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PubMedDate not supplied

The effect of interobserver variability on transrectal ultrasonography-based postimplant dosimetry.

PURPOSE: To investigate interobserver variability in contouring the prostate on postimplant transrectal ultrasonography (TRUS) images and its effect on dosimetric parameters that quantify implant quality. METHODS AND MATERIALS: Twenty preplanned peripherally loaded prostate implants were performed using 125I seeds and spacers linked together in linear arrays that maintain precise seed spacing and prevent seeds from rotating about their longitudinal axis. A set of two-dimensional transverse images spaced at 0.50-cm intervals was obtained with a high-resolution TRUS probe at the conclusion of the procedure with the patient still under anesthesia. A high percentage of the seeds (> 85%) were localized based on their visible echoes. The remaining seeds were identified based on the known locations of the "missing" seeds in the arrays. Two experienced ultrasonographers and a prostate brachytherapist independently contoured the prostate on the postimplant TRUS images. The prostate volumes defined by each observer were used to calculate the minimal dose received by 90% of the prostate volume (D90) and the percentage of the prostate volume receiving 100% of the prescribed minimal peripheral dose (V100). The observers also contoured the prostate on six preimplant TRUS studies to compare the variability in defining the prostate on pre- and postimplant TRUS images. RESULTS: The mean postimplant prostate volumes ranged from 20.8 to 66.9 cm3 (median: 45.7 cm3). The standard deviations (SDs), which reflect the variation in the volumes of the three observers, ranged from 1.4% to 26.1% of the mean (median: 11%). Multiple pairwise comparisons showed that the prostate volumes delineated by observer 3 differed significantly from those of observers 1 and 2 (p < 0.003). The volumes of observers 1 and 2 were not significantly different (p > 0.5). The mean values of D90 ranged from 124.2 to 171.1 Gy (median: 154.7 Gy) having SDs that ranged from 0.6% to 24.4% of the mean D90 (median: 7.8%). The mean values of V100 ranged from 82.3% to 95.1% (median: 92.8%) having SDs that ranged from 0.4% to 11.2% of the mean V100 (median: 4.0%). The values of both D90 and V100 calculated from the volumes of observer 3 were significantly (p < 0.003) different from those of observers 1 and 2, which did not differ significantly (p > 0.5). There was less interobserver variability in contouring the preimplant TRUS volumes. The mean volumes ranged from 20.3 to 54.3 cm3 having SDs that ranged from 1.9% to 14.1% (median: 8.6%). CONCLUSIONS: Significant interobserver differences in delineating the prostate volume on postimplant TRUS images were observed; however, these differences were less than generally reported for postimplant CT images. The interobserver differences in contouring the prostate in both TRUS and CT images produced significant differences in the dosimetric parameters, D90 and V100.

Brachytherapy↗

PubMed2005

Contrast media hypersensitivity--scope of the problem.

Hypersensitivity reactions to contrast media (CM) are frequent causes of anaphylactically induced fatalities. Adverse events after CM exposure are classified into immediate and non-immediate reactions, with differing pathomechanisms. In the majority of patients with immediate reactions, IgE-mediated allergy can not be demonstrated and the underlying mechanism remains unknown. However, recent data has provided evidence for skin test positivity and/or specific IgE in some patients with severe reactions. Cell-mediated hypersensitivity is the responsible mechanism for the majority of non-immediate skin eruptions. Skin tests have been employed to confirm this hypersensitivity. Previous reactors have an increased risk to develop new reactions upon repeated exposure, however, other risk factors are poorly defined. The use of skin tests for the selection of a "safe" CM is controversially discussed; information on sensitivity and specificity is lacking. New in-vitro assays have to be developed and/or validated. Premedication of previous reactors is common practice among radiologists, however, its precise role in the prevention of severe CM reactions to lower-osmolality CM has not been demonstrated. Thus, the main future tasks are to develop and validate allergic tests procedures, which may identify patients at risk and/or may confirm CM tolerance, and to reassess the value of different premedications in the prevention of hypersensitivity reactions.

