Shifts in bovine CD4+ subpopulations increase T-helper-2 compared with T-helper-1 effector cells during the postpartum period.

This study determined the cytokine profile of CD4+ T-helper cells to elucidate the specific CD4+ T-helper phenotype during the postpartum period. Peripheral blood mononuclear cells were isolated from cows during periods of increased susceptibility (3 d postpartum, n = 7) and decreased susceptibility (mid- to late lactation, n = 6) to mastitis. Isolated mononuclear cells were magnetically separated into CD4(+)-enriched or CD4(+)-depleted populations using specific bovine monoclonal antibodies and were confirmed to be enriched or depleted by flow cytometric analysis. T-helper-1 and T-helper-2 subpopulations were distinguished by cytokine profiles, at both the molecular and protein level, by competitive quantitative reverse transcriptase-polymerase chain reaction and specific bioassays, respectively. The CD4(+)-enriched cultures isolated postpartum had enhanced interleukin-4 and interleukin-10 mRNA transcript expression; cultures isolated during the mid- to late lactating period had enhanced interleukin-2 mRNA transcripts. Depletion of CD4+ lymphocytes decreased, and enrichment of CD4+ lymphocytes increased interferon-gamma transcripts in cultures isolated from mid- to late lactation cows. Interferon-gamma and interleukin-2 bioassays revealed that cytokine secretion paralleled mRNA transcript levels. These data suggest that CD4+ lymphocytes act predominantly as T-helper-2 compared with T-helper-1 within 3 d after calving. Alterations in the T-helper-1 and T-helper-2 responses, and therefore the repertoire of cytokines produced, may be an underlying reason for diminished host immune response during the postpartum period.

Characterization of the dose perturbation by stents as a function of X-ray beam energy.

PURPOSE: External beam irradiation of coronary arteries has been shown to be detrimental in an animal model for the prevention of neointimal hyperplasia in the presence of stents when orthovoltage x-ray beams are used. The present study investigated the effect of beam energy on the dose distribution in the wall of the artery in the presence of stents. MATERIALS AND METHODS: We used 250-kVp x-rays and 6-MV x-rays to irradiate a stent placed in a homogeneous phantom. Radiochromic film densitometry and Monte Carlo calculations were used to measure and to simulate the dose distribution in the proximity of the stent. RESULT: External beam irradiation not only failed to prevent neointimal hyperplasia, but actually accentuated the neointimal response to a prompt mechanical injury in the artery. The photoelectric effect, which dominates low-energy x-ray interactions, produces recoil electrons in the stent, which enhance the dose surrounding the intima. The photoelectrons generated in nickel and iron have an extremely short range in normal tissue, approximately 0.1 mm. Initial estimates of orthovoltage x-ray interactions with the stent indicate a dose enhancement in the orthovoltage range by a factor of 2-6 due to the rise in the photoelectric cross section in this energy range depending on the elemental composition of the stent. Film densitometry verifies this dose enhancement. The Monte Carlo calculation yields a dose enhancement and the dose fall-off with distance from the stent when irradiated with orthovoltage x-rays. Conversely when the tissue and stent are irradiated with megavoltage x-rays, the dose enhancement in this region is a factor of 1.15 in close proximity to the stent and 1.0 at distances greater than 0.1 mm. The 6-MV photon interactions in tissue and Ni/Ti are predominantly through Compton scattering. The Compton effect is dependent on the electron density in the medium, in contrast to the atomic number, which is more relevant for photoelectric absorption. The dose estimates for megavoltage x-rays adjacent to the stent are complicated by the lack of charged particle equilibrium. CONCLUSIONS: There is a limited but definite increase in the dose delivery to the arterial wall when stents are irradiated with orthovoltage x-ray energies. This increase may explain the negative response in other studies. The presence of the stent does perturb the character and magnitude of the dose in the normal arterial wall as a function of beam quality.

Differences in depressive symptoms between traditional workers and shiftworkers.

Shiftwork causes a number of physical and psychological problems. As a result, we predicted depression to be worse for shiftworkers than for workers with more traditional schedules. In addition, we predicted that women would report more depressive symptoms than men as is the case in the general population. Questionnaire packets which included the Beck Depression Inventory were mailed to 153 workers in a small community. Analysis showed that, contrary to expectation, shiftworkers as a group suffered no more depressive symptoms than traditional workers. However, while both sexes had similar mean scores on depression among the shiftworkers, women were significantly more depressed than men among traditional workers.

