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Biomedical subjects

S D Ferrara

Publications and source records attributed to S D Ferrara.

At least 19 recordsLinked to original sources
PubMed2001

Determination of midazolam in human plasma by solid-phase microextraction and gas chromatography/mass spectrometry.

A new method is described for the qualitative and quantitative analysis of midazolam, a short-acting 1,4-imidazole benzodiazepine, in human plasma. It involves a plasma deproteinization step, solid-phase microextraction (SPME) of midazolam using an 85-microm polyacrylate fiber, and its detection by gas chromatography/mass spectrometry (GC/MS) in selected ion monitoring (SIM) mode, using pinazepam as internal standard. The assay is linear over a midazolam plasma range of 1.5-300 ng/mL, relative intra- and inter-assay standard deviations at 5 ng/mL are below 7%, and the limit of detection is 1 ng/mL. The method is simple, fast and sufficiently sensitive to be applied in clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring.

Anti-Anxiety Agents↗
PubMed2001

[Medico-legal features of early discharge in acute myocardial infarction and chest pain].

The authors' aim is to outline some of the main medico-legal problems in cardiology, especially those regarding the premature hospital discharge of patients with undefined chest pain and/or with acute myocardial infarction. After a brief overview on the etiology and clinical definition of chest pain and myocardial infarction, premature hospital discharge is defined and the incidental medico-legal risks that physicians operating in such situations are exposed to are pointed out. Next, the profiles regarding both the positive and negative views of professional medical responsibility are described. In the negative frame, the authors outline the most frequent civil and penal aspects of the unpremeditated responsibility. Then the physician's error, in both qualitative (generic or specific guilt) and quantitative (degree) terms, is considered; particularly, negligence, imprudence and inexperience, as qualitatively accepted meanings of generic guilt, are dealt with by adopting illustrative cases settled in the light of the right legal interpretation. The phases of the diagnostic or prognostic error are evaluated, and clinical protocols, as a reference parameter for the identification of error, are considered. Lastly, the problem of causality, essential condition for the judgment about the professional responsibility, and the problem of the patient's consent, including an evaluation of the legal capability or incapability about the declaration of consent, are examined closely.

Chest Pain↗
PubMed2000

Determination of gamma-hydroxybutyric acid (GHB) in plasma and urine by headspace solid-phase microextraction and gas chromatography/positive ion chemical ionization mass spectrometry.

A new method for the qualitative and quantitative analysis of gamma-hydroxybutyric acid (GHB) in plasma and urine samples is described. It involves the conversion of GHB to gamma-butyrolactone (GBL), its subsequent headspace solid-phase microextraction (SPME), and detection by gas chromatography/positive ion chemical ionization mass spectrometry (GC/PICI-MS), using D(6)-GBL as internal standard. The assay is linear over a plasma GHB range of 1-100 microg/mL (n = 5, r = 0.999) and a urine GHB range of 5-150 microg/mL (n = 5, r = 0. 998). Relative intra- and inter-assay standard deviations, determined for plasma and urine samples at 5 and 50 microg/mL, are all below 5%. The method is simple, specific and reasonably fast. It may be applied for clinical and forensic toxicology as well as for purposes of therapeutic drug monitoring.

4-Butyrolactone↗
PubMed2000

[Alcohol, drugs, pharmacologic agents, and street safety].

Deaths due to road accidents during weekends have become a worrying phenomenon in Italy. With the aim of highlighting the role of psychotropic substances (alcohol, drugs of abuse) in causing road accidents, a survey based on clinical and chemico-toxicological analyses has been carried out on car drivers in the Veneto region during night weekends since 1994. Rapid clinical screening was carried out on 7952 drivers. 1399 of these, suspected to be under the influence of psychotropic substances, were subjected to complete clinical and toxicological ascertainment involving the following procedures: a) anamnesis, aiming at evidence of possible current or past use of psychotropic substances; b) objective clinical examination, aiming at finding evidence of recent (signs of acute or chronic intoxication) or past use (signs of withdrawal or associated organic pathologies) of psychotropic substances; c) double sampling of blood and urine and chemico-toxicological analysis using immunochemical, GC-HS and GC/MS-SIM techniques. As well as many data of social and behavioural interest, processing of results demonstrated that: a) 56.7% of the drivers examined had consumed alcoholic beverages; b) 30.4% had BACs higher than the threshold permitted in Italy (80 mg/100 ml); c) 15.7% of drivers were found to be under the influence of drugs of abuse or psychoactive drugs; d) the most frequently found substances were (in order): cannabinoids, stimulants (cocaine, amphetamines), opiates.

Accidents, Traffic↗
PubMed1999

Effects of single dose of gamma-hydroxybutyric acid and lorazepam on psychomotor performance and subjective feelings in healthy volunteers.