Anaphylaxis↗

PubMed2003

Rapamycin inhibits E2F-dependent expression of minichromosome maintenance proteins in vascular smooth muscle cells.

Rapamycin inhibits vascular smooth muscle cell (VSMC) proliferation and rapamycin-eluting stents represent a novel therapeutic strategy for preventing postangioplasty restenosis. The precise molecular mechanism, for rapamycin-mediated inhibition of VSMC cell cycle progression and DNA replication remain to be elucidated. Minichromosome maintenance proteins (MCM) are essential regulators of DNA replication and the objective of this study was to examine the effect of rapamycin on their expression in rat aortic VSMC. Rapamycin substantially inhibited mitogen-induced MCM6 and MCM7 mRNA and protein expression in a dose-dependent fashion. Transient transfection experiments revealed that rapamycin inhibited MCM6 and MCM7 promoter activity, implicating a transcriptional mechanism. MCM6 and MCM7 transcriptional activation is regulated by E2F and activity of a luciferase reporter plasmid driven by four E2F elements was also significantly inhibited by rapamycin. The inhibitory effect of rapamycin on MCM6 and MCM7 was reversed by overexpression of E2F, indicating that their downregulation by rapamycin involves an E2F-dependent mechanism. These observations suggest that rapamycin inhibits MCM6 and MCM7 expression by blocking their E2F-dependent transactivation which may contribute importantly to the inhibition of VSMC DNA synthesis by rapamycin.

Animals↗

PubMed1989

Improvement in the surgical results of treatment of duplicated thumb by preoperative splinting.

Seven patients with an angular deformity of their duplicated thumb were treated by splinting and taping before operation. In all patients, the angular deformity of the interphalangeal joint improved within a few months, and surgical centralization and osteotomy were not necessary. Furthermore the design of the fillet flap was easier and more accurate as was the adjustment of the joint ligament tension. After operation there was no recurrence of angular deformity, and the range of motion of the interphalangeal joint was good. We believe that this procedure simplifies the operative approach, making it more precise and helping to prevent postoperative complications in patients with angular deformity.

Hand Deformities, Congenital↗

PubMed1978

Purification of rat intestinal maltase/glucoamylase and its anomalous dissociation either by heat or by low pH.

Maltase-glucoamylase, a microvillous membrane ectoenzyme, was solubilized from rat intestinal mucosa by digestion with papain and subsequently purified to homogeneity with an overall yield of 10--20%. An antibody to the purified enzyme formed a single precipitin line in immunodiffusion experiments with an intestinal homogenate. The enzyme was shown to be an acidic glycoprotein (20% sugar by weight) which contained low amounts of cysteine and no sialic acid. At pH3--6, maltase activity was slowly lost, but the enzyme was re-activated by re-adjustment of the pH to neutrality. However, in the presence of sodium dodecyl sulphate, acid pH values inactivated maltase irreversibly, and at the same time converted the enzyme (mol.wt. 500000 approx.) into five new species with apparent molecular weights ranging from 134000 to 480000 as judged by polyacrylamide-gel electrophoresis. The same five fragments were also formed by boiling the enzyme for brief periods in the presence of sodium dodecyl sulphate or urea either with or without reducing agents. The dissociated species were stable on re-electrophoresis, and amino acid analysis showed them to be very similar to each other and to the original enzyme. The bands migrated anomalously on polyacrylamide gels of different concentration, thereby preventing the assignment of precise molecular weights. It is possible that the five species may represent stable aggregates of a common monomer of the enzyme.

Amino Acids↗

PubMed2000

Biliary atresia.

Although the prognosis of biliary atresia has been dramatically improved in the era of liver transplantation, the Kasai operation is still the first line of surgical treatment. Successful hepatic portoenterostomy depends on early diagnosis and surgery, adequate surgical technique, prevention of cholangitis, and precise postoperative management.

Biliary Atresia↗

PubMed2004

Can we eliminate severe ovarian hyperstimulation syndrome?

