Clinical pharmacology and safety evaluation of Timentin.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
D Jackson
Publications and source records attributed to D Jackson.
Fluoridation in Anglesey 1983: a clinical study of dental caries.
Explore the source record for details and available documents.
Adolescent↗
Pseudomonic acid, a new antibiotic for topical therapy.
Pseudomonic acid, a new wide-spectrum antimicrobial agent, was evaluated as a 2% formulation in a cream. Animal studies showed that this formulation was just capable of penetrating the skin. When administered parenterally to animals, pseudomonic acid was converted to inactive metabolites that were quickly eliminated from the body. When pseudomonic acid was applied as a cream to human skin, no sensitization was observed. In an open clinical study, sixty-eight patients with skin infections (mostly superficial conditions such as impetigo, infected eczema, folliculitis, or balanitis) applied pseudomonic acid cream three times a day for 5 days. In fifty patients the infections completely cleared within 2 days of the end of therapy, and considerable clinical improvement was noted in sixteen more. One patient stopped the treatment prematurely due to local burning pain, and one patient could not be evaluated clinically.
Administration, Topical↗
Temocillin. Summary of safety studies.
Temocillin is a novel injectable beta-lactam antibiotic designed for parenteral use. It is active against the majority of Gram-negative bacteria and is stable to a wide range of beta-lactamases. Disposition and metabolic studies on temocillin in animals and man demonstrate that the drug is well distributed throughout the body tissues and will cross the placenta. The major route of elimination is via the kidney (89%) where the drug is excreted unchanged as parent compound, mainly by the glomerular filtration of unbound temocillin. A full toxicological safety evaluation programme has been completed and includes acute, subacute and chronic toxicology in rat and dog, and reproductive and mutagenicity studies. Temocillin was well tolerated in animals at dosages of up to 1000 mg/kg and appears to be without any potential hazard for man in dosages which are well in excess of the proposed therapeutic dose.
Animals↗
Augmentin bioavailability following cimetidine, aluminum hydroxide and milk.
Previous studies [Jackson et al. 1980] have shown that the bioavailability of Augmentin is not affected by food. The present work has shown that aluminum hydroxide, milk and cimetidine do have some influence on the bioavailability of a single dose of oral Augmentin, but the small differences observed are unlikely to be of therapeutic importance. It is concluded that Augmentin may be administered in clinical practice with any of these substances.
Administration, Oral↗
Arrhythmogenic right ventricular dysplasia. Clinical, electrophysiological, and pathological features.
Arrhythmogenic right ventricular dysplasia (ARVD) describes the syndrome of recurrent ventricular tachycardia of right ventricular origin and cardiomyopathic changes of the right ventricle. We report the clinical, electrophysiologic, and angiographic characteristics of four patients who presented with ventricular tachycardia of left bundle branch block configuration, and in whom the right ventricular origin of tachycardia was confirmed by endocardial mapping, and a diagnosis of ARVD was substantiated by histological examination. ARVD should be suspected in all patients with ventricular tachycardia of left bundle branch block configuration, especially in young adults with an otherwise normal heart. Once suspected, diagnosis can often be established by non-invasive investigation. Surgical treatment may be difficult because of the diffuse nature of right ventricular involvement.
Adolescent↗
Segregation of mutant ovalbumins and ovalbumin-globin fusion proteins in Xenopus oocytes. Identification of an ovalbumin signal sequence.
The intramolecular signals for chicken ovalbumin secretion were examined by producing mutant proteins in Xenopus oocytes. An ovalbumin complementary DNA clone was manipulated in vitro, and constructs containing altered protein-coding sequences and either the simian virus 40 (SV40) early promoter or Herpes simplex thymidine kinase promoter, were microinjected into Xenopus laevis oocytes. The removal of the eight extreme N-terminal amino acids of ovalbumin had no effect on the segregation of ovalbumin with oocyte membranes nor on its secretion. A protein lacking amino acids 2 to 21 was sequestered in the endoplasmic reticulum but remained strongly associated with the oocyte membranes rather than being secreted. Removal of amino acids 231 to 279, a region previously reported to have membrane-insertion function, resulted in a protein that also entered the endoplasmic reticulum but was not secreted. Hybrid proteins containing at their N terminus amino acids 9 to 41 or 22 to 41 of ovalbumin fused to the complete chimpanzee alpha-globin polypeptide were also sequestered by oocyte membranes. We conclude that the ovalbumin "signal" sequence is internally located within amino acids 22 to 41, and we speculate that amino acids 9 to 21 could be important for the completion of ovalbumin translocation through membranes.
