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Biomedical subjects

E A Miller

Publications and source records attributed to E A Miller.

At least 19 recordsLinked to original sources

Repeated administration of vasopressin but not epinephrine maintains coronary perfusion pressure after early and late administration during prolonged cardiopulmonary resuscitation in pigs.

BACKGROUND: It is unknown whether repeated dosages of vasopressin or epinephrine given early or late during basic life support cardiopulmonary resuscitation (CPR) may be able to increase coronary perfusion pressure above a threshold between 20 and 30 mm Hg that renders defibrillation successful. METHODS AND RESULTS: After 4 minutes of cardiac arrest, followed by 3 minutes of basic life support CPR, 12 animals were randomly assigned to receive, every 5 minutes, either vasopressin (early vasopressin: 0.4, 0.4, and 0.8 U/kg, respectively; n=6) or epinephrine (early epinephrine: 45, 45, and 200 microg/kg, respectively; n=6). Another 12 animals were randomly allocated after 4 minutes of cardiac arrest, followed by 8 minutes of basic life support CPR, to receive, every 5 minutes, either vasopressin (late vasopressin: 0.4 and 0.8 U/kg, respectively; n=6), or epinephrine (late epinephrine: 45 and 200 microg/kg, respectively; n=6). Defibrillation was attempted after 22 minutes of cardiac arrest. Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after early vasopressin compared with early epinephrine (50+/-4 versus 34+/-3 mm Hg, P<0.02; 42+/-5 versus 15+/-3 mm Hg, P<0.0008; and 37+/-5 versus 11+/-3 mm Hg, P<0. 002, respectively). Mean+/-SEM coronary perfusion pressure was significantly higher 90 seconds after late vasopressin compared with late epinephrine (40+/-3 versus 22+/-4 mm Hg, P<0.004, and 32+/-4 versus 15+/-4 mm Hg, P<0.01, respectively). All vasopressin animals survived 60 minutes, whereas no epinephrine pig had return of spontaneous circulation (P<0.05). CONCLUSIONS: Repeated administration of vasopressin but only the first epinephrine dose given early and late during basic life support CPR maintained coronary perfusion pressure above the threshold that is needed for successful defibrillation.

Animals

Implementation of serum cardiac troponin I as marker for detection of acute myocardial infarction.

BACKGROUND: The goal of this prospective study was to assess whether cardiac troponin I (cTnI) could replace creatine kinase (CK)-MB mass as the serum biochemical marker for detection of acute myocardial infarction (AMI). METHODS AND RESULTS: Over a 3-month period, 327 nonselected, consecutive patients were evaluated for AMI with the use of modified World Health Organization criteria including serial electrocardiographs and CK-MB mass determinations at admission and 6, 12, and 24 hours after admission. cTnI measurements were also made at all time points. Sixty-two (19%) patients were diagnosed with AMI. Diagnostic sensitivity and specificity for peak concentrations were equivalent or better for cTnI (100%; 96.3%) compared with CK-MB (88. 2%; 93.2%) and total CK (73.5%; 84.6%), respectively. cTnI demonstrated 100% negative predictive accuracy for ruling out AMI. Further, cTnI maintained a high diagnostic sensitivity (>94%) up to 96 hours after onset of chest pain compared with CK-MB and total CK (both 50% sensitive) in patients with AMI. However, patients with documented Q-wave infarctions had a significantly longer clearance compared with non-Q-wave infarctions (dagger(1/2) 24.2 vs 7.3 hours, respectively; P <.01). There was a significant (P <.02) positive correlation (r = 0.89) between increasing CK-MB mass and increasing cTnI for AMI specimens. CONCLUSIONS: These findings have strongly supported our clinical implementation of cTnI, replacing CK-MB mass as the preferred marker for detection of AMI.

Biomarkers

Simultaneous augmentation cystoplasty and artificial urinary sphincter placement: infection rates and voiding mechanisms.

