Heat stress affects the expression of key genes in the placenta, placental characteristics, and efficiency of Saanen goats and the survival and growth of their kids.

Heat stress is detrimental during gestation; however, the effects of heat stress on goat placental characteristics and kid survival remain unclear. The objective of this study was to evaluate the effects of heat stress at final gestation on cortisol concentration, placenta characteristics, and the expression of genes related to placenta. Forty-six primiparous and multiparous Saanen goats were subjected to control (CT; under a thermoneutral environment: air temperature between 12°C and 25°C and the relative humidity from 45 to 73%, n = 23) or heat stress (HS; under a climatic chamber: air temperature at 37°C and the relative humidity at 60 to 70% from 0800 to 1600 h, n = 23) from the last 60 d of pregnancy until the first colostrum suckling. The heat challenge imposed on HS goats during the prepartum period increased their rectal temperature, respiratory frequency, and cortisol levels in plasma and amniotic fluid versus CT goats. In the placenta, HS treatment also increased the expression of the HSPA1A gene. Heat-stressed goats also showed significantly lower expression of HSD11B2 and greater expression of MC2R and NR3C1 than CT goats, suggesting that heat stress decreased the effectiveness by which the HSD11B2 enzyme converts cortisol to cortisone and increased placental responsiveness to cortisol. The HS goats took longer to release the placenta with lighter placental cotyledons, and HS goats had a lower ratio between the kid's weight at birth and placenta weight than CT goats. There was no treatment effect on the kids' survival or weights at birth, but the kids from goats subjected to HS presented lesser cortisol concentration and greater mortality rates at weaning than kids from CT goats. Finally, the overexpression of HSPA1A by HS goats suggests a protective response of placenta. However, the heat stress negatively affected the placenta's expulsion length, placental cotyledons number, weight and area, the ratio between kid's weight and placenta weight, and cortisol signaling. Indeed, the upregulation of MC2R and NR3C1 and downregulation of HSD11B2 on placenta caused by heat stress were associated with greater cortisol concentrations in the amniotic fluid of HS goats. Although HS and CT kids had adequate weights and survival rate during the first weeks of life, the heat stress increased the mortality at weaning of HS kids versus CT kids, suggesting that the heat stress effect persists and can change the ability of kids to respond to weaning challenge.

Effect of heat stress in late gestation on subsequent lactation performance and mammary cell gene expression of Saanen goats.

Little is known about the effects of heat stress during the late gestation period on lactation in dairy goats. For this reason, 32 Saanen goats were randomly assigned to 1 of 2 groups, control (CT; n = 16) or heat stress (HS; n = 16), during late gestation. The HS goats were housed in a climatic chamber before parturition and subjected to heat stress for the last 45 d. After parturition, the HS goats were housed in the same conditions as the CT group. Mammary gland biopsies were performed on 7 goats per treatment at -30, -15, 15, and 30 d relative to parturition, so that the expression levels of several genes could be determined. The HS goats produced less milk than the CT goats did during the first half of lactation, but not during the rest of lactation. Before parturition, apoptosis-related transcripts (TP53 and BAX) were higher in the mammary glands of the HS goats than in those of the CT goats. The HS goats also had higher levels of HSPB1 gene expression during gestation and lactation. However, expression of the prolactin receptor gene was lower after parturition in the mammary glands of HS, suggesting downregulation of prolactin signaling. In summary, heat stress during final gestation reduces milk yield in the subsequent lactation. Although the upregulation of apoptosis signaling in the HS goats suggests that heat stress affects mammary cell number, the loss of the effect on milk production is more compatible with an effect on cell activity, which could be due to a downregulation of prolactin signaling.

Electromagnetic Fields Associated with Commercial Solar Photovoltaic Electric Power Generating Facilities.

