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Fipronil is a widely used phytosanitary product and insecticide for pets. In the rat, fipronil can disrupt thyroid function by decreasing plasma concentrations of total thyroxine (T4) likely through increased T4 clearance. However, the mechanism of fipronil action on thyroid function remains unclear. The goals of the present study were to evaluate the effects of fipronil on thyroid hormone (TH) concentrations and elimination in the rat under well characterized plasma exposure to fipronil and its main metabolite fipronil sulfone. In thyroid-intact female rats, fipronil treatment (3 mg/(kg day) per os for 14 days) decreased both total and free TH plasma concentrations concomitantly to increased thyroid stimulating hormone plasma concentrations. A T4-free euthyroid-like model consisting of thyroidectomized rats treated with tri-iodothyronine (12 microg/(kg day), sc) was developed to evaluate both total and free T4 clearances. In this model, fipronil treatment induced a twofold increase in total and free T4 clearances. The same fipronil treatment increased antipyrine clearance in thyroid-intact rats suggesting an increase in the activity of cytochrome P450 enzymes. Finally, this treatment was also associated with an increase in hepatic microsomal 4-nitrophenol UDP-glucuronosyltransferase activity involved in T4 glucuronidation. Thus, fipronil-induced thyroid disruption results from an increased rate of T4 elimination likely mediated by increased hepatic enzyme activity. Plasma concentrations of fipronil sulfone were at least 20-fold higher than those of fipronil. This highlights the need to further investigate the contribution of fipronil sulfone to the fipronil-induced thyroid disruption.

The expression of interferon-tau (IFN-tau) is essential for bovine embryo survival in the uterus. An evaluation of IFN-tau production from somatic cell nuclear transfer (NT)-embryo-derived primary trophectoderm cultures in comparison to trophectoderm cultured from parthenogenote (P) and in vitro matured, fertilized, and cultured (IVP) bovine embryos was performed. In Experiment 1, the success/failure ratio for primary trophectoderm colony formation was similar for IVP and NT blastocysts [IVP = 155/29 (84%); NT 104/25 (81%)], but was decreased (P = .05) for P blastocysts [54/43 (56%)]. Most trophectoderm colonies reached diameters of at least 1 cm within 3-4 weeks, and at this time, 72 hr conditioned cell culture medium was measured for IFN-tau concentration by antiviral activity assay. The amount of IFN-tau produced by IVP-outgrowths [4311 IU/mL (n = 155)] was greater (P < .05) than that from NT- [626 IU/mL (n = 104)] and P - [1595 IU/mL (n = 54)] derived trophectoderm. Differential expression of IFN-tau was confirmed by immunoblotting. In Experiment 2, colony formation was again similar for IVP and NT blastocysts [IVP = 70/5 (93%); NT 67/1 (99%)] and less (P < .05) for P blastocysts [65/27 (70%)]. Analysis of trophectoderm colony size after 23 days in culture showed a similar relationship with P-derived colonies being significantly smaller in comparison to IVP and NT colonies. A differential expression of IFN-tau was also observed again, but this time as measured over time in culture. Maximal IFN-tau production was found at day-14 of primary culture and diminished to a minimum by the 23rd day., (2007 Wiley-Liss, Inc)

A previous cDNA microarray analysis in murine MC3T3-E1 osteoblasts revealed a cluster of genes involved in cell cycle progression that was significantly down-regulated after a single treatment with 1alpha,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] [L. Verlinden, G. Eelen, I. Beullens, M. Van Camp, P. Van Hummelen, K. Engelen, R. Van Hellemont, K. Marchal, B. De Moor, F. Foijer, H. Te Riele, M. Beullens, M. Bollen, C. Mathieu, R. Bouillon, A. Verstuyf, Characterization of the condensin component Cnap1 and protein kinase Melk as novel E2F target genes down-regulated by 1,25-dihydroxyvitamin D3, J. Biol. Chem. 280 (45) (2005) 37319-37330]. Among those genes were the DNA replication and DNA damage checkpoint proteins, Chk1 and Claspin, of which the human homologues were recently shown to be E2F-responsive. Quantitative real-time PCR experiments in 1,25(OH)(2)D(3)-treated MC3T3-E1 cells confirmed the down-regulation observed in the microarray experiment. Moreover, Chk1 and Claspin promoter activities were also reduced after incubation with 1,25(OH)(2)D(3), and this reduction was mediated through the E2F recognition motifs within their promoters because mutation of these motifs almost completely abolished the repressive effect of 1,25(OH)(2)D(3). The antiproliferative effect of 1,25(OH)(2)D(3) as well as its potential to down-regulate the expression of Chk1 and Claspin depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) lost its antiproliferative action and failed to repress these E2F-target genes in p107(-/-);p130(-/-)-cells, but not in pRb(-/-)-cells.

Tools and methods for analyzing differences in embryos resulting from somatic cell nuclear transfer (NT) in comparison to those derived from normal fertilization are needed to define better the nature of the nuclear reprogramming that occurs after NT. To this end, a collection of bovine blastocyst-derived cell lines was created. In vitro expanded or hatched blastocysts, used as primary culture tissue, were from NT; in vitro maturation, fertilization, and culture (IVF); or parthenogenetic (P) activation. Also, five in vivo-fertilized and developed blastocysts were collected by uterine flushing on the eighth d postfertilization. Whole blastocysts were physically attached to STO feeder layers to initiate all of the cell lines generated. The majority of the cell lines in the collection are trophectoderm, 38 NT-derived, 6 in vivo-derived, 20 IVF-derived, and 13 P-derived. Trophectoderm identity was ascertained by morphology and, in many cases, interferon-tau production. Several visceral endoderm cell lines and putative parietal endoderm cell lines were also established. At approximately 5% efficiency, epiblast masses from NT and IVF blastocysts survived and were isolated in culture. Two epiblast masses were also isolated from P blastocysts. Spontaneous differentiation from the epiblast outgrowths resulted in the establishment of fibroblast cell lines. The use of the trophectoderm cell lines as a comparative in vitro model of bovine trophectoderm and placental function is discussed in relation to NT reprogramming.

