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Biomedical subjects

A Hoffman

Publications and source records attributed to A Hoffman.

At least 19 recordsLinked to original sources

Cerebral hemodynamics in symptomatic and asymptomatic patients with severe unilateral carotid stenosis before and after carotid endarterectomy.

BACKGROUND: Data concerning hemodynamic status prior to and after carotid endarterectomy (CEA) in symptomatic and asymptomatic patients is insufficient. Transcranial Doppler (TCD) provides information regarding compensatory collateral flow as well as mechanisms of cerebral autoregulation in patients with carotid stenosis. PATIENTS AND METHODS: Forty eight symptomatic and 81 asymptomatic patients with unilateral severe carotid stenosis were examined by TCD before and in early postoperative period after CEA. RESULTS: Cigarette smoking was the only risk factor significantly more frequent in symptomatic patients. Preoperative anterior cerebral artery (ACA) and middle cerebral artery (MCA) asymmetry, basilar artery velocity and number of ophthalmic arteries with reversed flow, were not significantly different between the two groups. Pulsatility index, cerebrovascular reactivity and flow acceleration on the side of stenosis were significantly lower in symptomatic patients. After surgery there was a significant improvement of all TCD parameters in symptomatic as well as asymptomatic patients. CONCLUSIONS: The exhausted ability of cerebral autoregulation is an important factor differentiating between symptomatic and asymptomatic patients with severe carotid stenosis. Successful surgery provides good recovery of cerebral hemodynamics in both symptomatic and asymptomatic patients.

Aged↗

A novel phospholipid derivative of indomethacin, DP-155 [mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido]hexanoyl}-sn-glycero-3-phosophatidyl [corrected] choline], shows superior safety and similar efficacy in reducing brain amyloid beta in an Alzheimer's disease model.

Indomethacin has been suggested for the treatment of Alzheimer's disease (AD), but its use is limited by gastrointestinal and renal toxicity. To overcome this limitation, D-Pharm Ltd. (Rehovot, Israel) developed DP-155 (mixture of 1-steroyl and 1-palmitoyl-2-{6-[1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolyl acetamido] hexanoyl}-Sn-glycero-3-phosophatidyl [corrected] choline), a lecithin derivative of indomethacin. Safety was tested by daily oral administration of DP-155 or indomethacin to rats in a dose range of 0.007 to 0.28 mmol/kg. The prevalence of gastrointestinal ulceration was significantly lower (10-fold) for DP-155 than for indomethacin, and the ulcerations were delayed. Signs of renal toxicity, namely reduced urine output and increased urine N-acetyl glycosaminidase to creatinine ratio, were 5-fold lower for DP-155. Indomethacin, but not an equimolar dose of DP-155, reduced urine bicyclo-prostaglandin E(2). An equimolar oral dose of DP-155 or indomethacin, administered every 4 h for 3 days, was equally efficacious in reducing the levels of Abeta42 in the brains of Tg2576 mice. Indomethacin was the principal metabolite of DP-155 in the serum. After DP-155 oral administration, indomethacin's half-life in the serum and the brain was 22 and 93 h, respectively, compared with 10 and 24 h following indomethacin oral administration. The brain to serum ratio was 3.5 times higher for DP-155 than indomethacin. This finding explains the efficacy of DP-155 in reducing Abeta42 brain levels, despite the low systemic blood concentrations of indomethacin derived from DP-155. In conclusion, compared with indomethacin, DP-155 has significantly lower toxicity in the gut and kidney while maintaining similar efficacy to indomethacin in lowering Abeta42 in the brains of Tg2576 mice. This superior safety profile highlights DP-155's potential as an improved indomethacin-based therapy for AD.

Alzheimer Disease↗

Acetic acid-guided biopsies after magnifying endoscopy compared with random biopsies in the detection of Barrett's esophagus: a prospective randomized trial with crossover design.

