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Biomedical subjects

T J Ryan

Publications and source records attributed to T J Ryan.

At least 145 records · Page 8Linked to original sources
PubMed1993

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.

Animals↗
PubMed1993

Frequency and significance of right ventricular dysfunction during inferior wall left ventricular myocardial infarction treated with thrombolytic therapy (results from the thrombolysis in myocardial infarction [TIMI] II trial). The TIMI Research Group.

To determine the effect of thrombolytic therapy on the frequency of right ventricular (RV) dysfunction, and whether RV dysfunction is a risk factor for morbidity and mortality after discharge from the hospital, 1,110 patients in the Thrombolysis in Myocardial Infarction (TIMI) II trial with acute inferior wall left ventricular myocardial infarction were studied. RV dysfunction was defined as an RV wall motion abnormality on equilibrium radionuclide ventriculography performed a mean of 9 days after admission to the hospital. Fifty-eight patients (5%) had RV dysfunction. Baseline clinical characteristics among patients with and without RV dysfunction were similar. However, patients with RV dysfunction had a lower mean left ventricular ejection fraction (51.2 +/- 1.2% vs 55.5 +/- 0.3%; p < 0.001) and a greater frequency of in-hospital complications. Angiographic data from patients undergoing protocol catheterization 18 to 48 hours after hospital admission show that the infarct-related artery was more likely to be occluded in those with RV dysfunction (48% [15 of 31] vs 14% [68 of 495]; p < 0.001). There was no difference in the frequency of multivessel disease between the 2 groups. In patients with RV dysfunction in whom radionuclide ventriculography was repeated 6 weeks after hospital discharge, RV wall motion abnormalities persisted in only 18% (8 of 45). Mortality in the year after discharge was 3.5% (2 of 58) among patients with RV dysfunction compared with 1.7% (18 of 1,052; p = NS) among those without RV dysfunction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1993

A comparison of newborn versus old skin fibroblasts, their potential for tissue repair.

An assessment was made of the ability of human skin fibroblasts from newborn and old subjects to produce intracellular urokinase inhibitor and urokinase-plasminogen activator when exposed to phorbol myristate acetate. Urokinase inhibitor produced by human skin fibroblasts may be essential for cell growth regulation. The expression of urokinase inhibitor and/or urokinase-plasminogen activator may possibly be age-related. The principal observation that newborn skin fibroblasts show a low level and poorly sustained production of intracellular inhibitors of urokinase could help to explain the flexibility of the wound healing process in the foetus.

Blood Proteins↗
PubMed1993

Effects of tissue plasminogen activator therapy on the frequency of acute right ventricular myocardial infarction associated with acute left ventricular infarction.

To assess the effects of reperfusion therapy on acute right ventricular myocardial infarction, we studied at necropsy the hearts from 51 patients who died after receiving intravenous recombinant tissue plasminogen activator for acute left ventricular myocardial infarction as part of the Thrombolysis in Myocardial Infarction (TIMI) study. Right ventricular infarction occurred in none of 29 patients with infarction of the anterior wall of the left ventricle and in 8 of 22 patients (36%) with infarction of the posterior (inferior) wall of the left ventricle. Of the 22 patients with posterior wall infarction, the 8 patients with right ventricular infarction were compared to the 14 patients without right ventricular infarction. The patients with right ventricular infarction had a longer mean interval from tissue plasminogen activator infusion to peak creatine phosphokinase level (19 vs. 11 h, P < 0.03), a lower frequency of hemorrhagic necrosis (2 of 8 vs. 10 of 14, P < 0.04) and higher frequency of luminal thrombus in the infarct-related coronary artery (6 of 8 vs. 3 of 14, P = 0.054). Each of these findings is associated with the absence of coronary reperfusion. Thus, successful reperfusion following acute left ventricular myocardial infarction appears to be associated with a decreased frequency of concomitant right ventricular myocardial infarction.

Creatine Kinase↗
PubMed1993

Coronary artery perforation during excimer laser coronary angioplasty. The percutaneous Excimer Laser Coronary Angioplasty Registry.

OBJECTIVES: The aim of this study was to analyze the risk of vessel perforation during excimer laser angioplasty. BACKGROUND: Vessel perforation is a serious complication of angioplasty. METHODS: A total of 764 patients had 858 stenoses treated with excimer laser angioplasty. Laser catheters had a diameter of 1.4, 1.7 or 2 mm. Laser energy was delivered in pulses of 135 ns, at a frequency of 25 s-1 and at a fluence of 30 to 60 mJ/mm2. Follow-up angiography was requested for all patients who did not require emergency bypass surgery. RESULTS: In the 764 consecutive patients treated with excimer laser coronary angioplasty, vessel perforation occurred in 23 patients (3%). Nine patients had a major complication resulting directly from vessel perforation (cardiac tamponade, myocardial infarction or need for bypass surgery) and 14 had no clinical complications after successful sealing of the puncture site. No patient with a perforation died. Multivariate analysis showed that bifurcation lesions (odds ratio [OR] = 3.5; p = 0.049), diabetes mellitus (OR = 3.15; p = 0.029) and female gender (OR = 2.86; p = 0.013) were associated with an increased risk of vessel perforation. Lesions > 10 mm in length (OR = 0.45; p = 0.206), calcified stenoses (OR = 0.26; p = 0.088) and saphenous vein graft lesions (OR = 0.50; p = 0.295) were not at increased risk. Vessel perforation was seen in 10 (8.3%) of 120 lesions in which the laser catheter was equivalent in diameter to the target vessel (< or = 0.5 mm smaller in size) but in only 8 (1.5%) of 525 lesions in which the laser catheter was > 1 mm smaller than the target vessel (p = 0.001). CONCLUSIONS: Most lesions thought to be suitable for excimer laser treatment are not at increased risk of perforation. The complication may be avoided by improved patient and laser catheter size selection.

