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PubMed2003

Longevity regulation in Saccharomyces cerevisiae: linking metabolism, genome stability, and heterochromatin.

When it was first proposed that the budding yeast Saccharomyces cerevisiae might serve as a model for human aging in 1959, the suggestion was met with considerable skepticism. Although yeast had proved a valuable model for understanding basic cellular processes in humans, it was difficult to accept that such a simple unicellular organism could provide information about human aging, one of the most complex of biological phenomena. While it is true that causes of aging are likely to be multifarious, there is a growing realization that all eukaryotes possess surprisingly conserved longevity pathways that govern the pace of aging. This realization has come, in part, from studies of S. cerevisiae, which has emerged as a highly informative and respected model for the study of life span regulation. Genomic instability has been identified as a major cause of aging, and over a dozen longevity genes have now been identified that suppress it. Here we present the key discoveries in the yeast-aging field, regarding both the replicative and chronological measures of life span in this organism. We discuss the implications of these findings not only for mammalian longevity but also for other key aspects of cell biology, including cell survival, the relationship between chromatin structure and genome stability, and the effect of internal and external environments on cellular defense pathways. We focus on the regulation of replicative life span, since recent findings have shed considerable light on the mechanisms controlling this process. We also present the specific methods used to study aging and longevity regulation in S. cerevisiae.

Gene Expression Regulation, Fungal↗
PubMed2001

Acceptability research on female-controlled barrier methods to prevent heterosexual transmission of HIV: Where have we been? Where are we going?

Acceptability research is an important component of any product development process. As researchers move into a new, accelerated phase of vaginal microbicide development, it is important to take stock of the acceptability research conducted to date and determine future research priorities. In this paper, we review findings from acceptability research conducted to date in four categories: hypothetical product acceptability research, existing product research (spermicide acceptability studies), acceptability research within the context of clinical trials, and postmarketing acceptability research conducted around the female condom. Finally, we highlight areas where additional research is needed in light of recent progress in microbicide development and discuss a possible framework for the introduction and acceptability of new sexually transmitted disease (STD) prevention technologies.

Administration, Intravaginal↗
PubMed1986

Quantitative comparisons of healing in cranial fresh autografts, frozen autografts and processed autografts, and allografts in canine skull defects.

Adult dog skull defects larger than 17 mm do not spontaneously heal. A quest for a potentially viable, cosmetically, mechanically, and technically acceptable template for human cranial reconstruction prompted a comparison of processed autogeneic and allogeneic bone implants with a fresh autograft control in the dog. Quantitative reproducible observations demonstrated that fresh calvarial bone autografts were superior to the nonviable implants in volume percent defect filled, mm2 new cortical bone, mm2 new and old cortical bone, and cortical bone porosity. Frozen autografts achieved 75%, antigen-extracted, autolyzed, partially demineralized auto- and allografts, 50% of the overall efficiency of fresh autografts. Fresh cancellous bone added to allografts did not improve long-term repair. Remodeling of all grafts appeared consistent with osteoconductive invasion by peripheral host endosteal and diploic elements; host external periosteum and dura contributed less. Central osteoinductive recruitment of mesenchymal cells from muscle or dura seemed not to occur in the adult dog. Partially demineralized dog calvarial grafts were resorbed without acting as a template for new bone formation. Surface demineralization, antigen extraction, and autolytic digestion of autografts and allografts, with or without fresh iliac bone, did not improve calvarial bone regeneration in adult dogs.

Animals↗
PubMed1993

Referral of patients to an anticoagulant clinic: implications for better management.

