Low dose intraarterial thrombolysis with tissue plasminogen activator: does it deliver as promised?

The widespread use of intraarterial thrombolytic therapy has been based on perceived benefits over operative treatment and the downgrading of the magnitude of subsequent surgery. Thirty-three patients who had thrombolysis for peripheral artery occlusion were retrospectively analyzed at St. James's Hospital from 1991 to 1997. One patient received streptokinase unsuccessfully. Five other patient's records were inadequate for analysis. Twenty-seven patient's notes were analyzed for risk, duration of occlusion, duration of treatment, dosage of tissue plasminogen activator (tPA) and conduits thrombolysed. There were 15 males and 12 females. The mean age was 62 years (range, 20-87). Fourteen were current or reformed smokers. Five were diabetic. Indications for treatment included acute graft occlusion (n=13), embolus (n=6), and primary and secondary arterial thrombosis (n=8). Duration of occlusion was less than 24 hours in seven, 1 to 7 days in ten, and more than 7 days in ten patients. Twelve (44.44%) patients had complete clot lysis, four (14.81%) had partial clearance, and 11 (40.74%) remained occluded. Eight (29.63%) had serious complications including one death. Eighteen (66.66%) patients needed further surgical intervention to maintain graft patency. Data were analyzed using the chi-square and pooled t test. No significant difference was observed in results from thrombolysis from different conduits, gender, etiology, or smoking history. Increased duration of tPA administration was associated with an increased risk of failure. Administration of total dosages greater than 60 mg was associated with a higher risk of failure. Diabetics had a poor outcome (p=0.0520). Only 44 % of patients successfully underwent lysis. A primary surgical option may be a more sensible course than lysis, given that the vast majority of patients ended up having surgery anyway.     

Reporter Cell Lines to Monitor Steroid and Antisteroid Potential of Environmental Samples

In order to monitor the (anti)steroid activity of environmental samples, we established stable cell lines expressing luciferase under the control of estrogens, androgens, progestives and glucocorticoids. The breast cancer MCF-7 cells which express the estrogen receptor (ER), the glucocorticoid receptor (GR) and the progesterone receptor (PR) were transfected by an estrogen (ERE-Glob-Luc) or a glucocorticoid/progestin/androgen (MMTV-Luc) regulated luciferase plasmid in order to enable the detection of compounds which bind both ER, PR and GR (MELN and MMLN cells). Human prostatic cells PC3 were stably transfected by both an androgen receptor gene and the MMTV-luciferase plasmid (PALM cells). These three cellular models were validated as tools to check the estrogenic, progestive, glucocorticoid and androgenic activities using several potential xenohormones and environmental samples. As these environmental samples were fractionated after solid phase extraction to isolate active compounds, we used these cellular models to monitor the different fractions. In the estrogenic model mid-polar fractions of environmental samples were found active while in the androgenic model, the same fractions had antagonist activity.     

Generalized tonic-clonic status epilepticus: causes, treatment, complications and predictors of case fatality

We retrospectively reviewed the clinical course of 66 patients treated for generalized tonic-clonic status epilepticus at the Ege University neurological intensive care unit from 1988 to 1997. Seventy-two per cent of the study group had a pre-existing seizure disorder, and antiepileptic drug withdrawal was the most prominent cause of status epilepticus. The other causes included drug toxicity, central nervous system infection, cerebrovascular disease, tumour and trauma. Seventy-three per cent of all patients responded to the first-line therapy (diazepam and/or phenytoin), and the remainder were considered to have refractory status epilepticus and required pentobarbital anaesthesia. Overall case fatality was 21%, but death could be attributed directly to status epilepticus and/or treatment complication in 10% of the study group. Major determinants of fatal outcomes were: increasing age, longer duration of status epilepticus before initiation of therapy and central nervous system infection as a causal factor. Received: 9 December 1997 Received in revised form: 23 February 1998 Accepted: 30 March 1998     

The Three Transcobalamins in Myeloproliferative Disorders and Acute Leukaemia

The unsaturated vitamin B₁₂ binding capacity of whole serum (UBBC) and of the three transcobalamins (TC) has been studied in patients with various haematological diseases including myeloproliferative disorders (MPD) and acute leukaemia. The binding capacity of TC I and TC III was increased in MPD; TC I being particularly high in chronic granulocytic leukaemia (CGL) and TC III especially raised in polycythaemia rubra vera (PRV) and in infectious leucocytosis. The binding capacity of both TC I and TC III correlated with blood neutrophil count and the ratio TC III/TC I was low in CGL and increased in PRV. TC II was increased in acute myelogenous leukaemia, during remission and blast cell crisis of CGL and in refractory anaemia with excess of myeloblasts but not in acute lymphoblastic leukaemia (ALL). TC II correlated inversely with blood neutrophil count. There is an inverse ratio between TC II and TC I at least in myelogenous leukaemia. These abnormalities are discussed in relation to granulocyte kinetics. TC III and TC I reflect probably the total body granulocyte pool and share some biochemical and immunological properties supporting the view that they have a common origin in the more mature stages of the granulocyte cell line while TC II probably originates partly in more primitive granulocytes.     

