Technological mapping and trends in photobioreactors for the production of microalgae.

Photobioreactors (PBRs) are equipment of central importance for the massive cultivation of microalgae, providing controlled conditions for high cell productivity. There are a few popular PBR designs, with contrasting advantages and limitations, such as poor light distribution, mass transfer, or hydrodynamic behavior. Due to the environmental concerns in recent decades and the discovery of new, useful microalgal metabolites, the interest in finding alternatives to solve technological bottlenecks of PBRs has intensified. In this process, new geometries, materials, and modes of light supply were developed, generating a significant scientific and technological output, reported in papers and patents. We present a technological landscape analysis of photobioreactor design, focusing on improvements of the classical geometries and trends in industrial photobioreactors. The analysis of 412 patent documents showed a surge in innovation filing since 2005 and a reduction in the number of new documents along the last decade. The recent efforts in design improvement, the leading countries, institutes and companies that innovate, and the trends in PBR technology are presented and discussed.

Implementing a fracture liaison service open model of care utilizing a cloud-based tool.

PURPOSE: Although half of women and one-quarter of men aged 50 and older will sustain an acute low-trauma fracture, less than a quarter receive appropriate secondary fracture prevention. The goal of this quality improvement demonstration project was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in three open health care systems aided by a cloud-based tool. METHODS: The pre-post study design examined the proportion of men and women over age 50 who received appropriate assessment (bone mineral density, vitamin D levels) and treatment (calcium/vitamin D, pharmacologic therapy) in the six months following a recently diagnosed fracture. The pre-study (Pre FLS) included a retrospective chart review for baseline data (N = 344 patients) within each health care system. In the post-evaluation (Post FLS, N = 148 patients), the FLS coordinator from each health care system examined these parameters following enrollment and for 6 months following the recently diagnosed fracture. Data were managed in the cloud-based FLS application tool. RESULTS: Ninety-three participants completed the program. The FLS program increased the percentage of patients receiving bone mineral density testing from 21% at baseline to 93% (p < 0.001) Post FLS implementation. Assessments of vitamin D levels increased from 25 to 84% (p < 0.001). Patients prescribed calcium/vitamin D increased from 36% at baseline to 93% (p < 0.001) and those prescribed pharmacologic treatment for osteoporosis increased on average from 20 to 54% (p < 0.001) Post FLS. CONCLUSIONS: We conclude that the FLS model of care in an open health care system, assisted by a cloud-based tool, significantly improved assessment and/or treatment of patients with a recently diagnosed osteoporotic fracture. Future studies are necessary to determine if this model of care is scalable and if such programs result in prevention of fractures. Mini-Abstract: The goal was to implement a Fracture Liaison Service (FLS) focused on secondary prevention of an osteoporotic fracture in open health care systems aided by a cloud-based tool. This model significantly improved assessment and/or treatment of patients with a recently diagnosed fracture.

Development of a cloud-based application for the Fracture Liaison Service model of care.

UNLABELLED: The aims of this study are to develop a cloud-based application of the Fracture Liaison Service for practitioners to coordinate the care of osteoporotic patients after suffering primary fractures and provide a performance feedback portal for practitioners to determine quality of care. The application provides continuity of care, improved patient outcomes, and reduced medical costs. INTRODUCTION: The purpose of this study is to describe the content development and functionality of a cloud-based application to broadly deploy the Fracture Liaison Service (FLS) to coordinate post-fracture care for osteoporotic patients. METHODS: The Bone Health Collaborative developed the FLS application in 2013 to support practitioners' access to information and management of patients and provide a feedback portal for practitioners to track their performance in providing quality care. A five-step protocol (identify, inform, initiate, investigate, and iterate) organized osteoporotic post-fracture care-related tasks and timelines for the application. A range of descriptive data about the patient, their medical condition, therapies and care, and current providers can be collected. Seven quality of care measures from the National Quality Forum, The Joint Commission, and the Centers for Medicare and Medicaid Services can be tracked through the application. RESULTS: There are five functional areas including home, tasks, measures, improvement, and data. The home, tasks, and data pages are used to enter patient information and coordinate care using the five-step protocol. Measures and improvement pages are used to enter quality measures and provide practitioners with continuous performance feedback. The application resides within a portal, running on a multitenant, private cloud-based Avedis enterprise registry platform. All data are encrypted in transit and users access the application using a password from any common web browser. CONCLUSION: The application could spread the FLS model of care across the US health care system, provide continuity of care, effectively manage osteoporotic patients, improve outcomes, and reduce medical costs.

