Is there a role for fibreoptic bronchoscopy in patients presenting with haemoptysis and negative CT? A systematic review and meta-analysis.

INTRODUCTION: Haemoptysis can be a feature of lung cancer and patients are typically fast-tracked for evaluation with chest radiography, contrast-enhanced CT and fibreoptic bronchoscopy (FOB). OBJECTIVE: We aim to explore whether FOB should be conducted as a component of the routine evaluation of non-massive haemoptysis, especially in the context of suspected lung cancer. METHODS: MEDLINE, EMBASE and Cochrane Library were searched for studies comparing FOB with CT in the evaluation of non-massive haemoptysis while reporting at least one of the listed primary outcomes. Primary outcomes include sensitivity of diagnostic modality with respect to lung cancer. Secondary outcomes include detection of other aetiologies such as infection. Results were synthesised using a random effects meta-analysis. Sensitivity analysis was performed for patient age group and year of study. Risk of bias assessment was carried out with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. RESULTS: A total of 2273 citations were screened and 11 studies were included, comprising a total sample size of 2015 patients with 226 confirmed cases of lung cancer. A total of 1816 and 1734 patients received a CT scan and FOB, respectively. The pooled sensitivities for detection of lung cancer using CT scan and bronchoscopy were 98% (95% CI 93.0% to 99.0%) and 86% (95% CI 63.0% to 95.0%), respectively. The sensitivity of CT was higher than that of FOB for both primary and secondary outcomes. CONCLUSION: This study suggests that bronchoscopy does not offer significant additional diagnostic benefit in the evaluation of patients presenting with non-massive haemoptysis and a negative CT scan.

A Novel Report of Suspected Prostate Adenocarcinoma to Orbital Roof Meningioma Metastasis.

: Tumor-to-meningioma metastasis (TTMM) is an uncommon phenomenon, in which a primary malignant tumor metastasizes to a recipient preexisting meningioma. Herein, the authors report a case of a 74-year-old man with a known history of metastatic prostate adenocarcinoma who with frontal headache and right orbital apex syndrome. Initial CT studies demonstrated a right orbital roof osseous lesion. Subsequent MRI was reported as characteristic of an intraosseous meningioma with intracranial and intraorbital extensions. A biopsy of the right orbital mass was obtained and returned a diagnosis of metastatic prostate cancer. The combination of imaging and pathologic findings suggested that the clinical scenario was overall most in keeping with a skull bone-based prostate adenocarcinoma metastasis infiltrating a preexisting meningioma. This is a rare case of TTMM in an orbit-based meningioma, presenting with an orbital apex syndrome.

Outcomes of conjunctival-Müller's muscle resection surgery with and without epinephrine in local anesthetic.

PURPOSE: To determine the effect of epinephrine as an anesthetic adjunct on outcomes of conjunctival-Müller's muscle resection (CMMR) ptosis surgery. METHODS: A retrospective cohort study of patients having undergone CMMR with plain local anesthetic (LA) and local anesthetic combined with epinephrine (LA+Epi). Two measures of success were investigated: margin to reflex distance 1 (MRD1) success and overall success. MRD1 success was defined as a postoperative MRD1 between 2-4 mm. Overall success was defined as all of i) MRD1 success, ii) a ≤ 1 mm difference between the eyelid height following the preoperative phenylephrine test and post-operative MRD1 (PE-MRD1 Δ), and iii) symmetrical postoperative contour between both upper eyelids. Study inclusion criteria included blepharoptosis from levator aponeurotic dehiscence and satisfactory response to the phenylephrine test. Exclusion criteria included congenital ptosis, ptosis secondary to another cause, previous ipsilateral eyelid surgery, or a medical condition that may have impacted surgery. RESULTS: There were 26 eyelids in the LA+Epi group, and 19 eyelids in the LA group. There was no difference in the two groups in age (P =0.28), pre-operative MRD1 (P =0.37), levator function (P =0.27), intraoperative tissue resection amount (P =0.27), number of weeks postoperatively at final MRD1 measurement (P =0.99), and PE-MRD1 Δ (P =0.08). All patients achieved a symmetrical post-operative eyelid contour. The LA+Epi group had a higher attainment of MRD1 success (P =0.04) and overall success (P =0.045). CONCLUSIONS: Epinephrine as an anesthetic adjunct improves CMMR outcome. This suggests its use can be considered the standard of care.

