic Services , Remote Consultation , Telepathology/methods , Female , Humans , Military Medicine , Reproducibility of Results , United States
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