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Biomedical subjects

A Hassoun

Publications and source records attributed to A Hassoun.

At least 19 recordsLinked to original sources
PubMed2002

Bile analysis of drugs in postmortem cases.

Bile is, in certain cases, collected together with blood from different sites (heart, brain, femoral), urine and other organs or matrices. This study reports comparative results obtained from the analysis of blood and bile for different drugs found: acetaminophen, amphetamine and related compounds, several antidepressants, several benzodiazepines, cocaine and its metabolites, dextropropoxyphene and its metabolite, hydroxyzine, methadone and metabolite, morphine and codeine, levomepromazine, thioridazine, propranolol, tramadol and its metabolite. Several findings are presented: (1) There were no significant differences in the levels of the compounds among the samples of blood obtained from different sites. (2) Levels in bile are generally several fold higher than those in blood. The mean bile to blood ratios vary from about 1 (for acetaminophen, amphetamine) to about 2000 (for desmethylclobazam). (3) In certain cases (16 over 44), although the drug or its metabolite was not detected in blood from different sites, it was detected in bile. As other authors had advocated, it is very useful to ask the pathologist to take the gall bladder with its contents together with the other samples, in order that the sample of bile can be used in the comprehensive toxicological analysis and therefore be complementary to the other fluids or matrices. An additional advantage for using bile is that the concentrations of drugs or their metabolites are generally several fold higher than their blood concentrations.

Bile↗
PubMed2001

Highly heterogeneous nature of delta-aminolevulinate dehydratase (ALAD) deficiencies in ALAD porphyria.

The properties of 9 delta-aminolevulinate dehydratase (ALAD) mutants from patients with ALAD porphyria (ADP) were examined by bacterial expression of their complementary DNAs and by enzymologic and immunologic assays. ALADs were expressed as glutathione-S-transferase (GST) fusion proteins in Escherichia coli and purified by glutathione-affinity column chromatography. The GST-ALAD fusion proteins were recognized by anti-ALAD antibodies and were enzymatically active as ALAD. The enzymatic activities of 3 ALAD mutants, K59N, A274T, and V153M, were 69.9%, 19.3%, and 41.0% of that of the wild-type ALAD, respectively, whereas 6 mutants, G133R, K59N/G133R, F12L, R240W, V275M, and delTC, showed little activity (< 8%). These variations generally reflect the phenotype of ALAD in vivo in patients with ADP and indicate that GST-ALAD fusion protein is indeed useful for predicting of the phenotype of ALAD mutants. The location of F12L mutation in the enzyme's molecular structure indicates that its disturbance of the quaternary contact of the ALAD dimer appears to have a significant influence on the enzymatic activity. Mouse monoclonal antibodies to human ALAD were developed that specifically recognized a carboxy terminal portion of ALAD, or other regions in the enzyme. This study represents the first complete analysis of 9 mutants of ALAD identified in ADP and indicates the highly heterogeneous nature of mutations in this disorder.

Adolescent↗
PubMed2000

Molecular analysis of delta-aminolevulinate dehydratase deficiency in a patient with an unusual late-onset porphyria.

Cloning, expression, and genotype studies of the defective gene for delta-aminolevulinate dehydratase (ALAD) in a patient with an unusual late onset of ALAD deficiency porphyria (ADP) were carried out. This patient was unique in that he developed the inherited disease, together with polycythemia, at the age of 63. ALAD activity in erythrocytes of the patient was less than 1% of the normal control level. ALAD complementary DNA (cDNA) isolated from the patient's Epstein-Barr virus (EBV)-transformed lymphoblastoid cells had 2 base transitions in the same allele, G(177) to C and G(397) to A, resulting in amino acid substitutions K59N and G133R, respectively. It has been verified that the patient had no other ALAD mutations in this and in the other allele. By restriction fragment length polymorphism (RFLP) analysis, all family members of the proband who had one-half ALAD activity compared with the ALAD activity of the healthy control were shown to have the same set of base transitions. Expression of ALAD cDNA in CHO cells revealed that K59N cDNA produced a protein with normal ALAD activity, while G133R and K59N/G133R cDNA produced proteins with 8% and 16% ALAD activity, respectively, compared with that expressed by the wild type cDNA. These findings indicate that while the proband was heterozygous for ALAD deficiency, the G(397) to A transition resulting in the G133R substitution is responsible for ADP, and the clinical porphyria developed presumably due to an expansion of the polycythemic clone in erythrocytes that carried the mutant alad allele.

Age of Onset↗
PubMed1999

Immunologic factors: the major risk for decreased long-term renal allograft survival.

