Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study

The objectives were to determine quantitative liver function prospectively in patients with rheumatoid arthritis (RA) treated with low-dose methotrexate (MTX), to search for risk factors for a loss of quantitative liver function and to assess the relationship between quantitative liver function and histological staging. A total of 117 patients with RA (ACR criteria, 85 women, mean age 59 yr) had measurements of galactose elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes [aspartate amino transferase (AST), alanine amino transferase (ALT), alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids, bilirubin, albumin] before treatment with weekly i.m. MTX injections and every year thereafter. In 16 patients, liver biopsies were performed. Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th percentile (5-95 PC) 5.1- 8.5; reference range 6.0-9.1] and mean ABT was 0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC (-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol per year, t = 4.81, P < 0.001) were observed. Negative correlations were found between the annual change in GEC and GEC at baseline (Rs = -0.40, P < 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43, P < 0.0001). No correlations were found between the annual change in GEC or ABT and weekly MTX dose, age or percentage of increased liver enzymes, and no effect of a history of alcohol consumption > 30 g/week became evident. Two patients with Roenigk grade III had impaired quantitative liver function, while 14 patients with Roenigk grades I and II exhibited a high variability of GEC and ABT from normal to abnormal values. The continuous declines in GEC and ABT observed deserve attention in patients with prolonged treatment. Patients with a low GEC or ABT at baseline seem not to be at increased risk for a further loss of quantitative liver function. An impaired GEC or ABT does not necessarily concur with hepatic fibrosis on histological examination.      

Detection of human papillomavirus genes in human oral tissue biopsies and cultures by polymerase chain reaction

We have used the polymerase chain reaction to detect DNA sequences related to human papillomavirus type 16, by simultaneous priming with oligonucleotides from the E6 and L1/L2 open reading frames of the HPV16 genome. The HPV16-related sequence is present at low levels in normal oral tissue, in addition to biopsies and cell cultures from patients with benign and malignant disease. Ultimate analysis of the amplified sequences from the E6(120bp) and L1/L2(173bp) regions of HPV16 was achieved by gel electrophoresis and comparative nucleotide sequencing. The oral carcinoma biopsies and tissue cultures contained DNA sequences which were identical to the E6 region of HPV16, but only rarely contained sequences closely related to the L1/L2 region. The PCR technology should permit the detection, identification and cloning of latent viruses from extremely small tissue biopsies.     

The aetiological relationship between herpes simplex virus type 2 and carcinoma of the cervix: an unanswered or unanswerable question?

After two decades of investigation the proposed aetiological link between herpes simplex virus type 2 (HSV2) and human carcinoma of the cervix remains unproved. The initial seroepidemiological studies, which were of a retrospective nature, were in favour of the aetiological relationship, whereas the more recent prospective studies suggest that HSV infection is a co-variable. The detection of HSV genes and their products in tumour tissues has been plagued by problems of cross reactivity, but the most recent results indicate that while HSV2 DNA can be detected in a small proportion of cancer tissues, HSV proteins or tumour antigens probably do not persist in the tumours. The same situation applies with respect to in vitro transformation. Although HSV, and isolated DNA fragments from the viral genome, can transform tissue culture cells (mainly of rodent origin) and under some conditions can cause cervical abnormalities (including cancer) in experimental animals, in no instance need the viral genes be maintained in the transformed cells. A number of mechanisms, including viral mutagenesis, have been proposed to explain this unusual feature, but the relevance of this work to the induction of human cervical carcinoma by HSV2 in vivo may be difficult to prove.     

差示—线性组合导数光谱法测定扑咳灵片中扑尔敏和溴化丙胺太林

本文提出了差示一线性组合导数光谱法用于测定混合组分体系的基本原理和实验方法。并试用本法消除了扑尔敏、溴化丙胺太林、灵芝粉及附加剂之间的相互干扰,从而分别测定了扑咳灵片巾扑尔敏和溴化丙胺太林的含量,其平均回收率分别为100.2±1.49％(CV)和99.89±1.03％(CV)。其精密度、准确度均好。