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Biomedical subjects

N Gerber

Publications and source records attributed to N Gerber.

At least 73 records · Page 4Linked to original sources
PubMed1988

Primary hypertrophic osteoarthropathy.

We describe seven patients with primary HOA and review 125 cases reported in the English, French, and German literature. The salient clinical features of primary HOA are: a bimodal distribution of disease onset with one peak during the first year of life and the other at age 15, a male predominance (nine to one), uncommon benign joint effusion, and a variety of skin abnormalities resulting from cutaneous hypertrophy or glandular dysfunction. We concluded that HOA is not a synovial disease. It is suggested that synovial effusions, when present, are perhaps a sympathetic reaction to the neighboring periostitis. Proposed diagnostic criteria for HOA, including digital clubbing and radiographic periostitis, appear 86% sensitive. The clinical features, age of onset, and sex distribution suggest that a genetically controlled growth promoting factor, different from growth hormone, plays a role in the pathogenesis of this syndrome.

Adolescent↗
PubMed1988

Ectopic ossification following total hip arthroplasty: is diffuse idiopathic skeletal hyperostosis a risk factor?

Total hip arthroplasty may be followed by ectopic bone formation. An increased frequency has been suspected in patients with diffuse idiopathic skeletal hyperostosis (DISH). In 204 patients we found that, of the 38 subjects with pre-existing DISH, 29% developed postoperative ossification compared with only 10% in those without DISH (p less than 0.01). DISH is therefore a risk factor for postoperative ectopic bone formation. In a separate study of 1325 patients (not analysed for spinal DISH), we looked for correlations between the severity of postoperative ectopic bone and clinical measurements. Even for the more severe ossification grades (n = 112), only 10% reported serious pain and only 26% had reduced hip flexion (less than 70 degrees). Thus, periprosthetic ectopic bone is not sufficiently important to justify the routine use of preventative drugs such as bisphosphonates in patients with DISH undergoing total hip replacement.

Adult↗
PubMed1988

Chest pain without radiographic sacroiliitis in relatives of patients with ankylosing spondylitis.

The prevalence of complaints of thoracic pain or stiffness in the past 6 months was assessed by examination, HLA typing and sacroiliac radiographs in 420 relatives of 275 B27+ probands with ankylosing spondylitis (AS). AS or sacroiliitis was found in 15 of 420 relatives (3.6%). The gender of the proband did not influence the probability of AS or sacroiliitis among the relatives. In the absence of sacroiliitis, B27+ relatives had chest pain more often (31 of 208, or 14.9%) than B27- relatives (13 of 197, or 6.6%) (p less than 0.01). Chest pain assessed by questionnaire was associated with pain on pressure at the costosternal junctions. The concept of AS as a combination of radiographic sacroiliitis plus clinical signs or symptoms may be too narrow.

Adolescent↗
PubMed1987

[Pleuropulmonary manifestations in chronic polyarthritis].

Nine cases of rheumatoid arthritis with pleuropulmonary involvement illustrate the most common pulmonary symptoms of this disease: rheumatoid pleurisy, interstitial pneumopathy, pulmonary rheumatoid nodules and bacterial pleuropulmonary infections. Each of these pleuropulmonary manifestations may precede the joint disease and cause considerable diagnostic difficulties. Rheumatoid pleural effusion displays an interesting pathognomic constellation: low glucose- and elevated lactate-dehydrogenase concentration, acid pH, often pathologic C1q-binding assay, and characteristic cytomorphology of the pleural fluid. Interstitial pneumopathy is usually mild and slowly progressive. Additional spirometric tests to determine ventilation disturbances sometimes demonstrate airway obstruction. Lower-airway obstruction is probably not caused by the disease itself but may be due to other risk factors (eg cigarette smoking). Depending on their localization, intrapulmonary nodules may lead to severe complications (hemoptysis, bronchopleural fistula, pneumothorax, abscess formation). The possibility of pleuropulmonary infection must always be kept in mind as patients with rheumatoid arthritis have a higher susceptibility to infection.

Adult↗
PubMed1987

Disposition of aspirin and its metabolites in the semen of man.

The study was undertaken to determine the distribution of aspirin and its metabolites in the semen of humans after an oral dose of aspirin. Each of seven healthy male volunteers was given a single oral dose of 975 mg of aspirin on an empty stomach together with 200 mL of water. Timed samples of blood and semen were obtained from each subject, and the concentrations of aspirin, salicylic acid, and salicyluric acid determined by a specific high-performance liquid chromatographic assay. The mean peak concentration of aspirin was 6.5 micrograms/mL in plasma (range, 4.9-8.9 micrograms/mL), reached in 26 minutes (range, 13-33 minutes). The half-life of aspirin was 31 minutes. The concentration ratio of aspirin (semen/plasma) was 0.12 (except for one subject in whom it was 0.025). The mean peak concentration of salicylate in plasma was 49 micrograms/mL (range, 42-62 micrograms/mL), reached in 2.5 hours (range, 2.0-2.8 hours). Salicylate distributed rapidly into semen and maintained a concentration ratio (semen/plasma) of 0.15. Salicyluric acid (the glycine conjugate of salicylic acid) was found in the semen. Its high concentration in some subjects' semen (four times the concurrent plasma concentration) was attributed to contamination of semen sample with residual urine, containing salicylurate, in the urethra of those who urinated after the dose of aspirin. Possible side effects of aspirin and salicylate in semen include adverse effects on fertility, male-medicated teratogenesis, dominant lethal mutations, and hypersensitivity reactions in the recipients.

