A method for studying inhibitory activity in whole urine

Summary A method has been developed for inducing and quantifying calcium oxalate crystallisation in whole human urine. The propensity of a given urine to induce crystal formation was described in two ways: 1) its ability to resist spontaneous nucleation of calcium oxalate crystals was assessed by titrating 20 mls of the urine with increasing quantities of sodium oxalate (0–150 mol) to determine its practical metastable limit. This limit was inversely related to the endogenous calcium concentration. 2) its capacity to inhibit crystal growth was quantified by determining the rate of growth of calcium oxalate crystals precipitated in response to a fixed oxalate load (30 mol) above its metastable limit. The crystals produced were predominantly calcium oxalate dihydrate and were morphologically identical to those occurring naturally in urine. Citrate had no effect on the metastable limits of 3 urines examined, but markedly inhibited crystal growth. Pyrophosphate had a similar effect on crystal growth, and in addition, raised the metastable limit of one of the urine samples.     

Paramagnetic macrocyclic complexes as contrast agents for MR imaging: proton nuclear relaxation rate enhancement in aqueous solution and in rat tissues

Paramagnetic macrocyclic chelates show promise as magnetic resonance (MR) imaging contrast agents due to stability and relaxivity comparable to those of DTPA-type chelates. For the three copper and manganese macrocyclic complexes studied in aqueous solution, T1 and T2 relaxivities ranged from 0.14 to 5.88 mM-1sec-1 at 6.25 MHz. In rats, the intravenous administration of 16 mumol/kg of Mn(cyclam) caused the liver T1 relaxation rate to double at 15 minutes after injection. T1 measurements by pulsed MR imaging and manganese analyses on excised tissue showed that both relaxation rate (1/T1) and manganese content of liver and kidney increase linearly with the dosage of Mn(cyclam). The linear relationship between 1/T1 and manganese content can be considered an "in tissue" relaxivity plot for the agent. The resulting relaxivity is 54 mM-1sec-1 in liver, compared with 3.1 mM-1sec-1 in aqueous solution. Although this work is preliminary, the implication for medical MR imaging applications is that macrocyclic contrast agents can be effective at approximately one-tenth the current typical dose used for gadolinium DTPA.     

Human cognitive function following binedaline (50 mg and 100 mg) and imipramine (75 mg): Results with a new battery on tests

Rats were made diazepam dependent by chronic treatment with daily injections of the drug, 20 mg/kg, IP, for 3 weeks. On abrupt termination of the drug, the animals showed withdrawal hyperactivity which was indicated by increased horizontal locomotion and vertical activity, and diarrhoea. The peak effect was seen 3 days after the withdrawal of diazepam. Effects of various alpha₂ agonists, clonidine, guanfacine and B-HT 920, were studied on the diazepam withdrawal phenomena. Clonidine (100 g/kg, IP) given twice a day at an interval of 12 h prevented both withdrawal-induced hyperactivity and diarrhoea. On the contrary, equimolar doses of guanfacine and B-HT 920 failed to reverse withdrawal-induced hyperactivity but attenuated the effect of diarrhoea. However, higher doses (500 g/kg, IP) of guanfacine and B-HT 920 given twice a day at 12-h intervals were found to be effective. Pretreatment with yohimbine (1.5 mg/kg, IP) reversed the protective effect of clonidine, indicating the involvement of alpha₂ receptors in the action of clonidine.     

Cumulative renal tubular damage associated with cisplatin nephrotoxicity

Summary We assessed the acute and chronic effect of multiple courses of cisplatin therapy on renal tubules by monitoring the urinary excretion of alanine aminopeptidase, N-acetyl--D-glucosaminidase, and total protein. Urine specimens were obtained before and after doses of cisplatin (90 mg/m²) given to 12 patients. Each dose of cisplatin induced transient increases in enzyme excretion, followed by proteinuria 3–5 days later. Transient enzymuria after the last cisplatin dose was significantly greater than that after the first dose. Moreover, persistent increases in urinary N-acetyl--D-glucosaminidase and serum creatinine concentrations over pretherapy levels indicated chronic renal tubular damage. Our findings disclosed striking differences between patients in susceptibility to progressive nephrotoxicity.Supported by Biomedical Research Support Grant RR05584 (MPG), Cancer Center Support Grant (CORE) CA-21765, Chilhood Solid Tumor Program Project Grant CA-23099 and the American Lebanese Syrian Associated Charities (ALSAC)     