A web-based application for initial screening of living kidney donors: development, implementation and evaluation.

Most centers utilize phone or written surveys to screen candidates who self-refer to be living kidney donors. To increase efficiency and reduce resource utilization, we developed a web-based application to screen kidney donor candidates. The aim of this study was to evaluate the use of this web-based application. Method and time of referral were tabulated and descriptive statistics summarized demographic characteristics. Time series analyses evaluated use over time. Between January 1, 2011 and March 31, 2012, 1200 candidates self-referred to be living kidney donors at our center. Eight hundred one candidates (67%) completed the web-based survey and 399 (33%) completed a phone survey. Thirty-nine percent of donors accessed the application on nights and weekends. Postimplementation of the web-based application, there was a statistically significant increase (p < 0.001) in the number of self-referrals via the web-based application as opposed to telephone contact. Also, there was a significant increase (p = 0.025) in the total number of self-referrals post-implementation from 61 to 116 per month. An interactive web-based application is an effective strategy for the initial screening of donor candidates. The web-based application increased the ability to interface with donors, process them efficiently and ultimately increased donor self-referral at our center.

Dilated cardiomyopathy in cats: survey of veterinary cardiologists and retrospective evaluation of a possible association with diet.

INTRODUCTION/OBJECTIVES: The objectives were to conduct a survey of cardiologists on their recent experiences with cats that have dilated cardiomyopathy (DCM) and to retrospectively review individual cases of feline DCM. ANIMALS, MATERIALS AND METHODS: Part one: A survey was distributed to cardiologists with questions regarding caseload and clinical management of cats with DCM diagnosed over the past two years. Part two: Cardiologists completing the survey were invited to submit data from cats recently diagnosed with DCM. Data on signalment, clinical signs, diet, echocardiographic measurements and outcome were recorded. RESULTS: Part one: From 52 completed surveys, many cardiologists responded that measuring and supplementing taurine and recommending a diet change in cats with DCM are common practices. Few (15%) cardiologists reported an increase in the number of feline DCM cases over the past two years, although some had cases that improved even if taurine deficiency was not present. Part two: Twenty of 37 (54%) cats ate low pea/lentil (low PL) diets, and 14/37 (38%) ate high PL diets at the time of diagnosis; three had incomplete diet information. Two of 13 cats (15%) in which taurine was measured had levels below the reference range. After adjusting for other variables, cats eating high PL diets that changed diets after diagnosis had a significantly longer survival time than that of cats eating high PL diets that did not change diets after diagnosis (P = 0.025). CONCLUSIONS: Additional research is warranted to determine whether there could be a possible association between diet and DCM in cats.

What's New, What's Hot in Solid Organ Transplantation? Summary of the American Transplant Congress 2011.

Breakthroughs in basic and clinical science in solid organ transplantation were presented at the American Transplant Congress 2011. Key areas of presentation included the pathogenesis of late allograft failure, immune regulation and tolerance, pathways in allograft injury, electing appropriate patients for transplantation, determining the best allocation schemes to maximize effective utilization, organ preservation, monitoring the alloimmune response and immunosuppressive management. In this review, we present highlights of the meeting. These presentations demonstrate the exciting promise in translating from the bench to affect patient care.

