Effect of rofecoxib on platelet aggregation and blood loss in gynaecological and breast surgery compared with diclofenac.

BACKGROUND: Non-selective cyclooxygenase (COX) inhibitors or non-steroidal anti- inflammatory drugs (NSAIDs) are frequently omitted for perioperative pain relief because of potential side-effects. COX-2-selective inhibitors may have a more favourable side-effect profile. This study tested the hypothesis that the COX-2-selective inhibitor rofecoxib has less influence on platelet function than the NSAID diclofenac in gynaecological surgery. In addition, analgesic efficacy and side-effects of the two drugs were compared. METHODS: In this single-centre, prospective, double-blind, active controlled study, women undergoing vaginal hysterectomy (n=25) or breast surgery (n=25) under general anaesthesia received preoperatively 50 mg of rofecoxib p.o. followed 8 and 16 h later by two doses of placebo or three doses of diclofenac 50 mg p.o. at the same time points. We assessed arachidonic acid-stimulated platelet aggregation before and 4 h after the first dose of study medication, estimated intraoperative blood loss, and haemoglobin loss until the first morning after surgery. Analgesic efficacy, use of rescue analgesics, and side-effects were also recorded. RESULTS: In the rofecoxib group, stimulated platelet aggregation was disturbed less (P=0.02), and estimated intraoperative blood loss (P=0.01) and the decrease in haemoglobin were lower (P=0.01). At similar pain ratings, the use of anti-emetic drugs was less in the rofecoxib group (P=0.03). CONCLUSION: Besides having a smaller effect on platelet aggregation, one oral dose of rofecoxib 50 mg given before surgery provided postoperative analgesia similar to that given by three doses of diclofenac 50 mg and was associated with less use of anti-emetics and less surgical blood loss in gynaecological surgery compared with diclofenac.

Epizootics of cancer in fish associated with genotoxins in sediment and water.

Neoplasm epizootics in fish from a wide variety of freshwater, marine, and estuarine locations have been associated with genotoxins in sediment or water. The majority of cases have involved benthic or bottom feeding fish living in habitats with sediment contaminated by PAHs. The most common lesions involved in such epizootics include liver neoplasms, both biliary and hepatic, and skin neoplasms. Laboratory research has demonstrated the ability of fish to metabolize carcinogenic PAHs such as B(a)P into the ultimate carcinogen with the resulting formation of DNA adducts. Fish dosed with B(a)P or sediment extracts containing carcinogenic PAHs have developed skin and liver neoplasms. In the Black River, OH, neoplasm prevalence in wild brown bullhead has reflected PAH exposure as the latter has changed due to coke plant closures and remedial dredging activity. The weight of evidence supports a cause-and-effect relationship between exposure to genotoxins in sediment and water and neoplasm epizootics in wild fish populations.

Established acute respiratory distress syndrome: benefit of corticosteroid rescue therapy.

UNLABELLED: The mortality of the acute respiratory distress syndrome (ARDS) is still very high. There is some evidence based on case series suggesting that corticosteroids may be beneficial in the chronic fibroproliferative state of the disease. In a retrospective study we analysed the data of 31 non-trauma ARDS patients who had been on mechanical ventilation for at least 7 days. Thirteen cases received corticosteroids at a dosage equivalent to 100-250 mg methylprednisolone at the discretion of the attending physician in charge. Apart from corticosteroid administration, supportive care was identical in the treated and non-treated patient subgroups. Both groups were comparable regarding the relevant demographic, clinical and physiologic data, Apache-II score, radiological score, lung injury score and multiple organ failure score. Mortality in the treatment group was 38% (5/13) as opposed to 67% (12/18) in the untreated group (p = 0.117). There was a significant improvement in the PaO2/FIO2 ratio from a median of -26 to +5 mm Hg measured in a 48-hour period before and after corticosteroid treatment (p = 0.039). The response to corticosteroid therapy could not be predicted on the basis of clinical or physiologic data. Five patients responded within 48 h, and 3 showed a delayed response after 5-6 days. There were no significant complications attributable to corticosteroid treatment. CONCLUSIONS: Although the data of this first comparative study were retrospective, they suggest a beneficial effect of corticosteroid treatment in patients with established fibroproliferative ARDS. A prospective clinical trial, however, is highly warranted in order to fully elucidate the true effect of this therapeutic approach under controlled conditions.

