The Hospital at Home program: no place like home.

BACKGROUND: The treatment of children with cancer is associated with significant burden for the entire family. Frequent clinic visits and extended hospital stays can negatively affect quality of life for children and their families. METHODS: Here, we describe the development of a Hospital at Home program (H@H) that delivers therapy to pediatric hematology, oncology, and blood and marrow transplant (bmt) patients in their homes. The services provided include short infusions of chemotherapy, supportive-care interventions, antibiotics, post-chemotherapy hydration, and teaching. RESULTS: From 2013 to 2015, the H@H program served 136 patients, making 1701 home visits, for patients mainly between the ages of 1 and 4 years. Referrals came from oncology in 82% of cases, from hematology in 11%, and from bmt in 7%. Since inception of the program, no adverse events have been reported. Family surveys suggested less disruption in daily routines and appreciation of specialized care by hematology and oncology nurses. Staff surveys highlighted a perceived benefit of H@H in contributing to early discharge of patients by supporting out-of-hospital monitoring and teaching. CONCLUSIONS: The development of a H@H program dedicated to the pediatric hematology, oncology, or bmt patient appears feasible. Our pilot program offers a potential contribution to improvement in patient quality of life and in cost-benefit for parents and the health care system.

Screening of subfertile men for testicular carcinoma in situ by an automated image analysis-based cytological test of the ejaculate.

Testicular cancer (TC) is usually diagnosed after manifestation of an overt tumour. Tumour formation is preceded by a pre-invasive and asymptomatic stage, carcinoma in situ (CIS) testis, except for very rare subtypes. The CIS cells are located within seminiferous tubules but can be exfoliated and detected in ejaculates with specific CIS markers. We have built a high throughput framework involving automated immunocytochemical staining, scanning microscopy and in silico image analysis allowing automated detection and grading of CIS-like stained objects in semen samples. In this study, 1175 ejaculates from 765 subfertile men were tested using this framework. In 5/765 (0.65%) cases, CIS-like cells were identified in the ejaculate. Three of these had bilateral testicular biopsies performed and CIS was histologically confirmed in two. In total, 63 bilateral testicular biopsy were performed in conjunction with analysis of the ejaculates because of infertility work-up. Histological analysis of the biopsies for the presence of CIS yielded a test sensitivity of 0.67 and a specificity of 0.98. In addition, ejaculates from 45 patients with clinical signs of an overt TC were investigated and yielded a slightly lower sensitivity (0.51), possibly because of obstruction. We conclude that this novel non-invasive test combining automated immunocytochemistry and advanced image analysis allows identification of TC at the CIS stage with a high specificity, but a negative test does not completely exclude CIS. On the basis of the results, we propose that the assay could be offered to subfertile men and other patients who are at increased risk of TC.

Structure and dynamics of the protoplankton community in an environmentally protected urban stream.

We aimed to investigate spatial and temporal scales, abundance, and factors that structure the communities of protozoans in a tropical urban stream. METHODS: Samples of water for analysis of biological communities (testate amoebae, ciliates and bacteria) and limnological variables were taken in the Mandacaru stream located in the Conservation Unit of Parque do Cinquentenário, in the city of Maringá, Paraná State, Brazil, in two hydrological periods (dry and rainy). We calculated the Water Quality Index (WQI) composed by nine parameters of water quality (dissolved oxygen, thermotolerant coliforms, pH, BOD, water temperature, total nitrogen, total phosphorous, turbidity, and total solids), Trophic State Index (TSI) for phosphorous and we used a Redundancy Analysis (RDA) to verify the influence of environmental variables in the protozoan community. RESULTS: The WQI showed that water quality was considered good in some points and considered bad in other points. The TSI for phosphorus classified the stream as mesotrophic in the majority of sampled sites points (mean between 53.09 and 58.35). We identified 19 taxa of testate amoebae, belonging to six families, being Difflugiidae, Centropyxidae, and Arcellidae those with more species and 71 infrageneric taxa of ciliates, distributed in 12 orders being Peniculida the most representative order, followed by Euplotida. According to RDA analysis, samples of the dry period were characterized by higher values of bacteria density and concentrations of chlorophyll-a, total phosphorous, and total nitrogen. Ciliates and testate amoebae presented higher abundance values in some of the months characterized by higher precipitation and in conditions of higher system productivity. CONCLUSION: we may conclude that the Mandacaru stream, although strongly influenced by anthropic action, still presents an acceptable water quality. Lastly, we emphasize that protists abundance was strongly influenced by system productivity. This was evidenced by elevated protozoan densities where there was higher primary and bacterial productivity. Thus, these organisms must be considered in studies that aim at the identification of organisms that may indicate anthropic impacts and environmental quality.

