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PubMedDate not supplied

[Effect of home-made narcotics on infectious activity of HIV-1].

The stability of human immunodeficiency virus, type 1 (HIV-1), strain IIIB, was studied in liquid preparations of homemade drugs. The "Vint" preparation (containing Methamphetamine and obtained from Ephedrine) as well as "Khanka" (a liquid surrogate opiate made from poppy straw) were analyzed within the case study. HIV-1/IIIB was shown to maintain its infectious activity in "Khanka" at room temperature for least 7 days. The HIV-1 activity in neutralized "Vint" did not essentially change after a 30-minute incubation at pH 7.0. While an incubation in the acid "Vint" solution entailed a more rapidly decreasing activity. However, the virus infection ability preserved during the entire time period, during which the drug was fit for injections, i.e. for 30 minutes at room temperature or for 20 hours at 4 degrees C. Therefore, the infection virus could well preserve in the "Khanka" and "Vint" solutions after its entry, with infected blood, of large volumes of the discussed drugs. The mentioned big volumes of HIV-1 contaminated drugs, shared later into ready-to-use portions, could be the cause for HIV-1 dissemination among those who practice the parenteral administration of these substances. Besides, "Khanka" was shown to have little or no effect on the virus replication to cell culture MT-4. Its presence brought about an insignificant 1.5-fold increase in the viral stock (observed on days 2 and 3 after contamination) only when 2 x 10(5) MT-4 cells per ml and HIV-1/IIIB TCID 50 0.005 were used.

Anti-HIV Agents↗
PubMed1997

Determination of drug exposure using hair: application to child protective cases.

The use of hair as a specimen for the determination of drug use remains controversial. Scientists disagree upon whether environmental drug contamination (e.g. smoke) can be differentiated from actual drug use. Children whose parents use drugs (particularly crack) at home are considered to be at risk. Using the hair of the children to determine exposure gives extra credibility to the child protective services and allows them to remove children from dangerous households. Children are tested when there are credible reasons for suspecting drug exposure. In Blackhawk Country, Iowa, this program was implemented in late 1994, and since then many children have tested positively for drugs, the majority of the hair containing cocaine or methamphetamine. In some cases, cocaethylene and benzoylecgonine were also found in the hair of the children. While the presence of benzoylecgonine can be explained by exposure to crack smoke, the presence of cocaethylene suggests ingestion of cocaine and alcohol. Blackhawk Country Juvenile Court have found the program to be so useful in helping children, that they have extended hair testing from Child Protective allegation investigations to ongoing court cases and even delinquency hearings.

Adolescent↗
PubMed1995

Seroepidemiology of hepatitis B virus in a population of injecting drug users. Association with drug injection patterns.

To investigate the epidemiology of hepatitis B virus (HBV) infection among injecting drug users, the authors assessed the prevalence of HBV seromarkers among 2,558 injecting drug users recruited through street outreach in Baltimore, Maryland, in 1988-1989. Eighty percent of the drug users had at least one HBV seromarker. HBV seropositivity was associated with increasing age, duration of injecting drug use, African-American ethnicity, injecting drugs at least once daily, and sharing needles or visiting "shooting galleries" during the previous 11 years, but not with high-risk sexual behaviors or a history of sexually transmitted disease. This finding is possibly due to the relative inefficiency of sexual transmission as compared with parenteral transmission in injecting drug users. In addition, HBV seropositivity was strongly associated with seropositivity for hepatitis C virus and human immunodeficiency virus. The authors conclude that HBV transmission among injecting drug users occurs primarily through the sharing of contaminated drug injecting equipment rather than through sexual relations, and that efforts to prevent HBV infection must target injecting drug users early in their injecting careers.

Adult↗
PubMed1976

Detection of amphetamine and methamphetamine-type materials in pharmaceutical and biological fluids by fluorometric labeling.

A rapid and sensitive method for detecting amphetamine and methamphetamine in drug preparations and biological fluids has been developed. Amphetamine and methamphetamine in pharmaceutical and clandestine drug preparations can be easily screened from other contaminating drugs and readily identified by their fluorescence, with subsequent separation accomplished by TLC. The same general procedure can also be used to detect amphetamine and methamphetamine in human urine at concentrations of 0.1 mug/ml.

