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The management of delay in labour has been dominated by the use of oxytocin to augment the 'powers' of labour. However, this empirical approach has not been rigorously tested and 'failure to progress' remains a major clinical problem. A return to an analysis of the underlying pathophysiology is advocated.
Vascular smooth muscle is the cellular substrate of most significant arterial diseases. Restenosis after angioplasty and surgery mainly represents vascular smooth muscle reaction to trauma, a process which is also significant in the early stages of atherogenesis. Empirical approaches, based on findings in animal models of vascular injury, have notably failed to make any impact on human restenosis. We have developed and validated growth of the human VSMC in culture as a model of restenosis. Intimal hyperplastic lesions producing vascular restenosis contain cells that have reduced sensitivity to physiological growth inhibition by heparin in cell culture conditions, compared with cells from normal vascular tissue. Undiseased saphenous vein obtained from patients with intimal hyperplastic restenoses also contain cells that are relatively resistant to heparin inhibition. Arterial healing that progresses to restenosis may have distinct and fundamental differences at the cellular level from the normal process of arterial healing after injury.
Due to lack of structured epidemiological studies, the incidence of acute renal failure (ARF) cannot be established in France. An empirical approach method based on answered questionnaire sent by mail to nephrology centers affiliated or not to universities has been used to estimate the frequency of ARF requiring dialysis in 1991. We postulated that the French population was homogeneously distributed among the different regions and that the response rate of 74% could be extrapolated to 100%. We could therefore calculate an incidence of 64 ARF per million of inhabitants. However, this underestimates the exact incidence since the accurate evaluation of IRA in a controlled region (Champagne-Ardenne) is 104 per million of inhabitants. In addition, this study underlines the fact that many ARF are not treated in nephrology units, especially those associated with multiorgan failure requiring slow continuous hemofiltration and hemodialysis. It is suggested that the establishment of a national Registry for ARF and an adequate training of nephrologists are prerequisites to assess epidemiology and the global cost of ARF.
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When the results of a forensic comparison of highly polymorphic variable number tandem repeat (VNTR) loci fail to exclude a suspect as a possible contributor of biological evidence, it is desirable to convey to the trier of fact the significance of the match. Furthermore, in a forensic context, it is desirable that the estimated frequency of occurrence be conservative, that is, that any uncertainty in the estimate will favor the accused. Using an empirical approach with a data base of 2046 individuals belonging to one of four population groups, this study examined the effect of the method used to estimate frequency of occurrence of a VNTR profile from a reference data base, and the consequences of using a data base that may not represent the circumstances of the crime. The fixed bin method was at least as conservative as the floating bin and genotype counting (direct counting) methods. Secondly, for forensic purposes, profile frequency estimates from different reference populations do not deviate greatly. VNTR profiles are rare in any of the data bases.
Six site-directed mutants of cytochrome P450 2B1 were constructed, and function was evaluated in COS cell microsomes by monitoring testosterone and androstenedione hydroxylation and inactivation by chloramphenicol. Mutants Ile-114-->Val and Ile-114-->Ala exhibited marked decreases in androgen 16 beta-OH:16 alpha-OH ratios and increases in 15 alpha-OH:16-OH ratios. Since substitution of Gly-478 with Ala or Ser reduces 16 beta-hydroxylation in favor of 15 alpha-hydroxylation, four double mutants containing Val or Ala at position 114 and Ala or Ser at position 478 were examined. For any given residue at position 114 (Ile, Val, or Ala), the 15 alpha-OH:16-OH ratio increased as residue 478 was changed from Gly to Ala to Ser, and for any residue at position 478, this ratio increased as residue 114 was changed from Ile to Val to Ala. As a consequence, the Ile-114-->Ala, Gly-478-->Ser mutant displayed an approximately 1000-fold higher androgen 15 alpha-OH:16-OH ratio compared with the parental enzyme and functionally resembles mouse P450 2A4 much more closely than P450 2B1. All three mutants with Val at position 114 retained susceptibility to inactivation by chloramphenicol, whereas inactivation was suppressed by Ala at this position. The results suggest the feasibility of an empirical approach to P450 engineering involving the appropriate combination of residues at a few critical sites to confer new regio- and stereoselectivity with retention of overall monooxygenase activity.
