Heart failure: A case for subspecialized care management.
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Biomedical subjects
Publications and source records attributed to J J Smith.
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Ureterosciatic herniation is a rare benign event that can mimic diverticulosis or irritable bowel syndrome. This entity has been managed by a number of open surgical techniques. Laparoscopic repair of this entity enabled us to identify the defect, interpose mesh, and obliterate the hernia defect with minimal morbidity. This represents the first report of laparoscopic repair of a ureterosciatic hernia.
PURPOSE: We set out to assess the new Aberdeen Varicose Veins Questionnaire (Aberdeen Questionnaire) for the properties necessary for a valid measure of health outcome, to determine quality of life of patients with varicose veins, and to determine the effect of surgery on quality of life. METHODS: A prospective consecutive cohort of 137 patients undergoing varicose vein surgery completed the self-administered SF-36 and Aberdeen Questionnaire and 25 questions relating to the symptoms and concerns of patients with varicose veins. Follow-up was done by repeated questionnaires 6 weeks after surgery. The Aberdeen Questionnaire was assessed for reliability, validity, responsiveness, and practicality. Quality of life of patients with varicose veins was compared with an age- and sex-matched sample of the general population. RESULTS: Reliability estimates for the 8 scales short-form health survey (SF-36) and the Aberdeen Questionnaire were all above 0.7 (Cronbach's alpha). The Aberdeen Questionnaire had a highly significant correlation (r = 0. 74, P <.0001) with the patients' symptoms and concerns questionnaire, which is evidence of its validity. Patients with varicose veins score lower than United Kingdom norms (P <.001) in the physical domains of the SF-36, indicating worse health. After surgery, the SF-36 scores improved in all 8 domains of health, reaching significance in "Mental Health" (P <.05) and approaching significance in "General Health" (P =.066). The Health Transition Item of the SF-36 and the Aberdeen Questionnaire both showed a highly significant improvement in health (P <.001). CONCLUSION: The Aberdeen Questionnaire is a valid measure of quality of life for patients with varicose veins. Persons with varicose veins have a reduced quality of life compared with the general population, and this discrepancy is significantly improved at 6 weeks by operating on them.
OBJECTIVES: To determine the acceptability of performing distal limb bypass for occlusive vascular disease in the over 75's. METHOD: Patients undergoing surgery between January 1988 and December 1996 were included. Data were obtained from a card system, operating ledgers, admission diaries and hospital notes. RESULTS: A total of 166 patients were identified. There were 69 women and 97 men, 79 were aged 75-79 years, 81 were 80-89 years and six older than 90 years. A total of 171 procedures were performed: infrainguinal bypass in 131 (77%), aorto-femoral bifurcation grafts in 10 (6%) and extra-anatomic bypass in 30 (17%). This represents 28.1% of all reconstructions for occlusive disease during this time. Nine patients (5.4%) died within 30 days and one (0.6%) required a major amputation. During the follow-up period (median 12 months), 14 major and 10 minor amputations were required. Ten patients underwent a second successful reconstructive procedure. CONCLUSION: Reconstruction in this group of older patients can be carried out with acceptable 30-day mortality and limb salvage rates.
RATIONALE AND OBJECTIVES: The purpose of this study was to assess the effect of Health Care Financing Administration (HCFA) regulations on radiology fellowship training. MATERIALS AND METHODS: Surveys were sent to 157 fellowship program directors in body imaging and vascular/ interventional radiology. Questions addressed program accreditation status, faculty supervision of fellows, and any change in faculty supervision of fellows in response to HCFA's revised plan for Medicare Part B reimbursement. RESULTS: Eighty of 157 (51%) surveys were returned. Thirty (37%) respondents indicated supervision of fellows had changed after institution of the new HCFA rules in July 1996. Vascular/interventional program directors (n = 25, 49%) were more likely to have changed their practice than body imaging program directors (n = 5, 17%). Nearly all respondents (29 of 30, 97%) indicating a change stated supervision had increased. Twenty-seven (33%) respondents also indicated faculty supervision was beyond that necessary for patient care and house staff education; most of these respondents (21 of 27, 78%) stated the new HCFA regulations were responsible. Many program directors also expressed concern the HCFA regulations might prevent fellows from obtaining sufficient experience to effectively learn independent clinical decision-making. CONCLUSION: HCFA regulations intended to address attending physician billing practices at teaching institutions may have had the unintended effect of substantively altering the training of radiology fellows.