PURPOSE: Simultaneous augmentation cystoplasty and artificial urinary sphincter placement have recently been reported to be associated with a high incidence of infection. We reviewed our results to define the infection rate and outline the mechanisms of voiding in our patient population. MATERIALS AND METHODS: A total of 29 patients underwent a simultaneous procedure. The etiology of lower urinary tract disease was exstrophy in 14 patients, myelomeningocele in 10, lipomeningocele in 3, spinal cord injury in 1 and radical retropubic prostatectomy in 1. We used 19 gastric, 5 ileal and 5 colonic intestinal segments. Average followup was 33 months. All patients were followed for a minimum of 2 years. Preoperatively all cases had mechanical bowel preparation and documented sterile urine cultures or treated bacteriuria. RESULTS: Infection developed in 2 patients (6.9%) necessitating artificial urinary sphincter removal at 1 week and 9 months. There were no infections associated with gastrocystoplasty. Clean intermittent catheterization was required in 21 patients, while the remaining 8 voided spontaneously. Of the 8 patients 4 were catheterized at least once daily to monitor residual urine volumes. Of all patients 5 were catheterized with a gastric tube, 5 with an appendicovesicostomy and 14 per urethra. CONCLUSIONS: A simultaneous procedure was associated with an acceptable prosthetic infection rate and gastric segments were associated with the lowest incidence of infection. The minority of patients voided spontaneously. The combination procedure was effective in achieving continence. However, in the future a nonprosthetic means of providing urethral resistance may provide better treatment.

Adolescent

Emigration of New Zealand and Australian physicians to the United States and the international flow of medical personnel.

One in five physicians practising in the US received their initial medical qualifications in another country. Contrary to expectations, a large cadre come from developed nations such as New Zealand and Australia. In particular, these two countries provide a unique prism with which to view the international flow of medical talent. While they differ from developing nations that primarily export physicians without attracting others in return, they are distinguished from importing nations such as the US which rarely export. Our analysis is based on a unique dataset collected from three cross-sectional sources. We found that, compared to post-resident physicians remaining at home, New Zealand medical graduates (NZMGs) and Australian medical graduates (AMGs) in the US are typically older, more likely to be male, more likely to have received their initial medical qualifications from certain schools, less likely to be employed in a public hospital setting, more likely to work in a medical school and more likely to practice in a specialty than primary care. Additional findings show that NZMGs and AMGs in the US are more likely than other US physicians to have established themselves in areas with 50,000 or more people and are therefore more likely to serve a population with sociodemographic characteristics typical of the nation's urban centers. It appears then, that NZMGs and AMGs may be emigrating to the US for educational and professional opportunities that may be unavailable at home. In short, the emigration of NZMGs and AMGs may be an instance of what has come to be called the 'international equity problem' or 'brain drain'. However, losses resulting from the disproportionate migration of New Zealand and Australian physicians to the US may be compensated for by the importation of foreign trained physicians from other nations. Future analysis must be extended to take this facet of the international flow phenomena into account.

Age Factors

Identification of heterochronic mutants in Caenorhabditis elegans. Temporal misexpression of a collagen::green fluorescent protein fusion gene.

The heterochronic genes lin-4, lin-14, lin-28, and lin-29 specify the timing of lateral hypodermal seam cell terminal differentiation in Caenorhabditis elegans. We devised a screen to identify additional genes involved in this developmental timing mechanism based on identification of mutants that exhibit temporal misexpression from the col-19 promoter, a downstream target of the heterochronic gene pathway. We fused the col-19 promoter to the green fluorescent protein gene (gfp) and demonstrated that hypodermal expression of the fusion gene is adult-specific in wild-type animals and temporally regulated by the heterochronic gene pathway. We generated a transgenic strain in which the col-19::gfp fusion construct is not expressed because of mutation of lin-4, which prevents seam cell terminal differentiation. We have identified and characterized 26 mutations that restore col-19::gfp expression in the lin-4 mutant background. Most of the mutations also restore other aspects of the seam cell terminal differentiation program that are defective in lin-4 mutant animals. Twelve mutations are alleles of three previously identified genes known to be required for proper timing of hypodermal terminal differentiation. Among these are four new alleles of lin-42, a heterochronic gene for which a single allele had been described previously. Two mutations define a new gene, lin-58. When separated from lin-4, the lin-58 mutations cause precocious seam cell terminal differentiation and thus define a new member of the heterochronic gene pathway.