BACKGROUND: In contrast to standard video endoscopy, magnifying endoscopy after local acetic acid application enables recognition of mucosal surface architecture. OBJECTIVE: To investigate the diagnostic yield of magnifying endoscopy with acetic acid-targeted biopsies compared to random, 4-quadrant biopsies. DESIGN: Prospective randomized trial (ratio 1:1) with crossover design. SETTING: Two referral hospitals in Germany. PATIENTS: Thirty-one patients with Barrett's esophagus or visible columnar-lined lower esophagus. INTERVENTIONS: Patients were randomized to undergo either standard video endoscopy with 4-quadrant biopsies or magnifying endoscopy in conjunction with acetic acid application. All patients were re-examined 14 days after the initial endoscopy with the corresponding procedure. MAIN OUTCOME MEASUREMENTS: Primary outcome analysis (per protocol and per biopsy) was the histological proof of Barrett's epithelium. Secondary outcome analysis was the correlation between the surface architecture and the presence of Barrett's epithelium and the needed number of biopsies to confirm Barrett's epithelium for the 2 different procedures. RESULTS: Magnifying endoscopy enabled the prediction of Barrett's epithelium with a sensitivity of 100% and a specificity of 66%, respectively (accuracy 83.8%). Acetic acid-guided biopsies obtained a significantly higher percentage of tissues containing SCE (78%; 188/241) compared to random biopsies (57%; 159/280). LIMITATIONS: No data on the diagnosis of Barrett's dysplasia. CONCLUSION: Magnifying endoscopy with acetic acid-guided biopsies is superior to standard video endoscopy with random biopsies, and the number of biopsies needed to confirm Barrett's epithelium is half as much when compared to random biopsies.

Acetic Acid↗

Colonoscopy, tumors, and inflammatory bowel disease - new diagnostic methods.

Accurate detection of premalignant lesions and early cancers in the colon is essential for curative endoscopic or surgical therapy, since the prognosis for the affected patients is closely related to the size and stage of the neoplastic lesion. Total colonoscopy is the accepted gold standard for screening and surveillance of colorectal cancer. This review summarizes recently published diagnostic developments and key findings in the areas of colonoscopy, colonic tumors, and inflammatory bowel diseases. Relevant findings have been reported for chromo-endoscopy in the diagnosis of colitis-associated neoplasia, as well as flat and depressed adenomas. Real-time Doppler capabilities have now been added to endoscopic optical coherence tomography; the results of large-scale testing of narrow-band imaging endoscopy in the colon are being awaited; and fluorescence imaging has recently been added to the facilities available in video endoscopy. Most importantly, endomicroscopy now for the first time allows single-cell subsurface imaging during ongoing colonoscopy procedures, opening the way to in-vivo molecular and functional imaging.

Colitis↗

Confocal laser endomicroscopy: technical status and current indications.

Confocal laser endomicroscopy is a newly introduced endoscopic tool that makes it possible to carry out confocal microscopic examination of the mucosal layer during ongoing endoscopy. Different types of tissue and diseases can be diagnosed immediately, facilitating early diagnosis of gastrointestinal cancer. Analysis of the in vivo microarchitecture is helpful in targeting biopsies to relevant areas. In addition, subsurface imaging can unmask microscopic diseases - (microscopic colitis) or bacterial infection ( HELICOBACTER PYLORI), for example. Molecular imaging is becoming feasible, and this will shortly open the door to new indications in gastrointestinal endoscopy (e.g., in vivo receptor analysis).

Barrett Esophagus↗

Heterogeneous airway versus tissue mechanics and their relation to gas exchange function during mechanical ventilation.

