The provision of renal replacement therapy for adults in England and Wales: recent trends and future directions

We assessed the level of provision of renal replacement therapy for adults in England and Wales. All autonomous main renal units in England (n = 52) and Wales (n = 5) were surveyed in 1996. Data for England were compared to the 1993 National Renal Review. The acceptance rate in England 1995 was 82 (80-85) per million population (p.m.p.) compared with 67 (65-70) p.m.p. in 1991-2. The rate in 1995 in Wales was 109 (98- 122) p.m.p. The prevalence rate in England was 476 p.m.p. at end-1995 compared to 393 p.m.p. in 1993, in Wales it was 487 p.m.p. The number of main renal units in England did not rise between 1993 and 1995; capacity was increased by use of more treatment shifts and temporary haemodialysis stations, and by opening more satellite units. The main growth was in hospital haemodialysis. There was an uneven geographical distribution of services. Patients accepted were older with more comorbidity. The use of better-quality processes of dialysis increased. The steady-state position for RRT will not be reached for over a decade. Health authorities will face continued pressure to fund increases in quantity and quality improvements. A stronger evidence base of the effectiveness of therapies, and a national registry to monitor the equity and cost-effectiveness of services are needed.      

青少年和成年人无症状阻生智齿干预措施的疗效评价

目的评价在青少年和成人中拔除与保留无症状阻生智齿的效果.方法计算机检索Cochrane口腔健康组资料库(至2004年8月4日),Cochrane中心临床对照试验资料库(CENTRAL),Ovid-MEDLINE(1966～2004年8月4日),PubMed(1966～2004年8月4日)和EMBASE(1974～2004年8月4日).检索无语种限制.同时对主要相关杂志进行手检,并尽力获取正在进行和未发表的研究.纳入比较预防性拔除与保留阻生智齿效果的全部随机对照或临床对照研究.由3位作者分别独立评价所检出文献的相关性、真实性并提取数据,如有不确定性,联系作者以获取关于随机和失访的更多信息.对所有试验均进行了质量评价.结果共纳入3个研究,其中2个已完成的随机对照试验评价了青少年预防性拔除智齿对切牙拥挤的影响,另1个随机对照试验正在进行,但研究者不能提供任何资料,他们准备近期发表文章,如是,其资料将被纳入本评价的更新中.已完成的2个研究结局判断指标不同,不能进行数据合并.结论没有证据支持或反对常规预防性拔除成年人无症状阻生智齿,有一些可靠的证据表明在青少年预防性拔除阻生智齿既不能减少也不能预防切牙拥挤.     

Lung tumor-associated derepressed alloantigen coded for by the K region of the H-2 major histocompatibility complex

Transplacental induction of lung tumors in C3HfeB/HeN (C3Hf) strain mice can be readily achieved with the carcinogen 1-ethyl-1-nitrosourea. Several of these tumors express, as a tumor-associated transplantation antigen (TATA), a normal tissue alloantigen present in strain A and C3H/HeN (C3H) mice. In the present study it was shown that the tumor-associated alloantigen on the C3Hf-derived lung tumor 85 was present in all mice of H-2(a) and H-2(k) haplotypes tested and in CBA (532) strain mice (H-2(ka) haplotype). Studies using congenic-resistant and recombinant strains of mice indicated that the genetic locus controlling the expression of this antigen was either within or to the left of the H-2K region of the major histocompatibility complex (MHC). Thus the antigen was expressed in B10.A (4R) mice (kkbbbb MHC haplotype) but not in B10 (bbbbbb) or B10.AQR mice (qkkddd). The antigen was expressed in all tissues tested of C3H and A strain mice. It was not detected on any tissue tested including embryo tissue of C3Hf mice or mice of MHC haplotype other than H-2(k) or H-2(a). Because C3Hf strain mice were originally derived from C3H strain mice (H-2(k)), the MHC haplotype of C3Hf mice has been provisionally designated H-2(kb). The finding of a tumor-associated change in the expression of a H-2K region-coded antigen is consistent with the concept that MHC-coded antigens may act as targets for immunological surveillance of tumors.     

