Photochemically induced colonic ischaemic lesions: a new model of ischaemic colitis in rats

Background—Recent clinical studies suggest thatischaemic colitis is caused by a microcirculatory disturbance thatinvolves thrombosis of the colon.
Aim—To establish a new model of photochemicallyinduced ischaemic colitis in rats.
Methods—Thirty male Wistar rats were anaesthetisedwith amobarbital, the femoral veins were cannulated and laparotomieswere performed. The serosal surface of the proximal colon wasirradiated by using a krypton laser (wavelength 568 nm, 20 mW) forfour minutes. An intravenous infusion of a photosensitising dye, rosebengal (20 mg/kg body weight), was administered over 90 seconds,beginning at the start of irradiation. Rats were killed immediately(n=4), 12 hours (n=2), 24 hours (n=10), three days (n=4), seven days (n=4), 14 days (n=2), or 28 days (n=2) after irradiation. Two controlrats received laser irradiation without dye infusion. Specimens of theirradiated sites were examined by using histopathology.
Results—Localised ulcers of the colon were presentin rats killed at 12 hours, 24 hours, three days, and seven days after irradiation. Microscopy findings were consistent with the features ofhuman ischaemic colitis. Reproducible ulcerative lesions were producedby photothrombosis of microvessels in the colon.
Conclusion—This model may be useful for furtherinvestigation of the pathophysiology of ischaemic colitis.

Keywords:ischaemic colitis; photothrombosis; rose bengal

     

Preventable causative factors leading to hospital admission with decompensated heart failure

Objective—To assess the degree of agreement between impedance cardiography, using the NCCOM3-R7 device, and the gold standard—the dye dilution method—both under basal conditions and after stimulation of cardiac output.
Patients—35 paired measurements in five healthy male volunteers.
Interventions—To obtain higher levels of cardiac output, cardiac performance was stimulated with a dopamine infusion.
Results—In 35 paired measurements, the mean of all the impedance values was higher than that of the dye dilution values, at 10.2 v 7.4 l/min (p < 0.0001). The mean discrepancy between the two methods was 3.3 l/min, and the mean bias −2.9 l/min, with limits of agreement of −9.0 and 3.2 l/min. A change in cardiac output could not adequately be predicted by the NCCOM3-R7. In 20 of 25 measurements obtained during continuous intravenous dopamine infusions there was a rise in dye dilution cardiac output (range 0.2 to 5.9 l/min). Neither the magnitude nor the direction of the change in dye dilution values corresponded with the change measured by impedance cardiography. The mean discrepancy here between the two methods was 1.8 l/min, and the mean bias −0.8 l/min, with limits of agreement of −4.9 and 3.3 l/min.
Conclusions—In healthy volunteers, impedance cardiography with NCCOM3-R7 is inadequate for assessing cardiac output when compared with the dye dilution method.

Keywords: cardiac output;  impedance cardiography;  dye dilution     

Psychosocial components of cardiac recovery and rehabilitation attendance

OBJECTIVE—To examine the relations between demographic factors, specific psychosocial factors, and cardiac rehabilitation attendance.
DESIGN—Cohort, repeated measures design.
SETTING—A large tertiary care centre in western Canada
PATIENTS—304 consecutive consenting patients discharged following acute myocardial infarction and/or coronary artery bypass graft surgery.
MAIN OUTCOME MEASURES—The Jenkins self-efficacy expectation scales and activity checklists of behaviour performance for maintaining health and role resumption, modified version of the self-motivation inventory, and the shortened social support scale.
RESULTS—Those who had higher role resumption behaviour performance scores at two weeks after discharge were significantly less likely to attend cardiac rehabilitation programmes. At six months after discharge, those who attended cardiac rehabilitation demonstrated higher health maintenance self-efficacy expectation and behaviour performance scores. Health maintenance self-efficacy expectation and behaviour performance improved over time. Women reported less social support but showed greater improvement in health maintenance self-efficacy expectation. Changes in self-efficacy scores were unrelated to—but changes in health maintenance behaviour performance scores were strongly associated with—cardiac rehabilitation attendance.
CONCLUSIONS—Cardiac patients and practitioners may have misconceptions about the mandate and potential benefits of rehabilitation programmes. Patients who resumed role related activities early and more completely apparently did not see the need to "rehabilitate" while those who attended cardiac rehabilitation programmes enhanced their secondary prevention behaviours.


