bluuebunny/crossref_metadata_2025_split huggingface dataset:
A review of the epidemiological evidence for the ‘antioxidant hypothesis’
Authors: Stanner SA , Hughes J , Kelly CNM , Buttriss J 
Published: May 2004

AbstractObjective:The British Nutrition Foundation was recently commissioned by the Food Standards Agency to conduct a review of the government's research programme onAntioxidants in Food. Part of this work involved an independent review of the scientific literature on the role of antioxidants in chronic disease prevention, which is presented in this paper.Background:There is consistent evidence that diets rich in fruit and vegetables and other plant foods are associated with moderately lower overall mortality rates and lower death rates from cardiovascular disease and some types of cancer. The ‘antioxidant hypothesis’ proposes that vitamin C, vitamin E, carotenoids and other antioxidant nutrients afford protection against chronic diseases by decreasing oxidative damage.Results:Although scientific rationale and observational studies have been convincing, randomised primary and secondary intervention trials have failed to show any consistent benefit from the use of antioxidant supplements on cardiovascular disease or cancer risk, with some trials even suggesting possible harm in certain subgroups. These trials have usually involved the administration of single antioxidant nutrients given at relatively high doses. The results of trials investigating the effect of a balanced combination of antioxidants at levels achievable by diet are awaited.Conclusion:The suggestion that antioxidant supplements can prevent chronic diseases has not been proved or consistently supported by the findings of published intervention trials. Further evidence regarding the efficacy, safety and appropriate dosage of antioxidants in relation to chronic disease is needed. The most prudent public health advice remains to increase the consumption of plant foods, as such dietary patterns are associated with reduced risk of chronic disease.
Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3β
Authors: Jamali Amina El , Freund Christian , Rechner Cindy , Scheidereit Claus , Dietz Rainer , Bergmann Martin W. 
Published: May 2004

ABSTRACTIn vivo, left ventricular remodeling after myocardial infarction involves hypertrophy generally attributed to increased cardiac workload. We hypothesized that hypoxia/reoxygenation directly induces cardiomyocyte hypertrophy and studied several participating kinases and transcription factors in isolated cardiomyocytes. Hypoxia for 6 h followed by 42 h reoxygenation induced cardiomyocyte hypertrophy assessed by 3H leucine incorporation and immunohistochemistry. Inhibition of reactive oxygen species (ROS), serine/threonine kinase AKT, and ERK abolished reoxygenation‐induced hypertrophy. In addition, a β2‐adrenergic receptor (β2‐AR) antagonist, as well as Gi inhibitor pertussis toxin, blocked reoxygenation‐induced hypertrophy. Hypoxia for 6 h increased transcription factors CREB, NF‐κ B, and GATA DNA binding activities. However, only CREB DNA‐binding was sustained during reoxygenation. Inhibition of PI3‐kinase, ERK, and PKA abrogated reoxygenation‐induced CREB DNA‐binding without affecting CREB serine‐133 phosphorylation. These same pathways were found to regulate hypoxia/reoxygenation‐induced GSK3β kinase activity and CREB serine‐129 de‐phosphorylation. GSK3β mutants resistant to phosphorylation blocked the stimulation of CRE‐dependent transcription induced by hypoxia/reoxygenation. Transfection of cardiomyocytes with a dominant‐negative mutant of CREB abrogated hypoxia/reoxygenation‐induced hypertrophy. We suggest that hypoxia/reoxygenation induces cardiomyocyte hypertrophy through CREB activation. Inactivation of GSK3β by hypoxia/reoxygenation, possibly integrating PI3‐kinase and ERK pathways downstream of β2‐AR and ROS, is a prerequisite for CRE‐dependent transcription. Transient hypoxia may contribute to cardiac hypertrophy in ischemic heart disease independent of cardiac workload.
Formation of amyloid aggregates from human lysozyme and its disease‐associated variants using hydrostatic pressure
Authors: Felice Fernanda G. De , Vieira Marcelo N. N. , Meirelles M. Nazareth L. , Morozova‐Roche Ludmilla A. , Dobson Christopher M. , Ferreira Sérgio T. 
Published: May 2004

