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Biomedical subjects

John Butler

Publications and source records attributed to John Butler.

At least 19 recordsLinked to original sources
PubMed2006

Dietary fat reduction and breast cancer outcome: interim efficacy results from the Women's Intervention Nutrition Study.

BACKGROUND: Preclinical and observational studies suggest a relationship between dietary fat intake and breast cancer, but the association remains controversial. We carried out a randomized, prospective, multicenter clinical trial to test the effect of a dietary intervention designed to reduce fat intake in women with resected, early-stage breast cancer receiving conventional cancer management. METHODS: A total of 2437 women were randomly assigned between February 1994 and January 2001 in a ratio of 40:60 to dietary intervention (n = 975) or control (n = 1462) groups. An interim analysis was performed after a median follow-up of 60 months when funding for the intervention ceased. Mean differences between dietary intervention and control groups in nutrient intakes and anthropometric variables were compared with t tests. Relapse-free survival was examined using Kaplan-Meier analysis, stratified log-rank tests, and Cox proportional hazards models. Statistical tests were two-sided. RESULTS: Dietary fat intake was lower in the intervention than in the control group (fat grams/day at 12 months, 33.3 [95% confidence interval {CI} = 32.2 to 34.5] versus 51.3 [95% CI = 50.0 to 52.7], respectively; P<.001), corresponding to a statistically significant (P = .005), 6-pound lower mean body weight in the intervention group. A total of 277 relapse events (local, regional, distant, or ipsilateral breast cancer recurrence or new contralateral breast cancer) have been reported in 96 of 975 (9.8%) women in the dietary group and 181 of 1462 (12.4%) women in the control group. The hazard ratio of relapse events in the intervention group compared with the control group was 0.76 (95% CI = 0.60 to 0.98, P = .077 for stratified log rank and P = .034 for adjusted Cox model analysis). Exploratory analyses suggested a differential effect of the dietary intervention based on hormonal receptor status. CONCLUSIONS: A lifestyle intervention reducing dietary fat intake, with modest influence on body weight, may improve relapse-free survival of breast cancer patients receiving conventional cancer management. Longer, ongoing nonintervention follow-up will address original protocol design plans, which called for 3 years of follow-up after completion of recruitment.

Adult↗
PubMed2006

Neurosurgery in the elderly: brain tumors and subdural hematomas.

Primary malignant brain tumors present a formidable challenge to surgeons, patients, and families. Although the prognosis in elderly patients approaches only 6 months, aggressive resection and adjuvant treatment may be indicated in a select group of patients who have preserved functional status. Subdural hematomas in the geriatric population usually are chronic. Patients often benefit from evacuation but their advanced age and significant comorbidities often increase perioperative morbidity and mortality. Minimally invasive evacuation, possibly under local anesthesia, often is indicated as an initial treatment.

Aged↗
PubMed2006

Intraoperative eye position after sub-Tenon's anesthesia for cataract surgery.

BACKGROUND: To evaluate the incidence and extent of ocular deviation associated with sub-Tenon's anesthesia. METHODS: Seventy-five consecutive patients undergoing routine phacoemulsification with sub-Tenon's anesthesia at the Eye Unit, Royal Gwent Hospital, were prospectively enrolled in this observational case series. The exclusion criteria were patients taking warfarin, or patients with preexisting ocular motility disorders, allergy to local anesthetics, or previous surgery for squint or retinal detachment. Eleven patients were subsequently excluded from the study group as they required additional anesthesia blocks before measurements were taken for ocular deviation. We injected 5 mL of a local anesthetic mixture of 2% lignocaine and 7.5 mg/mL levobupivacaine in the sub-Tenon's space in the inferonasal quadrant. Ocular deviation was assessed objectively by means of the Krimsky test. Forced duction tests were performed before and after anesthesia. RESULTS: Hyperdeviation was documented in 49 (77%) eyes, exodeviation in 62 (97%), and hypodeviation in 6 (9.4%). No esodeviations were documented. Only 2 patients were orthophoric after anesthesia. Mean vertical deviation was 4.4 prism dioptres (PD) (SD 4.7 PD, 95% CI 3.2-5.5 PD, range 0-14 PD). Mean horizontal deviation was 19.5 (SD 9.6, 95% CI 17-22, range 0-50) PD. Forced duction test revealed no mechanical restriction before or after anesthesia. INTERPRETATION: This study suggests that there is an appreciable ocular deviation with sub-Tenon's anesthesia. Intraoperative ocular deviation may make certain procedures more difficult; therefore, we recommend a low threshold for an additional corrective block administered before surgery to rectify the deviation.

Anesthesia, Local↗
PubMed2006

Best evidence topic report. Hyperbaric oxygen therapy in acute fracture management.

A short cut review was carried out to establish whether hyperbaric oxygen therapy (HBOT) is advantageous in fracture healing. A total of 26 citations were found of which one answered the three part question. The clinical bottom line is that there is insufficient evidence to support the use of hyperbaric oxygen therapy for fracture healing.

