Detection of drug use during pregnancy

Several methods of drug testing are efficacious in identifying and monitoring drug use during pregnancy. Urine screening remains the most commonly used method despite the limited period during which drugs can be detected. Hair has been recognized as a possible alternate test specimen, but wider acceptance of hair testing must await better understanding of drug disposition in hair, answers to the issues relating to interpretation, and the development of less demanding laboratory techniques. Regardless of the matrix used, proper interpretation of the results of drug testing requires familiarity with the sensitivity, specificity, and limitations of the laboratory methodologies employed. Moreover, unconfirmed positive results may actually be false-positives and must be interpreted with caution, particularly if they are the basis for major clinical decisions.     

Using hair analysis, urinalysis, and self-reports to estimate drug use in a sample of detained juveniles

This paper reports select findings of a research project designed to estimate drug use prevalence in a youthful offender population using hair analysis as well as urine testing and interviewing. The project was carried out in Cleveland, Ohio, and Pinellas County, Florida. The findings are consistent with earlier reports on prevalence estimations utilizing a bioassay component. Generally, respondents report drug use infrequently and test positive by assays at rates greater than self-reported use. Urinalysis indicates more drug prevalence than does interview. Hair assays, which have a greater retrospective time window, show even more prevalence than does urine testing. The project affirms results reported in 1994 by Feucht, Stephens, and Walker.     

Yohimbine for erectile dysfunction: a systematic review and meta-analysis of randomized clinical trials

Well-founded pharmacokinetic information is one of the cornerstones of a New Drug Application (NDA) to the Food and Drug Administration (FDA) required to introduce a new drug or a generic equivalent (ANDA) to the marketplace. The service that laboratories engaged in therapeutic drug monitoring provide to support clinical activities is also needed by the pharmaceutical industry during the evaluation and introduction of drugs to the marketplace. In considering this alternative service activity, one must be aware of and compliant with rules established by the FDA for performance of such studies. As specified in CFR 21, Parts 58, 211, and 320, good clinical and laboratory practice indicates that the laboratory should employ a Lab Study Director, who is responsible for the validation of all procedures implemented to support a study protocol, ensures that the laboratory carries out the study following these defined procedures, and personally reviews the results of all testing. The laboratory must validate each procedure by demonstrating and documenting that the procedure does what it is designed to do while meeting the analytical performance specifications required by the study. Laboratory records of all activities must be maintained and available for inspection by the FDA on request. The FDA has authority over all activities related to NDA and ANDA submissions and can bring criminal charges if results of a study are changed because a laboratory deviates from standard procedure. Competent drug monitoring laboratories are fully capable of participating in clinical trials testing activities. Laboratory staff should be fully versed in the FDA rules governing these activities, validate all procedures, and establish systems to verify the procedures are carried out as specified.     

Urine drug testing for social service agencies. A Canadian experience

The introduction of urine drug testing for this program has been considered a success by the social services agencies in Nova Scotia for the following reasons: 1. The results of urine drug testing have been accepted by the Family Courts of Nova Scotia because the urine collection and testing are performed with chain of custody procedures from collection to reporting and the analysis includes confirmation of all positive immunoassay screening tests. 2. Urine drug testing (with established screening and confirmation cut-offs) provides an objective indication of recent drug use compared with relying on self-reporting of drug use. 3. Urine drug testing is believed to be a deterrent to drug use because several individuals with a history of drug use have consistently tested negative for 6 to 12 months (30% of the clients). 4. Some clients with a history of substance abuse are successful in becoming drug free with the support of the social workers and the deterrent effect of random drug testing.     

