The human germ-cell tumour cell line GCT 27 growing as subcutaneous xenograft tumours in male nude mice was used in the 4th and 5th passage to study chemotherapeutic drug responses. Recipient mice received 5 Gy whole body irradiation immediately before tumour transplantation. The median take rate was 62% (range 39-73%) and the median volume doubling time 14 days (range 7-28 days). For bleomycin, cisplatin and carboplatin a clear dose response for growth delay was observed. Bleomycin caused substantial weight loss at doses above 75 mg/kg whereas good response to cisplatin was obtained without serious toxic effects. Vinblastine and etoposide exerted no effect when given in non-toxic doses. The response to etoposide was not improved either by fractionated treatment or by combination with verapamil. However, the combination of 20 mg/kg etoposide and 2 mg/kg cisplatin, which when given alone were ineffective, led to a growth delay that was equal to that observed following the administration of higher cisplatin doses. This effect may be explained by the fact that etoposide, as an inhibitor of DNA-topoisomerase II, may interfere with the repair of DNA interstrand cross-links caused by cisplatin.

Animals↗

PubMed1988

In situ detection of human immunodeficiency virus (HIV) nucleic acid in H9 cells using nonradioactive DNA probes and an image cytophotometry system.

Rapid and sensitive nonradioactive methods to detect human immunodeficiency virus (HIV)-infected cells are needed in clinical medicine. We developed an in situ hybridization test using 2-acetylaminofluorene (AAF)-labeled HIV DNA as a hybridization probe. Hybridized probe was detected using rabbit anti-AAF antibody, followed by alkaline phosphatase-conjugated goat anti-rabbit, and the bromochloroindolyl phosphate-nitroblue tetrazolium reaction. An image cytophotometry system was used to quantitate the percentage of HIV-infected cells. These methods were used to determine the percentage of H9 cells infected with HIV. HIV was detected in 0% of cells on day 1 post infection, 7% on day 4, 41% on day 8, and 5% on day 15. These results paralleled those of the reverse transcriptase assay and an antigen capture ELISA assay for HIV antigen. Thus the AAF modified HIV DNA probe detected HIV nucleic acid in infected H9 cells and the image cytophotometry system improved the sensitivity and objectivity of detection.

2-Acetylaminofluorene↗

PubMed1988

Systemic-pulmonary polytetrafluoroethylene shunts in palliative operations for congenital heart disease. Revival of the central shunt.

The concept of central shunting in smaller children with the Waterston shunt was initially well accepted. It has been abandoned because of the difficult estimation of lumen size, preferential flow to the right side, and difficulty in the take-down of the shunt. We have replaced the Waterston shunt with a short segment of polytetrafluoroethylene between the ascending aorta and the main pulmonary artery. From January 1979 to December 1986, 190 shunt operations were performed in 157 patients, with the use of 26 classic Blalock-Taussig shunts (13.7%), six Waterston shunts (3.1%), nine Glenn shunts (4.7%), 80 central aortopulmonary polytetrafluoroethylene shunts (42.2%), and 69 modified Blalock-Taussig shunts (36.3%). Polytetrafluoroethylene grafts were used for 149 of the 190 (78.4%) shunts. Overall mortality was 15.2%, with nine early deaths (4.7%) and 20 late deaths (10.5%). Deaths were due to the complex nature of the congenital anomaly or definitive surgical repair. The patients weighed from 1.6 to 48 kg and ages ranged from 1 day to 22 years. We have modified our technique so that (1) graft length is less than 0.5 cm and both ends are beveled, (2) the aortotomy is fashioned with a punch, (3) the center of the polytetrafluoroethylene graft is never clamped, (4) heparin is given during the construction of the shunt, and (5) aspirin (10 mg/kg/day) is administered daily. Patency ranges from 1 to 4 years. We conclude that the polytetrafluoroethylene shunt provides excellent palliation and that the central shunt, in the smaller child and infant, offers the benefits of shunting without distortion of the peripheral pulmonary arteries.

Adolescent↗

PubMed1987

The response of murine stem spermatogonia to radiation combined with 3-aminobenzamide.