The quality of anticoagulant treatment of ambulatory patients is affected by the content of referral letters and administrative processes. To assess these influences a method was developed to audit against the hospital standard the referral of patients to one hospital anticoagulant clinic in a prospective study of all (80) new patients referred to the clinic over eight months. Administrative information was provided by the clinic coordinator, and the referral letters were audited by the researchers. Referral letters were not received by the clinic for 10% (8/80) of patients. Among the 72 referral letters received, indication for anticoagulation and anticipated duration of treatment were specified in most (99%, 71 and 81%, 58 respectively), but only 3% (two) to 46% (33) reported other important clinical information (objective investigations, date of starting anticoagulation, current anticoagulant dose, date and result of latest international normalised ratio, whether it should be the anticoagulant clinic that was eventually to stop anticoagulation, patients' other medical problems and concurrent treatment. Twenty two per cent (16/80) of new attenders were unexpected at the anticoagulant clinic. Most patients' case notes were obtained for the appointment (61%, 47/77 beforehand and 30% 23/77 on the day), but case notes were not obtained for 9% (7/77). The authors conclude that health professionals should better appreciate the administrative and organisational influences that affect team work and quality of care. Compliance with a well documented protocol remained below the acceptable standard. The quality of the referral process may be improved by using a more comprehensive and helpful referral form, which has been drawn up, and by educating referring doctors. Measures to increase the efficiency of the administrative process include telephoning the clinic coordinator directly, direct referrals through a computerised referral system, and telephone reminders by haematology office staff to ward staff to ensure availability of the hospital notes. The effect of these changes will be assessed in a repeat audit.

Adolescent↗
PubMed1999

Are societal judgments being incorporated into the uncertainty factors used in toxicological risk assessment?

The aim of this paper is to show that the uncertainty factors used in toxic risk assessment to develop exposure standards do contain societal judgments as well as technical judgments. The process generally used today originated in the 1950s, when a deterministic approach to risk was the norm. Technical judgments are required concerning the nature and the quality of the evidence used in the risk assessment. Judgments taken are essentially cautious. This caution may not matter when measured exposure is significantly below the standard and may be accepted when exposure occurs only following an approval process based on "gate keeping." More sophisticated judgments are required when actual exposure may exceed this type of standard or when risk needs to be compared with benefit. These circumstances can occur with patient exposure to human medicines and with occupational exposure to chemicals. Under these circumstances more explicitly considered societal judgments concerning what constitute "broadly acceptable" and "tolerable" risk criteria, and hence what are appropriate uncertainty factors, are required. The outcomes of those societal judgments are likely to vary according to the circumstances surrounding the exposure and have led to smaller uncertainty factors being considered appropriate for occupational exposure, when compared with widespread public exposure.

Humans↗
PubMed1988

Fetal ECG during labour: a suggested standard.

Recording the fetal ECG as a means of fetal monitoring during labour has been investigated by many researchers. Different signal processing methods have been used, making comparisons difficult so that agreement on several topics has not been reached. We suggest the basis of a standard method of recording and processing the signal which we believe will be acceptable to the research and clinical communities.

Animals↗
PubMed2004

Cutting edge: DGYW/WRCH is a better predictor of mutability at G:C bases in Ig hypermutation than the widely accepted RGYW/WRCY motif and probably reflects a two-step activation-induced cytidine deaminase-triggered process.

A feature of Ig hypermutation is the presence of hypermutable DNA sequences that are preferentially found in the V regions of Ig genes. Among these, RGYW/WRCY is the most pronounced motif (G:C is a mutable position; R=A/G, Y=C/T, and W=A/T). However, a molecular basis for the high mutability of RGYW was not known until recently. The discovery that activation-induced cytidine deaminase targets the DNA encoding V regions, has enabled the analysis of its targeting properties when expressed outside of the context of hypermutation. We analyzed these data and found evidence that activation-induced cytidine deaminase is the major source of the RGYW mutable motif, but with a new twist: DGYW/WRCH (G:C is the mutable position; D=A/G/T, H=T/C/A) is a better descriptor of the Ig mutation hotspot than RGYW/WRCY. We also found evidence that a DNA repair enzyme may play a role in modifying the sequence of hypermutation hotspots.

Amino Acid Motifs↗
PubMed2004

Molecular recognition by LARGE is essential for expression of functional dystroglycan.