Keywords: self-efficacy; motivation; social support; cardiac recovery; cardiac rehabilitation     

The role of xanthine oxidase in platelet activating factor induced intestinal injury in the rat

Background—Xanthine oxidase (XO) isan important source of reactive oxygen species in the small intestine.
Aims—To examine the interaction ofplatelet activating factor (PAF), XO, and neutrophils in mediatingintestinal injury in rats.
Methods—Two doses of PAF were usedto induce either reversible hypotension, or irreversible shock withintestinal necrosis. The activities of XO, and its precursor xanthinedehydrogenase (XD), in both the whole intestinal tissue and epithelialcells, were measured. XO was localised by histochemical staining.
Results—PAF dose dependentlyinduced an increase in XO activity, predominantly in the ilealepithelium, without altering the total activity of XD+XO. Most of theXD to XO conversion was via proteolysis. PAF induced XO activation andintestinal injury were prevented by prior neutrophil depletion. PAFinduced XO activation is probably not due to reperfusion, as XOactivation preceded the recovery of mesenteric flow. Allopurinolpretreatment substantially inhibited intestinal neutrophilsequestration induced by high dose (but not low dose) PAF.
Conclusions—PAF rapidly activatesintestinal XO through proteolytic XD-XO conversion, predominantly inthe ileal epithelium. This effect is mediated by neutrophils. XOactivation promotes PAF induced polymorphonuclear leucocytesequestration in the intestine.

Keywords:xanthine dehydrogenase; reactive oxygen species; leucocyte adhesion; neutrophils; shock

     

SEM Evaluation of Tooth Surface after a Composite Filling Removal Using Er:YAG Laser,Drills with and without Curettes,and Optional EDTA or NaOCl Conditioning

(1) Background: This study aimed to evaluate the microporosity of the tooth surface structure adjacent to the cemento-enamel junction (CEJ) after the removal of composite fillings with a drill in comparison with removal by an Er:YAG laser and after cleaning with a periodontal curette, chemical EDTA and NaOCl (sodium hypochlorite) conditioning. (2) Methods: The research material consisted of 30 extracted premolars with cervical composite fillings. The teeth were divided into six groups according to the method of tooth preparation: group G1 (n = 5)—a diamond drill; group G2 (n = 5)—a diamond drill + curette; group G3 (n = 5)—a diamond drill + 24% EDTA (PrefGel, Straumann, Switzerland); group G4 (n = 5)—an Er:YAG laser (LightWalker, Fotona, Ljubljana, Slovenia) set with the following parameters: power: 1.65 W (composite removal, CR), 1.2 (tooth conditioning, TC), energy: 110 mJ (CR), 80 mJ (TC), frequency: 15 Hz, pulse duration: 50 μs, tip diameter: 1 mm, air/fluid cooling: 4, distance 1.5 mm, energy density: 14.01 J/cm² (CR), 10.19 J/cm² (TC); group G5 (n = 5)—an Er:YAG laser + 2% sodium hypochlorite (NaOCl); group G6 (n = 5)—an Er:YAG laser + 5.25% NaOCl. In each tooth, three cavities were made and subjected to analysis. The dentin surface was evaluated using a scanning electron microscope (SEM). (3) Results: Groups G1 and G2 exhibited mechanical damage to the tooth surface structure caused by the rotary motion of a diamond drill. The SEM image showed a smear layer that could only be removed chemically using 24% EDTA gel (group G3). The tooth surfaces prepared with the Er:YAG laser (groups G4–G6) revealed a homogeneous structure without damage along with open dentinal tubules (without smear layer) and visible denaturation of collagen fibers. The sodium hypochlorite (NaOCl) conditioning did not increase the visibility of dentinal tubules. (4) Conclusions: Dentin surfaces have open dentinal tubules after removal of the composite filling using the Er:YAG laser and therefore do not require additional NaOCl conditioning.     