Terminology and Etymology in Oculoplastic Surgery.

PURPOSE: To provide a collection of important terms in oculoplastic surgery, their etymology, current usage, and clarification of terms with overlapping or often misconstrued definitions. METHODS: Commonly employed terms in oculoplastic surgery were collected, and their etymologies were determined. The authors then examined how these terms are being currently used in the published literature to determine how closely their usage matched the origin of the terms, if any terms had developed multiple meanings, or if multiple terms were being used to describe the same concept. RESULTS: This article assembles in one area much of the important terms in oculoplastic surgery, highlighting how the etymology of the terms both links to their meanings as well as clarifies the appropriate usage of terms that have evolved to develop several different definitions. Special attention is placed on clarifying the correct definitions of closely related but distinct terms. CONCLUSIONS: Most terms in ophthalmology are used in a uniform manner across the literature with definitions closely matching their etymology, but some terms in oculoplastic surgery are being used in a potentially confusing overlapping manner and warrant clarification.

Emerging Role of Vitamin D and its Associated Molecules in Pathways Related to Pathogenesis of Thrombosis.

Vitamin D, besides having an essential role in calcium and bone metabolism, also acts as a mediator of many non-calcemic effects through modulations of several biological responses. Vitamin D exists in its two major forms, vitamin D2, or commonly known as ergocalciferol, and vitamin D3, or commonly known as cholecalciferol. Both of these forms bind to vitamin D-binding protein to get transported to all vital target organs, where it serves as a natural ligand to vitamin D receptors for enabling their biological actions. Clinical reports corroborating vitamin D deficiency with an increase in thrombotic episodes implicate the role of vitamin D and its associated molecule in the regulation of thrombosis-related pathways. Thrombosis is the formation and propagation of a blood clot, known as thrombus. It can occur either in the arterial or the venous system resulting in many severe complications, including myocardial infarction, stroke, ischemia, and venous thromboembolism. Vitamin D, directly or indirectly, controls the expression of several genes responsible for the regulation of cellular proliferation, differentiation, apoptosis, and angiogenesis. All of these are the processes of potential relevance to thrombotic disorders. This review, thus, discussed the effects of vitamin D on pathways involved in thrombosis, such as hemostatic process, inflammatory pathway, and endothelial cell activation, with a focus on the molecular mechanisms associated with them.

Impact of Head Tilt on Optical Coherence Tomography Image Orientation.

PURPOSE: Head tilt can have an impact on the orientation of posterior pole images. We conducted this study to determine the effect of head tilt on image orientation measured by the fovea-Bruch's membrane opening (FoBMO) angle with optical coherence tomography (OCT) imaging. METHODS: The study included 56 healthy subjects with mean (range) age of 33 (18 to 61) years. The dominant eye was first determined. To measure head tilt, a smartphone with a built-in gyroscope was affixed to the subject's head with adjustable straps. OCT imaging was performed in both eyes (in randomized order) at 0, 5, and 10 degrees of head tilt in the direction of the imaged eye (ipsilateral head tilt), and then in the opposite direction (contralateral head tilt). For each image, the device software determined Bruch's membrane opening center and the foveal pit from which the FoBMO angle was derived. RESULTS: Thirty-eight (68%) subjects were right eye dominant and 18 (32%) were left eye dominant. Each 1 degree head tilt resulted in a mean change of 0.76 degree in the FoBMO angle (P<0.01), with no significant difference in effect between the 2 eyes (P=0.72). The magnitude of the effect increased from 5 to 10 degrees, and was similar for both ipsilateral and contralateral head tilt. Ocular dominance did not modulate the effect of head tilt (P=0.42). CONCLUSIONS: Head tilt significantly affects OCT image orientation as measured by the FoBMO angle, presumably because cyclotorsion is not fully compensatory. The magnitude and direction of the effect does not depend on the dominant eye.