The southwest region of the United States is expected to experience an expansion of commercial solar photovoltaic generation facilities over the next 25 years. A solar facility converts direct current generated by the solar panels to three-phase 60-Hz power that is fed to the grid. This conversion involves sequential processing of the direct current through an inverter that produces low-voltage three-phase power, which is stepped up to distribution voltage (∼12 kV) through a transformer. This study characterized magnetic and electric fields between the frequencies of 0 Hz and 3 GHz at two facilities operated by the Southern California Edison Company in Porterville, CA and San Bernardino, CA. Static magnetic fields were very small compared to exposure limits established by IEEE and ICNIRP. The highest 60-Hz magnetic fields were measured adjacent to transformers and inverters, and radiofrequency fields from 5-100 kHz were associated with the inverters. The fields measured complied in every case with IEEE controlled and ICNIRP occupational exposure limits. In all cases, electric fields were negligible compared to IEEE and ICNIRP limits across the spectrum measured and when compared to the FCC limits (≥0.3 MHz).

Stress during first gestation of ewes impairs memory and learning of male offspring.

This study aimed to investigate the influence of gestational stress induced by lipopolysaccharide (LPS, Escherichia coli) on the physiological changes of ewes, as well as on the subsequent behavioral interaction between ewes and lambs and on the memory and learning of 30-day-old offspring in a T-maze. Thirty-six nulliparous pregnant crossbred Santa Ines ewes with an initial live weight of 45 ± 6 kg, age of 12 ± 2 months, and body condition score between 3 and 3.5 (on a scale of 1 to 5) were divided into two treatments: LPS treatment (E. coli; 0.8 µg.kg-1) and Control (placebo/saline) administered in late pregnancy (day 120). Blood samples were collected before (0 h at 5:00 h) and 1 h, 2 h, 4 h, 8 h, 12 h, 24 h after the administration of LPS or placebo to determine the cortisol release curve. Rectal temperature was measured at the same time points. After birth, male lambs (N = 19) were used to evaluate the maternal-offspring behavioral interaction, weight, and cognitive ability in a T-maze. Blood cortisol and rectal temperature of ewes increased after LPS administration and returned to baseline levels after 24 h. The activities facilitating and stimulating suckling were higher on LPS group (P < 0.05). Lambs whose mothers were challenged with LPS during late pregnancy showed greater learning and memory disabilities including fear behavior and the inability to make decisions at 30 days of age in the T-maze. In sheep, the immunological stress induced by LPS in late pregnancy promotes an inflammatory response characterized by specific rectal temperature and cortisol release profiles, improving maternal care that can increase offspring survival; however, the exposure of sheep fetuses to maternal inflammation causes cognitive impairment in lambs at 30 days of age, which could not be reduced by the behavioral interaction between the mother and offspring.

Partial nephrectomy after previous radio frequency ablation: the National Cancer Institute experience.

PURPOSE: Development of new renal tumors or recurrence after radio frequency ablation not amendable for repeat ablation presents a difficult therapeutic dilemma. We report on the outcomes of partial nephrectomy on kidneys previously treated with radio frequency ablation. MATERIALS AND METHODS: We performed a chart review of 13 patients who underwent 16 attempted partial nephrectomies following radio frequency ablation. Hospital records and operative reports were reviewed for demographic data, perioperative data and outcomes. The outcomes of the present series were compared to historical controls of published studies in similar patient populations. RESULTS: No cases were converted to radical nephrectomy. Median time from radio frequency ablation to surgery was 2.75 years (range 1 to 7.1). A median of 7 tumors (range 2 to 40) were removed with a median estimated blood loss of 1,500 ml (range 500 to 3,500) and a median operative time of 7.8 hours (range 5 to 10.7). Operative notes commented on the presence of severe fibrosis in the operative field in 12 of 16 cases (75%). There was a modest but statistically significant decrease in renal function. Partial nephrectomy after radio frequency ablation had a higher reoperation rate compared to other series of primary or repeat partial nephrectomies but had the lowest rate of vascular or visceral injuries. CONCLUSIONS: Partial nephrectomy on kidneys previously treated with radio frequency ablation is a technically challenging but feasible procedure. Residual or metachronous disease after radio frequency ablation may be salvaged with partial nephrectomy with a modest decrease in renal function. A trend toward a higher chance of reoperation and urine leak after partial nephrectomy after radio frequency ablation may be useful information for the planning and discussion of treatment decisions.

The origin, molecular regulation and therapeutic potential of myogenic stem cell populations.

