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PubMed2006

Metal-binding thermodynamics of the histidine-rich sequence from the metal-transport protein IRT1 of Arabidopsis thaliana.

The widespread ZIP family of transmembrane metal-transporting proteins is characterized by a large intracellular loop that contains a histidine-rich sequence whose biological role is unknown. To provide a chemical basis for this role, we prepared and studied a peptide corresponding to this sequence from the first iron-regulated transporter (IRT1) of Arabidopsis thaliana, which transports Fe2+ as well as Mn2+, Co2+, Zn2+, and Cd2+. Isothermal titration calorimetry (ITC) measurements, which required novel experiments and data analysis, and supporting spectroscopic methods were used to quantify IRT1's metal-binding affinity and associated thermodynamics. The peptide, PHGHGHGHGP, binds metal ions with 1:1 stoichiometry and stabilities that are consistent with the Irving-Williams series. Comparison of the metal-binding thermodynamics of the peptide with those of trien provides new insight about enthalpic and entropic contributions to the stability of the metal-peptide complex. Although Fe2+ and other IRT1-transported metal ions do not bind very tightly, this His-rich sequence has a very high entropy-driven affinity for Fe3+, which may have biological significance.

Amino Acid Sequence↗
PubMed1976

Single layer anastomosis in the gastrointestinal tract.

Anastomotic leakage, often followed by serious morbidity or death, is an important complication of resection of the intestine. If surgical technique and judgment are sound, anastomotic leakage seldom occurs. In 205 elective, single layer anastomoses of stomach to duodenum, of small intestine, of colon and of colorectum, clinically apparent leakage did not occur except in one of 52 patients after colorectal anastomosis. After resection of the intestine performed as an emergency procedure, anastomotic leakage occurred but was infrequent and could clearly be attributed to poor judgment or technique. The results are presented to support a conviction that anastomotic leakage need seldom occur if surgical technique and judgment are sound and to draw attention anew to the efficacy and safety of single layer anastomosis.

Adolescent↗
PubMed1986

An investigation of data entry methods with a personal computer.

The features of three methods of data entry were investigated and a trial of them was carried out using operators with differing amounts of keyboard experience. The first method was a simple system of character entry using a word processing package, and the second and third systems were written in a commercial data base language; one was designed to possess limited intelligence, the other moderate intelligence. The amount of time and computing expertise required to set up each method increased in parallel with its sophistication. The most sophisticated method offered theoretical advantages of reduced error rates and increased keying rates but these were not realized in practice. The limited intelligence method, in which data were entered into a screen image of the record form, was fastest overall and was most popular with all users. This method together with verification by dual keying will provide a convenient, rapid, and high fidelity method of data entry. The simplest method was found to be adequate for short forms but incurred high error rates with longer forms.

Computers↗
PubMed2002

The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein.

The objective of this study was to determine the effects of grapefruit juice and seville orange juice on dextromethorphan (DM) pharmacokinetics. Eleven healthy volunteers were studied over a 3-week period consisting of 5 study days each separated by a three-day washout. All subjects refrained from drinking caffeine containing beverages (coffee, soda, etc.) 8 h before orally taking DM (30 mg) with 200 ml water, 200 ml grapefruit juice, 200 ml water, 200 ml seville orange juice, and 200 ml water on Study Days 1 to 5. Aliquots of urine samples were assayed and analysed for DM, and the DM metabolites dextrorphan, 3-methoxymorphinan and 3-hydroxymorphinan using a validated HPLC method employing a phenyl column and a fluorescence detection. Results suggests that DM could provide some useful information on P-glycoprotein or related membrane efflux protein activity in the human gastro-intestinal tract. Bioavailability (F) of DM increased significantly with grapefruit and seville orange juice, but only returned to half the baseline value after three days of washout. This confirms that grapefruit and seville orange juice are long-lasting and perhaps irreversible inhibitors of gut CYP3A/P-glycoprotein. Grapefruit and seville orange juice appeared to have the same overall effect on DM pharmacokinetics. In addition, this paper presents a novel method of phenotyping for CYP2D6, CYP3A and P-glycoprotein using DM as a probe.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Mastoid obliteration using bone pâté.