Outcomes in total elbow arthroplasty in patients with haemophilia at the University of California, San Francisco: a retrospective review.

Severe haemophilic arthropathy of the elbow is a significant cause of morbidity among adults with haemophilia. However, previous reports of total elbow arthroplasty (TEA) in the haemophilic population have been based on small numbers of patients with relatively short-term follow-up. The records of seven total elbow arthroplasties in six adult men with haemophilia at the University of California, San Francisco who underwent TEA over a period of 25 years were retrospectively reviewed. Type of haemophilia, age at time of TEA, HIV infection status, pre- and postoperative range-of-motion (ROM) scores, complications (including infections), need for subsequent surgical revision and functional outcomes were recorded. Four patients had severe factor VIII deficiency and two patients had severe factor IX deficiency. None of the patients had an inhibitor. The mean age at the time of surgery was 34 years (range, 22-46 years) and the mean follow-up period was 118 months (range, 37-176 months). One of the six patients had TEA in both elbows. Five of the six patients were infected with HIV. There were no immediate perioperative complications. At a mean of 19.2 months postoperatively, ROM had improved in five of seven TEAs: mean flexion had increased from 110.7° (SD = 15.0) to 120.1° (SD = 14.5), whereas mean preoperative extension increased from -44.3° (SD = 21.5) to -36.9° (SD = 27.0). One patient required a revision at 30 months because of ulnar component loosening. This same patient sustained a staph epidermidis infection and ultimate removal of the prosthesis 15 years postoperatively. At a mean of 118 months postoperatively, five of six patients continued to report reduced pain and preserved functionality, with ability to perform normal daily activities. TEA resulted in favourable results in six of seven procedures. Our findings support the viability of TEA for individuals with severe haemophilic arthropathy of the elbow, especially to reduce pain and preserve or restore functionality.

A nonimmunogenic sarcoma transduced with the cDNA for interferon gamma elicits CD8+ T cells against the wild-type tumor: correlation with antigen presentation capability.

To be recognized by CD8+ T lymphocytes, target cells must process and present peptide antigens in the context of major histocompatibility complex (MHC) class I molecules. The nonimmunogenic, low class I-expressing, methylcholanthrene (MCA)-induced murine sarcoma cell line, MCA 101, is a poor presenter of endogenously generated viral antigens to specific CD8+ T lymphocytes and cannot be used to generate tumor infiltrating lymphocytes (TIL). Since interferon gamma (IFN-gamma) has been shown to upregulate three sets of molecules important for antigen processing and presentation, we retrovirally transduced wild-type MCA 101 (101.WT) tumor with the mIFN-gamma cDNA to create the 101.NAT cell line. Unlike 101.WT, some clones of retrovirally transduced 101.NAT tumor expressed high levels of class I, and could be used to generate CD8+ TIL. More importantly, these TIL were therapeutic in vivo against established pulmonary metastases from the wild-type tumor. Although not uniformly cytotoxic amongst several separate cultures, these TIL did specifically release cytokines (IFN-gamma and tumor necrosis factor-alpha) in response to 101.WT targets. 101.WT's antigen presentation deficit was also reversed by gene modification with mIFN-gamma cDNA. 101.NAT had a greatly improved capacity to present viral antigens to CD8+ cytotoxic T lymphocytes. These findings show that a nonimmunogenic tumor, incapable of generating a CD8+ T cell immune response, could be gene-modified to generate a therapeutically useful immune response against the wild-type tumor. This strategy may be useful in developing treatments for tumor histologies not thought to be susceptible to T cell-based immunotherapy.

Successful DCD kidney transplantation using early corticosteroid withdrawal.