Immunoassay of digoxin in hair

Digoxin analysis in blood is an essential tool for therapeutic drug monitoring in cardiology because compliance with the treatment is a critical issue for the patient. Unfortunately, in postmortem cases blood digoxin concentration is of poor quality because there is a possible drug redistribution in the corpse and because of digoxin-like factors present in some people's blood. On the other hand, no biological fluid can be obtained at the autopsy. The aim of the present study was to evaluate the ability of an immunological method to determine digoxin in hair, in order to confirm that hair analysis can provide information on digoxin use before death. We studied 35 elderly patients who had been taking digoxin (60-250 micrograms/day) for 1-5 years. Two decontamination procedures were tested: washing by dichloromethane or by water and methanol. Three extraction procedures were compared: crushing in a ball mill and chloroform/acetone: crushing and methanol; enzymatic digestion. Immunoassays were performed by a microparticulate enzyme immunoassay. Serum digoxin levels were also assayed when sampling hair. The best results were obtained after decontamination with water and methanol followed by enzymatic digestion. Hair digoxin concentrations range from 3.6 to 11.4 pg/mg. Those very low concentrations are probably due to low and narrow range serum digoxin levels (0.3-1.4 ng/ml). No correlation was found between hair and blood digoxin. A forensic case is presented with 5 pg/mg digoxin in hair.     

Carbamazepine levels in head hair of patients under long-term treatment: a method to evaluate the history of drug use

Carbamazepine (CBZ) concentrations were determined in the sections of head hair from 40 patients (22 males and 18 females), ages 5 to 81, who were receiving this drug systemically. Hair treatment included dissolution, liquid phase extraction procedures, and immunoassay (Abbott TDx) or high-pressure liquid chromatography (HPLC) analytical techniques. The mean values of CBZ levels in the hair from the 1st section (close to hair root) to the 5th section for female patients were 26.82, 19.18, 17.28, 15.09, and 14.62 micrograms/g according to HPLC measurements. Immunoassay gave generally slightly higher results. The mean values of CBZ in the hair sections according to the immunoassay technique were 30.53, 21.90, 19.83, 17.45, and 16.99 micrograms/g, respectively, from the 1st to the 5th sections. The corresponding mean values for male patients by HPLC and immunoassay techniques were 21.97, 17.30, 15.03, 13.02, and 11.21 micrograms/g and 25.98, 20.52, 17.15, 14.87, and 12.31 micrograms/g. Generally, a reduction of drug concentrations in hair from the first to the subsequent segments was observed. Higher amounts of CBZ were deposited in black, untreated hair (e.g., not dyed or permed). CBZ concentrations in hair sections were found to be dependent on the dosage (r = 0.979, p < or = 0.001) but not on the gender. The data indicate the possible use of hair section testing as a marker of the dosage history and the compliance of patients under long-term treatment with CBZ.     

Evaluation of a flow cytofluorometric method for rapid determination of amphotericin B susceptibility of yeast isolates

A rapid-flow cytofluorometric susceptibility test for in vitro amphotericin B testing of yeasts was evaluated and compared to the National Committee for Clinical Laboratory Standards (NCCLS) M27-T reference broth macrodilution method. The flow cytofluorometric method is based on the detection of decreased green fluorescence intensity of cells stained with DiOC5(3), a membrane potential-sensitive cationic dye, after drug treatment. Testing was performed on 134 clinical isolates (Candida spp. and Torulopsis glabrata). From the dose-response curve obtained for each isolate, three endpoints were calculated by computer analysis (the concentrations at which the fluorescence intensity was reduced by 50, 80, and 90%, i.e., 50% inhibitory concentration [IC50], IC80, and IC90, respectively). A regression analysis correlating these endpoints with the M27-T MICs showed that the best agreement was obtained with IC80. The flow cytofluorometric method showed good reproducibility with control strains. These initial results suggest that the flow cytofluorometric method is a valid alternative to the NCCLS reference method.     

Nonscarring hair loss disorders: the basis for recognition and treatment

Hair loss can be assessed objectively by examining a hair pull sample for stage of growth and hair shaft diameter, getting an estimate of average daily hair loss, and mapping scalp hair density. The history of the loss, the clinical picture, and the growth stage and diameter of the hair when lost all help to establish the type of loss. Hair regrowth occurs without treatment in most types of hair loss. There is as yet no effective treatment for pattern or senescent alopecia, although in women the loss can now be retarded somewhat.     