The models of serial, parallel, and integrated treatment should help administrators and clinicians to think through resources they have and ones they may be able to share. Certain patients should do better with one or another of the models, but these empirical approaches need testing. Though large controlled outcome studies for various models of dual diagnosis treatment are pending, pilot studies of interventions have been positive, and the need for designing and implementing sensible programs to address the dual diagnosis patient is here right now.
In recent years the focus for the evaluation of health services has shifted from unnecessary treatment--specifically, unnecessary surgery--to appropriateness research. This new emphasis constitutes a shift in the burden of proof, indicating increased attention to the evidentiary basis of medical and surgical practice. The evaluation of the appropriateness of health services is also seen as integral to the reforming drive to contain health care costs and improve quality. Because of its pivotal role as a criterion in health care decision-making, the concept of appropriateness requires clarification. Three sources of value are defined that give meaning to "appropriateness" in patient care: the clinical point of view, the point of view of the individual patient, and the societal point of view. The framework is also used to shed light on the issue of medical futility.
This paper presents a review of the applications of texture analysis in medical imaging. Many authors take a great interest in this topic (75 papers have been published since 1984) and try to elaborate automatic methods for tissue characterization. The results are not really convincing and applications are often reduced to feasibility studies. This failure is due to the empirical approach to the problem: the first studies were performed on ultrasound images, in which visual texture is very present, but no data standardization is available with this imaging modality. A more rational approach should provide better results. For each organ or tissue, it is necessary to find the appropriate source and texture analysis method. This difficult task requires reflection concerning the interactions between tissues and imaging sources, to define judicious structuring elements. These structuring elements should facilitate the choice of the best texture analysis method, for the particular application. Considerable methodological progress has yet to be made, after which texture analysis should be a useful and efficient tool for clinical use.
The optimal management strategy for ventilator-dependent patients who develop symptoms suggestive of lung infection remains controversial. Proponents of the empirical approach prefer to treat most patients with fever and pulmonary infiltrates with one or more new antibiotics, even if it may be difficult (1) to determine whether pneumonia has developed in such patients, (2) in case of infection, to precisely identify the responsible microorganisms and thereby select the optimal antimicrobial treatment, and (3) to avoid resorting to broad-spectrum drug coverage in patients without true infection. Our personal bias is that using bronchoscopic techniques to obtain protected specimen brush and bronchoalveolar lavage specimens from the affected area in the lung permits to devise a therapeutic strategy superior to the one based only on clinical evaluation. These bronchoscopic techniques, when they are performed before new antibiotics are administered, enable physicians to identify most patients who need immediate treatment and select optimal therapy, in a manner that is safe and well tolerated by patients. Furthermore, they frequently permit the clinician to withhold antimicrobial treatment in patients without infection, minimizing the risk of the emergence of resistant microorganisms in the intensive care unit. In patients with clinical evidence of severe sepsis, the initiation of antibiotic therapy should not, however, be delayed while awaiting bronchoscopy, and patients should be given immediate treatment with antibiotics. In that case, "simplified" non-bronchoscopic diagnostic procedures might allow obtaining reliable distal pulmonary secretions for quantitative cultures on a 24-hour basis just before the initiation of a new antimicrobial therapy.
OBJECTIVE: Risch's lambda statistic (lambda R) is related to the heritability of traits and can be useful in several contexts, including the conduct of power analyses to determine sample size for gene mapping studies. However, values of lambda R have not been presented for human obesity. DESIGN AND RESULTS: Using both analytic and empirical approaches, the present study calculates estimates of lambda R. Examples are provided to illustrate the use of these estimates for determining sample size for genetic mapping studies.
Cancer susceptibility testing is likely to become routine in medical practice, despite many limitations and unanswered questions. These uncertainties greatly complicate the process of informed consent, creating an excellent opportunity to reconsider exactly how it should be conducted. Research with women's reactions to the availability of genetic susceptibility testing for breast cancer dramatically underscores that informed consent ought to be highly individualized, taking care to discern what patients believe about the disease and its causes and what role they want their physician to play.
A nonlinear mathematical model has been developed which relates the time to calcium-initiated formation of a detectable clot in citrated, factor-deficient plasma to the clotting activity of the factor deficient in the plasma. The data of clot-based factor assays fit well the exponential expression of this scheme, which can be used conveniently in the clinical laboratory to calibrate the clotting activity of individual coagulation factors in samples of citrated plasma. Aside from its clinical utility, the model may prompt the formulation of testable hypotheses not otherwise prompted by the existing, empiric approach to the quantitation of coagulation factor activity.
