The dermis can be divided into two morphologically different layers: the papillary and reticular dermis. Fibroblasts isolated from these layers behave differently when cultured in vitro. During skin ageing, the papillary dermis decreases in volume. Based on the functional differences in vitro, it is hypothesized that the loss of papillary fibroblasts contributes to skin ageing. In this study, we aimed to mimic certain aspects of skin ageing by using high‐passage cultures of reticular and papillary fibroblasts and investigated the effect of these cells on skin morphogenesis in reconstructed human skin equivalents. Skin equivalents generated with reticular fibroblasts showed a reduced terminal differentiation and fewer proliferating basal keratinocytes. Aged in vitro papillary fibroblasts had increased expression of biomarkers specific to reticular fibroblasts. The phenotype and morphology of skin equivalents generated with high‐passage papillary fibroblasts resembled that of reticular fibroblasts. This demonstrates that papillary fibroblasts can differentiate into reticular fibroblasts in vitro. Therefore, we hypothesize that papillary fibroblasts represent an undifferentiated phenotype, while reticular fibroblasts represent a more differentiated population. The differentiation process could be a new target for anti‐skin‐ageing strategies. 相似文献
Two new murine monoclonal antibodies, AK 1 and SZ 1, reactive with the human platelet glycoprotein (GP) Ib-IX complex have been produced by the hybridoma technique. Both AK 1 and SZ 1 immunoprecipitated the GP Ib-IX complex from Triton X-100-solubilized, periodate-labeled platelets. With trypsinized, labeled platelets, AK 1, SZ 1, and FMC 25 (epitope on GP IX) immunoprecipitated a membrane-bound proteolytic fragment of the GP Ib-IX complex consisting of GP IX and an congruent to 25,000 mol wt remnant of the alpha-chain of GP lb disulfide-linked to the beta-subunit. Unexpectedly, although AK 1 and SZ 1 immunoprecipitated purified GP Ib-IX complex, neither antibody immunoprecipitated the individual components of this complex, GP Ib or GP IX. When GP Ib and GP IX were recombined, however, AK 1 and SZ 1 again immunoprecipitated the reformed complex, strongly suggesting that both antibodies were recognizing an epitope present only on the intact complex. Cross-blocking studies indicated that AK 1 and SZ 1 recognized a very similar or identical epitope that was proximal to the epitope for FMC 25. Both AK 1 and SZ 1 bound to a similar number of binding sites (congruent to 25,000) on intact platelets as monoclonal antibodies directed against either GP lb or GP IX. The combined data suggests that GP lb and GP IX are fully complexed in the intact platelet membrane. 相似文献
The myeloproliferative syndrome induced by the myeloproliferative sarcoma virus (MPSV) in DBA/2 mice stimulates the proliferation of pluripotent hemopoietic stem cells (HSC) and of progenitors committed toward granulomacrophagic and erythroid cell lines. This stimulation may result from a direct effect of the MPSV on HSC or from an indirect effect via locally secreted factors. Normal isogenic bone marrow cells were incubated in the mixed colony-forming unit system in semisolid medium supplemented with conditioned media obtained after incubating neoplastic spleen cells for 3 days at 37 degrees C. These spleen conditioned media contain an activity that is physically separable from MPSV by ultracentrifugation and which, in the presence of a very low quantity of erythropoietin, can induce in vitro the proliferation and differentiation of pluripotent HSC, detected by this Mix-CFU technique. We termed this activity mixed-colonies promoting activity (MPA). These results suggest that the hyperplasia of the nonlymphoid hematopoietic system in the neoplastic spleen results from an indirect effect of the MPSV on pluripotent HSC via locally secreted factors. 相似文献
BACKGROUND: Saudi Arabia is hyperendemic for brucellosis, with more than 8000 cases reported each year to public health authorities. During 1998, brucellosis ranked as the No. 1 reportable communicable disease (22.5%) in Saudi Arabian National Guard communities. King Fahad Hospital is the major referral center for National Guard personnel in the nation's central region.Methods And Results: From 1991 to 2000, brucellosis developed in 7 expatriate hospital employees. Six employees were bacteriology technologists, and one was a pathologist. Each had a clinical syndrome compatible with brucellosis (headache, fever, rigors, sweats, and myalgias) plus elevated Brucella sp serum agglutinin titers > or = 1:1280; one patient also had positive blood cultures. All patients responded to anti-Brucella therapy. Two patients had relapses, and complications occurred in four patients (septic endophlebitis of the leg, infected prosthesis, epididymoorchitis, and lumbar spondylitis). In all these employees except the pathologist, the infection was associated with processing Brucella sp cultures. CONCLUSION: Despite the enforcement of stringent infection control measures including the use of a class II biosafety hood in the laboratory, the problem of nosocomial brucellosis persists because of the large number of infected specimens handled by the laboratory (17,500 specimens per year). Ultimately, risk reduction depends on efforts to reduce disease endemicity in the country. In the meantime, conversion of the laboratory to biosafety level 3 is under way. 相似文献
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
Introduction: Cardiac rehabilitation program is an evidence-based intervention and established model of exercise delivery following myocardial infarction and heart failure. Although it forms an important part of recovery and helps to prevent future events and complications, there has been little focus on its potential cognitive benefits.