Joint mobilization and manipulation stimulate mechanoreceptors, which may influence the joint and surrounding muscles. The purpose of this pilot study was to determine the effect of grade IV inferior hip joint mobilization on hip abductor torque. Thirty healthy subjects were randomly assigned to a control group (grade I inferior hip joint mobilization) or an experimental group (grade IV inferior hip joint mobilization). Subjects performed a pre- and post-intervention test of five isometric repetitions on the Cybex Normö dynamometer; the average torque was determined for both pre- and post-intervention measurements. These data were analyzed using the independent samples t-test with the significance level set at P<0.05. The results showed a statistically significant difference between the two groups for an increase in hip abductor torque in the experimental group (P=0.03). The experimental group demonstrated a 17.35% increase in average torque whereas the control group demonstrated a 3.68% decrease in average torque. These findings are consistent with other studies demonstrating that the use of grade IV non-thrust mobilization improves strength immediately post-intervention in healthy individuals. The results of this pilot study provide physical therapists with further support for the utilization of manual therapy in conjunction with therapeutic exercise to enhance muscle strength.

1,25-Dihydroxyvitamin D(3) (1,25(OH)(2)D(3)) has potent antiproliferative effects characterized by a hampered G(1)/S transition. cDNA microarrays were used to monitor expression of 21,492 genes in MC3T3-E1 mouse osteoblasts at 1, 6, 12, 24, and 36 h after treatment with 1,25(OH)(2)D(3). Statistical analysis revealed a cluster of genes that were strongly down-regulated by 1,25(OH)(2)D(3) and which not only function in cell cycle regulation and DNA replication but also mediate checkpoint control, DNA repair, chromosome modifications, and mitosis. Because many of these genes were shown earlier to be regulated by the transcriptional repressor E2F4, the intergenic regions of these 1,25(OH)(2)D(3)-down-regulated genes were searched for the presence of E2F binding sites. This led to the characterization of two novel E2F target genes, chromosome condensation-related SMC-associated protein 1 (Cnap1) and maternal embryonic leucine zipper kinase (Melk). Transfection studies and site-directed mutagenesis confirmed Cnap1 and Melk to be bona fide E2F targets. Repression of Cnap1 and Melk by 1,25(OH)(2)D(3) was confirmed not only in MC3T3-E1 cells but also in several other bone-unrelated cell types. This down-regulation as well as the antiproliferative effect of 1,25(OH)(2)D(3) depended on the pocket proteins p107 and p130 because 1,25(OH)(2)D(3) failed to repress these E2F target genes and lost its antiproliferative action in p107(-/-);p130(-/-) cells but not in pRb(-/-) cells.

The active form of Vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], has potent antiproliferative actions on various normal and malignant cells. Calcemic effects, however, hamper therapeutic application of 1,25-(OH)(2)D(3) in hyperproliferative diseases. Two 14-epi-analogs of 1,25-(OH)(2)D(3) namely 19-nor-14-epi-23-yne-1,25-(OH)(2)D(3) (TX522) and 19-nor-14,20-bisepi-23-yne-1,25-(OH)(2)D(3) (TX527), display reduced calcemic effects coupled to an (at least 10-fold) increased antiproliferative potency when compared with 1,25-(OH)(2)D(3). Altered cofactor recruitment by the Vitamin D receptor (VDR) might underlie the superagonism of these 14-epi-analogs. Therefore, this study aims to evaluate their effects at the level of VDR-coactivator interactions. Mammalian two-hybrid assays with VDR and the coactivators TIF2 and DRIP205 showed the 14-epi-analogs to be more potent inducers of VDR-coactivator interactions than 1,25-(OH)(2)D(3). TX522 and TX527 require 30- and 40-fold lower doses to obtain the VDR-DRIP205 interaction induced by 1,25-(OH)(2)D(3) at 10(-8)M. Evaluation of additional 1,25-(OH)(2)D(3)-analogs and their impact on VDR-coactivator interactions revealed a strong correlation between the antiproliferative potency of an analog and its ability to induce VDR-coactivator interactions. In conclusion, these data show that altered coactivator binding by the VDR is one possible explanation for the superagonistic action of the two 14-epi-analogs TX522 and TX527.

Background: Despite a lower prevalence of osteoporosis in African-American women, they remain at risk and experience a greater mortality than white women after sustaining a hip fracture. Lack of recognition of risk factors may occur in African-American women, raising the possibility that disparities in screening practices may exist., Objective: To determine whether there is a difference in physician screening for osteoporosis in postmenopausal, at-risk African-American and white women., Methods: We conducted a retrospective chart review at an urban academic hospital and a suburban community hospital. Subjects included 205 African-American and white women, age > or = 65 years and weight < or = 127 pounds, who were seen in Internal Medicine clinics. The main outcome was dual-energy x-ray absorptiometry (DXA) scan referral. We investigated physician and patient factors associated with referral. Secondary outcomes included evidence of discussion of osteoporosis and prescription of medications to prevent osteoporosis., Results: Significantly fewer African-American than white women were referred for a DXA scan (OR 0.39%, 95% confidence interval (CI): 0.22 to 0.68). Physicians were also less likely to mention consideration of osteoporosis in medical records (0.27, 0.15 to 0.48) and to recommend calcium and vitamin D supplementation for this population (0.21, 0.11 to 0.37). If referred, African-American women had comparable DXA completion rates when compared with white women. No physician characteristics were significantly associated with DXA referral patterns., Conclusions: Our study found a significant disparity in the recommendation for osteoporosis screening for African-American versus white women of similar risk, as well as evidence of disparate osteoporosis prevention and treatment, confirming results of other studies. Future educational and research initiatives should target this inequality.