Left ventricular beat to beat performance in atrial fibrillation: dependence on contractility, preload, and afterload

OBJECTIVE—To assess independent determinants of beat to beat variation in left ventricular performance during atrial fibrillation.
DESIGN—Prospective study.
SETTING—University hospital.
PATIENTS—Seven patients with chronic non-valvar atrial fibrillation.
INTERVENTIONS—Invasive and non-invasive haemodynamic variables were assessed using a non-imaging computerised nuclear probe, a balloon tipped flow directed catheter, and a non-invasive fingertip blood pressure measurement system linked to a personal computer.
MAIN OUTCOME MEASURES—Left ventricular ejection fraction, left ventricular volume, ventricular cycle length, pulmonary capillary wedge pressure, and measures of left ventricular afterload (end systolic pressure/stroke volume) and contractility (end systolic pressure/end systolic volume) were calculated on a beat to beat basis during 500 consecutive RR intervals. A statistical model of the beat to beat variation of the ejection fraction containing these variables was constructed by multiple regression analysis.
RESULTS—Positive independent relations with ejection fraction were found for preceding RR interval, contractility, and end diastolic volume, while inverse relations were found for afterload, preceding end systolic volume, and preceding contractility (all variables, p < 0.0001). A relatively strong interaction was found between end diastolic volume and afterload, indicating that ejection fraction was relatively more enhanced by preload in the presence of low afterload.
CONCLUSIONS—The varying left ventricular systolic performance during atrial fibrillation is independently influenced by beat to beat variation in cycle length, preload, afterload, and contractility. Beat to beat variation in preload shows its effect on ventricular performance mainly in the presence of a low afterload.


Keywords: atrial fibrillation; contractility; haemodynamic variables     

Comparison of Fluorescence Microscopy and Different Growth Media Culture Methods for Acanthamoeba Keratitis Diagnosis

Acanthamoeba keratitis (AK), a potentially blinding infection of the cornea, is caused by a free-living protozoan. Culture and microscopic examination of corneal scraping tissue material is the conventional method for identifying Acanthamoeba. In this article, we compared several methods for AK diagnosis of 32 patients: microscopic examination using fluorescent dye, specific culture on growth media—non-nutrient agar (NNA), culture on liquid growth media—peptone yeast glucose (PYG), and TYI-S-33. AK was found in 14 patients. Thirteen of the specimens were found AK positive by fluorescence microscopic examination, 11 specimens were found AK positive on PYG growth media, and 9 specimens were found AK positive on TYI-S-33 growth media. Only five specimens were found AK positive on NNA growth media. Therefore, we recommend using fluorescence microscopy technique and culture method, especially PYG liquid media.     

Chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in progressive versus non-progressive osteoarthritis

OBJECTIVE—To determine if a single time point estimation of chondroitin sulphate (CS) or keratan sulphate (KS) epitopes, hyaluronan (HA), or total glycosaminoglycans (GAG) in knee synovial fluid at time of hospital referral can predict subsequent radiographic progression of knee osteoarthritis.
METHODS—Two groups of hospital referred patients with knee osteoarthritis were compared: (1) a "progressive" group (n = 45), showing further reduction in radiographic joint space of at least one grade (0-3) in at least one compartment; and (2) a "non-progressive" group (n = 25) in whom radiographs showed no change during the mean follow up period of 2.3 years (median 2, range 1 to 5 years). Knee synovial fluid obtained at the first visit was examined by ELISA for: CS epitopes, using monoclonal antibodies 3B3 and 7D4; KS epitope, using monoclonal antibody 5D4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAG were measured by dye binding with 1:9 dimethylmethylene blue.
RESULTS—In patients with bilateral synovial fluid data right and left knee values were closely correlated for all variables. There were no significant differences between CS and KS epitopes, HA, total sulphated GAG, or ratios of individual CS or KS epitopes to total GAG, between progressive and non-progressive groups.
CONCLUSIONS—Single time point estimation of CS, KS, HA, or total GAG in synovial fluid does not distinguish radiographically progressive and non-progressive knee osteoarthritis patients followed for two years.

