Tolerance induction following in utero stem cell transplantation.
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Animals↗
Biomedical subjects
R M Walker
Publications and source records attributed to R M Walker.
Medicolegal aspects of vesicovaginal fistula.
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Catheterization↗
Pressure flow study data in a group of asymptomatic male control patients 45 years old or older.
PURPOSE: The role of pressure flow studies in the routine evaluation of patients with benign prostatic hyperplasia remains a controversial issue in urological practice. There are little data on age matched asymptomatic control groups. We evaluated pressure flow findings in such a group. MATERIALS AND METHODS: A total of 24 male patients 47 to 80 years old (mean age 62.5) attending a general surgical clinic were recruited for study after ethical committee approval. The volunteers had never sought medical attention for urinary symptoms and did not perceive themselves as having a urological problem. Volunteers were assessed by International Prostate Symptom Score (I-PSS) and Madsen symptom score, clinical examination, free uroflowmetry, post-void residual ultrasound, repeat pressure flow studies and transrectal ultrasonography. Pressure flow tracings were manually analyzed for standard urodynamic values and the degree of bladder outflow obstruction according to recognized International Continence Society, Abrams-Griffith nomogram, linear passive urethral resistance relation and urethral resistance factor classifications. RESULTS: Median I-PSS was 2.0 (interquartile range 1.2 to 5.7). For I-PSS quality of life the median was 1.0 (interquartile range 0.75 to 2.0). On pressure flow studies 3 patients (13%) had unequivocal obstruction, 7 (29%) were in the equivocal area and 14 (58%) had no obstruction, while 15 (63%) had unstable contractions on medium fill cystometry. CONCLUSIONS: The data show that a surprising number of apparently normal men are obstructed by commonly used criteria. This finding confirms asymptomatic obstruction, suggesting that obstruction may be less important in the development of symptoms than previously thought. Also, until the natural history of obstruction is more clearly defined surgery in obstructed asymptomatic patients is probably unwise.
Aged↗
Should patients with neuromuscular disease be denied the choice of the treatment of mechanical ventilation?
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Adolescent↗
The effects of overnight fasting, feeding, or sucrose supplementation prior to necropsy in rats.
This study was designed to investigate the acute effects on routine hematology, serum biochemistry, gastrointestinal contents and weight, and liver weight and morphology due to overnight sucrose feeding of rats prior to necropsy. Groups of rats (five males and five females/group) were fasted overnight, fed chow, or fed sucrose and were euthanized approximately 17 h later. At necropsy, blood was obtained for hematology and serum biochemistry profiling, and the livers and gastrointestinal tracts were weighed and examined. The livers also were evaluated microscopically. The blood glucose and urea nitrogen concentrations and liver weights of animals fed sucrose differed significantly from those of the other groups. Alterations were more striking in males than females. Marked histological changes were present in livers from animals fed sucrose prior to necropsy compared with fasted or chow-fed animals, and these changes were attributed to increased glycogen deposition in the sucrose-fed animals. Because of alterations in hepatic structure and function, we cannot recommend the practice of feeding sucrose to rats prior to necropsy for toxicology studies or any studies examining hepatic function.
Animals↗
Is it ethical to withdraw low-burden interventions in chronically ill patients?
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Chronic Disease↗
The in vitro activity of ABT773, a new ketolide antimicrobial agent.
The in vitro activity of ABT773, a ketolide antimicrobial agent, was investigated and compared with those of seven other antibiotics. Type strains and 733 Gram-positive, Gram-negative and anaerobic isolates of clinical origin and four CHLAMYDIA: isolates were used. The activity of ABT773 was very similar to that of telithromycin, the other ketolide tested. The MIC(90) was < or = 0.5 mg/L for all bacteria examined except methicillin-resistant Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Haemophilus influenzae and BACTEROIDES: spp. The antichlamydial activity of ABT773 was greater than that of telithromycin, erythromycin and ciprofloxacin. Neither an increase in the size of the inoculm nor the addition of human serum had any marked affect on the in vitro activity of ABT773.
Anti-Bacterial Agents↗
Efficacy of sperm mobility assessment in commercial flocks and the relationships of sperm mobility and insemination dose with fertility in turkeys.