The influence of 3-aminobenzamide (3-AB) on the radiation response of the stem spermatogonia of the CBA mouse has been investigated. Doses of 3-AB from 66 to 450 mg/kg, administered 1 h before irradiation, significantly enhanced stem-cell killing. Enhancement was observed when 3-AB (450 mg/kg) was given up to 5 h before, but not if administered after, irradiation. When radiation was delivered at a lower dose rate (5 cGy/min compared to 180 cGy/min) significant dose sparing was achieved for radiation alone. Pretreatment with 3-AB resulted in slightly less enhancement at the low dose rate than at the high. Split-dose studies (9 Gy total dose) with radiation alone resulted in a recovery ratio of 1.4-1.5. Administration of 3-AB before the first dose resulted in a similar recovery ratio, but if given immediately after the first dose the ratio was smaller. Pretreatment of mice with the radiosensitizer RSU-1069 indicated that at least some of the stem cells were radiobiologically hypoxic. We suggest therefore that the enhancement of spermatogonial stem-cell killing by 3-AB is not entirely due to inhibition of repair processes but may also involve modification of the oxygen status of the testis.

Animals↗

PubMed1986

Survival of murine clonogenic stem spermatogonia following combined radiation and cytotoxic drug treatments.

The effects of combined radiation and cytotoxic drug treatments on the survival of murine clonogenic stem spermatogonia have been investigated using an in vivo clonogenic assay. Drug doses (BCNU, 15 mg/kg; cyclophosphamide (CY) 150 mg/kg, and procarbazine (PCB) 200 mg/kg) were chosen to kill a high proportion of differentiated spermatogonia, but no stem-cells, and were administered as single doses up to 14 days prior to or after 9 Gy of X rays. BCNU produced a moderate enhancement of damage (DEF, 1.0-1.3) that was relatively time-independent. Both CY and PCB demonstrated considerable enhancement of damage (DEF, 1.6 +/- 0.03, respectively) when administered 1 day prior to radiation, and also 3 days prior to radiation for PCB (DEF = 1.4 +/- 0.05). The enhancement of damage may have been caused by either a change in the shoulder width of the cell-survival curve, or additive cell-killing as indicated by a dose-response study.

Animals↗

PubMed1986

Influence of timing of cytotoxic drug treatment on the response of murine clonogenic spermatogonia to X-irradiation.

The enhancement of radiation-induced stem spermatogonial cell killing by three cytotoxic compounds has been investigated using an in vivo clonogenic assay. Drug doses (carmustine (BCNU), 15 mg/kg; cyclophosphamide (CY), 150 mg/kg; procarbazine (PCB), 200 mg/kg) were chosen to kill a high proportion of differentiated spermatogonia but few stem-cells, as assessed by sperm-head counts (SHC) at 29 and 56 days respectively. Drug doses were administered up to 14 days prior to or after local irradiation with 9 Gy of 230 kVp X-rays. BCNU produced a moderate enhancement of damage that was relatively independent of time. Both CY and PCB produced a considerable enhancement of damage especially when administered 1 to 3 days before irradiation. Enhancement in the case of PCB consisted largely of a vertical displacement of the radiation dose-response curves, but with additional evidence for possible changes in slope.

Animals↗

PubMed1986

Protection from procarbazine-induced damage of spermatogenesis in the rat by androgen.

Protection of spermatogenesis from cytotoxic drug-induced damage has been investigated in the rat. Complete germinal aplasia was observed at 8 and 11 weeks after four doses of procarbazine hydrochloride administered weekly (150 mg/kg, first dose; 100 mg/kg, 3 subsequent doses). Pretreatment of rats for 6 weeks plus continued treatment during procarbazine administration with testosterone enanthate, 240 micrograms/100 g body weight, resulted in a marked protection of spermatogenesis. A mean of 22% of seminiferous tubule cross-sections at both 8 and 11 weeks exhibited spermatogenesis, and developing spermatids were observed in 60% of these repopulating tubules at the later time. These results provide evidence that protection of spermatogenesis during chemotherapy may be achieved by androgen treatment.

Androgens↗

PubMed1985

Acceleration of beam ions during major-radius compression in the tokamak fusion test reactor.

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Journal Article↗

PubMed1985

A controlled evaluation of paraspinal EMG biofeedback in the treatment of chronic low back pain.