We have advanced a commercially available ventilator (NPB840, Puritan Bennett/Tyco Healthcare, Pleasanton, CA) to deliver an Enhanced Ventilation Waveform (EVW). This EVW delivers a broadband waveform that contains discrete frequencies blended to provide a tidal breath, followed by passive exhalation. The EVW allows breath-by-breath estimates of frequency dependence of lung and total respiratory resistance (R) and elastance (E) from 0.2 to 8 Hz. We hypothesized that the EVW approach could provide continuous ventilation simultaneously with an advanced evaluation of mechanical heterogeneities under heterogeneous airway and tissue disease conditions. We applied the EVW in five sheep before and after a bronchial challenge and an oleic acid (OA) acute lung injury model. In all sheep, the EVW maintained gas exchange during and after bronchoconstriction, as well as during OA injury. Data revealed a range of disease conditions from mild to severe with heterogeneities and airway closures. Correlations were found between the arterial partial pressure of oxygen (PaO2) and the levels and frequency-dependent features of R and E that are indicative of mechanical heterogeneity and tissue disease. Lumped parameter models provided additional insight on heterogeneous airway and tissue disease. In summary, information obtained from EVW analysis can provide enhanced guidance on the efficiency of ventilator settings and on patient status during mechanical ventilation.

Animals↗

Improving clinical practice in stroke through audit: results of three rounds of National Stroke Audit.

BACKGROUND: The results of three rounds of National Stroke Audit in England, Wales and Northern Ireland are compared. METHODS: Audit of the organization of stroke services and retrospective case-note audit of up to 40 consecutive cases admitted per hospital over a 3-month period was conducted in each of 1998, 1999 and 2001/02. The changes in the organizational, case-mix and process results of the hospitals that had participated in all three rounds were analysed. RESULTS: 60% of all eligible trusts from England, Wales and Northern Ireland took part in all three audits in 1998, 1999 and 2001/02. Total numbers of cases were 4996, 4841 and 5152, respectively. Case-mix variables were similar over the three rounds. Mortality at 7 and 30 days fell by 3% and 5%, respectively. The proportion of hospitals with a stroke unit rose from 48% to 77%. The proportion of patients spending most of their stay in a stroke unit rose from 17% in 1998 to 26% in 1999 and 29% in 2001/02. Improvements achieved in process standards of care between 1998 and 1999 (median change was a gain of 9%) failed to improve further by 2001/02 (median change was 0%). In all three rounds process standards of care tended to be better in stroke units. CONCLUSIONS: Three rounds of national audit of stroke care have shown standards of care on stroke units were notably higher than on general wards. Slowing in the rise of the proportion managed on stroke units mirrors the slow down in improvement to overall national standards of care. To further improve outcomes and national standards of stroke care a much higher proportion of patients needs to be managed in stroke units.

Aged↗

Use of the Vector scaling unit in supportive periodontal therapy: a subjective patient evaluation.

BACKGROUND: Patient discomfort is one reason for poor compliance with supportive periodontal therapy (SPT). The aim of this study was to compare the levels of discomfort during SPT, using the Vector system and treatment with a conventional ultrasonic scaler. METHODS: Forty-six patients with an SPT programme were debrided using both the Vector system and a conventional piezo-electric scaler (Sirona) in a split mouth design. A visual analogue scale was used to evaluate of pain scores upon completion of treatment. A verbal response scale(VRS) was used to assess discomfort, vibration and noise associated with the scaling system, as well as the volume and taste of the coolant used by these systems. RESULTS: Patients instrumented with the Vector system experienced approximately half the amount of pain compared with the conventional ultrasonic scaling system. The VRS showed that the Vector system caused less discomfort than the conventional ultrasonic scaling system when assessed for pain, vibration, noise and volume of coolant. These findings were all statistically significant. There was, however, no statistically significant difference between the two systems when assessed for taste. CONCLUSION: During SPT the Vector system caused reduced discomforting sensations compared with conventional methods and may be useful in improving compliance with SPT programmes.

Adult↗

Stroke units: research and reality. Results from the National Sentinel Audit of Stroke.

