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Biomedical subjects

J Clague

Publications and source records attributed to J Clague.

17 recordsLinked to original sources

Systemic platelet effects of contrast media: implications for cardiologic research and clinical practice.

BACKGROUND: Angiographic contrast media cause platelet activation and decrease aggregability in vitro. We have previously shown in vitro a significant antiplatelet effect of contrast media at the concentrations obtained locally in the coronary artery during angioplasty. It is not known, however, whether a systemic effect is present. METHOD: Thirty patients undergoing diagnostic coronary angiography were prospectively randomized to receive the nonionic medium iohexol, ionic low-molecular-weight medium ioxaglate, or ionic high-molecular-weight medium diatrizoate. Platelet aggregability was measured before and after the investigation with whole blood electrical impedance aggregometry (WBEA) with collagen agonist and the PFA-100 (Dade, Miami, Fla) platelet function analyzer with combined shear, collagen, and adenosine diphosphate as agonists. RESULTS: With WBEA, with iohexol no difference in impedance change was seen: (medians and ranges) before, 9.8 Omega (4.8-19.2 Omega) versus after, 9.6 Omega (2-19.2 Omega) (P not significant [NS]). With ioxaglate a significant fall was seen: before, 8.6 Omega (6.4-15.2 Omega) versus after, 6.6 Omega (0-12.4 Omega) (P =.004). With diatrizoate a significant and greater fall was seen: before, 10.8 Omega (6.4-17.6 Omega) versus after, 6.6 Omega (0-10.8 Omega) (P =.002). With PFA, no difference in closure time was seen with any medium: iohexol before, 99 seconds (79-142 seconds) versus after, 142 seconds (63-128 seconds) (P NS); ioxaglate before, 120 seconds (75-258 seconds) versus after, 95 seconds (74-258 seconds) (P NS); and diatrizoate before, 114.5 seconds (65-250 seconds) versus after, 100.5 seconds (72-300 seconds) (P NS). CONCLUSIONS: Ionic but not nonionic contrast media have a systemic antiplatelet effect at diagnostic angiographic doses when measured with WBEA. Such an effect has not been shown before. This may explain the observed improved clinical outcome with ionic contrast media but also might confound platelet studies in coronary angioplasty.

Adult↗

Non-elective intra-coronary stenting: are the clinical outcomes comparable to elective stenting at 6 months?

The aim of this study was to compare prospectively the clinical outcome of patients treated with intra-coronary stents as a non-elective/bailout procedure for acute or threatened vessel closure, with those undergoing elective stenting at 6 months. Sixty-four patients (60.2+/-11.7 y) who underwent non-elective stenting for abrupt or threatened vessel closure and/or sub-optimal results were prospectively compared with 68 patients (62+/-10.0 y) who were stented electively. All patients had broadly similar pre-procedural clinical profiles. However, patients in the elective group had a higher incidence of previous PTCA (10.2% vs. 0%, P = 0.01) and bypass surgery (30.9% vs. 6.3%, P = 0.0003) compared with the non-elective group. A total of 158 stents (1.19 per patient) were implanted in 132 patients with a procedural success rate of 99.3%. At 6 months follow-up there was no statistical difference in the primary composite end-point of death, myocardial infarction and the need of repeat revascularisation (10.9% vs. 5.8%, P = 0.35) between the two groups. However, patients in the non-elective group showed a higher incidence of unstable angina compared with the elective group (25% vs. 1.4%, P = 0.0004). The findings of this study suggest that stents (single or multiple) can be effectively implanted in non-elective situations with no increase in the incidence of death, non-fatal myocardial infarction, and the need of repeat revascularisation at 6 months compared with elective stenting.

Aged↗

Stress long-axis function in coronary artery spasm.

In a patient with prior myocardial infarction who had complained of frequent angina repeat arteriograms proved normal coronary arteries. Both ECG exercise testing and thallium scanning excluded ischemia. Resting echocardiogram showed increased distal septal and right ventricular apical myocardial echo intensity. Dobutamine stress echo demonstrated right ventricular and posteroseptal abnormalities consistent with ischemia. Repeat angiogram with ergonovine confirmed distal right coronary spasm.

Aged↗

Cardiogenic shock secondary to mitral stenosis treated by balloon mitral valvuloplasty.

Percutaneous balloon mitral valvuloplasty is a well-established elective treatment for mitral stenosis in selected patients; it has been used to treat cardiogenic shock secondary to aortic stenosis but has not been previously used for cardiogenic shock secondary to mitral stenosis. We describe a case of cardiogenic shock secondary to severe mitral stenosis, treated by balloon mitral valvuloplasty.

