The combination of raltitrexed (Tomudex) and mitomycin-C in the treatment of advanced colorectal cancer--a phase II study.

AIMS: To investigate the combination of raltitrexed and mitomycin-C as first-line chemotherapy treatment in patients with advanced colorectal cancer. MATERIALS AND METHODS: A phase II study. RESULTS: In total, 22 patients were treated with a combination of raltitrexed 3 mg/m2 every 3 weeks and mitomycin-C 7 mg/m2 every 6 weeks for up to 24 weeks. The study was closed early for safety reasons as there were three unexpected treatment-related deaths. The overall response rate was 20%, and a further 40% achieved stable disease. The median time to progression was 3.9 months and the median overall survival time was 11.6 months. CONCLUSION: Owing to the potential for increased toxicity, the combination of raltitrexed and mitomycin-C cannot be recommended as first-line treatment in patients with advanced colorectal cancer.

Normative findings of electrically evoked compound action potential measurements using the neural response telemetry of the Nucleus CI24M cochlear implant system.

One hundred and forty-seven adult recipients of the Nucleus 24 cochlear implant system, from 13 different European countries, were tested using neural response telemetry to measure the electrically evoked compound action potential (ECAP), according to a standardised postoperative measurement procedure. Recordings were obtained in 96% of these subjects with this standardised procedure. The group results are presented in terms of peak amplitude and latency, slope of the amplitude growth function and ECAP threshold. The effects of aetiological factors and the duration of deafness on the ECAP were also studied. While large intersubject variability and intrasubject variability (across electrodes) were found, results fell within a consistent pattern and a normative range of peak amplitudes and latencies was established. The aetiological factors had little effect on the ECAP characteristics. However, age affected ECAP amplitude and slope of the amplitude growth function significantly; i.e., the amplitude is higher in the lowest age category (15-30 years). Principal component analysis of the ECAP thresholds shows that the thresholds across 5 electrodes can be described by two factors accounting for 92% of the total variance. The two factors represent the overall level of the threshold profiles ('shift') and their slopes across the electrode array ('tilt'). Correlation between these two factors and the same factors describing the T- and C-levels appeared to be moderate, in the range of 0.5-0.6.

Comparison between NRT-based MAPs and behaviourally measured MAPs at different stimulation rates--a multicentre investigation.

Seventeen adult subjects participated in a multicentre trial to compare the performance between an NRT-based MAP and their behavioural MAP. The NRT-based MAP was made using a correction factor to predict T/C levels, calculated from the difference between the ECAP threshold ('T-NRT') and the measured T/C levels at electrode 10, as described by Brown et al. (2000). A secondary aim was to compare T/C levels in behavioural MAPs at different stimulation rates with the predicted T/C levels in NRT-based MAPs. Performance with both MAPs was evaluated using CNC words and sentences. Variations in the T/C levels between all MAPs were found, although results of the speech discrimination tests demonstrated no statistically significant difference between behavioural and NRT-based MAPs.

Pilot study of intravenous magnesium sulfate in refractory cardiac arrest: safety data and recommendations for future studies.

UNLABELLED: Recent case reports have evidenced a temporal association between administration of i.v. magnesium sulfate (M) and resuscitation from prolonged cardiac arrest refractory to standard (S) ACLS attempts. However, speculation has arisen that M as a vasodilator, may decrease aortic diastolic and coronary perfusion pressure (CPP), aortic systolic and cerebral perfusion pressures (CePP), which may decrease resuscitation rates and neurologic recovery, as compared to standard ACLS alone (SA). OBJECTIVE: To resolve positive beginning evidence vs. negative theory, we conducted a pilot study of M+S vs. SA in refractory cardiac arrest on resuscitation rates (% R, return of stable pulses > 30 min without CPR, first in-hospital cardiac arrest > 5-min duration) and neurologic recovery/survival to hospital discharge (SHD). METHODS: All patients from 1 January 1990-31 December 1991 at Rose Hospital, in cardiac arrest refractory to S through the first epinephrine dose (including 3 defibrillation attempts with pulseless VT/VF) were included in the data analysis, except: (1) patients with trauma, known poisoning, < 18 years, pregnancy excluded; (2) Standard ACLS alone patients with cardiac arrest < 5-min duration were not included in the SA comparison group, because the shortest cardiac arrest time before i.v. MgSO4 administration in the M+S group was 5 min. M+S (N = 29) and SA (N = 33) groups were also comparable on mean age (72-73 years) in this open-label prospective case-matched control group study. RESULTS: SHD rates were nearly equivalent between M+S (5.2%) and SA (4.5%). Complete or partial neurologic recovery, as best neurologic status post-R, occurred in 21% (6/29) M+S patients vs. 9% (3/33) SA (P = 0.17), even though cardiac arrest time on the study code call for resuscitated patients averaged shorter with SA (14.2 min) than M+S (19.8 min). M was frequently administered late in the resuscitation attempt--code call to M administration averaged 16.5 min (< 10 min in only 4/28 patients). A trend toward increased % R with M was evidenced: 21% (7/33) SA vs. 35% (10/29) M+S (P = 0.21). A temporal association between M administration and first return of spontaneous circulation (ROSC) was also documented in 4 of 10 M+S patients (pulseless electrical activity (3)/pulseless VT (1)), who had first ROSC/R occur within 0.5-2.25 min following first i.v. M bolus delivery, after 11-30 min (mean = 20 min) of continuous pulseless rhythm refractory to standard ACLS. All M+S resuscitations occurred within the dose range 2.5-5 g (i.v. push): 3/6 (50%) and 7/13 (54%) R occurred with 1-3 g and 4-5 g MgSO4, respectively (at least 11/13 patients had peripheral i.v. delivery with 4-5 g M). Analyzing post-ROSC hypotension proved important, as 50% of pts with first recorded systolic BP post-ROSC < 90 mmHg were resuscitated vs. 83% with > 90 mmHg (P = 0.10). A trend toward increased post-ROSC hypotension was evidenced with i.v. MgSO4: Recorded first or second systolic BP < 90 mmHg post-ROSC occurred in 66% of M+S vs. 42% of SA patients. All 3 M+S patients having a wide open i.v. levophed infusion as vasopressor support, started immediately post-ROSC/i.v. MgSO4 with systolic BP < 90 mmHg and continued at least 15 min (titrating to a systolic BP approximately 110 mmHg), had a temporal association between M delivery and R after 14-30 min of continuous pulselessness refractory to S. CONCLUSION: Human research determining whether i.v. MgSO4 increases long-term survival from refractory cardiac arrest should be vigorously pursued, as it is safe to proceed given the above described considerations.