V(D)J recombinase-like activity mediates hprt gene deletion in human fetal T-lymphocytes.

Studies from several laboratories worldwide have developed a large database for in vivo hypoxanthine-guanine phosphoribosyltransferase gene mutations in human T-lymphocytes. Sufficient differences have been found thus far between the spectrum for spontaneous mutations in adults and that observed in the fetus to suggest fundamental differences in in vivo mutagenic mechanisms at these two life stages. In adults, only approximately 15% of hypoxanthine-guanine phosphoribosyltransferase mutations have structural alterations on Southern blots, while in the fetus 75% of mutations show alterations of which one-half are deletions of exons 2 and 3. We have now sequenced the breakpoint sites for these specific deletions in 18 mutant lymphocyte clones isolated from 13 normal newborns. Three classes of deletions were found. Each class had the same intron 1 breakpoint but a different intron 3 breakpoint. These mutations have all the signatures of a V(D)J recombinase-mediated event (a 5' consensus heptamer, 3' consensus heptamer and nonamer, nibbling, non-germline-encoded nucleotides, P-nucleotides). At the 3' breakpoint of the most common class (comprising 83% of the mutants) a perfect heptamer can be created by postulating a hairpin loop which could attain a Z-DNA configuration. This feature may indicate recombinase preference for certain DNA structures. These results implicate the V(D)J recombinase in illegitimate events causing mutation in this housekeeping gene during T-cell development. Inactivation of genes involved in the control of growth and differentiation (e.g., tumor suppressor genes) by this mechanism may have important implications for cancer development.

The glycosphingolipids of human prostate tissue.

Neutral glycolipids and gangliosides from surgical samples of benign human prostate tissue were analyzed by chemical, enzymatic and immunostaining procedures. The neutral glycolipids consisted of ceramide mono-, di-, tri- and tetrahexosides of the globo series plus paragloboside. The monosialoganglioside fraction contained GM3 and GM1 plus multiple species of monosialylated lactosamine-containing structures, including sialyl-alpha-2----3paragloboside plus at least two compounds having a non-reducing terminal sialyl alpha 2----6Gal linkage. The disialoganglioside fraction contained GD3 as the major component plus GD1a, GD2 and GD1b. GT1b was the major trisialoganglioside.

Structure and dynamics of the protoplankton community in an environmentally protected urban stream / Estrutura e dinâmica da comunidade de protoplâncton em um córrego urbano ambientalmente protegido

Abstract We aimed to investigate spatial and temporal scales, abundance, and factors that structure the communities of protozoans in a tropical urban stream. Methods: Samples of water for analysis of biological communities (testate amoebae, ciliates and bacteria) and limnological variables were taken in the Mandacaru stream located in the Conservation Unit of Parque do Cinquentenário, in the city of Maringá, Paraná State, Brazil, in two hydrological periods (dry and rainy). We calculated the Water Quality Index (WQI) composed by nine parameters of water quality (dissolved oxygen, thermotolerant coliforms, pH, BOD, water temperature, total nitrogen, total phosphorous, turbidity, and total solids), Trophic State Index (TSI) for phosphorous and we used a Redundancy Analysis (RDA) to verify the influence of environmental variables in the protozoan community. Results: The WQI showed that water quality was considered good in some points and considered bad in other points. The TSI for phosphorus classified the stream as mesotrophic in the majority of sampled sites points (mean between 53.09 and 58.35). We identified 19 taxa of testate amoebae, belonging to six families, being Difflugiidae, Centropyxidae, and Arcellidae those with more species and 71 infrageneric taxa of ciliates, distributed in 12 orders being Peniculida the most representative order, followed by Euplotida. According to RDA analysis, samples of the dry period were characterized by higher values of bacteria density and concentrations of chlorophyll-a, total phosphorous, and total nitrogen. Ciliates and testate amoebae presented higher abundance values in some of the months characterized by higher precipitation and in conditions of higher system productivity. Conclusion: we may conclude that the Mandacaru stream, although strongly influenced by anthropic action, still presents an acceptable water quality. Lastly, we emphasize that protists abundance was strongly influenced by system productivity. This was evidenced by elevated protozoan densities where there was higher primary and bacterial productivity. Thus, these organisms must be considered in studies that aim at the identification of organisms that may indicate anthropic impacts and environmental quality.