Survival benefit of hyperthermia in a prospective randomized trial of brachytherapy boost +/- hyperthermia for glioblastoma multiforme.

PURPOSE: To determine if adjuvant interstitial hyperthermia (HT) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy. METHODS AND MATERIALS: Adults with newly-diagnosed, focal, supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III randomized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea. Those patients whose tumor was still implantable after teletherapy were randomized to brachytherapy boost (60 Gy at 0.40-0.60 Gy/h) +/- HT for 30 min immediately before and after brachytherapy. Time to progression (TTP) and survival from date of diagnosis were estimated using the Kaplan-Meier method. RESULTS: From 1990 to 1995, 112 eligible patients were entered in the trial. Patient ages ranged from 21-78 years (median, 54 years) and KPS ranged from 70-100 (median, 90). Most commonly due to tumor progression or patient refusal, 33 patients were never randomized. Of the patients, 39 were randomized to brachytherapy ("no heat") and 40 to brachytherapy + HT ("heat"). By intent to treat, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.04 and p = 0.04). For the 33 "no heat" patients and 35 "heat" patients who underwent brachytherapy boost, TTP and survival were significantly longer for "heat" than "no heat" (p = 0.045 and p = 0.02, respectively; median survival 85 weeks vs. 76 weeks; 2-year survival 31% vs. 15%). A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with randomization to "heat" (p = 0.008; hazard ratio 0.51). There were no Grade 5 toxicities, 2 Grade 4 toxicities (1 on each arm), and 7 Grade 3 toxicities (1 on "no heat" and 6 on the "heat" arm). CONCLUSION: Adjuvant interstitial brain HT, given before and after brachytherapy boost, after conventional radiotherapy significantly improves survival of patients with focal glioblastoma, with acceptable toxicity.

Bovine CD8+ suppressor lymphocytes alter immune responsiveness during the postpartum period.

This study examined the immunoregulatory role of CD8+ lymphocytes during the postpartum period. Peripheral blood cells were isolated from postpartum and mid to late lactating animals. Flow cytometric analysis was performed to determine the frequencies of relevant cell populations. Depletion of CD8+ lymphocytes from whole cultures significantly decreased proliferation and cytotoxic ability of cells isolated from mid to late lactating animals. Enrichment of whole cultures with CD8+ lymphocytes further decreased their proliferative ability but pure CD8+ lymphocyte had increased cytotoxic activity. In contrast, neither depletion nor enrichment of whole cultures with CD8+ lymphocytes altered the already diminished proliferative responses of cells isolated from postpartum cows. No cytotoxic activity was observed by cells isolated from postpartum animals. Cultures from mid to late lactating cows mainly expressed IFN-gamma mRNA where as IL-4 mRNA was mainly expressed by cultures isolated from postpartum animals. Flow cytometric analysis revealed that CD8+ lymphocytes have a high level of activation and expression of the beta-chain during the postpartum compared with the mid to late lactating period. These data indicate that CD8+ lymphocytes are of the suppressor compared to the cytotoxic nature immediately following parturition.

Effect of modality in earwitness identification: memory for verbal and nonverbal auditory stimuli presented in two contexts.

Psycholegal researches have largely ignored the relevance of nonverbal auditory information in earwitness memory, nor have they compared its retention with visual or verbal information. Memory of nonverbal auditory stimuli was investigated in two different contexts. In Experiment 1, participants recalled more sounds (i.e., nonverbal auditory stimuli) than the sounds' verbal labels. However, with a more ecologically valid method in Experiment 2, participants recalled more verbal stimuli in conjunction with visual information than they did nonverbal stimuli. Even after a 1-week delay, participants' retention of the verbal-visual combination was highest.

Enhancing bactericidal activity of bovine lymphoid cells during the periparturient period.

The antibacterial activity of bovine lymphocytes was evaluated following in vitro stimulation with interleukin-2. Mononuclear cells were isolated from the blood, lymph node, and mammary parenchymal tissue of four lactating and four periparturient dairy cows. These cells were evaluated for antibacterial activity against Staphylococcus aureus following incubation for 48 h with or without interleukin-2. Cultures stimulated with interleukin-2 had higher bactericidal activity of all three isolated cell populations than did unstimulated cultures, regardless of lactational stage. This observation suggests that this effector function may possibly be activated in vivo and may potentially increase mammary gland resistance to bacterial infections during periods of increased susceptibility. Flow cytometric analysis of the cultured cells revealed that antibacterial effector cells were mainly CD2+ and were depleted of macrophages. Despite shifts in CD4+, CD8+, and gamma delta T lymphocytes during the periparturient period, bactericidal activity was similar among the three cell sources. This similarity suggests that these lymphocyte phenotypes might not be directly responsible for this effector function. Identification of the antibacterial effector phenotype and its mechanism of action may lead to immunoregulatory strategies aimed at enhancing this novel bactericidal function.

