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Biomedical subjects

M J Fitzgerald

Publications and source records attributed to M J Fitzgerald.

At least 19 recordsLinked to original sources
PubMed2001

Temporal indication of marijuana use can be estimated from plasma and urine concentrations of delta9-tetrahydrocannabinol, 11-hydroxy-delta9-tetrahydrocannabinol, and 11-nor-delta9-tetrahydrocannabinol-9-carboxylic acid.

Current technology establishes marijuana use based upon detection of the pharmacologically inactive cannabinoid metabolite (11-nor-delta9-carboxy-tetrahydrocannabinol-9-carboxylic acid, THC-COOH) in urine. No accurate prediction of time of use is possible because THC-COOH has a half-life of 6 days. To determine if a temporal relationship between marijuana use and metabolite excretion patterns could be established, eight healthy user-volunteers (18-35 years old) smoked marijuana cigarettes containing 0% (placebo), 1.77%, and 3.58% delta9-tetrahydrocannabinol (THC). Plasma and urine were collected prior to smoking, 5 min after smoking, and hourly thereafter for 8 h for measurement of cannabinoid concentrations by gas chromatography-mass spectrometry. Mathematical models proposed for determination of recent marijuana use were applied to data from this study and verified the temporal use of marijuana. One subject, who later admitted chronic marijuana use (urine baseline THCCOOH, 529.2 ng/mL; plasma, 75.5 ng/mL), excreted 8beta-dihydroxy-THC, peaking 2 h postsmoking (92.3 ng/mL). Urinary THC, the psychoactive component of marijuana, concentrations peaked 2 h after smoking and declined to assay limit of detection (LOD) (1.5 ng/mL) by 6 h. 11-Hydroxy-delta9-tetrahydrocannabinol (11-OH-THC) and THCCOOH were detectable for the entire 8-h testing period but continued to decrease. Urinary concentrations of THC greater than 1.5 ng/mL suggests marijuana use during the previous 8-h time period.

Adolescent↗
PubMed2000

Recurrent myelinoclastic diffuse sclerosis: a case report of a child with Schilder's variant of multiple sclerosis.

Myelinoclastic diffuse sclerosis (MDS, Schilder's disease) is a rare CNS demyelinating disorder affecting mainly children and usually presenting as an intracranial mass lesion. We report the first case of recurrent intracranial MDS where the third episode of demyelination involved the cervical spinal cord. This may represent a subset of the disease, which should be considered as Schilder's variant (childhood form) of multiple sclerosis.

Child↗
PubMed2000

Inadequacies of self-report data for exclusion criteria detection in marihuana research: an empirical case for multi-method direct examination screening.

Stringent exclusion criteria in drug abuse research are necessary to protect against methodological confounds compromising the interpretation of findings. However, reliance on self-report screening may fail to detect important exclusion variables. We compared three levels of exclusion criteria screening in a study of neurophysiological/neurocognitive sequelae of chronic marihuana use in normals. LEVEL 1 (self-report) consisted of telephone pre-screening. LEVEL 2 (also self-report) involved in-depth personal interviews. LEVEL 3 consisted of several direct examination assessments including a medical/psychiatric examination by a board certified psychiatrist, eight weeks of twice per week urine drug screens, an EEG exam and eight hours of neuropsychological testing. Results indicated that 39.0% of subjects passing self-report screening had significant exclusion criteria findings that were only detected through LEVEL 3 direct examination procedures. Of all subjects found to have exclusion criteria after being provisionally accepted following LEVEL 1 telephone pre-screening, 55.7% were detected only through more rigorous LEVEL 3 direct examination screening methods.

Adolescent↗
PubMed1995

Cannabinoids in humans. II. The influence of three methods of hydrolysis on the concentration of THC and two metabolites in urine.

Glucuronide conjugates of cannabinoids were previously identified in humans. For gas chromatographic-mass spectrometric (GC-MS) analysis of the unconjugated compounds in human urine, it is necessary to cleave the glucuronide moiety. Base hydrolysis and two forms of enzymatic hydrolysis were compared in this study to examine any quantitative differences between the hydrolysis methods. Human volunteers (n = 8) each smoked one marijuana cigarette containing 3.58% delta 9-tetrahydrocannabinol (THC) and submitted urine samples prior to smoking, 5 min after smoking, and hourly for 8 h thereafter. Urine (1 mL) was buffered to the optimum pH for each form of enzyme tested. beta-Glucuronidase from Escherichia coli (bacteria) or Helix pomatia (mollusk) was added to the specimens, followed by overnight incubation at 37 degrees C. Following hydrolysis, the samples were extracted using hexane-ethyl acetate (7:1) and derivatized with N,O-bis(trimethylsilyl)-trifluoroacetamide plus 1% trimethylchlorosilane, which converted the cannabinoids to their trimethylsilyl derivatives. GC-MS analysis revealed striking differences between the hydrolysis methods. Concentrations of unconjugated THC and 11-hydroxy-THC (11-OH-THC) using E. coli were significantly increased over all other methods tested (p < .05). These results demonstrate the species-dependent nature of glucuronidase activity in hydrolyzing THC and 11-OH-THC glucuronides and the ineffectiveness of base hydrolysis on these hydroxylated compounds. The need for further study to find the optimum conditions necessary for the complete hydrolysis of cannabinoid conjugates is suggested.

