Sexual behaviour and smoking as determinants of cervical HPV infection and of CIN3 among those infected: a case-control study nested within the Manchester cohort.

To distinguish risk factors for acquisition of cervical human papillomavirus (HPV) infection from the determinants of neoplasia among infected individuals we have conducted a three-arm case-control study nested within a large population-based cohort of women (the Manchester cohort) screened for HPV at entry using L1 consensus primer PCR. The study includes 181 HPV-positive controls who did not develop high-grade cervical intraepithelial neoplasia (CIN3) during follow-up, 203 HPV-negative controls, and 199 HPV-positive cases with histologically confirmed CIN3. Detailed information on sexual, reproductive and gynaecological history, oral contraceptive use and smoking was obtained at face-to-face interview. There was a striking division between risk factors for infection and those predictive of disease. Comparing the HPV-positive against the HPV-negative controls, the only risk factors for infection were number of sexual partners (OR for six or more = 3.89; 95% Cl = 1.99-7.62), a relatively recent new sexual relationship (OR for a new partner within the previous 2 years = 4.17; 95% Cl = 2.13-8.33), and a history of previous miscarriage (OR = 2.59; 95% Cl = 1.28-5.21). The determinants of CIN3 among infected women were, in contrast, early age at first intercourse (OR for 16 years old or less = 3.23; 95% Cl = 1.33-7.69), a long time since starting a new sexual relationship (OR for 6 years or more = 4.94; 95% Cl = 2.51-9.71), and cigarette smoking, with strong evidence for a dose- response (OR for current smoking habit 20+ per day = 2.57; 95% Cl = 1.49-4.45). Oral contraceptive use was not significantly associated with either HPV infection or CIN3.

Alcohol, smoking, passive smoking and caffeine in relation to breast cancer risk in young women. UK National Case-Control Study Group.

The UK National Case-Control Study Group has examined the relationship between smoking (both own smoking and passive), alcohol consumption and caffeine consumption and the risk of breast cancer. A total of 755 women with breast cancer diagnosed before the age of 36, each with an age-matched general population control, were interviewed, and detailed information on reproductive, contraceptive and medical history, personal attributes and habits were obtained. Additional data on passive smoking were obtained from a subgroup of women. There was no evidence of a statistically significant difference in breast cancer risk between subjects who had ever smoked as much as one cigarette per day and those who had not [relative risk (RR) = 1.01, 95% confidence interval (CI) 0.81-1.26]. Most relative risks for passive smoking exceeded unity, but there was little evidence of significant trends with increasing exposure. The lack of effect of own smoking, and the fact that such smokers are also themselves exposed to the effects of passive smoking, makes any relationship between exposure to others' smoking and breast cancer risk implausible. Alcohol consumption during the year prior to diagnosis and at ages 18 and 25 was examined. Consumers of 0.1-4.9 and 5.0-14.9 g per day generally had non-significantly increased risks compared with never drinkers, but consumers of more than 15 g per day had reduced risks.

The dose-rate effect in human tumour cells.

The radiation response of 12 cell lines derived from a variety of human tumours has been investigated over the dose-rate range from 150 to 1.6 cGy/min. As the dose rate was lowered, the amount of sparing varied widely; in 2 cell lines it was zero, in the other cell lines the dose required for 10(-2) survival ranged up to twice the value at high dose rate. Low dose-rate irradiation discriminates better than high dose rate between tumour cell lines of differing radiosensitivity. The data are equally well fitted by two mathematical models of the dose-rate effect: the LPL model of Curtis and the Incomplete Repair model of Thames. Analysis by the LPL model leads to the conclusion that the theoretical radiosensitivity in the total absence of repair was rather similar among the 7 cell lines on which this analysis was possible. What differs among these cell lines is the extent of repair and/or the probability of direct infliction of a non-repairable lesion. Recovery from radiation damage was also examined by split-dose experiments in a total of 17 human tumour cell lines. Half-time values ranged from 0.36 to 2.3 h and there was a systematic tendency for split-dose halving times to be longer than those derived from analysis of the dose-rate effect. This could imply that cellular recovery is a two-component process, low dose-rate sparing being dominated by the faster component. The extent of low dose-rate sparing shows some tendency to correlate with the magnitude of split-dose recovery; in our view the former is the more reliable measure of cellular recovery. The clinical implication of these studies is that some human tumour types may be well treated by hyperfractionation or low dose-rate irradiation, while for others these may be poor therapeutic strategies.

Experimental pharmacokinetics of RSU-1069 and its analogues: high tumor/plasma ratios.

