Veterans with post-traumatic stress disorder exhibit altered emotional processing and attentional control during an emotional Stroop task.

BACKGROUND: Post-traumatic stress disorder (PTSD) is often associated with attention allocation and emotional regulation difficulties, but the brain dynamics underlying these deficits are unknown. The emotional Stroop task (EST) is an ideal means to monitor these difficulties, because participants are asked to attend to non-emotional aspects of the stimuli. In this study, we used magnetoencephalography (MEG) and the EST to monitor attention allocation and emotional regulation during the processing of emotionally charged stimuli in combat veterans with and without PTSD. METHOD: A total of 31 veterans with PTSD and 20 without PTSD performed the EST during MEG. Three categories of stimuli were used, including combat-related, generally threatening and neutral words. MEG data were imaged in the time-frequency domain and the network dynamics were probed for differences in processing threatening and non-threatening words. RESULTS: Behaviorally, veterans with PTSD were significantly slower in responding to combat-related relative to neutral and generally threatening words. Veterans without PTSD exhibited no significant differences in responding to the three different word types. Neurophysiologically, we found a significant three-way interaction between group, word type and time period across multiple brain regions. Follow-up testing indicated stronger theta-frequency (4-8 Hz) responses in the right ventral prefrontal (0.4-0.8 s) and superior temporal cortices (0.6-0.8 s) of veterans without PTSD compared with those with PTSD during the processing of combat-related words. CONCLUSIONS: Our data indicated that veterans with PTSD exhibited deficits in attention allocation and emotional regulation when processing trauma cues, while those without PTSD were able to regulate emotion by directing attention away from threat.

Morbidity management and disability prevention: An agenda for developing nations initiated in India.

Treatment of patients with lymphedema focuses on reducing limb volume with more recent recognition of the importance of qualityof- life issues. Perhaps due to the incidence of filariasis-related lymphedema compared to breast cancer-related lymphedema in the western world, the Institute of Applied Dermatology (IAD) in Kerala, India has developed a low-cost and culturally acceptable treatment with quality-of-life focus that works well in that area. Worldwide, there is also recognition of chronic edema as a potential co-morbidity and the recent advances in genetic analysis continue to shed light on lymphedema development that may be important in filariasisrelated lymphedema. Although improvement in treatment outcomes by surgical means has been shown, there is often conventional treatment mixed in the therapy and no randomized controls of any therapy exist. In addition, these techniques require supermicrosurgical skill not available in many areas of the world. The WHO has documented the need in filariasis for both universal health care and innovative care for chronic conditions. The IAD has addressed these issues with its integrative model of treatment with patient quality-of-life at the forefront to incorporate traditional practice to involve the patient more fully in family and community support for an additional therapeutic tool.

Elephantiasis, elastin, and chronic wound healing: 19th century and contemporary viewpoints relevant to hypotheses concerning lymphedema, leprosy, erysipelas, and psoriasis--review and reflections.

Both wound healing and lymphedema have fibrosis of the skin in common. They also share destruction of elastin by elastases from neutrophils as a significant feature. These are not new observations, and the writings of Unna and Kaposi are recalled. The contemporary observations on elastin by Gerli and his team are discussed in the light of these much earlier opinions.

Fibrinogen degradation product fragment D induces endothelial cell detachment by activation of cell-mediated fibrinolysis.

We studied the effects of fibrinogen degradation product (FDP) fragment D on endothelial monolayer integrity and the mechanisms of fragment D-induced endothelial cell detachment from the substratum. Incubation of bovine pulmonary artery endothelial cells (BPAEC) with fragment D caused concentration- and time-dependent cell detachment from the substratum. The optimal response occurred at fragment D concentrations of 2 microM and required an incubation time of 24 h. BPAEC challenged with fragment D increased the concentration and activity of urokinase-type plasminogen activator (uPA) in the conditioned medium within 2 to 4 h of incubation. Fragment D also induced the release of tissue-type plasminogen activator, but to a lesser extent than uPA. Fragment D concurrently increased plasminogen activator (PA) activity in a concentration-dependent manner. Increased PA activity was followed by augmentation of cell-associated plasmin activity and subsequent increase in the degradation of 125I-fibrinogen and 125I-vitronectin precoated in the subendothelial matrix. Pretreatment of BPAEC with anti-uPA antibody, and inhibitors of uPA (dansyl-GGACK) and plasmin (aprotinin) prevented approximately 60% of the fragment D-induced endothelial cell detachment. We conclude that FDP fragment D increases secretion of endothelial PAs and enhances the generation of plasmin, thereby contributing to proteolysis of extracellular matrix and endothelial cell detachment. Fragment D may be a critical mediator linking activation of fibrinolysis to vascular endothelial injury in inflammatory disorders.