At periods greater than 1000 seconds, Earth's seismic free oscillations have anomalously large amplitude when referenced to the Harvard Centroid Moment Tensor fault mechanism, which is estimated from 300- to 500-second surface waves. By using more realistic rupture models on a steeper fault derived from seismic body and surface waves, we approximated free oscillation amplitudes with a seismic moment (6.5 x 10(22) Newton.meters) that corresponds to a moment magnitude of 9.15. With a rupture duration of 600 seconds, the fault-rupture models represent seismic observations adequately but underpredict geodetic displacements that argue for slow fault motion beneath the Nicobar and Andaman islands.

The active form of Vitamin D, 1alpha,25-dihydroxyvitamin D(3) [1,25-(OH)(2)D(3)], demonstrates potent antiproliferative actions on normal as well as on malignant cell types by blocking the transition from the G1- to the S-phase of the cell cycle. Key target genes for 1,25-(OH)(2)D(3) in this non-classic effect remain largely unknown. Therefore, this study aims to identify genes that, through changes in expression after 1,25-(OH)(2)D(3) treatment, contribute to the observed antiproliferative effect. cDNA microarrays containing 4600 genes were used to investigate changes in gene expression in MC3T3-E1 mouse osteoblasts at 6 and at 12h after treatment with 1,25-(OH)(2)D(3) (10(-8)M), preceding (6h) or coinciding with (12h) the G1/S block in these cells. Approximately one fifth of the genes that were significantly down-regulated after a 12h incubation period with 1,25-(OH)(2)D(3) were genes involved in the DNA replication process, a basic process for cell growth that starts at the end of G1-phase and continues in S-phase. Down-regulation of these genes by 1,25-(OH)(2)D(3) was confirmed by quantitative RT-PCR in MC3T3-E1. In conclusion, cDNA microarrays revealed that treatment of MC3T3-E1 cells with 1,25-(OH)(2)D(3) resulted in the down-regulation of DNA replication genes in parallel with the observed G1/S-arrest.

Unlabelled: To identify key genes in the antiproliferative action of 1,25(OH)2D3, MC3T3-E1 mouse osteoblasts were subjected to cDNA microarray analyses. Eleven E2F-driven DNA replication genes were downregulated by 1,25(OH)2D3. These results were confirmed by quantitative RT-PCR in different cell types, showing the general nature of this action of 1,25(OH)2D3., Introduction: 1Alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] has a potent antiproliferative action characterized by a blocked transition from the G1- to the S-phase of the cell cycle. This study aims to identify genes whose expression is markedly altered after 1,25(OH)2D3 treatment in parallel with or preceding the observed G1-arrest., Materials and Methods: The cDNA microarray technique was used, and the expression of approximately 4600 genes in MC3T3-E1 mouse osteoblasts was studied 6 and 12 h after treatment with 10(-8) M 1,25(OH)2D3. Quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analyses were performed on MC3T3-E1 cells and on wildtype and vitamin D receptor (VDR) knockout primary murine epidermal keratinocytes (VDRwt MEKs, VDR-/- MEKs) and murine mammary tumor cells (GR) to confirm the microarray data., Results and Conclusions: After 12 h of treatment, in parallel with the 1,25(OH)2D3-induced G1 arrest, a particular set of DNA replication genes including a cell division cycle 6 homolog, a DNA polymerase alpha subunit, proliferating cell nuclear antigen, two DNA polymerase delta subunits, and flap-structure specific endonuclease 1, was downregulated at least 2-fold. These genes are known targets of the E2F family of transcription factors, which are probably the central mediators of this action of 1,25(OH)2D3. Indeed, as shown by transfection assays with an E2F reporter construct, 12- and 24-h treatment of MC3T3-E1 cells with 1,25(OH)2D3 reduced E2F activity by 49% and 73%, respectively. Quantitative RT-PCR analyses confirmed the downregulation of these DNA replication genes by 1,25(OH)2D3 in MC3T3-E1, GR, and VDRwt MEKs cells, but not in VDR-/- MEKs cells, showing that this 1,25(OH)2D3-driven antiproliferative action is of a general nature and depends on a functional VDR.

Here, we report on the identification of nucleolar spindle-associated protein (NuSAP), a novel 55-kD vertebrate protein with selective expression in proliferating cells. Its mRNA and protein levels peak at the transition of G2 to mitosis and abruptly decline after cell division. Microscopic analysis of both fixed and live mammalian cells showed that NuSAP is primarily nucleolar in interphase, and localizes prominently to central spindle microtubules during mitosis. Direct interaction of NuSAP with microtubules was demonstrated in vitro. Overexpression of NuSAP caused profound bundling of cytoplasmic microtubules in interphase cells, and this relied on a COOH-terminal microtubule-binding domain. In contrast, depletion of NuSAP by RNA interference resulted in aberrant mitotic spindles, defective chromosome segregation, and cytokinesis. In addition, many NuSAP-depleted interphase cells had deformed nuclei. Both overexpression and knockdown of NuSAP impaired cell proliferation. These results suggest a crucial role for NuSAP in spindle microtubule organization.

We used a high-resolution mid-IR tunable-laser absorption spectroscopy (TLAS) system with a single IV-VI laser operating near 5.2 microm to measure the level of exhaled nitric oxide (eNO) in human breath. A method of internal calibration using simultaneous eNO and exhaled CO2 measurements eliminated the need for system calibration with gas standards. The results observed from internally calibrating the instrument for eNO measurements were compared with measurements of eNO calibrated to gas standards and were found to be similar. Various parameters of the TLAS system for eNO breath testing were examined and include gas cell pressure, exhalation time, and ambient NO concentrations. A reduction in eNO from elevated concentrations (approximately 44 parts in 10(9)) to near-normal levels (<20 parts in 10(9)) from an asthmatic patient was observed after the patient had received treatment with an inhaled glucocorticoid anti-inflammatory medication. Such measurements can help in evaluating airway inflammation and in monitoring the effectiveness of anti-inflammatory therapies.

