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Biomedical subjects

E A Ross

Publications and source records attributed to E A Ross.

At least 19 recordsLinked to original sources
PubMed2006

Method for detecting the disconnection of an extracorporeal device using a patient's endogenous electrical voltages.

Tubing (especially venous) disconnections using pumped devices cause significant hemorrhage, and current monitoring techniques are imperfect because they rely on intraluminal pressure changes. We devised a passive detection method based on a patient's electrical voltages being transmitted via blood tubing to our alarm circuit. As the arterial and venous access sites are in close proximity, the signals are nearly identical during connection, and markedly different with disconnection. We built a prototype and tested it in vitro with saline and during hemodialysis treatments (n=7). The connection status is determined by examining the difference between endogenous voltages in the blood tubing from and to the patient, and when it exceeds a threshold an alarm condition is triggered. We tested for possible confounding by an electrical shunt through the dialyzer and determined that pathway had an impedance approximately three times (>350 kOmega) that of the tubing to the patient. As the roller blood-pump periodically occluded the tubing, the resultant intermittent very high impedance prevented that potential shunting problem and improved the sensitivity of our device. Disconnections were detectable at various bloodline sites (needles, sampling ports, drip chambers). Thus, the circuit's sensors can be placed remotely at the dialysis machine, with electrical continuity to blood made by inexpensive conductive elements at the tubing wall or drip chambers. Appropriate threshold and noise-eliminating circuitry, as well as alarm states that alert the staff and stop the blood pump, make our prototype a promising low-cost safety enhancement.

Blood Pressure↗
PubMed2002

Strategy for the treatment of noncompliant hypertensive hemodialysis patients.

Hypertensive hemodialysis patients noncompliant for their medications do not benefit from pharmacologic advances in the treatment of high blood pressure, and increase their already high risk of cardiovascular complications. The medical staff often becomes frustrated by severe hypertension in those who refuse to take medicines at home, drink excessive fluids, miss multiple dialysis sessions and sign-off dialysis early. In addition to addressing the psychosocial, financial, educational and substance abuse problems which contribute to noncompliance, we have developed a medication strategy to serve as an at least interim means of lowering blood pressure. Antihypertensive agents which have long half-lives in renal failure (lisinopril) and/or are intrinsically long acting (transdermal clonidine and amlodipine) were administered on dialysis days by the unit personnel to those patients who did not or would not take that or any dose on their own. The lisinopril and amlodipine were assured to have been taken on at least the dialysis days (thrice weekly), and the clonidine patch replaced weekly. Sixteen patients were thus treated when they failed to reliably self-administer medications. They had a significant decline in the predialysis systolic pressure of 15 mm Hg (175 +/- 6 to 160 +/- 5 mm Hg), diastolic of 12 mm Hg (103 +/- 3 to 91 +/- 3 mm Hg), and mean pressure of 13 mm Hg (127 +/- 4 to 114 +/- 4 mm Hg). There was an improvement in post-dialysis bood pressures, with the mean pressure declining 13 mm Hg from 110 +/- 4 to 97 +/- 4 mm Hg. Many individuals had erratic blood pressure control, having intermittently missed dialysis and hence unit-administered medicine, as well as continued fluid or drug abuse. The patients had uniformly excellent acceptance of this regimen, even spontaneously requesting it, and had no appreciable adverse effects. In summary while noncompliance is being addressed by the entire medical team, dialysis unit administration of long-acting medicines helps many hypertensive dialysis patients who would otherwise be at increased risk for severe cardiovascular complications.

Adult↗
PubMed2001

High mass clearance of autoantibodies from a murine model of lupus nephritis by immunoadsorption using star-configured polyethylene glycols.