Preventable trauma deaths in Singapore

The international normalized ratio (INR) is the current standard for monitoring anticoagulation therapy. Although simple to determine, it normally requires venipuncture and extensive laboratory resources for specimen handling and analysis. The portable capillary whole blood coagulation monitor is an alternative to laboratory venipuncture. Its promoted advantages are: it obtains a blood sample by finger-stick versus venipuncture; rapid turnaround time for results; resultant dosage adjustments (as appropriate) performed in minutes versus hours or days after testing; relative ease of use by nonlaboratory personnel; and potential for home monitoring. This project compared the results of INRs obtained through the venipuncture/laboratory process to INRs obtained by the portable monitoring process at the National Naval Medical Center. A correlation coefficient of 0.97 was determined. The difference in the mean INR results of the two testing methods was not clinically significant (p = 0.269). The portable monitor was determined to be a viable alternative to laboratory testing.     

Uptake of nicotine in hair during controlled environmental air exposure to nicotine vapour: evidence for a major contribution of environmental nicotine to the overall nicotine found in hair from smokers and non-smokers

Hair from smokers and non-smokers has been exposed in a dynamic exposure chamber to air nicotine concentrations ranging from 1.5 to 45 and from 20 to 2000 micrograms/m3 for 8 weeks and 72 hr, respectively. Accumulated hair nicotine was quantified by GC/MS. Hair was also collected for direct measurements of nicotine in 0-2, 2-4 and 4-6 cm segments from the scalp. Human hair showed a high affinity for air nicotine and the chamber experiments revealed a linear relationship between the initial hair uptake rates of nicotine and the duration of exposure at all air nicotine concentrations applied. Hair nicotine uptake rate decreased with time after 4 to 6 weeks exposure to 15 and 45 micrograms/m3 air concentrations of nicotine, but not to the 1.5 micrograms/m2 nicotine concentration. Ratio between the hair uptake rate of nicotine and the applied air concentration of nicotine decreased with increasing air concentrations of nicotine. Segment analysis of hair revealed an outward increasing gradient of nicotine in hair. Hair uptake pattern of air nicotine suggests the uptake to be governed by an equilibrium between nicotine in air and nicotine on the hair surface, possibly combined with a slower diffusion process of nicotine from the hair surface into the hair core. The hair segment analysis of nicotine indicates that environmental nicotine is the dominating contributor to the overall nicotine found in hair both from smokers and non-smokers.     

Statistical considerations for design and analysis of a multiperiod crossover study to compare two treatments for migraine headache

The purpose of this paper is to discuss a long-term, multiperiod crossover study to compare two treatments for migraine headache. Principal attention is given to the analysis of an example in which patients randomly received a treatment sequence with test drug for three migraine headaches and placebo for one. An issue that requires attention for this example is the influence of a carryover effect for test drug that was greater when placebo was the subsequent treatment than when test drug was the subsequent treatment. A way to address this issue without excessive loss of power is to consider tests of "total treatment effects," which are weighted averages across headaches of differences between average response to test drug and average response to placebo. Since these weighted averages are linear combinations of treatment effects and carryover effects, their use requires an argument that carryover effects are at least partly a further form of treatment effects. For the example in this paper, this argument is realistic because the test drug could have provided much better relief to migraine headache than other treatment patients might have previously used. A second purpose of the paper is to present some alternative designs for situations like that represented by the example. The structure of variances for alternative specifications for treatment comparison is provided for models of interest for these designs.     

Quality of community drinking water and the occurrence of late adverse pregnancy outcomes

1. The aim of the study was to investigate whether there were differential effects of three different anti-hypertensive medications (cilazapril, atenolol, nifedipine) on cognitive function. 2. A sub-group of patients participating in a large clinical trial of these three drugs, randomly allocated between the three drug conditions, received cognitive assessment at two points before the commencement of treatment and then after 12 and 24 weeks of treatment. Seventy-six patients began treatment, and 55 completed the full course. 3. Tests of learning and memory were designed specially for the study, with a different but comparable version administered on each assessment occasion, in a fixed order. 4. No significant differences between drug groups were found in any index of learning or memory, at any testing occasion. The results were the same whether or not treatment non-completers were included in the analysis.     