Reduced ligand binding activity of alpha-dystroglycan is associated with muscle and central nervous system pathogenesis in a growing number of muscular dystrophies. Posttranslational processing of alpha-dystroglycan is generally accepted to be critical for the expression of functional dystroglycan. Here we show that both the N-terminal domain and a portion of the mucin-like domain of alpha-dystroglycan are essential for high-affinity laminin-receptor function. Posttranslational modification of alpha-dystroglycan by glycosyltransferase, LARGE, occurs within the mucin-like domain, but the N-terminal domain interacts with LARGE, defining an intracellular enzyme-substrate recognition motif necessary to initiate functional glycosylation. Gene replacement in dystroglycan-deficient muscle demonstrates that the dystroglycan C-terminal domain is sufficient only for dystrophin-glycoprotein complex assembly, but to prevent muscle degeneration the expression of a functional dystroglycan through LARGE recognition and glycosylation is required. Therefore, molecular recognition of dystroglycan by LARGE is a key determinant in the biosynthetic pathway to produce mature and functional dystroglycan.

Adenoviridae↗
PubMed1999

Clinical experience with carinal resection.

OBJECTIVE: Pathologic processes that involve the carina pose a tremendous challenge to thoracic surgeons. Although techniques have been developed to allow primary resection and reconstruction, few institutions have accumulated sufficient experience to allow meaningful conclusions about the indications and the morbidity and mortality rates for this type of surgery. METHODS: Since 1962, 135 patients have undergone 143 carinal resections (134 primary resection, 9 re-resection) at our institution. Indications for carinal resection included bronchogenic cancer (58 patients), other airway neoplasms (60 patients), and benign or inflammatory strictures (16 patients). Thirty-seven patients (28%) had a history of prior lung or airway surgery not involving the carina. Carinal resection without pulmonary resection was accomplished in 52 patients; 57 patients had carinal pneumonectomy (44 right, 13 left); 14 patients had carinal plus lobar resection, and 11 patients had carinal resection after pneumonectomy (9 left, 2 right). There were 15 different modes of reconstruction, based on the type and extent of resection. Techniques were used to reduce anastomotic tension. RESULTS: The operative mortality rate in the 134 patients after primary carinal resection was 12.7%. Adult respiratory distress syndrome was responsible for 9 early deaths. Predominant predictors of operative death included postoperative mechanical ventilation (P =.001), length of resected airway (P =.03), and development of anastomotic complications (P =.04). Mortality rates varied by the type of procedure and the indication for resection. Left carinal pneumonectomy was associated with a high operative mortality rate (31%). Complications were noted in 52 patients (39%), including atrial arrhythmias (20 patients) and pneumonia (11 patients). Anastomotic complications, both early and late, were seen in a total of 23 patients (17%) and resulted in death or surgical reintervention in 21 patients (91%). The operative mortality rate for carinal re-resection was 11.1%. CONCLUSIONS: Carinal resection with primary reconstruction may be accomplished with acceptable mortality rates, but the underlying pathologic process and chance for long-term survival must be carefully considered before the operation is recommended, especially in the case of left carinal pneumonectomy. Anastomotic complications exact a heavy toll on involved patients. Careful patient selection and meticulous anesthetic and surgical technique remain the key to minimizing morbidity and mortality rates.

Adolescent↗
PubMedDate not supplied

[Percutaneous tenodesis of the Achilles tendon. A new surgical method for treatment of acute Achilles tendon rupture using percutaneous tenodesis].