An Update on Omega-3 Polyunsaturated Fatty Acids and Cardiovascular Health

Interest in the potential cardiovascular (CV) benefits of omega-3 polyunsaturated fatty acids (Ω-3) began in the 1940s and was amplified by a subsequent landmark trial showing reduced CV disease (CVD) risk following acute myocardial infarction. Since that time, however, much controversy has circulated due to discordant results among several studies and even meta-analyses. Then, in 2018, three more large, randomized trials were released—these too with discordant findings regarding the overall benefits of Ω-3 therapy. Interestingly, the trial that used a higher dose (4 g/day highly purified eicosapentaenoic acid (EPA)) found a remarkable, statistically significant reduction in CVD events. It was proposed that insufficient Ω-3 dosing (<1 g/day EPA and docosahexaenoic acid (DHA)), as well as patients aggressively treated with multiple other effective medical therapies, may explain the conflicting results of Ω-3 therapy in controlled trials. We have thus reviewed the current evidence regarding Ω-3 and CV health, put forth potential reasoning for discrepant results in the literature, highlighted critical concepts such as measuring blood levels of Ω-3 with a dedicated Ω-3 index and addressed current recommendations as suggested by health care professional societies and recent significant scientific data.     

Gestational Women’s Perceptions About the Harms of Cigarette and E-Cigarette Use During Pregnancy

Objectives

The purpose of this study was to examine differences between perceived harm of cigarette and electronic cigarette (e-cigarette) use while pregnant and differences between healthcare providers’ communication about these products during pregnancy.

Methods

A convenience sample of gestational women (n?=?218; ages 18–45) living in the US completed an online survey between May and December 2017. Participants reported perceived likelihood of adverse health outcomes (e.g., low birth weight, sudden infant death syndrome) among infants/children born to mothers who used cigarettes/e-cigarettes. T-tests and two-way ANOVAs examined differences between risk perceptions of using cigarettes/e-cigarettes while pregnant based on pregnancy status (previously pregnant, currently pregnant, future pregnant). Chi-square analyses examined differences between healthcare provider communication about cigarette/e-cigarette use during pregnancy.

Results

Overall, participants believed adverse health outcomes were significantly more likely to be caused by maternal use of cigarettes than e-cigarettes. Participants who planned to be pregnant reported higher endorsement that smoking combustible cigarettes would cause a miscarriage (p?<?.05) or increased blood pressure (p?<?.05) for a child than currently pregnant participants. Participants reported healthcare providers asked about (p?<?.05), advised them not to use (p?<?.001), and talked to them about health effects of smoking combustible cigarettes while pregnant (p?<?.001) significantly more than e-cigarettes.

Conclusions for Practice

Healthcare providers working with pregnant women should perform the 5As behavioral intervention method to provide pregnant women with tobacco cessation care. They should also discuss the absolute harm nicotine exposure (via cigarettes or e-cigarettes) can have on fetal health and development.

     

Non-Hispanic Blacks undergoing distal pancreatectomy have higher risk-adjusted rates of morbidity and are more likely to be high-cost outliers

BackgroundFew studies evaluate racial disparities in costs and clinical outcomes for patients undergoing distal pancreatectomy (DP).MethodsWe queried the Healthcare Cost and Utilization Project State Inpatient Databases to identify patients undergoing DP. Multivariable regression (MVR) was used to evaluate the association between race and postoperative outcomes.Results2,493 patients underwent DP; 265 (10%) were black, and 221 (8%) were of Hispanic ethnicity. On MVR, black and Hispanic patients were less likely than whites to undergo surgery in high volume centers (OR 0.53, 95% CI [0.40, 0.71]; OR 0.45, 95% CI [0.32, 0.62]). Black patients had a greater risk of postoperative complication (OR 1.40, 95% CI [1.07, 1.83]), 90-day readmission (OR 1.53, 95% CI [1.15, 2.02]), prolonged length of stay (OR 1.74, 95% CI [1.25–2.44]), and of being a high cost outliers (OR 1.40, 95% CI [1.02, 1.91]) compared to white patients.ConclusionBlack patients have increased risk of having a postoperative complication, prolonged hospitalization, and of being a high-cost outlier than non-Hispanic whites.     