The extracorporeal immunoadsorption of antibodies as part of the therapy for human autoimmune diseases has been limited by technology with inadequate and nonselective mass clearance or problems with bioincompatibility. To overcome these shortcomings, we designed a method utilizing star-configured polyethylene glycols (star-PEGs) having up to 63 free arms with immunoreactive (tresylate ester) end-groups for each arm immobilized to a polymer support substrate. The flexibility and length of the arms are thought to allow optimization of epitope presentation and to permit interaction with immunoligands on adjacent arms. To demonstrate efficacy we used an in vitro murine antibody model of human lupus nephritis, wherein we could study the kinetics and mass clearance of hybridoma derived antihistone antibodies from human plasma. Histones were covalently bound to the star-PEG end-groups and the kinetics of antibody adsorption were assessed using a surface plasmon resonance technique. The equilibrium constants of antihistone antibody binding to histone-star-PEGs that were linked to a support grid demonstrated high affinity with a KA of 3.56E + 07 and a KD of 2.81E - 08. The optimum reaction conditions were determined to accomplish the hydrophilization of polysulfone (PS; by an aqueous nitration method) and polymethylmethacrylate substrates (PMMA; by hydrazine), using sheet casts of both polymer substances. Hollow fiber devices of these polymers (commercial hemodialyzers) were modified so that histone-bound star-PEGs were linked to their intracapillary luminal surfaces, using a process which we have shown retains their immunoadsorption properties for antihistone antibodies. A closed loop recirculating model was constructed to measure mass clearance of antibodies from a reservoir. After optimizing conditions using extraction from saline solutions, the removal of antibody from human plasma by control and surface-modified devices was assessed over 4 h. There was no measurable antibody clearance by the control fibers over this time interval. The 2.1 m2 luminal surface area PMMA devices removed 5.0 +/- 1.1 mg, with a maximum of 7.0 mg. The 1.8 m2 PS device cleared 11.3 +/- 6.2 mg with a maximum of 17.5 mg. In summary, star-PEG immunoadsorption is a promising technique for the treatment of human autoimmune disease because it can achieve very high-mass clearance of autoantibodies using modified biocompatible hollow-fiber polymer devices.

Animals↗
PubMed2000

Lead content of calcium supplements.

CONTEXT: Substantial quantities of lead have been reported in some over-the-counter calcium supplement preparations, including not only bone-meal and dolomite, but also over-the-counter natural and refined calcium carbonate formulations. Examination of this issue is warranted given recent increases in physician recommendations for calcium supplements for prevention and treatment of osteoporosis. OBJECTIVES: To determine the lead content of calcium supplements and to quantify the lead exposure from popular brands of calcium in dosages used for childhood recommended daily allowance, osteoporosis, and phosphate binding in dialysis patients. DESIGN AND SETTING: Analysis of lead content in 21 formulations of nonprescription calcium carbonate (including 7 natural [ie, oyster shell] and 14 refined), 1 brand of prescription-only calcium acetate, and 1 noncalcium synthetic phosphate binder conducted in March 2000. MAIN OUTCOME MEASURES: Lead content, assayed using electrothermal atomic absorption, expressed as micrograms of lead per 800 mg/d of elemental calcium, per 1500 mg/d of calcium, and for a range of dosages for patients with renal failure. Six microg/d of lead was considered the absolute dietary limit, with no more than 1 microg/d being the goal for supplements. RESULTS: Four of 7 natural products had measurable lead content, amounting to approximately 1 microg/d for 800 mg/d of calcium, between 1 and 2 microg/d for 1500 mg/d of calcium, and up to 10 microg/d for renal dosages. Four of the 14 refined products had similar lead content, including up to 3 microg/d of lead in osteoporosis calcium dosages and up to 20 microg/d in high renal dosages. No lead was detected in the calcium acetate or polymer products. Lead was present even in some brand name products from major pharmaceutical companies not of natural oyster shell derivation. CONCLUSIONS: Despite increasingly stringent limits of lead exposure, many calcium supplement formulations contain lead and thereby may pose an easily avoidable public health concern. JAMA. 2000;284:1425-1429.

Calcium↗
PubMed2000

Optimization of ligand presentation for immunoadsorption using star-configured polyethylene glycols.

Medical, pharmaceutical, and industrial applications of immunoadsorption are frequently limited by the technologic problems of low affinity, inadequate capacity, hydrophobicity, and bioincompatibility. To overcome these difficulties we studied the use of star-burst configured polyethylene glycols (star-PEGs) with immunoreactive molecules covalently bound to the end of each of the multiple flexible arms. The optimum pH ranges were determined to maintain stability of the tresyl chloride modified star reagents, and the chemistry was designed for their subsequent linkage to the immunoadsorbent moiety. We then devised the chemical reactions using nitration or hydrazine activation to tether these 64-arm structures to polymer supports made of polysulfone or polymethylmethacrylate, respectively. Transmission, scanning, and atomic force microscopy confirmed the preservation of the star configuration, even after linkage to the luminal surface of hollow fiber devices. To establish that these modified devices also maintained immunoadsorption reactivity, we used a model having relevance for human autoimmune disease and demonstrated the clearance of antihistone antibodies by tethered histones. This novel approach to increasing the capacity of immunoadsorption benefits from the star configuration which provides a high density of ligand, improved hydrophilicity of the surface, spacing of reactive molecules away from the support structure, and possible optimization of epitope immunoreactivity by arm-to-arm interaction of the bound molecules.