Animals

Managed care for elderly people: a compendium of findings.

Although managed care seems to serve well the interests of non-elderly enrollees and their payers, elderly people face more risks. Chronic conditions, multiple problems, and more limited resources make them more vulnerable, whereas multiple payer sources make them more complicated to cover. This synthesis of managed care delivered in Medicare and Medicaid demonstration projects serving elderly beneficiaries shows that managed care plans either select or attract enrollees who suffer fewer frailties than those served in fee-for-service settings, exhibit reluctance to enter rural markets, provide a broad range of elderly-specific services, offer more comprehensive coverage and services, and result in greater perceived access problems, particularly for vulnerable subgroups. Plans operate more cheaply by using fewer resources, even after adjusting for case mix differences. Managed care enrollees tend to be more satisfied with financial and coverage aspects, whereas fee-for-service enrollees report higher satisfaction on other dimensions. In acute care settings, process of care findings were mixed, whereas clinical and self-reported outcome indicators were no better and in some instances worse in managed care. Long-term care enrollees, in the few studies reported, consistently faired worse in both the processes and outcomes of care. These findings suggest that further research on the effects of managed care in its rapidly changing incarnations is needed, particularly with respect to how to improve the quality of acute and long-term care delivered to elderly people and the proper role of government and other key actors in the health care system.

Aged

The incidence of breast cancer following mantle field radiation therapy as a function of dose and technique.

BACKGROUND: There is an increased incidence of breast cancer following mantle field radiation therapy for Hodgkin's disease (HD). We reviewed the experience at the Mallinckrodt Institute of Radiology (MIR) for radiation factors related to the development of breast cancer after mantle field radiation therapy for HD. METHODS: The radiation therapy records of 152 women treated with mantle field irradiation for HD at MIR between 1966-1985 were reviewed for the development of breast cancer and treatment-related factors. All patients had a minimum of 5 years of follow-up. The treatment era (1966-1974 vs. 1975-1985), stage of HD, mediastinal dose, axillary dose, maximum dose from the anterior field (anterior d(max) dose), the anterior-posterior:posterior-anterior (AP:PA) ratio, age at the time of treatment, length of follow-up, and history of splenectomy were analyzed as possible contributing factors for the development of breast cancer. The observed number of breast cancers was compared to the expected number based on age-adjusted incidences from the Connecticut Tumor Registry. RESULTS: Ten breast cancers occurred in the population. Eight involved an upper outer quadrant. In a multivariate analysis, the development of breast cancer was significantly associated with axillary dose. Patients in the early treatment era were at an increased risk for the development of breast cancer due to high anterior d(max) and breast doses from weighting the fields anteriorly on a low energy linear accelerator. The use of current radiation therapy techniques was not related to an increased risk of breast cancer with a median follow-up of 13 years. CONCLUSIONS: A high dose to the axilla and the anterior d(max) point is significantly associated with the development of breast cancer after mantle field irradiation for HD. Efforts to protect the breast from high doses will likely lessen the increased risk of breast cancer in women treated with radiation therapy for HD.

Adolescent

Substratum adhesion and gliding in a diatom are mediated by extracellular proteoglycans.

Diatoms are unicellular microalgae encased in a siliceous cell wall, or frustule. Pennate diatoms, which possess bilateral symmetry, attach to the substratum at a slit in the frustule called the raphe. These diatoms not only adhere, but glide across surfaces whilst maintaining their attachment, secreting a sticky mucilage that forms a trail behind the gliding cells. We have raised monoclonal antibodies to the major cell surface proteoglycans of the marine raphid diatom Stauroneis decipiens Hustedt. The antibody StF.H4 binds to the cell surface, in the raphe and to adhesive trails and inhibits the ability of living diatoms to adhere to the substratum and to glide. Moreover, StF.H4 binds to a periodate-insensitive epitope on four frustule-associated proteoglycans (relative molecular masses 87, 112, and > 200 kDa). Another monoclonal antibody, StF.D5, binds to a carbohydrate epitope on the same set of proteoglycans, although the antibody binds only to the outer surface of the frustule and does not inhibit cell motility and adhesion.