     

Effect of intravenous amino acids on interdigestive antroduodenal motility and small bowel transit time

Background—Patients on totalparenteral nutrition have an increased risk of developing gallstonesbecause of gall bladder hypomotility. High dose amino acids may preventbiliary stasis by stimulating gall bladder emptying.
Aims—To investigate whetherintravenous amino acids also influence antroduodenal motility.
Methods—Eight healthy volunteersreceived, on three separate occasions, intravenous saline (control),low dose amino acids (LDA), or high dose amino acids (HDA).Antroduodenal motility was recorded by perfusion manometry andduodenocaecal transit time (DCTT) using the lactulose breath hydrogen test.
Results—DCTT was significantlyprolonged during LDA and HDA treatment compared with control. Theinterdigestive motor pattern was maintained and migrating motor complex(MMC) cycle length was significantly reduced during HDA compared withcontrol and LDA due to a significant reduction in phase II duration.Significantly fewer phase IIIs originated in the gastric antrum duringLDA and HDA compared with control. Duodenal phase II motility index was significantly reduced during HDA, but not during LDA, compared with control.
Conclusions—Separate intravenousinfusion of high doses of amino acids in healthy volunteers: (1)modulates interdigestive antroduodenal motility; (2) shortens MMC cyclelength due to a reduced duration of phase II with a lower contractileincidence both in the antrum and duodenum (phase I remains unchangedwhereas the effect on phase III is diverse: in the antrum phase III is suppressed and in the duodenum the frequency is increased); and (3)prolongs interdigestive DCTT.

Keywords:amino acids; antroduodenal motility; small boweltransit time; total parenteral nutrition

     

Pentagastrin gastroprotection against acid is related to H2 receptor activation but not acid secretion

Background—Pentagastrin enhancesgastric mucosal defence mechanisms against acid and protects thegastric mucosa from experimental injury.
Aims—To investigate whether thisgastroprotection is mediated by histamine receptors or occurs as asecondary effect of acid secretion stimulation.
Methods—The effects ofomeprazole (100 µmol/kg), ranitidine (20 mg/kg), and pyrilamine (10 mg/kg) on pentagastrin (80 µg/kg/h) induced gastroprotection againstacidified aspirin injury were examined in a luminal pH controlledmodel. The effects of these compounds on pentagastrin enhancedgastroprotective mechanisms were investigated using intravitalmicroscopy, in which intracellular pH of gastric surface cells(pH_i), mucus gel thickness, gastric mucosal blood flow, andacid output were measured simultaneously.
Results—Pentagastrin protected ratgastric mucosa from acidified aspirin injury. This gastroprotection wasabolished by ranitidine, but not omeprazole or pyrilamine. Pentagastrininduced a hyperaemic response to luminal acid challenge, increasedmucus gel thickness, and elevated pH_i during acidchallenge. Ranitidine reversed these enhanced defence mechanisms,whereas omeprazole and pyrilamine preserved these effects.
Conclusions—These dataindicate that pentagastrin associated gastroprotection and enhanceddefence mechanisms against acid result mainly from activation ofhistamine H₂ receptors, and not as an effect of thestimulation of acid secretion.

