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Biomedical subjects

P Sanders

Publications and source records attributed to P Sanders.

At least 73 records · Page 4Linked to original sources
PubMed1992

Pharmacokinetics of spiramycin after intravenous, intramuscular and subcutaneous administration in lactating cows.

Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

The second amino acid of alfalfa mosaic virus coat protein is critical for coat protein-mediated protection.

Transgenic plants expressing the coat protein (CP) of alfalfa mosaic virus (AIMV) are resistant to infection by AIMV. A mutation was introduced into the second amino acid of the cDNA for the CP of AIMV. Three different transgenic tobacco lines expressing the mutant CP and two different transgenic tobacco lines expressing the wild-type CP at similar levels were challenged with AIMV virions and viral RNA. Whereas the lines expressing the wild-type CP were highly resistant to infection by AIMV virions and viral RNA, the lines expressing the mutant CP were susceptible to infection by both. The binding affinity of the mutant and the wild-type CPs for the 3' terminal protein binding site on AIMV RNAs was similar, as determined by electrophoretic mobility shift assay. A mixture of AIMV genomic RNAs 1-3 was infectious on the plants expressing the mutant CP but not on vector control plants or plants expressing the wild-type CP, indicating that the mutant CP can activate the AIMV genomic RNAs for infection. These results demonstrate that the second amino acid of the AIMV CP is critical for protection from AIMV but not for the initial interaction between the AIMV RNA and CP, suggesting that this initial interaction does not play a major role in CP-mediated protection.

Journal Article↗
PubMed1991

Detection of human papillomavirus DNA by PCR in semen from patients with and without penile warts.

OBJECTIVES: To determine the prevalence of urethral HPV infection, as indicated by the presence of HPV DNA in semen, in males with and without penile warts. DESIGN: Prevalence study of HPV types 6/11 and 16 DNA using PCR and Southern blot hybridisation analysis of semen. SETTING: Department of Genitourinary Medicine, Blundell Street Clinic, Leeds General Infirmary and the Assisted Conception Unit (ACU) Kings' College, London. SUBJECTS: Patients attending the Genitourinary Clinic for treatment of sexually transmitted diseases including penile warts and males attending Kings' ACU for investigations of infertility. MAIN OUTCOME MEASURES: HPV DNA detected by polymerase chain reaction (PCR) and/or Southern blot hybridisation in semen. RESULTS: HPV DNA was detected by PCR in 23 of 27 (85%) specimens from patients attending the GUM clinic for treatment of genital warts and in one of two specimens from patients attending the clinic for other conditions. By Southern blot, nine (33%) of the 29 specimens from GUM clinic patients were HPV DNA-positive. HPV DNA was detected by PCR in 43 of 104 (41%) of specimens from males attending the ACU, whilst 70 of these tested by Southern blot hybridisation were all negative for HPV DNA. CONCLUSIONS: The data suggest that urethral HPV infections, as indicated by the presence of HPV DNA in semen, are prevalent in males with and without genital warts.

Blotting, Southern↗
PubMed1991

[Pharmacokinetics of colistin sulfate administered by intravenous and intramuscular routes in the calf].

Pharmacokinetic characteristics of an extemporaneous form of colistin sulfate in young calves were studied for a dosage of 25,000 IU.kg-1. The intravenous route (IV) is characterized by a 3-compartment model whose main parameters are: volume of distribution (1.02 l.kg), body clearance (0.15 l.h-1 kg-1) and mean residence time (3.87 h). By intramuscular route (IM), a mean serum peak of 37 IU.ml-1 was reached at a mean time of 0.5 h. The mean half-time of terminal phase (6.47 h) does not differ significantly from that of the intramuscular route (4.52 h). Absolute bioavailability calculated based on 4 calves was 109 +/- 28%. Repeated IM administrations seem to be adapted to maintain a bactericidal activity and to reduce risks of toxicity and neurological disorders (25,000 IU.kg-1) every 12 h over 3d.

Animals↗
PubMed1990

Engineering resistance to mixed virus infection in a commercial potato cultivar: resistance to potato virus X and potato virus Y in transgenic Russet Burbank.

Potato virus X (PVX) and potato virus Y (PVY) infection in potato may result in the loss of certification of seed potatoes and affect quality and yield of potatoes in commercial production. We transformed a major commercial cultivar of potato, Russet Burbank, with the coat protein genes of PVX and PVY. Transgenic plants that expressed both CP genes were resistant to infection by PVX and PVY by mechanical inoculation. One line was also resistant when PVY was inoculated with viruliferous green peach aphids. These experiments demonstrate that CP protection is effective against mixed infection by two different viruses and against mechanical and aphid transmission of PVY.

Amino Acid Sequence↗
PubMed1990

Pharmacokinetics of chloramphenicol in sheep after intravenous, intramuscular and subcutaneous administration.