Our objectives were to evaluate: 1) the efficacy of the Sperm Mobility Test on commercial turkey farms, and 2) the influence of sperm mobility phenotype on fertility when insemination parameters are varied. In research flocks, differences in sperm mobility among toms are predictive of fertility. We wanted to test the efficacy of this sire selection test in practical, real-world situations, evaluating its usefulness in terms of assessing large numbers of toms, different strains of turkeys, and variable management practices. Utilizing field study results, controlled studies were then conducted to improve test parameters. For the field trials, semen from each of 405 breeder toms (11 strains or lines) was evaluated either in duplicate (n = 285) or in triplicate (n = 120). Sperm mobility was normally distributed among all toms tested, except for one strain. Because the sperm mobility indices for toms evaluated in these field trials were higher than those observed in research flocks, the Sperm Mobility Test was modified to increase the separation between high and low sperm mobility phenotypes by increasing the concentration of Accudenz. To determine the effects of sperm mobility and insemination dose on sustained fertility through time, hens from a research flock were inseminated twice before the onset of lay with sperm from toms classified as high-, average-, or low-mobility in concentrations of 25 to 400 million sperm per artificial insemination dose, and egg fertility was evaluated over a 5-wk period. Toms with the high-mobility sperm phenotype maintained higher fertility (P < 0.05) over the 5-wk period at all insemination doses compared with toms with low-mobility sperm. Toms with high-mobility sperm sired equal numbers of poults in a sperm competition study in which numbers favored low-mobility toms by 3:1. These results demonstrate that the Sperm Mobility Test can be used for on-farm evaluation of semen quality of toms in commercial flocks and that sperm mobility influences fertility and sire fitness.
Animals↗
Deactivating the implantable cardioverter-defibrillator: a biofixture analysis.
Automatic implantable cardioverter-defibrillators (ICDs) are becoming increasingly common, as is refusal of resuscitative efforts at the end of life, both by patients and surrogate decision-makers. While it is clear that a terminally ill patient who lacks decisional capacity may, through a surrogate, refuse cardiopulmonary resuscitation (CPR), is it appropriate for physicians to infer from such a refusal that the patient's ICD should be deactivated? A proper answer to this question requires consideration of the nature of consent to a do-not-resuscitate (DNR) order, the context in which permission is given for the writing of the DNR order, and the ontologic status of implantable devices in general and ICDs in particular. We introduce the concept of "biofixtures" and suggest that a biofixture analysis is a novel way of approaching the difficult ethical issues that may confound the care of patients with implantable devices.
Aged↗
Absence of correlation between telomerase activity and hepatic neoplasia in B6C3F1 mice.
Telomeres are the physical ends of eukaryotic chromosomes, which maintain chromosome stability and are progressively shortened with aging in somatic cells. The enzyme telomerase elongates telometric DNA and while not usually detectable in human somatic cells is expressed in most human tumors. The present study was conducted to determine if telomerase activity is a marker for spontaneous hepatic neoplastic changes in B6C3F1 mice, a strain frequently used in rodent carcinogenicity studies. Telomerase activity was generally higher in microscopically normal liver tissue from 8-week-old compared to aged mice (110-week-old); however, telomerase activity was not consistently increased in hepatocellular adenomas and carcinomas. It is proposed that, while elevated telomerase activity may modulate human tumor development, modulation of telomerase activity is not a feature of hepatic tumors in B6C3F1 mice and therefore is unlikely to have utility as a molecular marker for hepatic neoplasia in this mouse strain.
Animals↗
Probabilistic approach to the establishment of maximal content limits of impurities in drug formulations: the case of parenteral diphenylhydantoic acid.
Diphenylhydantoic acid (DPHA) is a degradation product in parenteral formulations of the anticonvulsant phenytoin and the prodrug fosphenytoin. DPHA has also been reported to be a minor metabolite of phenytoin. Levels found in the urine of various species, including humans, after oral or intravenous (iv) phenytoin ranged from undetected to a few percent of administered dose. In the present analysis, the toxicologic profile of DPHA was integrated with exposure data in order to characterize its safety under recommended clinical regimens of fosphenytoin administration. In preclinical safety studies, DPHA was without effect in the Ames assay and at concentrations up to 3000 microg/plate in the presence or absence of metabolic activation, and in the in vitro micronucleus test with acute and 2-week repeated dose studies in Wistar rats at iv doses up to 15 mg/kg. In 4-week studies conducted in rats and dogs receiving fosphenytoin containing DPHA levels up to 1.1%, and in an in vitro structural chromosome aberration test with DPHA levels up to 2.0%, all findings were consistent with known effects of phenytoin (such as CNS signs and increased liver weight), and none were attributed to DPHA. Reports in the literature indicate that in murine in vivo and in vitro models, DPHA has much lower potential for reproductive toxicity than phenytoin. A no-observed-effect level (NOEL) of 15 mg/kg established from the 2-week study in rats was used with probabilistic techniques to estimate tolerable daily doses (TDDs) of DPHA. In this approach, interspecies correction was performed by allometrically scaling the NOEL based on a distributional power of body weight while intraindividual variability was accounted for by selecting the lower percentiles of the population-based distribution of TDDs. The results indicate that a DPHA content limit of 3.0% in an administered dose of fosphenytoin is unlikely to cause adverse effects in patients.
