bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical management of women with metastatic breast cancer: a descriptive study according to age group
Authors: Manders Klaartje , van de Poll-Franse Lonneke V , Creemers Geert-Jan , Vreugdenhil Gerard , van der Sangen Maurice JC , Nieuwenhuijzen Grard AP , Roumen Rudi MH , Voogd Adri C 
Published: July 2006

Abstract

Background
The primary aim of treatment of a patient who has developed metastatic disease is palliation. The objectives of the current study are to describe and quantify the clinical management of women with metastatic breast cancer from the diagnosis of metastatic disease until death and to analyze differences between age groups.

Methods
Data were collected from the medical files of all patients (n = 116) who had died after December 31, 1999, after a diagnosis of metastatic breast cancer in two teaching hospitals in the south of the Netherlands.

Results
Of the 116 patients included in our study, 10 (9%) already had metastatic disease at diagnosis and 106 developed distant disease after the diagnosis of localized breast cancer. Before they died, 70% of the 116 patients developed metastases in one or more bones, 50% in the lung and/or pleura, 50% in the abdominal viscera, 23% in the central nervous system, and 19% in the skin. Patients younger than 50 years were much more likely to develop metastases in the central nervous system than patients 50 years and older. Seventy-seven (66%) of the 116 patients with metastatic breast cancer received chemotherapy. This proportion decreased with age (p = 0.005), as did the number of schemes per patient. Together, they received 132 chemotherapy schemes, of which 35 (27%) resulted in partial remission or stabilization of the disease process. Ninety-eight patients (84%) received hormonal treatment. This proportion did not differ between the three age groups. Together, they received 216 hormonal treatments, 38 (16%) of which resulted in partial remission or stabilization of the disease process. Seventy-nine patients (68%) received palliative radiotherapy. This proportion decreased with age (p = 0.03). Together, they underwent 216 courses, 176 (77%) of which resulted in relief of the complaints.

Conclusion
Patients aged 70 years and older are less likely to receive chemotherapy or radiotherapy. Part of this difference could be explained by their shorter survival time after the diagnosis of metastatic disease and their lower risk of developing brain and bone metastases. However, more research is needed to understand the age-related differences in the treatment of metastatic breast cancer, and especially how comorbidity and frailty limit therapeutic choices.
Where do the elderly die? The impact of nursing home utilisation on the place of death. Observations from a mortality cohort study in Flanders
Authors: Van Rensbergen Gilberte , Nawrot Tim S , Van Hecke Ettiene , Nemery Benoit 
Published: July 2006

Abstract

Background
Most of the research concerning place of death focuses on terminally ill patients (cancer patients) while the determinants of place of death of the elderly of the general population are not intensively studied. Studies showed the influence of gender, age, social-economical status and living arrangements on the place of death, but a facet not taken into account so far is the influence of the availability of nursing homes.

Methods
We conducted a survey of deaths, between January 1999 and December 2000 in a small densely populated area in Belgium, with a high availability of nursing homes (within 5 to 10 km of the place of residence of every elderly). We determined the incidence of total mortality (of subjects >60 years) from local official death registers that we consulted via the priest or the mortician of the local parish, to ask where the decedent had died and whether the deceased had lived in a nursing home. We compared the distribution of the places of death between parishes with a nursing home and with parishes without nursing home.

Results
240 women and 217 men died during the two years study period. Only 22% died at home, while the majority (78%) died in an institutional setting, either a hospital (50%) or a nursing home (28%). Place of death was influenced by individual factors (age and gender) and the availability of a nursing home in the 'own' parish. The chance of in-hospital death was 65% higher for men (95% Confidence Interval [CI]: 14 to 138%; p = 0.008) and decreased by 4% (CI: -5.1% to -2.5%; p < 0.0001) for each year increase in age. Independent of gender and age, the chance of in-hospital death was 41% (CI: -60% to -13%; p = 0.008) lower in locations with a nursing home.

