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G Modin

Publications and source records attributed to G Modin.

At least 19 recordsLinked to original sources
PubMed2003

Basic fibroblast growth factor forms new trabeculae that physically connect with pre-existing trabeculae, and this new bone is maintained with an anti-resorptive agent and enhanced with an anabolic agent in an osteopenic rat model.

Osteoporosis is a disease of excess bone fragility that results from both the loss of bone mass and trabecular bone microarchitecture, thereby creating a very fragile skeleton. The purpose of this study was to determine whether treatment of ovariectomized (OVX) osteopenic rats with basic fibroblast growth factor (bFGF) would stimulate the production of new trabeculae, and whether the newly formed trabeculae would make physical connections with the pre-existing trabeculae after prolonged estrogen deficiency. Six-month-old Sprague Dawley rats were OVXed or sham-operated and were left untreated until day 60 post-OVX. A high resolution microscopic scan (XTM) of the right proximal tibia was performed on groups 1 and 2 on day 1 post-OVX, and was repeated in all animals on day 60 post-OVX. At day 60 groups 1 and 2 were treated with vehicle and groups 3 to 6 were injected with bFGF 200 microg/kg/d intravenously for 15 days. At day 82, all animals obtained another in vivo XTM scan of the right tibia; then group 4 were treated with 17B estradiol 10 microg/kg/3x a week, group 5 were treated with hPTH (1-34) at 80 microg/kg/d for 35 days, group 6 were sacrificed, and groups 1 and 2 were treated with vehicle injections for 35 days. At day 110, all remaining animals were sacrificed, and repeat ex vivo XTM scans of the right proximal tibia were performed. Trabecular bone structural variables-including trabecular bone volume, connectivity, number, and thickness-were obtained from all XTM scans. Biochemical markers of bone turnover were also obtained 24 hours before each XTM scan (osteocalcin and deoxypyridinoline), and analyzed by ELISA. Animals OVXed and treated with vehicle had decreased trabecular bone volume, connectivity and number compared to sham-operated animals at both day 60 and day 110. Animals treated with bFGF from day 60-75 post-OVX had evidence of new trabeculae that physically connected with pre-existing trabeculae and also of increased trabecular bone volume seven days after the injections were discontinued. Biochemical markers of bone formation had a small and insignificant increase over baseline levels during the bFGF injections. Bone resorption markers were significantly reduced during the injection period, but returned to baseline levels after the injections were stopped. In addition, we also demonstrated that these newly formed trabecular connections could be maintained or added to with either estrogen or hPTH (1-34) treatments. Thirty-five days after ending the bFGF treatment, trabecular bone volume and connectivity was 25-80% higher in the estrogen and hPTH (1-34) treated animals compared to the untreated animals ( p<0.01). These results support continued development of bFGF as a potential treatment for severely osteoporotic individuals.

Animals↗
PubMed2002

Quantitative computed tomography of the lumbar spine, not dual x-ray absorptiometry, is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy.

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3). CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.

Absorptiometry, Photon↗
PubMed2001

Electrophysiological effects of ibutilide in patients with accessory pathways.

BACKGROUND: Atrial fibrillation (AF) may cause life-threatening ventricular arrhythmias in patients with Wolff-Parkinson-White syndrome. We prospectively evaluated the effects of ibutilide on the conduction system in patients with accessory pathways (AP). METHODS AND RESULTS: In part I, we gave ibutilide to 22 patients (18 men, 31+/-13 years of age) who had AF during electrophysiology study, including 6 pediatric patients </=18 years of age. Ibutilide terminated AF in 21 of 22 patients (95%) during or 8+/-5 minutes after infusion and prolonged the shortest preexcited R-R interval during AF. Successful ablation was performed in all patients. In part II, ibutilide was given to 18 patients (14 men, 28+/-21 years) to assess its effects on the AP and conduction system. Ibutilide prolonged the antegrade atrioventricular node effective refractory period (ERP) (from 252+/-60 to 303+/-70 ms; P<0.02). Ibutilide caused transient loss of the delta wave in 1 patient and abolished inducible tachycardia in 2 patients, although retrograde mapping still allowed for successful AP ablation. The antegrade AP ERP prolonged from 275+/-40 to 320+/-60 ms (P<0.01), as did the antegrade AP block cycle length; the retrograde AP ERP and block cycle length similarly prolonged with ibutilide. The relative and effective refractory period of the His-Purkinje system increased in 61% of patients after ibutilide. There were no adverse side effects. CONCLUSIONS: We report the use of ibutilide in terminating AP-mediated AF, including the first report in the pediatric population. Ibutilide prolonged refractoriness of the atrioventricular node, His-Purkinje system, and AP.