BACKGROUND: Both antigen-dependent (immunologic) and non-antigen-dependent (nonimmunologic) factors have been implicated in long-term renal allograft loss. Differentiating between these two factors is important because prevention strategies differ. METHODS: To isolate the importance of these 2 factors, we studied long-term actuarial graft survival in a cohort of adult kidney recipients who underwent transplants at a single institution between January 1, 1984 and October 31, 1998. Excluded were recipients with graft loss as a result of death with function, technical failure, primary nonfunction, and recurrent disease, leaving 1587 recipients (757 cadaver [CAD], 830 living donor [LD]) who would be at risk for graft loss secondary to both immunologic and nonimmunologic factors. These recipients were analyzed in the following 2 groups: those treated for a previous episode of acute rejection (AR) (Group1; n = 588; 328 CAD, 260 LD) and those with no AR (Group 2: n = 999; 429 CAD, 570 LD). Actuarial graft survival and causes of graft loss were determined for each group. Presumably, graft loss in Group 1 would be caused by immunologic and nonimmunologic factors; graft loss in Group 2 would be caused primarily by nonimmunologic factors. RESULTS: The 10-year graft survival rate (censored for death with function, technical failure, primary nonfunction, and recurrent disease) in Group 2 was 91%. In contrast, the 10-year graft survival rate in Group 1 was 45% (P<0.001 vs. Group 2). Causes of graft loss in Group 2 were chronic rejection in 1.8% (3.0% CAD, 0.9% LD), de novo disease, 0.4%; sepsis, 0.2%; discontinuation of immunosuppressive therapy, 0.3%; and unknown, 0.6%. In contrast, 23.8% (29.9% CAD, 16.2% LD) of recipients in Group 1 had graft loss caused by chronic rejection (P = 0.001 vs. Group 2). CONCLUSIONS: This very low incidence of chronic rejection in recipients without previous AR suggests that immunologic factors are the main determinants of long-term kidney transplant outcome; nonimmunologic factors in isolation may have only a minimal impact on long-term graft survival.

Adult↗
PubMed1999

Simultaneous detection and quantification of acidic and basic drugs in serum toxicological screening: use of ion-pairing technique in liquid-liquid extraction.

The toxicological screening, using the combination of high performance liquid chromatography with diode array ultraviolet detector and ion-pairing technique in liquid-liquid extraction, is an effective tool in the identification and quantification of the acidic and basic substances in a single run. The use of an ion-pairing technique in the conventional extraction shows the co-extraction of the uncharged and charged form of the analytes present in a serum sample. The stationary phase used is C-18-bonded phase. The mobile phase is acetonitrile--phosphate buffer (pH 3; 25 mM) containing 25 mM triethylammonium as ion-pairing agent. The analytical validation shows reproducible recoveries, good day-to-day repeatability and sensible results compatible with clinical and forensic use.

Acute Disease↗
PubMed1998

Ethylene glycol poisoning treated by intravenous 4-methylpyrazole.

A 19-year-old woman was admitted 45 min after ethylene glycol (EG) ingestion. The initial serum EG concentration was 1.34 g/l (21.6 mmol/l), the anion gap 14.5, and the osmolal gap 24. Renal function was preserved (serum creatinine 75.1 micromol/l). As the patient was seen soon after poisoning, before the development of metabolic acidosis, therapy with 4-methylpyrazole (4-MP) was proposed as an antidote. 4-MP was administered via the intravenous route (7 mg/kg as loading dose, followed by 3.6, 1.2, 0.6, and 0.6 mg/kg at intervals of 12 h). 4-MP alone was effective in preventing EG biotransformation to toxic metabolites (absence of metabolic acidosis and renal injury). Ethanol therapy, hemodialysis, and sodium bicarbonate administration were not required. The half-life of EG during 4-MP therapy was 11 h, with a mean EG renal clearance of 26.9 ml/min, and a total of 65.3 g EG was eliminated unchanged in the urine. 4-MP therapy was also well tolerated.

Acid-Base Equilibrium↗
PubMed1998

Ethanol treatment of tendon allografts: a potential HIV inactivating procedure.

The penetration rate of ethanol in human tendons was studied to in order to define the conditions which were necessary to achieve an inactivating concentration against the Human Immunodeficiency Virus (HIV) within the tendon. The rate of alcohol penetration was found to be slow and did not differ with different types of tendons. An average ethanol concentration of 14% (v/v) was measured in human tendons after they had been immersed for 2 h in 70% (v/v) ethanol, and a concentration of 19% (v/v) was reached after 3 h. Ethanol immersion of human tendons may represent an additional safety procedure in inactivating the HIV virus provided the duration is at least 3 h.

Anti-Infective Agents, Local↗
PubMed1995

Accumulation of protoporphyrin isomers I and III, and multiple decarboxylation products of uroporphyrin in a case of porphyria in a slaughtered pig.