Animals

Improved detection of minor ischemic myocardial injury with measurement of serum cardiac troponin I.

This study compared the diagnostic accuracy of the measurement of serum cardiac troponin I (cTnI) with creatine kinase (CK) MB mass in patients with minor myocardial injury whose measured total CK activity did not exceed twice the upper reference limit (300 U/L for men; 200 U/L for women). Forty-eight consecutive patients presenting with chest pain and with in-hospital documentation of myocardial injury were enrolled. Electrocardiogram, echocardiogram, and serial serum CK-MB mass, cTnI, and total CK were measured over 36 h after admission. Peak total CK activity was within normal limits in 28 patients (58%). The mean (+/- SD) peak CK-MB mass and cTnI concentrations were: 16.4 (11.8) micrograms/L and 132 (13.0) micrograms/L; respectively. The peak biochemical marker index (defined as CK-MB or cTnI divided by its respective upper reference limit) was significantly (P < 0.05) higher for cTnI than for CK-MB from 7 to 36 h. The clinical sensitivity for detection of myocardial injury for cTnI was 100% [95% confidence interval (CI): 87.2% to 100%], compared with 81.8% (CI: 67.3% to 91.8%) for CK-MB. Thus, cTnI was more sensitive than CK-MB mass for detection of myocardial injury in patients with small increases of total CK.

Acute Disease

The effect of environmental odors emanating from commercial swine operations on the mood of nearby residents.

The effect of environmental odors emanating from large-scale hog operations on the mood of nearby residents was determined using the POMS (Profile of Mood States). The scores for six POMS factors and the TMD (total mood disturbance score) for 44 experimental subjects were compared to those of 44 control subjects who were matched according to gender, race, age, and years of education. The results indicated a significant difference between control and experimental subjects for all six POMS factors and the TMD. Persons living near the intensive swine operations who experienced the odors reported significantly more tension, more depression, more anger, less vigor, more fatigue, and more confusion than control subjects as measured by the POMS. Persons exposed to the odors also had more total mood disturbance than controls as determined by their ratings on the POMS. Both innate physiological responses and learned responses may play a role in the impairment of mood found here.

Affect

Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype.

Membrane cofactor protein (MCP) is a complement regulatory protein that is expressed on human cells and cell lines as two relatively broad species with Mr of 58,000-68,000 and 48,000-56,000. The structure of a previously reported cDNA clone indicated that MCP was a type 1 membrane glycoprotein and a member of the regulators of complement activation gene/protein cluster. However, it did not provide an explanation for the unusual phenotypic pattern of MCP. Therefore, in parallel with an analysis of the gene, additional cDNAs were cloned and characterized. Six different MCP cDNA classes were identified. All encode the same 5' untranslated signal peptide, four SCRs, transmembrane domain, and basic amino acid anchor. However, they differ in the length and composition of an extracellular serine/threonine/proline (STP)-rich area, a site of heavy O-glycosylation, and cytoplasmic tail. Analysis of the MCP gene demonstrated that the variation in cDNA structure was a result of alternative splicing. Peripheral blood cells and cell lines predominantly expressed four of the six isoforms. These varied by the presence or absence of an STP-rich segment of 15 amino acids (STPB) and by the use of one of two cytoplasmic domains. Analysis by polymerase chain reaction, Northern blots, and transfection indicated that the predominance of MCP cDNA isoforms with STPB correlated with the high molecular weight protein phenotype, while the predominance of isoforms without STPB correlated with the lower molecular weight phenotype. The expression in a single cell of four distinct protein species with variable STP-rich regions and cytoplasmic tails represents an interesting example of the use of alternative splicing to provide variability in a mammalian protein.

Amino Acid Sequence

Prophylactic ankle bracing.