Amino Acid Sequence↗
Neuropharmacology of delta-aminolaevulinic acid. II. Effect of chronic administration in mice.
delta-Aminolaevulinic acid (ALA) is suspected of being responsible for the neuropsychiatric symptoms of acute porphyria. The object of this study was to examine the effects of continuous administration of ALA in vivo on behaviour known to be affected in acute porphyria. ALA was administered to mice via minipumps implanted subcutaneously. Mean urinary excretion of ALA over the ensuing 7 days was approximately 80 mumol/kg b. wt./day. No significant effects on locomotor activity, motor co-ordination and grip and noci-perception were noted. These results do not support the hypothesis that chronic exposure of animals to ALA may produce a porphyria-like syndrome.
Aminolevulinic Acid↗
Pulmonary scar carcinoma. A case with two primaries.
The presence of scar tissue associated with peripheral pulmonary carcinomas has always evoked considerable interest. This report concerns a unique case of a 55-year-old white oil-field worker whose right pneumonectomy specimen disclosed two primary pulmonary scar cancers, involving both upper and lower lobes. Both carcinomas arose at the margins of pleural-based scars. The malignancy in the right upper lobe was a 2.5-cm large cell carcinoma, while that in the right lower lobe was a 2.0-cm adenocarcinoma. The bronchial and hilar lymph nodes were free of metastases. One month following pneumonectomy the patient suffered a cardiac arrest, and necropscopic examination failed to reveal evidence of metastases. Controversy continues concerning whether the scar precedes or follows the development of peripheral pulmonary carcinomas. Several recent studies favoring the latter theory have suggested that the scar is immunologically related to the carcinoma. In the current case, the pleural-based upper lobe scar was associated with an old, inactive granuloma, while the lower lobe pleural-based scar disclosed no clue as to its origin. The adenocarcinoma in the lower lobe might possibly be immunologically related to its associated scar; however, it would appear difficult to account for the scar of the upper lobe large cell carcinoma by a similar mechanism.
Adenocarcinoma↗
'Children's dental health 1983'.
Explore the source record for details and available documents.
Child↗
Sleep apnea precipitated by pharyngeal surgery in a patient with myotonic dystrophy.
A patient was seen for evaluation of excessive daytime sleepiness, which was exacerbated following complications secondary to surgical reconstruction of the pharynx for a submucous cleft palate. She underwent recordings in the sleep laboratory and was found to have sleep apnea. Also, a thorough clinical and laboratory assessment established the diagnosis of myotonic dystrophy. Following tracheostomy, both the patient's sleep apnea and daytime hypersomnia were eliminated. Our case demonstrates that surgical procedures involving the upper airway should be approached with considerable caution in patients with myotonic dystrophy and only after the presence of associated sleep apnea has been carefully excluded. An original finding is the suggestion of a decrease in the number of T-cell lymphocytes in a patient with myotonic dystrophy.
Adult↗
Factors related to subsequent reproductive outcome in couples with repeated pregnancy loss.
Specific factors in a couple's history may influence the recurrence risk following repeated pregnancy loss (RPL). Couples with RPL were contacted several years following evaluation and information concerning subsequent pregnancies was obtained. Linear regression analysis was utilized to determine which factors in the history were significant predictors of pregnancy outcome following evaluation. A family history of RPL or a "genetic defect" was a highly significant predictor of subsequent unsuccessful pregnancies. Surgical, but not medical, treatment for RPL was a significant predictor of eventual successful outcome. The number of abortions prior to evaluation for RPL, presence of a liveborn child, maternal age at evaluation, and intercurrent infertility all failed to be significant predictors of pregnancy outcome after evaluation.
Abortion, Habitual↗
The role of the laboratory in the diagnosis of cystic fibrosis.