The desire of some couples for children is so strong that they are willing to accept a modicum of risk to treat their infertility. Ideally, assisted reproduction technology practitioners seek a balance between optimum ovarian stimulation and successful treatment outcome with minimal rate of severe ovarian hyperstimulation syndrome (OHSS) or multiple pregnancies. However, despite many years of clinical experience, there are no precise methods to completely prevent severe OHSS, except by withholding the ovulation-inducing trigger of hCG. Individualization of treatment according to the specific risk factor and the specific response in the current cycle with the option of freezing of all embryos, or replacement of only a single embryo, has the potential of reducing the risk and the severity of the syndrome in susceptible cases. We offer a triage aimed at eliminating the occurrence of severe ovarian hyperstimulation syndrome on the basis of several clinical observations, including the role of GnRH antagonist in controlled ovarian stimulation protocols, the option of freezing of all embryos, or replacement of only a single embryo in the blastocyst stage.

Female↗

PubMed2004

Soft tissue injury threshold during simulated whiplash: a biomechanical investigation.

STUDY DESIGN: A newly developed biofidelic whole cervical spine (WCS) model with muscle force replication (MFR) was subjected to whiplash simulations of varying intensity, and the resulting injuries were evaluated through changes in the intervertebral flexibility. OBJECTIVES: To identify the soft tissue injury threshold based on the peak T1 horizontal acceleration and the association between acceleration magnitude and injury severity resulting from simulated whiplash using the WCS + MFR model. SUMMARY OF BACKGROUND DATA: Whiplash has been simulated using mathematical models, whole cadavers, volunteers, and WCSs. The measurement of injury (difference between prewhiplash and postwhiplash flexibilities) is possible only using the WCS model. METHODS: Six WCS + MFR specimens (C0-T1) were incrementally rear-impacted at nominal T1 horizontal maximum accelerations of 3.5, 5, 6.5, and 8 g, and the changes in the intervertebral flexibility parameters of neutral zone and range of motion were determined. The injury threshold acceleration was the lowest T1 horizontal peak acceleration that caused a significant increase in the intervertebral flexibility. RESULTS: The first significant increase (P <0.01) of 39.8% occurred in the C5-C6 extension neutral zone following the 5 g acceleration. At higher accelerations, the injuries spread among the surrounding levels (C4-C5 to C7-T1). CONCLUSIONS: A rear-end collision is most likely to injure the lower cervical spine by intervertebral hyperextension at a peak T1 horizontal acceleration of 5 g and above. These results may aid in the design of injury prevention systems and more precise diagnoses of whiplash injuries.

Aged↗

PubMed2002

Posture-dependent isometric trunk extension and flexion strength in normal male and female subjects.

The objective of this study was to quantify the relationship between trunk posture and trunk muscle function in a group of young, normal male and female subjects. Ten male and 10 female subjects performed isometric flexion and extension tasks using a trunk dynamometer. Peak isometric torque was recorded in flexion and extension at 10 degrees increments over a sagittal posture range of -20 degrees extension to +50 degrees of flexion. Significant differences in trunk strength (isometric torque) were found between males and females, at various sagittal plane trunk postures, and between flexion (F) and extension (E) tasks. Flexion torque was greatest at 20 degrees to 30 degrees flexion, whereas extension torque was greatest at 50 degrees flexion. Gender-specific differences in trunk strength were markedly reduced when the torque data were normalized by the subject's height multiplied by body weight. The E/F torque ratio showed a relatively linear, over twofold increase with increasing flexion angle, and was significantly greater for female subjects compared with male subjects at most sagittal postures. The baseline trunk isometric strength data provided by this study should help clinicians to use strength testing more precisely and specifically in prevention and diagnosis of patients at risk for back disorders.

Adult↗

PubMed2003

Improving aesthetic outcomes after alloplastic chin augmentation.

