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Biomedical subjects

E R Johnson

Publications and source records attributed to E R Johnson.

At least 37 records · Page 2Linked to original sources

Destabilization of peptide binding and interdomain communication by an E543K mutation in the bovine 70-kDa heat shock cognate protein, a molecular chaperone.

We have compared 70-kDa heat shock cognate protein (Hsc70) isolated from bovine brain with recombinant wild type protein and mutant E543K protein (previously studied as wild type in our laboratory). Wild type bovine and recombinant protein differ by posttranslational modification of lysine 561 but interact similarly with a short peptide (fluorescein-labeled FYQLALT) and with denatured staphylococcal nuclease-(Delta135-149). Mutation E543K results in 4. 5-fold faster release of peptide and lower stability of complexes with staphylococcal nuclease-(Delta135-149). ATP hydrolysis rates of the wild type proteins are enhanced 6-10-fold by the addition of peptide. The E543K mutant has a peptide-stimulated hydrolytic rate similar to that of wild type protein but a higher unstimulated rate, yielding a mere 2-fold enhancement. All three versions of Hsc70 possess similar ATP-dependent conformational shifts, and all show potassium ion dependence. These data support the following model: (i) in the presence of K+, Mg2+, and ATP, the peptide binding domain inhibits the ATPase; (ii) binding of peptide relieves this inhibition; and (iii) the E543K mutation significantly attenuates the inhibition by the peptide binding domain and destabilizes Hsc70-peptide complexes.

Adenosine Triphosphate↗

Potential economic impact of glycoprotein IIb-IIIa inhibitors in improving outcomes of patients with acute ischemic coronary syndromes.

Despite the institution of various cost control measures in the 1980s, healthcare costs have continued to rise. Following the adoption of the Medicare prospective payment system, the Health Care Financing Administration (HFCA) recognized the need to assess medical effectiveness as well as the cost of care. Coronary artery bypass graft (CABG) and percutaneous transluminal coronary angioplasty (PTCA) procedures have been reported as the primary cost drivers in hospitalized patients with unstable angina, a form of acute ischemic coronary syndromes. Evaluation of glycoprotein IIb-IIIa inhibitors as primary therapy for these patients suggests that good value for money is possible, especially if the use of these agents results in a reduction in revascularization procedures.

Angina, Unstable↗

Fifty years of plutonium exposure to the Manhattan Project plutonium workers: an update.

Twenty-six white male workers who did the original plutonium research and development work at Los Alamos have been examined periodically over the past 50 y to identify possible health effects from internal plutonium depositions. Their effective doses range from 0.1 to 7.2 Sv with a median value of 1.25 Sv. As of the end of 1994, 7 individuals have died compared with an expected 16 deaths based on mortality rates of U.S. white males in the general population. The standardized mortality ratio (SMR) is 0.43. When compared with 876 unexposed Los Alamos workers of the same period, the plutonium worker's mortality rate was also not elevated (SMR = 0.77). The 19 living persons have diseases and physical changes characteristic of a male population with a median age of 72 y (range = 69 to 86 y). Eight of the twenty-six workers have been diagnosed as having one or more cancers, which is within the expected range. The underlying cause of death in three of the seven deceased persons was from cancer, namely cancer of prostate, lung, and bone. Mortality from all cancers was not statistically elevated. The effective doses from plutonium to these individuals are compared with current radiation protection guidelines.

Aged↗

Economic analysis of adjuvant interferon alfa-2b in high-risk melanoma based on projections from Eastern Cooperative Oncology Group 1684.

PURPOSE: Interferon alfa-2b (IFN) in a randomized clinical trial (E1684) prolonged relapse-free and total survival in high-risk resected melanoma. However, the costs and toxicities of IFN are barriers to its widespread use. This study was undertaken to analyze the projected costs and long-term benefits of IFN by combining prospectively collected data on IFN actual dosage, time of recurrence, and survival with secondary data on long-term melanoma recurrence risks to project the cost-effectiveness of adjuvant IFN compared with observation. PATIENTS AND METHODS: Two hypothetical cohorts of 50-year-old melanoma patients whose mean IFN dosage and clinical results were directly taken from E1684 were included in the study. Melanoma recurrence risks beyond 5 years were derived from international databases. Melanoma recurrence care costs and quality-of-life adjustments, when considered, were based on expert consensus. End points were incremental costs, life-years gained, and cost per life-year gained with and without quality-of-life adjustments. RESULTS: The IFN cohort was projected to have an increased (undiscounted) survival of 0.52 years at 7 years and 1.90 years over a lifetime. The projected incremental cost (in 1996 United States dollars) per life-year gained in the IFN cohort ranged from $13,700 after 35 years to $32,600 at 7 years, the median follow-up of E1684. Using assigned quality-of-life values for IFN and recurrence, the lifetime cost per quality adjusted life-year increased to $15,200. Even if treatment costs for recurrence were excluded, the lifetime incremental cost per life-year gained was $21,600. CONCLUSION: The cost and toxicity of IFN must be balanced against its projected benefits in high-risk melanoma. The derived cost-effectiveness and cost-utility ratios for IFN were comparable to other cancer interventions for which cost-effectiveness analysis has been performed.