Adolescent↗
PubMed2001

Chemical cardioversion of atrial fibrillation or flutter with ibutilide in patients receiving amiodarone therapy.

BACKGROUND: Ibutilide is a class III drug that is used for the cardioversion of atrial arrhythmias, but it can cause torsade de pointes. Amiodarone also prolongs the QT interval but rarely causes torsade de pointes. There are no studies in which the concomitant use of the 2 agents was examined. The purpose of the present study was to assess the efficacy and safety of cardioversion with combination therapy in patients with atrial fibrillation or flutter. METHODS AND RESULTS: The study included 70 patients who were treated with long-term oral amiodarone and were referred for elective cardioversion of atrial fibrillation (57 of 70, 81%) or flutter (13 of 70, 19%). Patients were taking amiodarone (153+/-259 days, mean+/-SD) and were administered 2 mg intravenous ibutilide. Left ventricular ejection fraction was measured with echocardiography. The QT intervals were measured on 12-lead ECG. Fifty-five patients (79%) had structural heart disease. Patients were in arrhythmia for 196+/-508 days before cardioversion, with a left ventricular ejection fraction of 50+/-11%. In patients with atrial fibrillation, 22 (39%) of 57 and 7 (54%) of 13 patients with flutter converted within 30 minutes of infusion. Thirty-nine patients who did not convert after ibutilide were treated with electrical cardioversion, and 35 (90%) of 39 patients were successfully converted. The QT intervals were further prolonged after ibutilide for the group from 371+/-61 to 479+/-92 ms (P:<0.001). There was 1 episode of nonsustained torsade de pointes (1 of 70, 1.4%) after ibutilide. CONCLUSIONS: The use of ibutilide converted 54% of patients with atrial flutter and 39% of patients with atrial fibrillation who were treated with long-term amiodarone. Despite QT-interval prolongation after ibutilide, only 1 episode of torsade de pointes occurred. Our observations suggest that combination therapy may be a useful cardioversion method for chronic atrial fibrillation or flutter.

Aged↗
PubMed1999

Electrophysiologic effects of adenosine in patients with supraventricular tachycardia.

BACKGROUND: We correlated the electrophysiologic (EP) effects of adenosine with tachycardia mechanisms in patients with supraventricular tachycardias (SVT). METHODS AND RESULTS: Adenosine was administered to 229 patients with SVTs during EP study: atrioventricular (AV) reentry (AVRT; n=59), typical atrioventricular node reentry (AVNRT; n=82), atypical AVNRT (n=13), permanent junctional reciprocating tachycardia (PJRT; n=12), atrial tachycardia (AT; n=53), and inappropriate sinus tachycardia (IST; n=10). There was no difference in incidence of tachycardia termination at the AV node in AVRT (85%) versus AVNRT (86%) after adenosine, but patients with AVRT showed increases in the ventriculoatrial (VA) intervals (13%) compared with typical AVNRT (0%), P<0.005. Changes in atrial, AV, or VA intervals after adenosine did not predict the mode of termination of long R-P tachycardias. For patients with AT, there was no correlation with location of the atrial focus and adenosine response. AV block after adenosine was only observed in AT patients (27%) or IST (30%). Patients with IST showed atrial cycle length increases after adenosine (P<0.05) with little change in activation sequence. The incidence of atrial fibrillation after adenosine was higher for those with AVRT (15%) compared with typical AVNRT (0%) P<0.001, or atypical AVNRT (0%) but similar to those with AT (11%) and PJRT (17%). CONCLUSIONS: The EP response to adenosine proved of limited value to identify the location of AT or SVT mechanisms. Features favoring AT were the presence of AV block or marked shortening of atrial cycle length before tachycardia suppression. Atrial fibrillation was more common after adenosine in patients with AVRT, PJRT, or AT. Patients with IST showed increases in cycle length with little change in atrial activation sequence after adenosine.