OBJECTIVES: To use data from the 2001-2 National Stroke Audit to describe the organisation of stroke units in England, Wales and Northern Ireland, and to see if key characteristics deemed effective from the research literature were present. DESIGN: Data were collected as part of the National Sentinel Audit of Stroke in 2001, both on the organisation and structure of inpatient stroke care and the process of care to hospitals managing stroke patients. SETTING: 240 hospitals from England, Wales and Northern Ireland took part in the 2001-2 National Stroke Audit, a response rate of over 95%. These sites audited a total of 8200 patients. AUDIT TOOL: Royal College of Physicians Intercollegiate Working Party Stroke Audit Tool. RESULTS: 73% of hospitals participating in the audit had a stroke unit but only 36% of stroke admissions spent any time on one. Only 46% of all units describing themselves as stroke units had all five organisational characteristics that previous research literature had identified as being key features, while 26% had four and 28% had three or less. Better organisation was associated with better process of care for patients, with patients managed on stroke units receiving better care than those managed in other settings. CONCLUSION: The National Service Framework for Older People set a target for all hospitals treating stroke patients to have a stroke unit by April 2004. This study suggests that in many hospitals this is being achieved without adequate resource and expertise.

Health Services Research↗

Changing occupational therapy and physiotherapy practice through guidelines and audit in the United Kingdom.

BACKGROUND: The National Clinical Guidelines for Stroke (NCGS) were produced and three rounds of the National Sentinel Audit of Stroke conducted to improve the quality of stroke care in the UK. OBJECTIVE: To compare the results of the occupational therapy and physiotherapy elements of the most recent national sentinel audit with the occupational therapy- and physiotherapy-specific recommendations of the NCGS. METHODS: Retrospective case-note audit. RESULTS: Over 95% of hospitals/sites who manage stroke in England, Wales and Northern Ireland took part in the most recent round of the sentinel audit. The clinical audit took place from 1 April to 30 June 2001 and incorporated 235 hospitals/sites. The organizational audit took place in January 2002 and incorporated 240 hospitals/sites. Data are presented from the 235 with both clinical and organizational data, under the headings of: approaches to rehabilitation; carers/families; rehabilitation interventions; and transfer to the community. Low rates of compliance with national standards were observed for all domains. CONCLUSION: Our findings suggest that occupational therapists and physiotherapists are not fully complying with the national standards for stroke care.

England↗

Stroke unit care and outcome: results from the 2001 National Sentinel Audit of Stroke (England, Wales, and Northern Ireland).

BACKGROUND AND PURPOSE: Stroke unit care is one of the most powerful interventions available to help stroke patients. There are limited data available to assess the impact of stroke units in routine clinical practice outside randomized clinical trials. This article uses data from the 2001 to 2002 National Stroke Audit to assess the effectiveness of stroke unit care in England, Wales, and Northern Ireland in delivering effective processes of care and in reducing case fatality and disability. METHODS: An observational study of the organization, structure, process of care, and outcomes for stroke in 2001. Case fatality after stroke in England was compared using data from the audit and routinely collected data from the Department of Health. 240 hospitals (196 Trusts) from England, Wales, and Northern Ireland took part in the 2001 to 2002 National Stroke Audit, a response rate of >95%. These sites assessed a total of 8200 patients using the Royal College of Physicians Intercollegiate Working Party Stroke Audit Tool. RESULTS: The availability of stroke unit care varies hugely across the country. Case fatality after stroke was higher in Trusts with least availability of stroke unit care. These differences persisted after control for case mix. The process of care was better for patients managed on stroke units compared with other settings. Overall, the risk of death for patients who received stroke unit care was estimated to be approximately 75% that of the risk for those having no stroke unit care (95% CI, 60 to 90). CONCLUSIONS: Stroke unit care as provided in routine clinical practice in England, Wales, and Northern Ireland reduces case fatality by approximately 25%, which is in line with the figures obtained from systematic analysis of stroke unit trial data.

Aged↗

Visualization of diamond nucleation and growth from energetic species.

