Diltiazem reduces levels of NT-proBNP and improves symptoms compared with metoprolol in patients with permanent atrial fibrillation.

AIMS: Short-term treatment with calcium channel blockers lowers levels of N-terminal pro B-type natriuretic peptide (NT-proBNP) and reduces rhythm-related symptoms compared to treatment with beta-blockers. The aim of this study was to compare the longer-term effects of metoprolol and diltiazem for rate control in patients with permanent atrial fibrillation after six months. METHODS AND RESULTS: Men and women with permanent atrial fibrillation and preserved left ventricular systolic function were randomised to receive either diltiazem 360 mg or metoprolol 100 mg once daily. The primary endpoint was the level of NT-proBNP after a six-month treatment period. Secondary endpoints included heart rate, rhythm-related symptoms and exercise capacity. A total of 93 patients (mean age 71 ±7 years, 28 women) were randomised. After six months' treatment, mean levels of NT-proBNP decreased in the diltiazem group and increased in the metoprolol group, with a significant between-group difference (409.8 pg/mL, 95% CI: 230.6 - 589.1, P<0.001). Treatment with diltiazem significantly reduced rhythm-related symptoms compared to baseline, but no change was observed in the metoprolol group. Diltiazem and metoprolol had similar effects on heart rate and exercise capacity. CONCLUSION: Diltiazem reduced NT-proBNP levels and improved rhythm-related symptoms. Metoprolol increased peptide levels but had no impact on symptoms despite similar heart rate reduction. Non-dihydropyridine calcium channel blockers should be considered more often for rate control in permanent atrial fibrillation.

A retrospective analysis of catheter-based sources in intravascular brachytherapy.

PURPOSE: Coronary artery disease involves the deposition of plaque along the walls of a coronary artery leading to narrowed or blocked vessels (stenosis) and is one of the main causes of death in developed countries. Percutaneous transluminal coronary angioplasty (PTCA) is used to reverse stenosis. Restenosis (renarrowing) of the treated vessel is a major complication of PTCA. A metal mesh tube (stent) can be placed inside the vessel to prevent restenosis. Tissue stress incurred during PTCA and stenting can provoke neointimal cell proliferation leading to in-stent restenosis (ISR). Intravascular brachytherapy (IVBT), a form of internal radiotherapy, is used to treat ISR. Renewed interest in IVBT is being expressed as a treatment for patients with ISR in drug-eluting stents. Current treatment planning (TP) of IVBT is extremely limited and assumes human tissue can be approximated by water. The interactions of arterial plaque, guidewires, and the stent have been shown to attenuate radiation significantly but are ignored in TP. Other models have determined the degree of attenuation by each factor in isolation. For the first time, we create a model with several inhomogenities present to determine whether attenuation by multiple inhomogenities combines linearly or if a larger dose reduction than anticipated is realized. We are also able to evaluate a spatial distribution of dose around the source and in arterial walls. METHODS AND MATERIALS: A dosimetric analysis of two commercially available IVBT systems was performed in a Monte Carlo-based particle simulation (Geant4). Absorbed dose was calculated using a model of a human coronary artery with a calcified plaque and stent. Dose delivered in water was also calculated to evaluate the accuracy of a water approximation. RESULTS: Dose as a function of θ shows significant variation around IVBT sources. For the Guidant Galileo, dose is reduced by 20% behind stent struts and as much as 66% in a region occluded by the guidewire, plaque, and stent. For the Novoste Beta Cath device, delivered dose is reduced by 19% and 58%, respectively, in the same regions. CONCLUSIONS: Our findings show that the water approximation used in clinical practice to calculate dose is inaccurate when inhomogeneities are present. Methods proposed for calculating dose perturbations in IVBT may underestimate the magnitude of dose reduction. Increasing source dwell time seems unlikely to resolve dosimetric issues in IVBT. The effectiveness of currently existing ß-emitting devices may be reduced in patients with complex lesions at the treatment site. Investigation of new radioisotopes and off-centering devices should be considered to improve dose outcomes.

Track structure modeling in liquid water: A review of the Geant4-DNA very low energy extension of the Geant4 Monte Carlo simulation toolkit.