Resumo O objetivo foi investigar, em escalas espacial e temporal, a abundância das comunidades de protozoários bem como os fatores intervenientes na estruturação das mesmas em um córrego urbano. Métodos: Amostras de água para análise de comunidades biológicas (amebas testáceas, ciliados e bactérias) e para análise de variáveis limnológicas foram tomadas no córrego Mandacaru localizado na Unidade de Conservação do Parque do Cinquentenário, na cidade de Maringá, Paraná State, Brasil, em dois períodos hidrológicos (seco e chuvoso). Calculamos o Índice de Qualidade de Água (IQA), o Índice de Estado Trófico (ETI) para fósforo e utilizamos uma Análise de Redundância (RDA) para verificar a influência de variáveis ambientais na comunidade de protozoários. Resultados: O IQA mostrou que a qualidade da água foi considerada boa em alguns pontos e considerada ruim em outros pontos, e o ETI para o fósforo classificou o córrego como mesotrófico na maioria dos locais amostrados (média entre 53,09 e 58,35). Foram identificados 19 táxons de amebas testáceas, pertencentes a seis famílias, sendo Difflugiidae, Centropyxidae e Arcellidae as mais especiosas, e 71 táxons de ciliados, distribuídos em 12 ordens, sendo Peniculida a ordem mais representativa, seguida por Euplotida. De acordo com a análise RDA, amostras do período seco foram caracterizadas por maiores valores de densidade bacteriana e concentrações de clorofila-a, fósforo total e nitrogênio total. As amebas testáceas e os ciliados apresentaram valores de abundância maiores em alguns dos meses caracterizados por maior precipitação e em condições de maior produtividade do sistema. Podemos concluir que o córrego Mandacaru, embora fortemente influenciado pela ação antrópica, ainda apresenta uma qualidade de água aceitável. Por fim, enfatizamos que a abundância de protistas foi fortemente influenciada pela produtividade do sistema. Isto foi evidenciado pelas elevadas densidades de protozoários onde houve maior produtividade primária e bacteriana. Assim, esses protistas devem ser considerados em estudos que visem à identificação de organismos que possam indicar impactos antrópicos e qualidade ambiental.

Additional clinical and cytogenetic findings associated with Rett syndrome.

An analysis of all aphidicolin-inducible breakpoints has been carried out in PHA stimulated T-lymphocytes of five patients with classical Rett syndrome, their mothers and a group of age matched controls. Observed breakpoints were divided into two groups: common, rare, and those recorded by others but not assigned as fragile sites by CCM92 and a group of non-specified breakpoints recurrently found in our ongoing study of fragile sites. In addition cooccurrence of trisomy X in one patient and de novo pericentromeric inversion on chromosome 2 in another Rett syndrome patient are reported. The co-occurrence with the Tourette syndrome in two of our families, and the fact that both Rett and Tourette syndrome are associated with movement disorders, possible dopaminergic hypersensitivity and increased chromosomal fragility in subsets of fragile sites, may suggest a possible avenue for further research. The cytogenetic findings indicate that both X-linked and autosomal regulatory region(s) may be part of a complex genetic alteration in association with Rett syndrome.

Benign prostatic hyperplasia: appearance on magnetic resonance imaging.

Benign prostatic hyperplasia (BPH) has a variable appearance on magnetic resonance imaging (MRI). This study reviews and categorizes the MRI findings of this entity in a sample of 26 men. Cases where atypical or suspicious changes are incidental findings should be reported to the urologist for further investigation. In addition, familiarity with both the appearance of the normal prostate and the changes caused by BPH is necessary when staging patients with known prostate cancer.

Treatment of painful prostatic bone metastases with oral etidronate disodium.