Role of catalytic and lysine-binding sites in plasmin-induced neutrophil adherence to endothelium.

Plasmin resulted in increased neutrophil adherence to cultured ovine pulmonary artery endothelial cell monolayers in a concentration-dependent manner (10(-12)-10(-7) M). The adherence response increased fivefold above baseline within 60 min after addition of plasmin (10(-8) M) and the response persisted up to 30 min after removal of plasmin. The neutrophil adherence was mediated by the action of plasmin on neutrophils rather than endothelial cells. The response was the result of an increase in functional activity of CD18 neutrophil cell surface adhesive glycoprotein. Neutrophil adherence was inhibited by pretreatment of neutrophils with MAbs IB4 and 60.3 targeted against the beta chain of the CD18, whereas control isotypic MAb 60.5 against HLA class I antigen had no effect. The plasmin catalytic site was not involved in the response. Lys-plasminogen had reduced adherence-promoting activity relative to plasmin, whereas glu-plasminogen had no effect. Elastase-derived plasminogen fragments corresponding to kringle 1+2+3 and kringle 4 (both of which contained the lysine-binding sites) possessed neutrophil adherence-promoting activities similar to plasmin, whereas miniplasminogen (which contains the catalytic site but no lysine-binding sites) had minimal effect, indicating the involvement of lysine-binding sites in the response. Blocking lysine-binding sites of plasmin and elastase-derived plasminogen fragments with tranexamic acid (IC50 of 5 mM) inhibited neutrophil adherence. A monospecific polyclonal antibody against the lysine-binding sites also reduced the neutrophil adherence-promoting activity of plasmin. The results indicate that plasmin induces neutrophil adherence to the endothelium and that the effect is mediated by lysine-binding sites on plasmin.

Localization and differential regulation of angiotensinogen mRNA expression in the vessel wall.

Recent data demonstrate the existence of a vascular renin angiotensin system. In this study we examine the localization of angiotensinogen mRNA in the blood vessel wall of two rat strains, the Wistar and Wistar Kyoto (WKY), as well as the regulation of vascular angiotensinogen mRNA expression by dietary sodium. Northern blot analysis and in situ hybridization histochemistry demonstrate that in both strains angiotensinogen mRNA is detected in the aortic medial smooth muscle layer as well as the periaortic fat. In WKY rats fed a 1.6% sodium diet, angiotensinogen mRNA concentration is 2.6-fold higher in the periaortic fat than in the smooth muscle, as analyzed by quantitative slot blot hybridization. Angiotensinogen mRNA expression in the medial smooth muscle layer is sodium regulated. After 5 d of a low (0.02%) sodium diet, smooth muscle angiotensinogen mRNA levels increase 3.2-fold (P less than 0.005) as compared with the 1.6% sodium diet. In contrast, angiotensinogen mRNA level in the periaortic fat is not influenced by sodium diet. In summary, our data demonstrate regional (smooth muscle vs. periaortic fat) differential regulation of angiotensinogen mRNA levels in the blood vessel wall by sodium. This regional differential regulation by sodium may have important physiological implications.

Prognostic value of angiographic indices of coronary artery disease from the Coronary Artery Surgery Study (CASS).

The Coronary Artery Surgery Study, CASS, enrolled 24,959 patients between August 1975 and June 1979 who were studied angiographically for suspected coronary artery disease. This paper compares the prognostic value for survival without early elective surgery of eight different indices of the extent of coronary artery disease: the number of diseased vessels, two indices using the number of proximal arterial segments diseased, two empirically generated indices from the CASS data, and the published indices of Friesinger, Gensini, and the National Heart and Chest Hospital, London. All had considerable prognostic information. Typically 80% of the prognostic information in one index was also contained in another. Our analysis shows that good prediction from angiographic data results from a combination of left ventricular function and arteriographic extent of disease. Prognosis may reasonably be obtained from three simple indices: the number of vessels diseased, the number of proximal arterial segments diseased, and a left ventricular wall motion score. These three indices account for an estimated 84% of the prognostic information available. 6-yr survival varies between 93 and 16% depending upon the values of these three indices.