Genomic comparisons of Rhizobium species using in silico AFLP-PCR, endonuclease restriction, and AMPylating enzymes

Background: The whole-genome sequences of nine Rhizobium species were evaluated using different in silico molecular techniques such as AFLP-PCR, restriction digest, and AMPylating enzymes. The entire genome sequences were aligned with progressiveMauve and visualized by reconstructing phylogenetic tree using NTSYS pc 2.11X. The "insilico.ehu.es" was used to carry out in silico AFLP-PCR and in silico restriction digest of the selected genomes. Post-translational modification (PTM) and AMPylating enzyme diversity between the proteome of Rhizobium species were determined by novPTMenzy. Results: Slight variations were observed in the phylogeny based on AFLP-PCR and PFGE and the tree based on whole genome. Results clearly demonstrated the presence of PTMs, i.e., AMPylation with the GS-ATasE (GlnE), Hydroxylation, Sulfation with their domain, and Deamidation with their specific domains (AMPylating enzymes) GS-ATasE (GlnE), Fic, and Doc (Phosphorylation); Asparagine_hydroxylase and Collagen_prolyl_lysyl_hydroxylase; Sulfotransferase; and CNF (Cytotoxic Necrotizing Factors), respectively. The results pertaining to PTMs are discussed with regard to functional diversities reported in these species. Conclusions: The phylogenetic tree based on AFLP-PCR was slightly different from restriction endonuclease- and PFGE-based trees. Different PTMs were observed in the Rhizobium species, and the most prevailing type of PTM was AMPylation with the domain GS-ATasE (GlnE). Another type of PTM was also observed, i.e., Hydroxylation and Sulfation, with the domains Asparagine_hydroxylase and Collagen_prolyl_lysyl_hydroxylase and Sulfotransferase, respectively. The deamidation type of PTM was present only in Rhizobium sp. NGR234. How to cite: Qureshi MA, Pervez MT, Babar ME, et al. Genomic comparisons of Rhizobium species using in silico AFLP-PCR, endonuclease restrictions and ampylating enzymes.

Analysis and natural history of pituitary incidentalomas.

OBJECTIVES: Pituitary incidentalomas (PI) are frequently found on brain imaging. Despite their high prevalence, little is known about their long-term natural history and there are limited guidelines on how to monitor them. METHODS: We conducted a retrospective study to compare epidemiological characteristics at presentation and the natural history of PI in population-based vs referral-based registries from two tertiary-care referral centers in Canada. RESULTS: A total of 328 patients with PI were included, of whom 73% had pituitary adenomas (PA) and 27% had non-pituitary sellar masses. The commonest indications for imaging were headache (28%), dizziness (12%) and stroke/transient ischemic attack (TIA) (9%). There was a slight female preponderance (52%) with a median age of 55 years at diagnosis; 71% presented as macroadenomas (>10mm). Of PA, 25% were functioning tumors and at presentation 36% of patients had evidence of secondary hormonal deficiency (SHD). Of the total cohort, 68% were treated medically or conservatively whereas 32% required surgery. Most tumors (87% in non-surgery and 68% in post-surgery group) remained stable during follow-up. Similarly, 84% of patients in the non-surgery and 73% in the surgery group did not develop additional SHD during follow-up. The diagnosis of non-functioning adenoma was a risk factor for tumor enlargement and a change in SHD status was associated with a change in tumor size. CONCLUSIONS: Our data suggest that most PI seen in tertiary-care referral centers present as macroadenomas and may frequently be functional, often requiring medical or surgical intervention.

Sellar Masses: An Epidemiological Study.