Satellite cells, originating in the embryonic dermamyotome, reside beneath the myofibre of mature adult skeletal muscle and constitute the tissue-specific stem cell population. Recent advances following the identification of markers for these cells (including Pax7, Myf5, c-Met and CD34) (CD, cluster of differentiation; c-Met, mesenchymal epithelial transition factor) have led to a greater understanding of the role played by satellite cells in the regeneration of new skeletal muscle during growth and following injury. In response to muscle damage, satellite cells harbour the ability both to form myogenic precursors and to self-renew to repopulate the stem cell niche following myofibre damage. More recently, other stem cell populations including bone marrow stem cells, skeletal muscle side population cells and mesoangioblasts have also been shown to have myogenic potential in culture, and to be able to form skeletal muscle myofibres in vivo and engraft into the satellite cell niche. These cell types, along with satellite cells, have shown potential when used as a therapy for skeletal muscle wasting disorders where the intrinsic stem cell population is genetically unable to repair non-functioning muscle tissue. Accurate understanding of the mechanisms controlling satellite cell lineage progression and self-renewal as well as the recruitment of other stem cell types towards the myogenic lineage is crucial if we are to exploit the power of these cells in combating myopathic conditions. Here we highlight the origin, molecular regulation and therapeutic potential of all the major cell types capable of undergoing myogenic differentiation and discuss their potential therapeutic application.

A nested case-control study of brain tumors among employees at a petroleum exploration and extraction research facility.

Work-related exposures potentially associated with a cluster of brain tumors at a petroleum exploration and extraction research facility were evaluated in a nested case-control study. Fifteen cases were identified in the original cohort and 150 matched controls were selected. Odds ratios (ORs) for occupational exposure to petroleum, radiation, solvents, magnetic fields, and work activities were near or below 1.0. ORs near 1.5 were observed for: working with computers (OR = 1.47; 95% confidence interval [CI] = 0.30-9.35); work-related travel (OR = 1.48; 95% CI = 0.25-5.95), and travel immunizations (OR = 1.62; 95% CI = 0.23-9.45). Higher ORs were observed for work in administrative and marketing buildings and for achieving a master's or higher degree (OR = 2.0, 95% CI = 0.4-10.7). While some ORs above 1.5 were noted, no work-related chemical and physical exposures were significantly associated with the occurrence of brain tumors among employees at this facility.

Safety and potential efficacy of low-dose methotrexate for treatment of chronic graft-versus-host disease.

Low-dose methotrexate (MTX) is widely used in autoimmune diseases because of its anti-inflammatory activity. We report here the results of a retrospective study to review the outcomes of low-dose MTX used for treatment of refractory chronic graft-versus-host disease GVHD, with the goal of reducing the amount of prednisone needed to control the disease. In all, 14 patients with refractory chronic GVHD received MTX at a dose of 7.5 mg/m(2)/weekly for 3--0 weeks. Also, 11 patients had skin involvement, often with scleroderma or fasciitis. The median duration of chronic GVHD at the start of MTX was 38 (range 1--35) months. In this retrospective review, we found no grade 3-- toxicities, and none of the patients needed blood transfusion or growth factors. In 10 patients (71%), GVHD could be adequately controlled with prednisone at doses below 1 mg/kg every other day without the addition of other agents. Four patients decreased the amount of concomitant immunosuppressive treatment, five continued with the same regimen, four required an increase in immunosuppressive treatment, and one decided to discontinue all treatment. From this preliminary analysis, MTX appears to be a well-tolerated, inexpensive and possibly steroid-sparing agent that is worthy of further evaluation in prospective trials for treatment of chronic GVHD.

Correction for out-of-focal-plane blurring in a simulated multiplane tomographic scanner.

A technique has been developed to remove out-of-focal-plane blurring from coronal and axial images made using a multiplane tomographic scanner. The technique uses a combined smoothing and differential operator that is applied to the axial images. It has been tested using computer-simulated images, with favorable results. The usefulness of the technique in a real system has yet to be determined.

Interactive three-dimensional region of interest analysis of HMPAO SPECT brain studies.