A novel approach to increase chin projection with alloplastic material is presented. Key aspects of the technique include the consideration of anthropometric normal values in preoperative assessment and planning, a submental approach with wide subperiosteal exposure of the area to be augmented, the use of two-piece porous polyethylene implants for augmentation, and screw fixation of the implant to the mandible. Screw fixation improves the predictability and precision of reconstruction by preventing implant displacement, by obliterating gaps between the implant and the facial skeleton, and by facilitating final implant contouring. In a series of 46 patients (24 primary and 22 secondary) operated on over a 6-year period, this approach allowed anatomically correct, stable chin contours to be created. Iatrogenic problems with macrogenia, mentalis dysfunction, and soft-tissue distortion resulting from implant migration and capsular contracture have been avoided. There have been no infections. Two patients who had had multiple previous chin operations requested revisional surgery to refine contour.

Adolescent↗

PubMed2025

Multi-ancestry genome-wide and transcriptome-wide association analyses identified new risk loci and genes for inflammatory bowel disease.

To advance genetic understanding of inflammatory bowel disease (IBD), we conducted genome-wide association meta-analyses of 63,415 IBD cases of European and East Asian descendants and identified 90 previously unknown risk loci. Integrating multi-ancestry transcriptome-wide association studies (TWAS), cell type-specific TWAS, alternative splicing (AS-WAS), and alternative polyadenylation (APA-WAS) analyses using RNA-seq data from normal colon tissues of 707 European and 364 East Asian individuals, we uncovered 506 high-confidence IBD risk genes, including 384 not previously reported. These genes converge on immune regulation, microbial interaction, and other pathways central to IBD pathogenesis, with over half showing transcriptional dysregulation supported by single-cell and spatial omics analyses. Notably, 46 risk genes are targeted by 225 drugs that have been approved or in Phase II/III trials, including sulfasalazine already used in IBD therapy. Our study findings deepen the understanding of IBD genetics and support the development of precision medicine for its prevention and treatment.

GWAS↗

PubMed2002

Construction and characterization of protein libraries composed of secondary structure modules.

Only a minute fraction of all possible protein sequences can exist in the genomes of all life forms. To explore whether physicochemical constraints or a lack of need causes the paucity of different protein folds, we set out to construct protein libraries without any restriction of topology. We generated different libraries (all alpha-helix, all beta-strand, and alpha-helix plus beta-strand) with an average length of 100 amino acid residues, composed of designed secondary structure modules (alpha-helix, beta-strand, and beta-turn) in various proportions, based primarily on the patterning of polar and nonpolar residues. We wished to explore that part of sequence space that is rich in secondary structure. The analysis of randomly chosen clones from each of the libraries showed that, despite the low sequence homology to known protein sequences, a substantial proportion of the library members containing alpha-helix modules were indeed helical, possess a defined oligomerization state, and showed cooperative chemical unfolding behavior. On the other hand, proteins composed of mainly beta-strand modules tended to form amyloid-like fibrils and were among the least soluble proteins ever reported. We found that a large fraction of members in non-beta-strand-containing protein libraries that are distant from natural proteins in sequence space possess unexpectedly favorable properties. These results reinforce the efficacy of applying binary patterning to design proteins with native-like properties despite lack of restriction in topology. Because of the intrinsic tendency of beta-strand modules to aggregate, their presence requires precise topologic arrangement to prevent fibril formation.

Amino Acid Sequence↗

PubMed2002

Ketamine abolishes ischemic preconditioning through inhibition of K(ATP) channels in rabbit hearts.

Although ketamine inhibits ATP-sensitive K (K(ATP)) channels in rat ventricular myocytes and abolishes the cardioprotective effect of ischemic preconditioning in isolated rat hearts and in rabbits in in vivo, no studies to date specifically address the precise mechanism of this prevention of ischemic preconditioning by ketamine. This study investigated the mechanism of the blockade of ischemic preconditioning by ketamine in rabbit ventricular myocytes using patch-clamp techniques and in rabbit heart slices model for simulated ischemia and preconditioning. In cell-attached and inside-out patches, ketamine inhibited sarcolemmal K(ATP) channel activities in a concentration-dependent manner. Ketamine decreased the burst duration and increased the interburst duration without a change in the single-channel conductance. In the heart slice model of preconditioning, heart slices preconditioned with a single 5-min anoxia, pinacidil, or diazoxide, followed by 15-min reoxygenation, were protected against subsequent 30-min anoxia and 1-h reoxygenation, and the cardioprotection was blocked by the concomitant presence of ketamine. These data are consistent with the notion that inhibition of sarcolemmal or mitochondrial K(ATP) channels may contribute, at least in part, to the mechanism of the blockade of ischemic preconditioning by ketamine.