OBJECTIVE: This study investigated the possible effects of gamma-hydroxybutyric acid (GHB) on human psychomotor performance and subjective feelings important for the safety of skilled performance. METHODS: Twelve healthy volunteers, six males and six females, aged 22-36 years, participated as subjects. Drugs and placebo were administered according to a single-dose, double-blind, balanced, four-way, crossover design. Treatments were separated by a wash-out period of 1 week and consisted of placebo, lorazepam 0.03 mg x kg(-1), GHB 12.5 mg x kg(-1) and GHB 25 mg x kg(-1). Subjects' psychomotor performance was assessed at baseline and at 15, 60, 120 and 180 min after treatment. Mood was assessed using 16 visual analogue scales, before treatment and 120 min later. Psychomotor performance was measured using the following tests: Critical Flicker Fusion. Response Competition Test, Critical Tracking Task, Choice Reaction Time and Visual Vigilance Task. RESULTS: GHB at both doses had no effects on attention, vigilance, alertness, short-term memory or psychomotor co-ordination (delta-placebo, P > 0.05); calmness increased with the lower dose and contentedness decreased significantly at both doses (delta-baseline, P < 0.05); adverse effects were limited to slight subjective feelings of dizziness and dullness, which disappeared 30-60 min after administration of the dose. Lorazepam caused impairment of psychometric functions. CONCLUSION: After single therapeutic doses, GHB does not induce changes in psychomotor performance and therefore the drug does not influence the ability to drive or work. However, repeated reports of the abuse potential of GHB and its usefulness in treating ethyl alcohol addiction indicate that it may play an "agonist-like" role, which means that it should only used under close medical supervision.

Adult↗
PubMed1999

Proficiency testing for psychoactive substances in Italy.

This paper describes the general design and main results of the Italian proficiency testing program for the analysis of psychoactive substances in urine, a long-term initiative created in 1995 on an educational basis and characterized by an innovative internet-based service for data exchange between laboratories and the organizing body. Batches of six urine samples, validated by reference laboratories, are sent every 3 months to participating laboratories, which may choose which classes of substances to test from those planned by the program panel and, within those classes, which type of analytical commitment to work on: identification of just one class (Option 1), identification of single substances (Option 2), or identification and quantification of single substances (Option 3). Comprehensive periodical reports and annual reports are provided to participants with evaluation of their performance and an annual workshop is organized to discuss technical-scientific topics related to clinical, forensic and analytical toxicology. About 200 laboratories currently participate in the program and a total of 67,059 analyses have been carried out since 1995. The mean percentage of correct results was 96.8%, with a yearly improvement of about 0.4%. The best average false positive and false negative rates were obtained for methadone (0.2% and 2.1% respectively) and cocaine (0.3% and 2.2%). The worst average false positive rates were obtained for amphetamines and opiates (3.2% and 5.0%) and worst average false negative rates for amphetamines, barbiturates and cannabinoids (17.4%, 30.7% and 19.9%).

Accreditation↗
PubMed1996

Effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid.

OBJECTIVES: To assess the effect of moderate or severe liver dysfunction on the pharmacokinetics of gamma-hydroxybutyric acid (GHB). METHODS: The absorption and disposition kinetics of GHB were studied in eight cirrhotic patients without ascites (Child's class A) and eight cirrhotic patients with ascites (Child's class C), after administration of a single oral dose of 25 mg.kg-1. The liver metabolic function of each patient was evaluated by measuring antipyrine clearance and the formation rate of the lidocaine metabolite monoethylglycinexylidide (MEGX). RESULTS: Compared to those previously determined in eight healthy control subjects given the same GHB dose, mean AUC values were double or greater in the cirrhotic patients. Accordingly, apparent oral clearance was markedly reduced (from 9.1 to 4.5 and 4.1 ml.min-1.kg-1 in nonascitic and ascitic patients, respectively). Terminal half-life (t1/2), was significantly longer in nonascitic patients than in control subjects (32 vs 22 min). A further significant prolongation of t1/2, most likely due to an increased distribution volume, was observed in patients with ascites (56 min). Nonetheless, GHB plasma concentrations fell to either undetectable or negligible levels by the end of the usual dosing intervals (6-8 h). More limited changes were noted in the absorption parameters. The peak level (Cmax) increased only in nonascitic patients, but not proportionally to the increase in AUC. The time to Cmax increased from 30 to 45 min in both cirrhotic groups. These findings are consistent with a slowed rate of GHB absorption in cirrhotic patients. Adverse effects were similar, for intensity and duration, to those recorded in healthy volunteers, i.e., mild and transient. CONCLUSIONS: Although liver cirrhosis causes significant modifications of GHB disposition kinetics, the increase in t1/2 is not such as to cause drug accumulation on repetitive dosing. However, in consideration of the higher mean plasma levels observed in cirrhotic patients, it appears wise to keep the initial GHB daily dose at the lower end of the therapeutic range and to carefully monitor the patients if upward dose adjustments are required.