In Vitro Studies of Bone Marrow in Refractory Anaemia

S ummary . Bone marrows of six patients with refractory anaemia have been studied for their capacity to form colonies in vitro on agar gel medium. They are not capable of forming colonies, and in this they behave as do bone marrows from patients with acute myeloblastic leukaemia in relapse.     

Spectrofluorometric determination of montelukast in dosage forms and spiked human plasma

The native fluorescence of montelukast has been studied under different experimental conditions. The highest fluorescence intensity was obtained in methanol at 390 nm using 340 nm for excitation. Surfactants and sensitizers had either a negative or a slightly positive effect on its fluorescence intensity. The fluorescence intensity-concentration plot was rectilinear over the range 0.125 to 5 microg/ml with a lower detection limit of 0.02 microg/ml (3.4 x 10(-8) M). Interference likely to be introduced from co-formulated drugs (such as loratadine) or co-administered drugs (such as verapamil, carbazepam, propranolol) or other common drugs, was studied. The method was successfully applied to the determination of the drug in tablets (pediatric tablets, chewable tablets and adult tablets). The mean % recoveries were in agreement with those provided by the manufacturer. The method was further applied to the in vitro determination of montelukast in spiked human plasma, the mean % recovery (n = 5) was 100.08 +/- 1.40.     

Kinematic analysis of conventional and high-flexion cruciate-retaining total knee arthroplasties: an in vitro investigation

This study examined the kinematics of a cruciate-retaining (CR) total knee arthroplasty (TKA) component that attempts to enhance knee flexion by improving posterior tibiofemoral articular contact at high-flexion angles. Using an in vitro robotic experimental setup, medial and lateral femoral translations of this CR design were compared with that of a conventional CR TKA design and intact knee under a combined quadriceps and hamstring muscle load. Both CR TKA designs showed similar kinematics throughout the range of flexion (0 degrees -150 degrees ). The TKAs restored nearly 80% of the posterior femoral translation of the intact knee at 150 degrees . The posterior cruciate ligament (PCL) forces measured for the high-flexion CR TKA component indicate that the PCL is important in the mid-flexion range but has little effect on knee kinematics at high flexion.     

Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: Report of the ISPOR Task Force for Translation and Cultural Adaptation

In 1999, ISPOR formed the Quality of Life Special Interest group (QoL-SIG)--Translation and Cultural Adaptation group (TCA group) to stimulate discussion on and create guidelines and standards for the translation and cultural adaptation of patient-reported outcome (PRO) measures. After identifying a general lack of consistency in current methods and published guidelines, the TCA group saw a need to develop a holistic perspective that synthesized the full spectrum of published methods. This process resulted in the development of Translation and Cultural Adaptation of Patient Reported Outcomes Measures--Principles of Good Practice (PGP), a report on current methods, and an appraisal of their strengths and weaknesses. The TCA Group undertook a review of evidence from current practice, a review of the literature and existing guidelines, and consideration of the issues facing the pharmaceutical industry, regulators, and the broader outcomes research community. Each approach to translation and cultural adaptation was considered systematically in terms of rationale, components, key actors, and the potential benefits and risks associated with each approach and step. The results of this review were subjected to discussion and challenge within the TCA group, as well as consultation with the outcomes research community at large. Through this review, a consensus emerged on a broad approach, along with a detailed critique of the strengths and weaknesses of the differing methodologies. The results of this review are set out as "Translation and Cultural Adaptation of Patient Reported Outcomes Measures--Principles of Good Practice" and are reported in this document.     

Complications of craniofacial resection for malignant tumors of the skull base: report of an International Collaborative Study

BACKGROUND: Advances in imaging, surgical technique, and perioperative care have made craniofacial resection (CFR) an effective and safe option for treating malignant tumors involving the skull base. The procedure does, however, have complications. Because of the relative rarity of these tumors, most existing data on postoperative complications come from individual reports of relatively small series of patients. This international collaborative report examines a large cohort of patients accumulated from multiple institutions with the aim of identifying patient-related and tumor-related predictors of postoperative morbidity and mortality and set a benchmark for future studies. METHODS: One thousand one hundred ninety-three patients from 17 institutions were analyzed for postoperative mortality and complications. Postoperative complications were classified into systemic, wound, central nervous system (CNS), and orbit. Statistical analyses were carried out in relation to patient characteristics, extent of disease, prior radiation treatment, and type of reconstruction to determine factors that predicted mortality or complications. RESULTS: Postoperative mortality occurred in 56 patients (4.7%). The presence of medical comorbidity was the only independent predictor of mortality. Postoperative complications occurred in 433 patients (36.3%). Wound complications occurred in 237 (19.8%), CNS-related complications in 193 (16.2%), orbital complications in 20 (1.7%), and systemic complications in 57 (4.8%) patients. Medical comorbidity, prior radiation therapy, and the extent of intracranial tumour involvement were independent predictors of postoperative complications. CONCLUSIONS: CFR is a safe surgical treatment for malignant tumors of the skull base, with an overall mortality of 4.7% and complication rate of 36.3%. The impact of medical comorbidity and intracranial tumor extent should be carefully considered when planning therapy for patients whose tumors are amenable to CFR.