An interactive computer program has been developed to align a three-dimensional region of interest (ROI) model to technetium-99m-hexamethylpropylenamine oxime (99mTc-HMPAO) single-photon emission computed tomography (SPECT) studies of the brain. The ROI model subdivides the human brain into fourteen discrete regions. A study was performed to determine normal ranges for HMPAO uptake in the ROIs defined by the model, and to assess the relative interobserver variability using the fitting program. HMPAO SPECT studies of twelve normal volunteers were independently analyzed by four observers. Small but significant differences between operators occurred primarily because of difficulty in defining the angle of the orbitomeatal plane on sagittal SPECT images. Despite this difficulty, the program and model have proven useful in defining ranges for normal cerebral perfusion in a healthy adult population. A study of a small group of patients with Alzheimer's dementia suggests that this procedure may be of use in the diagnosis of this disease.

Effect of doxorubicin on [omega-I-131]heptadecanoic acid myocardial scintigraphy and echocardiography in dogs.

The effects of serial treatment with doxorubicin on dynamic myocardial scintigraphy with [omega-I-131]heptadecanoic acid (I-131 HA), and on global left-ventricular function determined echocardiographically, were studied in a group of nine mongrel dogs. Total extractable myocardial lipid was compared postmortem between a group of control dogs and doxorubicin-treated dogs. A significant and then progressive fall in global LV function was observed at a cumulative doxorubicin dose of 4 mg/kg. A significant increase in the myocardial t1/2 of the I-131 HA was observed only at a higher cumulative dose, 10 mg/kg. No significant alteration in total extractable myocardial lipids was observed between control dogs and those treated with doxorubicin. Our findings suggest that the changes leading to an alteration of myocardial dynamic imaging with I-131 HA are not the initiating factor in doxorubicin cardiotoxicity.

Autologous stem cell transplantation for Hodgkin's disease: busulfan, melphalan and thiotepa compared to a radiation-based regimen.

We evaluated prognostic factors and treatment outcome of patients with relapsed/refractory Hodgkin's disease (HD) receiving autologous stem cell transplantation (ASCT). In total, 92 patients received total body irradiation, cyclophosphamide and etoposide (TBI/CY/E) (n=42) or busulfan, melphalan and thiotepa (Bu/Mel/T) (n=50) supported with ASCT. A total of 33 (66%) patients receiving the Bu/Mel/T regimen had a prior history of dose-limiting irradiation. Mucositis, hepatic and pulmonary toxicities were the main causes of morbidity and mortality, irrespective of the conditioning regimen. The transplant-related mortality was 15%. With a median follow-up of 6 years (range 2.5-11), the cumulative probabilities of survival, event-free survival (EFS) and relapse at 6 years were 55, 51 and 32%. The 6-year Kaplan-Meier (KM) probabilities of EFS for patients with less advanced disease (patients in first chemotherapy-responsive relapse or second remission (n=42)) and more advanced disease (all other patients (n=50)) were 60 and 44%. No differences in toxicities and efficacy between the conditioning regimens were found. ASCT is an effective treatment for patients with refractory/relapsed HD. Female patients and patients with less advanced disease at transplant had a better outcome. Patients with prior irradiation benefited from the Bu/Mel/T regimen.

High-dose busulfan, melphalan and thiotepa as consolidation for non-inflammatory high-risk breast cancer.

The purpose of this study was to evaluate the toxicity and efficacy of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) in patients with high-risk non-inflammatory breast cancer defined as stage II disease > or =10 lymph nodes (n = 52) or stage III (n = 69), and prognostic factors for treatment outcome. One hundred and twenty-one patients (median age, 46 years) were treated with high-dose Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) (HDC) followed by autologous stem cell infusion (ASCI). One hundred patients were initially treated with surgery followed by standard adjuvant chemotherapy prior to HDC/ASCI. Twenty-one patients with stage III disease had inoperable tumors at diagnosis and were treated with neoadjuvant chemotherapy and surgery before HDC/ASCI. Transplant-related mortality was 6%. The probabilities of event-free survival (EFS) at 3 and 5 years (median follow-up of 36 months) from transplant were, for all patients: 0.62-0.60; stage II: 0.71-0.67: stage III: 0.55-0.55 (for stage III adjuvant and neoadjuvant groups: 0.60-0.60 and 0.42-0.42, respectively). Multivariate analysis did not identify variables associated with poor outcome. The efficacy of Bu/Mel/TT is similar to other HDC regimens reported for patients with high-risk non-inflammatory breast cancer. Bu/Mel/TT has high activity in stage II disease and a moderate benefit in stage III operable tumors.