Objective: The purpose of this study was to describe, qualitatively the use of service dogs by persons with physical disabilities and the meaning of this experience., Method: Five service dog owners were observed and interviewed on multiple occasions through an ethnographic approach., Results: Identified themes were increased community participation, "closer than family" increased social contact, personal skill development, having fun, responsibility, adjustment, challenges, independence, "someone to watch over me," and "feel like an able-bodied person.", Conclusion: Service dogs are used to enhance independence in occupational performance areas and contribute to improvements in psychosocial functioning. Given these benefits, service dogs could be viewed as a form of assistive technology that occupational therapists may want to consider as an alternative to traditional devices for some clients.

The preparation and distribution of fresh-cut produce is a rapidly developing industry that provides the consumer with convenient and nutritious food. However, fresh-cut fruits and vegetables may represent an increased food safety concern because of the absence or damage of peel and rind, which normally help reduce colonization of uncut produce with pathogenic bacteria. In this study, we found that Salmonella Enteritidis populations can (i) survive on fresh-cut melons and apples stored at 5 degrees C, (ii) increase up to 2 log units on fresh-cut fruits stored at 10 degrees C, and (iii) increase up to 5 log units at 20 degrees C during a storage period of 168 h. In addition, we examined the effect of lytic, Salmonella-specific phages on reducing Salmonella numbers in experimentally contaminated fresh-cut melons and apples stored at various temperatures. We found that the phage mixture reduced Salmonella populations by approximately 3.5 logs on honeydew melon slices stored at 5 and 10 degrees C and by approximately 2.5 logs on slices stored at 20 degrees C, which is greater than the maximal amount achieved using chemical sanitizers. However, the phages did not significantly reduce Salmonella populations on the apple slices at any of the three temperatures. The titer of the phage preparation remained relatively stable on melon slices, whereas on apple slices the titer decreased to nondetectable levels in 48 h at all temperatures tested. Inactivation of phages, possibly by the acidic pH of apple slices (pH 4.2 versus pH 5.8 for melon slices), may have contributed to their inability to reduce Salmonella contamination in the apple slices. Higher phage concentrations and/or the use of low-pH-tolerant phage mutants may be required to increase the efficacy of the phage treatment in reducing Salmonella contamination of fresh-cut produce with a low pH.

This study provides a detailed and exact evaluation of the interactions between vitamin D3 receptor (VDR), retinoid X receptor (RXR), and vitamin D3 responsive elements (VDREs) mediated by two novel 14-epianalogs of 1,25-dihydroxyvitamin D [1,25(OH)2D3], 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527). Both analogs were more potent (14- and 75-fold, respectively) than 1,25(OH)2D3 in inhibiting cell proliferation and inducing cell differentiation. However, DNA-independent experiments indicated that both analogs had a lower affinity to VDR and that the stability of the induced VDR conformation, as measured by limited protease digestion assays, was similar (TX 527) or even weaker (TX 522) than that induced by the parent compound. However, DNA-dependent assays such as gel shift experiments revealed that those analogs were slightly more potent (3-7 times) than 1,25(OH)2D3 in enhancing binding of VDR-RXR heterodimers to a direct repeat spaced by three nucleotides (DR3) type VDRE. The functional consequences of the ligand-VDR-RXR-VDRE interactions observed in vitro were subsequently evaluated in transfection experiments. Both 14-epianalogs enhanced transcription of VDRE containing reporter constructs more efficiently than 1,25(OH)2D3 in COS-1 and MCF-7 cells regardless of the presence of ketoconazole. Transactivation activity is suggested to be a cell-specific process because maximal transcriptional induction and the half-maximal transactivation concentration for each reporter construct were different in both cell lines. The superagonistic transactivation activity closely resembled the biological potency of these analogs on the inhibition of MCF-7 cell proliferation. These data clearly indicate that superagonistic activity starts beyond the binding of the ligand-heterodimer (VDR-RXR) complex to VDRE and thus probably involves coactivator/corepressor molecules.

The biological activity of two novel 14-epi-analogues of 1,25(OH)2D3, 19-nor-14-epi-23-yne-1,25(OH)2D3 (TX 522) and 19-nor-14,20-bisepi-23-yne-1,25(OH)2D3 (TX 527), is described. Both analogues were at least 10 times more potent than 1,25(OH)2D3 in inhibiting in vitro cell proliferation and had much lower in vivo calcemic effects than 1,25(OH)2D3. Treatment with 1,25(OH)2D3, TX 522, or TX 527 in vitro was accompanied by an accumulation of cells in the G1 phase of the cell cycle. Protein levels of cyclin C and cyclin D1 in in vitro cultures of MCF-7 cells were down-regulated to 50 and 30%, respectively, of control levels at 72 and 120 h after stimulation. Protein levels of p21 and p27 at 72 h were significantly enhanced by 1,25(OH)2D3 and TX 522 but surprisingly not by TX 527. The inability of TX 527 to up-regulate p21 seemed to be cell type specific because p21 was induced in other cell types. Diminished phosphorylation of the retinoblastoma protein after treatment with 1,25(OH)2D3, TX 522, or TX 527 may ultimately contribute to the growth inhibition caused by these compounds. According to the data presented, the induction of apoptosis seemed not to be a major mechanism responsible for the growth-inhibitory effect of 1,25(OH)2D3 and analogues. Both 14-epianalogues significantly retarded tumor progression (40% reduced compared with control mice) in an in vivo model of MCF-7 breast cancer cells established in nude mice. In conclusion, these novel analogues have the eligible profile to be tested as therapeutic agents for the treatment of hyperproliferative diseases such as breast cancer.