Delayed activation of quiescent donor hematopoietic stem cells in the host marrow cavity by anti-host monoclonal antibody

To understand the mechanisms controlling hematopoietic engraftment in untreated, normal recipients, we investigated the fate of parental, donor hematopoietic stem cells after apparent graft failures in unconditioned F1 hybrid recipient mice. By administering an anti-host H- 2K monoclonal antibody, which targets host cells but spares the donor, we found that chimerism could be induced by delayed conditioning in animals with apparent graft failure. Engraftment kinetics in the host were followed by typing individual colony forming unit-- granulocyte/macrophage (CFU-GM) colonies for their origin and showed that parental cells, which were otherwise virtually absent, become promptly detectable within the marrow cavity after antibody administration. Marrow transfers to secondary hosts suggested that parental stem cells were present in the marrow of the untreated recipients. These findings establish that the elimination of all parental cells cannot account for the absence of peripheral blood chimerism in the unconditioned F1 hybrid recipient. Thus, viable and functional donor stem cells, which remain quiescent in the host marrow, can be activated by a selective conditioning regimen and can rescue an apparent graft failure. The selective activation in vivo of marked stem cells in an unirradiated microenvironment may be a useful system to study the regulation of cellular proliferation within the marrow cavity.     

Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation

Studies of neutrophil nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in a cell-free system showed that the low molecular-weight guanosine triphosphatase (GTPase) Rac was required, and that Rap1a may participate in activation of the catalytic complex. Full-length posttranslationally modified Rac2 was active, whereas only the 1-166 truncated form of Rap1a was functional in the cell-free system, and thus, clarification of the function of Rap1a and Rac2 in intact human phagocytes is needed to provide further insight into their roles as signal transducers from plasma membrane receptors. In the present studies, oligonucleotide-directed mutagenesis was used to introduce a series of mutations into human rap1a or rac2 in the mammalian expression vector pSR alpha neo. HL60 cells transfected with wild-type or mutated rac2 or rap1a cDNA constructs and control HL60 cells transfected with the pSR alpha neo vector containing no inserted cDNA were selected in G418-containing media, then subclones were isolated. Compared with the parent HL60 cells, each of the stable transfected cell lines differentiated similarly into neutrophil-like cells and expressed comparable levels of NADPH oxidase components p47- phox, p67-phox and gp91-phox. The differentiated vector control cell line produced O2. in response to receptor stimulation at rates that were not significantly different from parent HL60 cells. O2-. production by differentiated cell lines expressing mutated N17 Rap1a or N17 Rac2 dominant-negative proteins was inhibited, whereas O2-. production by the subline overexpressing wild-type Rap1a was increased by fourfold. O2-. production by the differentiated cell line expressing GTPase-defective V12 Rap1a was also significantly inhibited, a finding that is consistent with a requirement for cycling between guanosine diphosphate- and GTP-bound forms of Rap1a for continuous NADPH oxidase activation in intact neutrophils. A model is proposed in which Rac2 mediates assembly of the p47 and p67 oxidase components on the cytosolic face of the plasma membrane via cytoskeletal reorganization, whereas Rap1a functions downstream as the final activation switch involving direct physical interaction with the transmembrane flavocytochrome component of the NADPH oxidase.     

Ophthalmic manifestations in the COVID-19 clinical spectrum

Purpose:The aim of this study was to determine the frequency and various types of ophthalmic manifestation of patients with COVID-19.Methods:This is a prospective observational study conducted on patients with SARS-Co-V-2 infection, at a dedicated tertiary COVID-19 hospital in South India from April 1 to July 31, 2020. At the time of their admission to the COVID hospital, demographic data such as name, age, sex was recorded. A thorough history regarding the onset, duration, progression, nature of symptoms and its associated factors, medication history, treatment history were elicited and documented. Ocular examination was performed under torchlight by an ophthalmologist posted for COVID duty. Further investigations including imaging were sought for, depending on clinical indications. Serial follow-up examinations of all patients were carried out every 72 hours or when patients complained of any ocular symptoms whichever earlier, until discharge. All relevant data were compiled and statistically analyzed.Results:A total of 2742 patients were examined. Of them, 1461 (53.28%) were males and 1281 (46.72%) were females. The mean age (±SD) was 39.46 ± 17.63 years. None of the patients in our study had any ocular symptoms or signs as the presenting complaint at the time of their admission. On subsequent follow-up, only 20 (0.72%) developed ocular manifestations, of which 19 (95%) had features suggestive of Bilateral viral conjunctivitis. However, 1 (5%) patient had orbital cellulitis secondary to pansinusitis.Conclusion:Ophthalmic manifestations in the clinical spectrum of COVID-19 infection are uncommon and unlikely to be the presenting clinical impression. However, it has broadened our view to a wider spectrum of COVID-19 presentations enhancing our clinical acumen for staunch detection of COVID-19 suspects in our daily practice, augmenting early diagnosis and management and also break the chain of transmission for the greater good of humanity.     

