Biomedical subjects
Publications and source records attributed to K Boyle.
Despite apparent curative resection of rectal carcinoma, local recurrence rates of between 3 and 32% have been reported. For those patients, radical surgical resection offers the only hope of cure. We present a review of the magnetic resonance imaging (MRI) findings and contraindications to curative surgery demonstrated using imaging.
New measurements are presented for charged hadron azimuthal correlations at midrapidity in Au+Au collisions at (square root)s(NN) = 62.4 and 200 GeV. They are compared to earlier measurements obtained at (square root)s(NN) = 130 GeV and in Pb + Pb collisions at (square root)s(NN) = 17.2 GeV. Sizeable anisotropies are observed with centrality and transverse momentum (pT) dependence characteristic of elliptic flow (upsilon2). For a broad range of centralities, the observed magnitudes and trends of the differential anisotropy, upsilon2(pT), change very little over the collision energy range (square root)s(NN) = 62-200 GeV, indicating saturation of the excitation function for upsilon2 at these energies. Such a saturation may be indicative of the dominance of a very soft equation of state for (square root)s(NN) approximately 60-200 GeV.
The mitochondrial oxidative phosphorylation and fatty acid oxidation pathways have traditionally been considered independent major sources of cellular energy production; however, case reports of patients with specific enzymatic defects in either pathway have suggested the potential for a complex interference between the two. This study documents a new site of interference between the two pathways, a site in respiratory complex II capable of producing clinical signs of a block in fatty acid oxidation and reduced in vitro activity of acyl-CoA dehydrogenases. The initial patient, and later her newborn sibling, had mildly dysmorphic features, lactic acidosis and a defect in mitochondrial respiratory complex II associated with many biochemical features of a block in fatty acid oxidation. Results of in vitro probing of intact fibroblasts from both patients with methyl[2H3]palmitate and L-carnitine revealed greatly increased [2H3]butyrylcarnitine; however, the ratio of dehydrogenase activity with butyryl-CoA with anti-MCAD inactivating antibody (used to reveal SCAD-specific activity) to that with octanoyl-CoA was normal, excluding a selective SCAD or MCAD deficiency. Respiratory complex II was defective in both patients, with an absent thenoyltrifluoroacetone-sensitive succinate Q reductase activity that was partially restored by supplementation with duroquinone. Although secondary, the block in fatty acid oxidation was a major management problem since attempts to provide essential fatty acids precipitated acidotic decompensations. This study reinforces the need to pursue broadly the primary genetic defect within these two pathways, making full use of increasingly available functional and molecular diagnostic tools.
Voriconazole (VfendTM) is a new triazole that currently is undergoing phase III clinical trials. This review summarizes the published data obtained by NCCLS methods on the in vitro antifungal activity of voriconazole in comparison to itraconazole, amphotericin B, fluconazole, ketoconazole and flucytosine. Voriconazole had fungistatic activity against most yeasts and yeastlike species (minimum inhibitory concentrations [MICs] < 2 microg/ml) that was similar or superior to those of fluconazole, amphotericin B, and itraconazole. Against Candida glabrata and C. krusei, voriconazole MIC ranges were 0.03 to 8 and 0.01 to > 4 microg/ml, respectively. For four of the six Aspergillus spp. evaluated, voriconazole MICs (< 0.03 to 2 microg/ml) were lower than amphotericin B (0.25 to 4 microg/ml) and similar to itraconazole MICs. Voriconazole fungistatic activity against Fusarium spp. has been variable. Against E oxysporum and F. solani, most studies showed MICs ranging from 0.25 to 8 microg/ml. Voriconazole had excellent fungistatic activity against five of the six species of dimorphic fungi evaluated (MIC90s < 1.0 microg/ml). The exception was Sporothrix schenckii (MIC90s and geometric mean MICs > or = 8 microg/ml). Only amphotericin B had good fungistatic activity against the Zygomycetes species (voriconazole MICs ranged from 2 to > 32 microg/ml). Voriconazole showed excellent in vitro activity (MICs < 0.03 to 1.0 microg/ml) against most of the 50 species of dematiaceous fungi tested, but the activity of all the agents was poor against most isolates of Scedosporium prolificans and Phaeoacremonium parasiticum (Phialophora parasitica). Voriconazole had fungicidal activity against most Aspergillus spp., B. dermatitidis, and some dematiaceous fungi. In vitro/in vivo correlations should aid in the interpretation of these results.