Capsular proteins from Helicoverpa armigera granulovirus (HaGV) have previously been shown to enhance H. armigera nucleopolyhedrovirus (HaSNPV) infection in H. armigera larvae. Yet, HaGV and HaS-NPV, as viable viruses, interfered with one another. In our study, we have examined the effects of co-infection of the slow-killing virus HaGV with the fast-killing virus Helicoverpa zea NPV (HzSNPV) on H. zea larvae. The mortality parameter measured was survival time. Virus stocks had 50% lethal concentrations of 3.2x10(-9) g HaGV-infected cadavers (GVC) (HaGV) and 32 occlusion bodies (HzSNPV) per cup. Average survival times were 16.8 and 5.5 days for larvae treated with HaGV and HzSNPV, respectively; death of HzSNPV-treated larvae was as early as 72 h posttreatment. In co-infection experiments in which larvae were treated concurrently with both viruses, the viruses competed in typical fashion for host resources. However, interference with disease progression in HzSNPV-fed larvae occurred even when HaGV was fed to larvae up to 36 h after the NPV, a time at which NPV infection should have been well established in host larvae. At death, co-infected larvae were observed microscopically to be filled with HaGV granules rather than HzSNPV polyhedra. The time study results imply that HaGV might be outcompeting HzSNPV by inhibiting its replication. We also observed that H. zea larvae treated with high dosages of HaGV (> or =3x10(-5) g GVC) were initially stunted but had survival times similar to those of larvae treated with lower dosages.

Background: To evaluate the effectiveness of sham radiation treatments in masking patients to their randomization group in the Radiation of Age-Related Macular Degeneration (ROARMD) Study., Methods: Patients with choroidal neovascularization complicating age-related macular degeneration were randomized to a treatment (RAD) group that received external beam irradiation (seven treatment sessions) or to a control (SHAM) group that received sham radiation (one sham treatment session). During a telephone survey, 62 of 73 randomized patients responded to the following questions: Do you think you received radiation? Why do you feel that way? Did the vision in your study eye worsen after enrollment?, Results: Eighty-one percent of the RAD group and 59% of the SHAM group thought that they had received radiation. In patients who thought that their vision had stabilized or improved, 82% thought that they had received radiation. In patients who thought that their vision was worse, only 39% thought that they had received radiation. In 54% of patients, subjective perception of vision influenced their guess as to whether they received radiation., Conclusions: Subjective patient perception of visual outcome was the most influential variable for masking. Variation between radiation treatment and sham session techniques, such as equipment used and duration of treatments, played a lesser role in the masking of patients. Seven treatment days correlated with a higher number of patients who thought that they had received radiation. Although our procedures do not strictly mask the two groups, one sham radiation session was effective in keeping patients guessing their randomization group.

This study evaluated the efficacy of low-dose dopamine for prevention of amphotericin B-induced nephrotoxicity in autologous bone marrow transplant and leukemia patients. Seventy-one patients undergoing cytoreductive therapy who required amphotericin B were randomly assigned in an unblinded fashion to a group receiving continuous-infusion low-dose dopamine (3 microgram/kg/min) or a group receiving no dopamine. Amphotericin B was dosed at 0.5 or 1.0 mg/kg/day based on computerized tomography scan results or presence of positive blood cultures. No patient received saline boluses. The rate of nephrotoxicity, severity as graded by Southwest Oncology Group toxicity criteria, and time to each grade of nephrotoxicity were compared between the two groups. Eighty percent of the no-dopamine group and 66.7% of the dopamine group developed nephrotoxicity, defined as a 1.5-fold or greater increase in baseline serum creatinine level (P = 0.20). No statistical difference was noted at any grade of nephrotoxicity between the two groups. Thirty-four percent of patients in the no-dopamine group versus 17.6% in the dopamine group had a 2.5-fold or greater increase in serum creatinine level, which was not statistically significant (P = 0.0888). Ten patients developed grade IV nephrotoxicity and were withdrawn from the study, 7 in the no-dopamine group and 3 in the dopamine group (P = 0.19). The time to each grade of nephrotoxicity was also not significantly different for the two groups. Eleven adverse drug reactions were reported in the dopamine group in comparison to one in the no-dopamine group. Thus, dopamine offers little in the way of prevention of nephrotoxicity associated with amphotericin B therapy. Although the significance of drug reactions in the dopamine group is not clearly established due to lack of cardiac monitoring in the no-dopamine group, dopamine therapy is not without complications.

Authors examine the experience of two nonelderly adult populations in Indiana and their difficulties in obtaining and retaining health insurance once diagnosed with a serious chronic or catastrophic disease.

It remains unclear whether preoperative mammograms are necessary in young patients having nononcologic breast surgery. Various authors have recommended mammography in all such cases, in conflict with guidelines from the American Cancer Society. We conducted a retrospective study to determine the utility of preoperative mammograms in young women. From 1989 through 1994, 208 patients under 35 years of age had elective breast surgery in our institution. Fifty-one (24.5%) had preoperative mammography. No malignancies were diagnosed. We believe mammograms are not routinely needed before elective breast surgery in patients under 35 years of age.