BACKGROUND: Sellar masses (SM) are mostly benign growths of pituitary or nonpituitary origin that are increasingly encountered in clinical practice. To date, no comprehensive population-based study has reported the epidemiology of SM from North America. AIM: To determine the epidemiology of SM in the province of Nova Scotia, Canada. METHODS: Data from all pituitary-related referrals within the province were prospectively collected in interlinked computerized registries starting in November 2005. We conducted a retrospective analysis on all patients with SM seen within the province between November 2005 and December 2013. RESULTS: A total of 1107 patients were identified, of which 1005 were alive and residing within the province. The mean age at presentation was 44.6±18 years, with an overall female preponderance (62%) and a population prevalence rate of 0.1%. Of patients with SM, 837 (83%) had pituitary adenomas and 168 (17%) had nonpituitary lesions. The relative prevalence and standardized incidence ratio, respectively, of various SM were: nonfunctioning adenomas (38.4%; 2.34), prolactinomas (34.3%; 2.22), Rathke's cyst (6.5%; 0.5), growth hormone-secreting adenomas (6.5%; 0.3), craniopharyngiomas (4.5%; 0.2), adrenocorticotropic hormone-secreting adenomas (3.8%; 0.2), meningiomas (1.9%), and others (3.9%; 0.21). At presentation, 526 (52.3%) had masses ≥1 cm, 318 (31.6%) at <1 cm, and 11 (1.1%) had functioning pituitary adenomas without discernible tumor, whereas tumor size data were unavailable in 150 (14.9%) patients. The specific pathologies and their most common presenting features were: nonfunctioning adenoma (incidental, headaches, and vision loss), prolactinomas (galactorrhea, menstrual irregularity, and headache), growth hormone-secreting adenomas (enlarging extremities and sweating), adrenocorticotropic hormone-secreting adenoma (easy bruising, muscle wasting, and weight gain) and nonpituitary lesions (incidental, headaches, and vision problems). Secondary hormonal deficiencies were common, ranging from 19.6% to 65.7%; secondary hypogonadism, hypothyroidism, and growth hormone deficiencies constituted the majority of these abnormalities. CONCLUSIONS: This is the largest North American study to date to assess the epidemiology of SM in a large stable population. Given their significant prevalence in the general population, more studies are needed to evaluate the natural history of these masses and to help allocate appropriate resources for their management.

Structures of native, substrate-bound and inhibited forms of Mycobacterium tuberculosis imidazoleglycerol-phosphate dehydratase.

Imidazoleglycerol-phosphate dehydratase (IGPD; HisB), which catalyses the conversion of imidazoleglycerol-phosphate (IGP) to imidazoleacetol-phosphate in the histidine biosynthesis pathway, is absent in mammals. This feature makes it an attractive target for herbicide discovery. Here, the crystal structure of Mycobacterium tuberculosis (Mtb) IGPD is reported together with the first crystal structures of substrate-bound and inhibited (by 3-amino-1,2,4-triazole; ATZ) forms of IGPD from any organism. The overall tertiary structure of Mtb IGPD, a four-helix-bundle sandwiched between two four-stranded mixed ß-sheets, resembles the three-dimensional structures of IPGD from other organisms; however, Mtb IGPD possesses a unique structural feature: the insertion of a one-turn 310-helix followed by a loop ten residues in length. The functional form of IGPD is 24-meric, exhibiting 432 point-group symmetry. The structure of the IGPD-IGP complex revealed that the imidazole ring of the IGP is firmly anchored between the two Mn atoms, that the rest of the substrate interacts through hydrogen bonds mainly with residues Glu21, Arg99, Glu180, Arg121 and Lys184 which protrude from three separate protomers and that the 24-mer assembly contains 24 catalytic centres. Both the structural and the kinetic data demonstrate that the inhibitor 3-amino-1,2,4-triazole inhibits IGPD competitively.

Molecular cloning, overexpression, purification, crystallization and preliminary X-ray diffraction studies of histidinol phosphate aminotransferase (HisC2) from Mycobacterium tuberculosis.