ABSTRACTFormation of amyloid deposits from the Ile56Thr or Asp67His variants of human lysozyme is a hallmark of autosomal hereditary systemic amyloidosis. It has recently been shown that amyloid fibrils can be formed in vitro from wild‐type (WT), I56T, or D67H lysozyme variants upon prolonged incubation at acidic pH and elevated temperatures (1). Here, we have used hydrostatic pressure as a tool to generate amyloidogenic states of WT and variant lysozymes at physiological pH. WT or variant lysozyme samples were initially compressed to 3.5 kbar (at 57°C, pH 7.4). Decompression led to the formation of amyloid fibrils, protofibrils, or globular aggregates, as indicated by light scattering, thioflavin T fluorescence, and transmission electron microscopy analysis. Increased 1‐anilinonaphthalene‐8‐sulfonate binding to the proteins was also observed, indicating exposure of hydrophobic surface area. Thus, pressure appears to induce a conformational state of lysozyme that aggregates readily upon decompression. These results support the notion that amyloid aggregation results from the formation of partially unfolded protein conformations and suggest that pressure may be a useful tool for the generation of the amyloidogenic conformations of lysozyme and other proteins.
HIV associated neurodegeneration requires p53 in neurons and microglia
Authors: Garden Gwenn A. , Guo Weiqun , Jayadev Suman , Tun Christina , Balcaitis Stephanie , Choi Jo , Montine Thomas J. , Möller Thomas , Morrison Richard S. 
Published: May 2004

ABSTRACTHIV infection of the central nervous system leads to HIV‐associated dementia (HAD) in a substantial subset of infected individuals. The pathogenesis of neuronal dysfunction in HAD is not well understood, but previous studies have demonstrated evidence for activation of apoptotic pathways. The tumor suppressor transcription factor p53 is an apical mediator of neuronal apoptosis following a variety of injurious stimuli. To determine whether p53 participates in HAD, we exposed cerebrocortical cultures from wild‐type and p53 deficient mice to the neurotoxic HIV envelope protein gp120. Using neuron/microglia co‐culture of mixed p53 genotype, we observed that both neurons and microglia require p53 for gp120 induced neuronal apoptosis. Additionally, accumulation of p53 protein in neurons was recently reported in post‐ mortem cortical tissue from a small group of HAD patients. Using a much larger cohort of HAD cases, we extend this finding and report that p53 protein also increases in non‐neuronal cells, including microglia. Taken together these findings demonstrate a novel role for p53 in the microglial response to gp120. Additionally, these findings, in conjunction with a recent report that monocytes expressing HIV‐Tat also secrete neurotoxins that promote p53 activation, suggest that distinct HIV proteins may converge on the p53 pathway to promote neurotoxicity.
Use of the Vacuum‐Assisted Closure Device in Enhancing Closure of a Massive Skull Defect
Authors: Marathe Umesh S. , Sniezek Joseph C. 
Published: May 2004

AbstractObjectives/Hypothesis: The objective was to describe a novel technique for reconstructing the cranial vertex without the use of free tissue transfer.Study Design: Case report, literature review, and discussion.Methods: A 50‐year‐old woman presented from a remote Pacific Island community with a 12 × 14‐cm, necrotic, grossly contaminated eccrine gland carcinoma of the cranial vertex that extended through the calvarium but did not invade the dura. Following tumor extirpation, the resulting bony defect was 10 × 12 cm in size, with a concomitant scalp defect of 14 × 16 cm. Free tissue transfer was impossible because of severe intimal peripheral vascular disease, posing a challenging reconstructive dilemma. After tumor resection, the bony edges were covered with local scalp flaps and the vacuum‐assisted closure device was placed over the wound at a constant setting of −50 mm Hg. The vacuum‐assisted closure device was changed three times per week for 3 weeks.Results: A thick, 1‐cm bed of granulation tissue developed over the dura, allowing temporary coverage by a split‐thickness skin graft, and the scalp defect decreased in size by approximately 25%. The patient did not develop meningitis, headache, or localized infection as a result of placement of the vacuum‐assisted closure device and tolerated the vacuum‐assisted closure well. After a requisite period of healing, tissue expanders and calvarial reconstruction will be performed.Conclusion: Use of the vacuum‐assisted closure device is a safe, reliable adjunct in the closure of large cranial defects with exposed dura and offers a novel reconstructive option for complex defects of the head and neck.
Management of Cerebrospinal Fluid Rhinorrhea: The Medical College of Wisconsin Experience
Authors: Lindstrom D. Richard , Toohill Robert J. , Loehrl Todd A. , Smith Timothy L. 
Published: May 2004