Keywords:gastric injury; gastric defence mechanisms; omeprazole; pyrilamine; ranitidine; intracellular pH

     

Ligustrum lucidum Leaf Extract-Assisted Green Synthesis of Silver Nanoparticles and Nano-Adsorbents Having Potential in Ultrasound-Assisted Adsorptive Removal of Methylene Blue Dye from Wastewater and Antimicrobial Activity

Present study was conducted to investigate the adsorption and ultrasound-assisted adsorption potential of silver nanoparticles (AgNPs) and silver nanoparticles loaded on chitosan (AgCS composite) as nano-adsorbents for methylene blue (MB) removal. AgNPs were synthesized using leaf extract of Ligustrum lucidum, which were incorporated on the chitosan’s surface for modification. UV–Vis Spectroscopy, FTIR, XRD, SEM, and EDX techniques were used to confirm the synthesis and characterization of nanomaterials. Batch adsorption and sono-adsorption experiments for the removal of MB were executed under optimal conditions; for fitting the experimental equilibrium data, Langmuir and Freundlich’s isotherm models were adopted. In addition, the antimicrobial potential of the AgNPs and AgCS were examined against selected bacterial and fungal strains. UV–Vis spectroscopy confirmed AgNPs synthesis from the leaf extract of L. lucidum used as a reducer, which was spherical as exposed in the SEM analysis. The FTIR spectrum illustrated phytochemicals in the leaf extract of L. lucidum functioning as stabilizing agents around AgNPs and AgCS. Whereas, corresponding crystalline peaks of nanomaterial, including a signal peak at 3 keV indicating the presence of silver, were confirmed by XRD and EDX. The Langmuir model was chosen as an efficient model for adsorption and sono-adsorption, which exposed that under optimum conditions (pH = 6, dye initial concentration = 5 mg L⁻¹, adsorbents dosage = 0.005 g, time = 120 min, US power 80 W), MB removal efficiency of AgNPs was >70%, using ultrasound-assisted adsorption compared to the non-sonicated adsorption. Furthermore, AgNPs exhibited promising antibacterial potential against Staphylococcus aureus with the maximum zone of inhibition (14.67 ± 0.47 mm). It was concluded that the green synthesis approach for the large-scale production of metallic nanoparticles is quite effective and can be recommended for efficient and cost-effective way to eradicate dyes, particularly from textile wastewater.     

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm² (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity     

Enhanced dispersion of epicardial activation-recovery intervals at sites of histological inhomogeneity during regional cardiac ischaemia and reperfusion

Objective—To examine how epicardial activation and repolarisation patterns change in the course of ischaemia, and how these changes are related to the underlying histological structures.
Methods—Langendorff perfused isolated rabbit hearts were submitted to 30 minutes of left anterior descending coronary artery occlusion followed by 30 minutes of reperfusion. A 256 channel epicardial map was plotted during the various experimental phases. Activation time points were determined as t(dU/dt_min) and repolarisation time points as t(dU/dt_max). From these data the local activation-recovery interval (ARI), its dispersion (SD of ARI), and the geometry of the activation spread could be analysed. After the experiments the hearts were processed histologically and the mapping data were projected onto histological slides.
Results—There was elevation of the ST segment within the occluded area, which recovered during reperfusion. Within this area, ARI was significantly shortened and its dispersion was maximally enhanced. The enhancement of dispersion was pronounced at sites of histological inhomogeneity like fat, connective tissue, or vessels. There was also a change in the preferential direction of activation spread within the occluded zone with a marked transverse propagation of the activation wavefront, whereas under normal conditions the activation followed the longitudinal fibre axis. In addition, the total activation time in the occluded area was significantly prolonged.
Conclusions—Ischaemia alters the local activation pattern with enhanced dispersion, especially at sites of histological irregularity, transverse shift of the activation waves, and a general slowing of conduction, which may explain the increased susceptibility to arrhythmia in hearts with enhanced histological irregularities—for example, an infarct or in multi-infarcted hearts, or after myocarditis.