Understanding the fundamental mechanisms involved in the induction of biological damage by ionizing radiation remains a major challenge of today's radiobiology research. The Monte Carlo simulation of physical, physicochemical and chemical processes involved may provide a powerful tool for the simulation of early damage induction. The Geant4-DNA extension of the general purpose Monte Carlo Geant4 simulation toolkit aims to provide the scientific community with an open source access platform for the mechanistic simulation of such early damage. This paper presents the most recent review of the Geant4-DNA extension, as available to Geant4 users since June 2015 (release 10.2 Beta). In particular, the review includes the description of new physical models for the description of electron elastic and inelastic interactions in liquid water, as well as new examples dedicated to the simulation of physicochemical and chemical stages of water radiolysis. Several implementations of geometrical models of biological targets are presented as well, and the list of Geant4-DNA examples is described.

ALGEBRA: ALgorithm for the heterogeneous dosimetry based on GEANT4 for BRAchytherapy.

Task group 43 (TG43)-based dosimetry algorithms are efficient for brachytherapy dose calculation in water. However, human tissues have chemical compositions and densities different than water. Moreover, the mutual shielding effect of seeds on each other (interseed attenuation) is neglected in the TG43-based dosimetry platforms. The scientific community has expressed the need for an accurate dosimetry platform in brachytherapy. The purpose of this paper is to present ALGEBRA, a Monte Carlo platform for dosimetry in brachytherapy which is sufficiently fast and accurate for clinical and research purposes. ALGEBRA is based on the GEANT4 Monte Carlo code and is capable of handling the DICOM RT standard to recreate a virtual model of the treated site. Here, the performance of ALGEBRA is presented for the special case of LDR brachytherapy in permanent prostate and breast seed implants. However, the algorithm is also capable of handling other treatments such as HDR brachytherapy.

Cross-fire doses from beta-emitting radionuclides in targeted radiotherapy. A theoretical study based on experimentally measured tumor characteristics.

A mathematical model based upon histological findings of cell cluster distributions in primary breast cancers and lymph node metastases was developed. The model is unique because it accounts for tumor cell cluster formations within both primary tumors and metastases. The importance of inter-cell cluster cross-fire radiation dose for beta-emitting radionuclides of different energies was studied. The cell clusters were simulated as spheres with 15, 25 and 50 microm radii having a homogeneous radioactivity distribution. The self-dose as well as the dose distribution around the spheres was calculated for seven radionuclides, (90)Y, (188)Re, (32)P, (186)Re, (159)Gd, (131)I and (177)Lu using the GEANT4 Monte Carlo code. Generally, the self-dose was decreasing with increasing energy of the emitted beta particles. An exception was (188)Re which, compared to (32)P, had higher beta energy as well as higher self-dose. This was due to the higher emission of conversion and Auger electrons in the (188)Re-decay. When the cell clusters had a mean distance that was shorter than the maximum range of beta-particles, then the inter-cluster cross-fire radiation contributed significantly to the absorbed dose. Thus, high-energy beta-particles may, in spite of a low self-dose to single clusters, still be favorable to use due to the contribution of inter-cluster cross-fire radiation.

Exercise activity, body size and premenopausal breast cancer survival.

We evaluated prediagnosis predictors of breast cancer survival among 717 premenopausal breast cancer patients enrolled in a population-based case-control study and followed for 10.4 years. Using Cox's proportional hazards models, lifetime exercise, weight, and height were not associated with survival. Higher body mass index (trend P=0.21) and recent exercise activity (trend P=0.31) were weakly associated with longer survival.

Stimulation of the left ventricle through the coronary sinus with a newly developed 'over the wire' lead system--early experiences with lead handling and positioning.