Adsorption↗
PubMed2000

Use of superficial femoral vein for hemodialysis arteriovenous access.

Maintaining hemodialysis access in the expanding number of patients with end-stage renal disease is a difficult and challenging problem. Published guidelines outline the initial recommendations for hemodialysis access; however, there is little consensus about the most appropriate options for the subset of patients with repeated access failures and/or unsuitable veins. Two case reports are presented describing the use of composite saphenous-superficial femoral vein autogenous accesses placed in the upper and lower extremities. The function of the autogenous accesses appeared to be similar to a mature arteriovenous fistula in the short-term, although further longitudinal studies are required. The superficial femoral vein may be a useful hemodialysis access conduit for patients with limited access options.

Adult↗
PubMed2000

Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience.

Only a minority of patients with a diagnosis of pancreatic adenocarcinoma (PA) have disease amenable to curative resection. Between April 1987 and March 1999, 40 patients with pancreatic adenocarcinoma deemed unresectable at exploration at other institutions were considered for neoadjuvant treatments and then re-evaluated for possible re-exploration. We retrospectively compared the clinical outcomes, including overall survival (OS), among three groups: Group A, 22 previously unresectable patients who were subsequently successfully resected, 20 after induction therapy; Group B, 31 patients who received preoperative chemoradiotherapy before their only operation; and Group C, 33 patients who were primarily resected, 27 of whom were then treated with adjuvant therapy. Of those resectable from Group A, 5 required portal venorrhaphy and 3 had hepatic artery reconstruction. Eighteen of the 40 patients were unresectable because of progression of disease with a mean OS of 8 months; 12 were assessed at second laparotomy; 6 were excluded from second operation on the basis of preoperative imaging studies. Kaplan-Meier curves showed no differences in OS among the three groups: OS in Group A was 34 months; Group B, 21; and Group C, 13 (P = 0.15). Margin status was comparable in all three groups (P = 0.52). As expected, nodal positivity was greatest in Group C (P = 0.001). There were no operative mortalities in Group A, and the morbidity rate was comparable with that of Groups B and C. Upon re-evaluation, many tumors (54%) previously deemed "unresectable" were surgically extirpated for cure with a median survival comparable with that of patients who did not undergo previous exploration.

Adenocarcinoma↗
PubMed1999

Interventional radiology placement of twin Tesio catheters for dialysis access: review of 75 patients.

PURPOSE: To evaluate the safety and efficacy of modern interventional radiology techniques and imaging guidance for placement of jugular vein twin Tesio hemodialysis catheters. MATERIALS AND METHODS: Eighty-two sets (75 patients) of twin Tesio catheters were percutaneously placed in the right (n = 70) and left (n = 12) internal jugular veins with use of ultrasound (US) and fluoroscopic guidance. Immediate procedural and late complications were recorded. The efficacy of the Tesio system was also evaluated. RESULTS: With US and fluoroscopic guidance, the technical success for access and catheter placement was 100%. Measured dialysis blood flow rate of greater than 375 mL/min was obtained in 95% of the patients and recirculation averaged 4.6% +/- 5%. An inadvertent common carotid artery puncture occurred in one (0.6%) patient and prolonged exit site bleeding occurred in another five patients (3%). Each of these was successfully controlled with compression. More chronically, catheter thrombosis and exit site infection occurred each at the rate of 0.16 episodes per 100 catheter days. All thrombosis and exit site infections responded to local thrombolysis and antibiotic therapy, respectively. Bacteremia occurred in 20 patients and required catheter removal in five patients. There was no clinical evidence of upper extremity or superior central vein thrombosis. CONCLUSION: Placement of internal jugular, twin Tesio catheters with use of imaging and interventional techniques provides a safe and efficacious means of either short or long-term hemodialysis.

Adult↗
PubMed1999

Modeling clustered, discrete, or grouped time survival data with covariates.

We have developed methods for modeling discrete or grouped time, right-censored survival data collected from correlated groups or clusters. We assume that the marginal hazard of failure for individual items within a cluster is specified by a linear log odds survival model and the dependence structure is based on a gamma frailty model. The dependence can be modeled as a function of cluster-level covariates. Likelihood equations for estimating the model parameters are provided. Generalized estimating equations for the marginal hazard regression parameters and pseudolikelihood methods for estimating the dependence parameters are also described. Data from two clinical trials are used for illustration purposes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Improved nutrition after the detection and treatment of occult gastroparesis in nondiabetic dialysis patients.