Conclusion
Demographic, but especially social-contextual factors determine where elderly will end their life. The majority of elderly in Flanders die in an institution. Age, gender and living situation are predictors of the place of death but the embedment of a nursing home in the local community seems to be a key predictor.
Gene expression in acute Stanford type A dissection: a comparative microarray study
Authors: Weis-Müller Barbara Theresia , Modlich Olga , Drobinskaya Irina , Unay Derya , Huber Rita , Bojar Hans , Schipke Jochen D , Feindt Peter , Gams Emmeran , Müller Wolfram , Goecke Timm , Sandmann Wilhelm 
Published: July 2006

Abstract

Background
We compared gene expression profiles in acutely dissected aorta with those in normal control aorta.

Materials and methods
Ascending aorta specimen from patients with an acute Stanford A-dissection were taken during surgery and compared with those from normal ascending aorta from multiorgan donors using the BD Atlas™ Human1.2 Array I, BD Atlas™ Human Cardiovascular Array and the Affymetrix HG-U133A GeneChip
®. For analysis only genes with strong signals of more than 70 percent of the mean signal of all spots on the array were accepted as being expressed. Quantitative real-time polymerase chain reaction (RT-PCR) was used to confirm regulation of expression of a subset of 24 genes known to be involved in aortic structure and function.

Results
According to our definition expression profiling of aorta tissue specimens revealed an expression of 19.1% to 23.5% of the genes listed on the arrays. Of those 15.7% to 28.9% were differently expressed in dissected and control aorta specimens. Several genes that encode for extracellular matrix components such as collagen IV α2 and -α5, collagen VI α3, collagen XIV α1, collagen XVIII α1 and elastin were down-regulated in aortic dissection, whereas levels of matrix metalloproteinases-11, -14 and -19 were increased. Some genes coding for cell to cell adhesion, cell to matrix signaling (e.g., polycystin1 and -2), cytoskeleton, as well as several myofibrillar genes (e.g., α-actinin, tropomyosin, gelsolin) were found to be down-regulated. Not surprisingly, some genes associated with chronic inflammation such as interleukin -2, -6 and -8, were up-regulated in dissection.

Conclusion
Our results demonstrate the complexity of the dissecting process on a molecular level. Genes coding for the integrity and strength of the aortic wall were down-regulated whereas components of inflammatory response were up-regulated. Altered patterns of gene expression indicate a pre-existing structural failure, which is probably a consequence of insufficient remodeling of the aortic wall resulting in further aortic dissection.
Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation—role of IL-10 and bone marrow precursors
Authors: Shibata Yoshimi , Gabbard Jon , Yamashita Makiko , Tsuji Shoutaro , Smith Mike , Nishiyama Akihito , Henriksen Ruth Ann , Myrvik Quentin N 
Published: July 2006

Abstract
Previous studies have shown that prostaglandin E2 (PGE2) release by splenic F4/80+ cyclooxygenase (COX)-2+ macrophages (MØ) isolated from mice, treated with mycobacterial components, plays a major role in the regulation of immune responses. However, splenic MØ, isolated from untreated mice and treated in vitro with lipopolysaccharide and interferon-γ, express COX-1 and COX-2 within 1 day but release only minimal amounts of PGE2 following elicitation with calcium ionophore A23187. For further characterization of in vivo requirements for development of PGE2-releasing MØ (PGE2-MØ), C57Bl/6 [wild-type (WT)], and interleukin (IL)-10-deficient (IL-10−/−) mice were treated intraperitoneally with heat-killed Mycobacterium bovis bacillus Calmette-Guerin (HK-BCG). One day following injection, COX-2 was induced in splenic MØ of both mouse strains. However, PGE2 biosynthesis by these MØ was not increased. Thus, expression of COX-2 is not sufficient to induce PGE2 production in vivo or in vitro. In sharp contrast, 14 days after HK-BCG treatment, PGE2 release by COX-2+ splenic MØ increased as much as sevenfold, and a greater increase was seen in IL-10−/− cells than in WT cells. To further determine whether the 14-day splenic PGE2-MØ could be derived from bone marrow precursors, we established a chimera in which bone marrow cells were transfused from green fluorescent protein (GFP)-transgenic donors to WT mice. Donors and recipients were treated with HK-BCG simultaneously, and marrow transfusion was performed on Days 1 and 2. On Day 14 after BCG treatment, a significant number of spleen cells coexpressed COX-2 and GFP, indicating that bone marrow-derived COX-2+ MØ may be responsible for the increased PGE2 production.
The Impact of Primary Hyperparathyroidism on the Oral Cavity
Authors: Padbury Allan D. , Tözüm Tolga F. , Taba Mario , Ealba Erin L. , West Brady T. , Burney Richard E. , Gauger Paul G. , Giannobile William V. , McCauley Laurie K. 
Published: July 2006