Aqueous chlorine, used to reduce surface bacteria populations on carcasses of slaughter animals after evisceration, during chilling, and after transport, dissipates in the presence of organic matter. This study characterized the amount of residual chlorine present when aqueous HOCI was exposed to bovine serum albumin, bovine lean muscle, porcine adipose tissue, or Trypticase soy agar (TSA) surfaces. Test chlorine solutions, made using Ca (OCl) 2 , contained 0, 50, 100, 200, 400, 800, 1,600, or 3,200 ppm chlorine, the latter two concentrations being used only in the case of albumin. Chlorine depletion by albumin was almost instantaneous, but was influenced by the amount of albumin present and the initial chlorine concentration. Chlorine exposed to organic surfaces was reduced most readily by lean muscle, then by TSA, and least by adipose tissue. Available chlorine was reduced by about 62% when the volume of aqueous chlorine was 22 ml/cm 2 of lean muscle and by about 89% when the volume of aqueous chlorine was 0.69 ml/cm 2 . With increasing exposure time, the exposure to lean and fat decreased available chlorine by an average of about 10% in 4 min, 27% in 32 min, and 45% in 96 min. Thirteen pure bacterial cultures and two mixed cultures associated with meat were exposed to aqueous chlorine to characterize the effectiveness of the chlorine. All cultures except Bacillus cereus and Enterococcus faecalis were destroyed within 15 s by 3 ppm chlorine. Based on the data, the authors conclude that (a) available chlorine reduction is dependent on exposure time, chlorine concentration, and amount/source of organic material and (b) bacterial inactivation by aqueous chlorine is species specific. These data are of value for estimating chlorine dose for carcass decontamination during washing/chilling and for confirming that bacterial resistance to HOCI is species specific.

Objective: To explore the feasibility of recruiting, training, and placing in the field volunteers to assist community practices in enhancing the provision of preventive care., Design: A case series design followed up a cohort of volunteers prospectively as they were recruited, trained, and assigned to practices., Setting: The New Hampshire Division of the American Cancer Society recruited and trained the volunteer facilitators., Intervention: Assistance from the volunteers in implementing a preventive services office system served as the intervention for practices. Volunteers were trained and supported by professional staff and an implementation manual., Main Outcome Measures: Recruitment, training, and volunteer experiences in working with practices, as well as the costs of supporting the program, were assessed., Results: Twenty-six volunteers were trained. Of the 15 assigned to practices, 11 had begun to assist their assigned practices to establish a preventive services office system. Extensive planning, patience, and support were required., Conclusion: Volunteers recruited and supported by an intermediary organization can provide assistance to practices in implementing a preventive services office system.

A new method was developed for determination of the doubling times of spiroplasmas. In this procedure, the time required for medium acidification of tubes in tenfold dilution series was recorded. Sixty-four spiroplasma strains, representing 24 groups and 11 subgroups, were studied. Eight strains representing putative new groups were also included in the study. Doubling times at 5, 10, 15, 20, 25, 30, 32, 37, 41, and 43&deg;C were determined. The range of temperatures for spiroplasma growth was 5&deg;-41&deg;C. Twenty-three spiroplasmas had optima of 30&deg;C, 29 had optima of 32&deg;C, and 13 had optima of 37&deg;C. The fastest growing spiroplasma was the MQ-4 strain (group XI), with a doubling time at optimal temperature of 0.6 h. The slowest was the Jamaican corn stunt strain B655 (subgroup I-3), with an optimal doubling time of 36.7 h. Spiroplasma strain B31 (group IV) had the widest range (5&deg;-41&deg;C), while the DW-1 strain and some subgroup I-3 strains had the narrowest, growing only at 25&deg; and 30&deg;C. Some spiroplasmas grew well at 41&deg;C, but none grew at 43&deg;C. The ability of spiroplasmas to withstand a wide range of temperatures may reflect the conditions to which they are exposed in nature, including the temperatures of the insect, tick, and/or plant hosts in which they are carried and the plant surfaces from which they may be acquired by arthropods.

The advancements in the treatment of ureterocele have prompted early diagnosis of this condition. We report on 45 cases of ureterocele (6 simple and 39 ectopic) that had been treated at our service from 1974 to 1992. The present series comprised 43 patients (32 females, 13 males), with ages ranging from 20 hours to 9 1/2 years; three cases had been diagnosed prenatally. All cases were evaluated by IVP and cystography. There were 16 cases of left ureteropelvic duplicity, 11 right and 10 bilateral. There was one case with right triplication and 6 cases with single system. Fourteen cases had reflux in the lower ipsilateral kidney, 5 in the contralateral kidney and 4 were bilateral. In some cases, patient evaluation included the use of isotopes, US, CT and cystography. Two cases required no surgical procedure; 2 required endoscopic incision; 6 resection and reimplantation; 1 heminephrectomy; 19 resection and heminephrectomy; 1 resection, reimplantation and ureteropyelostomy; 8 resection and nephrectomy; aspiration, nephrectomy and resection of the ureterocele was required in 1 case. Control evaluation at 6 and 18 months following treatment was satisfactory in 88.3%; of these, 41.8% had pyelonephritic scars, 16.2% had residual reflux and 4.6% urinary incontinence. There was only one death.

