Biomedical subjects
Publications and source records attributed to M Richardson.
The management of invasive fungal infection utilizes a variable multidisciplinary approach involving antifungals, appropriate surgery and immuno-correction. Conventional amphotericin B has been the mainstay of treatment but newer pathogens and poor outcomes has led to new formulations of this drug as well as to new and novel antifungals.
This article reports on research conducted in 1995 in Victoria, Australia with 12 nurse managers who were displaced through redundancy. This was a pilot study that employed a phenomenological approach to explore the personal impact of redundancy. Participants experienced three differing approaches to the redundancy processes undertaken. Data was managed by a thematic analysis. Powerful themes of being isolated in their agony and fear, of consent under duress, and trauma, emerged from the data. This paper tells the story graphically and emotionally, it is the people's story, an eloquent example of what is missed in current literature.
This chapter will outline a general approach to symptom assessment, using the interdisciplinary approach to pain as a model. Due to the implications of cognitive impairment for treatment compliance, consent, and caregiver burden, assessment of cognitive function will be reviewed in detail. Problem areas in assessment are identified, along with aids to improve assessment and emphasize the key contribution of the nurse. We will also focus on measurement issues from both clinical and research perspectives.
In palliative care, the focus is management of major symptoms and complications, and psychosocial support of the patient and family. Approaching the end of life, the patient's needs move beyond physical care to include the psychological, social, and spiritual dimensions. The main psychosocial interventions are counseling, education, and practical services directed at the needs identified by the multidimensional/multidisciplinary assessments. We will present the roles of the various team members and methods of psychosocial assessment.
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Acute invasive aspergillosis (IA) is a devastating disease. Early diagnosis allowing an early treatment may improve the prognosis. However, this goal remains difficult to achieve. When diagnosis is confirmed it is often already too late. Galactomannan antigen detection and DNA detection are under clinical evaluation to improve early diagnosis and management of treatment. Despite antifungal treatment mortality rate is still high. Clinical resistance is more often due to the intensity of immunodepression than to high minimum inhibitory concentrations to antifungal agents; however, resistance to itraconazole may occur in rare instances. Beside acute IA, a chronic form of this infection may be seen as chronic necrotizing pulmonary aspergillosis or chronic invasive sinusitis. Other sites of infection have been described. The patients are immunocompetent or present minor alteration of their immunity or of anatomic structure of the infected site. Among patients with solid organ transplantation, lung and liver transplant patients are at the highest risk of developing IA. A high degree of awareness and efforts for an early diagnosis may participate to improve the poor prognosis.
BACKGROUND: For decades it has been assumed that postprimary tuberculosis is usually caused by reactivation of endogenous infection rather than by a new, exogenous infection. METHODS: We performed DNA fingerprinting with restriction-fragment-length polymorphism analysis on pairs of isolates of Mycobacterium tuberculosis from 16 compliant patients who had a relapse of pulmonary tuberculosis after curative treatment of postprimary tuberculosis. The patients lived in areas of South Africa where tuberculosis is endemic. Medical records were reviewed for clinical data. RESULTS: For 12 of the 16 patients, the restriction-fragment-length polymorphism banding patterns for the isolates obtained after the relapse were different from those for the isolates from the initial tuberculous disease. This finding indicates that reinfection was the cause of the recurrence of tuberculosis after curative treatment. Two patients had reinfections with a multidrug-resistant strain. All 15 patients who were tested for the human immunodeficiency virus were seronegative. CONCLUSIONS: Exogenous reinfection appears to be a major cause of postprimary tuberculosis after a previous cure in an area with a high incidence of this disease. This finding emphasizes the importance of achieving cures and of preventing anyone with infectious tuberculosis from exposing others to the disease.
Vascular endothelial growth factor (VEGF) and its receptors Flt-1 and KDR play important roles in physiological and pathological angiogenesis. Ribozymes that target the VEGF receptor mRNAs were developed and their biological activities in cell culture and an animal model were assessed. Ribozymes targeting Flt-1 or KDR mRNA sites reduced VEGF-induced proliferation of cultured human vascular endothelial cells and specifically lowered the level of Flt-1 or KDR mRNA present in the cells. Anti- Flt-1 and KDR ribozymes also exhibited anti-angiogenic activity in a rat corneal pocket assay of VEGF-induced angiogenesis. This report illustrates the anti-angiogenic potential of these ribozymes as well as their value in studying VEGF receptor function in normal and pathophysiologic states.