Catheterization↗

McArdle's disease: a rare frameshift mutation in exon 1 of the muscle glycogen phosphorylase gene.

We have previously discovered a common nonsense mutation in exon 1 of the myophosphosphorylase gene in patients with McArdle's disease, but this failed to explain all cases. We now report a second mutation (G-->TT) in one patient, also in exon 1. This mutation causes a shift in the reading frame which results in the replacement of Val15 by Phe. A further 10 amino acids of mis-sense protein are synthesised before a stop codon is reached.

Amino Acid Sequence↗

McArdle's disease: a nonsense mutation in exon 1 of the muscle glycogen phosphorylase gene explains some but not all cases.

McArdle's disease is an inherited disease that results from a lack of functional muscle glycogen phosphorylase. We report here the identification of a C to T transition in exon 1 of the muscle phosphorylase gene found in all patients studied. This base pair mutation results in the substitution of a stop codon (TGA) for the codon (CGA) for Arg49 in the mature protein, and generates a novel restriction site for NlaIII. Of sixteen McArdle's patients, ten are homozygous for this mutation; the remainder are heterozygous. Additional unidentified mutations must lead to the McArdle's phenotype in the latter group of patients.

Base Sequence↗

A comparison of the effect of salmeterol and salbutamol in normal subjects.

1. The effects of salmeterol hydroxynaphthoate (50 micrograms, 8.3 x 10(-8) M) and salbutamol (200 micrograms, 3.5 x 10(-7) M) on sGaw were compared in a double-blind, placebo-controlled, randomised study in 10 normal subjects. 2. SGaw increased by 29% (14-43) (mean (CI)), 5 min after salmeterol and by 35% (19-51) at 15 min compared with an increase of 32% (14-51) and 37% (10-63) after salbutamol and 4% (-3-11) and 8% (0-16) after placebo. 3. The mean area under the sGaw-time curve (AUC480) after salmeterol inhalation was 22,500 kPa-1 (10,100-39,500) compared with 14100 kPa-1 (8020-24,500) after salbutamol and 5300 kPa-1 (1500-10,400) after placebo. 4. Salmeterol produced a significantly prolonged bronchodilator effect compared with salbutamol in normals.

Administration, Inhalation↗

Inhaled platelet-activating factor causes pulmonary neutrophil sequestration in normal humans.

Inhaled platelet-activating factor (PAF) causes bronchoconstriction and transient peripheral neutropenia in humans. We studied eight normal subjects to investigate whether inhaled PAF caused pulmonary neutrophil sequestration. All subjects received autologous 99mTc-red cells as a blood pool marker, seven received 111In-neutrophils, and one received 111In-platelets. Six subjects inhaled 48 micrograms of PAF. There was immediate pulmonary sequestration of 111In-neutrophils, maximal (218% baseline) at 6 min (p less than 0.001), returning to normal by 3 h. There was no change in circulating platelet count or pulmonary 111In-platelet transit. Methacholine inhalation caused equivalent bronchoconstriction to PAF, but it had no effect on neutrophil count or pulmonary 111In-neutrophil activity. We have demonstrated pulmonary neutrophil, but not platelet, sequestration after PAF. This supports a role for PAF as an inflammatory mediator in humans. This may be a useful model for exploring pulmonary neutrophil kinetics and preinflammatory processes.

Administration, Inhalation↗

Comparison of three different methods used to achieve local anesthesia for fiberoptic bronchoscopy.

A patient's tolerance of fiberoptic bronchoscopy depends on the effectiveness of local anesthesia. This study compares the three different methods of local anesthesia in common use After sedation, patients (n = 53) received either 4 ml of 2.5 percent cocaine by intratracheal injection (TI) (n = 18), by bronchoscopic injection (BI) (n = 19), or had 4 ml of 4 percent lidocaine delivered by nebulizer 20 min before the procedure (NEB) (n = 16). Patients and bronchoscopists scored the procedure using visual analog (VAS) and severity scales. Objective measurements of cough counts and episodes of stridor were recorded by phonopneumography. Patients' VAS scores showed a clear preference for the transtracheal method compared with either bronchoscopically injected cocaine (p less than 0.001) or nebulized lidocaine (p less than 0.001). Patients also reported that the TI method produced less cough during intubation of the larynx and inspection of the airways (BI and NEB, p less than 0.01). The TI method was also preferred by the bronchoscopists (BI and NEB, p less than 0.001); they reported less cough and easier tracheal intubation. The mean cough count was significantly lower for the TI group, 49 (43) compared with 95 (52) for BI (p less than 0.01), and 81 (43) for the NEB group (p less than 0.05). Patients' and bronchoscopists' VAS showed significant correlation with cough (r = 0.63-69, p less than 0.01). Stridor occurred in only two patients after TI, compared with 15 in the other two groups. Extra local anesthesia was required by 16 patients after BI, by all the NEB group, but by only one patient after TI. Subjective and objective measurement shows that 4 ml of 2.5 percent cocaine injected into the trachea produced excellent local anesthesia for fiberoptic bronchoscopy, there were no extra complications, and it was the method preferred by both patients and bronchoscopists.

