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Biomedical subjects

R Freeman

Publications and source records attributed to R Freeman.

At least 109 records · Page 6Linked to original sources

Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group.

OBJECTIVE: To evaluate the efficacy of a 10-mg dose of midodrine 3 times per day in improving blood pressure (BP) and ameliorating symptoms of orthostatic hypotension in patients with neurogenic orthostatic hypotension. Midodrine hydrochloride, an alpha-agonist, could improve orthostatic BP by increasing vasomotor and venomotor tone. DESIGN/METHODS: A total of 171 patients with orthostatic hypotension participated in a multicenter, randomized, placebo-controlled study. They were randomized to a 10-mg dose of midodrine or placebo 3 times per day in a 6-week study, comprising single-blind run-in (at week 1) and washout at weeks 5 and 6, with an intervening double-blind period (weeks 2 to 4). SETTING: Twenty-five centers, with most patients evaluated in referral centers. MAIN OUTCOME MEASURES: The primary end points were improvement in standing systolic BP, symptoms of lightheadedness, and a global symptom relief score (by the investigator and patient separately). RESULTS: Nine patients were not evaluable because of noncompliance or taking concomitant vasoactive medications (3 in the midodrine group, 6 in the placebo group). In the evaluable patients, midodrine resulted in improvements in standing systolic BP at all time points (P<.001 at visits 2, 3, 4, and 5), in reported symptoms by the end of the second week of treatment (P=.001), and in the global symptom relief score rated by both the patient (P=.03) and the investigator (P<.001). There was no effect by center, severity of orthostatic hypotension, use of fludrocortisone or compression garments, or diagnosis. The main adverse effects were those of pilomotor reactions, urinary retention, and supine hypertension. CONCLUSIONS: Midodrine is efficacious and safe in the treatment of neurogenic orthostatic hypotension.

Activities of Daily Living↗

The long-term course of severe anorexia nervosa in adolescents: survival analysis of recovery, relapse, and outcome predictors over 10-15 years in a prospective study.

OBJECTIVE: To assess the long-term course of recovery and relapse and predictors of outcome in anorexia nervosa. METHOD: A naturalistic, longitudinal prospective design was used to assess recovery and relapse in patients ascertained through a university-based specialty treatment program. Patients were assessed semiannually for 5 years and annually thereafter over 10-15 years from the time of their index admission. Recovery was defined in terms of varying levels of symptom remission maintained for no fewer than 8 consecutive weeks. RESULTS: Nearly 30% of patients had relapses following hospital discharge, prior to clinical recovery. However, most patients were weight recovered and menstruating regularly by the end of follow-up, with nearly 76% of the cohort meeting criteria for full recovery. Relapse after recovery was relatively uncommon. Of note, time to recovery was protracted, ranging from 57-79 months depending on definition of recovery. Among restrictors at intake, nearly 30% developed binge eating, occurring within 5 years of intake. A variety of predictors of chronic outcome and binge eating were identified. There were no deaths in the cohort. CONCLUSION: The course of anorexia nervosa is protracted. Predictors of outcome are surprisingly few, but those identified are in keeping with previous accounts. The intensive treatment received by these patients may account for the lower levels of morbidity and mortality when considered in relation to other reports in the follow-up literature.

Adaptation, Psychological↗

Decoupling: theory and practice. I. Current methods and recent concepts.

Current methods for broadband heteronuclear decoupling are reviewed from a historical perspective. The principal concern is that decoupling should be effective over a wide range of chemical shifts without undue radiofrequency heating of the sample, particularly when human patients are involved. Continuous-wave methods are the least efficient in this respect, followed by noise decoupling. Composite pulse schemes offer a more effective use of radiofrequency power, while adiabatic passage methods are the most efficient of all. Bi-level decoupling employs a low level of radiofrequency irradiation during the relaxation delay to maintain the nuclear Overhauser effect, with a higher level during signal acquisition in order to decouple over a wide frequency band. All decoupling sequences introduce cycling sidebands into the observed spectrum, and schemes are described to minimize the intensity of these artifacts. In part II, practical applications of decoupling methods are examined in the context of in vivo spectroscopy, where the improvements in sensitivity and resolution through broadband decoupling can be critical for solving clinical problems. Attention is focused on the regulatory limits on power deposition in these experiments. A tabulation of the existing work on decoupling in biological tissue is presented, mainly involving 31P and 13C spectroscopy in vivo or in vitro.

