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Biomedical subjects

S Husted

Publications and source records attributed to S Husted.

At least 19 recordsLinked to original sources
PubMed2005

FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease.

OBJECTIVE: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD). DESIGN: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease). SETTING: 58 Scandinavian hospitals. PATIENTS: 2457 patients with unstable CAD from the FRISC II study. MAIN OUTCOME MEASURES: One year rates of mortality and death/myocardial infarction (MI). METHODS: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified. RESULTS: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with > or = 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p = 0.006). Death/MI was also reduced in patients with 3-4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p = 0.02). Neither death nor death/MI was reduced in patients with 0-2 risk factors. CONCLUSION: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

Aged↗
PubMed2004

Capability of the nematode-trapping fungus Duddingtonia flagrans to reduce infective larvae of gastrointestinal nematodes in goat feces in the southeastern United States: dose titration and dose time interval studies.

Infection with gastrointestinal nematodes, particularly Haemonchus contortus, is a major constraint to goat production in the southeastern United States. Non-anthelmintic control alternatives are needed due to increasing resistance of these nematodes to available anthelmintics. Two studies were completed in Central Georgia in August 1999, and April-May 2000, using Spanish does naturally infected with Haemonchus contortus, Trichostongylus colubriformis, and Cooperia spp. to evaluate effectiveness of nematode-trapping fungi as a biological control agent. In the first experiment, five levels of Duddingtonia flagrans spores were mixed with a complete diet and fed once daily to the does (three per treatment) in metabolism crates. The treatment concentrations were (1) 5 x 10(5), (2) 2.5 x 10(5), (3) 10(5), and (4) 5 x 10(4) spores per kilogram body weight (BW), and (5) no spores. Fungal spores were fed for the first 7 days of the 14-day trial, and fecal samples were collected daily from individual animals for analysis of fecal egg count and establishment of fecal cultures. Efficacy of the fungus at reducing development of infective larvae (L3) in the fecal cultures was evaluated. The mean reduction in L3 from day 2 of the treatment period until the day after treatment stopped (days 2-8) was 93.6, 80.2, 84.1, and 60.8% for animals given the highest to lowest spore doses, respectively. Within 3-6 days after termination of fungal spore feedings, reduction in L3 development was no longer apparent in any of the treated animals. In a second experiment, effectiveness of 2.5 x 10(5) spores of D. flagrans per kilogram BW fed to does every day, every second day, and every third day was evaluated. Reduction in L3 development by daily feeding was less in the second experiment than in the first experiment. Daily fungal spore feeding provided more consistent larval reduction than intermittant feeding (every second or third day). When fed daily under controlled conditions, D. flagrans was effective in significantly reducing development of L3 and appears to be an effective tool for biocontrol of parasitic nematodes in goats.

Animals↗
PubMed2004

Alpha-ketoglutarate treatment early in postnatal life improves bone density in lambs at slaughter.

This study has investigated the long-term effect on skeletal development of a short postnatal period of oral alpha-ketoglutarate (AKG) administration, a compound known to regulate the synthesis of proline, which in turn is important for collagen production. Male lambs born to Shropshire ewes were used in this study. Lambs were randomly assigned to either an AKG-treated group or a control group receiving an equal volume of distilled water. AKG-treated lambs received 0.1 g/kg body weight orally from the first 14 days of postnatal life. Lambs were slaughtered at approximately 130 day of life and a body weight of 43-49 kg. Plasma samples, collected from lambs at days 14 and 130, were analyzed for IGF-1 concentration using sheep-specific RIA kits. Bone development was determined on the femur in terms of geometrical and mechanical properties and quantitative computed tomography (QCT). Trabecular bone density, cortical bone density, and the mechanical properties of the bones were significantly higher for AKG-treated compared with control lambs. However, neither plasma IGF-1 concentration nor the geometrical properties of the bones were significantly influenced by AKG treatment. It is concluded that early postnatal treatment of lambs with AKG positively affects bone strength, an effect that does not appear to be mediated by an increased plasma IGF-1 concentration.