In vitro analysis of the catalytic DNA polymerase encoded by vaccinia virus has demonstrated that it is innately distributive, catalyzing the addition of <10 nucleotides per primer-template binding event in the presence of 8 mM MgCl(2) or 40 mM NaCl (W. F. McDonald and P. Traktman, J. Biol. Chem. 269:31190-31197, 1994). In contrast, cytoplasmic extracts isolated from vaccinia virus-infected cells contain a highly processive form of DNA polymerase, able to catalyze the replication of a 7-kb template per binding event under similar conditions. To study this holoenzyme, we were interested in purifying and characterizing the vaccinia virus processivity factor (VPF). Our previous studies indicated that VPF is expressed early after infection and has a native molecular mass of approximately 48 kDa (W. F. McDonald, N. Klemperer, and P. Traktman, Virology 234:168-175, 1997). Using these criteria, we established a six-step chromatographic purification procedure, in which a prominent approximately 45-kDa band was found to copurify with processive polymerase activity. This species was identified as the product of the A20 gene. By use of recombinant viruses that direct the overexpression of A20 and/or the DNA polymerase, we verified the physical interaction between the two proteins in coimmunoprecipitation experiments. We also demonstrated that simultaneous overexpression of A20 and the DNA polymerase leads to a specific and robust increase in levels of processive polymerase activity. Taken together, we conclude that the A20 gene encodes a component of the processive DNA polymerase complex. Genetic data that further support this conclusion are presented in the accompanying report, which documents that temperature-sensitive mutants with lesions in the A20 gene have a DNA(-) phenotype that correlates with a deficit in processive polymerase activity (A. Punjabi et al, J. Virol. 75:12308-12318, 2001).
Although the vaccinia virus DNA polymerase is inherently distributive, a highly processive form of the enzyme exists within the cytoplasm of infected cells (W. F. McDonald, N. Klemperer, and P. Traktman, Virology 234:168-175, 1997). In the accompanying report we outline the purification of the 49-kDa A20 protein as a stoichiometric component of the processive polymerase complex (N. Klemperer, W. McDonald, K. Boyle, B. Unger, and P. Traktman, J. Virol. 75:12298-12307, 2001). To complement this biochemical analysis, we undertook a genetic approach to the analysis of the structure and function of the A20 protein. Here we report the application of clustered charge-to-alanine mutagenesis of the A20 gene. Eight mutant viruses containing altered A20 alleles were isolated using this approach; two of these, tsA20-6 and tsA20-ER5, have tight temperature-sensitive phenotypes. At the nonpermissive temperature, neither virus forms macroscopic plaques and the yield of infectious virus is <1% of that obtained at the permissive temperature. Both viruses show a profound defect in the accumulation of viral DNA at the nonpermissive temperature, although both the A20 protein and DNA polymerase accumulate to wild-type levels. Cytoplasmic extracts prepared from cells infected with the tsA20 viruses show a defect in processive polymerase activity; they are unable to direct the formation of RFII product using a singly primed M13 template. In sum, these data indicate that the A20 protein plays an essential role in the viral life cycle and that viruses with A20 lesions exhibit a DNA(-) phenotype that is correlated with a loss in processive polymerase activity as assayed in vitro. The vaccinia virus A20 protein can, therefore, be considered a new member of the family of proteins (E9, B1, D4, and D5) with essential roles in vaccinia virus DNA replication.