A public health approach for leprosy detection based on a very short term-training of primary health care workers in basic dermatology.

INTRODUCTION: In countries where leprosy control is integrated to general heath services, health workers, at primary health care level, often manage a large number of patients with skin diseases including leprosy. The distinction of leprosy from others skin diseases requires more skill and attention. Basic dermatological knowledge will help these staff to provide a better quality of care. A few years ago, a short term training programme focussed on leprosy and some common skin diseases was set up in Mali through a pilot project. This study will evaluate the impact of this training on the detection of leprosy at primary health care level. METHODS: health care workers from two health districts were invited to participate in the training. Trainee was submitted to an anonymous written test before training, immediately after and 12-18 months post-training using a standardized scoring system. The suspected or referred leprosy cases before and after training were compared. Data were recorded and analysed with the software Epi info version 6.04. RESULTS: Overall, 495 HCW attended the three anonymous written tests (before training, just after and 12-18 months later). The proportion of participants who gave correct answers before training, just after were respectively: 33 and 57% for correct diagnosis, 5 and 39% for test of sensation and 28 and 47% for referral. Eight patients suspected of leprosy were referred for further examination; in these, five cases of leprosy were detected. DISCUSSION: The training showed a huge improvement in the skill of the participants in managing leprosy patients. This study addresses how leprosy control can be improved by involving primary health care staff and by the implementation of only a single day's training on basic dermatology. CONCLUSION: The role of the dermatologist in this post-elimination era of leprosy needs to be reconsidered and adapted to the increasing need to take multiple programmes, inclusive of dermatology and leprosy, into primary health care services and those interested in leprosy control should fund these programmes.

Integrated management of filarial lymphedema for rural communities.

The Global Alliance for the Elimination of Lymphatic Filariasis (GAELF) has recommended exploring local health traditions of skin care and a low cost treatment paradigm for rural communities has been proposed by Vaqas and Ryan. Our case study incorporates these promising treatments for use in treating filariasis in rural communities. Patients having lymphedema of one or both lower limbs (skin: normal, thickened or with trophic/warty changes) received treatment components from ayurveda, yoga and biomedicine simultaneously: including soap wash, phanta soaking, Indian manual lymph drainage (IMLD), pre- and post-IMLD yoga exercises, and compression using bandages for 194 days, along with diet restrictions and oral herbal medicines indicated for "elephantiasis" in Ayurveda. Entry points when infected were treated with biomedical drugs. The study was conducted in the reverse pharmacology design. 112 patients and 149 lower limbs completed 194 days of treatment during 2003-2006. Significant improvements were observed in the limb circumference measurements and the frequency of acute dermatolymphangioadenitis, use of preventive antibiotics, and reduction in the number of entry points were also improved. The objective to obtain significant benefit for a common problem using locally available, sustainable and affordable means has been achieved. It has not been our purpose to show that the regimen employed is better than another but the results do pose the question--"Are there components of Ayurvedic medicine that deserve further study?" It is important to understand that the regimen has been delivered mostly at home and that participants we have treated, representing a population suffering from a common problem, have not had access to effective conservative therapy that is culturally acceptable, safe, and efficacious.

Future Research Priorities for Morbidity Control of Lymphedema.

