EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. II. Detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA).

The cross-reactivity, stereoselectivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine/methamphetamine immunoassay (EM) for the detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) in urine was evaluated. The cut-off concentrations of racemic MDA and MDMA were found to be approximately 800 ng/ml and 3000 ng/ml, respectively. The EM assay demonstrated a high selectivity for the S(+) isomer of both MDA and MDMA. Urines collected over a 24-h period from rats administered 20 mg i.v. racemic MDMA were all positive when analyzed by the EM assay. The EM was found vastly superior to the EMIT d.a.u. polyclonal amphetamine/methamphetamine assay for the detection of MDA and MDMA. The EM assay displayed sufficient sensitivity for detection of these drugs following clinical intoxication.

EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. I. Stereoselectivity and clinical evaluation.

The stereoselectivity, cross-reactivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine(A)/methamphetamine (MA) immunoassay (EM) were evaluated. The cut-off calibrator of the assay was 1000 ng/ml S(+)MA. Analysis of drug-added urines and 72 clinical specimens demonstrated a cut-off for S(+)-amphetamine of approximately 400 ng/ml. The stereoisomeric selectivity of the assay was determined in a concentration vs. response manner by adding pure S(+) or R(-)isomers of A and MA, to drug free urine. The EM assay demonstrated a high selectivity for S(+)-isomers with only one of 16 urine specimens collected following excessive use of nasal inhalers yielding a positive result. This specimen contained 6000 ng/ml R(-)MA. Five-hundred clinical urine specimens were simultaneously analyzed for A or MA by the EM and EMIT-d.a.u. polyclonal (EP) amphetamine assay with 131 positive results confirmed by GC/MS. In five specimens negative by EM while positive by EP, MA was present at concentrations below the 1000 ng/ml cut-off. Two ME false positive results were apparently caused by chlorpromazine (CPZ) metabolites. A study of other phenothiazines or their metabolites gave no false positive results. The possible cross reactivity of the EM assay was further studied for phenyl-isopropylamine analogs or drugs previously reported to react with the EP assay. The EM assay showed much less cross-reactivity than EP to all drugs tested.

The Medtronic-Hall valve: a design in 1977 to improve the results of valve replacement.

The prototype Medtronic-Hall valve was developed from improvements to the Lillehei-Kaster and Björk-Shiley valves. The housing was constructed of a single piece of titanium and the disc was composed of pyrolytic carbon; both materials had shown no structural breakdown in previous clinical use. The valve was tested with pulse simulator and electromagnetic flow meter studies and yielded a high effective orifice area. Results in 110 patients were significantly better with the Medtronic-Hall valve than with either of the previous valves. In the 21-mm aortic valve the peak-peak gradient was 12 mmHg; it was 9.2 mmHg in the 23-mm, 3.8 mmHg in the 25-mm, and 2.5 mmHg in the 27-mm. Studies found 5% of forward flow regurgitation in the aortic position and more than desired regurgitation through the mitral valve. After the opening angle of the mitral valve was reduced to 70 degrees, regurgitation reached an acceptable level and the improved hemodynamics resulted in lower transvalvular gradients than in previous mechanical valves. Some patients are naturally more prone to thromboembolism regardless of valve type or anticoagulant therapy; thus the human factor plays a large role in a valve's success. More randomized studies are needed for accurate valve comparison, in addition to investigations of sewing ring factors. Nevertheless, the Medtronic-Hall valve has been used successfully for 15 years and has exhibited no housing fractures.

Ranitidine interference with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay.

The interference of ranitidine with the monoclonal EMIT d.a.u. amphetamine/methamphetamine immunoassay (ME) was investigated. Urine specimens collected from 23 patients receiving 150-300 mg of ranitidine daily were found to contain 7-271 mg/L of the drug when analyzed by Remedi automated high pressure liquid chromatography. Only patient specimens and urine samples with ranitidine added at concentrations greater than 91 mg/L gave false positive ME results. Of the 63 patient urine samples analyzed by ME, 12 gave false positive results. All false positive results occurred in the first or second void after ingestion. No false positive results occurred with the polyclonal EMIT d.a.u. amphetamine or TDx amphetamine/methamphetamine II assays.

Evaluation of the ETS and ADx urine drug screening immunoassay analyzers.

The Syva ETS and Abbott ADx urine drug testing immunoassay systems were evaluated for analytical performance, ease of operation, data processing, and time of analysis. Urine specimens were analyzed by each system for six drugs of abuse. Discrepancies in drug detection were due to variations in the cut-off concentrations between ADx and EMIT d.a.u. (ETS) reagents. The ETS was found to have several major advantages over the ADx: greater sample load, more convenient "random access," and real time data processing. When analyzing multiple specimens, the turnaround time for the ETS as compared to the ADx was twice as fast for the six-analyte assay. The ADx assay calibrations were stable for two weeks, while the ETS required daily calibration with verification by cut-off calibrators every eight hours. The ETS was found superior to the ADx for multianalyte urine drug screening.