4-Chloro-7-nitrobenzofurazan↗
PubMed1977

[Quantitative analysis of particulate matter in infusion solutions, administration sets and additives (author's transl)].

There have been recevitly many comments on clinical and experimental reports which have demonstrated the safety problems associated with parenteral drugs contaminated with particles. Some countries have developed recommendations with a standard for counting of particles and their limits. Based on these limits, we have made a critical quantitative analysis of particulate matter in the most common commercially produced solutions, of particles added during manipulations in clinics and addition of drugs. Most authorities agree that particulate contamination should be kept to a minimum, above all in an intensive-care-unit where patients receive large quantities of solutions. As the risk to the patient is unacceptably high, many authors ask for filters to prevent the injection of particles in the bloodstream and their pathological consequences. A filter pore-size of 5 to 10 micron should be able to reduce this problem in a sufficient manner, without decreasing the infusion flow; whereas membrane-filters (0.22 micron), with their own problems, could also eliminate bacteria together with their microbiological hazards. Another source of particulate matter is represented by the injection of two or more drugs, administered at the same time, which may lead to chemical incompatibilities. This problem is not yet defined very well. To complete our quantitative analysis, we decided to start a prospective clinical study.

Critical Care↗
PubMed2005

Oral fluid collection: the neglected variable in oral fluid testing.

The potential to use oral fluid as a drug-testing specimen has been the subject of considerable scientific interest. The ease with which specimens can be collected and the potential for oral fluid (OF) drug concentrations to reflect blood-drug concentrations make it a potentially valuable specimen in clinical as well as forensic settings. However, the possible effects of the OF collection process on drug detection and quantification has often been over looked. Several studies have documented that drug-contamination of the oral cavity may skew oral fluid/blood drug ratios and confound interpretation when drugs are smoked, insufflated or ingested orally. OF pH is predicted to have an effect on the concentration of drugs in OF. However, in a controlled clinical study, the effect of pH was less than that of collection technique. Mean codeine OF concentrations in specimens collected a non-stimulating control method were 3.6 times higher than those in OF collected after acidic stimulation. Mean codeine concentrations were 50% lower than control using mechanical stimulation and 77% of control using commercial collection devices. Several factors should be considered if a commercial OF collection device is used. In vitro collection experiments demonstrated that the mean collection volume varied between devices from 0.82 to 1.86 mL. The percentage of the collected volume that could be recovered from the device varied from 18% to 83%. In vitro experiments demonstrated considerable variation in the recovery of amphetamines (16-59%), opiates (33-50%), cocaine and benzoylecgonine (61-97%), carboxy-THC (0-53%) and PCP (9-56%). Less variation in collection volume, volume recovered and drug recovery was observed intra-device. The THC stability was evaluated in a common commercial collection protocol. Samples in the collection buffer were relatively stable for 6 weeks when stored frozen. However, stability was marginal under refrigerated conditions and poor at room temperature. Very little has been published on the efficacy of using IgG concentration, or any other endogenous marker, as a measure of OF specimen validity. Preliminary rinsing experiments with moderate (50 mL and 2 x 50 mL) volumes of water did not reduce the OF IgG concentration below proposed specimen validity criteria. In summary, obvious and more subtle variables in the OF collection may have pronounced effects on OF-drug concentrations. This has rarely been acknowledged in the literature, but should to be considered in OF drug testing, interpretation of OF-drug results and future research studies.

Drug Stability↗
PubMed1994

[Significance of elevated transaminase levels at the end of pregnancy].