Autologous stem cell transplantation for non-Hodgkin's lymphoma: comparison of radiation-based and chemotherapy-only preparative regimens.

The aim of this study was to compare toxicity and efficacy of total body irradiation (TBI), cyclophosphamide (CY) and etoposide (E) (TBI/CY/E) vs busulfan, melphalan and thiotepa (Bu/Mel/T) in patients receiving autologous stem cell infusion (ASCI) for malignant lymphoma (NHL). Between September 1990 and July 1998, 351 patients with NHL were treated with TBI/CY/E (n = 221) or Bu/Mel/T (n = 130) followed by ASCI. Patients in first, or second remission, first responding or untreated relapse were defined as having less advanced disease before transplantation. The median follow-up was 5 years (range 1-9) and 3.5 years (1-6) for patients receiving TBI/CY/E and Bu/Mel/T, respectively. The cumulative probabilities of survival, event-free survival (EFS) and relapse at 5 years were 44%, 32%, 49% following TBI/CY/E and 42%, 34% and 42% following Bu/Mel/T. The probability of EFS at 5 years for patients who had prior dose-limiting radiation (n = 59) was 32% after Bu/Mel/T therapy. Transplant-related mortality was 16% for TBI/CY/E and 21% for Bu/Mel/T. In univariate and multivariate analyses, more advanced disease status was associated with poor outcome (TBI/CY/E: RR 0.70, CI 0.50 to 0.97 P = 0.04; Bu/Mel/T: RR 0.61, CI 0.39 to 0.97 P = 0.03). No significant differences in toxicities and outcomes were observed between these two regimens despite the inclusion of patients who had received dose-limiting irradiation in the Bu/Mel/T regimen.

Technical note: Sinogram merging to compensate for truncation of projection data in tomotherapy imaging.

An advantage of helical tomotherapy radiation therapy systems is that on-line megavoltage computed tomography (CT) images can be reconstructed to verify patient positioning. One limitation of such systems is that the field-of-view (FOV) of the photon fan-beam is limited by the aperture size of the binary multileaf collimator (MLC) used to modulate treatment beams. For patients larger than the FOV the acquired sinograms will be truncated causing artifacts in the resultant megavoltage CT images. Computer simulations are used to demonstrate that such artifacts can be eliminated or at least reduced by merging appropriately acquired truncated fan-beam sinograms to form a nontruncated parallel-beam sinogram. The necessary fan-beam sinograms are acquired with the patient translated to different offset locations within the gantry. The parallel-beam sinogram is then used to reconstruct the final CT image. The increase in patient dose due to the acquisition of more than one fan-beam sinogram can be reduced by using properly designed binary MLC fields to block redundant projection rays.

Rapid, parallel separations of d1S80 alleles in a plastic microchannel chip.

We have performed fast, parallel separations of alleles of the D1S80 locus in a plastic, multi-channel chip, replicated from a microfabricated master and laminated with a plastic film. The array of 16 channels was filled with a replaceable sieving polymer, and a size-dependent, electrophoretic separation of the DNA fragments was performed in all channels in less than 10 min, representing a 30-fold increase in throughput compared to that on a single-capillary instrument. To detect the fragments in all 16 channels in parallel during the run, we designed and built a scanning, confocal, laser-induced fluorescence system. The electropherograms were then used to determine the sample genotype. To demonstrate the use of multiplexed, microchannel arrays for real-life samples, we amplified D1S80 alleles from genomic DNA extracted from whole blood and separated these alleles by electrophoresis in the plastic chip. Evaluation of the electrophoretic data showed that, using a 300- and a 1,000-base pair fragment as internal mobility markers, 83% of the alleles were assigned correctly, using the allele identification from a single capillary instrument as a reference. This work demonstrates that, with improvements in the microchannel electrophoresis system, it is feasible to perform rapid, parallel genotyping in mass-produced, inexpensive, disposable plastic devices for large-scale applications in medicine and the life sciences.

Experimental and numerical investigation of the 3D SPECT photon detection kernel for non-uniform attenuating media.