Animals↗
PubMed2002

Atrial fibrillation or flutter and stroke: a Danish population-based study of the effectiveness of oral anticoagulation in clinical practice.

OBJECTIVES: A pooled analysis of randomized trials has shown that oral anticoagulation therapy reduces the risk of ischaemic stroke with 68% in patients with atrial fibrillation. We examined the effectiveness of oral anticoagulation on risk of stroke of any nature (fatal and nonfatal ischaemic and/or haemorrhagic stroke) in patients with nonvalvular atrial fibrillation or flutter living in the County of North Jutland, Denmark. DESIGN: Cohort study. SUBJECTS AND METHODS: We used the Hospital Discharge Registry covering the county (490 000 inhabitants) from 1991 to 1998 to identify 2699 men and 2425 women with atrial fibrillation or flutter, aged 60-89 years. Data on prescriptions of anticoagulation were obtained from the National Health Service. We defined use of oral anticoagulation as date of prescription or reiteration plus 90 days. Patients were followed in the County Hospital Discharge Registry until a diagnosis of stroke (fatal and nonfatal ischaemic and/or haemorrhagic stroke), emigration, death or the end of 1998. We used Cox regression analyses to estimate the relative risk of stroke associated with use of oral anticoagulation compared with no use, adjusted for age, diabetes and underlying cardiovascular diseases. RESULTS: Eight hundred and thirty-eight of 2699 men (31%) and 552 of 2425 women (23%) with atrial fibrillation had one or more recorded prescriptions of oral anticoagulation. The incidence rates of stroke were 31 per 1000 person-years of follow-up in men, and 30 per 1000 person-years of follow-up in women. The adjusted relative risks of stroke during anticoagulation were 0.6 [95% confidence interval (CI) 0.4-1.0] in men, and 1.0 (95% CI 0.7-1.6) in women compared with nonuse periods. CONCLUSIONS: The effectiveness of oral anticoagulation in clinical practice may be lesser than the efficacy of oral anticoagulation reported from randomized trials.

Administration, Oral↗
PubMed2002

Safety and efficacy of abciximab combined with dalteparin in treatment of acute coronary syndromes.

AIMS: The safety and efficacy of abciximab in addition to low-molecular-weight-heparin as the primary medical treatment of acute coronary syndromes has not previously been investigated. METHODS AND RESULTS: The GUSTO IV-ACS trial included 7800 patients with chest pain and either ST-segment depression or a positive troponin test. They were randomized to abciximab for 24 h, 48 h or placebo. In the dalteparin substudy, 974 patients received 5 days of s.c. dalteparin, instead of a 48 h infusion of unfractionated heparin (UFH). Major and minor bleedings were more frequent for abciximab (24 and 48 h combined) than placebo both in the dalteparin (abciximab 5.0% vs placebo 1.8% P<0.05) and in the UFH cohort (3.8% vs 1.8% P<0.001). However, stroke rates were low, < or = 0.6%. At 30 days there were no significant differences in the rate of death or MI, either in the dalteparin (abciximab 9.6% vs placebo 11.3%: O.R. 0.85; 95% C.I. 0.58-1.25) or in the UFH cohort (8.5% vs 7.6%: O.R.; 1.12: 0.95-1.34). CONCLUSION: Treatment with abciximab, aspirin and s.c. dalteparin is associated with a low risk of major side effects and is as safe as the combination of abciximab and UFH. Without early coronary intervention there is no indication for abciximab treatment.

Abciximab↗
PubMed2002

The regulation of ammonium translocation in plants.