The mixed-function radiosensitizer RSU-1069 and its analogues possess both alkylating and electron-affinic properties, and have been shown to be more efficient radiosensitizers than misonidazole both in vivo and in vitro. The pharmacokinetics following intraperitoneal injection of three members of this series, RSU-1069, RSU-1164, and RSU-1172 have been studied in C57BL mice bearing B16 melanoma. Peak tumor levels of each compound, and tumor/plasma ratios (T/P) were found to be high: T/P RSU-1069 = 3.8, RSU-1164 = 3.7; RSU-1172 = 4.0. In contrast, other normal tissues including brain showed tissue/plasma ratios close to 1. The mechanisms responsible for differential tumor uptake are unknown, but may depend on the basicity of the compounds, leading to preferential uptake in areas of low pH, or alternatively they may be associated with the alkylating function. This group of compounds appear to demonstrate highly favorable tissue distributions.

The radiobiology of human neuroblastoma.

The radiation response of a human neuroblastoma xenograft HX138 has been studied in vitro and in vivo using single cells in suspension, multicellular spheroids, and xenografts in immune-suppressed mice. End-points used were growth delay and clonogenic cell survival. Growth delay experiments with spheroids and xenografts showed a high degree of radioresponsiveness. Cell survival curves obtained from all systems were characterised by the lack of a shoulder. An increase in Do of the cell survival curve was seen after irradiation of intact spheroids and xenografts, perhaps due to the presence of a contact effect. Cellular capacity for split-dose recovery in vitro was modest. Delayed assay experiments using spheroids and xenografts showed some potentially lethal damage (PLD) repair in vitro but not in vivo. The results show this human tumour line to be intrinsically highly radiosensitive, with a limited repair capacity.

Technetium 99m-plasmin: a new test for the detection of deep vein thrombosis.

Deep vein thrombosis (DVT) is a common medical problem requiring early diagnosis and treatment in order to prevent serious sequelae. Currently available diagnostic acids are suboptimal, since they are either invasive (phlebography), insensitive (ultrasound), or slow (125I-fibrinogen uptake test). The 99Tcm-plasmin test was compared with the 125I-fibrinogen uptake test. The results were concordant in 38 of 40 cases studied (11 concordant positive and 27 concordant negative); a significant correlation (p < 0.05) was found. In a further 20 patients, the 99Tcm-plasmin uptake test was compared with X-ray contrast phlebography. In this series, 12 patients presented with concordant negative results, five patients with concordant positive results and three patients with a positive 99Tcm-plasmin uptake test in the presence of a negative phlebogram. Of these three cases, two presented with clinical evidence of pulmonary embolism and positive perfusion/ventilation lung scans. 99Tcm-plasmin appears to have the potential for early and rapid screening of deep-vein thrombosis 15 minutes after intravenous injection. The test is safe, quick, economic and easy to perform.

Emission and transmission brain tomography.

Comparative emission and transmission brain tomograms were obtained in 209 patients to establish the diagnostic accuracy of a new emission tomographic scanner in detecting space-occupying disease in the brain. Concordant results were obtained in 169 patients (81%). Computed transmission tomography (transmission CT) yielded an overall rate of false-positive results of 0.48% and a false-negative rate of 6%. Emission CT yielded a false-positive rate of 0% and false-negative rates of 2.4% for malignant disease and 10% for vascular disease. The higher rate of false-negative results for vascular disease with emission CT occurs because transmission CT can detect old infarction. The rates of detection of recent vascular disease with emission and trnasmission CT are identical. Thus emission CT is highly sensitive in detecting space-occupying disease in the brain. It represents an ideal screening procedure.

Is there a future for single photon emission tomography?

Emission tomography has the potential to be developed into a clinically useful technique. Its clinical applications, however, will be limited and not in the main stream of space occupying disease detection but in the definition of quantitative information particularly relevant in those disease processes where the metabolic component is the most important one. Special purpose designed instrumentation may prove to be the best of several possible compromises.

A new transverse-section brain imager for single-gamma emitters.

Physical and clinical data on a new emission transverse-section scanner are given. Comparative data from an earlier tomoscanner and a rotating gamma-camera system yield the following information for the three imagers. Resolution at the center of the field is 9 mm for this tomoscanner, 18 mm for the earlier tomoscanner, and 11 mm for the rotating camera; sensitivity (cps/muCi-ml) 36K, 15.4K, 1.9K; crystal area (cm2) 3096, 619, 490, respectively. The quantification of images is discussed. Clinical emission section scans of the brain, liver, chest and skull are presented and discussed. Forty brain scans were analyzed in conjunction with x-ray transmission tomography. No false positives were found. From a total of 15 lesions seen by the CT x-ray scanner, 14 were detected by the emission tomographic scanner, 12 by standard gamma-camera imaging. One false negative case (cyst) was seen by the transmission x-ray scanner but not by the emission scanner.