Adenosine↗
PubMed1999

Improved trauma care after reorganisation: a retrospective analysis.

OBJECTIVE: To shorten the time to make a diagnosis and to begin definitive treatment of severely injured patients, thereby improving their medical care. DESIGN: Retrospective analysis. SETTING: Teaching hospital, Sweden. SUBJECTS: 61 patients who had sustained high-energy injuries, including head injury which required surgical intervention, and fracture of the femoral shaft before (1987-1988 n = 23) and after (1991-1993 n = 38) the reorganisation. INTERVENTION: Trauma care was reorganised during the year 1989-1990 and the concept of early multidisiplinary treatment with the general surgeon as trauma-leader was adopted. MAIN OUTCOME MEASURES: The time required to make a diagnosis and begin definitive treatment as well as the assessment of medical care taking account of the patient's general condition and other injuries. RESULT: The immediate medical care was classified as delayed or inappropriate in 9 of 23 patients before, and in 2 of 38 patients after, the reorganisation (p = 0.001). The time needed to make a diagnosis was less than 4 hours in all cases. The time needed to start definitive treatment of head injuries was less than four hours in 9 of 12 patients before, and in 18 of 21 patients after the reorganisation. The internal fixation of femoral fractures was started within four hours in 2 of 11 femoral fractures before, compared with 12 of 17, after the reorganisation. CONCLUSION: The time to beginning definitive treatment of severe injuries was shorter after the reorganisation, as a result of early participation of members of the trauma team.

Accidental Falls↗
PubMed1999

Early estrogen replacement therapy reverses the rapid loss of trabecular bone volume and prevents further deterioration of connectivity in the rat.

To evaluate the ability of estrogen replacement therapy (ERT) to prevent changes in trabecular bone volume (BV/TV) and connectivity beginning either at ovariectomy (OVX) or 5-13 days after OVX in adult female rats, the right proximal tibial was examined by three-dimensional X-ray tomographic microscopy (XTM) in vivo. Animals had XTM scans of the right tibia and then were randomized into six groups (n = 9). Groups 2-6 had bilateral (OVX), while group 1 was sham-ovariectomized (OVXd) on day 0. Animals were treated with vehicle (groups 1 and 2) or 17beta-estradiol therapy (ERT) at 10 microg/kg three times per week starting at days 0, 5, 8, and 13 post-OVX (groups 3, 4, 5, and 6), until day 50 when they were rescanned by XTM and sacrificed. Trabecular bone structural variables were calculated from XTM data (BV/TVx and beta1/BV/TVx) and standard histomorphometry. Trabecular bone volume (BV/TVx) and the trabecular connections per cubic millimeter of trabecular bone (beta1/BV/TVx) were maintained in both sham-OVXd animals and OVX animals given ERT from the time of OVX. However, OVX + vehicle-treated animals lost 54% BV/TVx and 46% beta1/BV/TVx (p < 0. 01 from day 0). BV/TVx and beta1/BV/TVx decreased rapidly post-OVX to -22% and -25% at day 13 (p < 0.01 from day 0). ERT initiated at day 5, 8, and 13 post-OVX restored BV/TVx to baseline values at day 50 by modestly increasing trabecular plate thickness; however, beta1/BV/TVx was reduced in all OVX groups when compared with their baseline values. ERT also caused a significant reduction in bone turnover compared with OVX + vehicle; however, resorption was suppressed more than formation. These results demonstrate that ERT can restore the lost trabecular bone, but not trabecular connectivity, that occurs soon after OVX by allowing bone formation to continue in previously activated bone remodeling units while suppressing the production of new remodeling units. This may be the mechanism by which prompt intervention with estrogen and other antiresorptive agents can restore bone mass that has been lost from the increase in remodeling space, and thereby reduce the risk of osteoporotic fractures in postmenopausal women.