During normal pregnancy, serum transaminase levels remain within normal limits. An elevated level observed in a pregnant woman always signals a disease process, most often of hepatic origin, but in certain cases, of muscular origin. During the last three months of pregnancy and in the immediate post partum period a large number of liver diseases can cause elevated transaminase levels, depending upon the clinical presentation. In everyday practice, a complete liver battery together with specialized consultation is required for all pregnant women with raised transaminase levels. Toxaemia gravis may be evident in patients with severely raised blood pressure, especially if seizures occur. Epigastric or subcostal pain should suggest hepatic involvement. Hypertension may however be absent and epigastric or left shoulder pain may be the only clinical signs. Acute liver steatosis is 20 to 50 times more rare than toxaemia and may cause nausea and vomiting. Certain non-specific signs such as asthenia, anorexia, polyalgia, abdominal pain, diarrhoea and fever, together with pruritus should suggest acute hepatitis. A 25-fold increase in transaminase level is commonly encountered. The risk of fulminating hepatitis is less than 1/1000 but should always be entertained. All drugs should be stopped and careful research for recent xenobiotic contamination (drugs, infusions, alphamethyldopa, etc.) should be undertaken. Viral hepatitis requires serovaccination of the newborn at birth. Herpetic hepatitis is rare but requires rapid diagnosis (liver biopsy) and treatment with acyclovir in addition to cesarean section and treatment of the newborn at birth. Rare cases of hepatitis E may occur after a stay in North Africa, the Middle-East, Southeast Asia or Mexico. Chronic cases with or without temporary pruritus suggest infectious hepatitis B or C although, in chronic hepatitis C, serum transaminase levels often return to normal during pregnancy. Rare cases of asymptomatic elevations of serum transaminase levels can reveal subclinical chronic hepatitis.

Acute Disease↗
PubMed1990

Toxic risks of inappropriate therapy.

Drug therapy may produce toxicity. Patient individuality or drug interactions account for many cases of poisoning, but other factors such as genetic predisposition, drug contamination or human error are also known causes. Examples of various types of drug poisoning are given, illustrating the role of the clinical chemist in minimizing or studying drug toxicity.

Drug Interactions↗
PubMed1986

Demonstration of cutaneous doxorubicin extravasation by rhodamine-filtered fluorescence microscopy.

Accidental extravasation of the widely used antineoplastic anthracycline doxorubicin (adriamycin) is capable of causing serious and on-going skin and soft tissue necrosis leading to loss of limb function. The only effective cure has been the complete surgical excision of drug-contaminated tissue. Surgical excisions preparatory to skin grafting have often underestimated the extent of drug infiltration into tissue. Using an experimental technique utilizing the drug's natural property of red fluorescence, we were able to effect complete surgical excision by rhodamine fluorescence microscopy in frozen sections of resected skin.

Child, Preschool↗
PubMed1999

Bioassays for the detection of growth-promoting agents, veterinary drugs and environmental contaminants in food.

Residues of growth-promoting agents, veterinary drugs and environmental contaminants in food products are routinely analyzed with chemical-analytical methods, using physical and spectrometric properties of a compound. Since residue limits are in general based on biological properties of compounds, bioassays offer in theory a good alternative. As a consequence, these assays are much more suitable for the detection of mixtures of compounds with common biological properties, including possibly unknown agonists. Using modern molecular biological techniques, a new generation of bioassays has been developed, showing in general a higher sensitivity and specificity for the target compounds. The CALUX (chemical activated luciferase expression) assay was developed for the detection of polyhalogenated compounds, based on their affinity for the aryl hydrocarbon (Ah) receptor. This paper focuses on the specificity of the assay. The benzimidazole compounds oxfendazole, fenbendazole, febantel, thiabendazole, mebendazole, omeprazole, lanzoprazole and benomyl were shown to give a positive response in the assay. Similar results were obtained with dexamethasone, corticosterone and cortisol, which in addition were able to enhance the response obtained with TCDD. Similarly to the flavonoids alpha- and beta-naphtoflavone, the reported Ah receptor antagonist 4-amino-3-methoxyflavone showed a strong positive response at a concentration of 400 microM, but failed to inhibit the response obtained with TCDD. It is concluded that the chances of false-negative results appear to be minimal and can be recognized. False-positive or, better, unwanted results are in theory more likely to occur. Possible solutions to avoid or detect these type of results are discussed. In general, these kinds of assays offer great possibilities for screening of food samples. In addition to the further optimization of these assays, future work should be focused on the development of rapid, sample and selective extraction procedures.

Animals↗
PubMed2006

In vitro pyrogen test for toxic or immunomodulatory drugs.