Adolescent↗
Is there a clinically significant change in pressure-flow study values after urethral instrumentation in patients with lower urinary tract symptoms?
OBJECTIVE: To determine the effect of urethral instrumentation on pressure-flow study values and subsequent grading of bladder outflow obstruction (BOO) in men with lower urinary tract symptoms (LUTS) using suprapubic intravesical pressure monitoring. PATIENTS AND METHODS: Seventy-two men with LUTS underwent pressure-flow study using suprapubic intravesical pressure monitoring. The urethra was then instrumented successively with a 12 F catheter and a 17 F cystoscope, and a further pressure-flow study recorded after each procedure. Standard pressure-flow variables were measured for the three recordings. The presence and degree of obstruction were determined using commonly recognized grading systems, i.e. the Abrams-Griffiths nomogram. the linear passive urethral resistance ratio (LPURR) and the urethral resistance algorithm (URA). RESULTS: There were statistically significant differences in the detrusor pressure at maximum flow and detrusor opening pressure between the uninstrumented and instrumented studies (12 F and 17 F) but no difference in peak flow rates between the groups or in the Abrams-Griffiths number or URA value between studies. Using the LPURR, there was a tendency to a lower obstruction class after urethral instrumentation, ranking as 17 F > 12 F > no instrumentation. CONCLUSIONS: The changes seen after urethral instrumentation represent no more than the biological intra-individual variation normally seen in pressure-flow studies and do not lead to a clinically significant change in obstruction class.
Adult↗
Poison pen letters, due process, and medical schools' policies toward anonymous correspondence that disparages medical school faculty.
PURPOSE: To learn more about the frequency of and response to poison pen letters (anonymous correspondence that disparages faculty members) in academic medicine. METHOD: The authors surveyed all 143 deans of medical schools that are members of the AAMC about their practices and policies regarding the handling of poison pen letters. RESULTS: Of the deans surveyed, 119 (83%) responded. Sixty-seven deans (56%) reported having received poison pen letters during their tenure. Of those, 16 (24%) reported that they had discarded the letters based solely on the anonymity of the authors. The remaining 51 deans (76%) reported that they had either sequestered, investigated, or placed the letters into the faculty members' files, or that they had based their decisions to discard the letters on factors other than the authors' anonymity. Only one dean reported having a written policy for handling such correspondence. CONCLUSION: This survey of AAMC schools indicates that poison pen letters are not uncommon. The authors recommend a policy by which anonymous letters that disparage current or prospective faculty members would be categorically discarded.
Anonyms and Pseudonyms↗
Early effects of CI-924 on hepatic peroxisome proliferation, microsomal enzyme induction, PCNA, and apoptosis in B6C3F1 mice and Wistar rats.
The lipid lowering agent 5,5'[[1,1'-biphenyl]-2,5-diylbis(oxy)]bis[2,2-dimethylpentanoic acid] (CI-924) is a peroxisome proliferator in rats and mice, but increased the incidence of hepatic tumors in mice only. Male and female B6C3F1 mice and albino Wistar rats were treated with CI-924 at doses of 0, 25 and 75 mg/kg for 1, 3, 7 and 28 days. Our aim was to identify species differences potentially related to tumorigenicity and to establish the time course of early events related to or associated with peroxisome proliferation. After 24 h of exposure to CI-924 in the diet there were increases in carnitine acyl transferase and CYP4A1 activity in mice at 25 and 75 mg/kg. In rats, carnitine acyl transferase activity was increased after 24 h and CYP4A1 activity increased after 3 days at 75 mg/kg. Acyl CoA oxidase activity was increased at both doses in male and female rats and mice by 3 days. In general the changes in enzyme activity were of greater magnitude in rats. In contrast to the rapid peroxisome proliferation, increases in the amount of PCNA were observed in CI-924 treated rats and mice at later times after administration and only at 75 mg/kg. PCNA was increased to a similar extent in both rats and mice, while apoptosis was decreased at both doses of CI-924 after 3 days in female rats, 7 days in male rats, and was largely unchanged in mice. It was concluded that the sequence of peroxisome proliferation was generally similar in rats and mice. Early changes in cell proliferation and programmed cell death were not directly correlated with subsequent CI-924-induced hepatotumorigenicity.