[Acute myocardial infarct in Switzerland: results from the PIMICS Heart Infarct Register. PIMICS Project (Prospective Ischemia Myocardial Infarction Captopril Survey)]. / Der akute Myokardinfarkt in der Schweiz: Resultate aus dem PIMICS-Herzinfarkt-Register. PIMICS-Projekt (Prospective Ischemia Myocardial Infarction Captopril Survey).

The aim of the PIMICS project was to create, for the first time in Switzerland, a registry of data concerning epidemiology and therapy in patients hospitalised for acute myocardial infarction covering all regions of the country. During 1995/96 73 Swiss hospitals of all categories took part in the PIMICS project. The ratio between males and females in the 3877 registered patients was 2.6:1 (2791 men vs. 1086 women). Female patients were significantly older than males (70.4 +/- 12.0 years vs. 63.4 +/- 12.6 years; p < 0.0001). The prevalence of risk factors differed between men and women: significantly more women had hypertension or diabetes, whereas smoking was more prevalent in males. The median delay between onset of symptoms and arrival at the hospital was 5.5 hours. Thrombolysis and primary angioplasty were more frequently performed in men (40.4% vs. 31.2% in women, p < 0.0001, and 5.7% in men vs. 3.5% in women, p = 0.005 respectively). During the acute phase males were treated more frequently with betablockers. The overall in-hospital mortality was 9.1%. It was significantly higher in female patients (13.5% vs. 7.4% in men; p < 0.0001) and in patients with reinfarction (14.5% vs. 7.1%; p < 0.0001). The mean hospital stay was 12.6 +/- 5.3 days. Only 7.7% of all patients with acute myocardial infarction were discharged within 6 days. At discharge, 51.7% were treated with betablockers and 69.3% with aspirin; 44.8% received ACE-inhibitors and only 13.8% lipid-lowering drugs. Follow-up measures such as coronary angiography and/or angioplasty or bypass surgery were performed significantly more often in males (45.0% vs. 32.9%; p < 0.0001). Likewise, men were more frequently assigned to a rehabilitation program than women (38.2% vs. 32.9%; p = 0.0004). The pre-hospital delay in patients with acute myocardial infarction remains too long. Primary and secondary prevention should be intensified in high risk groups, particularly in females. Thrombolysis and primary angioplasty as mainstays of treatment in acute myocardial infarction are generally used too sparingly, especially in women. With such measures the hospital stay could be shortened further.

Fatal air embolism in an airplane passenger with a giant intrapulmonary bronchogenic cyst.

Considering the large number of airplane passengers with a variety of medical conditions, the incidence of in-flight emergencies on commercial airline flights is low. Only few cases of pulmonary barotrauma in airplane passengers with prior lung pathologies have been reported. We present the unusual case of a female airplane passenger with a previously diagnosed asymptomatic giant intrapulmonary bronchogenic cyst who experienced fatal air embolism on a commercial airline flight. We believe that preventive surgical resection is mandatory in asymptomatic patients with large intrapulmonary cysts prior to exposure to even small alterations in ambient pressure as, for instance, prior to airplane flight or use of mountain cable cars. However, screening for pre-existent lung pathologies in the growing mass of commercial airline travelers is not justified.

[Ethical aspects and problems in intensive care medicine]. / Ethische Aspekte und Probleme in der Intensivmedizin.

In the Intensive Care Unit important decisions in critically ill and often incompetent patients have to be made within a short period of time and without all the necessary information. Two main questions arise: 1. How can the autonomy of the patients be respected under these circumstances? 2. Which diagnostic and therapeutic activities are adequate and reasonable in each individual patient? An optimal communication between the people involved helps to find the best answers.

[Early results in the surgical treatment of type B aortic dissection]. / Frühresultate der chirurgischen Behandlung der Aortendissektion Typ B.

In contrast to type A aortic dissection, the indication for acute surgical repair as treatment of choice in type B aortic dissection is not the actual dissection, but the complications resulting from the dissection (rupture, potential rupture and ischemic syndromes of the aortic branches). Between 1978 and 1994, 92 patients underwent surgical repair of type B aortic dissection at our institution. Following diagnostic confirmation by echocardiography and/or CT scan, all patients received conservative antihypertensive therapy. 52% of the patients underwent emergency surgical repair. Symptoms prompting surgical repair were: visceral ischemia (23%), pleural effusion (19%), paraparesis (17%), refractory hypertension (12%), further aortic enlargement (12%), and rupture (10%). In chronic type B aortic dissection, the main symptom in 84% of the cases was further enlargement of the aorta. The early mortality decreased in the course of initial treatment from 33% to 16%, and to 8% after exclusion of patients operated on for ruptured aorta. Improved early mortality has led to an increase in acute surgical repair. In cases of chronic dissection, strict antihypertensive therapy is indicated and regular checks on the width of the aorta, as well expeditious diagnostic confirmation of its enlargement, are important.