Diminished mammary gland lymphocyte functions parallel shifts in trafficking patterns during the postpartum period.

Once activated, lymphocytes can regulate both specific and nonspecific immune responses. Alterations in lymphocyte function may increase the host's vulnerability to bacterial infections such as mastitis. Susceptibility to mastitis as well as diminished leukocyte functional capabilities have been shown to be influenced by lactational stage. Therefore, the present study characterized the phenotypes and functions of several bovine lymphoid populations at two points in the lactational cycle. Mononuclear cells were isolated from peripheral blood, supramammary lymph nodes, and mammary parenchyma of mid-lactating and postpartum dairy cows. The phenotypic composition, proliferative ability, cytokine secretion, and cytotoxic activity of isolated leukocytes were assessed with respect to lactational stage and tissue source. Lower percentages of T lymphocytes were consistent with diminished mitogen-stimulated proliferation and spontaneous cytotoxic activity by lymphocytes isolated from postpartum compared with mid-lactating animals. Stimulation with interleukin-2 did not enhance the cytotoxic activity or proliferative ability of lymphocytes isolated postpartum to similar levels observed for those isolated from mid-lactating animals. These data indicate that certain diminished lymphocyte functions observed during the postpartum period may result from shifts in leukocyte trafficking patterns.

Autobiographical recall and visual imagery.

If high visual imagery is a component of successful autobiographical recall for personal episodes, then those participants who have high imagery should have greater autobiographical recall for personal episodes. This hypothesis was tested by giving 30 selected participants, 15 who had high and 15 low visual imagery, 90 sec. to recall personal episodic information from three time periods in their lives. Also assessed were the effects of visual imagery on autobiographical recall for personal semantic and nonpersonal semantic information (vegetables and adjectives). Level of visual imagery was significantly related only for the group with lower visual imagery, who recalled more adjectives. The implications of the results for the semantic and episodic memory distinction within autobiographical memory were discussed.

Long-term follow-up after high-activity 125I brachytherapy for pediatric brain tumors.

A retrospective review including long-term follow-up (4.6-12.0 years) was performed of all 28 pediatric patients who underwent high-activity 125I brachytherapy at the University of California, San Francisco, for primary or recurrent brain tumors from 1980 until 1991. There were 4 glioblastomas, 11 high-grade nonglioblastoma multiforme (NGM) malignant gliomas, 10 contrast-enhancing low-grade NGM, 2 choroid plexus carcinomas, and 1 rhabdomyosarcoma. The 13 survivors included 7 of 8 patients with primary high-grade NGM, 2 of 3 patients with primary low-grade NGM, and 3 of 7 patients with recurrent low-grade NGM. Necrosis (with or without tumor) was identified in 17 of 22 reoperated patients. The mean Karnofsky performance status was 88 +/- 9 at the time of brachytherapy, 87 +/- 7 at 3 years, and 87 +/- 9 in 11 patients alive at 6-12 years. Brachytherapy is a useful modality for treating selected pediatric brain tumors, and although focal necrosis is a common sequela, it does not tend to have a major impact on the Karnofsky performance status, if the implant site is amenable to reoperation.

Demonstration of brachytherapy boost dose-response relationships in glioblastoma multiforme.