Animals↗
PubMed1999

Ethnic differences in N-glucuronidation of nicotine and cotinine.

We previously reported that the metabolism of cotinine, the proximate metabolite of nicotine, is significantly slower in black than in white cigarette smokers. To understand why the metabolism of nicotine and cotinine might differ between blacks and whites, we studied the pattern of nicotine metabolism in blacks and whites. One hundred eight healthy smokers (51 blacks and 57 whites), of similar age, gender distribution, and smoking history, received an i.v. infusion of deuterium-labeled nicotine and cotinine. The clearance of cotinine, the fractional conversion of nicotine to cotinine, and the metabolic clearance of nicotine to cotinine were significantly lower in blacks than in whites. Blacks excreted significantly less nicotine as nicotine-N-glucuronide and less cotinine as cotinine-N-glucuronide than whites, but there was no difference in the excretion of 3'-hydroxycotinine-O-glucuronide. Nicotine and cotinine glucuronidation appeared to be polymorphic, with evidence of slow and fast N-glucuronide formers among blacks but was unimodal with fast conjugators only among whites. Other findings of note included the demonstration of a significant correlation between the distribution volumes of nicotine and cotinine with lean body mass: there was a smaller distribution volume and a shorter half-life for cotinine in women than in men and a smaller volume of distribution of cotinine in blacks than in whites. We conclude that the metabolism of cotinine is slower in blacks than in whites because of both slower oxidative metabolism of nicotine to cotinine (presumably via cytochrome P-450 2A6) and slower N-glucuronidation. Ethnic differences in the metabolism of other drugs undergoing N-glucuronidation should be studied.

Adult↗
PubMed1998

A randomized comparison of the safety and efficacy of once-daily gentamicin or thrice-daily gentamicin in combination with ticarcillin-clavulanate.

PURPOSE: The primary purpose of the clinical trial was to assess the safety and efficacy of once-a-day compared with three-times-a-day gentamicin in patients with serious infections who had protocol-determined peak serum aminoglycoside concentrations. PATIENTS AND METHODS: A total of 249 hospitalized patients with suspected or proven serious infections were randomized in a 2:2:1 ratio to gentamicin given three times a day with ticarcillin-clavulanate (TC), gentamicin once a day with TC, or ticarcillin-clavulanate (TC) alone. The gentamicin once-a-day dosage for patients with estimated creatinine clearance values of > or =80 mL/min was 5.1 mg/kg. With lower creatinine clearance estimates, the mg/kg dosage of gentamicin was decreased, and the dosage intervals (once daily or three times a day) were maintained. Evaluability required documentation of achievement of protocol-defined peak serum gentamicin levels. RESULTS: Of the total 175 evaluable patients, there were no significant differences found between treatment regimens with respect to clinical or microbiologic efficacy. Bedside audiometry proved impractical due to the frequency of altered mental state in ill patients. Based on the traditional increase in serum creatinine values from baseline values, no differences in renal toxicity between the treatment groups was identified. When changes in renal function were reanalyzed based on maintaining, as opposed to worsening, of renal function, preservation of renal function was better in the gentamicin once-a-day patients as opposed to the gentamicin three-times-a-day patients, P <0.01. CONCLUSIONS: Gentamicin once a day plus TC, gentamicin three times a day plus TC, and TC alone had similar effects in seriously ill hospitalized patients. The incidence of nephrotoxicity was similar in the three treatment groups. Using a nonvalidated post-hoc analysis, renal function was better preserved in gentamicin once-a-day + TC and TC-only patients as opposed to gentamicin three-times-a-day + TC.

