BackgroundHydroxychloroquine (HCQ) is an antimalarial drug that is recommended as a safe, daily prophylactic intervention for individuals with systemic lupus erythematosus (SLE) based on previous studies that showed an association of HCQ use with reductions in flares compared with placebo. Our study aims to determine whether the discontinuation of HCQ leads to relapse of disease and whether the duration of HCQ use impacts the success of its eventual discontinuation.MethodsA retrospective chart review was performed on the medical records of patients diagnosed with SLE between July 1, 2006, and June 30, 2016. The data gathered included demographic factors, diagnostic symptoms, laboratory values, and SLE medications. Additionally, HCQ usage and discontinuation rates were collected as well as the timing and prevalence of flares during and after HCQ usage. Patients who were diagnosed with SLE but never used HCQ were excluded from the study. The occurrence of flares, clinical characteristics, and duration of treatment with HCQ were compared between the group that continued HCQ and the group that discontinued HCQ.ResultsOf the 509 patients who met inclusion criteria, 66.2% (n = 337) continued HCQ throughout the duration of their treatment (median duration of HCQ treatment was 8.0 years), whereas 33.8% (n = 172) did not (median duration of HCQ treatment was 1.9 years). Patients who received HCQ for less than 1 year before discontinuation (median duration of HCQ treatment was 2.5 months) were more likely to experience SLE flares compared with those who continued HCQ for more than 1 year (13.1% vs 5.7%, P = 0.019). Patients who experienced a flare while on HCQ were more likely to have arthritis, oral ulcers, leukopenia, and thrombocytopenia.ConclusionWith over 500 patient charts reviewed, this is the largest study comparing outcomes for patients on HCQ with those who discontinued it. Patients who discontinue HCQ after being on it for less than 1 year are at greater risk for flares compared with those who take HCQ for longer than 1 year. These findings should be used to guide treatment, educate patients on the role of continued treatment with HCQ, and ultimately reduce morbidity and mortality.
BackgroundProlactin is a polypeptide hormone responsible for proliferation and differentiation of the mammary gland. More recently, prolactin's role in mammary carcinogenesis has been studied with greater interest. Studies from our laboratory and from others have demonstrated that three specific isoforms of the prolactin receptor (PRLR) are expressed in both normal and cancerous breast cells and tissues. Until now, reliable isoform specific antibodies have been lacking. We have prepared and characterized polyclonal antibodies against each of the human PRLR isoforms that can effectively be used to characterize human breast cancers.MethodsRabbits were immunized with synthetic peptides of isoform unique regions and immune sera affinity purified prior to validation by Western blot and immunohistochemical analyses. Sections of ductal and lobular carcinomas were stained with each affinity purified isoform specific antibody to determine expression patterns in breast cancer subclasses.ResultsWe show that the rabbit antibodies have high titer and could specifically recognize each isoform of PRLR. Differences in PRLR isoform expression levels were observed and quantified using histosections from xenografts of established human breast cancer cells lines, and ductal and lobular carcinoma human biopsy specimens. In addition, these results were verified by real-time PCR with isoform specific primers. While nearly all tumors contained LF and SF1b, the majority (76%) of ductal carcinoma biopsies expressed SF1a while the majority of lobular carcinomas lacked SF1a staining (72%) and 27% had only low levels of expression.ConclusionsDifferences in the receptor isoform expression profiles may be critical to understanding the role of PRL in mammary tumorigenesis. Since these antibodies are specifically directed against each PRLR isoform, they are valuable tools for the evaluation of breast cancer PRLR content and have potential clinical importance in treatment of this disease by providing new reagents to study the protein expression of the human PRLR.
Obesity is a significant health concern and is associated with an increased risk of nephrolithiasis, particularly in women. The underlying pathophysiology of stone formation in obese patients is thought to be related to insulin resistance, dietary factors, and a lithogenic urinary profile. Uric acid stones and calcium oxalate stones are common in these patients. Use of surgical procedures for obesity (bariatric surgery) has risen over the past two decades. Although such procedures effectively manage obesity-dependent comorbidities, several large, controlled studies have revealed that modern bariatric surgeries increase the risk of nephrolithiasis by approximately twofold. In patients who have undergone bariatric surgery, fat malabsorption leads to hyperabsorption of oxalate, which is exacerbated by an increased permeability of the gut to oxalate. Patients who have undergone bariatric surgery show characteristic 24 h urine parameters including low urine volume, low urinary pH, hypocitraturia, hyperoxaluria and hyperuricosuria. Prevention of stones with dietary limitation of oxalate and sodium and a high intake of fluids is critical, and calcium supplementation with calcium citrate is typically required. Potassium citrate is valuable for treating the common metabolic derangements as it raises urinary pH, enhances the activity of stone inhibitors, reduces the supersaturation of calcium oxalate, and corrects hypokalaemia. Both pyridoxine and probiotics have been shown in small studies to reduce hyperoxaluria, but further study is necessary to clarify their effects on stone morbidity in the bariatric surgery population.
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