Morbidity in valvular heart replacement: risk factors of systemic emboli and thrombotic obstruction.

A study on a cohort of 839 patients with valvular heart replacement between June 1977 and May 1985 showed that the linearized rates of systemic emboli and thrombotic obstruction were 1.4/100 pts/year for Aortic Valve Replacement (AVR), 2.2/100 pts./year for Mitral Valve Replacement, and 3.00/100 pts./year for Double Valve Replacement (DVR). The 5-year free-from-thromboembolism (TE) survival was 95% for AVR and 92% for MVR. The hazard function (the instantaneous risk) for TE peaked in the first six months after operation for AVR and MVR. Another analysis using the Cox regression model to estimate risk factors of systemic emboli and thrombotic obstruction pinpointed two factors in the AVR group: presence of aortic regurgitation (AR) and age at operation. In the MVR group the sole predictor covariate was sex of the patients, with a higher hazard for females. Our results underline the importance of patient-related factors besides the type of prosthesis as predictors of morbidity from TE.

Surgical considerations for avoiding disc interference based on a ten-year experience with the Medtronic Hall heart valve.

All low profile valves are susceptible to problems related to implant technique, especially immobilization of the occluder. Because the disc-valve-ring clearance may be only a fraction of a millimeter, this complication is a small yet ever present possibility of which the surgeon must be aware. Special care must be taken when implanting low profile valves to eliminate the possibility of disc interference caused by suture ends or intracardiac structures. The surgeon can minimize the risk of disc immobilization by careful attention to precautionary surgical measures described herein.

Risk factors of morbidity and mortality in surgically treated chronic aortic valvular heart disease.

A cohort of 617 patients underwent aortic valve replacement (AVR) the median follow-up time was 3.4 years with a range (0-7.8) years. The incidence of early mortality was 5.0% and the five years survival (77.9 +/- 1.9)%. Risk factors of early mortality and morbidity (Low Output Syndrome) occurring the first 31 days after operation were pinpointed. Another analysis was done to estimate independent predictors of late premature death from all causes, and from specific causes (cardiac related, sudden cardiac). One of the major late morbid events was the appearance of systemic emboli. Its rate was 1.4% pats. Year. Its risk factors were presence of pure aortic regurgitation and advanced age at operation. The relative survival rate was at 5 years of 87.0% for the total cohort, but for our younger patients (age less than 30 years), we reached 99.4%. Our results suggest more aggressive measures to correct the hazard in AVR, and impose carefulness in comparing quality of AVR from different institutions for mortality and morbidity. Finally the results of AVR are rather palliative than curative except for our younger patients where we reached curability.

Risk factors in surgically treated mitral valve disease.

Risk factors for operative mortality and long term survival were identified in 144 patients undergoing mitral valve replacement (MVR). The 3-year survival was 77% at a median follow-up time of 3.01 years, including an early mortality of 7.6%. Nineteen preoperative and perioperative variables were analysed by univariate and multivariate methods. The sole risk factor independently predictive of postoperative death was a poor functional class with a relative risk (RR) of 3.17 compared to patients with a better functional class. Independent risk factors of long term survival were; prior heart operation, presence of mitral regurgitation, age at operation and poor functional class. Estimation of the parameters of the Cox's model gave a predicted 3-year survival ranging from 95% to 11% for the most favourable and the less favourable risk factor combinations. Risk factors that affected late death were the presence of ischemic coronary etiology and poor functional class. Two modes of late death were identified each with its prognostic factor. The most common mode was cardiac-related death, its sole risk factor was the presence of ischemic coronary etiology. The RR ratio was 3.2 for patients with ischemic coronary etiology, compared to patients with other etiologies. Sudden cardiac death was the next, its independent risk factor was the age at operation with increasing hazard for younger patients. The RR ratio was 8.55 for a 35-year-old patient compared to a 60-year-old patient.

Risk factors in surgically treated aortic and mitral valve disease.

Risk factors in simultaneous aortic and mitral valve replacement were studied in 78 patients. Risk factors for early mortality, according to a stepwise logistic regression model, were male sex, concomitant heart surgery and prior valve replacement. For low-output syndrome, the major morbid event, the risk factors were endocarditic etiology, concomitant heart surgery and prior valve replacement. Survival curves were used to estimate univariate risk factors for total mortality. With a multivariate procedure, using the Cox regression model, two covariates were pin-pointed as independent prognostic factors in total mortality, viz. mitral regurgitation and concomitant heart surgery. The Cox model also showed the two covariates ischemic heart disease and endocarditic etiology to be risk factors in late mortality. Predicted 3-year survival was estimated with different combinations of these risk factors. The results were compared with earlier reports.

Burns: epidemiology and the effect of a prevention programme.

Epidemiological data concerning 1391 patients hospitalized at the Burns Unit, Odense University Hospital during a 17-year period are presented. The annual incidence showed a steady downward trend of 3 per cent per year. Scald and fire were the most important causes of burn injuries. Among children a significant reduction in burns due to scalds and electrical or corrosive injuries was noted. The rate of injury among adults and the elderly was constant. These results might reflect an intensive information campaign in the media, revisions of laws and regulations and improvements in the safety of household products, especially directed towards thermal injuries among smaller children.

