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Biomedical subjects

J Hughes

Publications and source records attributed to J Hughes.

At least 91 records · Page 5Linked to original sources

Classification and risk-factor analysis of infections in a surgical neonatal unit.

BACKGROUND/PURPOSE: Nosocomial infection may result in significant morbidity in surgical neonates. Traditionally, nosocomial infections are classified using time cut-off points. Gastrointestinal carriage of microorganisms has not been used as a criterion for classifying infection in surgical neonates. The aims of the study were to (1) determine the overall infection rate, (2) distinguish between nosocomial and community acquired infections using a 48-hour postadmission cutoff and the carrier state criterion, and (3) determine risk factors for clinical infection. METHODS: A 1-year prospective observational cohort study was undertaken in a regional neonatal surgical unit between 1997 and 1998. All infants residing for >/=3 days in the unit were included in the study (n = 167). Patient demographics, including illness severity (PRISM score), were recorded for all infants. Surveillance throat and rectal swabs were obtained on admission and twice weekly thereafter to determine carrier status. Carriage was defined as isolation of the same microorganism from at least 2 consecutive surveillance samples. Infective episodes were diagnosed if a clinical diagnosis of local or general inflammation was microbiologically proven. RESULTS: A total of 167 infants responsible for 174 admissions were studied. Median gestational age was 38 weeks (range, 24 to 42), median birth weight was 3 kg (range, 1 to 3.6), median age on admission was 8 days (range, 0 to 142), median length of hospital stay was 8 days (range, 3 to 95). The diagnoses were gastrointestinal disorders (n = 96), abdominal wall defects (n = 22), neural tube defects and hydrocephalus (n = 17), thoracic disorders (n = 16), urologic disorders (n = 12), and abdominal tumours (n = 4). Twenty-five infants had 33 episodes of infection giving an overall infection rate of 14.9%. The predominant infecting organism was Stapylococcus aureus (n = 11); others were enterococcus, coagulase negative staphylococcus, Candida spp, Gram-negative bacilli, and anaerobes. A total of 27 of 33 infective episodes were caused by microorganisms carried by the infants on admission (primary endogenous). Only 6 children had "true" nosocomial infections. Using a traditional 48 hour cutoff, 87% of the infections were classed as nosocomial. Birth weight, presence of central venous line, PRISM score, and length of stay were identified as significant risk factors for developing clinical infection. CONCLUSIONS: (1) Carriage allowed us to identify the true nosocomial infection rate (microorganisms acquired in the unit), which was only 18%. In contrast, using a traditional 48 hour cutoff, 87% of the infections would have been classed as nosocomial and warranted unnecessary cross-infection investigations. (2) The results of this study confirm that birth weight, illness severity (PRISM score), presence of central venous catheter, and length of hospital stay were independent risk factors associated with clinical infection in surgical neonates.

Carrier State↗

Intensive care-management at home: an alternative to institutional care?

BACKGROUND: Care management and assessment of need are the cornerstones of the community care reforms in the UK. Although much of the research base has been on highly vulnerable older people, in practice, care management has been implemented for a wider group. OBJECTIVE: To examine how intensive care-management at home has developed. DESIGN: Postal survey of all local authority social services departments in England. METHOD: We used an overview questionnaire (85% response) and an old-age services questionnaire (77% response). We classified local authorities according to the presence or absence of seven indicators of intensive care management at home. RESULTS: 97% of social services departments had a goal of providing a community-based alternative to residential and nursing-home care. However, only 5% had specialist intensive care-management services for older people. Other key indicators of intensive care-management, such as devolved budgets, health service care managers, small caseloads and clear eligibility criteria, were uncommon. CONCLUSIONS: There was little evidence of intensive care-management at home in older peoples' services. This is of concern, given the move towards community-based provision for frail older people. Closer links between secondary health-care services (such as geriatric medicine) and intensive care-management at home may promote more effective care at home for those who are most vulnerable.

Aged↗

Designing meaningful industry metrics for clinical productivity for anesthesiology departments.