Aerosols↗

Allergen-induced changes in the nasal mucous membrane in seasonal allergic rhinitis: effect of nedocromil sodium.

We have obtained biopsy specimens of the nasal mucous membrane before and during the grass-pollen season in 22 patients with seasonal allergic rhinitis to grass pollen to assess the effects on cellular infiltration of natural exposure to allergen. Biopsy sections were examined by light microscopy, and quantitative assessment was made of numbers of mast cells and eosinophils. The patients were divided into 11 who were treated with placebo and 11 patients who were treated with topical nedocromil sodium. In the group as a whole, there was a significant (p less than 0.001) increase in mast cell density in tissue sections from biopsy specimens obtained during the season compared with out of season (median values, 55.0 and 15.5 cells per square millimeter, respectively). There was also a significant (p less than 0.02) increase in the density of eosinophil infiltration during the season compared with out of season (median values, 6.3 and 0 cells per square millimeter, respectively). Treatment with nedocromil sodium significantly (p less than 0.02) inhibited the accumulation of mast cells but not eosinophils. Compared with the placebo-treated group, the group treated with nedocromil demonstrated a significant (p less than 0.025) reduction in the requirements for treatment with concomitant medication (terfenadine tablets and xylometazoline/antazoline eye drops). These results indicate that natural exposure to allergen in patients with seasonal allergic rhinitis is accompanied by infiltration of mast cells and eosinophils into the nasal mucous membrane. The clinical efficacy of nedocromil sodium in this condition may be related to inhibition of infiltration by mast cells.

Adult↗

Thin-fiber cutaneous innervation and its intraepidermal contribution studied by labeling methods and neurotoxin treatment in rats.

Sensory nerves innervating rat distal limb skin were labeled by axonal transport of an enzyme-lectin conjugate injected into lumbar dorsal root ganglia (DRG), with emphasis on tracing the course of the thin axons. Selective neonatal neurotoxin destruction of most unmyelinated sensory or sympathetic axons was achieved by treatment with capsaicin (CAP) and 6-hydroxydopamine (6-OHDA), respectively. The relationship of substance P-immunoreactive (SPI) axons to the patterns of axonal transport-labeled thin axons was compared in normal and neurotoxin-treated animals. SPI is restricted to a limited population of unmyelinated axons, and electron-microscopic observation reveals its total absence in myelinated axons. SPI fibers of sensory origin, as determined by CAP susceptibility, can be traced into the epidermal stratum spinosum, in relation to guard hair follicles, mast cells, and a specific class of small blood vessels. These morphological features are not eliminated by neurotoxin sympathectomy, and some are inferred to contribute to the initial events associated with the neurogenic vasodilation and plasma extravasation associated with the inflammatory response. A re-evaluation of the concept of "free nerve endings" is suggested in the context of the variety of afferent and efferent patterns displayed by sensory peptidergic unmyelinated axons, their putative nociceptive role, and the functional diversity of sensory C fibers.

Animals↗

Femoral haemostasis after transcatheter therapeutic intervention: a prospective randomised study of the angio-seal device vs. the femostop device.

BACKGROUND: A number of haemostatic devices are available to facilitate early haemostasis following transfemoral interventional procedures. METHODS AND RESULTS: We have prospectively compared 150 patients (age: 57+/-12 years, mean+/-S.D.) who were randomly assigned to either external compression using the FemoStop device or direct closure of the arterial puncture using the Angio-Seal device. The Angio-Seal was deployed in the catheter laboratory after the conclusion of the procedure. Patients, randomised to FemoStop, had their sheath removed when the activated clotting time (ACT) was less than 100 s before applying the device. The primary endpoint was the composite of bleeding, haematoma formation, bruise, requirement for blood transfusion, clinical indication for ultrasound examination at 2 h and 24 h following the procedure and crossover to either method at 2 and 24 h after the device deployment. The 95% of the Angio-Seal and 96% of FemoStop patients were discharged on the day following the procedure. An increased number of patients in the Angio-Seal group reached a clinical end-point within the first 2 h (45% vs. 3%, P<0.0001). This difference became insignificant at 24 h (25% vs. 30%, P=0.6). CONCLUSION: Although less comfortable, the overall efficacy of the FemoStop appeared to be higher than that of the Angio-Seal device.

Catheterization, Peripheral↗