Evidence-Based Medicine↗
PubMed2005

Imaging in breast cancer: diffuse optics in breast cancer: detecting tumors in pre-menopausal women and monitoring neoadjuvant chemotherapy.

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are non-invasive diagnostic techniques that employ near-infrared (NIR) light to quantitatively characterize the optical properties of centimeter-thick, multiple-scattering tissues. Although NIR was first applied to breast diaphanography more than 70 years ago, quantitative optical methods employing time- or frequency-domain 'photon migration' technologies have only recently been used for breast imaging. Because their performance is not limited by mammographic density, optical methods can provide new insight regarding tissue functional changes associated with the appearance, progression, and treatment of breast cancer, particularly for younger women and high-risk subjects who may not benefit from conventional imaging methods. This paper reviews the principles of diffuse optics and describes the development of broadband DOS for quantitatively measuring the optical and physiological properties of thick tissues. Clinical results are shown highlighting the sensitivity of diffuse optics to malignant breast tumors in 12 pre-menopausal subjects ranging in age from 30 to 39 years and a patient undergoing neoadjuvant chemotherapy for locally advanced breast cancer. Significant contrast was observed between normal and tumor regions of tissue for deoxy-hemoglobin (p = 0.005), oxy-hemoglobin (p = 0.002), water (p = 0.014), and lipids (p = 0.0003). Tissue hemoglobin saturation was not found to be a reliable parameter for distinguishing between tumor and normal tissues. Optical data were converted into a tissue optical index that decreased 50% within 1 week in response to neoadjuvant chemotherapy. These results suggest a potential role for diffuse optics as a bedside monitoring tool that could aid the development of new strategies for individualized patient care.

Adult↗
PubMed2005

Preclinical evaluation of the pharmacodynamic properties of 2,5-diaziridinyl-3-hydroxymethyl-6-methyl-1,4-benzoquinone.

PURPOSE: The purpose of our study was to investigate the cellular accumulation, DNA cross-linking ability, and cellular toxicity of RH1 (2,5-diaziridinyl-3-[hydroxymethyl[-6-methyl-1,4-benzoquinone), a novel DNA alkylating agent currently in clinical trials. In addition, the in vivo efficacy of RH1 formulated in different vehicles was also compared. EXPERIMENTAL DESIGN: RH1 is activated by the two-electron reducing enzyme NQO1 [NADPH:quinone oxidoreductase] forming a potent cytotoxic agent that cross-links DNA. We have used whole blood, cell lines, and primary explanted tumor cultures to measure both the cellular accumulation, DNA cross-linking, and cytotoxicity of RH1. Furthermore, the pharmacokinetic and pharmacodynamic characteristics of RH1 formulated in different vehicles were measured in vivo using the validated comet-X assay in mice bearing human tumor xenografts. RESULTS: Accumulation of RH1 was shown to be both time and concentration dependent, reaching a maximum after 2 hours and correlated well with DNA cross-linking measurements. DNA cross-linking in vitro could be detected at low (1-10 nmol/L) concentrations after as little as 2 hours exposure. In primary tumor cultures, RH1 induces much higher levels of DNA cross-links at lower doses than either mitomycin C or cisplatin. In vivo efficacy testing using polyvinyl pyrrolidone, saline, or cyclodextrin as vehicles showed DNA cross-links readily detectable in all tissues examined and was enhanced when given in cyclodextrin compared with polyvinyl pyrrolidone or saline. CONCLUSIONS: RH1 represents a potent bioreductive anticancer drug, which may prove effective in the treatment of cancers, particularly those that overexpress NQO1. DNA cross-linking can be reliably measured in tissue using the validated comet-X assay.

Animals↗
PubMed2005

Best evidence topic report. Terlipressin or somatostatin for the treatment of bleeding oesophageal varices.

A short cut review was carried out to establish whether terlipressin or somatostatin is more effective at reducing acute bleeding in adults with known oesophageal varices. Altogether 170 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Acute Disease↗
PubMed2005

Best evidence topic report. Lignocaine as a pretreatment to rapid sequence intubation in patients with status asthmaticus.

A shortcut review was carried out to establish whether pretreatment with intravenous lignocaine is of benefit in asthmatic patients undergoing rapid sequence intubation (RSI). Altogether 157 papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date, and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated (table 3). It is concluded that there is no good evidence to support the use of lignocaine in this circumstance.

Anesthetics, Local↗
PubMed2005

Best evidence topic report. Cricoid pressure in emergency rapid sequence induction.

A short cut review was carried out to establish cricoid pressure reduced aspiration during rapid sequence induction (RSI) of anaesthesia. A total of 241 papers were identified using the reported search, of which three represented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results, and study weaknesses of these best papers are tabulated. There is little evidence to support the widely held belief that the application of cricoid pressure reduces the incidence of aspiration during a rapid sequence intubation.

Anesthesia, Inhalation↗
PubMed2005

Coregistration of dynamic contrast enhanced MRI and broadband diffuse optical spectroscopy for characterizing breast cancer.

