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Biomedical subjects

J E Burns

Publications and source records attributed to J E Burns.

At least 19 recordsLinked to original sources

Persistent pulmonary hypertension of the newborn associated with pulmonary atresia and intact interventricular septum.

Neonates with pulmonary atresia and intact interventricular septum (PAIVS) do not have pulmonary vascular disease secondary to their heart abnormality. Persistent pulmonary hypertension of the newborn has not been described in association with this condition. The case is reported of a female neonate born with PAIVS, who preoperatively had no clinical evidence or any risk factors for persistent pulmonary hypertension of the newborn, but whose postoperative course was highly suggestive of persistent pulmonary hypertension; necropsy confirmed the features of pulmonary vascular disease.

Fatal Outcome

Radiographic exposure slide rules.

Before automatic exposure control was fitted to diagnostic X-ray sets, radiographers were faced with the problem of choosing the parameters that would give the best radiographic image. For a new X-ray set whose performance was unknown, this was no easy matter, and often required considerable trial and error because of the number of variables involved. To reduce the amount of work, special slide rules were invented which calculated the effect of some of these variables. Five such slide rules, dating from between about 1910 and 1950, are illustrated and discussed, including the light they shed on changes in radiographic practice over the years.

History, 20th Century

Postneonatal circumcision with local anesthesia: a cost-effective alternative.

PURPOSE: Despite the controversy regarding the need for routine neonatal circumcision, most boys in the United States are circumcised. Physicians are commonly asked to perform circumcision after the neonatal period and are often unaware of the cost factors related to the timing and location of postneonatal circumcision. MATERIALS AND METHODS: We describe the medical and financial advantages of postneonatal circumcision with local versus general anesthesia. RESULTS: During a 30-month period 245 boys 6 months to 15 years old underwent circumcision under general anesthesia in the operating room. Hospital charges (facility and equipment) averaged $1,555 and anesthesia charges averaged $250. Therefore, the average cost for circumcision in the operating room was $1,805. During the same time period 287 infants 3 days to 9 months old (20% older than 3 months) underwent circumcision under local anesthesia in an office setting. The facility and equipment charge for these office procedures averaged $196. Overall, approximately $461,783 were saved in this 30-month period ($184,713 annually) by performing circumcision with local anesthesia in an office setting rather then in the operating room with general anesthesia. There was no significant difference in complication rates between the local and general anesthesia groups (1.4 versus 1.6%). CONCLUSIONS: Circumcision with local anesthesia can be performed easily and safely during the first several months of life and has many advantages. Parents prefer this method because it is more convenient and eliminates the risk of general anesthesia. The enormous cost savings using local as opposed to general anesthesia should prompt a reexamination of the location and timing of postneonatal circumcision.

Adolescent

Expression, crystallization and preliminary X-ray analysis of the E2 transactivation domain from papillomavirus type 16.

The N-terminal transactivation domain of the E2 protein from human papillomavirus type 16 has been crystallized by vapour diffusion. Crystals belong to the space group P3121 (or P3221) with unit-cell dimensions a = b = 54.3, c = 155.5 A. There is one molecule per asymmetric unit with a solvent content of 55%. Crystals diffract to at least 2.5 A resolution and complete X-ray data to 3.4 A have been collected on a conventional laboratory source. This 201 amino-acid domain of the E2 protein has been shown to interact functionally with both the HPV E1 protein and at least three cellular transcription factors, to fulfil its role in the control of viral transcription and replication. A knowledge of the structural basis of these multiple interactions should lead to a fuller understanding of the mechanism of action of this key regulator of the HPV life cycle.

Cloning, Molecular

Expression patterns of the human papillomavirus type 16 transcription factor E2 in low- and high-grade cervical intraepithelial neoplasia.