Pathological and biochemical examinations were made on tissues from a case of porphyria in a slaughtered pig. Bones, kidneys, teeth and lymph nodes showed a mahogany discoloration. Histologically, the pigment was negative on staining for iron (Gomori) and showed a strong red-orange fluorescence under UV light proving it to be porphyrin. Biochemical studies on the kidney, lymph nodes, bone and bone marrow revealed a 'mixed' erythropoietic protoporphyria-coproporphyria. This indicates that the case presented probably represented both a uroporphyrinogen decarboxylase and uroporphyrinogen-III-cosynthase dysfunction.

Abattoirs↗
PubMed1995

Outcome following organ removal from poisoned donors in brain death status: a report of 12 cases and review of the literature.

Experience with organ procurement from poisoned donors in brain death status is still limited in comparison with other etiologies. From 1963 to 1993, 2769 grafts (heart 141, kidney 1922, liver 623, pancreas 43) were performed in our University Hospital. Since 1975, among 1174 patients admitted to the ICU for acute poisoning, 12 patients who developed brain death status were considered for organ donation. The toxics involved were: methaqualone (1), benzodiazepines (1), benzodiazepines plus tricyclic antidepressants (2), barbiturates (2), insulin (2), carbon monoxide (1), cyanide (1), methanol (1), and acetaminophen (1). Exclusion criteria for organ removal were applied according to the nature of the toxin and the general criteria used for organ donation. The organs removed were: heart 5, heart valves for graft bank 2, kidneys 22, liver 4, pancreas 2, pancrease islet cells 2. Pertinent follow-up was obtained in 23 of 32 recipients. Immediate outcome was favorable in 20/23 patients (85%). Three patients died either from stroke, heart failure or preexisting encephalopathy. Two patients died from either chronic hepatic or renal graft rejection. None of these events could be directly related to a toxic origin. The one year survival rate of 75% is similar to that observed in the population who received organs from nonpoisoned donors. Organ procurement can be considered in few selected cases of acute poisoning. The accuracy of the diagnosis of irreversible brain damage is essential in this setting.

Brain Death↗
PubMed1995

HPLC-microparticle enzyme immunoassay specific for tacrolimus in whole blood of hepatic and renal transplant patients.

Tacrolimus is a relatively new immunosuppressant used in organ transplantation to prevent graft rejection. However, its use is not devoid of side effects, making it important to maintain blood concentrations within therapeutic ranges. Several analytical methods are currently available for routine drug monitoring. However, these methods are based on use of the same monoclonal antibody, which also cross-reacts with some metabolites, resulting in overestimation of some blood concentrations. Even though this antibody appears appropriate for therapeutic drug monitoring, no reference method measures only the parent drug, mainly because of the poor absorptivity of tacrolimus in ultraviolet light. We have developed a method displaying an increased specificity towards the unchanged drug, using conventional equipment available in most clinical laboratories. After chromatographic separation of the blood extract, the tacrolimus fraction is analyzed by an automated microparticle enzyme immunoassay (MEIA) performed on the IMx analyzer (Abbott Labs.). This method is linear from 0 to 40 micrograms/L, yields CVs from 8.5% to 18.2%, and has a detection limit of 5 micrograms/L. Tacrolimus concentrations obtained by HPLC-MEIA in hepatic and renal transplant patients are from 47.5% to 18.8% lower than those obtained by MEIA, according to liver function tests and metabolite accumulation, even though no significant differences were observed between the methods for drug-free blood samples supplemented with known amounts of tacrolimus.

Antibodies, Monoclonal↗
PubMed1994

Inhibitory effects of solvent and solid-phase extraction residues on mixed lymphocyte cultures.

Residues from eight solvents/solvent mixtures before and after their passage through C18- bonded phase columns were assayed for cytostatic activity using mixed lymphocyte cultures (MLC). All residues, except those from acetonitrile, exhibited cytostatic activity (15%-35% MLC inhibition as measured by 3H-thymidine incorporation). Passage of solvents through bonded phase columns contributed an additional and significant cytostatic effect (19%-69% MLC inhibition). Pretreatment of columns with methanol led to further increases in the release of cytostatic residues from the columns, only when followed by less polar solvents (hexane, ethylacetate, etc.). It is concluded that residues from solid-phase extraction columns may interfere with subsequent cell culture-based assays for proliferative/antiproliferative activity.

Antineoplastic Agents↗
PubMed1994

Unusual manifestations after malathion poisoning.

We report a case of organophosphate poisoning with a commercial preparation of malathion (deliberate ingestion of Malathane Garden Spray: malathion 15% in isopropyl alcohol) in which the initial cholinergic crisis was followed by cardiac, pulmonary, neurological and renal manifestations. They occurred when erythrocyte and plasma cholinesterases were reactivating. A chemical analysis of the pesticide preparation revealed, apart from malathion itself, the presence of isopropylmalathion and O,O,S-trimethylphosphorothioate. Although pure malathion is regarded as one of the safest organophosphate insecticides, this observation underlines the possibility of severe complications after exposure to a preparation which has been stored for a long period of time.

Aged↗