IMPLICATIONS: Clinical productivity measurements that account for differences in clinical settings and concurrencies provided more precise comparisons between two anesthesiology groups. The data show that different concurrencies confound the current industry standard, "per full-time equivalent" measurements, whereas "per operating room site" and "per case" measurements allowed for more meaningful comparisons.

Anesthesiology↗

The impact of longer-than-average anesthesia times on the billing of academic anesthesiology departments.

UNLABELLED: Academic anesthesiology departments provide clinical services for surgical procedures that have longer-than-average surgical times and correspondingly increased anesthesia times. We examined the financial impact of these longer times in three ways: 1) the estimated loss in revenue if billing were done on a flat-fee system by using industry-averaged anesthesia times; 2) the estimation of incremental operating room (OR) sites necessitated by longer anesthesia times; and 3) the estimated potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration. Health Care Financing Administration average times per anesthesia procedure code were used as industry averages. Billing data were collected from four academic anesthesiology departments for 1 yr. Each claim billed with ASA units was included except for obstetric anesthesia care. All clinical sites that do not bill with ASA units were excluded. Base units were determined for each anesthesia procedure code. The mean commercial conversion factor (US$45 per ASA unit) for reimbursement was used to estimate the impact in dollar amounts. In all four groups, anesthesia times exceeded the Health Care Financing Administration average. The loss per group in billed ASA units if a flat-fee billing system were used ranged from 18,194 to 31,079 units per group, representing a 5% to 15% decrease (estimated billing decrease of US$818,719 to US$1,398,536 per group). The number of excess OR sites necessitated by longer surgical and anesthesia times ranged from 1.95 to 4.57 OR sites per group. The potential gain in billed units if the hours of productivity of current anesthesia time were applied to surgical cases of average duration was estimated to be from 13,273 to 21,368 ASA units. Longer-than-average anesthesia and surgical times result in extra hours or additional OR sites to be staffed and loss of potential reimbursement for the four academic anesthesiology departments. A flat-fee system would adversely affect academic anesthesiology departments. IMPLICATIONS: We examined the economic impact of longer-than-average anesthesia times on four academic anesthesiology departments in three ways: the estimated loss in revenue under a flat-fee system, the excess operating room sites staffed, and the potential gain in revenue if the surgeries were of average length. These results should be considered both in productivity measurements and strategies for operating room management.

Accounting↗

Comparison of the BACTEC MYCO/F Lytic bottle to the isolator tube, BACTEC Plus Aerobic F/bottle, and BACTEC Anaerobic Lytic/10 bottle and comparison of the BACTEC Plus Aerobic F/bottle to the Isolator tube for recovery of bacteria, mycobacteria, and fungi from blood.

The BACTEC MYCO/F Lytic blood culture bottle (Becton Dickinson Diagnostic Instrument Systems, Sparks, Md.) is designed to optimize the recovery of fungi and mycobacteria; however, this bottle also supports the growth of most aerobic bacteria. We compared the MYCO/F Lytic bottle with two other BACTEC bottles and the Isolator system for the recovery of bacteria as well as fungi and mycobacteria from blood. A total of 6,108 blood culture sets were inoculated with blood obtained from adult patients. Twenty-five to 28 ml of blood collected by a phlebotomy team for each blood culture set was randomly distributed into each of four blood culture receptacles: the Isolator tube (Wampole Laboratories, Cranbury, N.J.) and three BACTEC bottles: the MYCO/F Lytic bottle, the BACTEC Plus Aerobic/F bottle, and the BACTEC Anaerobic Lytic/10 bottle. The sediment from the Isolator tube was inoculated onto chocolate agar (CA), brain heart infusion agar (BHI), and Sabouraud dextrose agar (SDA) and into a BACTEC 13A bottle. Incubation durations were as follows: MYCO/F Lytic bottle, 42 days; Plus Aerobic/F bottle, 5 days; Anaerobic Lytic/10 bottle, 5 days; sediment from Isolator tube on CA, 3 days; sediment from Isolator tube on BHI, 30 days; sediment from Isolator tube on SDA, 30 days; and sediment from Isolator tube in a BACTEC 13A bottle, 42 days. Two isolates of Histoplasma capsulatum were recovered from the Isolator tube only. Three isolates of Mycobacterium tuberculosis complex were recovered: two isolates from the MYCO/F Lytic bottle only and one isolate from the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle) only. Two isolates of Cryptococcus neoformans were recovered: one from the MYCO/F Lytic bottle only and the other from the MYCO/F Lytic bottle and the Isolator tube (whose sediment was inoculated into the BACTEC 13A bottle). For potential pathogens overall, there was a statistical difference in recovery that favored the Isolator system over the MYCO/F Lytic bottle (P = 0.0015), including statistically significant differences for Staphylococcus aureus (P = 0.0001) and Streptococcus pneumoniae (P = 0.0313). However, there was no statistically significant difference between the two blood culture systems when detection of bloodstream infection was considered. The time to detection for all potential pathogens combined was less for the MYCO/F Lytic bottle than for the Isolator system (P = 0.0004). Overall, the potential pathogen recovery was greater for the BACTEC Plus Aerobic/F bottle than for either the Isolator system (P = 0.0003) or the MYCO/F Lytic bottle (P = 0.0001). However, the BACTEC Plus Aerobic/F bottle did not recover M. tuberculosis, H. capsulatum, or C. neoformans isolates. The combination of the Isolator system and MYCO/F Lytic bottle may be useful as a selective blood culture method to optimize the recovery of fungi and mycobacteria from blood. Compared with the manual Isolator system, the MYCO/F Lytic system has the advantage of less preanalytic processing and continuous automated monitoring of bottles for growth by the BACTEC 9240 instrument.