Dronabinol↗
PubMed1993

The effect of increasing doses of beta-agonists on airflow in patients with chronic airflow limitation.

OBJECTIVE: To determine the increase in FEV1 associated with increasing doses of inhaled terbutaline and salbutamol, the reproducibility of the increase in FEV1, and the reproducibility of the associated optimal bronchodilator dose, in patients with chronic airflow limitation (CAL). DESIGN: Double-blind, randomized, controlled trial examining spirometric response to cumulative doses of bronchodilators. PATIENTS AND SETTING: Patients with clinical diagnosis of CAL, FEV1 below 70% predicted, and FEV1 to FVC ratio less than 0.7 after administration of bronchodilator recruited from secondary care respirology practices. MEASURES OF OUTCOME: The estimates of maximum and optimal bronchodilation, as well as the associated drug dosages, were established in each patient on three occasions (twice on terbutaline and once on salbutamol). The 'optimal' drug dose was defined as the lowest dose associated with an FEV1 not exceeded by 50 ml on any other dose. MAIN RESULTS: Thirty-five patients completed the trial. FEV1 improved from 0.93 to a maximum of 1.191 with terbutaline (average of the two administrations) and from 0.951 to 1.141 with inhaled salbutamol (difference in increase in FEV1 between terbutaline and salbutamol P = 0.006). In less than 50% of cases administration of more than four puffs of bronchodilator resulted in FEV1 increase by more than 50 ml. The average dose of salbutamol and terbutaline associated with optimal bronchodilation were 430 micrograms and 1160 micrograms respectively. Patients varied widely in the optimal dose. Estimates of optimal dose were not reproducible (intraclass correlation coefficient < 0.5). CONCLUSION: Substantial incremental increase in FEV1 in response to increasing doses of beta-agonists beyond those commonly used in clinical practice is restricted to a minority of patients. Lack of reproducibility limits the clinical usefulness of establishing the optimal dose of beta-agonist for a given patient.

Administration, Inhalation↗
PubMed1992

Early metabolic effects of sepsis in the preterm infant: lactic acidosis and increased glucose requirement.

The effects of sepsis on carbohydrate metabolism were studied in preterm newborn infants (weight > 1.2 kg, appropriate for gestational age) without maternal endocrine problems who were being examined for infection. Plasma glucose, lactate, and insulin concentrations were measured at initial evaluation and then every 8 hours for a total of 48 hours. Blood, urine, and spinal fluid were obtained for culture and counterimmunoelectrophoresis. Dextrose was administered to each patient to maintain glucose levels in the normal range. Dextrose infusion rates were calculated in milligrams per kilogram per minute. Of the 29 infants, 6 had sepsis (positive culture and counterimmunoelectrophoresis results). Infants with sepsis had significant elevations of plasma lactate concentration (p < 0.003) but normal pH. The dextrose infusion rate was also significantly elevated in the infected infants (p < 0.01). No hypoglycemia or hyperglycemia was observed in either group. No significant difference in plasma insulin concentration was observed. We conclude that significant elevations in plasma lactate concentrations and dextrose infusion rate may be early clinical markers of neonatal sepsis in the first 48 hours of life.

Acidosis, Lactic↗
PubMed1990

c-myc, c-fos, and c-jun regulation in the regenerating livers of normal and H-2K/c-myc transgenic mice.

We investigated the mechanisms of regulation of c-myc, c-fos, and c-jun at the early stages of liver regeneration in mice. We show that the transient increase in steady-state levels of c-myc mRNA at the start of liver regeneration is most probably regulated by posttranscriptional mechanisms. Although there was a marked increase in c-myc transcriptional initiation shortly after partial hepatectomy, a block in elongation prevented the completion of most transcripts. To gain further information on the mechanism of regulation of c-myc expression during liver regeneration, we used transgenic mice harboring the human c-myc gene driven by the H-2K promoter. In these animals, the murine c-myc responded to the growth stimulus generated by partial hepatectomy, whereas the expression of the transgene was constitutive and did not change in the regenerating liver. However, the mRNA from both genes increased markedly after cycloheximide injection, suggesting that the regulation of c-myc mRNA abundance in the regenerating liver differs from that occurring after protein synthesis inhibition. Furthermore, we show that in normal mice c-fos and c-jun mRNA levels and transcriptional rates increase within 30 min after partial hepatectomy. c-fos transcriptional elongation was restricted in nongrowing liver, but the block was partially relieved in the regenerating liver. Nevertheless, for both c-fos and c-jun, changes in steady-state mRNA detected after partial hepatectomy were much greater than the transcriptional increase. In the regenerating liver of H-2K/c-myc mice, c-fos and c-jun expression was diminished, whereas mouse c-myc expression was enhanced in comparison with that in nontransgenic animals.