PURPOSE: To evaluate brachytherapy dose-response relationships in adults with glioblastoma undergoing temporary 125I implant boost after external beam radiotherapy. METHODS AND MATERIALS: Since June 1987, orthogonal radiographs using a fiducial marker box have been used to verify brain implant source positions and generate dose-volume histograms at the University of California, San Francisco. For adults who underwent brachytherapy boost for glioblastoma from June 1987 through December 1992, tumor volumes were reoutlined to ensure consistency and dose-volume histograms were recalculated. Univariate and multivariate analysis of various patient and treatment parameters were performed evaluating for influence of dose on freedom from local failure (FFLF) and actuarial survival. RESULTS: Of 102 implant boosts, 5 were excluded because computer plans were unavailable. For the remaining 97 patients, analyses with adjustment for known prognostic factors (age, KPS, extent of initial surgical resection) and prognostic factors identified on univariate testing (adjuvant chemotherapy) showed that higher minimum brachytherapy tumor dose was strongly associated with improved FFLF (p = 0.001). A quadratic relationship was found between total biological effective dose and survival, with a trend toward optimal survival probability at 47 Gy minimum brachytherapy tumor dose (corresponding to about 65 Gy to 95% of the tumor volume); survival decreased with lower or higher doses. Two patients expired and one requires hospice care because of brain necrosis after brachytherapy doses > 63 Gy to 95% of the tumor volume with 60 Gy to > 18 cm3 of normal brain. CONCLUSION: Although higher minimum tumor dose was strongly associated with better local control, a brachytherapy boost dose > 50-60 Gy may result in life-threatening necrosis. We recommend careful conformation of the prescription isodose line to the contrast enhancing tumor volume, delivery of a minimum brachytherapy boost dose of 45-50 Gy in conjunction with conventional external beam radiotherapy, and reoperation for symptomatic necrosis.

The use of a partial transmission shield to reduce the optic chiasm doses during radiation therapy treatment of brain tumors.

Historically, brain tumors have been treated with lateral opposed beams for 40-45 Gy followed by more conformal reduced fields. Advances in treatment planning computers have led to the implementation of conformal non-axial techniques, allowing for escalation of dose. In patients where total doses exceed 50 Gy, adjacent critical structures can be protected with a partially shielded transmission block over the optic nerves and chiasm. By eliminating the conedown portion of the treatment a more cost and time effective treatment is achieved. Partially shielded blocks can be designed by using cerrobend or multileaf collimation. They can be included in the treatment plan and verified by an irregular field calculation and/ or thermoluminescent dosimeters.

Large effect of age on the survival of patients with glioblastoma treated with radiotherapy and brachytherapy boost.

A retrospective review was undertaken to study the influence of age on the survival of patients undergoing brachytherapy boost for glioblastoma multiforme. From February 1981 through December 1992, 159 adults with primary glioblastoma multiforme underwent high-activity iodine-125 brain implant boost after external beam radiotherapy. There were 98 men and 61 women, ranging in age from 18 to 73 years (median, 52 yr). Karnofsky performance scores ranged from 70 to 100 (median, 90). Surgery before radiotherapy consisted of biopsy in 7% of patients, subtotal resection in 66%, and gross total resection in 27%. External beam radiotherapy doses ranged from 39.6 to 76.8 Gy, with 91% of patients receiving 59.4 to 61.2 Gy. Brachytherapy doses ranged from 35.7 to 66.5 Gy (median, 55.0 Gy) at 0.30 to 0.70 Gy per hour (median, 0.43 Gy/h). Reoperations were performed in 81 patients (51%). Information on quality of life was available for 13 of the 14 living 3-year survivors; 10 patients were steroid independent, and mean Karnofsky performance scores had decreased from 92 at the time of brachytherapy to 75 at the last follow-up. Univariate and multivariate analyses showed that age was the most important parameter influencing survival (P < 0.0005). The nine patients 18 to 29.9 years old had a 3-year survival probability of 78 +/- 14% (median survival was not yet reached at the time of this report), with a follow-up of 145 to 511 weeks in living patients (median, 322 wk).(ABSTRACT TRUNCATED AT 250 WORDS)

Source localization for template implants with particular reference to stepping-source afterloaders.

Source localization from radiographs can be very difficult for template-guided implants if the needle images overlap. At UCSF several techniques to make this task easier have been developed. The techniques include selection of an optimum simulator gantry angle, use of different types of dummies, and differential dummy loading. In addition, several modifications have been made in our brachytherapy planning computer program to facilitate source entry. As a result of these improvements, source localization is now accomplished in much less time with improved accuracy.

Patterns of recurrence of glioblastoma multiforme after external irradiation followed by implant boost.