Adult↗

Post-cyclosporine-mediated hypertension and nephropathy: amelioration by vascular endothelial growth factor.

Recent studies have demonstrated a role for microvascular and tubulointerstitial injury in some models of salt-sensitive hypertension. We utilized a model of post-cyclosporin A (CsA) nephropathy and hypertension to test the hypothesis that treatment with an angiogenic factor aimed at ameliorating the microvascular and renal injury would prevent the development of hypertension. CsA was administered with a low-salt diet for 45 days, resulting in a renal lesion characterized by afferent arteriolopathy, focal peritubular capillary loss, and tubulointerstitial fibrosis. Rats were then placed on a high-salt diet and randomized to receive either vascular endothelial growth factor (VEGF(121)) or vehicle for 14 days. Placement of rats with established CsA nephropathy on a high-salt diet results in the rapid development of salt-sensitive hypertension. VEGF(121) treatment resulted in lower blood pressure, and this persisted on discontinuing the VEGF. VEGF(121) treatment was also associated with a decrease in osteopontin expression, macrophage infiltration, and collagen III deposition and markedly stimulated resolution of the arteriolopathy (20.9 +/- 7.8 vs. 36.9 +/- 6.1%, VEGF vs. vehicle, P < 0.05). In conclusion, CsA-associated renal microvascular and tubulointerstitial injury results in the development of salt-sensitive hypertension. Treatment of animals with established CsA nephropathy with VEGF reduces the hypertensive response and accelerates histological recovery. The vascular protective effect of VEGF may be due to the improvement of arteriolopathy. Angiogenic growth factors may represent a novel strategy for treating CsA-associated hypertension and renal disease.

Animals↗

Hypokalemia induces renal injury and alterations in vasoactive mediators that favor salt sensitivity.

We investigated the hypothesis that hypokalemia might induce renal injury via a mechanism that involves subtle renal injury and alterations in local vasoactive mediators that would favor sodium retention. To test this hypothesis, we conducted studies in rats with diet-induced K+ deficiency. We also determined whether rats with hypokalemic nephropathy show salt sensitivity. Twelve weeks of hypokalemia resulted in a decrease in creatinine clearance, tubulointerstitial injury with macrophage infiltration, interstitial collagen type III deposition, and an increase in osteopontin expression (a tubular marker of injury). The renal injury was greatest in the outer medulla with radiation into the cortex, suggestive of an ischemic etiology. Consistent with this hypothesis, we found an increased uptake of a hypoxia marker, pimonidazole, in the cortex. The intrarenal injury was associated with increased cortical angiontensin-converting enzyme (ACE) expression and continued cortical angiotensin II generation despite systemic suppression of the renin-angiotensin system, an increase in renal endothelin-1, a decrease in renal kallikrein, and a decrease in urinary nitrite/nitrates and prostaglandin E(2) excretion. At 12 wk, hypokalemic rats were placed on a normal-K+ diet with either high (4%)- or low (0.01%)-NaCl content. Despite correction of hypokalemia and normalization of renal function, previously hypokalemic rats showed an elevated blood pressure in response to a high-salt diet compared with normokalemic controls. Hypokalemia is associated with alterations in vasoactive mediators that favor intrarenal vasoconstriction and an ischemic pattern of renal injury. These alterations may predispose the animals to salt-sensitive hypertension that manifests despite normalization of the serum K+.