Cost-Benefit Analysis↗

Interactions between mivacurium, rocuronium, and vecuronium during general anesthesia.

This study was designed to examine the interactions between mivacurium and rocuronium or vecuronium when administered during a standardized anesthetic technique. Seventy healthy women undergoing abdominal hysterectomy procedures with a standardized thiopental-sufentanil-desflurane-nitrous oxide anesthetic technique were randomly assigned to one of seven treatment groups (10 patients each). After a tracheal intubating dose of vecuronium 100 micrograms/kg (Groups 1 and 2), rocuronium 600 micrograms/kg (Groups 3 and 4), or mivacurium 250 micrograms/kg (Groups 5, 6, and 7), patients received vecuronium, 25 micrograms/kg (Groups 1 and 6), rocuronium 150 micrograms/kg (Groups 3 and 7), or mivacurium 50 micrograms/kg (Groups 2, 4, and 5) for maintenance of neuromuscular blockade. Neuromuscular function was assessed using electromyography, with a train-of-four mode of stimulation at the wrist every 10 s. The clinical duration (time for T1 to return to 25% of baseline) of the maintenance dose of mivacurium was significantly longer after an intubating dose of rocuronium (40 +/- 8 min) and vecuronium (28 +/- 6 min) than after mivacurium (12 +/- 3 min). The clinical duration of maintenance doses of vecuronium (18 +/- 6 min) and rocuronium (13 +/- 2 min) were significantly shorter after an intubating dose of mivacurium than that after an intubating dose of vecuronium (30 +/- 5 min) or rocuronium (42 +/- 12 min), respectively. These data suggest that with consecutive administration of neuromuscular blocking drugs, the initial duration of action depends more on the kinetics of the first neuromuscular blocking drug than the subsequent drug. Thus, there appears to be no clinical advantage in using mivacurium for maintenance of neuromuscular blockade after initial administration of rocuronium or vecuronium.

Adult↗

Genetic improvement in beef cattle using a progeny testing system based on carcase merit.

A progeny testing system to measure beef carcase merit, the Abtech Test, has been developed. Nine carcase characteristics are measured objectively at a slaughter age of 300 days on the carcases of 12 steer progeny per sire. Five carcase characteristics were used to quantify the carcase, namely, carcase composition as submitted, carcase composition (adjusted to 20% total carcase fat), estimated lean meat yield (adjusted to 20% total carcase fat), muscle-bone ratio (adjusted to a common muscle plus bone weight), and eye muscle volume index (adjusted for total carcase muscle weight). Four carcase measurements used to describe quality were evaluated: eye muscle area at the 10th rib (adjusted for total carcase muscle weight), marbling of the eye muscle at the 10th rib (chemically determined and adjusted to 20% total carcase fat), muscle texture at the 10th rib (mean muscle bundle diameter) and fat colour (determined on intermuscular fat at the 10th rib under standard conditions). It is proposed that this testing system could be used for the genetic improvement of beef carcases.

Animals↗

Beef carcase characteristics that may be of value in selecting for genetic merit.