A class of drugs called diphosphonates have been used for several years in benign disorders of ossification such as Paget disease. Recently, these compounds have been applied to treating hypercalcemia of malignancy and painful bone metastases. We have used one of the oral diphosphonates, etidronate disodium, to palliate pain in 12 patients suffering from multiple bone metastases from prostate cancer. All of the patients had progressive metastatic disease following earlier endocrine therapy. Ten of 12 (83%) patients had a positive subjective and clinical response to treatment with oral etidronate disodium. Daily narcotic usage and pain intensity (measured by a zero to 10 pain scale) both decreased significantly on the etidronate protocol. There were no side effects associated with the drug in our patients.

Role of lactate dehydrogenase isoenzymes in testicular cancer.

Changes in the serum levels of lactate dehydrogenase have been noted to reflect growth and/or regression in many patients with testicular tumors, but they were nonspecific. However, elevation of the first of the LDH isoenzymes (LD-1) has been found specific to testicular cancer among all neoplasms. In this prospective preliminary report of 19 testicular cancer patients serum LD-1 was found to be normal in 4 patients with no tumor present. Therefore, there were no false positive findings. Of 6 patients with microscopic disease, LD-1 level was normal. Of 9 patients with gross disease, 5 had elevated serum LD-1 and 4 had normal LD-1. Of 4 patients with seminoma, 3 had elevated LD-1 while all 4 patients had no other elevated markers. It appears that elevation of serum LD-1 provides a marker for seminoma and a marker with some specificity for testicular cancer.

Detection of cell surface antigen in cancer of renal pelvis and ureter.

Thirty-five patients with transitional cell carcinoma of the renal pelvis or ureter of all stages and grades were studied for presence or absence of ABO(H) antigens utilizing an improved technique for staining and preserving the slides. Seventy per cent of the grade I tumors retained their antigens. Patients with antigen present had a longer duration of disease-free interval. Specific red cell adherence (SRCA) may predict the clinical course of patients with low-stage, low-grade transitional cell carcinomas and may be helpful in selecting patients for optimal therapy.

Early prostate-specific antigen failure following radical perineal versus retropubic prostatectomy: the importance of seminal vesicle excision.

OBJECTIVES: Because of renewed interest in the radical perineal prostatectomy, we chose to evaluate factors influencing differences in biochemical failure as measured by prostate-specific antigen (PSA) between radical perineal and the radical retropubic prostatectomies. METHODS: We undertook a retrospective review of 87 men with clinically localized prostate cancer who underwent radical retropubic (64%) or radical perineal (36%) prostatectomy, noting age, race, preoperative PSA, Gleason score, clinical stage, capsular penetration, surgical approach, and completeness of seminal vesicle (SV) excision. The two groups were comparable with respect to tumor factors such as preoperative PSA, Gleason score, clinical stage, and capsular penetration. Time to postoperative PSA failure (0.2 ng/mL or greater) was evaluated with univariate and multivariate analysis of multiple contributing factors. RESULTS: Twenty-eight percent of patients had a PSA level rising to 0.2 ng/mL or greater in the follow-up period. Patients who underwent perineal prostatectomy had a higher PSA failure rate (45%) than those treated by the retropubic approach (18%) and patients with incomplete SV excision had a higher failure rate (69%) than patients with bilateral SV excision (20%). When time to PSA failure was examined by multivariate analysis, completeness of SV excision, clinical stage, and Gleason score had a statistically significant impact on this outcome. In perineal prostatectomy patients, bilateral SV excision had a significantly longer time to PSA failure than in patients with incomplete excision. There was no significant difference in time to PSA failure between patients who underwent radical retropubic prostatectomy and the patients who underwent perineal prostatectomy with bilateral SV excision. CONCLUSIONS: Incomplete excision of SVs during a radical perineal prostatectomy contributes to an earlier postoperative biochemical recurrence as measured by a rising PSA, and may explain the higher disease recurrence rate for radical perineal prostatectomies as opposed to radical retropubic prostatectomies in this study.

Efficacy, tolerability, and effect on health-related quality of life of finasteride versus placebo in men with symptomatic benign prostatic hyperplasia: a community based study. CUSP Investigators. Community based study of Proscar.