Positive microscopic surgical margins: Is there an association with survival in resected small gastrointestinal stromal tumors?

BackgroundFew studies evaluate the relationships between surgical approach, histologic margin, and overall survival in gastrointestinal stromal tumor. We test the hypothesis that margin positive resection is associated with compromised overall survival.MethodsWe queried the National Cancer Data Base to identify patients undergoing resections for gastrointestinal stromal tumors ≤3 cm in size between 2010 and 2015. Multivariable logistic regression was used to identify factors associated with positive microscopic margins on final pathology. Cox proportional hazard methods were used to evaluate factors associated with overall survival.Results2064 patients met inclusion criteria; 135 (6.5%) had a microscopically positive surgical margin. On multivariable regression, minimally invasive approach was not associated with risk of a positive margin (OR 1.06 95% CI [0.71, 1.59]). On Cox analysis, positive margin status was not associated with OS (R1: 1.03, CI [0.46–2.31], reference R0).ConclusionsPositive microscopic surgical margins are not associated with compromised overall survival in patients undergoing resection of small gastrointestinal stromal tumors. Minimally invasive surgical approaches do not compromise oncologic outcomes in these cases.     

The importance of the margin of resection and external radiation in non-lipomatous retroperitoneal sarcoma

BackgroundPrior studies evaluating the impact of adjuvant or neoadjuvant radiation on clinical outcomes of patients with non-lipomatous retroperitoneal sarcoma have been underpowered.MethodsWe queried the National Cancer Database to identify patients undergoing surgical resection of retroperitoneal sarcoma with non-lipomatous histology from 2004 to 2016. Multivariable logistic regression and Cox proportional hazards modelling with patients stratified by tumor size were used to identify factors associated with overall survival.Results3,394 patients met inclusion criteria. 592 had small (<5 cm), 1,186 had intermediate (5–10 cm), and 1,616 had large (>10 cm) tumors. Use of either neoadjuvant or adjuvant radiotherapy was associated with improved survival for patients with intermediate (neoadjuvant HR 0.67, CI [0.46, 0.98]; adjuvant HR 0.61, CI [0.50, 0.76]) and large (neoadjuvant HR 0.50, CI [0.37, 0.68]; adjuvant HR 0.56, CI [0.47, 0.69]) tumors, while adjuvant radiation therapy was associated with a survival benefit for small-sized tumors (HR 0.67, CI [0.46, 0.99]).ConclusionsRadiation therapy is associated with an overall survival benefit in patients presenting undergoing resection of non-lipomatous retroperitoneal sarcoma.     

Unhealthy alcohol and drug use is associated with an increased length of stay and hospital cost in patients undergoing major upper gastrointestinal and pancreatic oncologic resections

BackgroundFew studies evaluate the impact of unhealthy alcohol and drug use on the risk and severity of postoperative outcomes after upper gastrointestinal and pancreatic oncologic resections.MethodsThe National Inpatient Sample was queried to identify patients undergoing total gastrectomy, esophagectomy, total pancreatectomy, and pancreaticoduodenectomy between 2012 and 2015. Unhealthy alcohol and drug use was assessed by the International Classification of Diseases, Ninth Revision, and National Inpatient Sample coder designation. Multivariable regression was used to identify associations between alcohol and drug use and postoperative complication, duration of stay, hospital cost, and mortality.ResultsIn the study, 59,490 patients met inclusion criteria; 2,060 (3.5%) had unhealthy alcohol use; 1,265 (2.1%) had unhealthy drug use. Postoperative complication rates were higher in patients with alcohol and drug use than in abstainers (67.5% vs 62.8% vs 57.2%; P < .01). On multivariable regression, alcohol use was independently associated with increased risk of a nonwithdrawal complication (odds ratio 1.33 [1.05, 1.68]), and alcohol and drug use were independently associated with increased length of stay (1.54 [0.12, 2.96]) and 2.22 [0.90, 3.55] days) and cost ($5,471 [$60, $10,881] and $4,022 [$402, $7,643]), but not mortality.ConclusionUnhealthy substance use is associated with increased rates of postoperative complications, prolonged length of stay, and costs in patients undergoing major upper gastrointestinal and pancreatic oncologic resections. Screening and abstinence interventions should be incorporated into the preoperative care pathways for these patients.