Commercially important carcase characteristics that may be used for the genetic improvement of Australia's beef cattle were evaluated using, predominantly, published data. Conclusions are based on the relationship of carcase measurements to the anatomical and commercial dissection products of 690 sides of beef and on other Australian and overseas work. Many measurements used as the basis for genetic selection are cost-effective but unlikely to lead to significant genetic gain. Some of the cost-effective measurements chosen will confound and impede genetic change. The commonly used saleable beef yield varies so widely in composition because of fat content that it is unlikely to be a reliable measurement for genetic purposes. Because of its homogeneous composition, estimated lean meat yield (muscle), which is seldom used for descriptive purposes in the cattle and beef industries, is a much more reliable measure of genetic merit than saleable beef yield. Eye muscle area, used alone or in conjunction with carcase weight and fat thickness, is of limited value in quantifying muscle, particularly in carcases of similar size. Butt profile, which is strongly influenced by subcutaneous fat deposits, is often negatively associated with beef yield. Subjective muscle score, assessed by competent muscle scorers, when used alone or together with carcase weight and fat thickness did not improve the estimation of saleable beef yield. A second subcutaneous fat thickness measurement generally does not improve upon the accuracy of a single fat thickness measurement for quantifying carcase muscle. Specific breed equations give significant improvements in the prediction of carcase muscle and should be used where possible. For meat quality characteristics, visual marbling score is so poorly correlated with actual marbling fat as to be of no practical value for genetic improvement. Tenderness measurements, because of their low variation between breeds and their susceptibility to slaughter and chilling stresses cannot be used for genetic selection.

Animals↗

Effect of preincision versus postincision infiltration with bupivacaine on postoperative pain.

STUDY OBJECTIVE: To compare the efficacy of preincision wound infiltration with bupivacaine to wound infiltration at the end of the operation. DESIGN: A prospective, randomized, double-blind study. SETTING: University medical center. PATIENTS: 56 ASA status I and II women scheduled for abdominal hysterectomy were randomly assigned to one of three treatment groups. INTERVENTIONS: Group 1 (control) received no local anesthetic infiltration. Group 2 received subcutaneous infiltration with 40 ml of bupivacaine 0.5% (pH 6.9) 15 minutes prior to incision. Group 3 received wound infiltration with a similar solution at the end of surgery. Anesthesia was induced with thiopental 3.0 mg/kg i.v., droperidol 50 micrograms/kg i.v., and sufentanil 0.5 microgram/kg i.v. and maintained with nitrous oxide 67% in oxygen and sufentanil 0.1 microgram/kg IV boluses as required. Postoperative pain was treated with morphine via a patient-controlled analgesia delivery system for 24 hours, followed by oral hydrocodone for 3 days. MEASUREMENTS AND MAIN RESULTS: The opioid consumption was recorded for 4 days postoperatively. Pain scores were measured at 4 to 8-hour intervals using 100 mm visual analog scales. There was no difference in either the opioid analgesic requirements or the pain scores between the three study groups. CONCLUSIONS: Wound infiltration, either preincision or postincision, had no clinically significant effect on the pain scores or analgesic requirements following abdominal hysterectomy.

Adult↗

Cefazolin is inferior to cefotetan as single-dose prophylaxis for women undergoing elective total abdominal hysterectomy.

The purpose of this prospective, randomized, double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy. A major operative site infection requiring parenteral antimicrobial therapy developed in 46 (9%) of 511 evaluable women: 30 (11.6%) of 258 women given cefazolin prophylaxis and 16 (6.3%) of 253 women given cefotetan prophylaxis (relative risk, 1.84; 95% confidence interval, 1.03 to 3.29; P < .05). Risk factors for major operative site infection were younger age, lower postoperative hemoglobin concentration, and a proliferative endometrium. Ten (3.9%) of 258 women given cefazolin prophylaxis had a postoperative pelvic abscess; two of these women required additional surgical procedures, compared with two (0.8%) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery (relative risk, 4.9; 95% confidence interval, 1.09 to 22.16; P = .04). A greater number of infections and more serious infections occurred following cefazolin prophylaxis; this treatment resulted in 234 additional hospital days for administration of parenteral antimicrobial therapy.

Adult↗

Use of the laryngeal mask airway after oesophageal intubation.

We have compared insertion of a tracheal tube and laryngeal mask airway (LMA) both with and without the presence of a tube in the oesophagus in 20 ASA I and II patients undergoing elective laparoscopy. After induction of anaesthesia and neuromuscular block, we measured the times for an experienced anaesthetist to correctly position both an LMA and a tracheal tube with and without a tube in the oesophagus. The time to intubation was significantly less with the LMA than with the tracheal tube, both with and without an oesophageal tube in place (P < 0.05). We conclude that if a tracheal tube is placed unintentionally in the oesophagus, an LMA may be used subsequently to provide rapid and effective oxygenation of the patient.

Adolescent↗

Mortality through 1990 among white male workers at the Los Alamos National Laboratory: considering exposures to plutonium and external ionizing radiation.