The technique of mastoid revision and obliteration using bone pâté and a superiorly based temporalis musculo-periosteal flap is described in detail. This method has evolved and been employed in our department over the past 10 years.

Bone Transplantation↗
PubMed1977

Ascending lumbar venography in the diagnosis of lumbar disc lesions.

Fifty-five patients suffering from low back pain with or without sciatica were submitted to ascending lumbar venography. Six patients had anatomical variations which prevented adequate catheterization and 6 had equivocal radiographic appearances, which we could not assess. Fourteen patients had normal venograms but in 29 an abnormality was demonstrated. These 43 patients were then submitted to radiculography and, where appropriate, surgery. The 14 patients with normal venograms also had normal radiculograms; while the 29 with abnormal venograms had an abnormality confirmed on radiculography and/or surgery. However, in 10 of the patients the lesion was found to be one disc space lower than that demonstrated on venography; Side-effects were very few, and the procedure can be used on out-patients. This technique would appear to be a useful addition to the radiological investigation of the spine.

Adolescent↗
PubMed2002

New technology and methodologies for intraoperative, perioperative, and intraprocedural monitoring of surgical and catheter interventions for congenital heart disease.

We review the new technology and methods available for support of intraoperative and intraprocedural imaging in the catheterization laboratory for surgical and interventional catheterization procedures in the treatment of congenital heart disease. The methods reviewed include miniaturized probes and new ways of using them perioperatively for cardiac imaging from transesophageal, substernal, and intracardiac imaging locations. The smaller and more versatile the probes, the better adapted they will be in providing methods to improve the outcomes in babies born with serious forms of congenital heart disease.

Cardiac Surgical Procedures↗
PubMed2006

HIV prevalence, sociodemographic, and behavioral correlates and recruitment methods among injection drug users in St. Petersburg, Russia.

OBJECTIVE: In St. Petersburg, Russia, we sought to describe the characteristics of active high-risk injection drug users (IDUs) to evaluate the associations between behavioral and demographic characteristics and HIV-1 infection and to describe 3 discrete recruitment methods. METHODS: Active high-risk IDUs were recruited in 3 ways: through street outreach, at facilities serving IDUs, and by network-based chain referral. Recruits were screened, counseled, and tested for HIV-1. Sociodemographic and behavioral data were collected. HIV-1 prevalence was analyzed as a function of sociodemographic and behavioral variables. RESULTS: During the 10-month recruitment period, data from 900 participants were collected: median age was 24 years, and in the previous month, 96% used heroin and 75% shared needles with others. The baseline HIV prevalence was 30% (95% confidence interval [CI]: 27 to 33). Recruitment through social networks was the most productive strategy. HIV-positive individuals were younger, but none of the other sociodemographic or behavioral characteristics differed significantly by HIV status. CONCLUSIONS: The estimated HIV prevalence of 30% places St. Petersburg among the worst IDU-concentrated epidemics in Europe. Recruitment through network-based chain referral is a useful method for recruiting active IDUs. Sociodemographic and behavioral links to prevalent HIV infection remain to be elucidated.

Adult↗
PubMed2005

Single versus sequential fine-needle aspiration biopsy in the management of thyroid nodular disease.

UNLABELLED: Fine-needle aspiration biopsy (FNAB) is considered a safe, reliable and cost-effective means of selecting thyroid nodules with risk for malignancy. However, there are limitations of this method including false positive/negative and "nondiagnostic" results that may be reduced by repeating FNAB. OBJECTIVE: To evaluate accuracy, sensitivity, specificity and costs of sequential FNAB in the management of thyroid nodular disease. METHODS: Charts of all patients who underwent thyroidectomy at a university teaching hospital in Toronto from 1998 to 2000 were reviewed. FNAB reports of "suspicious for malignancy," "follicular lesion" and "cellular atypia" were considered to be positive. Data were analyzed with chi2 and z tests. RESULTS: There were 268 patients (225 women and 43 men; age range 18-89 yr; mean age 47 yr) who underwent a total of 449 FNABs (mean 1.7 FNABs/patient) within a year before thyroidectomy. Accuracy (63.8%), sensitivity (73.8%) and specificity (69%) were determined for single FNABs. Sequential FNAB increased the accuracy of method by 22.6%, sensitivity by 13.8% and specificity by 6.2%, with reduction of false positive/negative results by 14.2% and "nondiagnostic" results by 100%. However, the costs of sequential cytology per patient were 70% higher than single FNAB. CONCLUSIONS: Multiple FNABs are unpleasant for patients, but useful in the selection for treatment of patients with thyroid nodular diseases. Although sequential FNAB increases the costs of method, the improvement of precision of FNAB may imply a reduction in overall health-care costs.

