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J M Neal

Publications and source records attributed to J M Neal.

At least 37 records · Page 2Linked to original sources
PubMed1994

Application of negative-ion chemical ionization isotope dilution gas chromatography--mass spectrometry to single-dose bioavailability studies of mefloquine.

An electron-capture negative-ion chemical ionization gas chromatographic-mass spectrometric assay for mefloquine, an antimalarial drug used in the treatment of drug-resistant Plasmodium falciparum malaria, is described. The method, developed in support of bioavailability studies involving the co-administration of different tableted formulations of the drug and an aqueous solution of its 13C3-labeled analog, enables quantification of both dosage forms. Quantitative analysis of extracted plasma samples was performed on the O-tert.-butyldimethylsilyl (t-BDMS) derivative of the drug by selected-ion monitoring, using a VG Trio 2000 quadrupole mass spectrometer and monitoring the [M-t-BDMSOH]-. ions of the analytes. The method, incorporating [2H6]mefloquine as an internal standard, demonstrated good accuracy and precision over the 1-200 ng ml-1 range, with correlation coefficients greater than 0.990 for all standard curves and a detection level of 50 fg on-column. Replicate analysis of plasma samples over a 90-day period exhibited a mean intra-day and inter-day variation of less than 4.5% and 5.5%, respectively. The high stability and sensitivity of the assay, combined with the inherent selectivity of mass spectrometric detection, make the method well-suited for such studies.

Biological Availability↗
PubMed1991

Thyrotoxic periodic paralysis in a Caucasian man: recognition and diagnosis.

Periodic paralyses are uncommon disorders characterized by episodic muscle weakness, often with hypokalemia. Thyrotoxic periodic paralysis (TPP) is the most common and is rarely seen in the Caucasian population; the relative unfamiliarity of TPP among physicians in the United States may lead to initial errors in diagnosis. This article presents the case of a 25-year-old white man with frequent episodes of skeletal muscle weakness and cramping, associated with profound hypokalemia. Laboratory evaluation demonstrated primary hyperthyroidism, and a diagnosis of TPP was made. The disorder is found more commonly in men between the ages of 20 and 40. Hypokalemia is the most consistent laboratory abnormality, representing a transcellular shift rather than a total body deficit; the exact mechanism is unknown. The exercise test demonstrates distinct electromyographical abnormalities in those with periodic paralysis. The definitive treatment of TPP is establishing a euthyroid state.

Adult↗
PubMed1990

Cooling potentiates lidocaine inhibition of median nerve sensory fibers.

To determine the effect of cooling on lidocaine potency, nine consenting volunteers underwent bilateral median nerve blocks using 1% lidocaine HCl solution. Room-temperature and ice-cold lidocaine were injected into either dominant or nondominant wrists. Subjects were blinded to the temperature of the anesthetic. Inhibition of A alpha sensory and motor fibers was assessed as the decline in sensory nerve action potentials and compound motor action potentials, respectively. Inhibition of C fibers was measured as an increase in skin temperature and a decline in galvanic skin potentials. All indices of nerve function demonstrated profound (P less than 0.001) time-related changes after injection of local anesthetic. When ice-cold lidocaine was injected, inhibition of sensory nerve action potentials was significantly greater at all time points (P = 0.001) than when room-temperature lidocaine was injected. Inhibition of C fibers as assessed by galvanic skin potentials was marginally faster (P = 0.07) when ice-cold lidocaine was used compared with room-temperature lidocaine. No differences between room-temperature and ice-cold lidocaine were observed in inhibition of compound motor action potentials, or in the increase in skin temperature. We conclude that inhibition of median sensory fibers may be increased by cooling 1% lidocaine HCl in an ice bath before injection.

Action Potentials↗
PubMed1985

Near-drowning.

Near-drowning is defined as survival for at least some period of time after suffocation from submersion in a liquid. This article is a comprehensive review of the demography, pathophysiology, treatment, and prevention of near-drowning, an accident that affects approximately 6,000 to 7,000 Americans per year. Forty percent of these victims are children younger than 5 years. Alcohol plays a role in approximately one-half of near-drownings of older victims. Major factors prolonging survival are an age of less than 2 years and immersion in cold water (less than 20 degrees C). Hypoxia and acidosis are the primary physiological derangements, and treatment must be directed toward their correction. The hypothermic patient requires special considerations. The role of aggressive cerebral resuscitation has not been elucidated. Prevention of the circumstances that lead to near-drowning must be stressed as a public service.

Acidosis↗
PubMed1985

Food injuries.

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Adolescent↗
PubMed1980

Simultaneous analysis of phenobarbital and p-hydroxyphenobarbital in biological fluids by GLC-chemical-ionization mass spectrometry.

A sensitive and specific GLC-chemical-ionization mass spectrometric method was developed for the simultaneous assay of phenobarbital (I) and p-hydroxyphenobarbital (II) in biological fluids (urine and plasma) using stable isotope analogs of the compounds as internal standards. After extraction, the compounds were methylated with diazomethane and quantitated by GLC-chemical-ionization mass spectrometry. The detection limit of the method was 0.1 micrograms/ml for both compounds. The intraday precision (RSD) for 0.4-2.4 micrograms/ml was < 2% for I and < 4% for II. The interday precision for 0.55 and 2.11 micrograms/ml of each compound was 5.5 and 2.9% for I and 7.3 and 5.0% for II, respectively. This method has been applied in several pharmacokinetic studies.

Gas Chromatography-Mass Spectrometry↗
PubMed1975

Pharmacokinetics of carbamazepine in normal man.

The bioavailability of commercial carbamazepine talbets with and without meals was compared to a propylene glycol solution respect to extent of absorption in 6 normal humans after a dose of 6 MG/KG. The presence of dose-dependent kinetics within a clinically sigificant range was also investigated. Serum and urine samples were assayed by gal-liquid chromatography (GLC). Carbamazepine is rapidly absorbed from the propylene glycol solution. Eight per cent of the dose was absorbed from the commercial tablet, resulting in therapeutic serum concentrations(30 to 6 mcg/ni). The data were consitent with disolution rate-limited absorption. Mean half-lives ranged from 31 to 35 hr. No dose-dependent kinetics were observed following administration of does of 3. 6. or 9 mg/kg. The fraction of dose abosrbed, the fraction excredted unchanged in urine, the time of maxium serum concentration, and absorption and elimination half-lives appear to be independent of dose. The time course of side effects could not be correlated with serum carbamazepine levels, suggesting that metabolities contributed to side effects.

Adult↗