Angiotensin II↗

Elevated uric acid increases blood pressure in the rat by a novel crystal-independent mechanism.

An elevation in circulating serum uric acid is strongly associated with the development of hypertension and renal disease, but whether uric acid has a causal role or whether it simply indicates patients at risk for these complications remains controversial. We tested the hypothesis that uric acid may have a causal role in the development of hypertension and renal disease by examining the effects of mild hyperuricemia in rats. Mild hyperuricemia was induced in rats by providing a uricase inhibitor (oxonic acid) in the diet. Hyperuricemic rats developed elevated blood pressure after 3 weeks, whereas control rats remained normotensive. The development of hypertension was prevented by concurrent treatment with either a xanthine oxidase inhibitor (allopurinol) or a uricosuric agent (benziodarone), both of which lowered uric acid levels. Blood pressure could also be lowered by reducing uric acid levels with either allopurinol or oxonic acid withdrawal. A direct relationship was found between blood pressure and uric acid (r=0.75, n=69), with a 10-mm Hg blood pressure increase for each 0.03-mmol/L (0.5-mg/dL) incremental rise in serum uric acid. The kidneys were devoid of urate crystals and were normal by light microscopy. However, immunohistochemical stains documented an ischemic type of injury with collagen deposition, macrophage infiltration, and an increase in tubular expression of osteopontin. Hyperuricemic rats also exhibited an increase in juxtaglomerular renin and a decrease in macula densa neuronal NO synthase. Both the renal injury and hypertension were reduced by treatment with enalapril or L-arginine. In conclusion, mild hyperuricemia causes hypertension and renal injury in the rat via a crystal-independent mechanism, with stimulation of the renin-angiotensin system and inhibition of neuronal NO synthase.

Animals↗

Electrosurgical smoke plume. Is it harmful to staff?

When a potential problem was identified by several staff regarding electrosurgical smoke plume, Angharad Hughes and Jonathan Hughes decided to look into the situation using an evidence-based approach. What follows is a precis of literature found, and information about how this approach was carried out. It shows that there is some evidence that particles present in smoke plume are potentially harmful to health, but that the extent of the risk is as yet unknown.

Electrosurgery↗

Recombinant phytochrome A in yeast differs by its spectroscopic and photochemical properties from the major phyA' and is close to the minor phyA": evidence for posttranslational modification of the pigment in plants.

Previously, two pools of phytochrome A (phyA' and phyA") have been detected by in situ low-temperature fluorescence spectroscopy and photochemistry; it was suggested that they might differ in the nature of their posttranslational modification. In order to verify this possibility Arabidopsis and rice (Oryza) phyA were expressed in yeast and the pigments were assembled in vivo with phycocyanobilin (PCB) and phytochromobilin (P phi B). The resulting recombinant phytochromes in the red-light-absorbing form (Pr) were characterized in the yeast cell by (1) the fluorescence emission spectra; (2) the temperature dependence of Pr fluorescence intensity and activation energy of fluorescence decay; and (3) the extent of photoconversion of Pr into photoproduct lumi-R (gamma 1) or far-red-light absorbing form (Pfr) (gamma 2). Both Arabidopsis phyA/PCB and Oryza phyA/P phi B had low gamma 1 of ca 0.05, allowing their attribution to the Pr" phenomenological type of phytochrome comprising phyA", phyB and cryptogam phytochromes. The spectroscopic properties of Oryza phyA/P phi B were also very close to phyA". However, both investigated holoproteins differed from phyA", both with respect to the character of temperature dependence of the fluorescence yield and activation energy. Thus, recombinant Oryza phyA/P phi B is similar but not identical to phyA". The data demonstrate that the low-abundance-fraction plant phyA (phyA") comes from the same gene as the major (phyA') fraction. Because both endogenous phyA fractions differ from the phytochrome expressed in yeast, they appear to be posttranslationally modified and/or bound to partner proteins or cellular substructures. However, the character of the presumed chemical modification is different in phyA' and phyA" and its extent is more profound in the case of the former.