Abstract
Context: Primary hyperparathyroidism (HPT) is a systemic disease causing bone loss. Periodontal disease is a local inflammatory disease characterized by alveolar bone loss. The older literature records that HPT is associated with loss of radicular lamina dura and brown tumors of the bone, but contemporary studies are lacking.
Objective: The objective of the study was to determine the effects of HPT on oral bony structures and periodontal disease in a contemporary population.
Design: This was a cross-sectional, case-controlled study.
Setting: The study was conducted at the clinics of endocrine surgery and hospital dentistry.
Patients and Other Participants: Fifty-nine patients, 39 with HPT and 20 thyroid controls, were included in the study.
Main Outcome Measures: Periodontal clinical measures and dental radiographic analyses were used in this study.
Results: HPT patients were more likely to have tori and reductions in radicular lamina dura on dental radiographs. Widening of the periodontal ligament space surrounding teeth correlated with serum PTH levels. Panoramic radiographs demonstrated reduced cortical bone thickness at the angle of the mandible in HPT patients but no evidence of brown tumors or other overt pathologies.
Conclusions: Changes in the oral cavity observed in patients with HPT suggested both decreased cortical density and increased likelihood of oral tori. The contemporary oral manifestations of primary HPT are different from those previously reported, and health care providers should be aware of newer, more subtle findings that may be present when treating patients with HPT.
Human Fetal Ovary Development Involves the Spatiotemporal Expression of P450c17 Protein
Authors: Cole Beth , Hensinger Krista , Maciel Gustavo A. R. , Chang R. Jeffery , Erickson Gregory F. 
Published: July 2006

Abstract
Objective: The purpose of this research was to characterize the spatiotemporal expression of P450c17 in the human fetal ovary.
Design: P450c17 protein was visualized in sections of control and anencephalic ovaries using immunohistochemistry.
Subjects: Subjects included control (nonanencephalic) and anencephalic human fetal ovaries during the second and third trimesters.
Results: In second-trimester control ovaries, P450c17 was highly expressed in primary interstitial cells (PIC) located between the ovigerous cords near the cortical-medullary border where meiosis and primordial follicle formation were occurring. Morphometric analysis revealed a progressive decrease in the number of PIC during the second trimester, suggesting that PIC might have a finite lifetime. Between 25 and 32 wk, relatively few cells stained positive for P450c17; however, after 33 wk, P450c17 was strongly expressed in theca interstitial cells (TIC) bordering developing follicles. Surprisingly, the TIC appeared remarkably early during folliculogenesis, e.g. as early as the primary-to-secondary transition, and exhibited notable hyperplasia throughout preantral and early antral follicle growth. Owing to large numbers of developing preantral follicles, the third trimester was characterized by an increased abundance of P450c17-positive TIC. During this time period, P450c17 was strongly expressed in the hilus interstitial cells juxtaposed to the rete ovarii. Studies of ovaries of anencephalic fetuses revealed a similar spatiotemporal pattern of P450c17 expression in the PIC, TIC, and hilus interstitial cells, consistent with the possibility that pituitary hormones may not be involved in P450c17 expression in fetal ovaries.
Conclusion: We identified three different classes of P450c17-expressing interstitial cells in the human fetal ovary, each having a different spatiotemporal pattern of P450c17 expression and, presumably, a different set of physiological functions.
Growth Hormone Treatment and Risk of Second Neoplasms in the Childhood Cancer Survivor
Authors: Ergun-Longmire Berrin , Mertens Ann C. , Mitby Pauline , Qin Jing , Heller Glenn , Shi Weiji , Yasui Yutaka , Robison Leslie L. , Sklar Charles A. 
Published: July 2006