Noninvasive monitoring of cardiac output in critically ill patients with thoracocardiography.

Thoracocardiography noninvasively estimates changes in cardiac output by recording ventricular volume curves from an inductive plethysmographic transducer placed around the chest near the xiphoid process. We evaluated performance of thoracocardiography for estimation of cardiac output in 21 critically ill patients in comparison to thermodilution. A total of 201 paired cardiac output measurements were obtained over periods of 35 to 254 min. Since thoracocardiography tracks relative changes in cardiac output but does not provide absolute values, the first cardiac output by thermodilution in each patient was used to calibrate thoracocardiography for comparisons of subsequent cardiac output estimates to thermodilution. The mean difference (bias) of cardiac output (thoracocardiography - thermodilution) was 0.0 L/min, the limits of agreement (bias +/- 2 SD) included a range from -1.5 to +1.6 L/min. For estimations of relative changes in cardiac output by thoracocardiography and thermodilution the bias was 0%, and the limits of agreement -21 and +22%. We conclude that thoracocardiography is a promising noninvasive technique for monitoring cardiac output in critically ill patients.

Severe respiratory insufficiency complicating Epstein-Barr virus infection: case report and review.

We report a case involving a young adult who had life-threatening bilateral pneumonitis in the course of an acute Epstein-Barr virus (EBV) infection. Because of severe hypoxemia, the patient required mechanical ventilation and additional oxygenation by an intravascular oxygenator. The patient was treated with corticosteroids and survived without sequelae. Severe pulmonary involvement associated with EBV infection is a rare but potentially fatal complication of infectious mononucleosis. Similar cases reported in the literature are reviewed, and the therapeutic options for this particular complication are discussed.

[Intensive care aspects in severe tropical malaria: clinical aspects, therapy and prognostic factors]. / Intensivmedizinische Aspekte bei schwerer Malaria tropica: Klinik, Therapie und prognostische Faktoren.

In a retrospective study we analyzed the clinical and blood chemical data of 12 patients with severe tropical malaria in the intensive care units of the University Hospital Zurich and the Stadtspital Triemli, Zurich, between 1991 and 1994. None of the 12 patients had been exposed to malaria before or had taken drugs for chemoprophylaxis. 7 patients survived, 5 died from complications of malaria. According to the criteria of severe tropical malaria defined by the WHO, the following pathological clinical and blood chemical parameters were noted on admission: cerebral coma (2/12); blood hemoglobin < 5 g/dl (0/12), < 8 g/dl (2/12); serum creatinine > 265 mumol/l (3/12); blood glucose < 2.2 mmol/l (0.12); circulatory collapse/shock (0/12); bleeding/signs of disseminated intravascular coagulation in laboratory tests (4/12); acidosis with pH < 7.25 (1/12). Further signs of severe tropical malaria were: hyperparasitemia > 5% (9/12); qualitative and quantitative disturbances of consciousness (6/12); thrombocytopenia < 30 x 10(9)/l (9/12); hyponatremia 125-135 mmol/l (9/12), < 125 mmol/l (2/12); rhabdomyolysis with creatine kinase > 1000 U/l (4/12). The basic treatment consisted of parenteral quinine hydrochloride in all patients; doxycycline was added in 8 cases, clindamycin in 3. Adjuvant therapy with desferrioxamin was given in 3 cases. 6 patients had exchange transfusions. Parasitemia cleared in all patients within 5 to 6 days. Later in the course, 5 patients developed acute respiratory distress syndrome, 6 required hemofiltration due to oliguria, and one became comatose.(ABSTRACT TRUNCATED AT 250 WORDS)

Decline in liver neoplasms in wild brown bullhead catfish after coking plant closes and environmental PAHs plummet.

Polycyclic aromatic hydrocarbons (PAHs) in both sediment and brown bullhead catfish tissues from the Black River in Lorain County, Ohio, declined by 65% and 93%, respectively, between 1980 and 1982. Sediment PAHs declined an additional 99% by 1987, coincident with the closure of a coking facility in 1983. Contemporaneously, liver cancer in 3- to 4-year-old brown bullheads declined to about one-quarter the 1982 frequency (10% versus 39%) by 1987, while the percentage of livers without any proliferative lesions doubled (42% versus 20%). These changes were significant within age group. Our data affirm a cause-and-effect relationship between PAH exposure and liver cancer in wild fish. The data also support the efficacy of natural, unassisted remediation once the source of the pollution is eliminated.