Aged↗
PubMed1995

Diagnosis of HIV infection from bloodstains by PCR. A further marker for identification.

The forensic usefulness of the detection of HIV infection in bloodstains is linked to the increasing spread of HIV infection and the consequent rise in the number of forensic cases involving HIV-positive subjects. This study was designed to detect HIV infection in bloodstains of various ages obtained from HIV-positive patients treated with zidovudine (3'-azido-3'-deoxythymidine, AZT) using PCR methods. Of the 3 kinds of extraction and amplification methods checked, only a nested PCR method for the amplification of a sequence located in the HIV Reverse Transcriptase (RT) region was successful. This method, involving 2 amplification steps (1: fragment of 768 bp; 2: codons 41-67-70-215-219), encompasses the mutations commonly observed during AZT therapy and overcomes the limitations inherent in serological testing. The discriminatory power of the method can detect specific mutation patterns in the RT gene linked to drug resistance and compares the specific pattern of the blood-stain with fresh blood or other specimens from the subject in question.

Antiviral Agents↗
PubMed1995

PCR analysis of the short tandem repeat (STR) system HUMVWA31. Allele and genotype frequencies in an Italian population sample.

A population study in a sample of 211 unrelated individuals from 2 cities in North and Central Italy was carried out to investigate the short tandem repeat (STR) system HUMVWA31. Separation of PCR- amplified DNA fragments was performed by high-resolution horizontal denaturing polyacrylamide gel electrophoresis (PAGE) followed by silver staining. The 7 common alleles were found, together with a new smaller allele. Distribution of the observed genotypes did not deviate from Hardy-Weinberg (H-W) equilibrium. The power of discrimination for this locus was 0.93 and the chance of exclusion was 0.61. Good agreement was found between the allele frequencies in 2 Italian population samples and previous studies on Caucasians. The results of this study suggest that this STR system may be a useful tool in forensic investigations.

Alleles↗
PubMed1995

Fatality due to gamma-hydroxybutyric acid (GHB) and heroin intoxication.

The first case of fatal intoxication due to ingestion of gamma-hydroxybutyric acid (GHB) and intravenous use of heroin is reported. A 42-year-old man, known to have been a heroin addict and to have taken other psychoactive substances, who had been in treatment with GHB for several months, was found dead. Anatomohistopathologic examination showed generalized visceral congestion, edema and pulmonary anthracosis, chronic bronchitis and chronic active hepatitis. Toxicological findings included fluid and tissue distributions of GHB, morphine and 6-monoacetylmorphine. GHB and morphine concentrations were respectively 11.5 and 0.77 micrograms/mL (blood), 84.3 and 0.3 micrograms/mL (vitreous humor), 258.3 and 1.35 micrograms/mL (urine), 57.0 and 14.3 micrograms/mL (bile), 40.0 and 0.43 micrograms/g (brain), 43.0 and 0.60 micrograms/g (liver), 47.0 and 0.68 micrograms/g (kidney). Blood and urine levels of 6-monoacetylmorphine were 28.5 and 12.1 ng/mL respectively. The presumed mechanism of action and pharmacokinetics of GHB are briefly reviewed, with reference to its therapeutic use and to reports of non-fatal GHB intoxication.

Adult↗
PubMed1994

Morphology of sweat glands in determining time of death.

This study demonstrates post-mortem autolytic alterations in the skin at cellular and subcellular levels and identifies parameters which may assist in determining the time of death in the first few hours post-mortem. Serial skin samples from the ventral surface of the arm were taken at intervals of 3, 6, 9 and 12 h after death in 29 subjects of various ages, with no signs of skin disease; causes of death were various. Three types of tests were performed: cytochemical (hematoxylin-eosin and alcian-PAS), immunohistochemical (S-100, CEA, Cytokeratin, ASM) and ultrastructural (electron microscopy). Electron microscopy proved useful for identifying transformations which were found to be specific for each chronological step considered: reduction of intracellular glycogen in clear cells and reduction of secretory granules in dark cells are typical signs of the first stage (3 h) after death; mitochondrial dilatation and rarefaction of cristae in clear and dark cells are typical of the second stage (6 h); rarefaction of microvilli in dark and clear cells is a sign of the last stage (12 h). Cytochemistry and immunohistochemistry supply useful information--not for all the chronological stage considered here, but for individual phases (3 h for hematoxylin-eosin and 6 h for alcian-PAS). However, it is particularly important to use the results from all such techniques simultaneously, so that the question of the exact time of death within the first 12 h post-mortem may be more accurately answered.

Actins↗
PubMed1994

Low blood alcohol concentrations and driving impairment. A review of experimental studies and international legislation.