Organs from donors after cardiac death (DCD) are being increasingly utilized. Prior reports of DCD kidney transplantation involve the use of prednisone-based immunosuppression. We report our experience with early corticosteroid withdrawal (ECSW). Data on 63 DCD kidney transplants performed between 2002 and 2007 were analyzed. We compared outcomes in 28 recipients maintained on long-term corticosteroids (LTCSs) with 35 recipients that underwent ECSW. DGF occurred in 49% of patients on ECSW and 46% on LTCS (p=0.8). There was no difference between groups for serum creatinine or estimated GFR between 1 and 36 months posttransplant. Acute rejection rates at 1 year were 11.4% and 21.4% for the ECSW and LTCS group (p=0.2). Graft survival at 1 and 3 years was 94% and 91% for the ECSW group versus 82% and 78% for the LTCS group (p>or=0.1). Death censored graft survival was significantly better at last follow-up for the ECSW group (p=0.02). Multivariate analysis revealed no correlation between the use of corticosteroids and survival outcomes. In conclusion, ECSW can be used successfully in DCD kidney transplantation with no worse outcomes in DGF, rejection, graft loss or the combined outcome of death and graft loss compared to patients receiving LTCS.

Clinical implications of advances in the basic science of liver repair and regeneration.

Recent advances in our understanding of the basic mechanisms that control liver regeneration and repair will produce the next generation of therapies for human liver disease. Insights gained from large-scale genetic analysis are producing a new framework within which to plan interventions. Identification of specific molecules that drive regeneration will increase the options for live-donor liver transplantation, and help treat patients with small-for-size syndrome or large tumors who would otherwise have inadequate residual mass after resection. In a complementary fashion, breakthroughs in the ability to manipulate various cell types to adopt the hepatocyte or cholangiocyte phenotype promise to revolutionize therapy for acute liver failure and metabolic liver disease. Finally, elucidating the complex interactions of liver cells with each other and various matrix components during the response to injury is essential for fabricating a liver replacement device. This focused review will discuss how a variety of important scientific advances are likely to impact the treatment of specific types of liver disease.

Acquired congenital heart block. Pattern of maternal antibody response to biochemically defined antigens of the SSA/Ro-SSB/La system in neonatal lupus.

The molecular basis of autoantibody reactivity with components of the SSA/Ro-SSB/La particle exhibited by sera of mothers of infants with severe and permanent manifestations of neonatal lupus (NLE) was investigated using immunoblotting and immunoprecipitation. The characteristics of NLE that were studied included congenital complete heart block (CCHB), second degree heart block, and hepatic fibrosis. Antibodies specific for one or more components of the SSA/Ro-SSB/La particle were found in sera from all 20 mothers of permanently affected infants. However, no antibody specific for a single peptide of this particle was common to all sera. Using tissue extracts from a human cell substrate, 80% of these sera had antibodies to one or more components of the SSA/Ro particle demonstrable by immunoblotting. The predominant antibody response in the NLE group was to the newly recognized 52-kD SSA/Ro peptide component. In contrast, antibodies to the 60-kD SSA/Ro component although present, were the least represented and not significantly increased in frequency among mothers of these infants, compared with a group of 31 mothers with autoimmune diseases such as systemic lupus erythromatosus (SLE) but who had healthy offspring. Antibodies directed to the 48-kD SSB/La antigen were demonstrated in 90% of the NLE mothers often accompanying antibodies against the 52-kD SSA/Ro component. The combination of antibodies to 48- and 52-kD structures was significantly increased in the NLE group, with an odds ratio of 35. The type of cell or tissue substrate was shown to influence detectability of antibodies. The 52-kD SSA/Ro peptide and the 48-kD SSB/La peptide were abundant in cardiac tissues from fetuses aged 18-24 wk, further supporting the possible relevance of these peptides to heart block.

The nephritogenic immune response.

Recent work has improved our understanding of a number of aspects of the nephritogenic immune response. Progress has been made in the understanding of the development of idiotypic networks, and in understanding the structural nature of the targets of self-reactive T cells and the paracrine mediators that are released as part of the local inflammatory response.