AIMS: This report describes the initial clinical results with a newly designed guiding catheter and an 'over the wire' pacing lead based on angiolasty technology to stimulate the left ventricle using the transvenous route via the coronary sinus (OTW-CV lead). METHODS AND RESULTS: In 75% of the 15 patients (6 males, 9 females, mean age of 53 +/- 9 years) with congestive heart failure, access to coronary sinus required less than 2 min; in one patient. the attempt failed. Mean R wave amplitudes plus or minus the standard deviation, measured at apical, mid-ventricular and basal positions the anterior (11.4 +/- 9.2, 10.8 +/- 6.2, 9.3 +/- 6.3 mV) and lateral or posterior veins (10.1 +/- 10.7, 8.6 +/- 6.4, 7.7 +/- 4.3 mV) showed a trend favouring the apex without statistical significance. Pacing impedance, measured at the same sites and vein tributaries, ranged from 670 +/- 191 to 915 +/- 145 ohms. Pacing thresholds measured at apical and mid ventricular sites were significantly lower than at the base in the anterior vein 2.5 +/- 2.8 and 2.8 +/- 1.8 vs 5.6 +/- 2.7 V at 0.5 ms, P<0.001). Thresholds in the lateral/posterior veins showed a similar trend but did not reach statistical significance (3.0 +/- 1.7, 3.6 +/- 1.4 +/- 1.8 V at 0.5 ms). In patients, in whom thresholds were determined in more than one vein, the 'best' mean threshold was 1.6 +/- 0.7 V. CONCLUSION: The new 'over the wire' lead and guiding catheter system allows uncomplicated access to the coronary sinus and the depth of the coronary vein tributaries. Left ventricular sensing and pacing thresholds are acceptable for chronic use in implanted cardiac rhythm management systems.

Body size, physical activity, and breast cancer hormone receptor status: results from two case-control studies.

We evaluated whether our previous reports of increased postmenopausal breast cancer risk with higher body mass index (BMI) or of reduced premenopausal and postmenopausal breast cancer risk with higher physical activity levels varied according to the tumor's estrogen receptor (ER) and progesterone receptor (PR) status. Participants enrolled in either of two population-based case-control studies in Los Angeles County, California: one of premenopausal women (ages < or = 40 years), and one of postmenopausal women (ages 55-64 years). Case participants were diagnosed for the first time with in situ or invasive breast cancer from 7/1/83 through 12/31/88 (premenopausal women) or from 3/1/87 through 12/31/89 (postmenopausal women). Joint ER/PR status was collected for 424 premenopausal and 760 postmenopausal case participants. The analysis included 714 premenopausal and 1091 postmenopausal age-matched, race-matched (white or Hispanic), parity-matched (premenopausal women only), and residential neighborhood-matched control participants. Among the postmenopausal women, obesity was associated with an increased odds of ER+/PR+ breast cancer (odds ratio, 2.45 for women in the highest versus the lowest body mass index quartile; 95% confidence interval, 1.73-3.47). Body mass index was associated with neither ER-/PR- tumors among the postmenopausal women nor with any ER/PR subgroup among the premenopausal women. For both premenopausal and postmenopausal women, higher recreational physical activity levels (> or = 17.6 MET-hours/week versus no activity) were associated with a 30-60% reduction in risk of nearly all ER/PR subtypes, although the associations were generally of borderline statistical significance. Examining these potentially modifiable breast cancer risk factors by tumor ER and PR status may provide us with greater insight into breast cancer etiology and the mechanisms underlying the risk factor associations.

Alcohol consumption and breast cancer oestrogen and progesterone receptor status.

We examined the role of alcohol on the risk of breast cancer by the joint oestrogen receptor (ER) and progesterone receptor (PR) status of the tumour using data from two case-control studies conducted in Los Angeles County, USA. Eligible premenopausal patients were 733 women aged < or =40 years and first diagnosed from 1 July 1983 to 1 January 1989. Eligible postmenopausal patients were 1169 women aged 55-64 years and first diagnosed from 1 March 1987 to 31 December 89. Patients were identified by the University of Southern California Cancer Surveillance Program. Neighbourhood controls were individually matched to patients by parity (premenopausal patients) and birth date (+/-3 years). ER and PR status were obtained from medical records for 424 premenopausal and 760 postmenopausal patients. The analyses included 714 premenopausal and 1091 postmenopausal control subjects. Alcohol use was generally not associated with premenopausal risk of breast cancer, regardless of hormone-receptor status. Among the postmenopausal women, those who consumed, on average, > or =27 g of alcohol/d experienced an odds ratio (OR) of 1.76 [95% confidence interval (CI) 1.14-2.71] for ER-positive/PR-positive breast cancer relative to women who reported no alcohol consumption. Alcohol use was less clearly associated with risk of other receptor types among postmenopausal women. These data suggest that alcohol may preferentially increase risk of ER-positive/PR-positive breast cancer in postmenopausal women.