Much controversy exists about whether or not NH(+)(4) is translocated in the xylem from roots to shoots. In this paper it is shown that such translocation can indeed take place, but that interference from other metabolites such as amino acids and amines may give rise to large uncertainties about the magnitude of xylem NH(+)(4) concentrations. Elimination of interference requires sample stabilization by, for instance, formic acid or methanol. Subsequent quantification of NH(+)(4) should be done by the OPA-fluorometric method at neutral pH with 2-mercaptoethanol as the reducing agent since this method is sensitive and reliable. Colorimetric methods based on the Berthelot reaction should never be used, as they are prone to give erroneous results. Significant concentrations of NH(+)(4), exceeding 1 mM, were measured in both xylem sap and leaf apoplastic solution of oilseed rape and tomato plants growing with NO(-)(3) as the sole N source. When NO(-)(3) was replaced by NH(+)(4), xylem sap NH(+)(4) concentrations increased with increasing external concentrations and with time of exposure to NH(+)(4). Up to 11% of the translocated N was constituted by NH(+)(4). Glutamine synthetase (GS) incorporates NH(+)(4) into glutamine, but root GS activity and expression were repressed when high levels of NH(+)(4) were supplied. Ammonium concentrations measured in xylem sap sampled just above the stem base were highly correlated with NH(+)(4) concentrations in apoplastic solution from the leaves. Young leaves tended to have higher apoplastic NH(+)(4) concentrations than older non-senescing leaves. The flux of NH(+)(4) (concentration multiplied by transpirational water flow) increased with temperature despite a decline in xylem NH(+)(4) concentration. Retrieval of leaf apoplastic NH(+)(4) involves both high and low affinity transporters in the plasma membrane of mesophyll cells. Current knowledge about these transporters and their regulation is discussed.

Amines↗
PubMed2001

Incident thromboembolism in the aorta and the renal, mesenteric, pelvic, and extremity arteries after discharge from the hospital with a diagnosis of atrial fibrillation.

BACKGROUND: The impact of atrial fibrillation (AF) on risk of peripheral arterial thromboembolism is unknown. METHODS: We analyzed the risk of thromboembolism (embolus and/or thrombosis) in the aorta and the renal, mesenteric, pelvic, and extremity arteries in a cohort of patients discharged from the hospital with an incident diagnosis of AF relative to the risk of thromboembolism in these vessels in the Danish population. In a random sample of half of the Danish population, 14 917 men and 14 945 women aged 50 to 89 years were identified in the Danish National Hospital Discharge Register with a diagnosis of AF from January 1, 1980, through December 31, 1993. Patients were followed up from diagnosis of AF in the Danish National Hospital Discharge Register and the Causes of Death Register until the first diagnosis of a thromboembolic event, death, or the end of 1993. Risk of a thromboembolic event relative to the risk in the Danish population was analyzed by means of Poisson regression modeling. RESULTS: Patients with a hospital diagnosis of AF had an increased risk of thromboembolic events in the aorta and the renal, mesenteric, pelvic, and extremity arteries (relative risk, 4.0 [95% confidence interval, 3.5-4.6] in men; and relative risk, 5.7 [95% confidence interval, 5.1-6.3] in women) compared with the Danish population. CONCLUSION: A hospital diagnosis of AF is an important risk factor for peripheral arterial thromboembolic complications.

Aged↗
PubMed2001

A critical review of clinical trials for low-molecular-weight heparin therapy in unstable coronary artery disease.

Unstable angina and non-ST-segment elevation myocardial infarction (MI) are collectively referred to as unstable coronary artery disease (UCAD). They are conditions that share a common pathophysiology and represent frequently encountered, potentially life-threatening clinical manifestations of advanced atherosclerosis. Therefore, treatment of UCAD is a major focus for practicing clinicians, and although pharmacologic agents have been developed that impact on patient outcome, recent data suggest that a further reduction in ischemic complications is possible. Acute-phase treatment with aspirin is associated with a significant reduction in death and nonfatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. In contrast, low-molecular-weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response, making them an attractive treatment alternative to UFH in patients with UCAD. The optimal duration of treatment with LMWH is an important question influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. Early trials, such as FRISC and FRIC, demonstrated the benefit of acute therapy with dalteparin sodium; however, the results of extended treatment with dalteparin were inconclusive. The extended phase of these studies included relatively low-risk patients, and a once-daily, relatively low-dose strategy was employed. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin, suggest a benefit for at least 60 days with extended treatment in high-risk patients with UCAD. Although an early-invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin for up to 45 days, especially those awaiting percutaneous coronary intervention. Extended treatment with dalteparin therefore provides a protective "bridge" to enhance the outcome of patients with UCAD awaiting revascularization.