Animals↗

PubMed2006

Frontal sinus surgery: its evolution, present standard of care, and recommendations for current use.

From a historical perspective, frontal sinus surgery has evolved from radical, highly invasive, disfiguring approaches to function-preserving, minimally invasive, and non-disfiguring intranasal procedures. Most sinus surgeons would agree that a sound surgical procedure is one that relieves patients' symptoms and provides a safe sinus in which future intracranial and orbital complications will not occur. For the future, sinus surgeons are searching for the ideal procedure, ie, one that is minimally invasive, reversible, and ensures the patient a safe frontal sinus for the long term. The ideal surgery will also leave minimal morbidity, will leave no cosmetic defect, and will allow for easy postoperative surveillance. To achieve this new standard in frontal sinus surgery, continuous refinements are required in the medical management and understanding of the disease processes that undermine long-term surgical success. Further advancements in instrumentation and visualization techniques are also necessary to enhance surgical precision, spare mucosa, and prevent the scarring and neo-osteogenesis that may cause surgical failures. Perhaps the most important development may be in the selection criteria for appropriate candidates who will benefit most from frontal sinus surgery.

Chronic Disease↗

PubMed1997

Work load, job control and risk of leaving work by sickness certification before delivery, Norway 1989.

Sickness absence in pregnancy has been shown to be associated with strenuous working conditions and parity. So far, few studies have made adjustments for possible interaction and confounding. Such adjustments are needed to more precisely identify targets for preventive measures. We have, therefore, in a representative population of pregnant employees in Norway 1989, computed adjusted odds ratios for leaving work by sickness absence more than three (LSC > 3) and eight (LSC > 8) weeks before delivery according to working conditions identified as risk factors in earlier studies; adjusted for job control, domestic conditions and sickness absence the year prior to pregnancy. The cumulative percentage of LSC > 8 and LSC > 3 was 26.4 and 51.1. Ergonomically strenuous postures and heavy lifting increased the risk of both outcomes. In addition, shift work and hectic work pace increased the risk of LSC > 3. Influence on breaks reduced risk. Only para experienced reduced risk of LSC when working part-time. Sicklisting the year prior to pregnancy had no confounding effect, which suggest that pregnancy represents a new incompatibility with work. Preventive measures should address work postures and heavy lifting, as well as conditions influencing the woman's control with her time.

Adult↗

PubMed1998

The role of F-cadherin in localizing cells during neural tube formation in Xenopus embryos.

The cell adhesion molecule F-cadherin is expressed in Xenopus embryos at boundaries that subdivide the neural tube into different regions, including one, the sulcus limitans, which partitions the caudal neural tube into a dorsal and ventral half (alar and basal plate, respectively). Here we examine the role of F-cadherin in positioning cells along the caudal neuraxis during neurulation. First, we show that ectopic expression of F-cadherin restricts passive cell mixing within the ectodermal epithelium. Second, we show that F-cadherin is first expressed at the sulcus limitans prior to the extensive cell movements that accompany neural tube formation, suggesting that it might serve to position cells at the sulcus limitans by counteracting their tendency to disperse during neurulation. We test this idea using an assay that measures changes in cell movements during neurulation in response to differential cell adhesion. Using this assay, we show that cells expressing F-cadherin localize preferentially to the sulcus limitans, but still disperse when located away from the sulcus limitans. In addition, inhibiting cadherin function prevents cells from localizing precisely at the sulcus limitans. These results indicate that positioning of cells at the sulcus limitans is mediated in part by the differential expression of F-cadherin.

Animals↗

PubMed2004

AICRG, Part I: A 6-year multicentered, multidisciplinary clinical study of a new and innovative implant design.

