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Biomedical subjects

M Kushnir

Publications and source records attributed to M Kushnir.

28 records · Page 2Linked to original sources

Abnormal orbicularis oculi reflex response in sleep apnea secondary to acromegaly. Evidence of pontomedullary dysfunction in sleep apnea syndrome.

Severe sleep apnea was present in a patient with upper airway obstruction due to acromegaly. The study of orbicularis oculi reflex responses (OORR) disclosed a marked prolongation of the late response prior to tracheostomy. Following the surgical relief of upper airway obstruction, sleep apnea disappeared, and the latency of the late response of the OORR was dramatically reduced but failed to normalize. The OORR and especially its late response were normal in a patient with acromegaly who did not experience sleep apnea. In two patients with sleep apnea, but without acromegaly, the late responses of the OORR were abnormal. It is suggested that the presence of abnormal OORR in sleep apnea may reflect a basic defect in pontomedullary control of respiration during sleep.

Acromegaly↗

A rapid gas chromatographic method quantitating clozapine in human plasma or serum for the purpose of therapeutic monitoring.

A gas chromatographic method using nitrogen-phosphorus detection was developed to quantitate clozapine in plasma or serum. Methyl clonazepam was used as an internal standard. Sample preparation included a single-step extraction with ethyl acetate, which was injected directly onto a wide-bore capillary column. Within-run and total precision, measured as percent coefficient of variation, were determined at low, therapeutic, and high clozapine plasma concentrations. The within-run precision for the low, therapeutic, and high clozapine plasma samples was 5.2, 2.7, and 2.4%, respectively. The total precision for the low, therapeutic, and high clozapine plasma samples was 10.0, 2.6, and 2.0%, respectively. Analytical accuracy was evaluated by comparing quantitative results with those obtained from a reference laboratory. Those samples containing therapeutic or high concentrations agreed within 3%; the sample containing a subtherapeutic concentration differed by 11.9%. The limit of quantitation was determined to be 35 ng/mL, and the upper limit of linearity was 3000 ng/mL. No significant interferences were detected after testing more than two dozen drugs and metabolites.

Antipsychotic Agents↗

Improving ion mass ratio performance at low concentrations in methamphetamine GC-MS assay through internal standard selection.

In federally regulated drug testing, laboratories must identify and quantitate drugs and their breakdown products by gas chromatography-mass spectrometry (GC-MS) to a concentration that is at least 60% below the cutoff concentration for reconfirmation purposes. Use of methamphetamine-d5 as an internal standard in routine testing with derivatization by HFBA was found to contribute m/z 91 and 118 ions to the same ions from the nondeuterated methamphetamine in the specimen. This resulted in poor chromatography and occasionally caused the 91/254 and 118/254 ion mass ratios to exceed the +20% acceptance limit established in the calibration process at low concentrations. The analogues methamphetamine-d8 and -d11 were evaluated for contributions to the nondeuterated methamphetamine ion fragments. Methamphetamine-d8 produced m/z 91 and 118 ions, but in less abundance than methamphetamine-d5. Methamphetamine-d11 was found to produce little or no detectable m/z 91 or 118. Replacing methamphetamine-d5 with methamphetamine-d11 eliminates this problem and allows the assay to consistently produce ion mass ratios and acceptable chromatography sufficient for identifying and quantitating methamphetamine at 60% below the 500-ng/mL cutoff concentration.

Gas Chromatography-Mass Spectrometry↗

Nitrite adulteration of workplace urine drug-testing specimens. I. Sources and associated concentrations of nitrite in urine and distinction between natural sources and adulteration.

The active ingredient in the commercial workplace urine drug-testing adulterant, Klear, was previously determined to be nitrite ion. Nitrite adulteration compromises the confirmation of some drugs, notably the marijuana metabolite. A previously reported bisulfite step overcomes some nitrite adulteration, but it cannot do so in every case, which leaves the laboratory to report the specimen as not suitable for testing. Unlike many other adulterants, nitrite is found in normal urine at low concentrations. In order to defend a report of nitrite adulteration, it is necessary to provide evidence that the amount of nitrite in a workplace urine specimen could not arise by normal means. The objectives of this study were to identify all sources of nitrite in urine and the range of concentrations associated with these sources and to determine if nitrite adulteration can be supported based upon a quantitative result. The scientific literature was reviewed for internal and external sources of nitrite and their concentration ranges and are reported. The following specimens were obtained and nitrite concentrations measured by a spectrophotometric method: clinical specimens nitrite positive by test strip (< 15 micrograms/mL); specimens culture positive for nitrate-reducing microorganisms (< 36 micrograms/mL); specimens from patients on medications that may metabolize to nitrite (< 6 micrograms/mL); and drug-test specimens, both negative (< 130 micrograms/mL) and others that appeared to be adulterated with nitrite (range 1910-12,200 micrograms/mL, mean 5910). The literature and the nitrite measurements of this study indicate a substantial difference between concentrations from natural sources compared with adulteration. A quantitative measurement of nitrite by a well-structured assay can provide scientifically valid and forensically defensible proof of adulteration with a nitrite-containing substance.

Drug Contamination↗