Adult↗
PubMed2003

Quality of perioperative AEP--variability of expert ratings.

BACKGROUND: Previous studies suggest that auditory evoked potentials (AEP) may be used to monitor anaesthetic depth. However, during surgery and anaesthesia, the quality of AEP recordings may be reduced by artefacts. This can affect the interpretation of the data and complicate the use of the method. We assessed differences in expert ratings of the signal quality of perioperatively recorded AEPs. METHODS: Signal quality of 180 randomly selected AEP, recorded perioperatively during a European multicentre study, was rated independently by five experts as 'invalid' (0), 'poor' (1), or 'good' (2). Average (n=5) quality rating was calculated for each signal. Differences between quality ratings of the five experts were calculated for each AEP: inter-rater variability (IRV) was calculated as the difference between the worst and best classification of a signal. RESULTS: Average signal quality of 57% of the AEPs was rated as 'invalid', 39% as 'poor', and only 4% as 'good'. IRV was 0 in only 6%, 1 in 62%, and 2 in 32% of the AEP, that is in 32% one expert said signal quality was good, whereas a different expert thought the identical signal was invalid. CONCLUSIONS: There is poor agreement between experts regarding the signal quality of perioperatively recorded AEPs and, as a consequence, results obtained by one expert may not easily be reproduced by a different expert. This limits the use of visual AEP analysis to indicate anaesthetic depth and may affect the comparability of AEP studies, where waveforms were analysed by different experts. An objective automated method for AEP analysis could solve this problem.

Adult↗
PubMed2002

A recombinant blood-stage malaria vaccine reduces Plasmodium falciparum density and exerts selective pressure on parasite populations in a phase 1-2b trial in Papua New Guinea.

The malaria vaccine Combination B comprises recombinant Plasmodium falciparum ring-infected erythrocyte surface antigen and 2 merozoite surface proteins (MSP1 and MSP2) formulated in oil-based adjuvant. A phase 1-2b double-blind, randomized, placebo-controlled trial in 120 children (5-9 years old) in Papua New Guinea demonstrated a 62% (95% confidence limits: 13%, 84%) reduction in parasite density in children not pretreated with sulfadoxine-pyrimethamine. Vaccinees had a lower prevalence of parasites carrying the MSP2-3D7 allelic form (corresponding to that in the vaccine) and a higher incidence of morbid episodes associated with FC27-type parasites. These results demonstrate functional activity of Combination B against P. falciparum in individuals with previous malaria exposure. The specific effects on parasites with particular msp2 genotypes suggest that the MSP2 component, at least in part, accounted for the activity. The vaccine-induced selection pressure exerted on the parasites and its consequences for morbidity strongly argue for developing vaccines comprising conserved antigens and/or multiple components covering all important allelic types.

Animals↗
PubMed2006

Do humans and baboons use the same information when categorizing human and baboon faces?

What information is used for sorting pictures of complex stimuli into categories? We applied a reverse correlation method to reveal the visual features mediating categorization in humans and baboons. Two baboons and 6 humans were trained to sort, by species, pictures of human and baboon faces on which random visual noise was superimposed. On ambiguous probe trials, a human-baboon morph was presented, eliciting "human" responses on some trials and "baboon" responses on others. The difference between the noise patterns that induced the two responses made explicit the information mediating the classification. Unlike the humans, the baboons based their categorization on information that closely matched that used by a theoretical observer responding solely on the basis of the pixel similarities between the probe and training images. We show that the classification-image technique and principal components analysis provide a method to make explicit the differences in the information mediating categorization in humans and animals.

Adult↗
PubMed1993

Improving the evaluation of renal transplant collecting system dilatation by computerized ultrasound image digitization.