Adult↗
PubMed1993

Excimer laser-assisted coronary angioplasty for lesions containing thrombus.

OBJECTIVES: The purpose of this study was to analyze the success rates for excimer laser-assisted coronary angioplasty performed in patients undergoing angioplasty for lesions containing thrombus. BACKGROUND: The presence of intracoronary thrombus increases the risk of a poor clinical outcome after balloon angioplasty. The effect of intracoronary thrombus on the safety and efficacy of excimer laser-assisted coronary angioplasty is unknown. METHODS: Percutaneous excimer laser-assisted coronary angioplasty was attempted in 142 patients, of whom 12 had angiographic evidence of intracoronary thrombus in 14 lesions, defined as a filling defect surrounded by contrast medium or an area of contrast staining. RESULTS: Clinical success (< 50% residual stenosis without myocardial infarction, death or bypass surgery at any time during hospitalization) was achieved in 7 (58%) of the 12 patients with intracoronary thrombus, compared with 123 (95%) of the 130 patients without thrombus (p = 0.00001). Angiographic and clinical complications were more common in patients with thrombus: embolization (25% vs. 1%, p < 0.001), myocardial infarction (33% vs. 2%, p < 0.001), abrupt closure (17% vs. 4%, p = 0.049). Angiographic restenosis at 6 months was seen at 7 (70%) of 10 treated sites with intracoronary thrombus and at 59 (51%) of 116 sites without thrombus (p = 0.245). Presence of intracoronary thrombus was identified as the most important predictor of clinical success (p = 0.013) by multivariable logistic regression analysis, which controlled for other co-variables, such as lesion complexity or lesion location in a saphenous vein graft. CONCLUSIONS: This analysis shows that the success of excimer laser-assisted coronary angioplasty is compromised when thrombus is detected angiographically. Further investigation of other strategies is needed to improve the outcome of angioplasty for this challenging problem.

Aged↗
PubMed1993

Incidence and significance of ventricular tachycardia and fibrillation in the absence of hypotension or heart failure in acute myocardial infarction treated with recombinant tissue-type plasminogen activator: results from the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial.

OBJECTIVES: The purpose of this study was to determine the incidence of ventricular tachycardia and fibrillation without hypotension or heart failure after treatment with recombinant tissue-type plasminogen activator (rt-PA), anatomic correlates of their development, the effect of immediate intravenous metoprolol on their occurrence and the outcome of patients with these arrhythmias. BACKGROUND: Malignant arrhythmias after thrombolytic therapy have been reported to occur as a result of coronary reperfusion, which is associated with reduced mortality in patients receiving thrombolytic therapy. METHODS: We analyzed data from 2,546 patients in the Thrombolysis in Myocardial Infarction (TIMI) Phase II trial without congestive heart failure or hypotension during the 1st 24 h after study entry. Forty-nine patients (1.9%) developed sustained ventricular tachycardia or ventricular fibrillation within 24 h of study entry (group 1), and 2,497 patients (98.1%) did not (group 2). RESULTS: Baseline characteristics and admission laboratory values were similar in the two groups. In patients undergoing protocol angiography 18 to 48 h after rt-PA, the infarct-related artery was patient in a greater percent of group 2 patients (87% [1,015 of 1,169]) than group 1 patients (68% [15 of 22], p = 0.01), although angiography was performed less frequently in group 1 than in group 2. More group 1 than group 2 patients died within 21 days (20.4%) (1.6%, p < 0.001). For patients surviving to 21 days, there was no difference in mortality between patients in the two groups in the following year. CONCLUSIONS: Ventricular tachycardia and fibrillation are not markers for reperfusion after thrombolytic therapy. These arrhythmias are associated with occlusion, not patency, of the infarct-related artery. Early mortality is increased in patients who develop ventricular tachycardia and fibrillation, even in the absence of congestive heart failure and hypotension.

Female↗
PubMed1993

Human papillomavirus type 6-induced condylomata: an unusual complication of intertrigo.

A 79-year-old virgo intacta presented with a 20-year-history of intertrigo, and a 3-month history of superimposed warty masses beneath both breasts and in the groin and perianal areas. There was no evidence of immunosuppression. Histology of the warty lesions showed squamous papillomata, with evidence of wart virus infection. Human papillomavirus (HPV) type 6 was identified by in situ DNA hybridization, in the submammary lesions. This is an unusual manifestation of both intertrigo and wart virus infection. HPV-6 is classically found in anogenital warts. We assume that these warts were acquired by a non-venereal route and/or by congenital infection some 78 years ago. We suggest that it is the warm, moist environment, rather than the specific site, which encourages HPV-6 to flourish.

Aged↗
PubMed1993

Overheating in bed as an important factor in many common dermatoses.

BACKGROUND: Extensive questioning of patients with a wide variety of skin disorders led to the impression that nocturnal overheating was probably an important factor in the initiation and the perpetuation of many skin disorders. METHODS: In order to test the hypothesis, 12 "clean-skinned" subjects (6M/6F) aged 18 to 45 years were monitored electronically every 30 seconds during an 8 hour sleep period (2300 to 0700 hours), sleeping under a standard 10 tog duvet. RESULTS: All the subjects were too hot by 3 to 4 degrees C. All showed changes in their EEG patterns with reduced REM sleep, increased awakenings, and all showed changes in their sleep stage patterns. In addition, they all showed evidence of increased sweating in the "heat-sink" area. CONCLUSIONS: The mechanisms where by such changes could be implicated in the precipitation and perpetuation of skin disease are discussed. "Lifestyle" modification as a very effective, noninvasive, therapeutic regime is recommended. Further research along these lines would probably be very valuable and instructive.

Adolescent↗