[Type B aortic dissections: surgical technique and results]. / Aortendissektionen Typ B: Operationstechnik und Resultate.

Between 1978 and 1992, 70 patients were operated for type B aortic dissection (tear in the descending aorta without involvement of the ascending aorta). 15/70 (21%) patients had an acute dissection (onset of symptoms < 24 h), 19/70 (27%) a subacute dissection (onset of symptoms < 14 days), and 36/70 (51) a chronic dissection (onset of symptoms > 14 days). The indications for surgery in cases of acute dissection were: hematothorax, oliguria, leg ischemia and persistent pain. Persistent hypertension was an additional indication in cases of subacute dissection. In large majority (93%) of chronic dissections the indication for surgery was enlarged aortic diameter. In 86% (60/70) graft replacement of the aorta was performed, in 6% (4/70) extra-anatomic bypass, in 3% (2/70) fenestration, in 3% (2/70) thrombendarterectomy, in 3% (2/70). The overall mortality was 17% (12/70); 27% of acute dissection, 26% for subacute dissection, and 8% for chronic dissection. The morbidity for acute dissection was 73%, of subacute dissection 43%, and of chronic dissection 12%. The most frequent complications were: leg ischemia (8 patients), renal failure (4 patients), paraparesis (4 patients) and sepsis (2 patients). No paraparesis was encountered in surgery of the chronic dissection. Conservative treatment was tried in all acute B-dissections, with surgical therapy being reserved for complications of the dissection, such as rupture, such as rupture, risk of rupture (hematothorax, large aortic diameter resp. expansion, persistent hypertension, persistent pain) or ischemia of distal vascular beds. Long-term survival for chronic type B dissections is good. Strong control of risk factors (hypertension) is essential.

Dissection of the descending thoracic aorta extending into the ascending aorta. A therapeutic challenge.

Proper management of dissections of the descending thoracic aorta with intimal disruption close to the left subclavian artery and retrograde extension of the dissection into the aortic arch or the ascending aorta is controversial, because the standard approach for ascending aortic aneurysms is surgical repair, which is difficult to achieve through a median sternotomy if the predominant aortic lesion is located in its descending part. Sixteen patients with descending thoracic aortic dissection, intimal disruption close to the subclavian artery, and extension of the dissection into the aortic arch or the ascending aorta are described here: Eleven patients underwent surgical repair including 9 emergency (82%) and 2 elective (18%) procedures. Retrograde aortic dissection included the aortic arch in 11 of 11 patients (100%) and the ascending aorta in 7 of 11 (63%). Pericardial effusion was present in 1 of 11 patients (9%) and mild aortic regurgitation was found in 1 of 11 (9%). Repair of the ascending aorta and arch with transaortic closure of the entrance tear in the descending thoracic aorta was performed in 4 of 11 patients (36%) via a median sternotomy. In 6 of 11 patients (55%) a lateral thoracotomy was used for repair of the descending thoracic aorta and closure of the entrance tear. Hospital mortality occurred in 1 of 11 patients (9%) and there was 1 late death. Paraplegia occurred in 1 of 11 patients (9%). Five patients with descending thoracic aortic dissection, intimal disruption close to the subclavian artery, and extension into the ascending aorta but without ascending aortic aneurysm (diameter 4.2 +/- 0.2 cm), pericardial effusion, or aortic incompetence were treated medically without early mortality. These results are compared with those achieved in 120 patients operated on during the same period for type A (89/120) and type B (31/120) aortic dissections. Considering the technical difficulties of simultaneous repair of dissections of the ascending and the descending thoracic aorta, we recommend that descending thoracic aortic dissection extending into the arch or the ascending aorta be managed in accordance with the site of the predominant lesion. Replacement of the arch with a varying portion of ascending aorta via a median sternotomy is recommended in patients with enlarged aortic diameter, pericardial effusion, and/or aortic insufficiency. Predominantly distal dissections with dilated descending thoracic aorta and/or distal complications are best approached via a lateral thoracotomy.

[Hemodynamic improvement during therapy using the intravascular oxygenator (IVOX)]. / Hämodynamische Verbesserung während Therapie mit intravaskulärem Oxygenator (IVOX).