The pharmacokinetics of chloramphenicol were studied in sheep after 3 single intravenous (IV), intramuscular (IM) and subcutaneous (SC) administrations (30 mg/kg). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After IV and SC administrations, the plasma-concentration time graphs were characteristic of a two-compartment model, and after IM administration it was characteristic of a monocompartment model. The two routes of absorption were not bioequivalent. Using the kinetic values, multidose regimens to maintain the therapeutic chloramphenicol blood level (5 micrograms/ml) were proposed: 60 mg/kg every 12 hours for 72 hours for the IM administration and 45 mg/kg administered subcutaneously according to the same regimen. A study of the chloramphenicol residues in tissues was carried out. Chloramphenicol residues remained at the injection site, and 400 hours would be necessary to obtain the level of 10 micrograms/kg. Determination of the creatinine phosphokinase serum values showed that the subcutaneous route induced less damage to muscle than the intramuscular route.

Animals↗
PubMed1990

DQw7 and the C4B null allele in rheumatoid arthritis and Felty's syndrome.

DQ beta and C4 null alleles have been defined in patients with rheumatoid arthritis, Felty's syndrome, and in control subjects. Comparison of DR4 positive subjects shows that rheumatoid disease without extra-articular features has no preferential associations with either DQ beta or C4 null variants. In Felty's syndrome there are significant associations with both the class II major histocompatibility complex (MHC) DQw7 allele (86% of DR4 positive patients with Felty's syndrome and 53% of DR4 positive controls) and the class III MHC C4B null allele (50% of patients with Felty's syndrome and 20% of DR4 positive controls). DQw7 and the C4B null allele are in linkage disequilibrium and the B44-Bf *S-C4A*3-C4B*Q0-DR4-DQw7 haplotype accounts for five of 24 DR4 positive haplotypes assigned in subjects with Felty's syndrome. The results were not accounted for by articular disease severity and suggest that articular and extra-articular forms of rheumatoid disease may be immunogenetically heterogeneous.

Alleles↗
PubMed1990

Deconvolution study of the absorption rate and disposition kinetic values of lindane in sheep.

Absorption rate and plasma and fat disposition of lindane after various lindane percutaneous treatments in shorn and unshorn sheep were investigated. To analyze data with a deconvolution method, IV administration was performed to determine the basic pharmacokinetic values of lindane in sheep. After IV administration, the steady state volume of distribution was very high (8.07 +/- 3.60 L/kg of body weight), and the mean residence time was long (28.1 +/- 11.7 hours). Deconvolution analysis indicated that lindane absorption was continuous until 33 to 41 days after spraying with a 0.025% lindane solution. Total amount of absorbed lindane in shorn (15,171 +/- 4,463 micrograms/kg) sheep was about twice that in unshorn (7,615 +/- 3,128 micrograms/kg) sheep; from deconvolution analysis, it was calculated that the time required for 50% of the available dose to be absorbed was between 115 and 179 hours. After percutaneous lindane administration, the fat concentration was compared with the available lindane dose. The apparent half-life of lindane elimination in fat was 225 +/- 47.4 hours, which is similar to the value calculated for the absorption rate constant. By comparing fat and plasma concentrations, it was calculated that for a mean plasma concentration of 5 ng/ml, the fat lindane concentration was 1.65 +/- 0.87 micrograms/g (ie, lower than the generally accepted tolerance level of 2 micrograms/g).

Adipose Tissue↗
PubMed1990

[The bioequivalence of intramuscular and subcutaneous administration of a formulation of oxytetracycline in the young bull].

A bioequivalence study was performed in 6 bullocks to compare intramuscular (im) and subcutaneous (sc) routes for repeated treatments with an oxytetracycline formulation. Basic pharmacokinetic parameters were determined after a 10 mg/kg intravenous administration. Bioavailabilities for both im et sc routes were close to 85%. The pharmacokinetic parameters were used to perform an analysis of variance, and to determine the 95% confidence intervals and Westlake symmetrical confidence intervals. The two routes were significantly different regarding maximum concentration. The following symmetrical confidence intervals were calculated: area under the curve (+/- 20%), minimum concentration (+/- 51.5%), period during which plasma concentration was above 1 microgram/ml (+/- 25%). The two routes were bioequivalent for the area under curve.

Analysis of Variance↗
PubMed1989

Immunoglobulin heavy chain constant region variants in rheumatoid arthritis.

Polymorphisms within the immunoglobulin heavy chain constant region at switch (S)mu and S alpha 1 loci were studied in patients with rheumatoid arthritis (RA) and controls in parallel with Gm and A2m allotyping. S mu and S alpha 1 restriction fragment length polymorphisms were defined using a S mu probe which was hybridised to SstI digests of DNA extracted from circulating white cells. There were no differences in S mu and S alpha 1 gene or phenotype frequencies between RA and control groups nor within the RA population between DR4 positive and negative subjects. The Gm allotype G1m(x), coded for by genes at the gamma-1 locus, was found in 29/92 (32%) of DR4 positive and 5/52 (10%) of DR4 negative subjects with RA, as compared with 25/115 (22%) cf controls. The A2m allotype A2m(2), coded for by the alpha 2 locus, was found in 11/92 (12%) of DR4 positive subjects with RA, zero of 52 DR4 negative subjects, and 5/115 (4%) of controls. These results exclude a major effect of genes within the heavy chain constant region linked to mu or alpha 1 loci on susceptibility to RA, but suggest that further study of variants closely linked to the alpha 2 locus is indicated.