HisC2 from Mycobacterium tuberculosis was overexpressed in M. smegmatis and purified to homogeneity using nickel-nitrilotriacetic acid metal-affinity and gel-filtration chromatography. Diffraction-quality crystals were grown using the hanging-drop vapour-diffusion technique from a condition consisting of 7 mg ml(-1) HisC2 (in 20 mM Tris pH 8.8, 50 mM NaCl and 5% glycerol), 1 M succinic acid pH 7.0, 0.1 M HEPES pH 7.0 and 1%(w/v) polyethylene glycol monomethyl ether 2000. The crystals belonged to the orthorhombic space group P2(1)2(1)2, with unit-cell parameters a = 255.98, b=77.09, c = 117.97 Å. X-ray diffraction data were recorded to 2.45 Å resolution from a single crystal using the in-house X-ray facility.

Association between Pus Cells and Semen Parameters in Infertile Pakistani Males.

OBJECTIVES: This study evaluated the association between pus cells and semen parameters in infertile Pakistani males. METHODS: A cross-sectional descriptive study was carried out in the Department of Reproductive Physiology/Health, National Institute of Health, Islamabad, Pakistan, from 2004 to 2009. A total of 1,521 subjects were analysed, along with 97 proven fathers as controls. RESULTS: The mean of pus cells was 7.43 ± 0.43, 4.35 ± 0.34, and 4.26 ± 0.17 per high field in teratozoospermic, oligoasthenozoospermic, and asthenozoospermic groups, respectively, while it was 3.25 ± 0.26, 3.10 ± 0.19, and 2.98 ± 0.04 per high field in azoospermic, oligozoospermic and the proven father groups, respectively. The fewest pus cells were observed among proven fathers, which varied non-significantly (P >0.05) with all cases, except with teratozoospermic, oligozoospermic, and oligoasthenozoospermic cases. Pus cells showed an inverse relationship to sperm motility and count, except in azoospemia cases. Similarly, the fewest pus cells were observed among groups where normal forms where significantly more frequent (P <0.05). More pus cells were observed in cases where motility, and concentration or morphology was compromised. Similarly, low pus cell counts were seen in cases where sperm had the fewest head and neck defects. All kinds of sperm defects varied non-significantly (P >0.05) between proven fathers and normal concentration cases. CONCLUSION: High pus cell counts were observed in various subclasses of infertile patients. Ignorance of this pyospermic factor will make pyospermic patients to be misdiagnosed as normozoospermic. Therefore, the presence of pyospermia must be considered by physicians as a male infertility factor.

HisB from Mycobacterium tuberculosis: cloning, overexpression in Mycobacterium smegmatis, purification, crystallization and preliminary X-ray crystallographic analysis.

HisB, encoded by open reading frame Rv1601, possesses enzymatic activity as an imidazoleglycerol-phosphate dehydratase in the histidine-biosynthetic pathway of Mycobacterium tuberculosis. A recombinant form of HisB was crystallized in three crystal forms: crystals grown using 20% PEG 1500 as a precipitant belonged to either the cubic space group P432 or the tetragonal space group P4, while an orthorhombic crystal form belonging to space group P2(1)2(1)2 was obtained using 15% PEG 5000 and 10 mM MnCl(2) as precipitant. The structure of HisB in the orthorhombic crystal form was solved by the molecular-replacement method using the crystal structure of its Arabidopsis thaliana counterpart, which shares 47% sequence identity with Rv1601, as the search model.

Status of zinc in pulmonary tuberculosis.

BACKGROUND: To study the status of zinc as a micronutrient in pulmonary tuberculosis, in our population, with the aim to see the effectiveness of therapy. METHODOLOGY: This prospective study includes 50 patients with pulmonary tuberculosis and 30 subjects as the control group. The patients were placed into three stages (1 to 3) on the basis of chest radiographic findings. Serum zinc levels were estimated before, during, and after completion of antituberculosis therapy. RESULTS: Statistically significant fall in serum zinc levels was seen with advanced age and disease, and the levels improved after initiation of antituberculosis therapy. CONCLUSION: Estimation of serum zinc levels is an important tool in diagnosis and monitoring of response to treatment in pulmonary tuberculosis, and even a booster of the immunological mechanisms if instituted during the course of treatment.