The effects of volume and speed of injection in peribulbar anaesthesia

Therapy of detrusor hyperactivity with anticholinergic agents often is followed by adverse drug reactions. Intravesical application may be an interesting alternative. A randomised, single-blind, placebo-controlled, mono-centre clinical trial was carried out in 84 patients with urgency or urge incontinence. Due to intravesical administration of oxybutynin (CAS 5633-20-5) (n = 21) and trospium chloride (CAS 10405-02-4) (n = 21), respectively, a significant increase in maximum bladder capacity and decrease of detrusor pressure accompanied by an increase of residual urine were found in comparison to placebo in urodynamical investigations. Improvement of uninhibited bladder contractions occurred leading to higher filling volume. Under verapamil (CAS 152-11-4) (n = 21) no marked changes in the efficacy variables were found compared with placebo. All patients completed the study and were assessed with regard to efficacy and safety. No adverse events or marked changes in the vital signs were reported. The immediate onset of effect and the lack of adverse drug reactions suggest that treatment with topical oxybutynin or trospium chloride is an effective alternative in patients with intolerable side effects when orally treated. In addition, intravesical administration may be indicated in patients with bladder spasms due to indwelling catheter or in order to increase bladder capacity before percutaneous cystostomy.     

Age-dependent changes in astroglial reactivity in human ischemic stroke. Immunohistochemical study

BACKGROUND: At this time, no definite treatment exists for osteoarthritis disease. Hyaluronate (ARTZ) is one of the most important components of synovial fluid. It is generally accepted that hyaluronic acid protects the articular cartilage and soft tissue surfaces from trauma during joint function. METHODS: Ninety patients with 116 knees diagnosed as early arthritis (mild to moderate) by four senior orthopaedic surgeons were selected to join this study. The trial design was applied with a double-blind model. The selected patients were randomly injected with 2.5 ml drugs (ARTZ or placebo) intra-articularly once a week for five consecutive weeks without the use of local anesthetic drugs. Evaluation results included grading of subjective and objective symptoms and daily activities. The follow-up period was up to six months after initial injection. RESULTS: According to the results of clinical evaluation and statistical analysis, SPH (ARTZ) is quite effective for osteoarthritis knees, and significantly better than the placebo. The effective peak was one week after five injections of ARTZ. The effective period could last up to three months without additional treatment. The efficacy of ARTZ on osteoarthritis knees was more prominent for relief of motion pain and improvement of knee movement. No side effects developed during a six month period. CONCLUSIONS: Based on clinical results here, SPH is a safe drug for administration as an alternative approach to treat the osteoarthritis knee.     

Derivatization procedures for gas chromatographic-mass spectrometric determination of xenobiotics in biological samples, with special attention to drugs of abuse and doping agents

The development of low cost MS detectors in recent years has promoted an important increase in the applicability of GC-MS system to analyze for the presence of foreign substances in the human body. Drugs and toxic agents are in vivo metabolized in such a way that more polar compounds are usually formed. Derivatization of these metabolites is often an unavoidable requirement for gas chromatographic analysis. Application of derivatization methods in recent years has been relevant, especially for silylation, acylation, alkylation and the formation of cyclic or diastereomeric derivatives. Given the relevance of drug of abuse testing in modern toxicology, main derivatization procedures for opiates, cocaine, cannabis, amphetamines, benzodiazepines and LSD have been reviewed. Papers describing the analyses of drugs of abuse in matrixes other than blood, such as hair or sweat, have received special attention. Advances in derivatization for sports drug testing have been particularly relevant for anabolic steroids, diuretics and corticosteroids. Among the several methodologies applied, the formation of trimethylsilyl, perfluoroacyl or methylated derivatives have proved to be both versatile and extensively used. Further advances in derivatization for GC-MS applications in clinical and forensic toxicology will depend on the one hand on the degree of further use of GC-MS for routine applications and, on the other hand, on the alternative progress made for developments in LC-MS or CE-MS. Last but not least, the appearance of comprehensive libraries in which reference spectra for different derivatives of many drugs and their metabolites are collected will have an important impact on the expansion of derivatization in GC-MS for toxicological applications.     