Specific antibodies against the C-terminus of E2, produced by affinity purification of polyclonal antisera, have been used to identify the cellular populations which express the HPV 16 E2 transcription factor, in a series of formalin-fixed, paraffin-embedded cervical tissues. Cases were selected for both the presence of HPV 16 DNA (confirmed by multiple gene-specific PCR detections) and the presence of multiple grades of cervical intraepithelial neoplasia (CIN). The data indicate that E2 expression is highest in CIN I and in koilocytic lesions. Lower expression was observed in CIN II and little in CIN III lesions. In contrast, there was some restoration of E2 expression in invasive carcinomas, although the intracellular distribution was much more diffuse. The location of E2 expression to the superficial layers of the cervical epithelium, as well as the occurrence of some basal expression in CIN I, suggests that antibodies against HPV 16 E2 could be a useful adjunct to standard histological techniques for the detection of 'at-risk' patients as part of a cervical screening programme.

DNA-Binding Proteins

Race and delayed kidney allograft function.

BACKGROUND: Allograft survival among black recipients is poorer than among whites. Delayed allograft function is associated with a significant reduction in renal allograft survival. The relationship between delayed allograft function and black race is incompletely specified and was the focus of this investigation. METHODS: A non-concurrent study of 325 recipients of cadaveric allografts followed for the occurrence of delayed allograft function defined as dialysis during the first week following transplantation for the principal analysis. A secondary definition of delayed allograft function was formulated based on the serum creatinine 2 weeks after transplantation. Unadjusted and adjusted logistic regression analysis were used to examine the unconfounded relationship between race and delayed allograft function. RESULTS: Fifty-seven of 91 (62.6%) black recipients experienced delayed allograft function compared to 113 of 234 (48.3%) whites. The odds ratio for black race as a predictor of delayed allograft function was 1.80, P=0.02, (95% CI, 1.09, 2.95). This finding was stable despite adjustment for other predictors of delayed allograft function in a multivariate model, but the precision of this estimate was less (P=0.10) because of missing data. Additionally, adjusted models with imputed values for missing covariates, models using a secondary definition of delayed allograft function, and models excluding patients whose cyclosporin therapy was delayed, all consistently demonstrated a similar association between black race and delayed allograft function. CONCLUSIONS: This study demonstrated an increased risk of delayed allograft function among black recipients. This relationship may play a role in the poorer allograft outcomes experienced by black recipients. Given the negative effect of delayed allograft function on allograft survival, efforts to identify its modifiable risk factors should be a high priority.

Adult

Design, testing, and results of an outcomes-managed approach to patients requiring prolonged mechanical ventilation.

BACKGROUND: Outcomes management that uses critical pathways may decrease costs while improving outcomes for patients who require prolonged mechanical ventilation. OBJECTIVE: To study the efficacy of an outcomes-managed approach to weaning patients from prolonged (more than 3 days) mechanical ventilation. METHODS: A method of multidisciplinary care delivery was designed that included an outcomes manager, a care pathway for patients receiving mechanical ventilation, and weaning protocols. Data collection consisted of three parts: a retrospective review of 124 patients who required prolonged ventilation during a 1-year period before implementation of the care model, a 6-month prospective study in which 91 patients were alternately assigned by month to an outcomes-managed approach or a non-outcomes-managed approach, and a 6-month prospective study of 90 patients in which an outcomes-managed approach without alternate-month assignment was used. RESULTS: Outcomes management had no significant effect on total duration of mechanical ventilation or length of stay in the hospital, days of mechanical ventilation without tracheostomy, days of mechanical ventilation with tracheostomy, or outcome (weaned, withdrawal from mechanical ventilation, death, or transfer without weaning). However, duration of mechanical ventilation was 1.3 days shorter, length of stay in the hospital was 2.1 days shorter, and the cost per case was $ 3341 less for patients in the outcomes-managed group than for patients in the non-outcomes-managed group. CONCLUSION: Outcomes-managed care did not have a significant effect on duration of ventilation, length of stay in the hospital, or outcome in patients receiving long-term mechanical ventilation.

Adult

Single-chain Fv fragments of anti-neuraminidase antibody NC10 containing five- and ten-residue linkers form dimers and with zero-residue linker a trimer.