Animals↗
PubMed1989

Encapsulated nerve endings in murine dorsal ear skin.

Encapsulated nerve endings in the hairy skin of mice were identified by means of cholinesterase histochemistry. They were especially numerous in the dorsal skin of the ear and where totals ranged from 150 to 597; clustering of corpuscles was an obvious feature. The use of silver impregnation as a counterstain revealed that clusters comprised one or more sets of lamellated corpuscles, each being attached to a single parent axon. The members of each set resembled one another morphologically. Corpuscles from different sets could be classified as simple, branched or coiled. In the hairy skin of cheek, trunk and hindlimb a much lower density of corpuscles was observed; they were all simple in form and occurred in small clusters.

Aging↗
PubMed1986

Motor innervation of rodent diaphragm.

In order to investigate the possibility of an intercostal nerve contribution to the motor innervation of the diaphragm, the phrenic nerve was interrupted unilaterally in the root of the neck in rats and mice and the pattern of innervation was later studied histologically. The results showed the phrenic nerve to be the sole source of motor innervation. The only contribution from intercostal nerves was to blood vessels and to intramuscular connective tissue.

Animals↗
PubMed1985

Internodal segments in human laryngeal nerves.

The laryngeal nerves of a recently deceased patient were examined in order to determine whether the prenatal elongation of the recurrent nerves (especially of the left) is accompanied by significant elongation of internodal segments among their myelinated fibres. No evidence was found to support this notion. In the nerve roots of the cauda equina, internodal elongation is known to accompany ascent of the spinal cord during fetal life. The difference in behaviour in the two cases seems to lie in the fact that the laryngeal nerves reach their final positions before myelination commences, whereas the spinal nerve roots elongate later, at a time when Schwann cell multiplication has largely ceased.

Humans↗
PubMed1982

Sources of innervation of the neuromuscular spindles in sternomastoid and trapezius.

The sources of innervation of neuromuscular spindles in sternomastoid and trapezius have been investigated in rats and mice, by degeneration experiments. The entire motor supply, both extrafusal and intrafusal, to both muscles, was from the spinal accessory nerve. The sensory supply to the spindles in sternomastoid and rostral trapezius was from cervical spinal nerves, and to those in the caudal trapezius was from thoracic spinal nerves.

Acromion↗
PubMed1981

A method of staining basal-cell plasma membranes in epidermal sheets.

An adenosine triphosphatase method was devised to stain basal epidermal cell plasma membranes in sheet preparations of humans, rat, mouse and guinea pig epidermis. The method is useful for direct observation of sizes, shapes, and numbers of basal epidermal cells.

Adenosine Triphosphatases↗
PubMed1979

The structure and source of lingual proprioceptors in the monkey.

The proprioceptive innervation of the tounge has been investigated in the Cynamolgus monkey by silver impregnation methods following unilateral section of lingual, hypoglossal, and cervical nerves. Muscle spindles were constantly present in the intrinsic and extrinsic muscles. They varied greatly in number, averaged half the length of lumbrical spindles, and showed an unusual arrangement of chain fibre nuclei. Other, inconstant proprioceptors included tendon endings, Ruffini endings, Pacinian corpuscles, paciniform and lamellated endings. Topologically, the endings other than spindles were extra-muscular, so that the overall pattern of proprioceptive innervation resembled that of skeletal muscle in general. Lingual nerve section was without apparent effect on the proprioceptors. Section of the hypoglossal nerve at its point of entry into the tongue caused severe depletiion of ipsilateral proprioceptors and of fusimotor nerves. In the anterior tongue there was evidence of transmedian overlap by efferent and afferent axons contained in the hypoglossal nerve. Hypoglossal section at the skull base caused degeneration of fusimotor nerves but not of proprioceptors. Section of (a), the connexion of C2-C3 ventral rami with the hypoglossal, together with section of (b), the ramus descendens hypoglossi, coused depletion of lingual proprioceptors; again there was evidence of transmedian overlap. Procedures (a) or (b) alone had a lesser effect. It was concluded that lingual proprioceptive afferent fibres occupy the distal hypoglossal nerve, leaving it in the ramus descendens and in the C2-C3 connexion to enter the spinal cord via nerves C2 and C3.

Animals↗