Pyrogenic contaminations of some classes of injectable drugs, e.g. toxic or immunomodulatory as well as false-positive drugs, represent a major risk which cannot yet be excluded due to the limitations of current tests. Here we describe a modification of the In vitro Pyrogen Test termed AWIPT (Adsorb, Wash, In vitro Pyrogen Test), which addresses this problem by introducing a pre-incubation step in which pyrogenic contaminations in the test sample are adsorbed to albumin-coated beads. After rinsing, the beads are incubated with human whole blood and the release of the endogenous pyrogen interleukin-1beta is measured as a marker of pyrogenic activity. Intentional contaminations with lipopolysaccharide were retrieved from the chemotherapeutic agents paclitaxel, cisplatin and liposomal daunorubicin, the antibiotic gentamicin, the antifungal agent liposomal amphotericin B, and the corticosteroid prednisolone at lower dilutions than in the standard in vitro pyrogen test. This represents a promising new approach for the detection of pyrogenic contamination in drugs or in drugs containing interfering additives and should lead to improved safety levels.

Adsorption↗
PubMed1990

The Edinburgh cohort of HIV-positive drug users: current intellectual function is impaired, but not due to early AIDS dementia complex.

Eighty people, all infected by HIV-contaminated drug injection equipment between 1983 and 1984, completed the National Adult Reading Test (NART) and selected revised Wechsler Adult Intelligence Scale (WAIS-R) subtests. Demographic variables (age, sex, years of education, and social class) were recorded as additional indices of premorbid functioning. Cross-sectional comparison of NART and WAIS-R scores showed that cognitive function was not more impaired with increasing severity of HIV illness, as defined by clinical staging. Nor were HIV-positive patients more impaired than a control group of seronegative drug users. Mean NART scores did not differ significantly from that predicted by a regression model, indicating that the NART can be reliably used to estimate premorbid intelligence for this population. However, current performance on WAIS-R subtests was below that expected from population models of cognitive function that combine measures of premorbid IQ and demographic factors, providing evidence of impaired intellectual function. Currently observed cognitive deficits are probably more due to drug use than to the insidious onset of AIDS dementia complex.

AIDS Dementia Complex↗
PubMed2005

Drug sharing among heroin networks: implications for HIV and hepatitis B and C prevention.

Qualitative and quantitative findings from the baseline survey of a longitudinal, socially-focused blood-borne disease intervention study among 611 heroin IDU in Denver indicate that high risk injection practices-the sharing of contaminated drug solution in particular-often occur as a consequence of how heroin is obtained, the quantity obtained and the setting where it is injected. Contamination occurs if a contaminated syringe is used to liquefy and apportion the shared drug. In our cohort of 304 heroin injecting networks there was at least one member who, when asked to describe their last injection, reported dividing the drug as a liquid (82%), using a reservoir of water that syringes had been rinsed in to mix drugs (67%), using a common cooker (86%)-a proxy for drug sharing-and beating a shared cotton filter (58%). In contrast, only 22% reported syringe sharing. Variables associated with various injection practices included location of the last injection episode, quantity of drug injected, dope sickness, and years injecting. When compared to those who injected in a safe setting, those in an unsafe location had almost three times the odds (OR = 2.9; 95% CI: 1.9, 4.6) of being part of an injection episode where there was cooker sharing; and the smaller the quantity of heroin (< or =1/4 gram v. > 1/4 gram) present at the episode, the greater the odds that cooker sharing occurred (OR = 1.8; 95% CI: 1.2, 2.6). Use of a used, unbleached syringe to prepare shared drugs had twice the odds of occurring in "unsafe" v. safe settings (OR = 2.2; 95% CI: 1.3, 4.0) and in episodes in which a participant was dopesick (OR = 2.1; 95% CI: 1.2, 3.6). In summary, risky injection practices occur within an injection process that is, in part, a response to a structurally imposed risk environment. Lessening the blood-borne disease risks embedded within this process requires interventions designed to mitigate the environmental factors that influence it, including syringe accessibility, law enforcement strategies and the settings where IDU inject drugs.

Adolescent↗
PubMed2005

Environmental contamination with cytotoxic drugs in healthcare using positive air pressure isolators.