Single-chain variable fragments (scFvs) of anti-neuraminidase antibody NC10 were constructed by joining the VH and VL domains with 10-residue (Gly4Ser)2 and five-residue (Gly4Ser) linkers; a zero-residue linker scFv was constructed by joining the C-terminal residue of the VH domain to the N-terminus of the VL domain. The scFv with the 10- and five-residue linkers exclusively formed dimeric antibody fragments (M(r) 52000). These were shown to be bivalent and were able to cross-link two neuraminidase tetramers to form a 'sandwich' type complex; each antigen combining site could also bind an anti-idiotype Fab'. The zero-residue linker scFv (M(r) 70000) was shown to form a trimer with three active antigen combining sites, each binding an anti-idiotype Fab' to yield a complex of M(r) 212000. The orientation of the combining sites in the zero-residue linker scFv, however, was such that it could not cross-link tetramers of neuraminidase. BIAcore biosensor experiments showed that the affinity of each individual antigen combining site in both the 10- and five-residue linker scFv dimers and zero-residue linker scFv trimer was essentially the same when the scFvs were immobilized onto the sensor surface. However, when the scFvs were used as the analyte, the dimeric and trimeric scFvs showed an apparent increase in binding affinity due to the avidity of binding the multivalent scFvs.

Amino Acid Sequence

Recipient body size and cadaveric renal allograft survival.

Transplantation of renal allografts inadequate to meet recipient metabolic demands has been hypothesized to be one cause of chronic allograft failure. This cohort study examined the relationship of each of three measures of recipient body size and one measure of recipient metabolic rate to the rate of allograft failure among 239 recipients of cadaveric renal allografts between 1985 and 1990. All subjects were followed until allograft failure, death, or December 31, 1992, whichever occurred first. Using multivariate Cox proportional hazards analysis, all measures of recipient size and metabolic rate were found to be strong and statistically significant predictors of allograft survival adjusted for other predictors of allograft survival including allograft rejection, delayed allograft function, recipient race, prior renal transplantation, and donor age. The adjusted relative risk (RR) of allograft failure for a 15-kg increase in recipient body weight was 1.47, P < 0.0001 (95% confidence interval (CI), 1.21-1.78); adjusted RR for a 10-U increase in recipient body mass index was 2.34, P < 0.0001 (95% CI, 1.53-3.58); adjusted RR for a 0.5 m2 increase in recipient body surface area was 2.34, P < 0.001 (95% CI, 1.40-3.91); and adjusted RR for a 250 Kcal increase in metabolic rate was 1.49, P < 0.01 (95% CI, 1.17-1.89). These results are consistent with prior research indicating that a renal tissue supply-demand mismatch may accelerate failure of renal allografts. Alternative explanations of this relationship between recipient body size and allograft survival include inadequate immunosuppressive medication administration among recipients with a larger body size. Additional research is warranted to examine more fully the relationship between recipient body size and allograft survival.

Adolescent

Delayed function reduces renal allograft survival independent of acute rejection.

BACKGROUND: Mechanisms by which delayed allograft function reduces renal allograft survival are poorly understood. This study evaluated the relationship of delayed allograft function to acute rejection and long-term survival of cadaveric allografts. METHODS: 338 recipients of cadaveric allografts were followed until death, resumption of dialysis, retransplantation, loss to follow-up, or the study's end, which ever came first. Delayed allograft function was defined by dialysis during the first week following transplantation. Multivariate Cox proportional hazards survival analysis was used to assess the relationship of delayed allograft function to rejection and allograft survival. RESULTS: Delayed allograft function, recipient age, preformed reactive antibody levels, prior kidney transplantation, recipient race, rejection during the first 30 days and rejection subsequent to 30 days following transplantation were predictive of allograft survival in multivariate survival models. Delayed allograft function was associated with shorter allograft survival after adjustment for acute rejection and other covariates (relative rate of failure [RR]+1.72 [95% CI, 1.07, 2.76]). The adjusted RR of allograft failure associated with any rejection during the first 30 days was 1.99 (1.23, 3.21), and for rejection subsequent to the first 30 days was 3.53 (2.9 08, 6.00). The impact of delayed allograft function did not change substantially (RR=1.84 [1.15, 2.95]) in models not controlling for acute rejection. These results were stable among several subgroups of patients and using alternative definitions of allograft survival and delayed allograft function. CONCLUSIONS: This study demonstrates that delayed allograft function and acute allograft rejection have important independent and deleterious effects on cadaveric allograft survival. These results suggest that the effect of delayed allograft function is mediated, in part, through mechanisms not involving acute clinical rejection.