Improvement of Sporobolomyces ruberrimus carotenoids production by the use of raw glycerol.

The red yeast Sporobolomyces ruberrimus H110 was able to use glycerol as a carbon source. The highest concentration (0.51gL(-1)) and productivity (0.0064gL(-1)h(-1)) of carotenoids were achieved when raw glycerol from biodiesel production, containing around 1gL(-1) of fatty acids, was used as the carbon source, which represented increases of 27% and 1.5×, respectively, in relation to pure glycerol. Mass spectrometry analysis led to the identification of four carotenoids in the fermented samples, torularhodin, torulene, ß-carotene and γ-carotene. The use of raw glycerol also enhanced the proportion of torularhodin (69% against 59% in pure glycerol). The addition of individual fatty acids (palmitic, stearic, oleic and linoleic acids) to pure glycerol resulted in increases between 15% and 25% in maximum concentration and between 1.6× and 2.0× in productivity of carotenoids. The presence of palmitic and oleic acids increased the torularhodin proportion to 66%.

Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer.

We performed an escalating dose study of the combined administration of interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) in 94 patients with metastatic cancer. Patients received alpha-IFN at a dose of 3 x 10(6) U/m2 in conjunction with IL-2 at doses of either 1 x 10(6) U/m2 (six patients), 3 x 10(6) U/m2 (32 patients), or 4.5 x 10(6) U/m2 (26 patients). Thirty patients received alpha-IFN at 6 x 10(6) U/m2 plus IL-2 at 4.5 x 10(6) U/m2. Patients each received cytokine as an intravenous bolus infusion every 8 hours for up to 5 consecutive days and after a 10-day rest received a second cycle of combination cytokines. Of the 91 patients evaluable for response, seven patients had a complete regression of cancer, and 18 had a partial regression. At the four increasing dose levels used in patients with renal cell cancer (35 patients) or melanoma (39 patients), objective responses were seen in 17% (of six patients), 24% (of 25 patients), 38% (of 16 patients), and 41% (of 27 patients), respectively. Of the 25 total responding patients, 16 are still responding 5 to 14 months after treatment. The toxicities associated with the combined administration of IL-2 and alpha-IFN were similar to those expected from each agent alone. There was one treatment-related death in the 94 patients treated in this study. Thus, using increasing doses of the combination of IL-2 and alpha-IFN, it appears that response rates may be related to the doses of the cytokines used, and that at the highest doses of these combination cytokines, response rates may be higher than those for either cytokine alone. A prospective randomized trial comparing the cytokine combinations with each cytokine administered alone is necessary as is the extension of this combination cytokine treatment to patients with other types of solid cancer.

Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer.

Germ-line mutations in BRCA1 confer an increased risk of developing breast and ovarian cancer, but little is known about the clinical course of breast cancer in BRCA1 mutation carriers compared with noncarriers. Two recurrent BRCA1 mutations (185delAG and 5382insC) are common ( approximately 1.3%) in Ashkenazi Jews and account for about 20% of breast cancers diagnosed before age 40 in this group. We assayed paraffin-embedded tumor blocks from 117 unselected Ashkenazi Jewish women with primary breast cancer, diagnosed before age 65 at a single institution, for the presence of either of the two BRCA1 mutations. We reviewed the medical records and constructed survival curves for BRCA1-positive and -negative subgroups. Twelve of the women (10.3%) were found to carry BRCA1 mutations (eight mutations were 185delAG, and four were 5382insC). The probability of death from breast cancer in the first 5 years was 35.7% in the BRCA1 mutation-positive group and 4.3% in the 100 women without a mutation (P = 0.0023). The 5-year distant disease-free survival was 68.2% in BRCA1 mutation carriers and 88.7% in noncarriers (P = 0.019). These data suggest that breast cancer occurring in an Ashkenazi Jewish woman carrying a germ-line BRCA1 mutation has an adverse prognosis. This information is available before the diagnosis of breast cancer, and therefore, this finding may have important implications for prevention of breast cancer in BRCA1 mutation carriers.