Arabidopsis Proteins↗

The prevention of osteoporotic progression by means of steroid loaded TCPL drug delivery systems.

Numerous studies have suggested that there is a link between the age-related decreases in Estradiol and adrenal androgens, and the subsequent development of senile osteoporosis. The specific objectives of this investigation were: 1) to deliver Dehydroepiandrosterone (DHEA), Diosgenin (DG), and Estradiol (E) at sustained levels by Tri-Calcium Phosphate Lysine drug delivery systems (TCPL), and 2) to study the effects of the sustained delivery of DHEA, DG, and E on the bone turnover of adult female rats following withdrawal of the endogenous hormonal milieu by means of ovariectomization (OVX). In this study, 20 female Sprague-Dawley rats were randomly divided into five groups containing four rats per group. The rats in Group 1 served as intact controls. Animals in groups 2-5 were ovariectomized, and groups 3-5 were implanted immediately with TCPL drug delivery capsules containing DHEA, DG, and E, respectively. Group 2 served as the SHAM (OVX only) group. At the end of 33 days post implantation, the vital organs, reproductive organs, and femurs were collected and evaluated. Bone histomorphometric analyses as well as mechanical strength testing was performed. Data obtained from this study demonstrated that body weights were increased in all OVX animals, and that E replacement resulted in body weights that were not significantly different from intact controls. No differences were seen in the wet weights of any vital organs. However, a decrease in the weights of the cervix and oviducts were evident in all ovariectomized groups, with the exception of the E group. Thirty-three days following OVX, the OVX-only group exhibited an increased inner medullary area, decreased thickness of the cortical layer of bone, and decreased mechanical strength. The group treated with DHEA and the group treated with E were shown to maintain both the medullary area and the cortical thickness (as compared to the intact control group). The three point bending test of the femora showed that OVX-only induced a slight decline in mechanical strength, and that DHEA and DG, but not E, showed increases in mechanical strength. Results of this experiment suggest that DHEA and E may reduce bone remodeling as evidenced by the reduction in the medullary area, and that DHEA may possibly be used in postmenopausal patients to reduce osteoporotic progression.

Animals↗

The use of estrogen, DHEA, and diosgenin in a sustained delivery setting as a novel treatment approach for osteoporosis in the ovariectomized adult rat model.

It is well established that the pattern of bone loss from the cortex in osteoporotic bone begins from the endosteal surface of the cortex, where there is enlargement of the medullary canal at the expense of the inner cortex. Bone loss does not occur at the periosteal surface. The objective of the following study was to induce osteoporosis in female rats by ovariectomy, followed by treatment with sustained delivery of Diosgenin (DG), dehydroepiandrosterone (DHEA), or estrogen (E) after clinical signs of osteoporosis. Female Sprague Dawley rats were divided randomly into five groups containing four rats/group. Rats comprising group 1 were left intact and served as a control group. Animals in groups 2-5 were ovariectomized (OVX) and, after a 14 day delay to allow for induction of osteoporosis, were implanted with TCPL capsules containing DG, DHEA, and E, respectively. The experiment was ceased after 33 days of treatment, at which time the vital and reproductive organs for each group were collected, weighed, and analyzed histomorphometrically for differences. Further analysis of the progression of osteoporosis in the experimental animals was obtained by performing x-ray analysis of each group on a semi-weekly basis. By collecting and analyzing the femurs from each animal, we were also able to obtain important information about the histologic changes associated with osteoporosis (left femur), as well as data regarding the effects of osteoporosis on the mechanical strength of bone via three point bending analysis (right femur). The data generated by this study revealed important information as to the efficacy and safety of the alternative treatments DHEA, E, and DG for osteoporosis. First, histomorphometric analysis revealed that treatment with DHEA, E, and DG reduced the endosteal perimeter and cortical area to values very similar to controls (intact). Second, results of the bending stress and modulus in OVX and treated animals were not statistically different from the intact control animals, which suggests that the material properties of the bone were unaltered. Third, there is an increase in total body weight associated with OVX that is reduced to control levels after replacement therapy. Finally, OVX also resulted in reproductive tissue atrophy, which was reversed by all three of the treatment regimens in this study. These data suggest that bone loss after OVX can be significantly reduced by supplementation with sustained levels of DHEA, E, and DG without jeopardizing other body organs.