Reciprocal embryo transfers were made between scrapie-inoculated and scrapie-free sheep (Cheviot and Suffolk breeds) to measure scrapie transmission via the embryo (using offspring from embryos of scrapie-inoculated donors and scrapie-free recipients) and via the uterus (using offspring from embryos of scrapie-free donors and scrapie-inoculated recipients taken by cesarean section). Two control groups of offspring, 1 from scrapie-free parents (negative) and 1 from scrapie-inoculated parents (positive), also were included. All sheep were observed for clinical signs of scrapie until death or for a minimum of 60 months. Final diagnosis was made on the basis of histopathologic findings or results of mouse inoculation and/or proteinase-K-resistant protein analysis. Thirty to 61% of the scrapie-inoculated donor/recipient sheep within groups developed scrapie within 8 to 44 months after inoculation. None of the scrapie-free donor/recipients, including those gestating embryos from scrapie-inoculated donors, developed scrapie. Also, none of the offspring observed to > or = 24 months of age from reciprocal cross, via embryo (0/67), or via the uterus (0/25), or from the negative-control group (0/33) developed scrapie. Fifty-six of the offspring via embryo, 19 of these via the uterus, and 31 negative controls survived to > or = 60 months of age. Of the 21 sheep in the positive-control group, 2 (9.5%) developed scrapie, 1 at 31 months of age and 1 at 42 months of age. In the Cheviot offspring, the percentage of sheep carrying the short incubation allele ranged from 24 to 44% and the percentage in the Suffolk offspring ranged from 61 to 83%.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To report a case of cephalexin-induced Stevens-Johnson syndrome (SJS), a devastating adverse drug reaction that involves the entire skin surface and mucosal areas of the body., Data Sources: MEDLINE search (key terms cephalosporins, Stevens-Johnson syndrome, erythema multiforme, and systemic lupus erythematosus) and references identified from bibliographies of pertinent articles., Data Synthesis: Clinical presentation and manifestations of SJS include the skin, eyes, gastrointestinal tract, and pulmonary system. Infectious complications are the leading cause of mortality. Early intervention is important to prevent progression of SJS. The case described is consistent with the features of this syndrome. The patient presented with fever, arthralgias, and malaise. Skin lesions included a diffuse violet macular rash with erythema and multiple bullous lesions on her neck and abdomen. The skin biopsy was consistent with SJS. Multiple mucocutaneous ulcers were found in her mouth, but no evidence of lower gastrointestinal tract involvement was documented. She remained relatively free of pulmonary complaints except for the presenting bronchitis., Conclusions: Cephalexin should be added to the list of agents to consider as iatrogenic causes of SJS.

The decade of the 80's has seen the implementation of the problem-based curriculum (PC) (also called "parallel" or "student-centred" curriculum) in several medical schools in the United States. This new educational technique emphasizes active student participation and a hands-on learning process supplemented by judicious intervention by the faculty teachers. The students (often volunteers) are usually selected for their motivation rather than for highest intelligence or class ranking. For a period of two years, they meet twice or thrice-weekly in group sessions to explore problem cases developed by faculty for that special purpose. We describe the parallel curriculum here in some detail and suggest that medical educators in India give serious consideration to implementation of such a curriculum or its modification in their institutions. Medical graduates will benefit from the hands-on emphasis of this curriculum as well as the development of a disciplined approach in the handling of clinical problems. PC diminishes the stress levels associated with the traditional curriculum and lets the students play an active role in their education. PC will make them better prepared to face challenges during their clinical years and subsequent careers and should offset some of the weaknesses in the current educational system.

Twenty multiparous, crossbred, black-faced ewes and their newborn twin lambs were assigned to one of four dietary treatments in a 2 x 2 factorial experiment to examine the effects of increased supply of CP or a mixture of encapsulated methionine and lysine or both on the performance of ewes and their nursing twin lambs. Ewes were fed ad libitum amounts of either a 10.2% low CP diet or a 16.2% moderate CP diet with or without additional encapsulated amino acids. Nitrogen metabolism trials were conducted simultaneously on both ewes and lambs at wk 2, 4, and 8 of lactation. Analyses were conducted for blood urea N, plasma 3-hydroxybutyrate, lactate, NEFA, insulin, and amino acids (plasma, feed, and milk). Ewe DMI, BW, BW gain, and milk yield were not changed by dietary treatments. Balance of N and N digested were increased by moderate CP treatment. The portion of retained N used for milk synthesis was increased by low CP treatment. Methionine and total branched-chain amino acids were increased by encapsulated amino acids and by protein treatment. Gains in BW and N balance were increased in lambs nursing ewes fed protected amino acids. Increased growth of nursing lambs would be an important beneficial effect of supplementing diets of ewes with encapsulated methionine and lysine.

Crosses made between tetraploid and diploid, 2n pollen-producing species directly transfer from one-half to the entire diploid genome from the diploid to the tetraploid level, depending on the mechanism of 2n pollen formation and the amount of crossing-over that occurs. Tetraploid plants that result from tetraploid x diploid hybridizations can be further utilized in a breeding program. It is postulated that preferential pairing between homologous chromosomes derived from the original tetraploid or diploid parent occurs in the tetraploid x diploid hybrid. Depending on the genetic divergence of the species involved, preferential pairing of homologous chromosomes may range from zero to one. Theoretical estimates of the amount of preferential pairing and the standard errors of these estimates are derived for cases where the diploid parent produces 2n gametes by either a first division or a second division restitution mechanism.

Although severe hypophosphatemia has been associated with significant morbidity, little quantitative information is available on the magnitude of the risk. The objective of this study was to determine the frequency and timing of severe hypophosphatemia, the relative risk associated with various medical diagnoses, and the choice of therapy. Among 10,197 patients hospitalized over a 1-year period, the incidence of severe hypophosphatemia (serum phosphate less than or equal to 0.33 mmol/l) was 0.43%. The incidence was 0.91% in alcoholics, 2.42% in septic patients, 10.4% in patients with malnutrition, and 14.6% in patients with diabetic ketoacidosis. The odds ratio for developing the metabolic abnormality was 4.2 (95% confidence interval 2.2-8.1) in alcoholics, 6.4 (1.9-18.9) in septic patients, 46.9 (16.6-125.6) in patients with diabetic ketoacidosis, and 60.7 (31.4-117.5) in malnourished patients. There was a 4-fold increase in mortality in patients with severe hypophosphatemia (18.2 vs. 4.6%; p less than 0.001). The metabolic abnormality was not recognized or was inappropriately treated in 42% of patients. Severe hypophosphatemia is a relatively common finding in hospitalized patients, especially in those with certain well-defined medical conditions. It is associated with significant excess mortality. Its recognition and treatment remain suboptimal.