OBJECTIVES: We wished to determine whether early rejection after lung transplantation as assessed by surveillance transbronchial biopsy predicts for survival. METHODS: Between 1990 and 1997, 96 consecutive patients had lung transplantation: 89 had a minimum 1-month follow-up. For 71 consecutive patients we have 1-year follow-up and for 69 patients we have the results of the first 3 biopsies. Cytomegalovirus status, bronchiolitis obliterans prevalence, and use of total lymphoid irradiation are noted. Biopsies were done at 1 week and 1, 3, and 6 months. Standard immunosuppression consisted of induction antilymphocyte globulin and high-dose methylprednisolone induction for 1 week and standard maintenance triple therapy. Acute rejection treatment was with pulse methylprednisolone. Bronchiolitis obliterans syndrome was treated with total lymphoid irradiation and a change to tacrolimus and mycophenolate. Blinded grading using International Society for Heart and Lung Transplantation classification was done retrospectively. RESULTS: Survival at 1 month and 1, 2, and 3 years for the 96-patient cohort with 1-year follow-up was 93%, 74%, 62%, and 56%. Survival was not significantly different for subsets with rejection on any combination of the first 3 biopsies (1/3, 2/3, 3/3) or absence of rejection on the first 3 biopsies. Ninety-one positive biopsy results were graded. Eighteen of 71 patients had one or more moderate or severe rejection episodes without survival difference relative to the others. There was no statistically significant association between acute rejection on the first 3 surveillance biopsy results and bronchiolitis obliterans. CONCLUSIONS: Intensive induction and maintenance immunotherapy with surveillance transbronchial biopsies and aggressive treatment of acute rejection is associated with a survival similar to that of patients without early acute rejection. This regimen appears to uncouple the association between early acute rejection and bronchiolitis obliterans. Further study may elucidate this mechanism.
PURPOSE: To assess the incidence and characteristics of early postoperative complications in patients following neurosurgical procedures. METHODS: All patients undergoing neurosurgery during a four month period were followed postoperatively for up to four hours in the post anesthetic care unit or intensive care unit. Patient information and all complications were documented by the investigators on a standardized form. Complications were classified as respiratory, cardiovascular, nausea and vomiting, shivering and other. Risk factors analyzed for the occurrence of complications included age, sex, ASA status, type of surgery, elective or emergency surgery and postoperative placement. RESULTS: Four hundred eighty six adult patients were followed, but in 55 patients the trachea remained intubated during the four hour study period and they were eliminated from the analysis of postoperative complications. At least one complication occurred in 54.5% of the remaining 431 patients. Respiratory problems occurred in 2.8%, trauma to the airway in 4.4%, cardiovascular complications in 6.7%, neurological in 5.7% and nausea and/or vomiting in 38%. The highest incidence of patients with complications was during spine (65%) and vascular (66%) surgery, compared with tumour (47%) and other (43%) surgery, P < 0.05. Other risk factors included age < 70 yr for nausea and vomiting (P < 0.02), and elective surgery for spine and vascular surgery (P < 0.001). CONCLUSION: There was a high incidence of early postoperative complications in neurosurgical patients. The most common problem was nausea and vomiting especially in the younger patient undergoing elective spine surgery.
The epidemic of cocaine abuse has led to numerous studies on the substance. While extent of use, characteristics of users, patterns of use, and consequences of dependence are well documented for both powder cocaine and crack, few studies have dealt with the sequence or progression of use between the two forms of cocaine. This paper draws on arrestee data collected from county jails in Los Angeles, California. It identifies four sequences of powder cocaine and crack use and examines each sequence in terms of user characteristics, history of use, dependence, contact with the criminal justice system, and concomitant use of other drugs. Findings not only confirm some already established observations, but also offer new knowledge on powder cocaine and crack abuse. For instance, (a) whereas powder cocaine-initiated users are more likely to progress to crack than to restrict their use to powder cocaine only, crack-initiated users tend more often to use crack only than to progress to powder cocaine; and (b) powder cocaine and crack, when used interchangeably, can interact and reinforce each other, resulting in a higher level of use and dependence on both forms of the substance. This paper contributes to the understanding of powder cocaine and crack use among criminal offenders, in particular, and across the adult population, in general. It also sheds light on prevention, treatment, and social control policies of both cocaine abuse and overall illicit drug use.
This paper examines the validity of self-report of drug use in several important high-risk samples by comparing survey answers with urinalysis results. The analyses include data obtained from face-to-face interviews with 1536 patients in sexually transmitted disease (STD) clinics, 1564 patients in hospital emergency rooms (ERs), and 2034 recent arrestees in jails. Using urinalysis as the criterion measure, considerable underreporting was observed, particularly among STD and ER subjects using cocaine and opiates. A logistic regression analysis on factors related to the underreporting was conducted for both cocaine and opiates. The results showed that a lower degree of underreporting was associated with subjects at jail sites (compared to STD subjects) and those who self-reported lifetime drug dependence.