Angina, Unstable↗
PubMed2001

Impaired fibrinolysis determines the outcome of percutaneus transluminal coronary angioplasty (PTCA).

BACKGROUND: Coronary artery stenosis lesions dilated by percutaneus transluminal coronary angioplasty (PTCA) show a disappointingly frequent recurrence of stenosis. We have investigated the possible role of fibrinolysis and various platelet-release factors - specifically in the locality of the affected vessel - by following 19 patients for 6 months after PTCA. METHODS: PTCA was performed on 19 patients with a significant primary coronary stenosis, proven by quantitative CAAS analysis. Blood for measurement of local fibrinolysis and platelet activity was drawn from the aortic root and the coronary sinus, at three times: just before PTCA, 10 min after it, and 6 months later. RESULTS: The incidence of restenosis at the 6 months follow-up was 37%. PTCA almost doubled the platelet-derived growth factor level (PDGF) in coronary sinus blood in all patients. The seven restenosis patients had a substantially higher tissue plasminogen activator inhibitor antigen (PAI-1ag) level in the aortic root before PTCA than the 12 who remained stenosis-free (mean 62.4 +/- 31.6 ng mL -1 compared with 33.1 + 25.3; P < 0.04) and a lower tissue plasminogen activator activity (t-PAac) level (mean 0.32 +/- 0.19 IU mL-1 compared with 0.68 +/- 0.34; P < 0.03). This was corroborated by the levels of tissue plasminogen activator inhibitor activity (PAI-1ac). At reassessment after 6 months, the restenosis patients had developed, in coronary sinus blood, a large rise of PAI-1ac (7.7 +/- 4.8 IU mL-1 rising to 15.7 +/- 13.9, P < 0.04) and a large rise of of PAI-1ag (48.8 +/- 31.3 ng mL-1 vs. 72.4 +/- 47.2; P < 0.03). But no such increase occurred in the patients who remained stenosis-free. Conclusion Our results indicate that the minor balloon injury, which is inseparable from PCTA, stimulates the local release of PDGF. We suggest that, in those patients whose fibrinolytic activity is inherently low, this rise of PDGF could be a major causative factor in restenosis. We also discuss the possibility that the preoperative level of PAI-1ac could provide a limited but useful prediction of the outcome of PTCA.

Angioplasty, Balloon, Coronary↗
PubMed2000

Outcome at 1 year after an invasive compared with a non-invasive strategy in unstable coronary-artery disease: the FRISC II invasive randomised trial. FRISC II Investigators. Fast Revascularisation during Instability in Coronary artery disease.

BACKGROUND: The Fragmin and Fast Revascularisation during Instability in Coronary artery disease II trial (FRISC II) compared an early invasive with an early non-invasive strategy in unstable coronary-artery disease. We report outcome at 1 year. METHODS: 2457 patients were randomly assigned invasive or non-invasive treatment and 3 months of dalteparin or placebo. Complete information at 1 year was available for 1222 in the invasive group and 1234 in the non-invasive group. Analyses were by intention to treat. FINDINGS: Revascularisation was done within the first 10 days in 71% of the invasive group and 9% of the non-invasive group and within the first year in 78% and 43%. During the first year, 27 (2.2%) patients in the invasive group and 48 (3.9%) in the non-invasive group died (risk ratio 0.57 [95% CI 0.36-0.90], p=0.016). 105 (8.6%) versus 143 (11.6%) had myocardial infarction (0.74 [0.59-0.94], p=0.015). The composite of death or myocardial infarction occurred in 127 (10.4%) versus 174 (14.1%) patients (0.74 [0.60-0.92], p=0.005). There were also reductions in readmission (451 [37%] vs 704 [57%]; 0.67 [0.62-0.72]), and revascularisation after the initial admission (92 [7.5%] vs 383 [31%]; 0.24 [0.20-0.30]). The results did not interact with the dalteparin/placebo allocation. INTERPRETATION: After 1 year in 100 patients, an invasive strategy saves 1.7 lives, prevents 2.0 non-fatal myocardial infarctions and 20 readmissions, and provides earlier and better symptom relief at the cost of 15 more patients with coronary-artery bypass grafting and 21 more with percutaneous transluminal angioplasty. Therefore, an invasive approach should be the preferred strategy in patients with unstable coronary-artery disease and signs of ischaemia on electrocardiography or raised levels of biochemical markers of myocardial damage.