BACKGROUND: Innovation in the treatment of lower extremity lymphedema has received low priority from the governments and pharmaceutical industry. Advancing lymphedema is irreversible and initiates fibrosis in the dermis, reactive changes in the epidermis and subcutis. Most medical treatments offered for lymphedema are either too demanding with a less than satisfactory response or patients have low concordance due to complex schedules. A priority setting partnership (PSP) was established to decide on the future priorities in lymphedema research. METHODS: A table of abstracts following a literature search was published in workshop website. Stake holders were requested to upload their priorities. Their questions were listed, randomized, and sent to lymphologists for ranking. High ranked ten research priorities, obtained through median score, were presented in final prioritization work shop attended by invited stake holders. A free medical camp was organized during workshop to understand patients' priorities. RESULTS: One hundred research priorities were selected from priorities uploaded to website. Ten priorities were short listed through a peer review process involving 12 lymphologists, for final discussion. They were related to simplification of integrative treatment for lymphedema, cellular changes in lymphedema and mechanisms of its reversal, eliminating bacterial entry lesions to reduce cellulitis episodes, exploring evidence for therapies in traditional medicine, improving patient concordance to compression therapy, epidemiology of lymphatic filariasis (LF), and economic benefit of integrative treatments of lymphedema. CONCLUSION: A robust research priority setting process, organized as described in James Lind Alliance guidebook, identified seven priority areas to achieve effective morbidity control of lymphedema including LF. All stake holders including Department of Health Research, Government of India, participated in the PSP.

Regionalization: a strategy that will assist with bovine tuberculosis control and facilitate trade.

It is expected that the revised chapter on bovine tuberculosis in the Terrestrial Animal Health Code of the Office Internationale des Epizooties (OIE) will embrace regionalization as a functional means of assisting countries, states or regions to meet the requirements for freedom from tuberculosis and to facilitate trade. The benefits and applications of regionalization, which comprises zoning and compartmentalisation, are discussed. Regionalization requires that a country's veterinary administration is able to implement transparent and auditable biosecurity measures that will ensure that the tuberculosis-free status of a subpopulation of cattle is maintained despite the presence of infection in another cattle subpopulation, or in other domestic or wild animal species. Zoning, which requires cattle subpopulations to be separated by geographic boundaries, provides a practical basis whereby countries, states or regions, can progress towards freedom from tuberculosis, regardless of the source of infection for defined cattle subpopulations. Compartmentalisation however, requires that husbandry or management practices will be used to prevent a tuberculosis-free cattle subpopulation from contacting interspecific and intraspecific sources of infection. This will be difficult to achieve except for specialised cases such as artificial breeding centers.

Advances in understanding disease epidemiology and implications for control and eradication of tuberculosis in livestock: the experience from New Zealand.

A deteriorating tuberculosis problem in cattle and deer in New Zealand has been halted and then reversed over the last decade. Mycobacterium bovis infection in both wild and domestic animal populations has been controlled. This has been achieved by applying a multi-faceted science-based programme. Key features of this have been a comprehensive understanding of the epidemiology of tuberculosis in animals, confidence in sampling wild animal populations, effective application of diagnostic tests in cattle and deer, and the ability to map M. bovis genotypes.

Photoaffinity labeling of functionally different lysine-binding sites in human plasminogen and plasmin.

Photoaffinity labeling of human plasmin using 4-azidobenzoylglycyl-L-lysine inhibits clot lysis activity, while the activity toward the active-site titrant, p-nitrophenyl-p'-guanidinobenzoate, or alpha-casein are maintained. Photoaffinity labeling of native Glu-plasminogen with the same reagent causes incorporation of approximately 1.5 mol label per mol plasminogen. This labeled plasminogen can be activated to plasmin by either urokinase or streptokinase. The resulting plasmin has full clot lysis activity and can be subsequently photoaffinity labeled with a loss of clot lysis activity. The rate of activation of labeled plasminogen by urokinase is increased relative to that of native plasminogen. epsilon-Aminocaproic acid blocks incorporation of photoaffinity label into both plasminogen and plasmin, indicating that the labeling is specific to the lysine-binding sites. The labels are located in the kringle 1+2+3 fragment in either photoaffinity-labeled plasminogen or plasmin. These results indicate that the specific lysine-binding site blocked in plasmin acts in concert with the active-site in binding and using fibrin as a substrate. This clot lysis regulating site is not available for labeling in plasminogen, but is exposed or changed upon activation to plasmin. The different lysine-binding sites labeled in plasminogen may regulate the conformation of the molecule as evidence by an enhanced rate of activation to plasmin.