Breastfeeding experience and breast cancer risk among postmenopausal women.

Results of studies of breastfeeding and postmenopausal breast cancer risk have been inconsistent, with many investigators concluding that breastfeeding does not influence risk. We examined whether breastfeeding reduces postmenopausal breast cancer risk as well as the details of this relationship, including possible modification in risk by the age that a woman first breastfed a child and the number of children she breastfed. This population-based case-control study compared 974 women who were residents of Los Angeles County and newly diagnosed with breast cancer to 973 women with no history of breast cancer who were matched to patients by age (within 3 years) and neighborhood of residence. Subjects were parous and postmenopausal. Breast cancer patients were ages 55-64 years at diagnosis. Women who breastfed at least 16 months experienced a reduced odds of breast cancer relative to women who never breastfed (odds ratio, 0.73; 95% confidence interval, 0.52-1.01). Risk decreased as the number of children breastfed increased, but the association was attenuated after accounting for lifetime duration of breastfeeding. Breast cancer risk was 30% lower among women ages 20-24 years at first breastfeeding than women who had never breastfed (odds ratio, 0.69; 95% confidence interval, 0.54-0.88), independent of the effect of age at first birth. This study provides some evidence that the protective effect of breastfeeding persists into the postmenopausal years. The potential for nondifferential error in recall of breastfeeding habits among postmenopausal patients and controls may explain the inconsistent results observed across studies and underscores the need for careful assessment of this relationship.

Recent and past physical activity and prevalence of colorectal adenomas.

Epidemiological evidence has generally supported a protective association of physical activity with large-bowel adenomas, but whether the protective effects are restricted to recent or past activity is uncertain. We determined whether recent and past recreational or total daily activity was associated with prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, aged 50-74 years, completed a 126-item semiquantitative food frequency questionnaire and were also interviewed regarding non-dietary risk factors in 1991-93. In the univariate analysis, all measures of recent recreational physical activity were associated with reduced prevalence of polyps. After adjustment for body mass index, smoking status, daily servings of fruit and vegetables, use of non-steroidal anti-inflammatory agents and intakes of calories, saturated fat and alcohol, the associations were weakened. For subjects engaging in high-intensity activities compared with subjects not engaging in vigorous activities, the multivariate odds ratio (OR) for recent recreational activity was 0.7 [95% confidence interval (CI) 0.4-1.1, trend P = 0.08]. Past recreational activity and past or recent total daily activity were not associated with prevalence of adenomas. These results support a modest association of recent recreational physical activity with prevalence of colorectal adenomas.

Breastfeeding history, pregnancy experience and risk of breast cancer.

Epidemiological evidence suggests that breastfeeding protects against breast cancer. Whether an effect of age at first breastfeeding is independent of an effect of age at first birth is unclear. We hypothesized that nausea and vomiting in pregnancy, which are associated with elevated serum oestradiol levels during pregnancy, may increase risk. Cases were 452 parous, premenopausal women, 40 years or younger, diagnosed with breast cancer in Los Angeles County from July 1983 to December 1988. Control subjects were matched to cases on age, race, parity and neighbourhood. Pregnancy and breastfeeding histories were obtained from in-person interviews. Odds of breast cancer among women who breastfed for at least 16 months relative to those among women who did not breastfeed was 0.66 [95% confidence interval (CI) 0.41-1.05]. Number of children breastfed was not associated with risk. Risk was lower in women who first breastfed at older ages. Having ever been treated for nausea or vomiting during pregnancy was associated with an increased risk, especially in women experiencing recent pregnancies (OR = 2.03, 95% CI 1.05-3.92). These results support a protective role of breastfeeding and an adverse role of nausea or vomiting during pregnancy in the development of premenopausal breast cancer, especially in the years immediately following pregnancy.

Risk factors for in situ breast cancer.