Adult↗
PubMed2000

Incident stroke after discharge from the hospital with a diagnosis of atrial fibrillation.

PURPOSE: Atrial fibrillation is an important risk factor for stroke. We analyzed stroke risk over time in patients discharged from the hospital with a diagnosis of incident atrial fibrillation as compared with the risk of stroke in the Danish population. SUBJECTS AND METHODS: In a random sample of half of the Danish population, we identified 13,625 men and 13,577 women, aged 50 to 89 years, with a hospital diagnosis of atrial fibrillation and no prior diagnosis of stroke during 1980 to 1993. Data on other medical conditions were also available from 1977 to 1993, but medication data were not available. Patients were followed from the diagnosis of atrial fibrillation until the first diagnosis of stroke (nonfatal or fatal cerebral ischemic infarct and cerebral hemorrhage), death, or the end of 1993. The risk of stroke in these patients was compared with the risk in the Danish population using Poisson regression modeling to estimate relative risks (RR) and 95% confidence intervals (CI). RESULTS: For men with atrial fibrillation, the stroke rates increased by age, from 13 per 1,000 person-years in those ages 50 to 59 years, to 22 per 1,000 person-years in those ages 60 to 69 years, to 42 per 1,000 person-years in those ages 70 to 79 years, to 51 per 1,000 person-years in those ages 80 to 89 years. Age-specific stroke rates were similar in women with atrial fibrillation. Patients with a hospital diagnosis of atrial fibrillation had an increased risk of stroke (RR = 2.4; 95% CI, 2.3 to 2.5 in men and RR = 3.0; 95% CI, 2.9 to 3.2 in women) compared with the Danish population. Stroke risk was greatest during the first year after discharge and decreased thereafter. Hypertension, diabetes, and peripheral atherosclerosis were also associated with an increased risk of stroke among patients with atrial fibrillation. Ischemic heart disease and heart failure were risk factors in men only. There was no reduction in the risk of stroke from 1980 to 1993. CONCLUSIONS: Men and women with atrial fibrillation are at a substantially increased risk of stroke, particularly in the first year after the diagnosis.

Age Distribution↗
PubMed2000

Acute and prolonged treatment with low-molecular-weight heparin therapy in patients with unstable coronary artery disease.

Unstable angina and non-ST-segment elevation myocardial infarction (MI) are known as unstable coronary artery disease (UCAD). They are syndromes that share a common pathobiology and represent a frequently encountered and potentially life-threatening medical condition. Acute-phase treatment with aspirin is associated with a significant reduction in death and non-fatal MI in patients with UCAD. This benefit is enhanced by the addition of unfractionated heparin (UFH) to the treatment strategy; however, UFH requires careful monitoring and titration. In contrast, low-molecular-weight heparins (LMWHs), produced by chemical or enzymatic depolymerization of UFH, yield a predictable and consistent pharmacokinetic profile and anticoagulant response making them an attractive alternative treatment to UFH in patients with UCAD. In several studies, acute-phase treatment with LMWH has been shown to be at least as effective and safe as UFH. The optimal duration of treatment with LMWH is an important question that has been influenced by the observation that reactivation of coagulation occurs following the early and abrupt discontinuation of heparin treatment. In early trials, such as FRISC (Fragmin during instability in coronary artery disease) and FRIC (Fragmin in unstable coronary artery disease), the results of extended treatment were inconclusive; however, the trial populations included patients of relatively low risk and used a once-daily dosing regimen. In the TIMI 11B (Thrombolysis in myocardial infarction) extended treatment beyond the few days of acute treatment with enoxaparin did not add to the beneficial LMWH effect, but in this study 40% of the high-risk patients did not continue on extended treatment. The findings derived from the FRISC II trial, which used a twice-daily dose of dalteparin sodium, suggest a benefit for up to 45 days with extended treatment in high-risk UCAD patients. Although an early invasive treatment strategy is particularly beneficial, patients in whom early revascularization is not possible should be considered for extended treatment with dalteparin sodium awaiting percutaneous coronary intervention.