PURPOSE: To study patterns of recurrence in patients with focal primary glioblastoma treated on Northern California Oncology Group protocol 6G-82-2 including surgery, focal external beam radiotherapy (59.4-60 Gy) with oral hydroxyurea followed by temporary brain implant with high-activity iodine-125 sources (50 Gy), and six cycles of chemotherapy with procarbazine, lomustine, and vincristine. METHODS AND MATERIALS: Serial brain imaging scans were available for review in 25 of 34 patients with glioblastoma who underwent brain implant boost. Of 381 scans performed between the date of diagnosis and the date of death or last follow-up, 362 (95%) were re-reviewed. Disease progression was scored as local (within 2 cm of the implant site), separate within the brain parenchyma (> or = 2 cm from the implant site), subependymal, or systemic. Both initial and subsequent failures were scored. RESULTS: Three patients are 5-year survivors, without evidence of disease, at 267, 292, and 308 weeks. Of the 22 initial sites of failure, 17 (77%) were local, three (14%) were separate brain lesions (one of which was due in retrospect to multicentric disease at diagnosis), one (5%) subependymal, and one (5%) systemic. Five patients with local failure later had other sites of failure, including a separate brain lesion in 1, subependymal spread in 3, and both in 1. One patient with separate brain failure later had local progression and then subependymal spread. CONCLUSION: Although there was a significant risk of separate brain lesions or subependymal spread over time, local tumor progression was the predominant pattern of failure.

Applicability of standard irregular field calculations for high-energy photon beams.

Irregular-field calculations are usually based on a sector-summation technique. This technique typically involves separating the dose into primary and scatter components. While the conceptual basis for this procedure is valid at lower energies, it becomes suspect at higher energies. However, despite this limitation, a straightforward application of the technique yields good accuracy for 18 MV X-rays if certain limitations are observed. This work describes the calculational formalism used and the approximations made. Computed results are compared with measurements. The levels of uncertainty in both are discussed.

High intensity 125-iodine (125I) plaque treatment of uveal melanoma.

PURPOSE: Episcleral 125I plaque therapy of uveal melanoma is an important treatment modality to control tumor, salvage the globe, and potentially preserve vision. We retrospectively analyzed our experience in 239 patients to assess treatment outcome with this technique. METHODS AND MATERIALS: Between 1983 and 1990, 239 uveal melanoma patients were treated with 125I plaques at the University of California, San Francisco. High intensity 125I seeds in the range of 3-20 mCi were used to give a minimum tumor dose of 70 Gy in 4 days. Initial mean tumor size was 10.9 mm x 9.2 mm x 5.5 mm with a range in tumor diameter from 4 to 18 mm and tumor height from 1.9 to 11.1 mm. Best corrected pre-treatment visual acuity was 20/200 or better in 92% of patients. RESULTS: Local tumor control was maintained in 91.7% of patients with a mean follow-up of 35.9 months; 19 patients had local tumor progression; mean time to progression was 27.3 mo (1.8 to 60.1 mo). Actuarial local control is 82% at 5 years. Multivariate analysis demonstrates significant correlation of local failure with larger maximum tumor diameter (p = 0.0008), closer proximity to the fovea (p = 0.0001), lower radiation dose (p = 0.0437), and smaller ultrasound height (p = 0.0034). The actuarial incidence of distant metastases is 12% at 5 years with multivariate analysis showing significant correlation only with maximum tumor diameter (p = 0.0064). Visual outcome is 20/200 or better in 58% of patients. CONCLUSION: While the tumor control rates appear favorable, ocular morbidity is significant. A current randomized trial comparing 125I plaque with Helium ion therapy is in progress with specific comparison of tumor control, survival, and visual outcome.

Correlations between scores on the Wechsler Intelligence Scale for Children-III and the General Purpose Abbreviated Battery of the Stanford-Binet IV.

Estimations of some relationships among scores on the "General Purpose Abbreviated Battery" of the Stanford-Binet: Fourth Edition and the Wechsler Intelligence Scale for Children-III were based on the responses of 14 boys and 18 girls enrolled in Grades 3, 4, and 5 and who took both tests. Of 13 Pearson correlations between the Binet IV composite score and the Wechsler subtest scores and IQs 12 were statistically significant (rs = .45 to .74). The new Wechsler scale appears to be a valid instrument for the 32 children (8-8 to 11-11) who were tested.

Null effect of mood as a semantic prime.

Semantic tasks, such as lexical decision making and word recognition, have not produced a mood priming effect. Earlier studies have been criticized because they included (a) mood induction techniques that required instruction to feel the mood, and (b) the use of overlearned tasks that did not require controlled processing. In this pair of experiments, the authors attempted to address these criticisms. However, the results of this study did not demonstrate a mood priming effect for happy and sad subjects who appraised sentence content as being happy or sad. The results of this study supported the dissociation of semantic and episodic memory.