Keywords: dispersion; epicardial activation-recovery interval; ischaemia     

Synovial fluid chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in arthritic and normal knees

OBJECTIVES—To determine concentrations of chondroitin sulphate (CS) and keratan sulphate (KS) epitopes, glycosaminoglycans (GAGs) and hyaluronan (HA) in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables may be used as markers of the OA process.
METHODS—OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA). Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Knee SF was examined by enzyme linked immunosorbent assay for: CS epitopes, using monoclonal antibodies 3-B-3 and 7-D-4; KS epitope using monoclonal antibody 5-D-4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAGs were measured by dye binding with 1:9 dimethylmethylene blue.
RESULTS—Increased SF 3-B-3 concentrations and 3-B-3/GAG ratio were found in OA, compared with RA or normal knees, with higher 3-B-3 and 3-B-3/GAG in LJOA and NGOA than in CPA. SF 7-D-4 and 7-D-4/GAG were reduced in RA, compared with normal and OA; SF 5-D-4 was reduced in OA compared with normal. GAG and HA concentrations were decreased in both OA and RA. No correlations with radiographic scores were observed, but SF 7-D-4 was lower in `inflamed' compared with `non-inflamed' RA and OA knees. In patients with bilateral samples there were strong correlations between right and left knees for all SF variables.
CONCLUSIONS—Changed concentrations of SF CS and KS can be detected in OA with a profile that differs from that seen in RA. Clinical subgrouping and local joint inflammation may influence these measures, supporting different pathogenesis within OA subgroups and requirement for careful patient characterisation in SF studies.

     

Transcatheter closure of atrial septal defects using the Cardio-Seal implant

OBJECTIVE—To review the outcomes of transcatheter closure of atrial septal defects using the Cardio-Seal implant.
DESIGN—A prospective interventional study.
SETTING—Tertiary referral centre.
PATIENTS—The first 50 patients (median age 9.7 years) who underwent attempted percutaneous occlusion.
INTERVENTIONS—Procedures were done under general anaesthesia and transoesophageal guidance between December 1996 and July 1998.
MAIN OUTCOME MEASURES—Success of deployment, complications, and assessment of right ventricular end diastolic diameter, septal wall motion, and occlusion status by echocardiography.
RESULTS—The median balloon stretched diameter was 14 mm. Multiple atrial septal defects were present in 11 patients (22%) and a deficient atrial rim (< 4 mm) in 19 (38%). In four patients (8%), a second device was implanted after removal of an initially malpositioned first implant. There were no significant immediate complications. All patients except one were discharged within 24 hours. At the latest follow up (mean 9.9 months) a small shunt was present in 23 patients (46%), although right ventricular end diastolic dimensions (mean (SD)) corrected for age decreased from 137 (29)% to 105 (17)% of normal, and septal motion abnormalities normalised in all but one patient. No predictors for a residual shunt were identified. Supporting arm fractures were detected in seven patients (14%) and protrusion of one arm through the defect in 16 (32%), the latter being more common in those with smaller anterosuperior rims. No untoward effects resulted from arm fractures or protrusion. There were no complications during follow up, although five patients (10%) experienced transient headaches.
CONCLUSIONS—The implantation of the Cardio-Seal device corrects the haemodynamic disturbances secondary to the right ventricular volume overload, with good early outcome.


Keywords: congenital heart disease; interventional catheterisation; atrial septal defects     

Interleukin 1 receptor antagonist gene polymorphism and restenosis after coronary angioplasty