Experimental tests for non-uniform attenuating media are performed to validate theoretical expressions for the photon detection kernel, obtained from a recently proposed analytical theory of photon propagation and detection for SPECT. The theoretical multi-dimensional integral expressions for the photon detection kernel, which are computed numerically, describe the probability that a photon emitted from a given source voxel will trigger detection of a photon at a particular projection pixel. The experiments were performed using a cylindrical water-filled phantom with large cylindrical air-filled inserts to simulate inhomogeneity of the medium. A point-like, a short thin cylindrical and a large cylindrical radiation source of 99Tcm were placed at various positions within the phantom. The values numerically calculated from the theoretical kernel expression are in very good agreement with the experimentally measured data. The significance of Compton-scattered photons in planar image formation is discussed and highlighted by these results. Using both experimental measurements and the calculated values obtained from the theory, the kernel's size is investigated. This is done by determining the square N x N pixel neighbourhood of the gamma camera that must be connected to a particular radiation source voxel to account for a specific fraction of all counts recorded at all camera pixels. It is shown that the kernel's size is primarily dependent upon the source position and the properties of the attenuating medium through Compton scattering events, with 3D depth-dependent collimator resolution playing an important but secondary role, at least for imaging situations involving parallel hole collimation. By considering small point-like sources within a non-uniform elliptical phantom, approximating the human thorax, it is demonstrated that on average a 12 cm x 12 cm area of the camera plane is required to collect 85% of the total count recorded. This is a significantly larger connectivity than the 3 cm x 3 cm area required if scattering contributions are ignored and only the 3D depth-dependent collimator resolution is considered.

Does gallium uptake in the pulmonary hila predict involvement by non-Hodgkin's lymphoma?

67Ga imaging of non-Hodgkin's lymphoma is useful for evaluating the presence of viable tumour in a residual mass after treatment. However, we have frequently seen gallium uptake in the pulmonary hila without other evidence of lymphoma. To study the significance of this finding, 79 patients with intermediate grade non-Hodgkin's lymphoma were reviewed. Thirty-seven (47%) had abnormal hilar gallium uptake. Twenty-three of these could be fully evaluated, and only five (22%) had hilar lymphoma. A pattern of bilateral, symmetric hilar uptake was seen in 19 patients, but only one had evidence of lymphoma. In 15 cases, this pattern was seen only on single photon emission computed tomography (SPECT). The aetiology of this uptake remains unknown. It is not treatment related, as 12 patients had hilar gallium uptake prior to chemotherapy. Unless confirmed by other methods, hilar gallium uptake should not be attributed to lymphoma, and should not influence patient management.

MAb 170H.82: an evaluation of a novel panadenocarcinoma monoclonal antibody labelled with 99Tcm and with 111In.

A novel method for generating monoclonal antibodies against synthetic tumour-associated glycoconjugates has been developed. One of these monoclonal antibodies, designated 170H.82, was derived against the TF antigen and has been shown in vitro to have a wide range of reactivity with adenocarcinoma. This antibody has been labelled with 111In and 99Tcm and has been evaluated in pilot clinical trials involving 48 patients with a range of adenocarcinoma. Overall clinical accuracy with the radiolabelled antibody was 92%, with the antibody appearing to have particular clinical utility in gynaecological and breast cancers. Single photon emission computed tomographic (SPECT) imaging was shown to improve the quality of the images and to improve the diagnostic sensitivity. We believe that this unique antibody, labelled with 99Tcm, appears to offer promise for routine clinical use in the evaluation of patients with a range of primary and metastatic adenocarcinoma.

Tc-99m HMPAO to demonstrate diffuse cortical necrosis in vivo.

Tc-99m hexamethylpropylene amineoxime (HMPAO) is a novel radiopharmaceutical demonstrated to be a sensitive indicator of abnormalities of cerebral perfusion. Most reports in the literature have evaluated patients with gross perfusion deficits, such as cerebrovascular accidents, and with dementia, where patterns of diffuse perfusion deficit were reported comparable with those seen in PET studies. We report a patient in whom there was the rapid onset of dementia, with the HMPAO images demonstrating diffuse loss of cortical perfusion in a nonfocal, and nonsegmental, fashion. Correlation with postmortem examination demonstrates good concordance between the diffuse nature of HMPAO loss, and diffuse cortical necrosis throughout both cerebral hemispheres. The technique was shown to be more sensitive than transmission CT scanning in demonstrating the extent of the deficit, and it correlated closely with the functional deficits noted in the patient.