Resuscitation from prolonged cardiac arrest with high-dose intravenous magnesium sulfate.

We present evidence of resuscitation from prolonged (70-min) cardiac arrest, temporally associated with administration of 8 g intravenous (IV) magnesium sulfate (MgSO4). A patient undergoing liposuction surgery developed bradycardia and a fall in oxygen tension after reversal of general anesthesia with physostigmine. The electrocardiogram (ECG) rhythm degenerated to ventricular asystole, which was refractory to standard therapy, including multiple boluses of epinephrine, atropine, wide-open dopamine, and attempts at right heart pacing. External cardiopulmonary resuscitation (CPR) was continuously maintained with the patient intubated on 100% oxygen. Multiple electric countershocks (x7) and lidocaine were also administered when ventricular tachycardia/ventricular fibrillation (VT/VF) occurred, but without clinical success. Approximately one hour into the resuscitation, after all of the above occurred, 8 g IV MgSO4 was given and countershock repeated. Whereas the 7 previous countershocks had resulted in unsuccessful conversion of VT/VF to a pulseless rhythm (EMD), the 8th countershock (applied immediately after two 4 g boluses of IV MgSO4) resulted in a stable pulse and normal sinus rhythm developing within 4 minutes. The patient recovered without neurologic deficit.

The physical examination in acute cardiac ischemic syndromes.

The physical examination in acute cardiac ischemia remains a valuable tool when done with skill. Ischemia without infarction alters cardiac function, and the physical examination yields findings that reflect these changes. Ischemia with infarction alters structure and function, resulting in physical findings that are usually more dramatic and of longer duration, sometimes permanent. Carefully done, the physical examination provides information that helps in management of the immediate course, predicts prognosis, and allows for better interpretation of cardiovascular tests, both invasive and noninvasive.

Hypothesis: warfarin administered simultaneously with heparin infusion will prevent heparin-discontinuance associated coronary thrombosis.

Recent studies have evidenced an association between the time of heparin discontinuance and coronary artery reocclusion. Some investigators have concluded that inadequate heparinization was responsible, and further heparin infusion or an increase in dose would have been indicated. However, several investigators (Rao: Thrombosis Research 24:181-186, 1981; Marciniak and Gockerman: Lancet September 17:581-584, 1977; Fisken et al.: Lancet December 10: 1231, 1977; Conard et al.: Thrombosis Research 22:507-511, 1981; Kakkar et al.: Lancet January 12:103-104; Green: Lancet February 16:374, 375; Harborne and Nicolaides: Thrombosis Research 43:657-662, 1986; Bonen et al.: Thrombosis Research 27:123-124, 1982; Blomback et al.: Acta Physiologica Scandinavica 58:306-318, 1963; Holm et al.: Scandinavian Journal of Haematology 35:564-569, 1985; Andersson et al.: Thrombosis Research 34:333-340, 1984) have demonstrated that antithrombin III levels are reduced in patients on intravenous heparin. Both reduced antithrombin III levels and reduced rate of antithrombin inhibition of thrombin at the time of heparin discontinuance may increase the risk of coronary rethrombosis. If this theory is correct, increasing heparin infusion may exacerbate this risk. We propose an investigation that will provide evidence for or against the decreased antithrombin III theory, and in doing so, test an experimental therapy designed to prevent coronary reocclusion upon heparin discontinuance. In a randomized, placebo-controlled double-blinded study, we will determine whether simultaneous administration of warfarin with heparin initiation provides more time to increase antithrombin III levels and prevent coronary reocclusion upon heparin discontinuance, compared to heparin without warfarin therapy.

Spontaneous rupture of a coronary artery with false aneurysm formation. Successful surgical repair.

A patient with diffuse atherosclerotic coronary arterial disease was demonstrated to have a spontaneous rupture of the proximal right coronary artery, with formation of a false aneurysm. This was recognized at angiographic study, and the patient subsequently underwent a revascularization operation with suture ligation of the aneurysm.

Systemic embolization of the disk occluder of the Wada-Cutter prosthetic valve. A late complication.

The results in 22 patients in the Denver area with Wada-Cutter prostheses were reviewed. There were 14 late deaths, with an average follow-up of six years. Four cases of valve malfunction not related to thrombosis were documented. There were three cases of embolization of the occluder. A survivor is reported. Clinical evaluation of the group suggested new mitral regurgitation to be a sensitive indicator of impending embolization of the occluder. Documentation of valve malfunction warrants valvular replacement.