BACKGROUND—Percutaneous transluminal coronary angioplasty (PTCA) is limited by the recurrence of luminal stenosis, which occurs in up to 50% of procedures. It has been shown that patient specific factors, perhaps genes, contribute to this process.
OBJECTIVE—To determine whether completion of healing after PTCA is part of an acute self limiting inflammatory process and whether polymorphism at important inflammatory gene loci might determine susceptibility to restenosis after PTCA.
DESIGN—DNA samples were collected from 171 patients attending for elective PTCA in Sheffield (S) and Leicester (L), who were scheduled to undergo follow up angiography (at four months (L) or six months (S)) as part of other restenosis studies. At follow up angiography, the patients were separated into restenosers (> 50% luminal narrowing) and non-restenosers (< 50% luminal narrowing). Four DNA polymorphisms within interleukin 1 (IL-1) related loci (IL-1A (−889), IL-1B (−511), IL-1B (+3954), and IL-1RN intron 2 VNTR (variable number tandem repeat)) were genotyped using methods based on polymerase chain reaction. Significance was assessed by χ² analysis of the relevant contingency table, and the magnitude of effect was estimated by calculating odds ratios. The Mantel-Haenszel (MH) test was applied to summarise data across the two populations.
RESULTS—Allele 2 at IL-1RN (IL-1RN*2) was significantly over represented in the non-restenoser group (L+S, 34% v 23% in restenosers). Furthermore, IL-1RN*2 homozygosity was increased in the non-restenoser population compared with the restenosers (MH test: p = 0.0196 (L+S); p = 0.031 (L+S, single vessel disease only), and the effect seemed to be restricted to the single vessel disease subpopulation. For other polymorphism within IL-1 related loci no significant associations were found with either restenosis or non-restenosis.
CONCLUSIONS—IL-1RN*2 may be associated with protection from restenosis after PTCA for individuals with single vessel disease. As this polymorphism has functional significance, this finding suggests that alteration in an individual's inflammatory predisposition may modulate the blood vessel response to injury.


Keywords: restenosis; inflammation; angioplasty; interleukin-1 receptor antagonist     

Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial

We conducted a phase III study to test the hypothesis that initial therapy with “lower dose” prednisone is effective and safe for patients with newly diagnosed acute graft-versus-host disease. We hypothesized that a 50% decrease in the initial dose of prednisone for treatment of acute graft-versus-host disease would suffice to control graft-versus-host disease without increasing the incidence of secondary treatment. Patients with grade IIa manifestations (upper gastrointestinal symptoms, stool volumes <1.0 L/day, rash involving <50% of the body surface, no hepatic dysfunction; n=102) were randomized to start treatment with prednisone at 1 mg/kg/day or 0.5 mg/kg/day. Those with grade IIb or higher manifestations (rash involving ≥50% of the body surface, stool volumes ≥1.0 L/day or hepatic involvement; n=62) were randomized to start treatment with prednisone at 2 mg/kg/day or 1 mg/kg/day. The primary study end point (a ≥33% relative reduction of the mean cumulative prednisone dose by day 42 after initial treatment with lower dose prednisone) was not reached. With a median follow up of 36 months (range 7–53), initial treatment with lower dose prednisone appeared to be effective for patients presenting with grade IIa manifestations since it did not increase the likelihood of requiring secondary immunosuppressive therapy. Further exploratory analyses suggested that for patients presenting with skin-predominant grade IIb or higher manifestations, initial treatment with lower dose prednisone was associated with an increased risk of requiring secondary immunosuppressive therapy (41% vs. 7%; P=0.001). In summary, initial treatment of newly diagnosed acute graft-versus-host disease with lower dose prednisone is effective. Within the statistical limitations of the study, results showed no suggestion that initial use of lower dose prednisone adversely affected survival.     

Controlled trial of antituberculous chemotherapy in Crohn's disease: a five year follow up study

Background—It has been suggested thatMycobacterium paratuberculosis is the cause of Crohn'sdisease. In a previous report the immediate effect of two yearstreatment with antituberculous chemotherapy showed no clinical benefit.
Aims—To assess both the immediate and longer termeffect of treatment on the disease.
Methods—Patients were followed for five yearsfrom their date of entry to the study. One hundred and thirty patientsentered the initial study, and of these 111 (81%) were followed regularly.
Results—Overall, there was no evidence ofconsistent benefit or disadvantage from antituberculous chemotherapy inany of the assessments made, including the number of acute relapses,surgical episodes, hospital admissions, disease activity, blood tests, or medication required for Crohn's disease during the follow up period.
Conclusion—The absence of any benefit at the endof the initial two year trial period, and during the three yearsubsequent follow up, fails to support the hypothesis that mycobacteriaplay an important part in the pathogenesis of Crohn's disease, or that antituberculous chemotherapy may be of benefit.