AbstractIntroduction: The management of cerebrospinal fluid (CSF) rhinorrhea has evolved in recent years. The purpose of this comprehensive retrospective study is to assess issues related to the management of skull base defects associated with CSF rhinorrhea involving the nose and paranasal sinuses.Methods: A retrospective review of CSF leak management was conducted. This study included patients with CSF rhinorrhea managed by the Department of Otolaryngology, Medical College of Wisconsin, Milwaukee, WI, from 1992 to 2002. Data collected included site of leak, surgical approach, and any recurrence of leak.Results: Fifty‐seven CSF leaks occurred in 53 patients with CSF rhinorrhea originating from the nose or paranasal sinuses. Twenty‐eight of the 53 had iatrogenic injuries resulting in CSF rhinorrhea, 16 had leaks from trauma, and 13 developed spontaneous CSF leaks. Ten patients responded to nonoperative management with bed rest with or without lumbar drain placement. Forty‐three patients with 47 leaks underwent surgical repair of CSF rhinorrhea, of which 38 resolved after initial repair. Five of these patients developed recurrent CSF leaks at the repair site but resolved with subsequent surgery. Of these, two initially presented with spontaneous CSF leaks, one patient had a gunshot wound with massive skull base injury, and two recurred after repair of an iatrogenic injury. Factors associated with failure included lateral sphenoid leaks and elevated body mass index (BMI).Discussion: Multiple approaches to the management of CSF rhinorrhea can be successful. An endoscopic repair results in resolution of CSF rhinor‐rhea in the majority of cases. Patients with spontaneous CSF rhinorrhea, elevated BMI, lateral sphenoid leaks, and extensive skull base defects are at increased risk for recurrence. Alternative management options may need to be considered in these cases.
Vibration With the Canalith Repositioning Maneuver: A Prospective Randomized Study to Determine Efficacy
Authors: Macias John D. , Ellensohn Andrea , Massingale Shelly , Gerkin Richard 
Published: May 2004

AbstractObjectives/Hypothesis: The objective was to determine whether the inclusion of vibration and additional treatment cycles has an effect on short‐ and long‐term success rates in the treatment of benign paroxysmal positional vertigo with the canalith repositioning maneuver.Study Design: Prospective randomized study of patients treated at a tertiary vestibular rehabilitation center.Methods: Variables identified for statistical analysis included patient age, gender, vibration used, and canalith repositioning cycles. Analysis using Student t test, χ2 test, Kaplan‐Meier curves with log rank test, and Cox proportional hazards regression was performed.Results: One hundred two patients with benign paroxysmal positional vertigo treated over a 1‐year period (August 2001–August 2002) were randomly assigned to receive the canalith repositioning maneuver with or without vibration. Average duration of follow‐up was 9.44 months. The single treatment success rate was 93.1%. To relieve symptoms, 29.4% of patients required more than one canalith repositioning cycle. The relapse rate was 30.5%. Thirty‐nine patients were assigned to the canalith repositioning group with vibration, and 63 to the canalith repositioning group without vibration. There was no statistical difference in age, gender, initial success rates, or relapse rates between the canalith repositioning groups with and without vibration. On average, patients required 1.38 canalith repositioning cycles for successful treatment. Vibration did not affect the number of canalith repositioning cycles required to convert the Dix‐Hallpike test result to normal. The need for additional canalith repositioning cycles had no statistical effect on initial treatment success or relapse rates.Conclusion: Vibration provided no additional benefit in initial treatment success or in reducing long‐term relapse rates when included in the canalith repositioning maneuver. Many patients with benign paroxysmal positional vertigo require more than one canalith repositioning cycle at the time of initial treatment to relieve symptoms, but this does not indicate a higher likelihood for recurrence. No variable predicted a higher rate of recurrence.
Cathepsin Gene Expression Profile in Rat Acute Pneumococcal Otitis Media
Authors: Li‐Korotky Ha‐Sheng , Swarts J. Douglas , Hebda Patricia A. , Doyle William J. 
Published: May 2004