Abstract
Context: GH deficiency is common in childhood cancer survivors. In a previous report, although we did not find an increase in the risk of disease recurrence in survivors treated with GH, GH-treated survivors did have an increased risk of developing a second neoplasm (SN) (rate ratio, 3.21).
Objective: In this analysis, we have reassessed the risk of GH-treated survivors developing an SN after an additional 32 months of follow-up.
Design and Setting: We conducted a retrospective cohort multicenter study.
Patients: Among a total of 14,108 survivors who were enrolled in the Childhood Cancer Survivor Study, a retrospective cohort of 5-yr survivors of childhood cancer, we identified 361 who were treated with GH.
Main Outcome: We assessed the risk of developing an SN.
Results: During the extended follow-up, five new SN developed in survivors treated with GH, for a total of 20 SN, all solid tumors. Using a time-dependent Cox model, the rate ratio of GH-treated survivors developing an SN, compared with non-GH-treated survivors, was 2.15 (95% confidence interval, 1.3–3.5; P &lt; 0.002). Meningiomas were the most common SN (n = 9) among the GH-treated group.
Conclusion: Although cancer survivors treated with GH appear to have an increased risk of developing SN compared with survivors not so treated, the elevation of risk due to GH use appears to diminish with increasing length of follow-up. Continued surveillance is essential.
Model for the Pharmacologic Treatment of Crouzon Syndrome
Authors: Perlyn Chad A. , Morriss-Kay Gillian , Darvann Tron , Tenenbaum Marissa , Ornitz David M. 
Published: July 2006

AbstractOBJECTIVECrouzon syndrome is caused by mutations in FGFR2 leading to constitutive activation of receptors in the absence of ligand binding. The syndrome is characterized by premature fusion of the cranial sutures that leads to abnormal skull shape, restricted brain growth, and increased intracranial pressure. Surgical remodeling of the cranial vault is currently used to treat affected infants. The purpose of this study was to develop a pharmacologic strategy using tyrosine kinase inhibition as a novel treatment for craniosynostotic syndromes caused by constitutive FGFR activation.METHODSCharacterization of cranial suture fusion in Fgfr2C342Y/+ mutant mice, which carry the most common Crouzon mutation, was performed using MicroCT analysis from embryogenesis through maturation. Whole calvarial cultures from wild-type and Fgfr2C342Y/+ mice were then established and calvaria cultured for 2 weeks in the presence of DMSO control or PD173074, an FGFR tyrosine kinase inhibitor. Paraffin sections were prepared to show suture morphology and calcium deposition.RESULTSIn untreated Fgfr2C342Y/+ cultures, the coronal suture fused bilaterally with loss of overlap between the frontal bone and parietal bone. Calvaria treated with PD173074 (2 (M) showed patency of the coronal suture and were without evidence of any synostosis.CONCLUSION: We report the successful use of PD173074 to prevent in-vitro suture fusion in a model for Crouzon syndrome. Further studies are underway to develop an in-vivo treatment protocol as a novel therapeutic modality for FGFR associated craniosynostotic syndromes.
Extraction of Alkali Metal Picrates with Benzo-18-crown-6 into Various Organic Solvents. Fundamental Equilibria which Govern the Highest Extraction Selectivity for K+ among Alkali Metal Ions
Authors: Takeda Yasuyuki , Kawarabayashi Atsuhiro , Takahashi Keiko , Kudo Yoshihiro 
Published: July 2006

Abstract
For the determination of the actual overall extraction equilibrium constant (Kex) and the ion-pair formation constant (KMLA) in water of a crown ether–metal salt 1 : 1 : 1 complex, a more completed method is established by considering the concentration of the resulting 1 : 1 : 1 crown ether complex and ion-pair formation between the uncomplexed metal ion and the anion in the aqueous phase. The theoretical predictions were verified experimentally by solvent extraction with benzo-18-crown-6 (B18C6), alkali metal (Na, K, Rb) picrates, and various diluents of low dielectric constant. The actual log KMLA values in water at 25 °C of the 1 : 1 : 1 B18C6-alkali metal picrate complexes are 1.54 ± 0.16 for Na, 3.30 ± 0.20 for K, and 3.11 ± 0.24 for Rb. The distribution constants of the 1 : 1 : 1 B18C6 complexes were calculated from the partition constants of B18C6, the formation constants in water of the B18C6-alkali metal-ion complexes, and the actual Kex and KMLA values obtained in this study. The distribution behavior of the 1 : 1 : 1 B18C6 complexes is explained based on regular solution theory. The molar volumes and solubility parameters of the complexes were determined. Moreover, the fundamental equilibria which govern the highest extraction selectivity of B18C6 for K+among the alkali metal ions were completely elucidated.
Highly Stereoselective Synthesis of the Anti-Platelet Activating Factor, 4-Thiazolidinones, Using Silyl Derivatives of 2-Mercaptoalkanoic Acids
Authors: Tanabe Yoo , Okumura Hitomi , Nagaosa Masaki , Murakami Masanari 
Published: July 2006