Investigation of cytokine levels and their association with SCORAD index in adults with acute atopic dermatitis

Background Atopic dermatitis (AD) is a chronic inflammatory skin disease with increasing frequency over the last decades, especially in adults. Cytokines orchestrate atopic skin inflammation. Objectives The aim of this study was to compare serum levels of cytokines in adult patients with acute AD (AD1) with other groups of AD patients and controls and investigate the possible association between such cytokines and disease severity. Methods We measured cytokine levels using flow cytometry in 21 adult patients with acute AD, 12 adults with chronic AD, 10 children with acute AD and 10 healthy adults. Results Flow cytometry analysis of cytokines revealed that interleukin 10 (IL‐10), IL‐6, interferon γ (IFN‐γ) and IL‐4 levels were significantly decreased in AD1 group compared with controls, whereas IL‐2 and tumour necrosis factor (TNF) did not differ. Comparison of AD1 group with adults chronic phase group showed that IgE, eosinophil and IL‐2 levels remained unaltered, whereas IL‐10, IL‐6, IFN‐γ, IL‐4 and TNF were significantly decreased. SCORAD and IgE levels were significantly increased, IL‐10, IL‐6 and IFN‐γ were decreased and TNF, IL‐2, IL‐4 and eosinophil levels remained unchanged in AD1 group compared with children acute phase group. Within AD1 group correlation analysis revealed that IgE and TNF levels were significantly associated with AD severity. Coefficient of determination analysis revealed that TNF and IgE levels could explain 49.14% and 35.28% of the variance of SCORAD. Conclusions These data indicate that serum IgE and TNF levels correlate with AD severity and that serum cytokines are downregulated in AD1 group. Further studies are clearly needed to elucidate cytokines’ role in adults with AD .     

Efficacy,safety and tolerability of green tea catechins in the treatment of external anogenital warts: a systematic review and meta‐analysis

Background External anogenital warts (EGWs) are non‐malignant skin tumours caused by human papillomavirus. They are one of the fastest growing sexually transmitted diseases. Current treatments are unsatisfactory. Green tea sinecatechin Polyphenon E ointment is a botanical extract from green tea leaves exhibiting anti‐oxidant, anti‐viral and anti‐tumour properties. Objective The aim of this study was to integrate valid information and provide basis for rational decision making regarding efficacy and safety of green tea extracts in the treatment of EGWs. Methods A systematic search in electronic databases was conducted using specific key terms. Main search was performed independently by two reviewers. The accumulated relevant literature was subsequently systematically reviewed and a meta‐analysis was conducted. Results Three randomized, double‐blind, placebo‐controlled studies evaluating efficacy and safety of Polyphenon E 15% and 10% in the treatment of warts were included in the systematic review and meta‐analysis. A total of 660 men and 587 women were enrolled. Regarding primary outcome, both Polyphenon E 15% and 10% demonstrated significantly higher likelihood of complete clearance of baseline and baseline and new warts compared with controls. No significant heterogeneity was detected. Recurrence rates were very low. Commonest local skin sign was erythema and local skin symptom was itching. Conclusions Efficacy of Polyphenon 15% and 10%, at least for the primary endpoint, is clearly indicated. Polyphenon E treatment exhibits very low recurrence rates and appears to have a rather favourable safety and tolerability profile. Recommendations for future studies should include evaluation of the efficacy of green tea catechins in the treatment of internal anogenital warts and direct comparison with its principal comparator, imiquimod.