Angina, Unstable↗
PubMed1999

Single-bolus tenecteplase compared with front-loaded alteplase in acute myocardial infarction: the ASSENT-2 double-blind randomised trial.

BACKGROUND: Bolus fibrinolytic therapy facilitates early efficient institution of reperfusion therapy. Tenecteplase is a genetically engineered variant of alteplase with slower plasma clearance, better fibrin specificity, and high resistance to plasminogen-activator inhibitor-1. We did a double-blind, randomised, controlled trial to assess the efficacy and safety of tenecteplase compared with alteplase. METHODS: In 1021 hospitals, we randomly assigned 16,949 patients with acute myocardial infarction of less than 6 h duration rapid infusion of alteplase (< or = 100 mg) or single-bolus injection of tenecteplase (30-50 mg according to bodyweight). All patients received aspirin and heparin (target activated partial thromboplastin time 50-75 s). The primary outcome was equivalence in all-cause mortality at 30 days. FINDINGS: Covariate-adjusted 30-day mortality rates were almost identical for the two groups--6.18% for tenecteplase and 6.15% for alteplase. The 95% one-sided upper boundaries of the absolute and relative differences in 30-day mortality were 0.61% and 10.00%, respectively, which met the prespecified criteria of equivalence (1% absolute or 14% relative difference in 30-day mortality, whichever difference proved smaller). Rates of intracranial haemorrhage were similar (0.93% for tenecteplase and 0.94% for alteplase), but fewer non-cerebral bleeding complications (26.43 vs 28.95%, p=0.0003) and less need for blood transfusion (4.25 vs 5.49%, p=0.0002) were seen with tenecteplase. The rate of death or non-fatal stroke at 30 days was 7.11% with tenecteplase and 7.04% with alteplase (relative risk 1.01 [95% CI 0.91-1.13]). INTERPRETATION: Tenecteplase and alteplase were equivalent for 30-day mortality. The ease of administration of tenecteplase may facilitate more rapid treatment in and out of hospital.

Aged↗
PubMed1997

Long-term low-molecular-weight heparin (Fragmin) and/or early revascularization during instability in coronary artery disease (the FRISC II Study).

The Fragmin and/or Early Revascularisation during Instability in Coronary Artery Disease (FRISC II) trial will, in a prospective multicenter factorially randomized study, compare the efficacy of 3 months continuation of subcutaneous treatment with the low-molecular-weight heparin dalteparin (Fragmin) with that of placebo and will also compare a direct invasive strategy with a stepwise selective approach with regard to the utilization of coronary angiography and revascularization in patients with unstable coronary artery disease. The primary endpoints are death or myocardial infarction after 3 and 6 months respectively. Secondary endpoints are the same events after 12-24 months and also cardiac symptoms, exercise capacity, and/or signs of myocardial ischemia, readmission, and costs. Analyses will also be made of subgroups based on inclusion diagnosis, initial elevation of biochemical markers of myocardial damage, elevation of fibrinogen or C-reactive protein, signs of ischemia in electrocardiography at rest or at continuous 24-hour ischemia monitoring, and left ventricular function at echocardiography. Altogether, 3,100 patients will be recruited in 65-70 Scandinavian centers. Completion of follow-up is anticipated in the second half of 1998. The FRISC II study will further elucidate new alternatives for antithrombotic, invasive, and individually tailored treatment of unstable coronary syndromes.

Angina, Unstable↗
PubMed1990

Concurrent chemotherapy and radiation therapy followed by transhiatal esophagectomy for local-regional cancer of the esophagus.