Many choices are available to athletes seeking an ankle support. The time-honored tradition of ankle taping with adhesive tape does offer protection against ankle sprains during activity. Laced stabilizers offer an equal or possibly greater amount of support, are less costly and easier to apply, and can be retightened frequently during activity. The physician should become familiar with one of these two methods and choose one based on availability and feasibility in the community. The air stirrup may be indicated for patients with a history of ankle injury who are undergoing a graduated rehabilitation program. Nevertheless, the air stirrup has not been shown to provide significantly greater inversion restriction than taping or lace-on braces and is not recommended as a first-line method of support for individuals with no history of recent ankle sprain. High-top shoes are better when the ankle is taped, although low-top shoes are better when a laced stabilizer is worn. Elastic guards help reduce ankle edema but do not provide ankle stability.

Ankle Injuries

A comparison of hypochlorite and phenolic disinfectants for disinfection of clean and soiled surfaces and blood spillages.

Suspension test methods were used to compare phenolic and hypochlorite disinfectants under conditions as recommended for use in hospitals. Using plasma to simulate soiled conditions, Clearsol (1% v/v) and Stericol (2% v/v) produced satisfactory disinfection, (i.e. 5 log reduction in 5 mins against Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa in the presence of up to 50% v/v plasma (25 mg ml-1 plasma protein). Although sodium dichloroisocyanurate (NaDCC) at 2500 ppm AvCl2 was effective in the presence of up to 20% plasma, compared to 10% plasma for sodium hypochlorite 2500 ppm, sensitivity of NaDCC to inactivation was greater than for phenolics. In the presence of blood, both hypochlorites and phenolics were substantially inactivated, although here the effectiveness of NaDCC at 10,000 ppm was equivalent to the phenolics. Our results indicate that hypochlorites at 10,000 ppm, Clearsol 1% and Stericol 2% may be ineffective for treatment of blood spills unless applied at v:v ratios of 9 parts disinfectant to 1 part blood. In this situation, chlorine-releasing powder formulations, which produce higher AvCl2 concentrations and contain spilled material, offer an effective alternative.

Body Fluids

Complications of eyelid reconstruction using a semicircular flap.

Complications of the semicircular flap technique of eyelid reconstruction include lateral canthal webbing, ectropion, lid notching, symblepharon, and tissue fullness of the lateral lid. These difficulties occur infrequently and rarely cause significant problems. Attention to surgical details, however, can minimize unfavorable results. It should be emphasized that the semicircular flap remains a superb technique for reconstruction of defects involving up to 80% of the lower eyelid.

Ectropion

Comparison of L-thyroxine and a saturated solution of potassium iodide in preventing damage to the thyroid following iodine-131-labeled antibody injection.

Following injection of radioiodinated antibodies in diagnostic amounts, there is variable uptake of radioiodine by the thyroid. Unless preventive steps are taken, radiation damage to the gland may occur. We have evaluated the role of L-thyroxine and a saturated solution of potassium iodide (SSKI) in preventing radiation damage to the thyroid glands of Sprague-Dawley adult male rats by measuring DNA strand breakage by the nucleoid sedimentation gradient method. Pretreatment with SSKI reduced DNA damage and also reduced 131I accumulation in the thyroid. Pretreatment with L-thyroxine also reduced DNA damage without significantly reducing 131I accumulation in the thyroid. The possible mechanisms of action of L-thyroxine and SSKI in preventing radiation damage to the thyroid are addressed.

Animals

Radioimmunodetection of implanted tumors with gamma probe.

Tumor uptake of 125I- and 131I-radiolabeled anti-CEA antibodies was compared in female Swiss nude mice, each bearing a CEA-producing human colon adenocarcinoma xenografted in one flank. Counts from the tumor and contralateral flank were recorded with a manipulatable, cadmium-telluride crystal gamma detector at 24, 48, and 72 hours following injection. The animals were killed, and the tumors and other organs were removed, weighed, and then assessed in an automatic gamma counter. The cadmium-telluride counter was more efficient at counting 125I-labeled antibodies than 131I antibodies. The tumor to contralateral flank ratios improved with the use of a monoclonal anti-CEA and polyclonal anti-CEA in combination compared with the single antibodies. The investigation of the external counting characteristics of the portable gamma detector demonstrated the potential of the adjunctive use of intraoperative detection with external radioimmunoscintigraphy for detection and localization of gastrointestinal tumors.

Adenocarcinoma