This study sought to assess the efficacy, tolerability, and effect of finasteride on health-related quality of life (HRQL) in a diverse population of men with moderate-to-severe symptomatic benign prostatic hyperplasia (BPH). This double-blind study evaluated finasteride and placebo for 12 months in 2342 men with BPH (16.2% black, 14.5% Hispanic, 69.3% Caucasian/other) in a community-based setting. At 3-month intervals, urinary symptoms were measured by use of the American Urologic Association symptom index. HRQL was assessed by use of the BPH impact index (BII), which evaluated degree of bother, worry, physical discomfort, and restriction in activities as a result of urinary symptoms. Additional questions regarding activities of living were administered, and global assessments of change in urologic status were performed by both patients and investigators. Compared with placebo, patients treated with finasteride had a statistically significant decrease in symptom scores when first measured at month 3. Symptom scores continued to improve in finasteride-treated patients throughout the study; at month 12, the mean decrease in symptom scores in the finasteride-treated patients was -4.8 compared with -3.4 for placebo patients ( P = 0.0001). Statistically significant differences in favor of finasteride also were noted at month 12 on the BII (P = 0.0465), and finasteride-treated patients experienced less interference with activities of living (P = 0.0518). Patient and investigator global assessments of urologic status showed that significantly more patients in the finasteride group considered themselves improved and were considered improved by investigators at month 12 (P = 0.000). Finasteride was generally well tolerated. The incidence of drug-related sexual adverse experiences was significantly higher in the finasteride group (P = 0.000), but led to withdrawal in only 1.5% of patients. The demonstrated efficacy and tolerability of finasteride in reducing symptoms and improving quality of life confirm observations of previous trials and make finasteride a highly desirable treatment option for many men with symptomatic BPH.

Analysis of human HPRT deletion mutations with X-linked probes and pulsed field gel electrophoresis.

Because the human hprt gene is used in numerous mutation studies, it is important to fully characterize this gene. Therefore, our laboratory has undertaken to map the region around the hprt gene at band q26 of the human X chromosome. Utilizing hprt mutant T-cell clones isolated using the hprt clonal assay, which have deletions of all or part of the hprt gene, we have ordered 5 anonymous probes previously known to map in Xq26. Results suggest that this region includes between 460 kb and 18 Mb of DNA, which is at least 10 times the size of the hprt gene itself (43 kb). Pulsed field gel analysis of the region is underway to determine the exact distances between each of the anonymous probes and hprt and to determine deletion sizes in the mutant T-cell clones.

Sensitivity of somatic mutations in human umbilical cord blood to maternal environments.

To assess the potential effect of maternal environments on human embryonic/fetal somatic mutation, we measured the frequencies of hypoxanthine-guanine phosphoribosyltransferase (HPRT, hprt gene), mutant T lymphocytes (Mf), and glycophorin A (GPA) variant erythrocytes (Vf) of both allele-loss (phi/N) and allele-loss-and-duplication (N/N) phenotypes in umbilical cord blood. The mean hprt Mf (1.40 +/- 1.11 x 10(-6), N = 66) and GPA Vf (phi/N 4.0 +/- 2.2 x 10(-6), N = 114; N/N 2.7 +/- 2.0 x 10(-6), N = 91) were significantly lower than those previously reported for adult populations. In addition, the hprt Mf was significantly higher than that of a published study of newborn cord blood samples from a geographically distant population (0.64 +/- 0.41 x 10(-6), N = 45, P < 0.01; t test, P < 0.01, Mann-Whitney U test). An examination of the demographic data from these two populations led to the sampling of 10 additional newborns specifically matched to the published study for maternal socioeconomic status. The hprt Mf (0.70 +/- 0.49 x 10(-6)) of this selected population was consistent with the published report and significantly lower than that of our initial population (P < 0.03, t test; P < 0.01, Mann-Whitney U test). These results indicate that there is an environmental effect related to maternal socioeconomic status on the frequency of embryonic/fetal somatic mutations. Molecular analyses of hprt mutants from this cohort with elevated Mf revealed a significant decrease in the relative contribution of gross structural mutations to the overall Mf (25 of 38, 66% vs. 34 of 41, 83%, P = 0.024, chi 2 test), suggesting that the higher Mf resulted from an elevated level of "point" mutations. No individual maternal demographic or environmental factor was identified as contributing more significantly than other any factor to the observed variability in hprt Mf or GPA Vf.

