Evaluation of a rapid air thermal cycler for detection of Mycobacterium tuberculosis.
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Bronchoalveolar Lavage Fluid↗
Biomedical subjects
R Freeman
Publications and source records attributed to R Freeman.
A rapid polymerase chain reaction technique for detecting M tuberculosis in a variety of clinical specimens.
A rapid in-house polymerase chain reaction (PCR) assay is described for the direct detection of Mycobacterium tuberculosis complex in clinical material. Its performance is compared with two kit based systems. The results of the in-house assay were comparable with the commercial assays, detecting M tuberculosis in 100% of smear positive, culture positive samples. The in-house assay proved to be rapid, easy, and inexpensive to perform, and the inclusion of an internal inhibitor control permitted validation of the PCR results.
Bronchoalveolar Lavage Fluid↗
Endothelial dysfunction and the expression of endothelial nitric oxide synthetase in diabetic neuropathy, vascular disease, and foot ulceration.
We studied endothelial-mediated microvascular blood flow in neuropathic diabetic patients to determine the association between endothelial regulation of the microcirculation and the expression of endothelial constitutive nitric oxide synthetase (ecNOS) in the skin. Vasodilation on the dorsal foot in response to heating and iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent) were measured using single-point laser Doppler and laser Doppler imaging in diabetic patients with neuropathy (DN), with neuropathy and vascular disease (DI), with Charcot arthropathy (DA), and without complications (D), and in healthy control subjects (C). The response to heat was reduced in the DN (321 [21-629] percentage of increase over the baseline, median [interquartile range]) and DI (225 [122-470]) groups but was preserved in the DA (895 [359-1,229]), D (699 [466-1,029]), and C (810 [440-1,064], P < 0.0001) groups. The endothelial-mediated response to acetylcholine was reduced in the DN (17 [11-25]), DA (22 [2-34]), and DI (13 [2-30]) groups compared with the D (47 [24-58]) and C (44 [31-70], P < 0.001) groups. The non-endothelial-mediated response to sodium nitroprusside was also reduced in the DI (4 [0-18]), DN (17 [9-26]), and DA (21 [11-31]) groups compared with the D (37 [19-41]) and C (44 [26-67], P < 0.0001) groups. There was a significant reduction in vasodilation in the DI group compared with all other groups (P < 0.0001). Full thickness skin biopsies from the dorsum of the foot of 15 DN, 10 DI, and 11 C study subjects were immunostained with antiserum to human ecNOS, the functional endothelial marker GLUT1, and the anatomical endothelial marker von Willebrand factor. The staining intensity of ecNOS was reduced in both diabetic groups. No differences were found among the three groups in the staining intensity of von Willebrand factor and GLUT1. We conclude that the endothelium-dependent and endothelium-independent vasodilations are impaired in diabetic patients predisposed to foot ulceration and that neuropathy is the main factor associated with this abnormality. Reduced expression of ecNOS may be a major contributing factor for endothelial dysfunction. These data provide support for a close association of neuropathy and microcirculation in the pathogenesis of foot ulceration.
Acetylcholine↗
Differences in foot and forearm skin microcirculation in diabetic patients with and without neuropathy.
OBJECTIVE: We have compared the hyperemic response to heat and the endothelium-dependent and endothelium-independent vasodilatation between the dorsum of the foot and the forearm in diabetic neuropathic and non-neuropathic patients and healthy control subjects. RESEARCH DESIGN AND METHODS: We studied the cutaneous microcirculation in the forearm and foot in 15 diabetic patients with neuropathy, in 14 diabetic patients without neuropathy, and in 15 control subjects matched for age, sex, BMI, and in the case of diabetic patients, for the duration of diabetes. Patients with peripheral vascular disease and/or renal impairment were excluded. The cutaneous microcirculation of the dorsum of the foot and the flexor aspect of the forearm was tested in all subjects. Single-point laser Doppler was employed to measure the maximal hyperemic response to heating of the skin to 44 degrees C and laser Doppler imaging scanner was used to evaluate the response to iontophoresis of 1% acetylcholine chloride (Ach) (endothelium-dependent response) and 1% sodium nitroprusside (NaNP) (endothelium-independent response). RESULTS: The transcutaneous oxygen tension was lower in the neuropathic group at both foot and forearm level, while the maximal hyperemic response to heat was similar at the foot and forearm level in all three groups. The endothelium-dependent vasodilation (percent increase over baseline) was lower in the foot compared to the forearm in the neuropathic group (23 +/- 4 vs. 55 +/- 10 [mean +/- SEM]; P < 0.01)], the non-neuropathic group (33 +/- 6 vs. 88 +/- 14; P < 0.01), and the control subjects (43 +/- 6 vs. 93 +/- 13; P < 0.001). Similar results were observed during the iontophoresis of NaNP (P < 0.05). No differences were found among the three groups when the ratio of the forearm:foot response was calculated for both the endothelium-dependent (neuropathic group, 2.25 +/- 0.24; non-neuropathic group, 2.55 +/- 0.35; and control subjects, 2.11 +/- 0.26; P = NS) and endothelium-independent vasodilation (neuropathic group, 1.54 +/- 0.27; non-neuropathic group, 2.08 +/- 0.33; and control subjects, 2.77 +/- 1.03; P = NS). The vasodilatory response, which is related to the C nociceptive fiber action, was reduced at the foot level during iontophoresis of Ach in the neuropathic group. In contrast, no difference was found during the iontophoresis of NaNP at the foot and forearm level and of Ach at the forearm level among all three groups. CONCLUSIONS: In healthy subjects, the endothelial-dependent and endothelial-independent vasodilatation is lower at the foot level when compared to the forearm, and a generalized impairment of the microcirculation in diabetic patients with neuropathy preserves this forearm-foot gradient. These changes may be a contributing factor for the early involvement of the foot with neuropathy when compared to the forearm.