A psychophysical method was used to estimate the timing of perception of kinesthetic stimuli with different velocities in normal volunteers. A 1 ms auditory click occurred randomly before or after an imposed flexion movement at either 20, 40 or 60 deg/s of the metacarpophalangeal joint. Subjects reported whether the click was perceived before or after the movement onset (experiment 1) or perception of movement velocity (experiment 2). The time at which there was a 50% chance that subjects reported movement or velocity perception after the click was taken as an estimate of the time subjects perceived the stimuli. The difference in time of perceived movement velocity discrimination and movement onset was only significant when the velocity was 20 deg/s (52 ms). This suggests that movement onset and identification of the velocity of the faster movements are perceived nearly simultaneously.
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OBJECTIVE: To compare the therapeutic interventions provided to newborn and pediatric patients by a dedicated combined neonatal pediatric critical care transport team. METHOD: From November 1987 through December 1989 we prospectively compared the number of therapeutic interventions performed by the critical care transport team on newborns and pediatric patients. The transport team (critical care physician [PL3 or greater], pediatric respiratory therapist, critical care nurse), recorded all therapeutic interventions, including both procedural and pharmacologic, for 213 newborn and 149 pediatric consecutive transports. Data were analyzed by analysis of variance or chi 2 statistic. RESULTS: All patients were admitted to either the pediatric or the neonatal intensive care unit, and over 80% of both age groups received assisted ventilation. Newborns commonly suffered from respiratory diseases (159/213), while pediatric patients suffered from respiratory (52/149), central nervous system (28/149), and traumatic conditions (37/149). Airway maintenance procedural interventions (intubation, ventilation) were the commonest in both groups, although more frequent in neonates. Neonates received antibiotics and morphine (P < 0.05) while pediatric patients received anticonvulsants and respiratory drugs (P < 0.05) more frequently. Newborns received significantly more interventions than pediatric patients (average 3.56 vs 2.93, P < 0.05). Newborns also received significantly more procedural interventions (2.06 vs 1.36, P = < 0.05) including intubation (34.7% vs 15.4%, P < 0.05) and the initiation of mechanical ventilation (38% vs 22%, P < 0.05). CONCLUSION: Overall, newborns received more interventions, including intubation, and ventilation from the transport team than did pediatric patients. Our data suggest that combined pediatric neonatal transport teams should be prepared to intervene in a wide range of conditions from preterm respiratory distress to the multiply traumatized adolescent.
The objective of this study was to determine the influence of: a) pediatrician versus nonpediatrician referrals on a transport team's therapeutic interventions and b) referring physician's year of graduation on interventions performed by the transport team. From November 1987 through December 1989 we prospectively compared the therapeutic interventions performed by the critical care transport team on newborns and pediatric patients with the referring physician's specialty and year of graduation. The transport team (critical care physician [PL3 or greater], registered respiratory therapist, critical care nurse), recorded all therapeutic interventions, including both procedural and pharmacologic, for 213 newborn and 149 consecutive pediatric transports. Referring physicians were categorized as pediatricians and nonpediatricians. Data were analyzed by analysis of variance, chi2, or linear regression. All patients were admitted to either the pediatric or the neonatal intensive care unit, and over 80% of both age groups received assisted ventilation. Newborns referred by nonpediatricians required significantly more procedural interventions (2.64 vs 1.91, P = 0.016) than those referred by pediatricians. The opposite relationship was observed among pediatric patients in that children referred by pediatricians received more frequent intervention (P = 0.008) than those referred by nonpediatricians. There was a significant inverse relationship between the referring physicians year of medical school graduation and the number of therapeutic interventions (total interventions = 6.17 - 0.040 x graduation year, P = 0.01) and procedural interventions (procedural interventions = 3.54 - 0.024 x graduation year, P = 0.01). We found that the referring physicians' medical training affected the number of interventions their patients received. Similarly, patients were likely to receive more interventions if the referral physicians training was not recent. These data have educational implications and support the concepts of continuing medical education, recertification, and maintenance of skills among physicians providing care to critically ill newborns and pediatric patients.
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In response to the phenomenon of earlier-than-ever discharge, the post-hospitalization concerns of medical-surgical patients were investigated in a descriptive survey conducted in physicians' offices and clinics. The 150 recently discharged patients typically identified multiple concerns including understanding their progress, activity, insurance, medications, and pain control. Differences were found in number of concerns according to age, gender, length of hospital stay, type of treatment (medical or surgical), and perceived presence or absence of discharge planning.
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