AbstractObjectives/Hypothesis: Acute otitis media, often caused by infection with Streptococcus pneumoniae, is characterized by inflammation of the middle ear mucosa. A prominent feature of the host response to bacterial infection of the middle ear mucosa is an influx of inflammatory cells that contributes to the local pool of inflammatory mediators by releasing additional inflammatory chemicals, which in turn cause further tissue injury. The objective was to identify candidate effector and signaling molecules involved in acute otitis media pathogenesis caused by S pneumoniae infection.Study Design: Male Sprague‐Dawley rats were randomly assigned to 1 of 5 groups, including 1 control group without treatment, 2 placebo groups (12 and 48 hours) and 2 infected groups (12 and 48 hours). The rat middle ear was bilaterally inoculated with either 25 μL of tryptic soy broth (TSB group) or 25 μL of TSB containing approximately 1.24 × 1010 cfu/mL of S pneumonias type 6A (SP group). Rats were killed at 12 and 48 hours after inoculation and the middle ear mucosa was collected. Total RNA was extracted and pooled from each group for gene expression assays.Methods: Gene expression profiles for rat middle ear mucosa at 12 and 48 hours after S pneumoniae or placebo inoculation were constructed using microarray technology (Clontech Atlas Rat 1.2 Array, 1176 cDNAs). Genes of interest were further validated by real‐time polymerize chain reaction.Results: Middle ear mucosa expression of a gene cluster encoding the lysosomal cysteine proteases, cathepsins B (Ctsb), L (Ctsl), and K (Ctsk), was modified after S pneumoniae challenge. Specifically, at 12 hours, Ctsk and Ctsl messenger RNA that was abundantly expressed in the normal middle ear mucosa was decreased, whereas Ctsb transcript was induced. The changes in Ctsb and Ctsk gene expression were sustained at 48 hours.Conclusion: The constitutive expression of Ctsk and Ctsl messenger RNA in normal middle ear mucosa supports a function in the maintenance of middle ear mucosa homeostasis, and their downregulation as an early event in acute otitis media may reflect a disruption in that function. The induction of Ctsb messenger RNA in the infected middle ear mucosa suggests a role in early tissue injury; thus, Ctsb may represent a potential target for molecular diagnostics and/or rational intervention during the development of acute otitis media.
Facial Translocation Approach in the Management of Central Skull Base and Infratemporal Tumors
Authors: Suárez Carlos , Llorente José L. , Muñoz Cristina , García Luis A. , Rodrigo Juan P. 
Published: May 2004

AbstractObjectives/Hypothesis: The objectives were to systematize the indications of various types of facial translocation and to present a technical modification to avoid some sequelae of this approach.Study Design: Retrospective analysis was made of patients treated with different types of facial translocation approach to resect nasopharyngeal, infratemporal, and sinonasal tumors.Methods: Thirty‐nine patients underwent facial translocation approaches for neoplasms originally involving the nasopharynx (27) infratemporal fossa (7), and nasal cavity (5). Of the 21 malignant tumors, 2 were stage T2, 5 were stage T3, and 14 were stage T4. From the entire series of patients, 10 received a unilateral medial translocation, 3 a bilateral medial translocation, 25 a standard facial translocation, and 1 an extended medial facial translocation.Results: Fifteen patients (38%) developed some kind of complication, such as wound infection (nine cases) and osteomyelitis and cerebrospinal fluid leak (five cases each). Two patients died as a result of postoperative complications (5.2%). Overall 5‐year survival for malignant tumors was 43%. Neither the histological appearance of the tumor nor the T stage influenced the survival of patients. Survival of patients with intracranial involvement was significantly decreased compared with patients with involvement of other areas (P = .0003).Conclusion: The facial translocation approach offers an excellent exposure in tumors with large degree of involvement of the nasopharynx, infratemporal fossa, nasal cavity, and maxillary sinus. More limited osteotomies are indicated in smaller tumors. The use of midfacial degloving minimizes the number of sequelae of these approaches.
Extracorporeal Lithotripsy for Salivary Calculi: A Long‐Term Clinical Experience
Authors: Capaccio Pasquale , Ottaviani Francesco , Manzo Raffaele , Schindler Antonio , Cesana Bruno 
Published: May 2004