Arthritis, Rheumatoid↗
PubMed1988

Pharmacokinetics of a long-acting chloramphenicol formulation administered by intramuscular and subcutaneous routes in cattle.

The pharmacokinetic properties of a long-acting formulation of chloramphenicol were determined in six yearling cattle after a single intravenous (i.v.) administration (40 mg/kg body weight) and after two sequential subcutaneous (s.c.) or intramuscular (i.m.) administrations (90 mg/kg/48 h). The two extravascular routes were studied during a crossover trial for a bioequivalence test. After i.v. administration, the plasma concentration-time graph was characteristic of a two-compartment open model. Mean values were a half-life of 4.1 h, a volume of distribution of 0.86 l/kg and a body clearance of 0.128 l/kg/h. Plasma concentrations of chloramphenicol following i.m. and s.c. administrations increased slowly to a broad peak at 10-15 micrograms/ml between 9 and 12 h. Bioavailability was 19.1% after i.m. injection and 12.4% after s.c. administration. The extent of absorption from the two routes did not differ significantly. The rate of absorption was significantly lower after s.c. application than it was after i.m. injection. The time necessary for the plasma concentration to exceed 5 micrograms/ml was the same for the two routes. Thus, i.m. and s.c. routes are bioequivalent.

Animals↗
PubMed1988

[Pharmacokinetic study of chloramphenicol in the rabbit].

Chloramphenicol was administered intravenously and orally at a dose of 50 mg/kg to ten rabbits. Pharmacokinetic parameters were calculated (rate constant of terminal phase: beta = 0.21 +/- 0.09 1/h, total body clearance: Cl = 22.7 +/- 2.1 ml/min.kg, bioavailability: F = 42.5 +/- 11.9%) and were used to discuss the proposed dosage. However, caecotrophy might occur and increase absorption of chloramphenicol.

Administration, Oral↗
PubMed1987

Two-year evaluation of misoprostol for carcinogenicity in CD Sprague-Dawley rats.

The carcinogenic potential of misoprostol, a synthetic prostaglandin E1 analogue with anti-ulcer potential, was evaluated in CD Sprague-Dawley rats. The compound was given daily by gavage at 24, 240, and 2,400 micrograms/kg, up to 150 times the daily human dose for 2 years. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic finding was epithelial hyperplasia and hyperkeratosis of the gastric mucosa. These changes, which are characteristic of some prostaglandins, were expected. Other non-neoplastic findings were typical of known spontaneous conditions in this strain of rats. The most frequent neoplasm was the pituitary adenoma, followed by the mammary fibroadenoma, mammary adenoma, mammary adenocarcinoma, and thyroid C-cell adenoma. A rare neoplasm, squamous cell carcinoma of the ovary was found in two rats. There was no evidence that misoprostol is carcinogenic for CD Sprague-Dawley rats.

Alprostadil↗
PubMed1987

Twenty-one-month evaluation of misoprostol for carcinogenicity in CD-1 mice.

Misoprostol, a synthetic prostaglandin E1 methyl ester analogue with anti-ulcer potential, was evaluated for its carcinogenic potential in CD-1 strain mice. The compound was given daily by gavage at 160, 1,600, and 16,000 micrograms/kg for 21 months. Necropsies were done on all animals and the incidences of non-neoplastic and neoplastic changes analyzed for significance by life table methods. The only statistically significant non-neoplastic compound-related findings were epithelial hyperplasia and hyperkeratosis of the gastric mucosa and hyperostosis of bone in the marrow cavity of sternebrae and femurs. The changes in the gastric epithelium are characteristic of some prostaglandins and were expected. The bone hyperostosis was associated with misoprostol in high dosages, and was considered unique to the mouse. Other non-neoplastic findings were typical of known spontaneous conditions in mice. The most frequent neoplasm was the hepatocellular adenoma followed by lymphosarcoma, lung alveolar carcinoma, and Harderian gland adenoma. Several proliferative lesions of the duodenum were considered to be spontaneous. These were focal avillous hyperplasia, focal atypical hyperplasia, and junctional polyp. There was no evidence that misoprostol is carcinogenic for CD-1 mice.

Alprostadil↗
PubMed1987

Abraham Groves.

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Appendectomy↗
PubMed1986

Genetics of rheumatoid arthritis.

The haplotype sharing distribution in affected sib pairs are used to demonstrate the linkage of a susceptibility gene for rheumatoid arthritis (RA) to the HLA region. Family and population studies suggest heterogeneity in the etiology of RA.

Alleles↗
PubMed1977

Benign lesions of the tunica albuginea.

Although most testicular masses are malignant we present 7 cases to demonstrate that benign lesions of the tunica albuginea do occur and that these may be a source of diagnostic confusion. Consideration should be given to the possibility of a benign lesion of the tunica albuginea when the lesion is small, discrete, painless and projecting above the surface of the tunica albuginea. All of our patients were referred to us with a tentative diagnosis of testicular malignancy. We do not wish to decrease the importance of vigilance concerning testicular masses but the cases presented herein demonstrate that all masses of the testis are not malignant.

Adult↗