In the past few years, it has become widely appreciated that apoptotic cell death generally involves activation of a family of proteases, the caspases, which undermine the integrity of the cell by cleavage of critical intracellular substrates. Caspases, which are synthesized as inactive zymogens, are themselves caspase substrates and this cleavage leads to their activation. Hence, the potential exists for cascades of caspases leading to cell death. However, it has been recently recognized that another, perhaps more prominent route to caspase activation, involves the mitochondria. Upon receipt of apoptotic stimuli, either externally or internally generated, cells initiate signaling pathways which converge upon the mitochondria to promote release of cytochrome C to the cytoplasm; cytochrome c, thus released, acts as a potent cofactor in caspase activation. Even cell surface "death receptors" such as Fas, which can trigger direct caspase activation (and potentially a caspase cascade), appear to utilize mitochondria as part of an amplification mechanism; it has been recently demonstrated that activated caspases can cleave key substrates to trigger mitochondrial release of cytochrome c, thereby inducing further caspase activation and amplifying the apoptotic signal. Therefore, mitochondria play a central role in apoptotic cell death, serving as a repository for cytochrome c.
BACKGROUND: Previous studies have related deep venous incompetence to reduced venous ulcer healing rates. The aim of this study was to determine the relationship between the pattern of venous incompetence and ulcer healing. METHODS: A total of 198 legs with venous ulceration were investigated with colour venous duplex imaging to determine the presence and site of venous incompetence. All were treated initially with the four-layer bandage technique. RESULTS: At 6 months, 74 per cent of the venous ulcers had healed using the four-layer bandage technique. There was no significant correlation between the pattern of incompetence and the healing rate of the ulcer. Previous deep vein thrombosis (DVT), increased size of the ulcer and previous episodes of ulceration were associated with a poor healing rate. CONCLUSION: The four-layer bandage technique achieved an ulcer healing rate of 74 per cent after 6 months, irrespective of the pattern of venous incompetence. Patients with a large ulcer, previous DVT or previous episodes of ulceration had delayed healing, supporting the previous literature.
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Two cDNAs encoding gibberellin 2-oxidases were isolated from maturing pea seeds. The first, PsGA2ox1, was isolated by activity screening of a Lambda-ZAP cDNA library excised into phagemid form and expressed in Escherichia coli. The second, PsGA2ox2, was obtained initially as a PCR product using degenerate primers designed according to conserved regions of plant 2-oxoglutarate-dependent dioxygenases. E. coli heterologous expression products of PsGA2ox1 and PsGA2ox2 converted GA1 to GA8, as shown by HPLC-radiocounting, and gas chromatography-MS. PsGA2ox1 converted GA20 to GA29, but GA20 was a poor substrate for the PsGA2ox2 expression product. Furthermore, PsGA2ox1 converted GA29 to GA29-catabolite at a low level of efficiency while PsGA2ox2 did not catalyse this step. A cDNA of PsGA2ox1 isolated from plants of genotype sln contained a single base deletion which was predicted to produce a truncated protein and gibberellin 2-oxidase activity could not be demonstrated from this cDNA. A 10 bp size difference between the introns of the SLN and sln PsGA2ox1 genes was used to show co-segregation between the SLN and sln phenotypes and the size of the PCR products. PsGA2ox1 transcripts were more abundant in cotyledons than in shoots, while the reverse was the case for PsGA2ox2. The expression patterns of the genes, together with the effects of the sln mutation, indicate that PsGA2ox1 plays a major role in GA20 deactivation in both shoots and maturing seeds, while the PsGA2ox2 gene might be important for GA1 deactivation in the shoot.
Human airways produce several antimicrobial factors; the most abundant are lysozyme and lactoferrin. Despite their likely importance in preventing infection, and their possible key role in the pathogenesis of cystic fibrosis (CF), we know little about their antibacterial activity in the context of the CF airway. We found that abundant airway antimicrobial factors kill common CF pathogens, although Burkholderia was relatively resistant. To study the antibacterial activity, we developed a rapid, sensitive, and quantitative in vitro luminescence assay. Because NaCl concentrations may be elevated in CF airway surface liquid, we tested the effect of salt on antibacterial activity. Activity of individual factors and of airway lavage fluid was inhibited by high ionic strength, and it was particularly sensitive to divalent cations. However, it was not inhibited by nonionic osmolytes and thus did not require hypotonic liquid. The inhibition by ionic strength could be partially compensated by increased concentrations of antibacterial factors, thus there was no one unique salt concentration for inhibition. CF airway secretions also contain abundant mucin and elastase; however, these had no effect on antibacterial activity of lysozyme, lactoferrin, or airway lavage fluids. When studied at low NaCl concentrations, CF and non-CF airway lavage fluids contained similar levels of antibacterial activity. These results suggest approaches toward developing treatments aimed at preventing or reducing airway infections in individuals with CF.
P2X purinergic receptor (P2XR) channels bind ATP and mediate Ca(2+) influx--2 signals that stimulate secretory Cl(-) transport across epithelia. We tested the hypotheses that P2XR channels are expressed by epithelia and that P2XRs transduce extracellular ATP signals into stimulation of Cl(-) transport across epithelia. Electrophysiological data and mRNA analysis of human and mouse pulmonary epithelia and other epithelial cells indicate that multiple P2XRs are broadly expressed in these tissues and that they are active on both apical and basolateral surfaces. Because P2X-selective agonists bind multiple P2XR subtypes, and because P2X agonists stimulate Cl(-) transport across nasal mucosa of cystic fibrosis (CF) patients as well as across non-CF nasal mucosa, P2XRs may provide novel targets for extracellular nucleotide therapy of CF.