Adult↗
PubMed1998

Acute changes in trabecular bone connectivity and osteoclast activity in the ovariectomized rat in vivo.

Estrogen deficiency results in a loss of trabecular bone mass and structure that leads to an increased incidence of osteoporotic fractures. The purpose of this study was to determine the time course for trabecular structure deterioration and changes in bone turnover just after ovariectomy in the rat. Six-month-old female virgin Sprague-Dawley rats had their right proximal tibia scanned by X-ray tomographic microscopy (XTM) at baseline (day 0). Animals were then randomized into two groups, and in each group 9 were sham-operated and 11 were ovariectomized and had repeat XTM scans on days 5, 13, 29, and 42 postovariectomy in group 1 and on days 8, 13, 33, and 50 postovariectomy in group 2. Urine was collected for deoxypyridinoline (DPD) cross-link measurements 24 h before each XTM scan and analyzed by ELISA. Trabecular bone structural variables and bone turnover endpoints were calculated from XTM data and standard histomorphometry. Trabecular connectivity decreased 27% by days 5 and 8 postovariectomy (p < 0.01) and continued to decrease up to day 50 postovariectomy (p < 0.01). The trabecular bone volume decreased 25% by 8 days postovariectomy (p < 0.01), and it continued to decrease through day 50. DPD cross-link excretion had increased 37% on day 13 (p < 0.01) and by over 100% of baseline by day 50 postovariectomy. Trabecular bone connectivity and volume deteriorate rapidly while DPD cross-link excretion increased more slowly in acute estrogen deficiency. These data suggest that if an agent is to preserve fully trabecular bone structure, it must be instituted very early in the estrogen-deficient state. They also suggest that a lag time exists before DPD excretion properly mirrors newly induced conditions of high bone turnover in this rat model.

Amino Acids↗
PubMed1997

Inorganic phosphate and coronary perfusion pressure mediate contractile dysfunction during mild ischemia.

During mild graded ischemia in perfused rat hearts, we (V.M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992) previously found a relationship between decreased left ventricular developed pressure (LVDP) and increased Pi, in which intracellular pH, cytosolic Ca2+ concentration ([Ca2+]i), ATP, and free-energy change of ATP hydrolysis were not altered enough to affect contractility. However, the contribution of decreased coronary perfusion pressure (CPP) to decreased LVDP could not be determined. Thus, in the present study, graded hypoxia in perfused rat hearts (95-37.5% O2) was used to increase Pi to similar levels produced during mild ischemia without altering CPP and minimizing changes of other potential mediators of contractile dysfunction. 31P-magnetic resonance spectroscopy and indo 1 fluorescence were used to assess energy metabolites and [Ca2+]i, respectively. The relationship between LVDP and Pi during graded hypoxia was fit to a monoexponential (LVDP = 105 x e-0.04Pi). These data were compared with the relationship of LVDP and Pi during mild ischemia (LVDP = 106 x e-0.08Pi) (V. M. Figueredo, R. Brandes, M. W. Weiner, B. M. Massie, and S. A. Camacho. J. Clin. Invest 90: 1794-1802, 1992). The exponential constant, which describes the effect of Pi on LVDP, was 50% lower during graded hypoxia relative to mild ischemia. This suggests that another mediator, which accounted for approximately 50% of the decrease of LVDP during mild ischemia, was not present during hypoxia. Because CPP decreased during ischemia but not hypoxia, these data suggest that CPP and Pi contribute similarly in mediating contractile dysfunction during mild ischemia.

Animals↗
PubMed1996

Bone mineral density and turnover following forelimb immobilization and recovery in young adult dogs.