43% of the renal allografts transplanted at our centre demonstrate pelvicalyceal dilatation on ultrasonography. However, only 6% of grafts are ultimately shown to be obstructed by antegrade pyelography. We have attempted to improve the specificity of ultrasonography by a quantitative analysis of 394 serial ultrasound studies from 150 renal transplant recipients. Representative images in the longitudinal and transverse axes were selected by a single observer for each of the studies and the outline of the kidney and its pelvicalyceal system was traced out. The images were then digitized using a Summagraphics tablet so that the length, width and area of the kidney and its pelvicalyceal system were calculated for each image. A step-wise discriminant analysis was performed which showed that the ratio of the area of the kidney to its pelvicalyceal area in both axes discriminated between normal, dilated but non-obstructed, and obstructed grafts. The median ratio of kidney to collecting system area in the obstructed grafts was 5.2 in the longitudinal and 4.4 in the transverse scan planes (vs median ratios of 32.8 and 22.0 for non-dilated grafts). Using canonical discriminant function, an index was derived which combines these ratios for the longitudinal and transverse images of the same kidney and this has further improved the diagnostic accuracy (median index of 2.45 in obstructed group vs -0.85 in non-dilated kidneys). This method improves upon the radiologist's report and identifies those grafts which require intervention.

Adolescent↗
PubMed1987

The surgical management of pancreatic abscess.

In the past 6 years we have operated on 13 patients with pancreatic abscess. Sepsis recurred in all 12 in whom the primary procedure was closed drainage. Following further surgical debridement of these recurrent abscesses 2 patients had further closed drainage and in 10 the cavities were packed open to heal by granulation. One patient underwent primary open packing which eliminated the pancreatic abscess but the patient subsequently died. Six patients (46%) died: one of lung abscesses after recovering completely from secondary open packing, one of an unsuspected carcinoma of the pancreas after secondary closed drainage and 4 of multiple organ failure after secondary open packing. There were no residual intraabdominal abscesses in any of these at autopsy. Four of those who died had initially presented with catastrophic pancreatitis according to Ranson's criteria and all 3 patients with initial sepsis scores of greater than or equal to 15 died. Open packing, whilst appearing to provide better drainage of pancreatic abscesses than closed drainage does not have a dramatic influence on mortality. Future reports of the results of open and closed methods of treating pancreatic abscesses should take account of both the severity of pancreatitis and of sepsis.

Abscess↗
PubMed2005

Treatment of ulcerative colitis with a humanized antibody to the alpha4beta7 integrin.

BACKGROUND: Selective blockade of interactions between leukocytes and vascular endothelium in the gut is a promising strategy for the treatment of inflammatory bowel diseases. METHODS: We conducted a multicenter, double-blind, placebo-controlled trial of MLN02, a humanized antibody to the alpha4beta7 integrin, in patients with active ulcerative colitis. We randomly assigned 181 patients to receive 0.5 mg of MLN02 per kilogram of body weight, 2.0 mg per kilogram, or an identical-appearing placebo intravenously on day 1 and day 29. Eligible patients also received concomitant mesalamine or no other treatment for colitis. Ulcerative colitis clinical scores and sigmoidoscopic assessments were evaluated six weeks after randomization. RESULTS: Clinical remission rates at week 6 were 33 percent, 32 percent, and 14 percent for the group receiving 0.5 mg of MLN02 per kilogram, the group receiving 2.0 mg per kilogram, and the placebo group, respectively (P=0.03). The corresponding proportions of patients who improved by at least 3 points on the ulcerative colitis clinical score were 66 percent, 53 percent, and 33 percent (P=0.002). Twenty-eight percent of patients receiving 0.5 mg per kilogram and 12 percent of those receiving 2.0 mg per kilogram had endoscopically evident remission, as compared with 8 percent of those receiving placebo (P=0.007). For the minority of patients in whom an MLN02 antibody titer greater than 1:125 developed, incomplete saturation of the alpha4beta7 receptor on circulating lymphocytes was observed and no benefit of treatment was identifiable. CONCLUSIONS: In this short-term study, MLN02 was more effective than placebo for the induction of clinical and endoscopic remission in patients with active ulcerative colitis.

Adult↗