Few data exist on risk factors for in situ breast carcinoma. We examined risk factors for in situ breast carcinoma in data from two population-based case-control studies of breast cancer conducted among female residents of Los Angeles County. Cases with in situ or invasive disease were identified through the cancer registry for Los Angeles Country in the 1980s. We included all cases ages 40 years or younger diagnosed over a 5.5-year period and all cases ages 55-64 years diagnosed over a 3-year period. Control subjects were individually matched to cases by age (+/-3 years), neighborhood of residence, and, for younger controls, parity (nulliparous versus parous). The analysis included 233 cases with in situ cancer, 2057 cases with invasive cancer, and 2203 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for screening mammography and established risk factors. In general, risk factors for in situ breast cancer were similar to those for invasive disease in this population. In premenopausal women, however, the risk of in situ breast cancer decreased with increasing body mass index, whereas for invasive disease, body mass index was unrelated to risk. In addition, in postmenopausal women with known age at menopause, use of unopposed estrogen replacement therapy was associated with increased risk of in situ disease [OR for ever use of estrogen alone was 1.60 (95% CI, 1.00-2.58)], whereas for invasive disease the OR was 1.23 (95% CI, 1.00-1.50). A similar difference was seen for combined hormone replacement therapy. Unmeasured increased screening among estrogen or combined replacement hormone users compared with nonusers could account for some of the association of in situ breast cancer risk with hormone replacement use.

Dietary intake of specific carotenoids and vitamins A, C, and E, and prevalence of colorectal adenomas.

We determined whether intakes of the main dietary carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

Epidemiologic data on alcoholic beverage consumption and risk of cancer.

Recent epidemiologic data confirm the results of earlier studies in supporting that alcoholic beverage consumption is a cause of cancer of the mouth, pharynx, larynx, esophagus, and liver. The effect of a specified level of alcohol intake on absolute risk of cancers of the head, neck, and esophagus depends on the presence of other risk factors, especially smoking. Whether alcoholic beverage consumption is a cause of cancer of the breast or large bowel is unclear. Alcohol intake appears not to increase risk of cancer of the lung, bladder, prostate, stomach, ovary, endometrium, or of melanoma. Indirect epidemiologic evidence suggests that alcohol may be a weak causal factor for pancreatic cancer. Although heavy alcohol consumption increases risk of cancer of the head, neck, esophagus, and liver, whether moderate alcohol consumption increases risk at these sites is unclear.

Questionnaire assessment of intake of specific carotenoids.

We determined whether estimation of intake of specific carotenoids with a standard food-frequency questionnaire (FFQ) could be improved by collection of additional data on the intake of carotenoid-rich food items. The foods included on an addendum to the standard FFQ were potentially important dietary contributors of alpha- and beta-carotene, beta-cryptoxanthin, lutein, zeaxanthin, or lycopene. Participants (n = 215), ages 50-74 years, provided fasting blood samples and completed the FFQ and the addendum. The participants were enrolled in a prepaid health plan and had undergone screening sigmoidoscopy for detection of colorectal polyps. Addendum foods were identified that accounted for variation in blood levels of specific carotenoids, conditional on intake of foods on the standard FFQ. Estimated carotenoid intakes from the standard FFQ, and from the modified FFQ with the selected addendum foods, were examined in relation to plasma carotenoid levels. The correlation coefficient between estimated carotenoid intake and plasma levels (adjusted for age, sex, serum cholesterol, alcohol intake, smoking status, and energy intake) were essentially the same for the standard and modified FFQs. The adjusted correlations for the standard FFQ only were 0.26 for alpha-carotene, 0.22 for beta-carotene, 0.36 for beta-cryptoxanthin, 0.32 for lutein+zeaxanthin, and 0.34 for lycopene. Adding carotenoid-rich foods to the FFQ did not improve estimation of intake for the carotenoids examined in this population. We conclude that assessment of intake of specific carotenoids with the FFQs currently in use may not necessarily be improved by a modified list of carotenoid-rich foods.

DNA strand breaks and DNA repair response in lymphocytes after chronic in vivo exposure to very low doses of ionizing radiation in mice.