Malnutrition in dialysis patients is of multifactorial etiology and is associated with greatly increased morbidity and mortality. A low serum albumin level is one of the most powerful predictors of death and may persist despite optimization of the dialysis prescription. We retrospectively reviewed our experience in improving nutrition in nondiabetic patients with unexplained hypoalbuminemia. Using radionuclide solid-phase gastric emptying scans, we identified 6 patients who had occult gastroparesis. These patients (one on hemodialysis and five on peritoneal dialysis) were then treated with prokinetic medications (erythromycin elixir or metoclopramide) selected on the basis of their effectiveness in improving the scanning results after being given intravenously. Gastric emptying half-times improved from a median of 122 minutes (range, 95 to >300 minutes; normal, < or = 90 minutes) to 12 +/- 2 minutes (mean +/- SEM). The serum albumin increased from 3.3 +/- 0.04 g/dL to 3.7 +/- 0.08 g/dL at 3 months, with every patient's value higher than 3.5 g/dL. This improvement was statistically significant (P = 0.008) over the 5-month period of observation, which encompassed the 2 months before and 3 months after treatment. There was a linear improvement (P = 0.008) that showed a quadratic trend (P = 0.078) for a plateau at the final sampling point. The serum blood urea nitrogen, creatinine, and hematocrit levels remained unchanged (P > 0.1). We conclude that gastric emptying scans are valuable in identifying occult gastroparesis in high-risk patients and can guide the selection of prokinetic therapy, which may significantly increase serum albumin levels.

Erythromycin↗
PubMed1997

Long-term performance and complications of the Tesio twin catheter system for hemodialysis access.

The Tesio twin catheter system (Medcomp, Harleysville, PA) was developed to overcome the problems with the existing central venous catheters in providing high-efficiency dialysis, such as inadequate blood flows, high recirculation rates, and need for surgical insertion. The relatively large internal lumens and multiple side holes in a spiral pattern allow for high blood flow rates and lower tendency to thrombosis. In this series, 82 catheter pairs were placed in 75 patients and monitored for a period encompassing 231 patient-months. We achieved mean nominal blood pump flow rates of 400 +/- 6 mL/min and an average recirculation of 4.6% +/- 0.5%. In 20 sets of catheters, a nominal blood flow rate of 388 +/- 6 mL/min was measured ultrasonically at 352 +/- 8 mL/min, representing an error of 36 +/- 5 mL/min. Thrombosis of the catheter occurred at a rate of one episode per 21 patient-months, and on all occasions responded to local instillation of urokinase. Despite having two exit sites, the infection rates were comparable to other catheters: exit site infections occurred at a rate of one per 21 patient-months and bacteremic episodes occurred at one per 11.5 patient-months, necessitating catheter removal once per 46 patient-months. Based on these data, we believe that the Tesio twin catheter system is an excellent long- and short-term vascular access for providing high-efficiency dialysis.

Acute Kidney Injury↗
PubMed1997

Low whole blood and erythrocyte levels of glutathione in hemodialysis and peritoneal dialysis patients.

Dialysis patients are reported to have impaired antioxidant mechanisms, including those involving glutathione-dependent enzymes. This study used high-performance liquid chromatography assays that directly measure total (oxidized + reduced) glutathione and its precursor cysteine (CYS) to compare the whole blood of hemodialysis (prehemodialysis and posthemodialysis) and peritoneal dialysis patients to that of blood donors with no known kidney disease (n=20 in each group). The levels in erythrocytes were calculated from that data (as nmol/g hemoglobin) because these cells are the major compartment of blood glutathione and their survival may be shortened by oxidant damage. Both dialysis groups had significantly (P=0.0001) higher CYS levels in the plasma compartment than the controls (251 nmol/mL), with prehemodialysis levels (432 nmol/mL) being greater than peritoneal dialysis levels (334 nmol/mL). Hemodialysis acutely lowered CYS levels (215 nmol/mL) below those of controls. Expressed per milliliter whole blood, both dialysis groups had significantly (P=0.0001) lower glutathione levels than controls (1,276 nmol/mL), with prehemodialysis and peritoneal dialysis levels being similar (778 and 912 nmol/mL). Values increased prehemodialysis to posthemodialysis, consistent with hemoconcentration. Expressed per gram hemoglobin, the dialysis groups had significantly (P < 0.015) lower glutathione levels than the controls (8,938 nmol/g hemoglobin), with similar prehemodialysis, posthemodialysis, and peritoneal dialysis values (7,207, 7,315, and 7,915 nmol/g hemoglobin, respectively). In summary, hemodialysis and peritoneal dialysis patients are at increased risk from oxidative stress due to glutathione deficiency in whole blood and erythrocytes.