APPROACH TO THE PROBLEM: Various studies (3, 6, 9, 14, 22, 28, 30, 33) have shown that, on average (26), the surgical treatment of a freshly ruptured Achilles tendon can be considered a more appropriate and better treatment than a conservative immobilisation therapy. On the other hand the rate of complications in openly executed reconstructions is quite considerable at 11-29% (13, 19, 20, 31). It therefore seems reasonable to develop a process which, by using minimal invasive measures on the tendon, reduces the risk of complications arising from surgery and simultaneously makes an early post operative treatment encouraging maximum mobility possible. METHOD: We have developed a percutaneous tenodesis of the Achilles tendon using two Lengemann extension wires and fibrin bonding at the point of rupture (8, 18). This process has been applied to 21 patients since 1995. Check-up period for further examination: 1 year. RESULTS: Exclusively male patients have been treated, average age 42 years. The Achilles tendon ruptures occurred in sporting activities and were handled with operations in an average time span of 22 hours. In one case there was a re-rupture resulting from traumatic conditions. All other results were good to very good and free of complications. CONCLUSIONS: The percutaneous tenodesis of the Achilles tendon using Lengemann extension wires and fibrin bonding provides a simple, good value and reliable process which should be used for freshly occurred Achilles tendon ruptures. CLINICAL RELEVANCE: Particularly worthy of mention are the problem-free treatment, the good results and the broad acceptance by the patients. These advantages make the demonstrated process ideal for routine clinical application.

Achilles Tendon↗
PubMed2004

Violence in institutional care for elderly people from the perspective of involved care providers.

The aim of the present study was to describe violent events as narrated by care providers involving themselves. During a 12-month period, care providers reported 149 violent events. Using consecutive purposive sampling with maximum variation, 61 events were further investigated using narrative interviews with involved care providers. They were involved either as victims, perpetrators or as witnesses. The narratives were analysed using a qualitative descriptive analysis. The presentation of the result includes contextual aspects and three themes: 'misunderstanding each other', 'invasion of personal space' and 'acceptance of violence in work'. These themes represent a process of violence in the narratives. Mutual misunderstanding may be seen as an antecedent to violent events. Invasion of personal space is a theme revealing what violence is about. Acceptance of violence seems to be a natural consequence for the caregivers because the events are seen as unavoidable, impossible to solve and as a constituent of daily work.

Adult↗
PubMed1993

AZTDIS--a two-phase real-time ECG data compressor.

An ECG sampled at a rate of 360 samples s-1 or more produces a large amount of redundant data that are difficult to store and transmit; we therefore need a process to represent the signals with clinically acceptable fidelity and with as small a number of code bits as possible. In this paper, a real-time ECG data-compression algorithm, AZTDIS, is presented. AZTDIS is an efficient algorithm which locates significant samples and at the same time encodes linear segments between them by using linear interpolation. The significant samples selected include, but are not limited to, the samples that have significant displacement from the encoded signal such that the allowed maximal error is limited to a constant epsilon, which is specified by the user. The way that AZTDIS computes the displacement of a sample from the encoded signal guarantees that the high activity regions are more accurately coded. The results from AZTDIS are compared with those from the well-known data-compression algorithm, AZTEC, which is also a real-time algorithm. It is found that under the same bit rate, a considerable improvement of root-mean-square error (RMSerr) can be achieved by employing the proposed AZTDIS algorithm. An average value of RMSerr of 9.715 can be achieved even at an average bit rate of 0.543 bits per sample by employing AZTDIS. By tuning the allowed maximal error of AZTDIS such that it has similar bit rate to AZTEC, the average value of RMSerr achieved by AZTDIS is 5.554 while the average value of RMSerr achieved by AZTEC under the same bit rate is 19.368.

Algorithms↗
PubMed1998

Densitometric evaluation of four radiographic processing solutions.

OBJECTIVE: To determine the performance of different processing solutions using an automatic processor for dental radiography. STUDY DESIGN: One brand of dental X-ray film (Minimax, Chicago, IL, USA) was developed in an automatic processor using four different brands of processing solution: Megasan (MGS, Megasan, Ankara, Turkey), (HAC, Ankara, Turkey), Fuji (Fuji Medical, Hacettepe Cedex, France) and RP X-Omat (Eastman Kodak, Rochester, NY, USA) at a range of temperatures. Performance was evaluated with respect to base plug fog density, relative speed and contrast. RESULTS: All solutions produced acceptable base plus fog values. MGS produced significantly greater densities (P < 0.05) than the other three solutions. Contrast obtained with Kodak and Fuji solutions was less than with MGS and HAC. Developing temperature recommended by the manufacturer of the processor were found to be higher than that needed to achieve a clinically acceptable film. CONCLUSIONS: Depending on the processor and processing solutions used, exposure time and processing temperature can be modified while maintaining image quality. The cheapest processing solution (MGS) gave the same results as the more expensive.

