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Biomedical subjects

B Davidow

Publications and source records attributed to B Davidow.

At least 19 recordsLinked to original sources

delta-Aminolevulinic acid dehydratase isozymes and lead toxicity.

ALAD is a zinc metalloenzyme whose inhibition by lead is the first and most sensitive indicator of lead exposure and whose decreased activity has been implicated in the pathogenesis of lead poisoning. This heme biosynthetic enzyme is encoded by a gene located at chromosome 9q34, which has two codominant alleles, ALAD1 and ALAD2. The occurrence of two frequent alleles for ALAD stimulated an investigation into the possible pharmacogenetic role of the enzyme polymorphism in lead poisoning. In a New York City population at high risk for lead exposure, individuals heterozygous or homozygous for the less common allele, ALAD2, had blood lead levels greater than or equal to 30 micrograms/dl more frequently than expected. These findings suggest a potential genetic susceptibility to lead poisoning in individuals with the ALAD 1-2 and 2-2 phenotypes.

Alleles↗

Free erythrocyte protoporphyrin and zinc protoporphyrin measurements compared as primary screening methods for detection of lead poisoning.

We compared two commonly used primary screening methods (FEP and ZnP) for detecting Pb poisoning in children, used according to three major protocols. The results showed that FEP and ZnP values were comparable for only 36% of the children examined; 54% had FEP greater than ZnP and 10% had ZnP greater than FEP. One would identify approximately twice as many children with Pb greater than 300 micrograms/L by an FEP (500 micrograms/L cutoff) as with a ZnP (400 micrograms/L cutoff) screen. With a cutoff of 350, as compared with 500 micrograms/L for ZnP, one would perform 33% additional confirmatory blood Pb determinations with a 3% increased detection of Pb intoxication. If the number of false-negative Pb specimens is to be minimized, the cutoff "action level" for hematofluorometers should be lowered from the currently recommended 500 micrograms/L of whole blood to 350 micrograms/L. Our long experience and that of other laboratories leads us to recommend a revision of Centers for Disease Control risk categories and cutoff values, depending on whether FEP or ZnP is measured in combination with a patient's blood Pb concentration. Our finding of above-normal values for ZnP and FEP with Pb concentrations less than 300 micrograms/L indicates that iron deficiency constitutes an equally important public-health problem for children in New York City.

Child, Preschool↗

Threshold for lead damage to heme synthesis in urban children.

Although lead has no physiological function and is present in only negligible amounts in the blood of remote populations, it has become customary to accept the usual blood Pb level(s) (BPb) observed in industrialized society as "normal." Pb interferes with many biochemical systems, among them the heme biosynthetic pathway; this is reflected by an exponential increase in erythrocyte protoporphyrin concentration (EP) as PBb increases. The present study estimated the threshold PBb at which an increase of EP occurs in a population of urban children. In the 2,004 children studied, BPbs ranged from 2 to 98 micrograms/dl, with 1,852 having a BPb of less than or equal to 30 micrograms/dl, a value presently considered normal. Preliminary analysis suggested that an exponential increase in the concentration of EP occurred after a threshold BPb (apparently between 12 and 20 micrograms/dl) was reached. Precise definition of the threshold BPb for an increase of EP was next determined by two approaches: segmented line techniques and probit analysis. Whether the entire population was analyzed or only the subset of samples with "normal" BPb (less than or equal to 30 micrograms/dl), both methods yielded a threshold BPb of 15-18 micrograms/dl (average value, 16.5). These studies indicate that the heme synthetic pathway is affected by Pb at a level of exposure commonly observed in urban children, which is well below the limit that is presently too easily accepted as normal.

Child↗

Drug abuse patterns of patients on methadone treatment in New York City.

Urine specimens from methadone treatment clinics were screened for various abused drugs between 1974-1979 by thin-layer chromatography (TLC) and immunoassay techniques (IAT). A comparison of the relative incidence of drugs abused reveals that IAT are more sensitive and detect far greater number of subjects abusing drugs than TLC. The results also show a significant abuse of heroin and cocaine during the period studied and a variation of the incidence of other drugs used during the same period. While these patients did not receive benzodiazepenes and tricyclic antidepressants by prescription, their abuse alone and in combination with each other was also found to be widespread. Low levels of PCP and/or its analogs were found in 1978 and 1979. The frequent finding of low levels of PCP in combination with other drugs indicates the availability of this hallucinogen and point to its use in combination with other illicit drugs such as cocaine, amphetamine, and heroin. The suggestion is made that more sensitive analytical methods for drugs screening be utilized in methadone monitoring programs, and that other classes of drugs be added than are currently required.

Amphetamines↗

Health status of cable splicers with low-level exposure to lead: results of a clinical survey.