Mitigation of coagulation by removing clotting factors part 1: in vitro feasibility study.

Heparin is associated with adverse effects in some patients during extracorporeal circulation. A potential alternate anticoagulation strategy explored in this investigation involved mitigation of coagulation by removing clotting factors from blood by adsorption on a protamine-immobilized Sepharose matrix (PSM). Human or porcine plasmas treated with PSM in vitro were tested for clotting factors I (fibrinogen), II (prothrombin), VIII, and X, and proteins C and S, and for prothrombin time (PT), activated partial thromboplastin time (APTT), and total protein concentration. Bovine blood treated with PSM was also perfused through a hollow-fiber cartridge to assess thrombogenic potential in a shear flow system. PT increased with increasing protamine-Sepharose-to-plasma ratios and with increasing mixing time. When the PT and APTT of treated plasma were prolonged three to six times the baseline, Factors II and X were significantly removed (>90%), Factors I and VIII were partly removed (<35%), and total protein concentration remained >80% of the initial value. When blood depleted of clotting factors was perfused through hollow-fiber cartridges without an anticoagulant, cartridge patency was prolonged compared with cartridges perfused with untreated blood. This investigation demonstrated that inhibition of blood coagulation by removal of key clotting proteins is feasible.

Mitigation of coagulation by removing clotting factors part 2: heparin-free extracorporeal circulation in a porcine model.

A subpopulation of patients would benefit from an anticoagulation strategy during extracorporeal circulation (ECC) that does not involve systemic administration of heparin and protamine. Inhibition of coagulation by adsorption of plasma clotting factors using protamine immobilized on a Sepharose matrix (PSM) has been explored. This investigation extends previous in vitro studies and demonstrates the feasibility of heparin-free ECC. In a porcine ex vivo circuit, plasma was separated from blood via plasmapheresis, passed through a column containing PSM beads, and returned to the animal. Hemodialyzers and stents were placed in the circuit before, during, and after ECC and examined for device thrombosis. After 90 minutes, prothrombin time (PT) was prolonged >10 times the baseline, and blood clotting Factors I, II, VIII, and X were decreased significantly (>90%); this state was maintained for 2.5 hours without detectable adverse consequences. After cessation of ECC, PT approached normal levels within 60 minutes. Examination of hemodialyzers and coronary stents placed in the circuit revealed that the removal of clotting factors significantly reduced device thrombosis and that transfusion of homologous blood ( approximately 10% V/V) resulted in immediate restoration of hemostasis. It is possible to remove clotting factors from circulating blood to allow extracorporeal circulation of blood without the use of heparin.

Mitigation of device-associated thrombosis and thromboembolism using combinations of heparin and tirofiban.

Combined anti-platelet-anticoagulant therapy is increasingly being used to reduce the risk of device-induced thrombosis and thromboembolism. However, direct quantitative confirmation of the effectiveness of this combination approach is lacking. This study was undertaken to quantify the effects of various combinations of heparin (anticoagulant) and tirofiban (antiplatelet agent) on device-induced thrombosis and thromboembolism using a coronary stent as a prototype device. Adult sheep were implanted with ex vivo carotid-carotid shunts containing replaceable tubing segments in which nitinol stents were deployed. Nine combinations of heparin (average activated clot time = 129, 199, and 355 seconds) and tirofiban (0%, 50%, and 100% platelet inhibition) were tested at random with three replicates per animal. Thrombus weight on the stent at the end of each experiment (1 hour) was measured, and emboli released from the stent were continuously monitored during the experiment using a light scattering microemboli detector. With no tirofiban, increasing the heparin concentration was associated with a decreased endpoint thrombus weight (p < .05) but with a slight (non-significant) increase in the number of downstream thromboemboli. However, the presence of tirofiban decreased both thrombus weight and thromboemboli numbers (p < .05), regardless of the heparin concentration. In the presence of medium or high tirofiban, an increase of heparin from low to medium levels also decreased both thrombus weight and thromboemboli numbers (p < .05). Heparin alone does not provide adequate protection against thromboembolism (and may actually increase it by reducing thrombus cohesive strength). However, the combination of heparin and tirofiban is effective in reducing both thrombus and thromboemboli, and an optimal combination may exist.