A cohort mortality study was conducted of 15,727 white men employed by the Los Alamos National Laboratory, a nuclear research and development facility. Some of the workers at this facility have been exposed to various forms of ionizing radiation and other potentially hazardous materials. These analyses focused on whole-body ionizing radiation exposures and internal depositions of plutonium. The results indicated that overall mortality among this cohort is quite low, even after nearly 30 y of follow-up. No cause of death was significantly elevated among plutonium-exposed workers when compared with their unexposed coworkers; however, a rate ratio for lung cancer of 1.78 (95% CI = 0.79-3.99) was observed. A case of osteogenic sarcoma, a type of cancer related to plutonium exposure in animal studies, was also observed. Dose-response relationships for whole-body dose from external ionizing radiation and tritium were observed for cancers of the brain/central nervous system, the esophagus, and Hodgkin's disease.

Cohort Studies↗

Kinematic pharyngeal transit times in myopathy: evaluation for dysphagia.

Measurement of kinematic pharyngeal transit times, a new videofluoroscopy technique, provides useful quantitative data to supplement the qualitative data previously available from videofluoroscopy swallowing studies. Kinematic pharyngeal transit times have not previously been reported for subjects with myopathy. This study demonstrates the use of quantitative kinematic pharyngeal transit times for dysphagia evaluation in 15 patients with myopathy. The successful treatment of dysphagia by cricopharyngeal myotomy is reported in two patients with limb-girdle syndrome.

Adult↗

Aspiration pneumonia in stroke.

Aspiration pneumonia developed within 1 year in 29 of 60 stroke patients referred for videofluoroscopic evaluation of poststroke dysphagia and drawn from a total population of 304 acute stroke patients. The presence of vallecular pooling, piriform pooling, or bolus penetration to or through the true vocal cords on videofluoroscopy did not correlate with the development of aspiration pneumonia. Kinematic pharyngeal transit times did show a significant correlation with the development of aspiration pneumonia (time of first movement, p = .038; time of arrival of bolus at valleculae, p = .0008; time of return of epiglottis to resting position, p = .0001). Those patients with total kinematic pharyngeal transit times (Em) of less than 2.00 sec were at little or no risk for aspiration pneumonia (0%), those with 2.01 to 5.00sec at moderate risk (38.5%), and those with more than 5.00sec were at marked risk (90%).

Cerebrovascular Disorders↗

Contractures in neuromuscular disease.

The percentage of subjects with contractures, mean maximal loss of range, and relative contracture indices are reported in 230 patients, with 11 diseases seen in a neuromuscular disease clinic during a five-year period. The highest percentage of contractures occurred in patients with Duchenne muscular dystrophy. The number of contractures was significantly greater (p less than .001) (1) in the lower than in the upper extremities; (2) in diseases considered myopathic than in those considered neuropathic; (3) in diseases that are X-linked than in those that are not; and (4) in rapidly progressive than in slowly progressive diseases.

Adolescent↗

Dysphagia following stroke: quantitative evaluation of pharyngeal transit times.

Forty stroke subjects referred for dysphagia and studied by videofluoroscopy were compared with 16 individuals with no known pharyngeal swallowing difficulty. Kinematic pharyngeal transit time was defined as the time from the first movement of the bolus posteriorly resulting in a complete swallow to the return of the epiglottis to its original position. The mean transit time was 1.00 second for the comparative group and 6.15 seconds for the stroke group (p less than 0.001). Other component transit times are described and were all significantly prolonged for the stroke group. There was no significant difference in transit times between right-sided and left-sided lesions except for the segmental interval from onset of bolus movement to arrival at the valleculae, which was significant at p = 0.05. Measurement of transit times using the method described in this study requires equipment available in most hospitals. These measurements may be used in the evaluation of dysphagia in various pathologic disorders, in following the progress of patients with dysphagia, and in evaluating the effects of remedial therapies.

Adult↗

Laryngeal diversion in the treatment of intractable aspiration in motor neuron disease.

Motor neuron disease/amyotrophic lateral sclerosis (MND/ALS) often causes bulbar palsy with subsequent aspiration. Laryngeal diversion procedures are not commonly mentioned in the literature. However, they are viable but infrequently used surgical treatment options that have several advantages over a routine tracheostomy. We report a case of a 67-year-old man with MND/ALS and severe aspiration. He underwent a laryngeal diversion procedure with complete relief of signs and symptoms of aspiration. Laryngeal diversion, unlike tracheostomy, completely eliminates the possibility of aspiration as well as the need for suctioning. The primary disadvantage is complete loss of phonation. These procedures appear worthy of trial in patients with MND/ALS, and may ultimately be the preferred treatment in this setting.

Aged↗

Cefazolin for hysterectomy prophylaxis.

Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration.

Cefazolin↗