The results of a cross-sectional clinical field survey of 90 telephone cable splicers are presented. Despite the rare occurrence of clinically overt lead poisoning among cable splicers, the observed prevalence of symptoms was 29% for lead-associated central nervous system symptoms and 21% for gastrointestinal symptoms. These two groups of symptoms were directly related to zinc protoporphyrin (ZPP) levels but no relationship was found between them and blood lead concentrations. Only 5% of the workers had significantly elevated blood lead levels (greater than 40 microgram/100ml). Because of the intermittent lead exposure encountered in this trade, individuals were identified with "normal" blood lead levels associated with "elevated" zinc protoporphyrin concentrations, indicating the difference in biological significance between exposure-(blood lead) and biological-response tests (ZPP). Suggestion is made that both types of diagnostic tests be utilized in the medical surveillance of lead-exposured workers.

Adult↗

Radioimmunoassay screening test for detection of phencyclidine (PCP, "angel dust") abuse among teenagers.

An immunogen was prepared from a succinamide derivative preparation of phencyclidine (PCP) and coupled to bovine gamma globulin by means of water-soluble carbodiimide. Phencyclidine, 10 of its analogs, and a 3,4-3H-PCP all bound competitively to antibodies induced in rabbits. An assay was developed using the ammonium sulfate precipitation separation method. The minimum detection limit to PCP was 2 ng/mL and that for various analogs ranged from 50 pg/mL to approximately 100 ng/mL. No cross reactivity was observed with at least 25 commonly used drugs. A double blind qualitative clinical evaluation of the assay was conducted with gas-liquid chromatography (GLC) and GLC-mass spectrometry methods. No false positive or false negative results were observed. For qualitative screening a "cut-off" level equivalent to 5 ng/mL was used for both serum and urine to distinguish between positive and negative specimens. Urine and serum samples from emergency room patients with neuropsychiatric symptoms and methadone clinic patients and autopsy material showed a significant incidence of PCP abuse, particularly among adolescents and young adults.

Adolescent↗

Evaluation of the expanded newborn screening program in New York City.

Since September 1974, New York State public health law has mandated that all newborn infants be tested for phenylketonuria, maple syrup urine disease, homocystinuria, histidinemia, galactosemia, adenosine deaminase deficiency, and sickle cell anemia in accordance with regulations of the state commissioner of health. During the period from May 1, 1975, to April 30, 1976, a total of 110,180 babies born in New York City were tested for these seven conditions. One year's experience with the screening program demonstrated a paucity of technological problems, low observed rate of both false-negatives and -positives, and the expected incidence of the conditions of highest prevalence, incidentally found during screening: i.e., sickle cell traits, AS and AC. What is equally apparent in reviewing this first year's experience is the extent to which the New York State law, its structure, and implementation have fallen short of the ultimate objective. The major reason for this failure is lack of funds and facilities in the areas of education, case retrieval, continuing medical care, and counseling. This report is presented with the hope that it will benefit all involved in genetic screening and especially those concerned with establishing similar programs.

Adenosine Deaminase↗

Determination of morphine by electron capture gas-liquid chromatography.

We describe a micromethod for determining as little as 0.1 microgram of morphine per liter of human urine. The procedure is about 20-fold more sensitive than are currently used gas-liquid chromatographic methods. It is particularly suitable for use as a confirmatory method for large-scale radioimmunoassay screening tests. The procedure involves extraction of morphine from urine and analysis of its heptafluorobutyryl derivative by gas-liquid chromatography with electron capture detection. Morphine can be determined by this procedure over a range of 0.1-200 microgram/liter of urine, 2 pg of the pure derivative being the lowest amount detectable. Urine samples from patients receiving methadone were analyzed by thin-layer chromatography, radioimmunoassay, and our procedure. The results by our procedure agreed well with those obtained by radioimmunoassay.

Chromatography, Gas↗

The deveolopment of a radioimmunoassy for detection of cocaine metabolites.

This paper describes the production of antibenzoylecgonine (BE) serum in rabbits and sheep from an ecgonine-sheep gamma globulin conjugate. With the use of this antiserum a radioimmunoassay was developed capable of detecting 5 to 10 ng of benzoylecgonine, a major cocaine metabolite in human urine. The antibody recognized ecgonine approximately 1/2, benzoylnorecgonine 1/10, cocaine, 1/5, and norcocaine and ecgonine methyl ester less than 1/50 as much as benzoylecgonine. The radioimmunoassay has been utilized in the measurement of benzoylecgonine levels in human urines and in organs and biological fluids of rabbits and rats. Qualitative results were compared with the Enzyme Multiplied Immunoassay Technique and thin-layer chromatography and found to be in good agreement. The technique is the most sensitive one available for monitoring cocaine ingestion by man and allows for specific determination of benzoylecgonine directly in urine without extraction and/or derivatization. Although ecgonine-sheep gamma globulin was used as the immunogen, the total antibody produced by both species was more reactive with respect to BE. The greater reactivity to BE suggests a possible conversion of a significant portion of the conjugated ecgonine in vivo to compound(s) conformationally more closely related to BE against which the major portion of the total antibody subsequently elicited was directed.

Animals↗