In view of the expanding roles of the betagamma subunits of the G proteins in signaling, the possibility was raised that the rich diversity of betagamma subunit combinations might contribute to the specificity of signaling at the level of the receptor. To test this possibility, Sf9 cell membranes expressing the recombinant alpha2A-adrenergic receptor were used to assess the contribution of the betagamma subunit composition. Reconstituted coupling between the receptor and heterotrimeric Gi protein was assayed by high affinity, guanine nucleotide-sensitive binding of the alpha2-adrenergic agonist, [3H]UK-14,304. Supporting this hypothesis, the present study showed clear differences in the abilities of the various betagamma dimers, including those containing the beta3 subtype and the newly described gamma4, gamma10, and gamma11 subtypes, to promote interaction of the same alphai subunit with the alpha2A-adrenergic receptor.
BACKGROUND: Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS: Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS: PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.
Tuberculosis (TB) is still a major cause of morbidity and mortality. It is clear that control requires more than simple availability of antibiotics. In order to gain insight into the disease, DNA fingerprinting has been applied to the study of bacterial population structure. This technology has been used to quantitate various components of the disease in a high-incidence community, viz. recent transmission (RT) and reactivation (RA) and to monitor these over time as a tool to quantitate changes in the epidemic. In our high-incidence community, we find unexpectedly high strain diversity, lower than predicted RT, and that reactivation disease dominates. This technology can be used to examine and challenge traditional dogmas. Quantitative measure of RT varies over time, using a two-year sliding window for estimation as a useful period. The results show that the "epidemic" consists of subepidemics characterized by strain families that wax and wane in the community of TB patients. The technology is shown to be a useful and quantitative tool to assess disease status and can therefore be used to monitor intervention strategies and refine and monitor results of new control measures.
OBJECTIVE: To evaluate the efficacy of a 6-week exercise and educational program for patients with fibromyalgia. METHODS: Forty-one subjects were randomly assigned to the program or served as waiting list controls. Program outcome was assessed with a 6-minute walk test, the Fibromyalgia Impact Questionnaire, a Self-Efficacy Scale, and a "knowledge" questionnaire (based on information provided during the educational sessions). Waiting list control subjects subsequently completed the program. Program outcome was reassessed 3 or 6 months post-program. RESULTS: The program produced significant improvements in 6-minute walk distance, well-being, fatigue, self-efficacy (for controlling pain and other symptoms), and knowledge. At followup, immediate gains in walk distance, well-being, and self-efficacy were maintained, but gains in fatigue and knowledge were lost. CONCLUSION: Short-term exercise and educational programs can produce immediate and sustained benefits for patients with fibromyalgia. The benefits of our program may be due to exercise or education since both interventions were given.
BACKGROUND: Diabetes mellitus is a major risk factor for the development of atherosclerosis but the mechanisms involved remain unclear. The expression of leukocyte adhesion molecules at the endothelial surface is a primary step in the recruitment of leukocytes into the intima and the subsequent development of lipid-containing foam cell lesions. Increased levels of circulating adhesion molecules have been identified in diabetic patients, but the distribution in the arterial wall has not been described. MATERIALS AND METHODS: Frozen sections were prepared from aorta and internal mammary artery obtained during bypass surgery from 12 diabetic and 16 nondiabetic patients. Adhesion molecules (intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and E-Selectin), macrophages, and lymphocytes were identified and quantified using immunohistochemistry; intimal hyperplasia was quantified. RESULTS: Endothelial expression of VCAM-1 and intimal smooth muscle cell expression of both VCAM-1 and ICAM-1 was increased in the aortas from diabetic patients. Intimal hyperplasia in aorta and internal mammary artery sections was significantly greater in diabetic tissue. Macrophages, T-lymphocytes, oil-red-O-stained lipid, glycated albumin, and glycated LDL were observed in the aorta of both diabetic and nondiabetic samples. CONCLUSIONS: The increased incidence of VCAM-1 and ICAM-1 in the aorta may partly explain the enhanced atherosclerosis associated with diabetes mellitus, and their presence in established lesions may emphasize their long-term importance. The intimal hyperplasia observed in the bypass vessel may be a contributing factor to the increased incidence of restenosis in diabetic patients.
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In the rabbit blood stream, plasminogen circulates as two glycoforms, plasminogen I (PLG-I) and plasminogen II (PLG-II), in a molar ratio of 1:2.2. To compare their relative behaviors toward a site of vascular injury, radiolabeled samples of PLG-I and PLG-II were coinjected intravenously into NZW rabbits before inducing a de-endothelializing (balloon catheter) injury to the thoracic aorta. At various times (5 to 60 minutes) after injury, each rabbit was anesthetized and exsanguinated, the aorta was excised, and the radioactivity per centimeters squared of aortic intima-media (IM) was measured relative to that of blood at exsanguination. The uptake of iodine 125-labeled PLG-I and iodine 131-labeled PLG-II showed that the IM was essentially saturated by both glycoforms by 30 to 40 minutes after injury. Extrapolation of the flux rates to 1 minute after injury indicated that the uptake of PLG-II (2.4 pmol/min/cm2) exceeded PLG-I (0.5 pmol/min/cm2) almost five-fold. This result is consistent with an earlier report (Metabolism 1994;43:1430-7) that PLG-II is released by the liver and catabolized in vivo approximately five times faster than PLG-I. By molar comparison, the flux of total plasminogen (ie, PLG-I plus PLG-II) into the injured aorta wall in vivo was 2.4 times greater than that for prothrombin. Assuming both zymogens are converted to their respective proteases within the wound site, then approximately 2 to 3 molecules of plasmin are released for each molecule of thrombin in vivo. The possible significance of this plasmin:thrombin ratio is discussed in respect to the turnover of fibrin(ogen) within the site of vascular injury.