Electromagnetic Fields↗

Does the chronic fatigue syndrome involve the autonomic nervous system?

PURPOSE: To investigate the role of the autonomic nervous system in the symptoms of patients with chronic fatigue syndrome (CFS) and delineate the pathogenesis of the orthostatic Intolerance and predisposition to neurally mediated syncope reported in this patient group. PATIENTS AND METHODS: Twenty-three CFS patients and controls performed a battery of autonomic function tests. The CFS patients completed questionnaires pertaining to autonomic and CFS symptoms, their level of physical activity, and premorbid and coexisting psychiatric disorders. The relationship between autonomic test results, cardiovascular deconditioning, and psychiatric disorders was examined with multivariate statistics and the evidence that autonomic changes seen in CFS might be secondary to a postviral, idiopathic autonomic neuropathy was explored. RESULTS: The CFS subjects had a significant increase in baseline (P < 0.01) and maximum heart rate (HR) on standing and tilting (both P < 0.0001). Tests of parasympathetic nervous system function (the expiratory inspiratory ratio, P < 0.005; maximum minus minimum HR difference, P < 0.05), were significantly less in the CFS group as were measures of sympathetic nervous system function (systolic blood pressure decrease with tilting, P < 0.01; diastolic blood pressure decrease with tilting, P < 0.05; and the systolic blood pressure decrease during phase II of a Valsalva maneuver, P < 0.05). Twenty-five percent of CFS subjects had a positive tilt table test. The physical activity index was a significant predictor of autonomic test results (resting, sitting, standing, and tilted HR, P < 0.05 to P < 0.009); and the blood pressure decrease in phase II of the Valvalsa maneuver, P < 0.05) whereas premorbid and coexistent psychiatric conditions were not. The onset of autonomic symptoms occurred within 4 weeks of a viral infection in 46% of patients-a temporal pattern that is consistent with a postviral, idiopathic autonomic neuropathy. CONCLUSION: Patients with CFS show alterations in measures of sympathetic and parasympathetic nervous system function. These results, which provide the physiological basis for the orthostatic intolerance and other symptoms of autonomic function in this patient group, may be explained by cardiovascular deconditioning, a postviral idiopathic autonomic neuropathy, or both.

Adult↗

Curie-point pyrolysis mass spectrometry as a tool in clinical microbiology.

Pyrolysis mass spectrometry is a well established analytical tool that has received a considerable boost from the development of low cost, dedicated instruments and sophisticated statistical analyses on personal computers. Further analytical developments, especially in the area of neural networks, are pushing the technology to the forefront of methods for the discrimination and identification of microorganisms and their products. The speed and reproducibility of pyrolysis mass spectrometry and its applicability to a wide range of microorganisms make it an attractive method for epidemiological studies. For inter-strain comparisons, the method is at least as discriminatory as conventional typing systems and usually gives discrimination similar to that of nucleic acid fingerprinting techniques. There has been some success in using neural networks to make identifications across pyrolysis mass spectrometric batches. Further development of methods used to handle data from multiple PyMS analyses can be expected to extend the value of pyrolysis mass spectrometry in clinical microbiology.

Bacteria↗

An apparent outbreak of infection with Acinetobacter calcoaceticus reconsidered after investigation by pyrolysis mass spectrometry.

In a previously reported apparent outbreak of infection due to Acinetobacter calcoaceticus on a Regional Burns Unit in which both clinical and environmental isolates were available for study, investigations of the organisms by electrophoretic typing of surface proteins, plasmid profiling and antibiograms were inconclusive and unable to identify a single epidemic strain of the organism. The same collection of isolates has been analysed for inter-strain comparison by pyrolysis mass spectrometry (PyMS). PyMS analysis suggested that a few isolates were very different from the majority but that most of the collection comprised a group of closely similar but nonetheless distinct isolates. These isolates may well be representatives of a limited variety of strains occupying an ecological niche but not yet a single emergent strain. The ability of PyMS to detect a single epidemic strain of A. calcoaceticus when present in such a collection of isolates was demonstrated by analysis of a "constructed outbreak collection", using some of the original isolates. This study illustrates the versatility of PyMS for inter-strain comparison studies of species not yet amenable to conventional typing methods. The application of rapid, highly discriminatory, high-volume inter-strain comparison methods such as PyMS to apparent outbreaks of nosocomial infection is likely to reveal patterns of organism acquisition other than point-source transmission.