The intensity of a pain-only decompression sickness (DCS) symptom with respect to time at altitude increases, peaks, and then declines in some cases. A similar pattern is also seen in a graph of the probability density function [f(t)] for DCS. The f(t) is the proportion of DCS per unit time with respect to time at altitude. The integration of f(t) with respect to time provides the cumulative probability of DCS [P(DCS)]. We suspect that the perceived intensity of pain with a given stimulus intensity is related to the P(DCS); it may be related to the intensity of the stimulus to a power (alpha). Our stimuli are defined as pressure ratio [PR = (phi P1N2/ P2)-11] or pressure difference [delta P = phi P1N2-P2], where phi P1N2 is the N2 partial pressure calculated in the 360 min half-time (t1/2) compartment or t1/2 is estimated with other parameters and P2 is ambient pressure after the ascent. Both stimuli represent a potential released volume of gas. We tested the null hypothesis that alpha > 1 was no better than alpha = 1 in PR alpha and delta P alpha in a log logistic survival analysis of 1085 exposures in hypobaric chambers. The log likelihood number increased from -1198 for alpha = 0 for the null model to -724 for PR alpha when alpha = 3.52 with a 42 min t1/2 and -714 for delta P alpha when alpha = 8.44 with a 91 min t1/2. We conclude that the improvement in our expressions for decompression dose with alpha > 1 is not by random chance and that alpha may link the physics of gas evolution to the biology of pain perception. Because of our empirical approach, we do not exclude other possible interpretations.
A review of the literature demonstrated the difficulties in evaluating the teratogenic effect of drugs in man. Since epidemiologic studies provide suggestive rather than definitive data and results of the current drug testing in laboratory animals may not be applicable to man, the need to develop alternative methods of predicting teratogenicity was apparent. To develop such techniques by studying a possible mechanism of teratogenesis, experiments were performed using a teratogenic folic acid-deficiency and antagonism with 9-methyl pteroylglutamic acid in the pregnant rat. Embryos developing abnormally in response ot this regimen consumed oxygen at a significantly decreased rate. Similar significant reductions in oxygen consumption were found both in rat embryos malforming in response to maternal vitamin A acetate administration, and in mouse embryos in response to teratogenic doses of diphenylhydantoin. It was suggested that such measurements of oxidative metabolism or related techniques may have application in predicting drug teratogenicity and could aid present epidemiologic and empiric approaches to identification of human teratogens.
This is a empirical approach about professional fatigue of the hospital nurse. The fatigue concept was based on the Burnout Syndrome and some hospital variables associated. The sample consisted of 341 nurses of whom demographic data is available. Results of the application of the psychometric analysis of Burnout Inventory, as well as statistic correlation between the three scales and demographic data are presented. Considerable presence of emotional exhaustion and cognitive weariness as a consequence of the working atmosphere in the hospital critical sectors and the nursing chief responsibility were found.
This study aims at understanding the view about the nursing leadership question, through critical analysis of the literature produced predominantly in Brazil on this theme, from 1930 to 1995, contributing to its "dismythification". From the assumption that nursing is a social practice, and therefore articulated with other health practices, we conducted the investigation under a historical-social approach. Empirical data were obtained from the discourses about the issue or related themes, contained in 14 periodicals, from which 12 were of nursing. Besides them, we used proceedings from nursing events, as well as research and researcher catalogs and 3 theses. We analysed data according to time delimitation, distributed in four historical periods, intending to maintain the similarity of the peculiar discourses of each period, according to the context in these moments. The study demonstrated that the nursing leadership question has been treated, in the profession, in an idealized, mythical and crystalized way, contributing, thus, to the maintenance of the status quo and nursing professional's alienation.
An empirically-based approach which permits the comparison of changes in plasma clearance caused by pharmacokinetic drug-interactions is described. The analysis is based on the calculation of simple probability ratios for defined ranges of clearance changes that are caused by one of the interacting drugs. Examples of drugs increasing the clearance of a second drug through enzyme induction and of drugs decreasing the clearance of a second drug through enzyme inhibition are given. Data for each pair of interacting drugs is empirically fitted using either exponential or logarithmic functions. For each type of interaction a family of curves is generated which permits quantitative comparisons of both the extent and frequency of changes in plasma clearance caused by the interaction.