The properties of the secreted gamma-glutamyl hydrolases from H35 hepatoma cells.

gamma-Glutamyl hydrolase has been partially purified and characterized from conditioned culture medium of H35 hepatoma cells. Evidence for heterogeneity of the enzyme is derived from its elution as three distinct peaks of enzymatic activity when the enzyme is purified by TSK-butyl-Sepharose column chromatography. These three enzyme fractions appear to have identical catalytic properties but, as yet, the basis for their resolution is not understood. A rapid, sensitive and simple assay based on reverse-phase HPLC fluorescent detection with pre-column derivatization using o-phthalaldehyde (OPA) was developed to separate OPA-derivatives of poly-gamma-glutamates and glutamic acid. Using this assay and the standard HPLC assay for pteroylpolyglutamates, the enzyme appears to be an endopeptidase with respect to pteroylpenta-gamma-glutamate (PteGlu5), methotrexate penta-gamma-glutamate (4-NH2-10-CH3PteGlu5) and p-aminobenzoyl-penta-gamma-glutamate (pABAGlu5). The initial products are PteGlu1 (or 4-NH2-10-CH3PteGlu1 or pABAGlu1) and intact tetra-gamma-glutamate, which is subsequently degraded to glutamic acid. When penta-gamma-glutamate is the substrate, the cleavage of the gamma-bonds by the enzyme is less ordered, with the early appearance of mono-, di-, tri- and tetraglutamate. Poly-alpha-glutamate is not a substrate nor are pABA-gamma-Glu5 or penta-gamma-glutamate covalently linked to albumin. 4-NH2-10-CH3PteGlu2 or Glu5 bound to dihydrofolate reductase is not a substrate for the enzyme, offering further evidence that protein-associated poly-gamma-glutamates are poor substrates for gamma-glutamyl hydrolase from H35 hepatoma cells.

Esterase A is a proteinase from rat urine that can activate plasminogen.

A proteinase which can activate human, dog and rat plasminogen to plasmin has been isolated from the urine of female rats, using affinity chromatography on benzamidine-coupled Sepharose. Inhibition by diisopropylfluorophosphate, tosyl-L-lysine chloromethylketone and benzamidine classified the enzyme as trypsin-like. The proteinase has weak activity on alpha-casein and hemoglobin, but will not lyse fibrin clots. It readily cleaves arginyl amides, including synthetic substrates specific for human glandular kallikrein and other serine proteinases. A chromogenic substrate for human urokinase (pyro Glu-Gly-Arg-pNA) is a poor substrate for the rat proteinase. Characteristics of the enzyme, such as its molecular weight (25 900), kinetic parameters and inhibition by aprotinin, indicate that this proteinase is esterase A, described by several investigators. Esterase A is shown not to be a true urinary plasminogen activator but rather is a unique arginine-specific proteinase. Urokinase-like and kallikrein-like activity are part of a broader proteolytic activity displayed by this enzyme.

Arm exercise-thallium imaging testing for the detection of coronary artery disease.

Patients with lower limb impairment are often unable to undergo a standard bicycle or treadmill test for the evaluation of coronary artery disease. To establish an alternative method of testing, 50 subjects (aged 56 +/- 10 years) performed arm ergometry testing in conjunction with myocardial thallium scintigraphy. All underwent coronary angiography; significant coronary artery disease (greater than or equal to 70% stenosis) in at least one vessel was present in 41 (82%) of the 50 patients. Thallium scintigraphy was found to have an 83% sensitivity and 78% specificity for detecting coronary disease, compared with a sensitivity and specificity of 54% (p less than 0.01) and 67% (p = NS), respectively, for exercise electrocardiography. In the subgroup of 23 patients who had no prior myocardial infarction or left bundle branch block and were not taking digitalis, thallium scintigraphy had a sensitivity of 80% versus 50% for exercise electrocardiography. Scintigraphy yielded a sensitivity of 84, 74 and 90% for one, two and three vessel disease, respectively. Noninvasive arm ergometry exercise-thallium imaging testing appears to be reliable and useful and should be considered in the evaluation of coronary artery disease in patients with lower limb impairment.

Experimental angioplasty: circumferential distribution of laser thermal energy with a laser probe.