PROBLEM: Repetitive microstrains, which occur at the bone-implant interface during function, can lead to implant loss. In an attempt to improve survival by directing the stresses during function away from the dense cortical bone and toward the resilient trabecular bone, the Ankylos implant was developed with a roughened, progressive thread and a smooth cervical collar. The highly polished collar reduces the stresses in areas of the crestal bone. A precisely machined Morse taper prevents rotation of the abutment on the implant and eliminates the microgap present in many 2-stage implant systems. Clinical studies of other implants at different clinical research centers have demonstrated varying degrees of survival. PURPOSE: The purpose of this paper was (1) to assess the overall clinical survival of this new implant design and (2) to compare implant stability (ie, Periotest values [PTVs]) over time with other implants. METHOD: The investigation represented a comprehensive, multicentered, international clinical study conducted over a period of 6 years. It was conducted under an Investigational Device Exemption (IDE) protocol that was reviewed and accepted in the United States by the Food and Drug Administration (FDA). Over 1500 implants were placed and restored, and follow-up data were gathered for a period of up to 3 to 5 years. RESULTS: Over 44% of the clinical research centers reported no failures (100% survival). A total of 63% of the centers had none or only 1 failure during the study. One center reported 6 failures in 1 patient, which were not related to the implant design. Overall survival for implants in function for 3 to 5 years was 97.5%. Using failure criteria of earlier studies of other implants, 5-year survival was 98.3%. Higher handpiece speeds were associated with an increase in the number of failures. This new design produced a slightly more resilient trabecular bone-implant complex with a difference of about 1 PTV in all bone densities when compared with other implants. CONCLUSIONS: The following conclusions can be made: (1) the implant design was effective under all clinical conditions; (2) no significant and unexpected complications or risk factors were evident; (3) survival was found to be excellent; and (4) this implant is well suited for use in the restoration of masticatory function and esthetics in patients with missing natural teeth.

Adult↗

PubMed2000

Evidence and possible mechanisms of altered maximum heart rate with endurance training and tapering.

Exercise physiologists, coaches and athletes have traditionally used heart rate (HR) to monitor training intensity during exercise. While it is known that aerobic training decreases submaximal HR (HRsubmax) at a given absolute exercise workload, the general consensus is that maximum HR (HRmax) is relatively unaltered regardless of training status in a given population. It has not been seriously postulated as to whether HRmax can change modestly with aerobic training/detraining. Despite several sources stating that HRmax is unaltered with training, several studies report that HRmax is reduced following regular aerobic exercise by sedentary adults and endurance athletes, and can increase upon cessation of aerobic exercise. Furthermore, evidence suggests that tapering/detraining can increase HRmax. Therefore, it is plausible that some of the same mechanisms that affect both resting and HRsubmax may also play a role in altered HRmax. Some of the proposed mechanisms for changes in HRmax that may occur with aerobic training include autonomic (extrinsic) factors such as plasma volume expansion and(enhanced baroreflex function, while some nonautonomic (intrinsic) factors are alteration of the electrophysiology of the sinoatrial (SA) node and decreased beta-adrenergic receptor number and density. There is a high correlation between changes in both maximal oxygen uptake (VO2 max) and HRmax that occurs with training, tapering and detraining (r= -0.76: p < 0.0001; n = 314), which indicates that as VO2max improves with training, HRmax tends to decrease, and when detraining ensues, HRmax tends to increase. The overall effect of aerobic training and detraining on HRmax is moderate: effect sizes based on several studies were calculated to be -0.48 and +0.54, respectively. Therefore, analysis reveals that HRmax can be altered by 3 to 7% with aerobic training/detraining. However, because of a lack of research in the area of training on HRmax, the reader should remain speculative and allow for cautious interpretation until further, more thorough investigations are carried out as to the confirmation of mechanisms involved. Despite the limitations of using HR and HRmax as a guide to training intensity, the practical implications of monitoring changing HRmax are: (i) prescribed training intensities may be more precisely monitored; and (ii) prevention of overtraining may possibly be enhanced. As such, it may be sensible to monitor HRmax directly in athletes throughout the training year, perhaps at every macrocycle (3 to 6 weeks).

Adaptation, Physiological↗