Adolescent↗
PubMed1987

Methoxsalen is a potent inhibitor of the metabolism of caffeine in humans.

The acute effect of a single oral dose of methoxsalen on the pharmacokinetics of caffeine was investigated in five nonsmoking volunteers with psoriasis. Caffeine, 200 mg orally, was administered to each subject at baseline before treatment with methoxsalen. One week later each subject was given a single oral dose of 1.2 mg/kg methoxsalen 1 hour before administrations of another oral dose of 200 mg caffeine. The clearance of caffeine declined markedly from 110 +/- 17 ml/min (mean +/- SE) in the control study to 34 +/- 5 ml/min after methoxsalen. During the period of maximum inhibition the mean elimination half-life of caffeine increased from 5.6 hours at baseline to 57 hours after administration of methoxsalen. The peak concentration of caffeine and the time to reach the peak concentration of caffeine were not affected by pretreatment with methoxsalen. Thus, methoxsalen, administered acutely, is a potent inhibitor of caffeine metabolism in humans with psoriasis. Results of this investigation suggest that the elimination of concurrently administered drugs may be inhibited in patients receiving methoxsalen. In comparison with other drugs, methoxsalen is the most potent inhibitor of drug metabolism in humans. Other work has shown that inhibition of drug metabolism by methoxsalen is associated with both extensive covalent binding of metabolite(s) of methoxsalen to liver microsomal protein in vitro and in vivo and inactivation of cytochrome P-450.

Adult↗
PubMed1987

Inhibition and induction of drug biotransformation in vivo by 8-methoxypsoralen: studies of caffeine, phenytoin and hexobarbital metabolism in the rat.

The effects of 8-methoxypsoralen (8-MOP) on drug metabolism in vivo were studied in catheterized rats. Rats were pretreated with a single i.p. injection of 5.4 or 27 mg/kg of 8-MOP, 30 min before an i.v. injection of either caffeine (CA; 10 mg/kg), hexobarbital (HB; 40 mg/kg), phenytoin (DPH; 15 mg/kg) or 5-(4'-hydroxyphenyl)-5-phenylhydantoin (HPPH; 15 mg/kg). Clearance of CA, HB and DPH, respectively (drugs eliminated primarily by phase-1 biotransformation), decreased from 0.25 +/- 0.02, 2.9 +/- 0.2 and 1.6 +/- 0.1 liters/kg/hr (means +/- S.E.) in control rats to 0.062 +/- 0.006, 0.65 +/- 0.15 and 0.09 +/- 0.03 liters/kg/hr in rats pretreated once with 27 mg/kg of 8-MOP. In contrast, the clearance of HPPH, which is eliminated primarily by glucuronidation, decreased only slightly from 1.3 +/- 0.1 liters/kg/hr in controls to 0.89 +/- 0.02 liters/kg/hr in rats pretreated with a single injection of 27 mg/kg of 8-MOP. Induction of drug metabolism by 8-MOP was studied in vivo in rats pretreated with 50 mg/kg/day of 8-MOP for 3 days and given an i.v. injection of CA, HB, DPH or HPPH 24 hr after their last pretreatment. This regimen increased the clearance of CA from 0.25 +/- 0.02 liters/kg/hr in controls to 1.08 +/- 0.04 liters/kg/hr in pretreated rats but had no significant effect on the elimination of HB, DPH and HPPH. Thus, acutely, 8-MOP is a potent, nonselective inhibitor of phase-1 metabolism in vivo. In contrast, chronically, it is a specific inducer of the metabolism of CA.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Inhibition of elimination of caffeine by disulfiram in normal subjects and recovering alcoholics.

The kinetics of caffeine elimination were investigated in 10 normal male subjects and in 11 recovering alcoholics before and during disulfiram dosing. In normal subjects the total body clearance of caffeine declined 30% (142 to 99 ml/min) at the maintenance dose of disulfiram, 250 mg/day, and 29% (161 to 114 ml/min) at the loading dose of 500 mg/day. In recovering alcoholics, the total body clearance decreased from 333 to 253 ml/min, a 24% change. The mean caffeine t1/2 increased 39% and 34% in normal subjects after 250 and 500 mg disulfiram, respectively, and 29% in recovering alcoholics. The inhibition of caffeine elimination was moderate in most subjects. However, the clearance of caffeine decreased by greater than or equal to 50% after disulfiram in three of the 11 recovering alcoholics. These patients may have an increased risk of cardiovascular and cerebral excitation associated with higher concentrations of caffeine, which could complicate withdrawal from alcohol.