BACKGROUND: There are currently many on-going clinical trials assessing therapies for the treatment of patients with heart failure. AIMS: The purpose of this series of papers is to present concise summaries of current randomised trials in the field of heart failure and myocardial infarction (MI). METHODS: Data from large double-blind, placebo-controlled trials, which are on-going or have only recently been published, are given in a format allowing easy comparison. Where appropriate, data from smaller studies are included. RESULTS: Major studies which are examined in this issue include CIBIS II, MERIT-HF, RESOLVD, SPICE, VEST, MACH-1, ATLAS, RALES, CIDS and CASH. These trials assess the efficacy and safety of beta-blocker, angiotensin-II-receptor blocker, positive inotropic agent, calcium antagonist, angiotensin-converting enzyme (ACE) inhibitor, aldosterone receptor blocker, and antiarrhythmic interventions in the treatment of heart failure. CONCLUSIONS: The presentation of data from these on-going trials should allow an up-to-date assessment, by physicians, of the most appropriate and effective treatment for patients with heart failure. It is evident that some therapies may play no further role in the treatment of heart failure, due to the increased risk of mortality associated with their administration, whilst others may convey significant benefits.
BACKGROUND: In the operative management of gastro-oesophageal reflux, a balance must be achieved between adequate control of reflux and excessive dysphagia. The ideal technique is not known. A randomized study was performed to determine whether laparoscopic anterior fundoplication is associated with a lower incidence of postoperative dysphagia than laparoscopic Nissen fundoplication, while achieving equivalent control of reflux. METHODS: Patients presenting for laparoscopic antireflux surgery were randomized to undergo either a Nissen fundoplication (n = 53) or an anterior 180 degrees hemifundoplication (n = 54). Patients were blinded to which procedure had been performed, and follow-up was obtained by a blinded independent investigator. Standardized clinical grading systems were used to assess dysphagia, heartburn and patient satisfaction 1, 3 and 6 months after operation. Objective measurement of lower oesophageal sphincter pressure, oesophageal emptying time, distal oesophageal acid exposure and endoscopic healing of oesophagitis was also performed. RESULTS: Operating time was similar for the two procedures (58 min for the Nissen procedure versus 60 min for anterior fundoplication). Resting and residual lower oesophageal sphincter pressures were lower following anterior fundoplication (29 versus 18 mmHg, and 13 versus 6 mmHg), and oesophageal emptying times were faster (92 versus 116 s). Acid exposure times and ability to heal oesophagitis were similar. At 3 months' follow-up clinical outcomes were similar for the two procedures. At 6 months, however, patients who had undergone anterior fundoplication experienced significantly less dysphagia for solid food and were more likely to be satisfied with the clinical outcome. CONCLUSION: Laparoscopic anterior fundoplication achieved equivalent control of reflux, more physiological postoperative manometry parameters, and an improved clinical outcome at 6 months. Continued follow-up remains necessary to confirm the long-term efficacy of the partial fundoplication procedure.
A compact, high-resolution, laser-plasma, x-ray contact microscopy method using a table-top Nd:glass laser system has been developed. This x-ray microscopy system was applied for the observation of macrophage ultrastructures. These images were produced using proximity imaging in which a 5-ns pulse of soft x-rays with wavelengths near and inside the water windows (23A-44A) produced by the laser-plasma were absorbed by the specimen and then registered on a photo resist. The x-ray images imprinted on the photo resist were then developed and analyzed with an atomic force microscope (AFM). Mouse thioglycollate-elicited peritoneal macrophages in suspension were examined by this new x-ray microscope. The x-ray images of the macrophages were compared with those observed by conventional transmission electron microscopy (TEM). The x-ray images showed no obvious organelles, including the nucleus and endoplasmic reticulum, as can be seen with TEM, but high- and low-contrast structures caused by mass distribution of carbon were observed. Thus, using the x-ray microscopy we visualized the first x-ray images of macrophage ultrastructures. The successful x-ray imaging of macrophage ultrastructure indicates that proximity x-ray microscopy may be of value in studying physiology linked to the dynamics of a cell.