In a more years-lasting field trial the influence of a second crop cultivation of rye and rape in winter time on the incidence of Rhizoctonia solani Kühn on potato or mustard as indicator plants was studied. The second crops were ploughed in during spring time. On part of the trial was artificially infested by this causal agent. Three crop rotations with different proportions of host plants (potato) were compared. The results obtained demonstrate the following: 1. On the part of experimental area arficially infested the incidence rate was higher for 3 till 4 years than on the control plots, but later it became equally to the control one, which also was very high (approximately 50). 2. In the last very dry year (1969) the disease developed only a little. 3. The second crop cultivation decreased the incidence of R. solani in 7 (rye) or 8 (rape) of 10 cases, but mostly the rate of decreasing was low. 4. A high weed density induced by a diminished mechanical cultivation increased the incidence of R. solani at the end of the experiment (1969), specially in the rotation with 80% host plants. 5. The number of soil bacteria, the respiration rate, and partly also the activity of dehydrogenase and the soil acidity were increased by green manuring of the second crop, however, the number of the actinomycetes, and the cellulolytic activity didn't be influenced remarkably. 6. The second crop cultivation ist nounced as a measure stimulating the soil fertiligy and discussed in connection with the microbial processes taking place in soil.

1. In glass-house trials the influence of residues of clover, grass, and mixtures (1:1) of them added to natural and partially sterilized loam soil upon the parasitic activity of Rhizoctonia solani and the soil micro-organisms and their activity was analyzed. 2. Burying of plant residues (1%) increased the content of organic substance in soil for 8 weeks and longer. 3. The soil reaction (pH) was not noteworthy affected by application of clover or grass residues. 4. However, the populations of bacteria and actinomycetes were increased, especially by adding clover dried. In natural soil, the maximum of stimulation was reached later than in soil sterilized. Adding of grass and roots of grass enlarged the spectrum of fungi observed in the soil amended. Roots of grass stimulated the cellulose-decomposing organisms remarkably. 5. The activity of dehydrogenase (AD) was influenced in different manner: in natural soil fresh clover, grass, mixtures of them, and clover dried increased, and fresh roots of clover, grass, and mixtures of them diminished AD; in soil sterilized the most variants stimulated this activity. 6. All plants residues increased the cellulolytic activity of soil for a long time, but in sterilized soil this effect reached its maximum earlier than in natural soil amended and did not last so long, too. 7. The possible explanations for the inhibition of parasitic activity of Rhizoctonia solani caused by burying plant residues are discussed.

In a five-years field trial, the influence of two winter catchcrops, rye and rape, upon the incidence of Cercosporella herpotrichoides has been studied. The winter catch-crops had been repeated three times, followed either by stubble-crop or without in fall of the fourth year. The variants (blocks) had been completed by two variants without catch-crop, either carefully cultivated or overgrown with weeds. Each of the four blocks had been divided three times to be grown with three different crop sequences containing 80%, 60% (with the insusceptible corn), or 40% haulm fruit, respectively. Each of the 12 variants had been divided into two parts by continuous fallow stripe, one part being artificially infested with the pathogen in the beginning (1st winter wheat). In the 2nd, 3rd, and 4th year, only spring crops were grown, followed by winter wheat in the 5th year. The final exploration resulted in a medium to heavy degree of infection, being significantly higher in the 80% cereal crop sequence than in the 60% and 40% sequences. Concerning the catch-crops, infection in the rye variants was equal or significantly lower than in the carefully cultivated variants without catch-crop. On the other hand, infection of the rape variants had become significantly higher than that of the catch-crop-free ones, about as heavily as in the weed-infested variants. From fall 1966 to summer 1969, the development of the saprophytic soil microflora and several other edaphic parameters had been investigated. Remarkable differences in intensity of disintegration have been observed under the influence of the main crops, cereals or potatoes, respectively, but no differences could be stated resulting from the matter of disintegration--residues of rye or rape--, which might interpret the contrasting effects on the pathogen. Too, no indication for antagonistic activity of bacteria or actinomycetes has been noted. The results are compared with known facts of Cercosporella and of other soil borne pathogens. The difference in biology of Cercosporella on the one hand, and of root infecting fungi on the other hand seems to be most important to explain the results obtained.

Tyramine induces coma in phenelzine-treated dogs. Development of coma in these animals is associated with brain edema, abnormal brain scans of Tc-99m-diethylene-triamine-penta-acetic acid (Tc-99m-DTPA), and elevated levels of CSF catecholamines. We found that the intravenous administration of 6-7 mg/kg of a single dose of L-644,711 given fifteen minutes after the oral administration of tyramine to phenelzine-pretreated animals followed by an infusion of normal saline containing 6-7 mg/kg of the drug given over a period of 2 hr caused reversal of brain injury. This was accompanied by full recovery within a period of 24 hr of all the animals tested. A follow-up study revealed that 24 hr after treatment with L-644,711 CSF levels of catecholamines and brain images of Tc-99m-DTPA were indistinguishable from normal controls. Animals that received no drug died from unresolved coma within 4 to 24 hr. Animals that had recovered due to therapy with L-644,711 were given 10-14 days rest followed by a repetition of the phenelzine and tyramine treatment but denied L-644,711 therapy. These animals also died of unresolved coma within 24 hr. This preliminary study suggest that the use of L-644,711 may constitute an important advance in treatment of brain edema of a wide range of neurological disorders.

This report describes a patient with right lower lung (RLL) pneumonia of a subacute nature. Sputum and bronchial washings both grew N asteroides. Open lung biopsy showed bronchiolitis obliterans. Both the clinical and radiologic picture dramatically improved during three weeks of treatment with trimethoprim and sulfamethoxazole (TMP - SMX), indicating the possibility that N asteroides infection contributed to bronchiolitis obliterans pneumonia in this patient.

The majority of women physicians will have children, and they will also shoulder the major responsibility for child care arrangements, in spite of immense professional responsibilities. To date, little information has been made available regarding the child care choices of women physicians. This article summarizes the results of a national survey of women physicians' child care choices.