Laboratory investigations used for detecting cystic fibrosis have been critically reviewed. The sweat test is still the only investigation that can be used for detecting the disease at any age. Trypsin in blood or serum might have the same discriminatory power during the first three months of life and could be used for neonatal screening. There is no immediate prospect for prenatal diagnosis or heterozygote detection. The change of the pattern of plasma proteins in cystic fibrosis is the same as in other chronic disorders with varying clinical intensity. Albumin and alpha-1-antitrypsin may be used to monitor treatment. The plasma concentration of alpha-2-macroglobulin is considerably decreased in many younger patients.
Adolescent↗
Antigenic variation during infection with Neisseria gonorrhoeae: detection of antibodies to surface proteins in sera of patients with gonorrhea.
Neisseria gonorrhoeae were cultured from the urethra of male patients and from the cervix and urethra of female contacts. Isolates from a given group of individuals were of the same strain but differed considerably in terms of the molecular weight of both protein II and pili. Radioimmunoprecipitation assays showed that most patients produced serum antibodies to protein I. Antibodies to pili, when present, showed limited cross-reactivity with the different pili produced by a single strain. Antibodies to protein II were highly specific, reacting with only one of the protein II-types produced by a single strain; this observation suggested that the host immune response may be an important factor in antigenic variation. Several sera also contained antibodies to a common surface protein with a molecular weight of 43,000 that was present in all strains tested.
Antibodies, Bacterial↗
The in-vitro activity of metronidazole against strains of Escherichia coli with impaired DNA repair systems.
The minimal inhibitory concentration (MIC) of metronidazole was lower for strains of Escherichia coli with lesions in their DNA repair systems than for their parent strains. The viable numbers of all strains of E. coli tested were considerably reduced by metronidazole, even at sub-MIC levels, and the effect was greater when DNA repair lesions were more severe. In addition, metronidazole caused cell elongation of E. coli and slowly disappeared from the medium upon incubation with the bacterium. The drug-induced decrease in viable numbers of E. coli was followed by an increase. Most cells in this 'recovery' population were found to be anaerogenic and were relatively unaffected by subsequent exposure to metronidazole. The results show that E. coli consumes and is susceptible to metronidazole, under anaerobic conditions. DNA damage is involved in the antibacterial action of the drug, and E. coli resistant to the drug can be obtained readily in in-vitro incubations.
DNA Repair↗
Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis.
We report the case of an infant with hypoglycemia, progressive lactic acidosis, an increased serum lactate/pyruvate ratio, and elevated plasma alanine, who had a moderate to profound decrease in the ability of mitochondria from four organs to oxidize pyruvate, malate plus glutamate, citrate, and other NAD+-linked respiratory substrates. The capacity to oxidize the flavin adenine dinucleotide-linked substrate, succinate, was normal. The most pronounced deficiency was in skeletal muscle, the least in kidney mitochondria. Enzymatic assays on isolated mitochondria ruled out defects in complexes II, III, and IV of the respiratory chain. Further studies showed that the defect was localized in the inner membrane mitochondrial NADH-ubiquinone oxidoreductase (complex I). When ferricyanide was used as an artificial electron acceptor, complex I activity was normal, indicating that electrons from NADH could reduce the flavin mononucleotide cofactor. However, electron paramagnetic resonance spectroscopy performed on liver submitochondrial particles showed an almost total loss of the iron-sulfur clusters characteristic of complex I, whereas normal signals were noted for other mitochondrial iron-sulfur clusters. This infant is presented as the first reported case of congenital lactic acidosis caused by a deficiency of the iron-sulfur clusters of complex I of the mitochondrial electron transport chain.
Acidosis↗
Parenteral augmentin: pharmacokinetics.
The pharmacokinetics of intravenous Augmentin have been investigated and the data found to fit a two compartment model. In the first study, to a crossover design, a bolus injection of 1.2 g Augmentin was given to 8 healthy volunteers with and without probenecid. It was found that the serum concentrations of amoxycillin were increased in the presence of probenecid, but those of clavulanic acid were unaffected. In a second study a further 8 volunteers received an infusion over 30 min of 2.2 g Augmentin. At the end of the infusion, peak concentrations in excess of 100 micrograms/ml were recorded for amoxycillin and 14 micrograms/ml for clavulanic acid. In both studies the serum and urinary concentrations of amoxycillin and clavulanic acid obtained were well above those considered necessary to achieve a therapeutic effect.
Adult↗