Administration, Oral↗
PubMed1986

Disposition of 8-methoxypsoralen in the rat: methodology for measurement, dose-dependent pharmacokinetics, tissue distribution and identification of metabolites.

The pharmacokinetics and metabolism of 8-methoxypsoralen (8-MOP) were measured in the catheterized rat after a single i.v. dose. Blood samples were collected serially and analyzed using a sensitive and specific assay for [14C]-8-MOP. Total body clearance of 8-MOP was 7.3, 3.9, 1.7, 1.0, 0.78 and 0.42 liters/kg/hr at doses of 0.2, 1.0, 2.5, 5.0, 10 and 20 mg/kg, respectively. The decline in total body clearance indicates that elimination of 8-MOP is dose-dependent in the rat. After i.v. administration of 10 mg/kg of 8-MOP, 71 and 26% of the dose was recovered within 72 hr in the urine and feces, respectively. Unchanged 8-MOP accounted for less than 1% of the excreted radioactivity. In tissue distribution studies at 0.5, 2 and 5 hr after i.v. administration, 8-MOP distributed rapidly to all tissues and concentrated in the fat and kidneys. The concentration of 8-MOP in the skin was 0.4 to 0.6 times that in the blood. Eleven metabolites of 8-MOP were detected in the urine. The metabolites identified after enzymatic hydrolysis were 8-hydroxypsoralen; 5-hydroxy-8-methoxypsoralen; 5,8-dihydroxypsoralen; 5,8-dioxopsoralen; 6-(7-hydroxy-8-methoxycoumaryl)-acetic acid and 8-MOP (formed by ring closure of a coumaric acid metabolite). Thus, these studies indicate that 8-MOP is metabolized in the rat by 1) O-demethylation; 2) hydroxylation at position 5; 3) hydrolysis of the lactone ring and 4) oxidation of the furan ring, a pathway already confirmed in insects, dogs and humans.

Animals↗
PubMed1985

Metabolism, distribution, seminal excretion and pharmacokinetics of caffeine in the rabbit.

The pharmacokinetics, tissue distribution and metabolism of caffeine were studied in male New Zealand White rabbits after an i.v. dose of 4 mg/kg. The mean (n = 4) distribution half-life was 0.2 hr and the mean elimination half-life was 3.8 hr. The mean clearance was 0.20 liters/kg/hr and the mean volume of distribution was 0.82 liters/kg. Concurrent samples of blood and semen from three rabbits, trained to ejaculate into an artificial vagina, were analyzed. The mean semen/blood concentration ratio of caffeine was 1.0. The concentrations of caffeine in the tissues of three rabbits were examined at 1 hr after an i.v. dose of 4 mg/kg. Most tissues exhibited a tissue/blood concentration ratio of approximately 1.0. Exceptions to this included fat, adrenals, liver and bile in which the ratios were 0.2, 0.6, 1.5 and 2.7, respectively. Urinary metabolites were investigated after an i.v. dose of 4 mg/kg of [14C]caffeine. The metabolites of caffeine were separated by high-pressure liquid chromatography and quantified by liquid scintillation counting. The major urinary metabolites of caffeine in the rabbit were 1-methylxanthine (22%), 1-methyluric acid (19%), 7-methylxanthine (16%) and 1,7-dimethylxanthine (14%).

Animals↗
PubMed1984

Improved method for the determination of aspirin and its metabolites in biological fluids by high-performance liquid chromatography: applications to human and animal studies.

An improved method has been developed for the determination of acetylsalicylic acid, salicylic acid, gentisic acid, and salicyluric acid in plasma and urine of rabbits and man. Samples are extracted with dichloromethane containing mephenytoin as an internal standard, the solvent is evaporated under reduced pressure, the residue reconstituted and analyzed by high-performance liquid chromatography. Extraction efficiencies, linearity and assay precision were determined. This method has been applied to human bioavailability studies and the data are presented.

Animals↗
PubMed1983

Identification and characterization of the glucuronide metabolite of diethyldithiocarbamic acid in the bile from the isolated perfused rat liver by gas chromatography and mass spectrometry.

The glucuronide metabolite of diethyldithiocarbamic acid has been identified in bile from the isolated perfused rat liver. The bile was chromatographed on XAD-2 resin, pertrimethylsilylated with BSTAF + 1% TMCS, identified and characterized by combined gas chromatography and mass spectrometry. The glucuronide characterized as the silylated derivative showed no molecular ion but a small fragment ion at M-15(598).

Animals↗