Occupational exposure to cytotoxic drugs of hospital personnel involved in their preparation and administration is a major issue: ever since the introduction of protective measures in recent decades, the handling of these drugs has always been referred to as an occupational health hazard. Isolator technology was one of the protective equipments aimed at providing safe handling, but it has not yet been studied regarding contamination. The present study evaluates surface contamination with four cytotoxic drugs [cyclophosphamide (CP), ifosfamide (IF), 5 fluorouracil (5FU) and methotrexate (MTX)] by wipe sampling in two hospital pharmacies. Wipe samples were taken from work surfaces both located inside and outside the isolators. In addition, working gloves, the surface of infusion bags filled with 5FU or CP, and gloves used in simulation of drug administration were analyzed. Contamination was routinely found inside the isolators but rarely outside the isolators, indicating that the isolator technology is offering good protection of the cytotoxic drug handlers as well as the environment during preparation. On the other hand, contamination was found on the surfaces of infusion bags and gloves in contact with infusion bags filled with cytotoxic drugs. Consequently, personal protective equipment is still recommended during the manipulation and administration of the drugs because of potentially contaminated drug vials and final products.

Antineoplastic Agents↗
PubMed2002

The general mixing of addicts and needles in a variable-infectivity needle-sharing environment.

In this paper we develop and analyse a model for the spread of HIV/AIDS amongst a population of injecting drug users. The model we discuss focuses on the transmission of HIV through the sharing of contaminated drug injection equipment and in particular we examine the mixing of addicts and needles when the AIDS incubation period is divided into three distinct infectious stages. The impact of this assumption is to greatly increase the complexity of the HIV transmission mechanism. We begin the paper with a brief literature review followed by the derivation of a model which incorporates three classes of infectious addicts and three classes of infectious needles and where a general probability structure is used to represent the interaction of addicts and needles of varying levels of infectivity. We find that if the basic reproductive number is less than or equal to unity then there exists a globally stable disease free equilibrium. The model possesses an endemic equilibrium solution if the basic reproductive number exceeds unity. We then conduct a brief simulation study of our model. We find that the spread of disease is heavily influenced by the way addicts and needles of different levels of infectivity interact.

Computer Simulation↗
PubMed2004

Sternoclavicular septic arthritis: review of 180 cases.

We review 170 previously reported cases of sternoclavicular septic arthritis, and report 10 new cases. The mean age of patients was 45 years; 73% were male. Patients presented with chest pain (78%) and shoulder pain (24%) after a median duration of symptoms of 14 days. Only 65% were febrile. Bacteremia was present in 62%. Common risk factors included intravenous drug use (21%), distant site of infection (15%), diabetes mellitus (13%), trauma (12%), and infected central venous line (9%). No risk factor was found in 23%. Serious complications such as osteomyelitis (55%), chest wall abscess or phlegmon (25%), and mediastinitis (13%) were common. Staphylococcus aureus was responsible for 49% of cases, and is now the major cause of sternoclavicular septic arthritis in intravenous drug users. Pseudomonas aeruginosa infection in injection drug users declined dramatically with the end of an epidemic of pentazocine abuse in the 1980s. Sternoclavicular septic arthritis accounts for 1% of septic arthritis in the general population, but 17% in intravenous drug users, for unclear reasons. Bacteria may enter the sternoclavicular joint from the adjacent valves of the subclavian vein after injection of contaminated drugs into the upper extremity, or the joint may become infected after attempted drug injection between the heads of the sternocleidomastoid muscle. Computed tomography or magnetic resonance imaging should be obtained routinely to assess for the presence of chest wall phlegmon, retrosternal abscess, or mediastinitis. If present, en-bloc resection of the sternoclavicular joint is indicated, possibly with ipsilateral pectoralis major muscle flap. Empiric antibiotic therapy may need to cover methicillin-resistant Staphylococcus aureus (MRSA).

Adolescent↗
PubMed2004

Monocyte activation test for pro-inflammatory and pyrogenic contaminants of parenteral drugs: test design and data analysis.

An optimised test designed for an in vitro monocyte activation test for pro-inflammatory and pyrogenic contaminants of parenteral drugs is described, together with ways to address the inherent variability of such assays in which cells are cultured using 96-well plates. The test preparation is cultured with peripheral blood mononuclear cells (PBMNC) and the contaminants in the test article stimulate the release from the cells of the endogenous pyrogenic cytokine interleukin-6 (IL-6). The test system is in use within the pharmaceutical industry and at a national control authority for detecting pro-inflammatory and pyrogenic contaminants, including 'rabbit-negative' and 'LAL-negative' non-endotoxin pyrogens. Products tested include small molecules, biologicals and vaccines. The PBMNC/IL-6 monocyte activation test has been approved by the US FDA as an 'end-product release test' and also is being used for in-process testing.

Cell Culture Techniques↗