The effects of estrone (Ogen) on spinal bone density of postmenopausal women.

The effects of cyclical treatment with estrone sulfate (0.3, 0.625, or 1.25 mg), plus calcium carbonate, on spinal trabecular bone density were compared with placebo in 120 postmenopausal women in this 2-year, multicenter, double-blind study. While the placebo and 0.3-mg treatment groups lost bone density (-3.6% and -5.1%), the 0.625- and 1.25-mg treatment groups experienced no significant change from baseline at 24 months (-0.8% and +0.7%). The 1.25-mg treatment group was significantly different from the placebo group at 12, 18, and 24 months. Although the 0.625-mg treatment group was significantly different from the placebo group only at 18 months, the data suggest that 0.625 and 1.25 mg of estrone sulfate had different effects than placebo and 0.3 mg of estrone sulfate and, given with supplemental calcium, are effective doses for the prevention of spinal bone loss.

Hexokinase type II: a novel tumor-specific promoter for gene-targeted therapy differentially expressed and regulated in human cancer cells.

The use of tissue- or tumor-selective promoters in targeted gene therapy for cancer depends on strong and selective activity. Hexokinase type II (HK II) catalyzes the first committed step of glycolysis and is overexpressed in tumors, where it is no longer responsive to normal physiological inhibitors, e.g., glucagon. We show, in a reporter gene assay, activation of HK II in non-small cell lung carcinomas NCI-H661 and NCI-H460 at 61 and 40%, respectively, relative to the activation observed with a constitutive promoter, while it was only 0.9% in different preparations of primary normal human bronchial epithelial cells (NHBECs). Similar results were observed in a variety of normal and tumor cells. Moreover, treatment of the transfectants with glucagon did not inhibit promoter activation in the transformed H661 cells, while endogenous HK II in NHBECs is suppressed by glucagon. H460 and H661 cells infected with a recombinant adenovirus carrying an HK II/LacZ expression cassette, AdHexLacZ, demonstrated beta-galactosidase activity that correlated with the level of HK II promoter activation in these cells. Under similar conditions, no enzyme activity was observed in NHBECs. Cells were then infected with AdHexTk and treated with GCV. Our results demonstrate selectivity in toxicity, with a 10- to 100-fold increase in IC50 between lung cancer cell lines H661 and H460, respectively, and NHBECs. There was also a 100-fold increase in IC50 in NHMECs relative to breast carcinoma cell line MCF-7. In HepG2 cells, an IC50 of 1 microg/ml was observed, comparable to that of other tumor cell lines. This represents a novel use of the hexokinase type II as a selective promoter in cancer gene therapy.

The lifetime risks of breast cancer in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations.

Several studies using families with multiple occurrences of breast cancer have provided evidence for a very high lifetime penetrance in carriers of BRCA1 or BRCA2 mutations. However, there are reasons to suspect that the estimates of penetrance from studies of cancer families may be inflated. Access to the genotypes of incident cases of breast cancer in three hospitals and from a large series of unaffected survey participants provided the basis for direct estimation of the age-specific relative risks attributable to these mutations, and the resulting lifetime penetrance, without any reference to familial aggregation of cancer. Cases were identified from incident series of Jewish patients treated for primary breast cancer at the three hospitals. Control data were obtained from the large series of Jewish women recruited in the Washington, D.C., area by investigators at the National Cancer Institute and limited to 3434 women with no previous history of breast or ovarian cancer. All subjects were genotyped for the three mutations that are relatively common in Ashkenazi Jews, namely 185delAG and 5382 insC in BRCA1 and 6174delT in BRCA2. For BRCA1, the relative risks of breast cancer were estimated to be 21.6 in women under 40 years of age, 9.6 in women 40-49 years of age, and 7.6 in women > or = 50 years of age. On the basis of these estimates, the penetrance of breast cancer at age 70 among BRCA1 mutation carriers is estimated to be 46% (95% confidence, 31%-80%) rising to 59% (95% confidence, 40%-93%) at age 80. For BRCA2, the relative risks in the same three age categories were estimated to be 3.3, 3.3, and 4.6, respectively, resulting in a penetrance at age 70 of 26% (95% confidence, 14%-50%) rising to 38% (95% confidence, 20%-68%) at age 80. The lifetime risk of breast cancer in Jewish women who are mutation carriers estimated via this approach is substantially lower than the reported lifetime risks estimated using multiple-case families. The risks appear to be different for carriers of BRCA1 and BRCA2 mutations.