Acute Disease

Movement and force produced by a single myosin head.

Muscle contraction is driven by the cyclical interaction of myosin with actin, coupled to the breakdown of ATP. Studies of the interaction of filamentous myosin and of a double-headed proteolytic fragment, heavy meromyosin (HMM), with actin have demonstrated discrete mechanical events, arising from stochastic interaction of single myosin molecules with actin. Here we show, using an optical-tweezers transducer, that a single myosin subfragment-1 (S1), which is a single myosin head, can act as an independent generator of force and movement. Our analysis accounts for the broad distribution of displacement amplitudes observed, and indicates that the underlying movement (working stroke) produced by a single acto-S1 interaction is approximately 4 nm, considerably shorter than previous estimates but consistent with structural data. We measure the average force generated by S1 or HMM to be at least 1.7 pN under isometric conditions.

Actins

Single-molecule mechanics of heavy meromyosin and S1 interacting with rabbit or Drosophila actins using optical tweezers.

Single-molecule mechanical interactions between rabbit heavy meromyosin (HMM) or subfragment 1 (S1) and rabbit actin were measured with an optical tweezers piconewton, nanometer transducer. Similar intermittent interactions were observed with HMM and S1. The mean magnitude of the single interaction isotonic displacements was 20 nm for HMM and 15 nm with S1. The mean value of the force of single-molecule interactions was 1.8 pN for HMM and 1.7 pN with S1. The stiffness of myosin S1 was determined by applying a sinusoidal length change to the thin filament and measuring the corresponding force; the mean stiffness was 0.13 pN nm-1. By moving an actin filament over a long distance past an isolated S1 head, we found that cross-bridge attachment occurred preferentially at a periodicity of about 40 nm, similar to that of the actin helical repeat. Rate constants for the probability of detachment of HMM from actin were determined from histograms of the lifetime of the attached state. This gave a value of 8 s-1 or 0.8 x 10(6) M-1 s-1 for binding of ATP to the rigor complex. We conclude (1) that our HMM-actin interactions involve just one head, (2) that compliance of the cross-bridge is not in myosin subfragment 2, although we cannot say to what extent contributions arise from myosin S1 or actin, and (3) that the elemental movement can be caused by a change of shape of the S1 head, but that this would have to be much greater than the movements suggested from structural studies of S1 (Rayment et al., 1993).

Actins

Comparison of nasogastric tube securing methods and tube types in medical intensive care patients.

BACKGROUND: Nasogastric tube displacement can result in serious complications such as aspiration and inadvertent migration of the tube into the lungs. Replacement of the tubes is costly, time- and effort-intensive, uncomfortable for the patients, and potentially dangerous. OBJECTIVE: To determine the best of three methods for securing nasogastric tubes in a medical intensive care population and to identify variables related to the failure of tube securing methods. METHODS: A convenience sample of 103 patients requiring duodenal or standard gastric tubes for feeding, medication delivery, or decompression were randomly assigned to one of three taping methods: pink tape, clear tape, or "butterfly," for a total of 264 taping episodes. Data collection included the mean time until failure of the securing methods as well as variables such as patient alertness and mobility. RESULTS: The mean time until failure was 100 hours with pink tape versus 56 hours with clear tape and 30 hours with the "butterfly." Differences were significant. Duodenal tubes stayed secured longer than standard sump tubes (mean time until failure was 86 vs 41 hours) for all taping methods, but not significant relationship was demonstrated between mean time until failure and variables such as alertness, sedation, confusion, mobility, and the use of restraints. CONCLUSION: Our results showed that the pink tape method was superior. Nasogastric tube securing methods in adult critical care patients vary in efficacy and should be selected carefully.

Adhesives