Acinetobacter Infections↗

Differentiation of Mycobacterium senegalense from related non-chromogenic mycobacteria using pyrolysis mass spectrometry.

Twenty-six representative strains of Mycobacterium chelonae, Mycobacterium fortuitum, Mycobacterium peregrinum and Mycobacterium senegalense were compared by Curie point pyrolysis mass spectrometry. The M. chelonae and M. senegalense strains formed distinct groups. A third, relatively diffuse group, contained the M. fortuitum and M. peregrinum strains. These results, together with those from corresponding analyses, suggest that pyrolysis mass spectrometry provides a rapid and reliable way of distinguishing between members of closely related mycobacterial species which are difficult to differentiate using conventional taxonomic procedures.

Mass Spectrometry↗

A highly discriminatory method for the direct comparison of two closely related bacterial populations by pyrolysis mass spectrometry.

The ability of pyrolysis mass spectrometry (Py-MS) to discriminate between paired groups of closely related bacteria has been examined. The technique was challenged with increasing levels of biological difference; from that between different subcultures of the same isolate of Staphylococcus aureus, through that between separate isolates of the same strain and eventually to that between different staphylococcal species and Streptococcus pyogenes. By using an analytical method in which the spectral data from any two groups can be directly compared at a time, it was shown that Py-MS was capable of measuring statistically significant differences between staphylococci and Streptococcus pyogenes, between different Staphylococcus species and between two isolates of the same strain of S. aureus from different sources. Two subcultures of the same isolate were found to be indistinguishable. The differing magnitude of the Py-MS-derived differences corresponded to the "biological differences", being much larger between staphylococci and streptococci than between staphylococcal species and only just statistically significant between isolates of the same strain from different sources. The technique described allows the assessment of the magnitude and significance of Py-MS-derived differences between any two bacterial populations.

Mass Spectrometry↗

Differentiation between bacterial species and sub-species by pyrolysis mass spectrometry of extracted DNA.

Whole cell samples from cultures of Staphylococcus aureus, S. hominis, S. epidermidis and Streptococcus pyogenes were analysed by pyrolysis mass spectrometry and the results were compared with Py-MS-derived analyses of samples of DNA extracted from the same organisms. Py-MS analysis differentiated the four organisms in both circumstances. These results challenge previous assumptions that Py-MS is restricted to detecting phenotypic differences, although the basis for the differentiation of the DNA extracts has yet to be determined.

DNA, Bacterial↗

Assessing child dental anxiety: the validity of clinical observations.

For children there are few validated psychometric measures of dental anxiety. The study reported here aims to examine the validity of using clinical observations as a measure of child dental fear. 100 children consecutively attending a community clinic were asked to complete the validated Child Fear Survey Schedule (CFSS). After the dental examination both dental nurse and dentist separately assessed the subject's dental fear using a checklist based on the CFSS schedule. High agreement was found between the child, the dentist and dental nurse respectively and principal components analysis suggested that a dual nature of anticipatory dental anxiety existed in children. The findings of this work suggest that clinical observations may be a valid means of assessing child dental anxiety status.

Child↗

Clinical and epidemiological predictors of recurrent cytomegalovirus disease in orthotopic liver transplant recipients. Boston Center for Liver Transplantation CMVIG Study Group.

Predictors of recurrent cytomegalovirus (CMV) disease after the first episode of successfully treated CMV disease in orthotopic liver transplant recipients were studied. Recurrent CMV disease was defined as disease diagnosed > 14 days after the end of a minimum 8-day course of ganciclovir therapy for the first episode and was classified as early or late if it occurred within or after 90 days, respectively, after completion of ganciclovir treatment. Eleven (27%) of 41 patients had recurrent CMV disease (nine early recurrences and two late recurrences). Death was more likely to occur in patients with recurrent CMV disease than in those without it (55% vs. 13%, respectively; P = .006). Initial episodes of multiorgan CMV disease (P = .001) and CMV pneumonia (P = .012) were associated with early recurrence. Multivariate analysis showed that multiorgan CMV disease was independently associated with early recurrence (P = .003; odds ratio, 13.5; 95% confidence interval, 2.4-76.8). Recognition of risk factors for recurrent CMV disease may help identify patients for whom a more intensive therapeutic or diagnostic approach is needed.