Animals↗

Morphometric analysis of cortical bone upon the exposure to sustained delivery of anabolic promoting agents using adult male rats as a model.

Several investigations have documented that the use of anabolic agents could promote osteogenesis and enhance bone ingrowth in traumatized bone. Previously, anabolic steroids have been shown to increase the mineralization of bone. However, their clinical use has been limited because of the unwanted virilizing activity. The previous studies used systemic administration of anabolic steroids, which subjects other tissues within the body to high concentrations of hormones. In addition, different anabolic/androgenic steroids have varying affinities to different cell types within tissues. The specific objectives of this study were (i) to histopathologically evaluate the structural changes associated with sustained delivery of testosterone (T), dihydrotestosterone (DHT), and androstendione (AED) using adult male rats as a model, and (ii) to morphometrically evaluate the cortical areas and length upon the exposure of the aforementioned hormones for 90 days. A total of 23 adult rats were randomly divided into five groups (group I = control, group II = sham, group III = AED, Group IV = T and group V = DHT treated). At the end of the treatments the animals were euthanized and the x-rays, blood, and bones were analyzed using standard laboratory protocols. Data obtained from this investigation revealed the following: (A) all treated femurs appeared healthy with no traumatic responses observed in comparison to control animals, (B) measurements of the inner perimeter of the bone on the endosteal side showed significant reduction in the androgen treated animals. This suggesting that the androgens caused increases in the cortical bone. The differences seen in the amount of reduction was in the following ease: T > DHT > AED. C) quantitative measurements of the cortical length showed slight increases in the cortical lengths in the androgen treated rats in comparison to the control.

Anabolic Agents↗

The application of a PCR technique for the detection of immunoglobulin heavy chain gene rearrangements in fresh or paraffin-embedded skin tissue.

Although detection of a clonal sequence of the heavy chain gene of immunoglobulin by the polymerase chain reaction (PCR) is frequently used to assess lymphoid infiltrates in skin biopsy specimens, there are no data on the sensitivity and specificity of this test in detecting clonal B cell populations. Having refined a PCR technique for the detection of immunoglobulin heavy chain (IgH) gene rearrangement in both fresh and formalin-fixed, paraffin-embedded skin samples, we undertook to define the role of this assay in the diagnostic setting. Thirty-one cases of cutaneous B cell lymphoma (CBCL), 19 cases of B cell pseudolymphoma (lymphocytoma cutis), 34 cases of benign lymphocytic infiltrates of the skin and one case of cutaneous T cell lymphoma (CTCL) were studied using the polymerase chain reaction assay. All biopsies were formalin-fixed, paraffin-embedded skin sections apart from 13 of the 31 CBCL specimens which were fresh skin specimens. DNA from the framework region 3 (FR3) sequence of the IgH genes was amplified to ascertain the presence of a clonal IgH gene rearrangement. The findings were correlated with histological and immunophenotyping results on all samples. The assay performed with 73% sensitivity and 100% specificity, comparable to results obtained examining fresh lymphoid tissue specimens from patients with B cell tumours. The results indicate that this technique is a useful tool in the work up of suspected CBCL and in differentiating between CBCL and mixed lymphocytic infiltrates, a clearly important distinction with regards to prognosis and treatment.

Clone Cells↗