While noting that there is no international scientific or legislative uniformity in blood alcohol concentration (BAC) levels admissible for driving motor vehicles, the authors analyse problems concerning the effects of low levels of ethyl alcohol on driving ability. A summary of the international literature on this subject reveals: the existence of contrasting assumptions, with scientific evidence clearly demonstrating altered psychomotor functions; the need to adopt sufficiently complex psychometric tests to reveal the effects of low BACs; the need to improve standardization of experimental studies on man-machine interaction; the need to investigate the following areas: tolerance to alcohol; low BACs with inexperienced, infrequent drinkers and chronic, heavy drinkers; hangover effects; alcohol-gender-age interactions, and specific effects on young drivers; alcohol-drug combinations. The analysis of legislation and enforcement policies also reveals the need for: re-evaluation of the international legal BAC threshold and standardization of procedures for ascertaining the degree of driving disability; further scientific research to compare and evaluate selected legislative initiatives currently in place in most states; to identify the best strategies and procedures to detect and arrest impaired drivers; to determine the optimum random testing rate to maximize deterrent effects in the workplace at minimal cost; to design innovative and comprehensive approaches to rehabilitation programs needed for subgroups of offenders and of workers; to study the effectiveness of new legislations and policies.

Alcohol Drinking↗
PubMed1994

PCR typing of the locus D17S30 (YNZ22 VNTR) in an Italian population sample.

A sample of 202 subjects living in 2 Italian provinces (Ancona and Parma) was tested for YNZ22 polymorphism by the polymerase chain reaction (PCR). After amplification, the phenotypes were separated by agarose gel electrophoresis, stained with ethidium bromide and identified by comparison with a molecular weight marker. No heterogeneity was found between the 2 populations. Alleles, pooled in 4 groups to calculate the Hardy-Weinberg (H-W) equilibrium, showed good accordance between observed and expected values. The power of discrimination (PD) was 0.95 and the chance of exclusion was 0.69. The allele comparison with previous studies on Caucasians showed no significant difference.

Alleles↗
PubMed1994

Clinical efficacy of gamma-hydroxybutyric acid in treatment of opiate withdrawal.

This paper describes the role of gamma-hydroxybutyric acid (GHB) in the treatment of opiate withdrawal syndrome. In the two patients described, after having abruptly withdrawn from long-term methadone treatment, GHB was orally administered (each dose given every 4-6 h) for 8-9 days. The GHB showed both a high efficacy (some mild and transient symptoms attributable to opiate withdrawal were observed, but only in the first days of therapy) and a good tolerability (no clinical phenomena interpreted as GHB side effects were found). These results could be of interest in improving the pharmacological treatment of drug addiction.

Adult↗
PubMed1994

Drugs-of-abuse testing in urine: statistical approach and experimental comparison of immunochemical and chromatographic techniques.

This study deals with the experimental and statistical comparison of six immunochemical techniques, including noninstrumental on-site and instrumental formats (EIA-EMIT and EZ-SCREEN; FPIA-ADx; RIA-Coat-A-Count; LI-Abuscreen ONTRAK; CBI-Triage), and three chromatographic techniques (TLC-Toxi-Lab; HPLC; HPLC-REMEDi drug profiling system), using GC-MS as a reference technique for analyzing amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, methadone, and opiates in the urine of various kinds of drug users. The study reports (a) the values of sensitivity, specificity, false-positive rates, and false-negative rates of each technique; (b) the results of bayesian statistical analysis, which are based on prevalence values of the samples examined and expressed as positive and negative predictive values and cumulative predictive values for each single technique and for combinations of paired immunochemical and chromatographic techniques; and (c) the results of a rough classification of the various degrees of predictability of these techniques. Lastly, this study proposes a decision-making process for establishing the best combination of analytical techniques for the goals in question, according to the characteristics and facilities of each laboratory.

Chromatography↗
PubMed1993

Dose-dependent absorption and elimination of gamma-hydroxybutyric acid in healthy volunteers.

Gamma-hydroxybutyric acid (GHB) is effective in treatment of the alcohol and opiate withdrawal syndromes. Its absorption and disposition kinetics have been studied in 8 healthy male volunteers following oral administration of single doses of 12.5, 25 and 50 mg kg-1. The AUC increased disproportionately with the dose and so the apparent oral clearance decreased significantly as the dose was increased, whereas the terminal half-life and mean residence time increased. The peak plasma concentrations normalised to the lowest dose fell significantly with increasing doses, whilst the corresponding peak times increased. These findings suggest that both the oral absorption and the elimination of GHB are capacity-limited processes. GHB did not bind to significant extent to plasma proteins over the therapeutic concentration range. The pharmacokinetic parameters in healthy volunteers were not significantly different from those previously observed in alcohol-dependent patients with compensated alcoholic liver disease.

Absorption↗