Modulation of immunoradiometric and bioactive follicle stimulating hormone secretion and clearance in young and elderly men during treatment with tamoxifen or flutamide.

The secretion and clearance of immunoactive and bioactive follicle-stimulating hormone (FSH) in healthy young men (N = 10) and elderly men (N = 7) during blockade of endogenous sex steroid hormones with tamoxifen, an antiestrogen, and flutamide, an antiandrogen, was investigated. To this end, subjects underwent blood sampling basally every 10 minutes for 24 hours, and then received 2 consecutive intravenous pulses of synthetic gonadotropin releasing hormone (GnRH; 10 micrograms and 100 micrograms) every 2 hours. This paradigm was repeated on two subsequent visits, in which subjects received either flutamide HCl, a specific nonsteroidal competitive antagonist of the androgen receptor (750 mg daily for 3 days), or tamoxifen, a selective antagonist of the estrogen receptor (20 mg daily for 9 days). Serum immunoactive FSH concentrations were measured in each sample by immunoradiometric assay (IRMA). Serum bioactive FSH concentrations were determined by an in vitro bioassay (rat granulosa cell aromatase system) on 24-hour serum pools. Deconvolution analysis was used to analyze both the FSH IRMA 24-hour time series and FSH release after GnRH. Comparisons between young and elderly men of the basal state showed significantly increased 24-hour mean serum immunoactive and bioactive FSH concentrations and significantly decreased free testosterone concentrations in elderly men. By deconvolution analysis, elderly men had a significant decrease in FSH secretory burst duration, and an increase in FSH half-life and FSH secretory burst amplitude compared with younger men. In response to sex steroid receptor blockade in young men, there was a significant increase in mean serum bioactive FSH concentrations during antiandrogen treatment, but not during antiestrogen treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased transcription decreases the spontaneous mutation rate at the thymidine kinase locus in human cells.

Transcription increases DNA repair efficiency and modulates the distribution of certain types of DNA damage. Furthermore, increased transcription level stimulates spontaneous mutation rate in yeast. We explored whether transcription level affects spontaneous mutation rate in human cells. We first developed two thymidine kinase (tk) inducible human cell lines using the Gal4-Estrogen receptor system. In our TK6i-G3 and G9 tk heterozygous cell lines, the active tk allele is linked to an inducible promoter element. Tk mRNA is induced following treatment with estrogen. Spontaneous mutation rate was significantly decreased in human cell lines after induction in contrast to the report in yeast. Thus, humans may have evolved different or additional mechanisms to deal with transcription related spontaneous mutagenesis.

Physical mapping of the human hprt chromosomal region (Xq26).

The human hprt chromosomal region (Xq26) was physical-mapped using pulsed field gel electrophoresis (PFGE). This work involved: (i) the recovery of three new genomic DNA markers (DXS1327, DXS1328, and DXS1329), (ii) the ordering of new markers relative to 11 previously available hprt-linked markers by deletion mapping, and (iii) the completion of human T-lymphocyte PFGE Southern blots using the 14 Xq26 markers. A contiguous 1.5-Mb physical map of the region telomeric to hprt was determined. As this map identifies clusters of in vivo unmethylated rare-cutter restriction sites, potential CpG islands are revealed.

Pulsed field analysis of hprt T-cell large deletions: telomeric region breakpoint spectrum.

In order to determine a large deletion breakpoint spectrum, 25 independent hprt T-lymphocyte mutants with deletions extending from hprt into the telomeric or centromeric flanking chromosomal region were analyzed by pulsed field gel electrophoresis (PFGE). PFGE was used to determine deletion sizes which allowed localization of breakpoints external to hprt to specific chromosomal positions in mutants containing an intra-hprt breakpoint. A breakpoint spectrum based on 19 large deletion mutants is reported for the Xq26 chromosomal region telomeric to hprt. A potential cluster of breakpoints (4/19) was observed approximately 60 kb from hprt. In addition, maximum recoverable deletion size was at least 3.5 Mb. Three of the 25 mutants analyzed appeared to be complex deletion events.