Adult↗
Drug-resistant pulmonary tuberculosis in the Baja California-San Diego County border population.
A study was conducted to determine the frequency of, and risk factors for, drug-resistant pulmonary tuberculosis (TB) among Baja California (BC) and San Diego County (SDC) residents. Another purpose was to document the amount of contact between pulmonary TB patients and residents of the opposite side of the the border. During the period from February 1995 to May 1996, pulmonary TB patients from BC (n = 427) and SDC (n = 331) were evaluated with cultures, drug susceptibility tests, and questionnaires. Drug resistance was found in 41% of the BC Mycobacterium tuberculosis complex (MTB) isolates and 20% of the SDC isolates. Resistance to both isoniazid (INH) and rifampin (RIF) varied from 1% of isolates from SDC patients to 17% of isolates from BC patients. Patients with a history of previous treatment had increased odds of drug-resistant disease. Older BC patients were more likely to have INH- or RIF-resistant TB. Although 42% of Tijuana TB patients reported recent contact with residents from SDC, travel to Mexico and contact with residents from Mexico were not significant risk factors for drug-resistant TB among SDC residents. However, the demonstrated contact between TB patients and residents on opposite sides of the border indicates the importance of coordinating efforts internationally to control TB.
California↗
Echocardiography for primary care evaluation of hypertension.
OBJECTIVE: To reexamine the changing role of echocardiography for primary care evaluation of essential hypertension since the 1993 Canadian Hypertension Society Consensus Conference. QUALITY OF EVIDENCE: New recommendations from the Canadian Cardiovascular Society and the Canadian Hypertension Society. Recommendations from the American College of Cardiology based on a prospective, randomized controlled trial of limited echocardiograms. Further results from the Framingham Heart Study and the Treatment of Mild Hypertension Study. MAIN MESSAGE: For patients with essential hypertension, left ventricular hypertrophy (LVH) continues to be a strong predictor of many cardiovascular end points, and echocardiography is a much more sensitive tool for detecting LVH than electrocardiogram (ECG). Although limited echocardiograms are not usually used, they are a less costly method of evaluating LVH than standard echocardiograms and have recently been recommended in the United States to assist in the decision to initiate pharmacotherapy for patients with stage 1 hypertension and no other evidence of target organ damage. Problems with intrareader and interreader variability of results are being addressed by technical and mathematical standards established by the Canadian Cardiovascular Society and the Canadian Hypertension Society. CONCLUSIONS: Using limited echocardiograms for assessing LVH coupled with implementing Canadian technical standards might lead to a greater role for echocardiography in evaluating essential hypertension in certain patients.
Adolescent↗
Efficacy of midodrine for neurogenic orthostatic hypotension. Reply.
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Adrenergic alpha-Agonists↗
Cytomegalovirus disease is associated with increased cost and hospital length of stay among orthotopic liver transplant recipients.
Cytomegalovirus (CMV) is a cause of considerable morbidity and mortality among orthotopic liver transplant (OLT) recipients. To study the impact of CMV on cost and hospital length of stay in this population, we undertook an analysis of a cohort of OLT recipients from four transplant centers in Boston who participated in a CMV prophylaxis trial. First posttransplant year hospital length of stay (including the hospital stay after transplantation and readmissions within 1 year after transplantation) was available for all 141 patients included in the study. In a multiple linear regression model bacteremia (P=0.0001), CMV disease (P=0.0007), abdominal reexploration (excluding retransplantation) (P=0.0070), recipient age < or = 16 years (P=0.0352), and the number of units of blood products (red blood cells, platelets, or fresh frozen plasma) administered during transplantation (P=0.0523) were shown to be independently associated with longer first posttransplant year hospital length of stay. Cost data for in-hospital care for the year beginning with admission for liver transplantation were available for 66 OLT recipients. Using a multiple linear regression model, development of CMV disease (P=0.0001), the number of units of blood products administered during transplantation (P=0.0001), bacteremia (P=0.0002), decreased pretransplant renal function (estimated by creatinine clearance) (P=0.0109), and need for retransplantation (P=0.0619) were shown to be independently associated with higher cost. These data strongly suggest that CMV disease has a direct impact on cost and hospital length of stay in liver transplantation.
Adolescent↗
The practice of dentistry: an assessment of reasons for premature retirement.
AIM: To assess reasons for premature retirement among practising dentists and to evaluate their association with occupational stress. DESIGN: Retrospective analysis. SETTING: Records from one organisation operating in the private medical sickness industry in the UK. MATERIALS: Reasons for premature retirement of 393 dentists due to illness between 1981 and 1992. RESULTS: The most frequent causes of premature retirement were musculoskeletal disorders (29.5%), cardiovascular disease (21.1%), and neurotic symptoms (16.5%), 82.7% of cases examined were in the > 50 years age group. CONCLUSIONS: Musculoskeletal disorders and stress related illnesses were the two most important groups which influenced premature retirement.
Adult↗
Ciprofloxacin-resistant Enterobacteriaceae.
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Anti-Infective Agents↗
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↗
Information shared in mentoring must remain confidential.
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Confidentiality↗
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↗