Adult↗
PubMed1997

Employee response to a company-sponsored program of colorectal and prostate cancer screening.

Studies done in the mid-1970s documented increased risk for respiratory cancer and leukemia among employees in a chemical company manufacturing plant where chloromethyl ethers were used in production from 1948 to 1971. In the late 1980s, the company informed current and former employees about the results of follow-up studies which showed a moderation of risk of respiratory cancer and leukemia. New data showing elevated rates of mortality from colorectal, prostate, bladder, and pancreatic cancer in the population were also reported. Via mailed correspondence, the company made a no-cost program of colorectal and prostate cancer screening available to employees upon request; and information about bladder and pancreatic cancer was made available. Thirteen percent of employees in the population indicated interest in colorectal and prostate cancer screening (response). Thirty-one percent of these responders were screened (adherence). Multivariate analyses showed that education and length of employment in the plant were positively associated with response. Being white was positively associated with response for younger workers; while among older workers being male was positively associated with response. In terms of adherence, we found that older, more highly educated workers were more likely to have a screening examination. Findings indicate that employee participation in workplace-sponsored colorectal and prostate cancer screening can vary according to worker sociodemographic factors and length of employment in areas of potential exposure.

Age Factors↗
PubMed1996

Mast cells process bacterial Ags through a phagocytic route for class I MHC presentation to T cells.

The pivotal role of mast cells in allergic reactions and inflammatory processes is well established and recent studies have suggested that mast cells may also have a role in specific immune responses. Because mast cells have been shown to phagocytose and kill enterobacteria, we wished to determine whether they could also process bacterial Ags for presentation to T cells. Using a model system in which a well-characterized T cell epitope is expressed within bacteria as a fusion protein, we demonstrate in this paper that mast cells are indeed capable of processing bacterial Ags for presentation through class I MHC molecules to T cell hybridomas after phagocytic uptake of live bacteria. Processing occurs from a number of Gram-negative enterobacteria including Salmonella typhimurium and Escherichia coli. Parallel assays show that processing of the model Ag from enterobacteria by mast cells is similar in efficiency to processing by peritoneal macrophages. Consistent with earlier observations demonstrating a function of the bacterial fimbrial protein FimH in promoting bacterial binding to mast cells, the magnitude of the Ag processing response of E. coli is influenced by bacterial expression of FimH. Taken together, these observations extend the range of cell types capable of the phagocytic pathway of Ag processing and suggest that mast cells may have a previously unrecognized role in the induction of specific immune responses to bacteria.

Adhesins, Bacterial↗
PubMed1996

Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk.

Despite the fact that breast cancer is the most common non-cutaneous cancer and a leading cause of cancer deaths in women, accepted markers of breast cancer risk miss up to 40% of these tumors. Moreover, screening methods involving the analysis of tissue or cells are limited by the need for a surgical biopsy. Nipple aspiration is a quick, efficient, noninvasive method to obtain breast epithelial cells, the cells at risk for transformation to carcinoma. Prostate-specific antigen (PSA), a protein thought to be specific to the prostate but recently found in a subset of breast tumors, has been correlated with improved survival. The purpose of this study was to measure PSA in a group of women with increasing breast cancer risk (no risk or family history of breast cancer, precancerous mastopathy, and invasive cancer) and determine if PSA correlates with risk. Nipple aspirate fluid was obtained from the intact breast and from surgical specimens using a modified breast pump. PSA was then measured in the fluid using a highly sensitive and specific immunofluorometric procedure. PSA was found at levels ranging from 0-13,423 ng/g of total protein, and there was a significant relationship between PSA level and breast cancer risk (P = 0.001). That is, all women with no risk factors and 90% of those with a family history had high PSA levels, whereas 68% of subjects with precancerous mastopathy or invasive cancer had low PSA levels. PSA was higher in premenopausal subjects (P = 0.002). After adjusting for the effect of menopausal status, there remained a significant association between PSA and breast cancer risk. These findings suggest that PSA in nipple aspirate fluid may be a useful marker of breast cancer risk.

Adult↗