Abstract
The cyclo-condensation of silyl 2-mercaptoalkanoates and arylmethyleneamines proceeded with high stereoselectivity to give alternatively both the cis- and trans-2,5-disubstituted 4-thiazolidinones, some of which are known as anti-platelet activating factor-active drugs. The use of the piperidine catalyst and no catalyst showed very high cis-stereoselectivity (cis/trans = 10/1—50/1) during the reaction. On the other hand, the trans-selective reaction was promoted by Ti(O-i-Bu)4 and Al(O-s-Bu)3 catalysts (cis/trans = 1/8—1/25). Both reactions were conducted with higher cis- and trans-selectivities as compared with those of the alkyl 2-mercaptoalkanoates under mild conditions. The cyclo-condensation using trimethylsilyl 2-(trimethylsilylthio)propionate and methyl 2-(trialkylsilylthio)propionates proceeded by the action of a catalytic amount (0.02 molar amount) of tetrabutylammonium fluoride with moderate cis-selectivity.
Synaptic Regulation of Translation of Dendritic mRNAs
Authors: Schuman Erin M. , Dynes Joseph L. , Steward Oswald 
Published: July 2006

The selective localization of protein synthetic machinery at postsynaptic sites makes it possible for the synthesis of particular proteins to be regulated by synaptic signals. Here we consider how the structure of the machinery constrains synthetic capacity and the evidence that mRNA translation is locally controlled by synaptic signals.Since the discovery of protein synthetic machinery at synaptic sites on dendrites (Steward and Levy, 1982), substantial progress has been made in identifying dendritic mRNAs and in showing that dendritic protein synthesis is critical for persistent synaptic modifications like long-term potentiation (LTP) and long-term depression (LTD). Although many pieces of the puzzle have been identified, major questions remain. Here we focus on one of the unknowns: how translational activity at synapses is regulated and whether regulation involves upregulation or downregulation of overall translation or differential regulation of the translation of particular transcripts. It is useful to begin by considering constraints imposed by the nature of the protein synthetic machinery at synapses.
Gender Differences in Lymphocyte Populations, Plasma HIV RNA Levels, and Disease Progression in a Cohort of Children Born to Women Infected With HIV
Authors: Foca Marc , Moye Jack , Chu Clara , Matthews Yvonne , Rich Ken , Handelsman Ed , Luzuriaga Katherine , Paul Mary , Diaz Clemente ,   Women and Infants Transmission Study
Published: July 2006

OBJECTIVE. We sought to document gender differences in lymphocyte subsets and plasma RNA levels in a pediatric cohort with presumed minimal hormonal differences (on the basis of age).
METHODS. Blood samples from antiretroviral therapy-treated, HIV-infected children (n = 158) and HIV-uninfected children (n = 1801) who were enrolled in the Women and Infants Transmission Study were analyzed at specified study intervals with consensus protocols, and various parameters were compared.
RESULTS. Antiretroviral therapy-treated, HIV-infected female children had, on average, 0.38 log10 copies per mL lower plasma RNA levels than did their male counterparts, but lymphocyte differences were not noted in this cohort. Despite their higher plasma RNA level, a greater proportion of male children survived through 8 years of age. There were no gender differences with respect to the age of diagnosis of HIV, time to antiretroviral therapy after diagnosis of HIV, or type of antiretroviral therapy. Lymphocyte differences were noted for uninfected children.
CONCLUSIONS. Plasma RNA levels differed among antiretroviral therapy-treated, HIV-infected children according to gender, in a manner similar to that noted in previous pediatric and adult studies. Lymphocyte subsets varied according to gender in a cohort of HIV-exposed but uninfected children. Most importantly, overall mortality rates for this cohort differed according to gender.