In contrast to the well-documented negative effects of high-dose oxidant exposure, accumulating evidence supports a positive, perhaps essential physiologic role for very low-level oxidant stress. For example, low-level oxidant exposure, within or below the physiologic range, has been reported to stimulate membrane signal transduction, proliferation, antioxidant defense and DNA repair. In the present study, we have examined whether whole-body exposure to low-dose radiation (LDR) results in an alteration in constitutive (steady state) levels of DNA-strand breaks and whether an adaptive increase in DNA-repair response is induced. C57B1/6J mice were exposed to 0.04 Gy (4 cGy) of gamma-radiation as a model of low level oxidant stress. End points measured after chronic in vivo LDR included: (1) constitutive expression of DNA-strand breaks in quiescent spleen cells; (2) sensitivity to DNA damage after high-dose radiation exposure in vitro; (3) repair of constitutive and radiation-induced DNA strand breaks after mitogen stimulation: (4) activity of the DNA-repair associated enzyme, poly(ADP-ribose)transferase (ADPRT) and its substrate, NAD. The results indicated that the constitutive expression of DNA-strand breaks is significantly decreased after chronic LDR; however, DNA-repair capacity after high-dose radiation exposure is not increased above that observed in sham-irradiated mice. Associated with the reduction in constitutive DNA-strand break accumulation was a decrease in resting levels of the DNA-repair-associated enzyme poly(ADP-ribose) transferase (ADPRT). These results are consistent with the interpretation that cumulative DNA damage and associated DNA-repair activity in unstimulated cells are both reduced after chronic LDR exposure.

Immune potentiation after fractionated exposure to very low doses of ionizing radiation and/or caloric restriction in autoimmune-prone and normal C57Bl/6 mice.

Very low doses of ionizing radiation can enhance immune responsiveness and extend life span in normal mice. Total lymphoid irradiation at relatively high doses of radiation can retard autoimmune disease in genetically susceptible mice, but may impair immune function. In order to determine whether fractionated low dose exposure would enhance immune response and retard lymphadenopathy in autoimmune-prone mice, groups of C57B1/6 lpr/lpr mice were sham irradiated, exposed 5 days/week for 4 weeks to 0.04 Gy/day (0.8 Gy cumulative dose), or to 0.1 Gy/day (2.0 Gy cumulative dose). After the radiation protocol, the mice were evaluated for splenic T cell proliferative capacity, T cell subset distribution, and total spleen cell numbers. The independent and additive effect of caloric restriction was additionally assessed since this intervention has been shown to increase immune responsiveness and retard disease progression in autoimmune-prone mice. The congenic C57B1/6 +/+ immunologically normal strain was evaluated in parallel as congenic control. The results indicated that mitogen-stimulated proliferation was up-regulated in both strains of mice after exposure to 0.04 Gy/day. The proliferative capacity was additively enhanced when radiation at this dose level was combined with caloric restriction. Exposure to 0.1 Gy/day resulted in further augmentation of proliferative response in the lpr/lpr mice, but was depressive in the +/+ mice. Although the proportions of the various T cell subpopulations were altered in both strains after exposure to LDR, the specific subset alterations were different within each strain. Additional experiments were subsequently performed to assess whether the thymus is required for LDR-induced immune potentiation. Thymectomy completely abrogated the LDR effect in the +/+ mice, suggesting that thymic processing and/or trafficking is adaptively altered with LDR in this strain. In contrast, augmentation in proliferative activity after LDR in the lpr/lpr mice was maintained, although attenuated, in thymectomized mice. Taken together, these results indicate that fractionated exposure to LDR augments the proliferative response of spleen cells in both autoimmune-prone and immunologically normal mice; however, within each strain, the mechanisms appear to be different.

Prevalence of hepatitis A antibodies in a normal population and some selected groups of patients in Norway.

The prevalence of hepatitis A virus antibodies was tested by radioimmunoassay in Norway in healthy blood donors, in patients without clinical signs of liver diseases and in two selected groups of patients. The presence of hepatitis A antibodies was highly age-dependent in 625 normal persons. A major reduction occurred from 50 per cent or more in those born before 1938 to 10 per cent or less among those born after 1943. The decline of hepatitis A antibody prevalence was correlated to the history of infectious hepatitis epidemics in the entire country during World War II. The prevalence was not different from controls in a group of patients with various liver disorders. Hepatitis A antibodies were more prevalent in males than in females in blood donors, patients with chronic liver disorders and their controls. Hepatitis A antibodies were frequently present in prison inmates; their presence was associated with the presence of antibodies against hepatitis B virus and with anamnestic data on drug addiction.