Areas covered: Coronary artery disease and heart failure are common heart problems associated with significant morbidity and mortality, and cognitive decline is commonly seen in affected individuals. Cognitive impairment may influence patient self-management by reducing medication adherence, rendering patients unable to make lifestyle modifications and causing missed healthcare visits. Cognitive assessment in cardiac rehabilitation as an outcome measure has the potential to improve clinical, functional and behavioral domains as well as help to reduce gaps in the quality of care in these patients.
Expert commentary: Limited evidence at present has shown that cardiac rehabilitation and exercise has potential in preventing cognitive decline. Cardiac prehabilitation, a rehabilitation-like program delivered before cardiac surgery, may also play a role in preventing postoperative cognitive dysfunction, but needs future research studies to support it. 相似文献
We employed the research-to-practice consensus workshop (RTP; workshops held in
New York City and Tompkins County, New York, in 2013) model to merge researcher
and practitioner views of translational research priorities in palliative care.
In the RTP approach, a diverse group of frontline providers generates a research
agenda for palliative care in collaboration with researchers. We have presented
the major workshop recommendations and contrasted the practice-based research
priorities with those of previous consensus efforts. We uncovered notable
differences and found that the RTP model can produce unique insights into
research priorities. Integrating practitioner-identified needs into research
priorities for palliative care can contribute to addressing palliative care more
effectively as a public health issue.Over the past 2 decades, palliative care has become established as a promising approach
for addressing the needs of individuals with life-threatening illnesses from a holistic,
interdisciplinary perspective. For this project, we defined palliative care as an
approach that improves the quality of life of patients and families facing the problems
encountered in life-threatening illness by preventing and relieving suffering. Core
components of palliative care include providing relief from pain and other distressing
symptoms, affirming dying as a normal process, integrating psychological and spiritual
aspects of care, enhancing the quality of life of patients, and offering support systems
to patients and their families to help them live as fully as possible until death
occurs.Research suggests that palliative care results in positive patient outcomes, greater
patient and family satisfaction, and significant cost savings.1,2 The American Public Health Association, the
World Health Organization, and the Institute of Medicine3–6 have identified the
development of a robust palliative care delivery system as a key public health issue
because of the documented ability of palliative care to deliver effective and efficient
patient- and symptom-focused care to a growing population in need.In its 2013 report the American Public Health Association specifically detailed the
public health implications of palliative care, acknowledged the growing burden of
advanced chronic illness and disease in older adults, and recommended key steps to
address the problem. This policy statement called for federal, state, and local efforts
to promote effective symptom management in populations with serious illness or at the
end of life. Other recommended initiatives included the development of a palliative care
workforce, educational programs to improve uptake and use of palliative and hospice
care, and research funding to support the expansion of palliative care initiatives.
Achieving these goals will require moving beyond traditional medical practices to
include both policies and initiatives at the public health level.Despite the potential of palliative care to address the mental and physical health needs
of individuals with advanced illness, significant knowledge gaps impede its reach and
effectiveness. Reports from scientific bodies and consensus workshops have highlighted
weaknesses in the literature and called for more research on palliative care and
improved research methods.7–10 Thus, although both interest in and demand for
palliative care are increasing, reviews of the knowledge base continue to lament the
lack of research on many key issues.11,12Especially urgent is a research agenda that fits most closely with the needs of providers
who deliver palliative care. The systematic engagement of community practitioners in a
consensus process can lead to particularly useful and actionable recommendations for
research,13–15 which are greatly needed at this stage in the
development of the field. Therefore, to shed new light on research priorities in
palliative care, we used a structured, participatory method designed to solicit
practitioner input on research priorities: the research-to-practice consensus workshop
(RTP) model.16We employed the RTP approach to identify knowledge gaps and types of studies that should
be conducted to improve providers’ ability to deliver palliative care most
effectively. This model harnesses practice wisdom by engaging clinicians, agency staff,
and other practitioners with researchers in a process of articulating and refining
research questions and research priorities that honors scientific expertise and practice
wisdom. 相似文献
To evaluate the effectiveness and potential benefits of topical tranexamic acid (TXA) in the management of acute epistaxis.
Methods
Retrospective review was performed among all patients presenting to the institution's emergency department (ED) with epistaxis between September 2014 and August 2016. Patients achieving hemostasis with standard of care agents, such as oxymetazoline, lidocaine, or epinephrine were excluded. The primary outcome was the ED length of stay (LOS). Secondary outcomes included the incidence of hospital admission, otolaryngologist consultation, nasal packing, prophylactic antibiotic use, and ED visit for rebleeding within seven days of treatment.
Results
Among 122 patients, 30 received topical TXA (500 mg injectable solution soaked onto packing material and applied to the affected nostril) and 92 were managed with standard care. Nearly half (46.7%) of TXA-treated subjects received TXA either alone or in combination with standard of care agents as their initial treatment strategy. No significant difference was observed in the ED LOS (272 vs 232 min in TXA and standard care arms, respectively, p = 0.26). However, TXA was associated with a significant reduction in otolaryngologist consults (30.0% vs 65.2%, p = 0.002) and nasal packing (16.7% vs 23.9%, p = 0.003).
Conclusions
This investigation did not demonstrate a significant difference in ED LOS among patients with acute epistaxis treated with topical TXA or standard care. However, this data does add to existing evidence that TXA may be associated with a reduction in resource utilization, suggesting it may provide more effective bleeding control. Overall, more data is needed to confirm the potential benefits of this practice. 相似文献