The mystery of diamond nucleation by energetic species is resolved via a special deposition scheme. The evolution of the precursor material for diamond nucleation and the development of the nanodiamond crystallites are visualized by high resolution electron microscopy and other spectroscopies. The diamond precipitation and growth are explained in terms of our recently proposed mechanism [Science 297, 1531 (2002)]]: (i) precipitation of sp(3) clusters a small fraction of which are perfect diamond; (ii) growth of diamond crystallites by preferential displacement of amorphous carbon atoms leaving diamond atoms intact. This general scheme is applicable to other materials such as cubic boron nitride.

Journal Article↗

Effect of dietary sodium intake on the expression of endothelin-converting enzyme in the renal medulla.

BACKGROUND/AIM: Endothelin-converting enzyme (ECE) catalyzes the generation of endothelin-1 (ET-1) from its inactive precursor big-ET-1. Previous studies suggested that the ET-1 system is involved in the regulation of sodium excretion by the kidney. In particular, ET-1 via the ET(B) receptor-mediated signaling has been shown to increase renal medullary blood flow and decrease sodium transport in the collecting duct, both acting to promote renal sodium excretion. The present study was designed to evaluate the possibility that alterations in dietary salt intake may regulate the ECE-1. METHODS: Wistar rats were fed for 3 days either with a diet containing low salt (0.01% NaCl), normal salt (0.5% NaCl), or high salt intake, either by high salt diet (4% NaCl) or normal salt diet plus 0.9% saline drinking. The expression of and immunoreactive protein levels of ECE-1 in the renal medulla was studied by RT-PCR, Northern blotting and Western blotting techniques. RESULTS: The expression of ECE-1 mRNA (by RT-PCR and Northern blotting), as well as the immunoreactive levels of ECE-1, were significantly higher in the renal medulla of rats exposed to high salt intake than in rats on normal salt diet. CONCLUSION: The findings suggest that upregulation of ECE-1, leading to increased generation of ET-1 in the renal medulla, may be a compensatory mechanism promoting enhanced sodium excretion by the kidney in response to high salt intake.

Animals↗

Reduction of occult metastatic disease by extension of the supraomohyoid neck dissection to include level IV.

BACKGROUND: Patients with clinically N0 necks will undergo elective removal of lymphatic tissue from levels I, II, and III as part of their routine surgical management. Level IV is omitted on the basis that there is negligible chance of containing significant occult disease. Evidence to support this approach is minimal, and the aim of this study was to increase the yield of metastatically involved lymph nodes by simply extending the supraomohyoid neck dissection (SOHND) to include level IV. METHODS: The records of 49 patients with cancer of the oral cavity undergoing extended supraomohyoid neck dissection (ESOHND) during the period January 1996-March 1999 were reviewed. All patients were staged as having N0 disease. The follow-up period ranged from 12 to 36 months. RESULTS: Thirteen of 55 N0 stage necks showed occult metastasis (26.5%). Neck failure rate occurred in 4 of 49 patients (8.2%). Neck failure rate in the pN0 group was 5.4% and in the pN+ group was 16.6%. Complication rates of ESOHND were noted as 3.6%. No long-term morbidity arose. Occult metastasis in level IV occurred in 5 of 49 cases (10%). Two cases involved other surgical levels. CONCLUSIONS: ESOHND as performed in this study removed occult level IV metastatic regional disease from an extra 10% of patients that, if the patients had undergone SOHND, would have remained undiscovered. No long-term morbidity is associated with this procedure that the authors now recommend as a first-line treatment in all patients with N0 necks.

Carcinoma↗

Cognitive performance following endarterectomy in asymptomatic severe carotid stenosis.

Cognition and the effects of carotid endarterectomy (CEA) were evaluated in 22 non-demented subjects with vascular risk factors (VRF) and asymptomatic severe carotid artery stenosis (ASCAS), 14 volunteers with VRF but without stenosis, and 24 healthy controls (HC) without VRF. Non-demented subjects with VRF, with or without carotid stenosis scored inferior to HC. It is concluded that carotid stenosis is not a primary cause of cognitive deterioration and CEA does not improve cognition in patients with ASCAS.

Aged↗