ANCA-associated crescentic glomerulonephritis with mesangial IgA deposits.

Antineutrophil cytoplasmic autoantibodies (ANCA) are commonly associated with a necrotizing and crescentic glomerulonephritis (GN) that is pauci-immune, with few or no glomerular immune complex deposits detectable by immunofluorescence (IF) or electron microscopy (EM). Immunoglobulin A (IgA) nephropathy may also be manifest as a crescentic GN, but it is characterized by mesangial immune complex deposits containing IgA and is rarely associated with myeloperoxidase (MPO)- or proteinase 3 (PR3)-specific ANCA when an enzyme immunoassay is used to detect these antibodies. This report describes six patients with severe crescentic GN with mesangial IgA deposits by IF and mesangial electron-dense deposits by EM in patients with positive ANCA serological test results (four patients, anti-PR3; one patient, anti-MPO; one patient, anti-PR3 and anti-MPO). Patients presented with acute or progressive renal insufficiency, hematuria, proteinuria (nephrotic range in two patients), and hypertension. Three patients had evidence of systemic vasculitis: two patients at initial presentation and one patient later in the clinical course. Renal biopsy specimens showed crescents in greater than 50% of glomeruli in all cases, but only mild, focal and segmental mesangial and endocapillary hypercellularity, more typical of ANCA-associated crescentic GN than of crescentic IgA nephropathy without associated ANCA. Semiquantitative analysis of mesangial and endocapillary cellularity performed on renal biopsy slides from these six patients and from eight ANCA-negative patients with IgA nephropathy and crescents in greater than 50% of glomeruli showed significantly greater hypercellularity in the ANCA-negative cases. Three of five ANCA-positive patients for whom follow-up clinical data were available showed improved renal function after treatment with cyclophosphamide and corticosteroids and have not developed end-stage renal disease 17, 20, and 25 months postbiopsy. The remaining two patients were dialysis dependent at the time of biopsy and have remained so despite treatment with cyclophosphamide and corticosteroids. The findings suggest an overlap syndrome of ANCA-associated crescentic GN and IgA nephropathy that resembles the former both histologically and in its potential to respond to aggressive therapy if detected relatively early in its course.

Effect of cyclic estrone sulfate treatment on lipid profiles of postmenopausal women with elevated cholesterol levels.

The effects of two doses of cyclic unopposed estrone sulfate therapy on the lipid profiles of 153 healthy postmenopausal women with baseline total cholesterol levels above 219 mg/dL were compared in a multicenter, double-blind, placebo-controlled study. Patients were assigned randomly to one of three treatment groups: estrone sulfate 0.625 mg (N = 59) or 1.25 mg (N = 43), or placebo (N = 51). The median baseline total cholesterol levels of the three treatment groups were 262, 269, and 262 mg/dL, respectively. Total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), and the HDL/LDL ratio were assessed after 6, 9, and 12 months of treatment. There was a significant monotonic dose-response relationship of estrone sulfate in raising HDL levels, lowering LDL levels, and raising the HDL/LDL ratio at all intervals measured. These results indicate that estrone sulfate is effective in creating a beneficial change in the lipid profile of postmenopausal women with elevated baseline total cholesterol.