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Stress urinary incontinence affects millions of women. Many treatment options are available, ranging from behavioral or nonsurgical therapies to surgical intervention. The clinical findings of a multicenter trial using the CapSure (Re/Stor) continence shield to evaluate the safety and efficacy of this device for treating women with stress urinary incontinence are reported here. Additionally, the role of patient education and selection is discussed.
Pex mutants are defective in peroxisome assembly. In the pex20-1 mutant strain of the yeast Yarrowia lipolytica, the peroxisomal matrix protein thiolase is mislocalized exclusively to the cytosol, whereas the import of other peroxisomal proteins is unaffected. The PEX20 gene was isolated by functional complementation of the pex20-1 strain and encodes a protein, Pex20p, of 424 amino acids (47,274 D). Despite its role in the peroxisomal import of thiolase, which is targeted by an amino-terminal peroxisomal targeting signal-2 (PTS2), Pex20p does not exhibit homology to Pex7p, which acts as the PTS2 receptor. Pex20p is mostly cytosolic, whereas 4-8% is associated with high-speed (200,000 g) pelletable peroxisomes. In the wild-type strain, all newly synthesized thiolase is associated with Pex20p in a heterotetrameric complex composed of two polypeptide chains of each protein. This association is independent of PTS2. Pex20p is required for both the oligomerization of thiolase in the cytosol and its targeting to the peroxisome. Our data suggest that monomeric Pex20p binds newly synthesized monomeric thiolase in the cytosol and promotes the formation of a heterotetrameric complex of these two proteins, which could further bind to the peroxisomal membrane. Translocation of the thiolase homodimer into the peroxisomal matrix would release Pex20p monomers back to the cytosol, thereby permitting a new cycle of binding-oligomerization-targeting-release for Pex20p and thiolase.
Apoptosis often involves the release of cytochrome c from mitochondria, leading to caspase activation. However, in apoptosis mediated by CD95 (Fas/APO-1), caspase-8 (FLICE/MACH/Mch5) is immediately activated and, in principle, could process other caspases directly. To investigate whether caspase-8 could also act through mitochondria, we added active caspase-8 to a Xenopus cell-free system requiring these organelles. Caspase-8 rapidly promoted the apoptotic program, culminating in fragmentation of chromatin and the nuclear membrane. In extracts devoid of mitochondria, caspase-8 produced DNA degradation, but left nuclear membranes intact. Thus, mitochondria were required for complete engagement of the apoptotic machinery. In the absence of mitochondria, high concentrations of caspase-8 were required to activate downstream caspases. However, when mitochondria were present, the effects of low concentrations of caspase-8 were vastly amplified through cytochrome c-dependent caspase activation. Caspase-8 promoted cytochrome c release indirectly, by cleaving at least one cytosolic substrate. Bcl-2 blocked apoptosis only at the lowest caspase-8 concentrations, potentially explaining why CD95-induced apoptosis can often evade inhibition by Bcl-2.
OBJECTIVES: We sought to evaluate the relation between warfarin anticoagulation and survival and morbidity from cardiac disease in patients with left ventricular (LV) dysfunction. BACKGROUND: Warfarin anticoagulation plays a major role in the management of patients who have had a large myocardial infarction and in those with atrial fibrillation. However, its use in patients with LV systolic dysfunction has been controversial. METHODS: We reviewed data on warfarin use in 6,797 patients enrolled in the Studies of Left Ventricular Dysfunction (SOLVD) trial and analyzed the relation between warfarin use and all-cause mortality, as well as the combined end point of death or hospital admission for heart failure. We used Cox regression to adjust for differences in baseline characteristics and to test for the interaction between warfarin use and selected patient variables in relation to outcome. RESULTS: On multivariate analysis, use of warfarin was associated with a significant reduction in all-cause mortality (adjusted hazard ratio [HR] 0.76, 95% confidence interval [CI] 0.65 to 0.89, p = 0.0006) and in the risk of death or hospital admission for heart failure (HR 0.82, 95% CI 0.72 to 0.93, p = 0.0002). Risk reduction was observed when each trial or randomization arm was analyzed separately, as well as in both genders. It was not significantly influenced by the presence of atrial fibrillation, age, ejection fraction, New York Heart Association functional class or etiology. CONCLUSIONS: In patients with LV systolic dysfunction, warfarin use is associated with improved survival and reduced morbidity. This association is primarily due to a reduction in cardiac events and does not appear to be limited to any particular subgroup.