Admissions to a new burn unit in Gizan, Saudi Arabia.

In an attempt to introduce western treatment principles, Danish chiefs have been in charge of a new Burn Unit in Gizan for the first 2 years and 9 months. We have treated 348 burned patients with a median 16 per cent estimated area of burn (EAB). One-quarter of the patients had more than 25 per cent EAB. Flame burns were the most frequent and females suffered the more severe injury. The mechanisms of burning are discussed.

Burn treatment in a new burn unit in Gizan, Saudi Arabia.

During the 2 years and 9 months when a new burn unit was under Danish leadership, 348 admitted patients were treated. Exposure treatment and Ringer's lactate were used for burn shock. Due to lack of blood, infections and discharge against medical advice, only 106 patients had operations. Fifty-six patients died from their burns and concomitant diseases, 44 of these were women, often with very extensive burns. Our results are comparable to those reported from departments in similar geographic areas. The special problems in treatment are discussed.

Intra-aortic balloon pumping support in surgically treated valvular heart disease: prognostic factors and survival.

Prognostic factors of Low Output Syndrome (LOS) requiring operative circulatory support by intra-aortic balloon-pumping (IABP) counterpulsation, were analysed in a population of 841 patients who underwent heart valve replacement surgery between June 1977 and May 1985. The incidence of IABP circulatory support was 6.8%. Mean survival time of patients who needed IABP was 2.35 years +/- 0.425 vs 6.30 years +/- 0.103 for patients who didn't have this complication. A multivariate analysis using the logistic model was done to pinpoint factors predictive of IABP support. The prognostic factors were pre-operative functional class, presence of prior valve replacement, presence of concomitant surgery and presence of endocarditic etiology. The subgroup of 58 patients undergoing balloon counterpulsation was analysed for factors predictive of survival using a multivariate analysis of the Cox' model. Presence of aortic or mitral regurgitation was found to be the independent risk factor of mortality. Using a combination of prognostic factors, we pinpointed groups of patients at high risk of needing post-operative balloon pump counterpulsation support. The necessity of an alternative procedure for the mechanical support of the failing circulation is underlined.

Prognostic variables in late follow-up of aortic valve replacement using the proportional hazard model: a study on patients using the Medtronic-Hall cardiac prosthesis.

An alternative approach to the study of the follow-up of patients with heart prostheses is the use of the reliability theory (hazard function) and proportional hazard model (Cox's model). In a population of 480 patients who underwent AVR in the period from June 1977 to January 1983, with a mean follow-up time of 2.8 years, 16 preoperative variables were considered. From this pool of variables, six entered the regression model in a time-independent mode. These were age at operation, sex, preoperative NYHA classification, presence of AI, presence of endocarditis and presence of atrial fibrillation on ECG, none of which entered the model in the time-related mode. Another multifactorial approach, using a stepwise regression analysis to examine primary predictive factors that independently correlate with survival, while simultaneously accounting for the other previous variables, showed that the variables with additive prognostic value were age at operation, presence of AI and presence of endocarditis. Based on this model, a forecast five-year survival rate ranging from 88 to 14 per cent was found at the end of the fifth year. For the most favourable and the worst combinations of these prognostic variables, a patient-specific forecast five-year survival rate was drawn up. Our results were compared, using univariate and multivariate methods, with the results found in the literature, and the implications of this comparison were discussed.

Continuous monitoring of cardiac output postoperatively using an implantable Doppler probe.

The authors evolved a Doppler probe which can be attached to the ascending aorta intraoperatively. Using a pulsed echo Doppler flowmeter operating at 2 mHz, cardiac output was continuously measured during the first 2 days after open-heart surgery in 20 patients. The internal diameter of the aorta was assessed with ultrasound echo technique. The probe was fixed to the ascending aorta with a double suture through the adventitia. The suture was tightened by means of a long tourniquet which was passed through an infraxiphoid skin incision, between the two chest drains. A stable position providing adequate signals was achieved by use of probes with stabilizing "side flaps". In 8 cases the method was compared with the thermodilution technique using Swan-Ganz catheters. Analysis of 44 simultaneously performed measurements revealed a highly significant correlation between the two methods, and the results remained comparable throughout the 48-hour test period. There were no complications and all the probes could be easily removed.

Prognostic factors for survival in surgically treated aortic regurgitation.

Aortic valve replacement was performed for 'pure' aortic regurgitation on 118 patients in a 5 1/2-year period ending in January 1983. In an analysis of prognostic factors, 12 variables were considered. The long-term survival rate was significantly greater in men than in women. Other significant factors were the relative heart volume, left ventricular systolic pressure and size of the implanted valve. A multivariate analysis with the Cox regression model, using the pool of variables simultaneously, showed primary predictive factors independently affecting survival to be left ventricular systolic pressure and size of the implanted valve. Based on this model, a patient-specific survival forecast was constructed.