Keywords:Crohn's disease; mycobacteria; antituberculuschemotherapy

     

Evidence of increased platelet activation after thrombolysis in patients with acute myocardial infarction

Objective—To assess platelet activation after thrombolysis in patients with acute myocardial infarction.Design—Platelet function was assessed by measurement of the in vivo synthesis of thromboxane by gas chromatography-mass spectrometry of thromboxane''s major urinary metabolite, 2,3-dinor-thromboxane-B₂.Setting—Coronary care unit of Huddinge University Hospital.Subjects—30 patients with acute myocardial infarction given either streptokinase 1·5 million units intravenously over one hour + 500 mg aspirin (n = 10), 500 mg aspirin (n = 10), or neither thrombolysis nor aspirin (n = 10).Results—Patients treated by thrombolysis had a 20-fold increase in thromboxane formation during thrombolysis compared with control patients not treated by thrombolysis (p = 0·0001). Until two days after thrombolysis thromboxane production in patients treated with streptokinase did not decrease to a value comparable with patients treated with aspirin but not given thrombolysis.Conclusions—Thromboxane production increased considerably during thrombolysis, possibly reflecting greatly enhanced platelet activation. The slow decrease in thromboxane formation after treatment with aspirin suggests that the efficacy of thrombolysis might be improved by more efficient antiplatelet treatment.     

Vasodilator myocardial perfusion imaging: demonstration of local electrophysiological changes of ischaemia

Objective—To examine the incidence and severity of myocardial ischaemia provoked in the course of perfusion scintigraphy by coronary vasodilators using endocardial recordings of steady state monophasic action potentials as an independent marker of early localised myocardial ischaemia.

Patients—31 men undergoing routine cardiac catheterisation for investigation of chest pain were studied.

Setting—A tertiary cardiac referral centre.

Design—Single site monophasic action potentials were recorded from the left or right ventricle or both (50 recording sites) during intravenous infusion of dipyridamole (0·015 mg/kg/min) for four minutes. Heart rate was held constant with atrial pacing at 20% above the patient's resting rate. Technetium-99m hexakis-2-methoxy-2-methylpropyl-isonitrile (MIBI) was administered four minutes after dipyridamole, and single photon emission tomographic imaging was performed an hour later. Rest images were obtained the next day (two day, two dose protocol). Recordings were divided into three groups based on the scintigraphic perfusion characteristics and coronary anatomical data for the action potential recording site: group 1—recordings from areas with a normal perfusion pattern (n = 30), group 2—recordings from areas with a perfusion defect and subtended by significantly narrowed coronary arteries without obvious angiographic collateral supply (n = 10), and group 3—recordings from areas with a perfusion defect and subtended by occluded arteries with angiographically evident collaterals from adjacent vessels (n = 10).

Results—There were changes in the duration of the monophasic action potential indicative of ischaemia—that is, shortening of duration of steady state action potential—in 18 of the 20 recordings from areas of abnormal perfusion. Peak changes were apparent eight minutes from the start of the dipyridamole infusion. Mean (SEM) values for duration of the action potential between control and peak effect at eight minutes were 276·5 (5·3) ms ν 276·6 (5·4) for group 1 (NS), 289·6 (4·7) ms ν 278·4 (4·9) ms for group 2 (p < 0·001), and 269·6 (5·7) ms ν 242·0 (4·4) for group 3 (p < 0·0001). These changes were significantly different between the three groups (p < 0·01). ST segment changes on the surface electrocardiogram were seen in only eight patients, all with areas of viable myocardium supplied by collateral vessels.

Conclusions—These data provide strong evidence for the presence of myocardial ischaemia in regions of reversible perfusion defects induced by dipyridamole. This study also shows that such ischaemia is more intense and more likely to be seen when myocardial viability is dependent on collateral circulation.