Forty-three patients with local-regional squamous-cell carcinoma of the esophagus or adenocarcinoma of the esophagus, cardia, or gastroesophageal junction were treated with concurrent cisplatin, vinblastine, fluorouracil (5-FU), and radiation therapy (RT) over 21 days. A transhiatal esophagectomy (THE) was planned on day 42. Seventy-nine percent had T2 primaries by clinical staging and 56% had enlarged regional nodes (N) on computed tomographic (CT) scan. Forty-one patients completed the preoperative treatment and went to surgery (95% operability rate), and 36 (84%) were completely resected. Ten of the 41 operative candidates had no evidence of tumor in the resected esophagus and nodal tissue (tumor0 node0; T0N0), 24% complete response (CR). Myelosuppression was the major toxicity with grade 3 or 4 leukopenia in 93% of patients and two preoperative treatment-related deaths. At a median follow-up of 26 months, the median survival time (MST) of all 43 patients registered on study has not been reached. The MST of the 36 completely resected patients and the 10 complete responders has not been reached; 70% and 100%, respectively, are alive at 24 months. The MST by histology is 21 months for the 22 squamous patients and has not been reached for the 21 adenocarcinoma patients registered on study. In a prognostic factor analysis, clinical N status, histology, and the percent of cisplatin and vinblastine tolerated were significant predictors for survival. These survival results suggest a significant improvement over the 14-month MST observed in our previous trial using preoperative chemotherapy only in a similar patient population, and a 12-month MST in a historic control group undergoing THE. A randomized trial is now in progress to convincingly determine if survival is prolonged by this therapy.

Adenocarcinoma↗
PubMed1985

Effect of postoperative extradural morphine on lower urinary tract function.

The effect of postoperative extradurally administered morphine on lower urinary tract function was studied in female patients undergoing uterine surgery. Urodynamic measurements were made on the day before and on the day after the operation, using a DISA 2-channel carbon dioxide (CO2) cystomictrograph. In ten patients without postoperative urinary retention no changes in cystometry were found during morphine administration, while two patients who developed acute urinary retention had a marked increase in bladder capacity and of detrusor pressure. In contrast, the urethral pressure profile was unchanged in both groups of patients. Intravenously administered naloxone tended to normalize the bladder capacity in the patients with urinary retention. These findings seem to indicate a marked effect in some patients of extradurally administered morphine and the acute urinary retention, following morphine administration, may be treated with naloxone.

Adult↗
PubMed1983

Direct effects of adenosine and adenine nucleotides on isolated human urinary bladder and their influence on electrically induced contractions.

Adenosine triphosphate concentration-dependent contracted strips of isolated human urinary bladder. Three types of responses were recognized. One consisted of an initial, transient, phasic contraction followed by a sustained tonic response, another lacked the tonic part and the 3rd had intermediate-type characteristics. Adenosine diphosphate produced an intermediate type of contraction, while adenosine monophosphate, adenosine and 2-chloroadenosine had no effect. Preparations obtained from hypertrophic bladders were more sensitive to adenosine triphosphate than macroscopically normal preparations. Indomethacin abolished tonic responses and reduced phasic adenosine triphosphate and adenosine diphosphate induced responses by about 30 per cent; addition of PGE2 and PGF2 alpha reestablished the phasic responses. Atropine, physostigmine, hexamethonium and phentolamine had no effect on the adenosine triphosphate induced contractions. These contractions were reduced by 33 to 48 per cent after nifedipine pretreatment and abolished within 10 minutes in a calcium-free medium. The response to transmural nerve stimulation was initially stimulated and then reduced by 30 to 80 per cent by purines in the order of potency ATP greater than APPCP = ADP greater than AMP greater than adenosine = 2-chloroadenosine. Acetylcholine induced contractions were reduced by 10 to 30 per cent. Indomethacin inhibited the response to transmural nerve stimulation by about 30 per cent but did not influence inhibition produced by adenosine triphosphate. Atropine-resistant responses to transmural nerve stimulation were significantly reduced by both adenosine triphosphate and indomethacin; nifedipine abolished the responses. The results suggest that adenosine triphosphate has a calcium-dependent direct contractive effect on isolated human urinary bladder and also that it may release prostaglandins. Muscular hypertrophy seems to increase the sensitivity to adenosine triphosphate. The response to transmural nerve stimulation was influenced by adenosine triphosphate probably both by prejunctional and postjunctional effects.

Acetylcholine↗