The purpose of this experiment was to study changes in bone mass, structure, and turnover in the canine forelimb after unilateral immobilization and recovery. The right forelimbs of 14 adult mongrel dogs were immobilized for 16 weeks. Six dogs served as controls. Seven immobilized and three control dogs were euthanized at the end of the immobilization period. Recovery consisted of 16 weeks of kennel confinement followed by 16 weeks of treadmill exercise. Seven once-immobilized and three control dogs were euthanized at the end of the recovery period. Bone mineral density of both the proximal (PBMD) and central (CBMD) radius was determined by dual X-ray absorptiometry. Standard histomorphometric endpoints for bone mass and turnover were determined in the cancellous bone of the proximal radius. After immobilization, PBMD, CBMD, and trabecular thickness were lower in the immobilized limb than in either the contralateral or control limbs (P < 0.05). Only CBMD remained significantly lower (P < 0.05) after recovery. At the end of immobilization, bone formation endpoints were significantly higher in the immobilized limb than both the contralateral and control limbs. Bone turnover was also significantly lower in the contralateral limb than in the immobilized and control limbs. After recovery, all differences in bone turnover had resolved. Immobilization of 16 weeks duration caused an elevation in cancellous bone formation rate and reduced bone density in both cortical and cancellous bone. After 32 weeks of recovery, turnover abnormalities disappeared, cancellous bone normalized, but cortical bone mass remained low. Recovery of cortical bone from immobilization takes longer than recovery of cancellous bone.

Animals↗
PubMed1995

Outcome for hospitalized patients with fever and neutropenia who are infected with the human immunodeficiency virus.

We conducted a retrospective cohort study to evaluate the occurrence of bacteremia and associated mortality among hospitalized patients who were seropositive for the human immunodeficiency virus (HIV) and who developed fever and neutropenia following antineoplastic chemotherapy or for other reasons. Review of medical records revealed 224 episodes in 142 patients. Of these episodes, 57% occurred following antineoplastic chemotherapy, and 43% occurred under other circumstances. Members of the chemotherapy group had significantly less-advanced HIV disease, a lower mean absolute-neutrophil-count nadir, and a shorter duration of hospitalization. There was no difference between the two groups in the frequency of bacteremia or mortality due to all causes when they were compared by multivariate analysis. Statistically significant univariate and multivariate predictors of bacteremia included sepsis syndrome and concurrent infection. Predictors of mortality included sepsis syndrome, concurrent infection, bacteremia, and antimicrobial therapy. This study suggests that the cause of neutropenia in HIV-seropositive patients is not a predictor of the outcome of fever and neutropenic episodes. Instead, clinical presentation and concomitant illnesses have a greater impact on outcome for a patient.

AIDS-Related Opportunistic Infections↗
PubMed1991

Amiloride improves hemodynamics in patients with chronic congestive heart failure treated with chronic digoxin and diuretics.

Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin. We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure. Eleven men with a history of congestive heart failure were studied in a double blind, cross-over, placebo controlled trial with the patients on digoxin alternating placebo with amiloride. After 7 days on the trial drug, a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise. Right-sided and pulmonary artery wedge pressures and systemic arterial pressures, as well as cardiac outputs, were measured. After a 7 day washout period, placebo (P) and Amiloride (A) were switched and after 7 days on the therapy, a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated. At rest there were no significant differences in the right-sided, pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride (A) versus placebo (P). During exercise there were significant differences between (P) and (A) at the 50 watt-second stage of exercise.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1991

[Reocclusion following thrombolytic treatment in acute myocardial infarct].

Currently there are five thrombolytic substances undergoing evaluation: streptokinase, tissue plasminogen activator, acylated plasminogen streptokinase activator complex, urokinase and single chain urokinase plasminogen activator. Equal results for mortality reduction (25 per cent) and reocclusion (6-24 per cent) has been reported in the literature for the five substances. Reocclusion can be divided into an early (greater than 24 hours) and a late phase. The early phase is most likely due to an imbalance between thrombolysis and the formation of a thrombus. During late reocclusion there is formation of a thrombus on the underlying coronary plaque or residual thrombotic mass, following thrombolytic therapy. The residual stenosis following thrombolysis seems to be the most important prognostic factor for reocclusion. A residual stenosis of over 75 per cent is unfavourable. Early reocclusion is prevented through simultaneous antithrombotic and thrombolytic therapy. Patients with a residual stenosis of over 75 per cent should be considered for some sort of active intervention to prevent late reocclusion.