A hand-held scanning probe based on broadband Diffuse Optical Spectroscopy (DOS) was used in combination with dynamic contrast enhanced MRI (DCE-MRI) to quantitatively characterize locally-advanced breast cancers in six patients. Measurements were performed sequentially using external fiducial markers for co-registration. Tumor patterns were categorized according to MRI morphological data, and 3D DCE-MRI slices were converted into a volumetric matrix with isotropic voxels to generate views that coincided with the DOS scanning plane. Tumor volume and depth at each DOS measurement site were determined, and a tissue optical index (TOI) that reflects both angiogenic and stromal characteristics was derived from broadband DOS data. In all six cases, optical scans showed significant TOI contrast corresponding to MRI morphological information. Sharp TOI peaks were recovered for well-circumscribed masses. A reduction in TOI was found inside a tumor with a necrotic center. A broadened peak was observed for a diffuse tumor pattern, and an inflammatory septal case provided two TOI peaks that correlated qualitatively with MRI enhancement. These results provide qualitative confirmation of the common signal origin and complementary information content that can be achieved by combining optical and MR imaging for breast cancer detection and clinical management.

Adult↗
PubMed2004

Self-assembled virus-membrane complexes.

Anionic polyelectrolytes and cationic lipid membranes can self-assemble into lamellar structures ranging from alternating layers of membranes and polyelectrolytes to 'missing layer' superlattice structures. We show that these structural differences can be understood in terms of the surface-charge-density mismatch between the polyelectrolyte and membrane components by examining complexes between cationic membranes and highly charged M13 viruses, a system that allowed us to vary the polyelectrolyte diameter independently of the charge density. Such virus-membrane complexes have pore sizes that are about ten times larger in area than DNA-membrane complexes, and can be used to package and organize large functional molecules; correlated arrays of Ru(bpy)(3)(2+) macroionic dyes have been directly observed within the virus-membrane complexes using an electron-density reconstruction. These observations elucidate fundamental design rules for rational control of self-assembled polyelectrolyte-membrane structures, which have applications ranging from non-viral gene therapy to biomolecular templates for nanofabrication.

Bacteriophage M13↗
PubMed2004

The effect of socioeconomic deprivation on fracture incidence in the United Kingdom.

Lifestyle factors such as diet and physical activity vary in different social and income groups, and are known to be important influences on the incidence of osteoporotic fractures. Financial and social pressures are a common concern for older people. We set out to study the effect of socioeconomic deprivation on the incidence of fracture in older people and to compare the findings with those for younger groups. The All Wales Injury Surveillance System (AWISS) is a computerized system that collects injury data from most A&E departments throughout Wales. In this population-based study of 1.8 million people living in the 445 electoral tracts covered by AWISS in south, west, and northeastern Wales, we identified all 60,106 residents who presented with a fracture in 1999 and 2000. We linked details of their fracture with published Townsend deprivation scores for the electoral tract in which they were living and calculated fracture rates by fifths of deprivation. We observed the expected pattern of increasing fracture incidence in older age groups. Fracture incidence was significantly higher in electoral wards with poorer Townsend scores, resulting from a marked effect of socioeconomic deprivation on fracture incidence among younger adults with a rate ratio of 1.64 (95% CI, 1.57 to 1.72). This effect diminished with age, and was not observed in older age groups. At ages 85 and over the rate ratio was 0.94 (95% CI, 0.87 to 1.01). Socioeconomic factors clearly play a part in the causation of fracture in younger adults. Lifestyle influences are important in older age groups, but socioeconomic deprivation does not appear to be a risk factor for the development of osteoporotic fractures in elderly people.

Accidents, Home↗
PubMed2004

Best evidence topic report. Use of heliox for acute asthma in the emergency department.

A short cut review was carried out to establish whether heliox is of benefit in patients with an exacerbation of asthma resistant to standard treatments. Eighteen papers were found using the reported search, of which one presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of this best paper are tabulated. A clinical bottom line is stated.

Acute Disease↗
PubMed2004

Best evidence topic report. Therapeutic hypothermia after out of hospital cardiac arrest.

A short cut review was carried out to establish whether therapeutic hypothermia improves outcome in comatose post cardiac arrest patients. Altogether 176 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Brain Damage, Chronic↗
PubMed2004

Best evidence topic report. Two thumb compared with two finger cardiopulmonary resuscitation in infants.

A short cut review was carried out to establish whether the two thumb technique was superior to the two finger technique in delivering effective chest compressions in infants with cardiac arrest. Altogether 175 papers were found using the reported search, of which four presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Cardiopulmonary Resuscitation↗
PubMed2004

Best evidence topic reports. Hypertonic or isotonic saline in hypotensive patients with severe head injury.

A short cut review was carried out to establish whether hypertonic or isotonic saline improved the outcome most in patients with severe head injury. Altogether 66 papers were found using the reported search, of which three presented the best evidence to answer the clinical question. The author, date and country of publication, patient group studied, study type, relevant outcomes, results and study weaknesses of these best papers are tabulated. A clinical bottom line is stated.

Craniocerebral Trauma↗