A new laser probe that converts argon laser energy to heat in a metallic cap on a fiberoptic fiber was compared with a bare argon laser fiberoptic catheter system for the dissolution of atherosclerotic obstructions under fluoroscopic guidance in 24 atherosclerotic rabbits. Twelve animals were randomly assigned to receive treatment with either a bare fiberoptic system or a laser probe coupled to an argon laser. Both fibers had similar outer (0.9 mm) and core (400 mu) diameters. Pulses of 1 watt for 1 second's duration were delivered from the tip of the fiberoptic system, while pulses of 6 watts for 2 seconds' duration were delivered to the laser probe. The results of angiography indicated that widening of luminal stenosis was seen in only 2 of 12 animals treated with the fiberoptic system compared with 8 of 12 animals treated with the laser probe. Perforation of the vessel wall occurred more frequently with the fiberoptic fiber (9 of 12 animals) as compared with the laser probe (1 of 12 animals). Histologic examination of direct laser radiation with the fiberoptic fiber revealed a small localized laser defect along one side of the vessel wall associated with charring, a gradient of thermal injury and considerable thrombus formation. In contrast, those vessels treated with the laser probe showed histologic evidence of thermal injury distributed evenly around the entire luminal circumference. This was associated with minimal charring, a gradient of thermal injury and thinner, flatter thrombus formation. Carbonization of the metallic tip and adherence of atherosclerotic debris with secondary vessel tearing were potential adverse effects of the laser probe.(ABSTRACT TRUNCATED AT 250 WORDS)

Persistent left superior vena cava and right superior vena cava drainage into the left atrium without arterial hypoxemia.

A 46 year old patient who presented with an acute myocardial infarction was discovered to have a systemic venous communication with the left heart during attempted insertion of a pulmonary flotation catheter. There was no evidence of cyanosis or systemic arterial desaturation. A right superior vena cava that emptied into the right superior pulmonary vein and a persistent left superior vena cava draining into the coronary sinus were confirmed pathologically after death related to a brain abscess. The embryology, physiology and noninvasive diagnostic approach to this unique venous anomaly are discussed.

Percutaneous coronary laser thermal angioplasty.

Percutaneous coronary laser thermal angioplasty was successfully performed before conventional balloon angioplasty in a 55 year old white man with a 90% left anterior descending artery stenotic lesion and angina at rest (Canadian Heart Association class IV). The lesion was reduced to 50% residual stenosis using a 1.7 mm laser-heated metallic capped fiber and two pulses of 8 W of argon laser energy, each delivered for 5 seconds. With subsequent balloon angioplasty, the lesion was further decreased to 10% residual stenosis. The entire procedure was well tolerated without chest pain or burning, vessel perforation or spasm, thrombus formation or embolization of debris. The patient was free of pain at 1 month follow-up. This case demonstrates the feasibility of safely performing percutaneous coronary laser thermal angioplasty. Additional studies are indicated to determine the clinical role and potential benefits of coronary laser thermal angioplasty in relation to the established procedures of bypass surgery and conventional balloon angioplasty.

Physiologic responses to arm ergometry exercise relative to age and gender.

Arm ergometry exercise testing is a valuable alternative method used in the evaluation and management of patients with both cardiac disease and lower limb impairment. The purpose of this study is to provide information concerning the physiologic responses of normal healthy subjects to arm ergometry relative to age and gender, which could serve as a standard for comparison. Eighty healthy subjects (age 22 to 59 years) cycled at 75 to 80 rpm (on a bicycle adapted for arm ergometry) starting at a power output of 10 W, increasing at 10 W/2 min until exhaustion. Sixty subjects were classified on the basis of age into three groups, each with 10 men and 10 women. Men achieved significantly (p less than 0.001) higher power output (95 +/- 25 W) and oxygen consumption (20.7 +/- 3.9 ml/kg per min) than did women (56 +/- 19 W and 15.5 +/- 3.1 ml/kg per min, respectively). The heart rate response to total body oxygen demand during arm ergometry was significantly higher in women than in men (p less than 0.001). These findings were also present when men and women of each age group were analyzed separately. Older subjects reached a significantly (p less than 0.02) lower peak power output than did younger subjects although they reached a similar level of oxygen consumption. Separate regression equations for predicting oxygen consumption at each power output were formulated for men and women and validated in 20 other subjects. Small differences in measured and predicted oxygen consumption at each stage were found. These data provide additional information concerning arm ergometry testing and should prove useful in diagnostic exercise testing and cardiac rehabilitation.