Acute Disease↗
PubMed1990

Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients.

Colon cancers typically produce mucin. However, it is not known whether tumor mucin plays a biological role in cancer cell behavior. To address this issue, the expression of a mucin-associated antigen, sialosyl-Tn, was examined by immunohistochemical study in 128 primary colorectal carcinoma specimens from 137 patients who underwent curative surgical resection. Antigen expression was correlated with disease-free and overall 5-year survival. Sialosyl-Tn antigen expression occurred in 112 (87.5%) tumors, and was independent of age, gender, tumor location, Dukes' stage, depth of invasion, degree of differentiation, and ploidy status. Survival at 5 years for patients with sialosyl-Tn-negative versus sialosyl-Tn-positive tumors was 100% versus 73% (P less than 0.05) and disease-free survival was 94% versus 73%, respectively (P = 0.12). Although more advanced Dukes' stage, deeper invasion, and aneuploidy were all associated with poorer overall 5-year survival, antigen-negative tumors within each of these groups had much better prognoses than antigen-positive tumors. Multivariate regression analysis revealed that tumor ploidy (P less than 0.001) and sialosyl-Tn expression (P less than 0.05) were the two variables of most importance for predicting both disease-free and overall survival. The authors conclude that sialosyl-Tn expression is an independent predictor of poor prognosis in colon cancer, and therefore suggest that qualitative mucin alterations may reflect important differences in the biological behavior of these neoplasms.

Aged↗
PubMed1990

Oral therapy for Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A controlled trial of trimethoprim-sulfamethoxazole versus trimethoprim-dapsone.

BACKGROUND: Antimicrobial drugs that can be taken orally are needed for the treatment of Pneumocystis carinii pneumonia in patients with the acquired immunodeficiency syndrome (AIDS). Preliminary data indicate that dapsone with trimethoprim may be an effective alternative to trimethoprim-sulfamethoxazole, which is frequently toxic. METHODS: In a double-blind trial, 60 patients with AIDS and mild-to-moderately-severe first episodes of P. carinii pneumonia (partial pressure of oxygen in arterial blood, greater than 60 mm Hg while breathing room air) were randomly assigned to 21 days of treatment with either trimethoprim-sulfamethoxazole (20 and 100 mg per kilogram of body weight per day, respectively) or trimethoprim-dapsone (20 mg per kilogram per day and 100 mg per day). RESULTS: The orally administered treatment failed because of progressive pneumonitis in 3 of the 30 patients assigned to trimethoprim-sulfamethoxazole and in 2 of the 30 assigned to trimethoprim-dapsone (P greater than 0.3). Major toxic effects required a switch to intravenous pentamidine for 17 patients (57 percent) in the trimethoprim-sulfamethoxazole group, as compared with 9 (30 percent) in the trimethoprim-dapsone group (P less than 0.025). With trimethoprim-sulfamethoxazole, there were more instances of severe chemical hepatitis (six, as compared with one in the trimethoprim-dapsone group) and marked neutropenia (five vs. one). Intolerable rash (three in each treatment group) and severe nausea and vomiting (two in each group) occurred with equal frequency with both drug combinations. Methemoglobinemia occurred in most of the patients treated with trimethoprim-dapsone, but it was asymptomatic and the level exceeded 20 percent in only one patient. Mild hyperkalemia (serum potassium level, 5.1 to 6.1 mmol per liter) also occurred in 53 percent of the patients treated with trimethoprim-dapsone. CONCLUSIONS: In patients with AIDS, oral therapy with trimethoprim-sulfamethoxazole and with trimethoprim-dapsone are equally effective for mild-to-moderate first episodes of P. carinii pneumonia, but with trimethoprim-dapsone there are fewer serious adverse reactions than with trimethoprim-sulfamethoxazole.

Acquired Immunodeficiency Syndrome↗