Sixty-six chronic low back pain sufferers were randomly divided into three groups. Following individual assessments consisting of psychological questionnaires, pain monitoring, and measurement of paraspinal electromyogram (EMG), one group received paraspinal EMG biofeedback and another a placebo treatment. The third group received no intervention. Two further assessments were carried out on all groups immediately after treatment and at a 3-month follow-up. All groups showed significant reduction in pain, anxiety, depression, and paraspinal EMG following treatment and at follow-up, but there were no differences between groups. A regression analysis failed to identify subjects' characteristics that predicted positive outcome in the biofeedback group. However, high scores on the Evaluative scale of the McGill Pain Questionnaire and high hypnotizability were significant predictors of positive outcome for the placebo group. It is concluded that paraspinal EMG biofeedback is not a specific treatment for chronic low back pain in a nonhospitalized population.

Adult↗

PubMed1985

Aortic valve replacement with concomitant myocardial revascularization.

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Aged↗

PubMed1984

Hemodynamic correlates for timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve.

This study was designed to more clearly define the relation between various invasive hemodynamic measurements and left ventricular (LV) timing intervals, ejection rate and filling rate derived from the radionuclide angiographic volume curve. Twenty-eight patients were studied with simultaneous intracardiac micromanometer pressure and dP/dt recordings, gated radionuclide angiography and M-mode echocardiography. These techniques permitted multiple variables of systolic and diastolic function to be measured at a constant atrial paced rate of 100 beats/min. There was a strong correlation between peak ejection rate and ejection fraction (r = -0.97) and between peak ejection rate and maximum positive dP/dt (r = -0.85). There also was a strong correlation between peak filling rate and maximum negative dP/dt (r = -0.85). A weaker correlation existed between the time constant of LV relaxation and the peak filling rate (r = -0.49) and between the LV end-diastolic pressure and the peak filling rate (r = -0.62). There was no correlation between the modulus of chamber stiffness and filling rates, and no association was observed between the time to peak filling rate and the hemodynamic variables. Thus, under the conditions studied, the measured peak ejection and filling rate, determined from the radionuclide angiographic volume curve, correlated well with accepted invasive hemodynamic measurements.

Adult↗

PubMed1982

Stress and chronic headache: a psychophysiological analysis of mechanisms.

This study investigated the effects of three types of laboratory stressors (stressful imagery, mental arithmetic, pain) on temporal artery, skeletal muscle, general autonomic [digital blood volume pulse (DBVP), spontaneous resistance responses (SRR's)] and self-report measures of distress in chronic migraine, mixed, muscle contraction and non-headache controls. All subjects were female, free of medication at time of testing and equated for age. Headache subjects reported a 19 year history of headache. Results revealed a pattern of digital BVP (constriction), SSR's (increase) and frontal EMG (increase) indicative of a general autonomic-skeletal muscle arousal response to all three stressors in all groups, while the temporal artery response to the pain stimulus was vasodilation. Distress ratings were elevated during the stress periods for all four group. Pain threshold and tolerance and the tendency to utilize cognitive coping strategies during exposure to pain did not differ across the four groups. The results do not support the general autonomic dysfunction theory of migraine or the specificity hypothesis implicating an overreactive temporal artery or skeletal muscle response to stress in migraine and muscle contraction headache, respectively. Despite epidemiological research supporting the stress-headache relationship, the present results indicate that the psychophysiological mechanism underlying this relationship does not appear to involve abnormal tonic levels or phasic response to stress. It is argued that the temporal artery dilation response to pain questions the role of stress in triggering the two stage vasoconstriction-dilation mechanism of migraine and suggests the need to evaluate a four stage model as a potential psychophysiological mechanism underlying the stress-headache relationship.

Adult↗

PubMed1982

Self-control and chronic headache.

The relationship between self-control and headache pain was studied in a sample of 42 female subjects with migraine or mixed migraine-muscle contraction headaches. Subjects completed questionnaires evaluating self-control tendencies and social desirability. The McGill Pain Questionnaire was also completed during a single representative migraine headache and daily ratings of headache severity (duration, intensity, disability due to pain) and medication intake were collected over a seven-week period. A significant discriminant function which resulted in 71% correct classification of High and Low Self-Control subjects was obtained. The pattern of responses associated with the high self-control group was characterized by lower ratings of pain intensity, less focus on sensory dimensions of pain and more frequent use of certain medications. A correlation between self-control and social desirability was also observed. These findings suggest that the trait self-control may be associated with a particular pattern of pain, although the influence of social desirability cannot be ruled out as an alternative explanation.

Adaptation, Psychological↗