The intravascular oxygenator (IVOX) is a new device which is implanted in the vena cava sup. and inf. where it oxygenates the blood and removes CO2. We report on its successful use in a young patient with severe pneumonia. This 21-year-old female was admitted to hospital with acute respiratory distress due to pneumococcal pneumonia and sepsis following chickenpox. Considering the rapidly progressive course with severe hypoxia and shock, PaO2/PaCO2 values of 6.5/6.4 kPa on mechanical ventilation with an FiO2 of 1.0 and a PEEP of 13 mbar, we decided to implant an intravascular oxygenator. Besides rapid improvement of oxygenation, we observed remarkable recovery of cardiovascular function such as an increase in mean arterial pressure and mixed-venous saturation, while the dose of vasopressors could be decreased. The intravascular oxygenator was removed without problems after 29 days of continuous use, when pulmonary function allowed an FiO2 of 0.45. The patient was discharged from the intensive care unit after 99 days in a good neurological and stable cardiovascular state.

Hemodynamic effects and concentration-effect relationship of a graded infusion of piroximone in patients with severe heart failure.

Piroximone is a new phosphodiesterase III inhibitor that combines inotropic and vasodilator properties. To elucidate the optimal dose regimen and the dose-concentration-effect relationships, we studied eight patients with congestive heart failure of New York Heart Association class IV during a continuous multistage infusion over a 24-h period followed by a 4-h washout. After a bolus of 0.5 mg/kg, infusions at a rate of 2.5, 5.0, and 10.0 micrograms/kg/min for 8 h each were given to determine the maintenance dose of piroximone required to achieve an increase in cardiac index > or = 30%. Serial assessment of hemodynamics, plasma piroximone levels, and ventricular ectopic beats was performed. Following the loading dose and at higher infusion rates (5 and 10 micrograms/kg/min) Piroximone produced significant hemodynamic changes compared to baseline, i.e., a maximum increase in cardiac index from 2.2 +/- 0.4 to 3.6 +/- 0.8 L/min/m2 (67 +/- 21%), decreases in right atrial pressure from 14 +/- 3 to 9 +/- 3 mm Hg (40 +/- 16%), pulmonary capillary wedge pressure from 29 +/- 5 to 23 +/- 7 mm Hg (28 +/- 18%), pulmonary vascular resistance from 249 +/- 93 to 151 +/- 59 (45 +/- 19%), and systemic vascular resistance from 1,330 +/- 442 to 752 +/- 272 dyn s/cm5 (44 +/- 19%). Piroximone increased the heart rate by 10% at the highest dose and produced a decrease in mean arterial pressure by 13%. There was a slight increase in ventricular ectopy in two patients (2.2 and 3 VPBs/min) and no change in the remaining six.(ABSTRACT TRUNCATED AT 250 WORDS)

[Thrombolysis in acute myocardial infarct. An established therapy with open questions]. / Thrombolyse beim akuten Myokardinfarkt. Eine etablierte Therapie mit offenen Fragen.

Intravenous thrombolysis is an established form of therapy within the first 4-6 hours of acute myocardial infarction. In numerous randomized controlled trials it has been shown to be effective in restoring myocardial perfusion, reducing mortality and improving ventricular function. The data so far available do not allow conclusions regarding the best lytic substance. The complication rate is surprisingly low. As adjunctive therapy, aspirin exerts an additive effect and heparin should be given for the first 48 hours. Its exact role is still under investigation. Several ongoing studies are designed to answer the remaining questions: (1.) Which patients with symptoms of more than 6 hours' duration could benefit from thrombolysis? (2.) Should patients with unstable angina be given this treatment? (3.) To minimize delay, it might be beneficial to start thrombolysis in the prehospital phase, but the problems of information and organization need to be solved. (4.) Attempts are being made to further improve thrombolytic and adjunctive therapy.

Carcinogens and cancers in freshwater fishes.

Epizootics of neoplasms in freshwater fish species are considered in relation to circumstantial and experimental evidence that suggest that some epizootics of neoplasia of hepatocellular, cholangiocellular, epidermal, and oral epithelial origin may be causally related to contaminant exposure. Although there is concern for the safety of consuming fish affected with neoplasms, this concern may be misdirected as direct transmission of cancer by ingesting cancerous tissue would seem unlikely. Of greater concern is the matter of toxic and cancer-causing chemicals present in edible fish that exhibit neoplasia as a symptom of past exposure via residence in a polluted waterway. There is ample evidence to suggest that contaminant chemicals ingested via contaminated Great Lakes fish may already be affecting both human and ecosystem health, but these effects are subtle and may require new approaches to the study of the affected systems.