Elevated fibrinogen fragment levels in uremic plasma inhibit platelet function and expression of glycoprotein IIb-IIIa.

Hemostatic dysfunction is frequently noted in uremia, but the mechanisms responsible for it are poorly understood and are assumed to be multifactorial. Preliminary findings from our laboratory suggest that elevated levels of circulating fibrinogen fragments (FF) might contribute to the hemostatic defect in uremic patients. Defibrinated plasma obtained from chronic hemodialysis (HD) patients as well as normal subjects were examined by SDS-PAGE and immunoblotting and quantified by an immunoassay. In addition, endogenous FF isolated from normal and uremic plasma using affinity chromatography were examined by flow cytometry for their effect on glycoprotein (GP) IIb-IIIa receptor expression and tested for their ability to inhibit platelet aggregation. The mean FF concentration in uremic plasma (1.14 +/- 0.85 mg/ml) was noted to be eight times greater than in normal plasma (0.15 +/- 0.01 mg/ml) (P < 0.05). Moreover, the mean FF level decreased by 48.25% following HD (from 1.14 +/- 0.85 mg/ml to 0.59 +/- 0.33 mg/ml; P < 0.05). SDS-PAGE and immunoblotting experiments showed that the decrease was observed in both medium-sized (20-60 kDa) as well as large (>100 kDa) FF. Further, FF isolated from uremic plasma inhibited platelet aggregation by (46.8 +/- 18.1)% (P < 0.05) and the GP IIb-IIIa receptor expression by (28.0 +/- 7.6)% (P < 0.05 vs. control). The results show that (1) FF levels are elevated in uremic plasma, (2) HD results in significant decrease in FF and (3) endogenous FF inhibit platelet function, presumably via competitive binding to the fibrinogen receptor GP IIb-IIIa. The decrease in plasma levels of FF > 100 kDa following HD suggests that adsorption to the dialysis membrane contributes to their removal.

Different responses by cultured aortic and venous smooth muscle cells to gamma radiation.

BACKGROUND: Stenosis of hemodialysis arteriovenous grafts is usually focal and caused by the proliferation of vascular smooth muscle cells (SMCs). External radiation of the graft is a potential strategy to prevent stenosis; however, the relative responsiveness of arterial and venous SMCs to radiation is unknown. METHODS: Human aortic and saphenous vein SMCs were cultured in a medium containing growth factors and serum and treated with 0 to 50 Gy in a gamma irradiator. At 2 to 20 days post-irradiation, cell counting, methylthiazoletetrazolium dye reduction, [(3)H]-thymidine uptake, and bromodeoxyuridine (BrdU) incorporation assays were performed. RESULTS: All assays showed that 1 to 50 Gy inhibited the proliferation of both aortic and venous SMCs in a dose-dependent manner. Importantly, venous cells were less susceptible to radiation in all assays, compared to aortic cells. At day 10, 1 to 50 Gy of radiation inhibited the increase in the number of aortic cells by 24% to 66% and venous cells by 8% to 25% (P < 0.01) (aortic vs. venous). The differences between aortic and venous cells varied among different assays and were most pronounced in the BrdU assay. CONCLUSION: Inasmuch as myointimal hyperplasia occurs at both arterial and venous anastomoses, future strategies using radiation to prevent hemodialysis vascular access stenosis should take these differences into consideration.