AbstractObjectives/Hypothesis: The objective was to assess in a large series of patients with a long‐term clinical follow‐up the validity of extracorporeal electromagnetic shock wave lithotripsy as a minimally invasive therapy for sialolithiasis.Study Design: Consecutive patient series.Methods: Three hundred twenty‐two consecutive symptomatic outpatients with single or multiple calculi in the submandibular (234 patients) or parotid (88 patients) gland underwent a complete extracorporeal electromagnetic shock wave lithotripsy treatment. Treatment results were classified into three groups: successful result with complete ultrasonographic elimination of the stone after lithotripsy, successful result with residual ultrasonographic fragments that were less than 2 mm in diameter, and unsuccessful result with residual ultrasonographic fragments that were greater than 2 mm in diameter. Univariate and multivariate statistical analyses were performed.Results: Complete elimination of the stone was achieved in 45% of patients. On ultrasonography, residual fragments (<2 mm in diameter) were detected in 27.3% of patients, and persisting fragments greater than 2 mm in diameter were assessed in 27.7% of patients. In 3.1% of patients, all with submandibular gland stones, sialoadenectomy was performed. Recurrence of calculi in the treated gland was observed during a median follow‐up period of 57 months in four patients with complete ultrasonographic clearance of the stone occurring 10 to 58 months after lithotripsy. Univariate analysis showed that a favorable treatment result was significantly associated with the younger age of the patients (≤46 y), parotid and intraductal localization of the stone, diameter of the stone (≤7 mm), and number of therapeutic sessions (≤6). On multivariate analysis, the age of the patient, parotid site of the stone, stone diameter, number of therapeutic sessions, and number of shock waves were associated with favorable outcome.Conclusion: Extracorporeal electromagnetic shock wave lithotripsy is to be considered an efficient, minimally invasive treatment modality for salivary calculi.
Difluoromethylornithine‐Induced Reversible Hearing Loss Across a Wide Frequency Range
Authors: Smith Mark C. , Tinling Steve , Doyle Karen Jo 
Published: May 2004

AbstractObjectives: Alpha‐difluoromethylornithine (DFMO) is an antineoplastic agent that causes reversible hearing loss (HL) by an unknown mechanism. Previous neonatal gerbil studies have identified a dosing regimen of 1 g/kg per day of DFMO given for 3 weeks that results in reversible HL on click‐evoked auditory brainstem response (ABR). The objectives of this study are 1) to measure HL and recovery at several frequencies in neonatal gerbils after DFMO therapy at two different dosing regimens and 2) to identify any effects of DFMO on cochlear histology.Study Design: Prospective, nonrandomized, experimental design with placebo controls.Methods: ABR to tone pips at 2, 4, 8, 16, and 32 kHz were recorded on 62 21‐day‐old Mongolian gerbils after daily subcutaneous injections of DFMO (group A at 1 g/kg, group B at 750 mg/kg) or saline from day 3 to day 20 after birth. Thirty‐seven animals were retested after a 3‐week drug‐free recovery period. Twenty‐seven animals were killed for analysis of cochlear histology.Results: Animals that were administered DFMO demonstrated higher ABR thresholds across all five frequencies, with mean threshold differences of 21 to 29 dB in group A and 11 to 17 dB in group B as compared with controls. Higher thresholds were demonstrated at higher frequencies. Fewer side effects were noted at the lower dose. After a 3‐week drug‐free recovery period, auditory thresholds returned to pretreatment levels. No significant cochlear structural abnormalities were identified under light microscopy.Conclusion: An 18‐day regimen of 750 mg/kg per day of DFMO given subcutaneously in neonatal gerbils causes minimal side effects with broad‐frequency HL that, after 3 weeks of recovery, is fully reversible.
John Watt's map of the Clyde
Authors: Hills R. L. 
Published: May 2004

John Smeaton was engaged from 1755 to 1761 in an abortive attempt to improve the navigation of the river Clyde up to Glasgow. His volumes of Civil and Mechanical Engineering Designs in the Library of the Royal Society contain the maps and plans of the scheme. One is entitled ‘The River of Clyde surveyed by John Watt’. Although surveyed by John Watt in 1734, it was only published posthumously by his nephew James Watt, the famous steam engine improver, in 1759 who revised it with the assistance of his own father and brother. James Watt had helped survey the Clyde in conjunction with Smeaton's schemes in 1758.
The background of Smeaton's work is outlined and the story of the revision of the map and its printing in Edinburgh covered. A second edition was run off in 1794 when John Rennie discovered the engraved copper plate at the Edinburgh printers.