Characterization of ciliary activity in distal Fallopian tube biopsies of women with obstructive tubal infertility

Biopsy specimens were obtained from the distal end of the Fallopian tubes of 62 women with tubal infertility and examined by light and electron microscopy. Ciliary beat frequency (CBF) measurements were obtained using laser light spectroscopy. Neither demographic nor behavioural characteristics nor serological evidence of past chlamydial infection were associated with CBF measurements. In contrast, CBF were significantly lower (P < 0.05) in tissues with oedema compared to tissues without oedema (6.7 versus 12.9) and in tissues with erythema compared to tissues without erythema (9.2 versus 13.7). Furthermore, CBF measurements did vary by chlamydial serotype pattern, with lower values observed among the tissues of women with antibodies to serotype C or E (without D) as compared to the tissues of women with other serotypes (P < 0.04). However, these data must be interpreted with caution as the numbers of subjects with chlamydial antibodies to serotype C (n = 3) or E without D (n = 5) were few in number and serotyping of IgG antibodies in blood is not as accurate as it is in bacterial isolates. Confirmation of the suggested association between chlamydial serotype and risk of adverse sequelae could indicate potential new avenues for vaccine research.      

High-Pressure Liquid Chromatographic Assay of Netilmicin in Plasma

A high-pressure liquid chromatographic method for the quantitative determination of netilmicin in plasma was developed. The procedures involve acetonitrile protein precipitation, methylene chloride extraction, and dansylation to form the fluorescent dansyl derivative of netilmicin, which is extracted into ethyl acetate and chromatographed on a reverse-phase column with aqueous acetonitrile as the mobile phase. A good linear relationship between peak height measurements and netilmicin concentrations was found. This method is sensitive and reproducible; a netilmicin concentration as low as 0.5 μg/ml can be measured with only 0.1 ml of plasma sample. The results of assays of plasma or serum samples by this high-pressure liquid chromatographic method correlate well with those obtained by microbiological assays.     

Mutations in the herpes simplex virus major DNA-binding protein gene leading to altered sensitivity to DNA polymerase inhibitors

Five herpes simplex virus mutants containing temperature-sensitive mutations in the gene for the major DNA-binding protein were assayed for their sensitivities to the DNA polymerase inhibitors aphidicolin and phosphonoacetic acid (PAA). Four of the mutants (tsA1, tsA15, tsA24, and tsA42) exhibited altered sensitivity to one or both of the inhibitors relative to the wild-type parent. In tsA1, a mutation or mutations conferring aphidicolin and PAA hypersensitivity were mapped by corescue with the temperature-sensitivity marker of tsA1 to a region of the DNA-binding protein locus, between map coordinates 0.385 and 0.398. The mutation conferring PAA hypersensitivity in tsA24 similarly corescued with the tsA24 temperature-sensitivity marker, mapping to the DNA-binding protein locus between coordinates 0.398 and 0.413. Thus, mutations outside the DNA polymerase locus and within the DNA-binding protein locus can confer altered sensitivity to certain DNA polymerase inhibitors. Assays of the aphidicolin and PAA sensitivities of ts+ recombinants derived by marker rescue of the DNA-binding protein mutants revealed the presence of additional mutations, separable from the ts mutations, in each of three mutants examined. One such mutation, which contributed to the aphidicolin-hypersensitivity phenotype of tsA1, mapped between coordinates 0.422 and 0.448, and resides, most probably, within the DNA polymerase locus. These additional mutations possibly confer compensating modifications to the DNA polymerase such that functional interaction with altered DNA-binding protein is restored. These findings provide strong evidence that the major DNA-binding protein and the DNA polymerase of herpes simplex virus interact in infected cells.     

Method for the rapid estimation of the total body drug clearance and adjustment of dosage regimens in patients during a constant-rate intravenous infusion

A simple method is proposed to estimate the total body clearance and biological half-life of drugs in patients by determining two blood or plasma levels of drugs separated by an appropriate interval during the constant-rate intravenous infusion. The method is based on the assumptions that the drug disposition in the body can be adequately described by the linear onecompartment open model and its apparent volume of distribution can be estimated with a reasonable degree of accuracy from the literature data. The validity of this newly proposed method was demonstrated in three rabbits using theophylline as a test drug. Results of theoretical error analyses indicate that the method is potentially useful in providing an early guide for dosing adjustments for those potent drugs whose elimination rates have been shown to vary greatly in patients. The method may be particularly useful in patients with changing elimination kinetics of drugs. Effects of the accuracy in V_d estimate, plasma level assay, and sampling time interval on the error of total body clearance estimation are discussed.