Platelet aggregation inhibitors in neurology

This literature review reports on secondary prevention of ischaemic stroke. The aim of secondary prevention is to protect patients who belong to a risk group from the occurrence of brain infarction. Symptomatic patients with a demonstrated carotid artery stenosis of 70% and more will most probably benefit from carotid endarterectomy if performed by a skilled surgeon in the absence of contraindications. Oral anticoagulant drugs play a minor role in the medical prevention of brain infarction. Antiplatelet drugs, however, have been in use for almost two decades and (meta-)analysis of clinical trials points to acetylsalicylic acid as a drug with a modest but certain contribution of about 15% in the endpoint reduction, even at lower dosages. The addition of dipyridamole to classic acetylsalicylic acid dose appears to increase the endpoint reduction to 30%. Neither dipyridamole nor sulfinpyrazone as monotherapy have been demonstrated to be efficacious in the secondary prevention of ischaemic stroke. Ticlopidine seems a promising alternative for acetylsalicylic acid in those patients who suffer adverse effects from acetylsalicylic acid. Ticlopidine itself, however, has a number of side-effects that limit its application. New clinical trials are under way in order to improve the efficacy of drug treatment in the secondary prevention of brain infarction.     

Biochemical Implications.

Discusses the use of experimental animals, particularly rats, in research exploring the effectiveness of compounds such as painkillers. The author describes an experiment testing the effectiveness of a pain killer, Pentazockine. In past clinical trials, if the drug failed to produce the desired analgesic effect with the rats, further experimentation was terminated. In one particular instance, the investigators in a clinical study chose to ignore past failure of the drug on rats and tested the effect of the drug with humans--and it worked. The implications of these unexpected results on further experimentation with rats is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The diagnosis of drug allergies. Utilizing in vitro mast cell test and IgE inhibition test

With the ever-increasing use of pharmaceuticals and the relatively high risk of developing drug allergies, particularly for patients in hospitals and for ambulatory patients with a history of drug allergy, the need to develop in vitro assays for drug allergy is great. In the early 1970's a mast cell technique was developed for diagnosis of drug allergies. A PRIST inhibition assay has also recently been developed to detect IgE antibodies to drug allergens. This test has also been referred to as the Total IgE Inhibition Test by Specific Drug Allergen, and is a variant of the in vitro RAST Test. In vitro mast cell and IgE inhibition tests are applied for identification of drug and chemical allergens and for their cautious clinical trial to prevent future drug and chemical reactions. Over the last eight years, over 1,300 patients were examined utilizing the mast cell technique. Over 100 drugs were tested, with penicillin, barbiturates, "caine" derivatives and sulfonamides most frequently employed. Of 270 patients with well-defined drug reactions, 190 (70 per cent) gave a positive response to the mast cell test. Eighty-five per cent of sera tested with Type I reactions gave a mast cell response. Of these, a group of 30 patients was studied with PRIST inhibition as well. Procedures for comparative testing of necessary drugs and/or chemicals in cases of high anaphylaxis risk of reaction in the clinical setting, hospital or office are included in the study as well as individual case reports. Mast cell assay coupled with IgE inhibition has been successfully used to diagnose drug and chemical allergic reactions. The incidence of positivity is high when the offending drug causes a Type I allergic reaction. The cases reported indicate that both the Mast Cell and the PRIST inhibition assays are useful for diagnosing and setting the clinical treatment and clinical course of the patient. The mast cell assay would be potentially employed for patient use in hospitals where the incidence of drug allergy is highest and for occupational health in the chemical industry. The greatest potential would be in outpatient care applied to patients with multiple drug allergies in the selection of safe drugs (test negative by both methods, and other clinical studies) for future drug usage.     

Drugs for conversion of atrial fibrillation

Atrial fibrillation is the most common arrhythmia in patients visiting a primary care practice. Although many patients with atrial fibrillation experience relief of symptoms with control of the heart rate, some patients require restoration of sinus rhythm. External direct current (DC) cardioversion is the most effective means of converting atrial fibrillation to sinus rhythm. Pharmacologic cardioversion, although less effective, offers an alternative to DC cardioversion. Several advances have been made in antiarrhythmic medications, including the development of ibutilide, a class III antiarrhythmic drug indicated for acute cardioversion of atrial fibrillation. Other methods of pharmacologic and nonpharmacologic cardioversion remain under development. Until the results of several large-scale randomized clinical trials are available, the decision to choose cardioversion or maintenance of sinus rhythm must be individualized, based on relief of symptoms and reduction of the morbidity and mortality associated with atrial fibrillation.