Antiviral Agents↗

Mycobacterium novocastrense sp. nov., a rapidly growing photochromogenic mycobacterium.

A strain isolated from a biopsy sample taken from a slowly spreading skin granulation on a child's hand was found to have properties consistent with its classification in the genus Mycobacterium. An almost complete gene sequence of the 16S rRNA of the strain was determined following the cloning and sequencing of the amplified gene. The sequence was aligned with those available for mycobacteria, and phylogenetic trees were inferred with four tree-making algorithms. The organism, which formed a distinct phyletic line within the evolutionary radiation occupied by rapidly growing mycobacteria, was readily distinguished from members of validly described species of rapidly growing mycobacteria on the basis of its mycolic acid pattern and a number of other phenotypic features, notably its ability to form yellow pigmented colonies when incubated in the light. The name proposed for this new species is Mycobacterium novocastrense. The type strain is DSM 44203.

DNA, Bacterial↗

Pyrolysis mass spectrometry in epidemiological and population genetic studies of Haemophilus influenzae.

Haemophilus influenzae serotype b (Hib) vaccines have reduced the amount of invasive Hib disease in immunised infants. However, Hib disease remains in unvaccinated infants and adults and non-capsulate H. influenzae (NCHi) still causes infections, including outbreaks of respiratory disease. Characterisation of strains and the bacterial population as a whole is therefore necessary to detect outbreaks of infection with NCHi or changes in the population, for example, to vaccine-resistant clones of Hib. The rapid, simple and objective technique of pyrolysis mass spectrometry (PMS) was investigated as an alternative to current complex, subjective methods. PMS was compared with ribotyping and multilocus enzyme electrophoresis (MLEE) for population genetic analyses of Hib and with ribotyping and protein profiling for epidemiological analyses of NCHi. PMS clustered all the isolates of Hib together whereas MLEE and ribotyping distinguished certain clones - this is probably because the three methods examine different (and unrelated) characteristics of the organisms. The PMS results were essentially similar to those from ribotyping and protein profiling for the epidemiological analyses of outbreaks of NCHi disease. Therefore, PMS is probably unsuitable for comparisons of Hib populations but it is a useful addition to the arsenal of techniques for the characterisation of NCHi.

Adult↗

Differentiation of strains of Mycoplasma fermentans from various sources by pyrolysis mass spectrometry.

Mycoplasma fermentans has attracted much interest both as a cofactor for the progression of AIDS and as a pathogenic agent in non-AIDS related diseases. Previous studies with serological and genetic techniques suggest that M. fermentans represents a homogeneous group of organisms, with no significant differences identified among the strains examined. In this study, 25 cultures of M. fermentans, including isolates from human sources and tissue culture cells, were compared by pyrolysis mass spectrometry (PMS). It was possible to distinguish the 'type' strain PG-18 from an AIDS-associated M. fermentans strain 'incognitus' by this technique. PMS was also able to differentiate laboratory-induced aminoglycoside-resistant variants from their fully susceptible parents. Four AIDS-associated isolates were distinguished from each other, whilst five European cell culture isolates were shown to be closely related, as were six M. fermentans isolates from an outbreak of acute respiratory infection in Canada. PMS has proved useful in distinguishing isolates of M. fermentans, providing epidemiological data. In addition, PMS may help in determining the likely origin of a given isolate, and in the future may be of use in assessing the role of this micro-organism in human disease.

Acquired Immunodeficiency Syndrome↗

Understanding decision-making processes for sugar consumption in adolescence.

The mechanisms by which adolescents make food choices are not clear. The interaction and combination of the many social and psychological factors must be considered when examining adolescents' decision-making processes for sound food choices. The aim of this investigation is to examine one specific food choice, namely, the use of sucrose in hot drinks. One hundred and eighty-seven adolescents in their 16th year completed a questionnaire on the consumption of sugar using the method developed by AJZEN & FISHBEIN in their 'Theory of Reasoned Action'. The group was randomly divided into two groups so that decision-making processes with respect to two behavioural intentions-adding sugar to tea and coffee and excluding it-could be examined. The findings suggest that the immediate pleasurable taste of sugar outweighed and deferred the recognition of dangers associated with its consumption. Past dental health experiences, behaviours and education together with the role of parental figures acted as important influences. An awareness of these factors should assist dental health professionals to highlight the importance of sound food choices when negotiating dental health goals with adolescents.

Adolescent↗