Animals↗
Pressure-flow studies in the diagnosis of bladder outlet obstruction: a study comparing suprapubic and transurethral techniques.
OBJECTIVE: To compare suprapubic and transurethral methods of measuring intravesical pressure in a group of men undergoing investigation for lower urinary tract symptoms (LUTS), to identify which urodynamic variables are affected by the presence of an urethral catheter during the voiding phase, and consequently whether there is any change in the grading of bladder outflow obstruction (BOO) using the commonly recognised grading systems. PATIENTS AND METHODS: Thirty-five men with LUTS underwent both suprapubic and transurethral pressure-flow studies during a single session. Standard pressure flow variables were measured in all patients with both methods, enabling calculation of obstruction using the commonly used grading systems, i.e. the Abrams-Griffith number, linear passive urethral resistance ratio (LPURR) and urethral resistance algorithm (URA). RESULTS: There were statistically significant differences between the methods in the mean values of maximum flow rate and the detrusor pressure at that maximum: 60% of men were in the same LPURR class with either method. Using the transurethral method, 26% of patients increased the LPURR class by one and 6% by two classes. Using the Abrams-Griffiths nomogram, 17% moved from a classification of equivocal to obstructed and 3% from unobstructed to equivocal. Using the criterion of a value of URA > 29, 57% were obstructed using the suprapubic and 74% using the transurethral method. CONCLUSION: According to the method used, there were differences in the classification of obstruction between the suprapubic and transurethral routes; transurethral studies tended to indicate greater obstruction. The interpretation of urodynamic studies should take into account the technique used and where the route is transurethral, the smallest catheter available should be used.
Adult↗
Life values, resuscitation preferences, and the applicability of living wills in an older population.
OBJECTIVES: To determine whether life values are related to resuscitation preferences and living will completion in an older population and to assess beliefs about the applicability of living wills. DESIGN: Individual structured interviews. SETTING: An independent retirement community. PARTICIPANTS: One hundred thirty-two subjects older than 63 years of age. MEASUREMENTS: Resuscitation preferences were elicited in five hypothetical scenarios. Subjects with living wills were asked whether their living will would play a role in the scenarios. Subjects rated the importance of 13 life value statements. RESULTS: The percentage of subjects desiring CPR in each scenario was as follows: current condition (66%); acute illness (33%); terminal disease (8%); functional impairment (8%); and dementia (7%). The percentage of those with a living will who thought their living wills would play a role in the scenarios was as follows: acute illness (84%); terminal disease (93%); functional impairment with intact cognition (66%); and dementia (91%). Factor analysis of the life value statements revealed five meaningful factors: quality of life; capacity/autonomy; family relations; physical comfort; and treatment philosophy. Multiple correlations were found between four of five life value factors and hypothetical resuscitation preferences or the presence of a living will. CONCLUSION: Subjects misinterpreted the applicability of living wills in nonterminal illness scenarios. A relationship between life values and resuscitation preferences was noted, which emphasizes the importance of eliciting and including life values when discussing advance directives.
Aged↗
Living wills and resuscitation preferences in an elderly population.
BACKGROUND: Living wills are considered clear and convincing evidence of a person's preferences for end-of-life treatment. Unfortunately, living wills often use vague language that forces physicians and others to infer specific treatment choices, like the choice to forgo cardiopulmonary resuscitation (CPR). To test the validity of such inferences we examined the relationship between living will completion and CPR preference. We also examined whether CPR choices were fixed or could be influenced by detailed information on CPR. METHODS: We interviewed 102 retired elderly persons, many of whom had living wills. We obtained CPR preferences in five hypothetical scenarios before and after providing CPR information. We then analyzed differences in desire for CPR between the group of subjects with living wills and the group without. RESULTS: In each scenario there were subjects in both groups who desired CPR. The group with living wills desired less CPR in scenarios involving functional impairment and cognitive impairment, but not in scenarios involving current health, severe illness, and terminal illness. After receiving CPR information, both groups changed their preferences such that intergroup differences were no longer seen. CONCLUSIONS: Preferences for CPR among subjects with living wills are not homogeneous, but distributed across the clinical scenarios. Therefore, one cannot infer CPR preference from the mere presence of a living will. Cardiopulmonary resuscitation information can influence preferences even among persons with living wills, implying that preferences are neither fixed nor always based on adequate information. Physicians should view vaguely worded documents as unreliable expressions of treatment preference that should not supplant informed discussion.
Aged↗