Absorptiometry, Photon↗
PubMed2005

A prospective study of acceptance of pain and patient functioning with chronic pain.

Acceptance of chronic pain is emerging as an important concept in understanding ways that chronic pain sufferers can remain engaged with valued aspects of life. Recent studies have relied heavily on cross-sectional investigations at a single time point. The present study sought to prospectively investigate relations between acceptance of chronic pain and patient functioning. A sample of adults referred for interdisciplinary treatment of severe and disabling chronic pain was assessed twice, an average of 3.9 months apart. Results showed that pain and acceptance were largely unrelated. Pain at Time 2 was weakly related to measures of functioning at Time 2. On the other hand, acceptance at Time 1 was consistently related to patient functioning at Time 2. Those patients who reported greater acceptance at Time 1 reported better emotional, social, and physical functioning, less medication consumption, and better work status at Time 2. These data suggest that willingness to have pain, and to engage in activity regardless of pain, can lead to healthy functioning for patients with chronic pain. Treatment outcome and process studies may demonstrate the potential for acceptance-based clinical methods for chronic pain management.

Activities of Daily Living↗
PubMedDate not supplied

A multicenter 12-month evaluation of single-tooth implants restored 3 weeks after 1-stage surgery.

The time-intensive, multi-step process of dental implant therapy limits patient acceptance. This 3-year prospective multicenter study sought to determine the safety of an expedited therapy that consisted of loading unsplinted maxillary anterior single-tooth implants 3 weeks after 1-stage surgical placement, and determination of the peri-implant cortical bone and mucosal responses to the expedited procedure. Fifty-two patients missing 1 or 2 maxilliary anterior teeth were enrolled in a study approved by the Institutional Committee on Human Subjects Research and based on strict inclusion and exclusion criteria. Astra Tech ST implants placed in a 1-stage procedure were restored 3 weeks later with ST abutments and a provisional crown (baseline); 7 to 9 weeks later, a porcelain-fused-to-metal or all-ceramic crown was cemented. Radiographic and clinical examinations were made at baseline and at 6 and 12 months. Implant survival was recorded. Cortical bone responses and peri-implant mucosal responses were evaluated. Fifty-eight implants were placed. During the 3-week period after implant placement, 4 patients were dismissed because of smoking cigarettes (a protocol deviation), and 1 patient was excluded because of deviation in loading time. Of the remaining 53 implants, 2 failed before definitive crown cementation. The resultant 96.2% survival rate was independent of implant length, tooth position, and bone quality/quantity. The mean change in marginal bone level was 0.4 mm at 12 months. The number of surfaces with plaque decreased from 3.4% at baseline to 0.5% at 12 months. The surfaces with inflammation also decreased. A mean gain in papilla length of 0.61 mm occurred, and a gain in buccal gingiva (x = 0.34 mm) was observed. A high success rate with positive tissue responses was achieved for maxillary anterior unsplinted single-tooth implants placed in a 1-stage surgery and restored at 3 weeks. This 2-component system is suited to a single-stage, rapid loading protocol for esthetic single-tooth replacement.

Adaptation, Physiological↗
PubMed2006

[Computerized physician order entry of pharmacotherapeutic protocols in a colorectal surgery unit].

INTRODUCTION: Computerized physician order entry was introduced in our hospital. We present the pharmacotherapeutic protocols that we use in patient care. MATERIAL AND METHODS: Six pharmaceutical protocols were designed by consensus in a colorectal surgery unit and were applied over a 2-year period. Patients undergoing ambulatory or urgent surgery were excluded. RESULTS: We treated 772 patients. Two hundred twenty patients (28.5%) were assigned to the preoperative protocol for minor proctologic surgery. After surgery, all 220 patients were included in the postoperative protocol for minor proctologic surgery. The remaining 552 patients (71.5%) were assigned to the protocol for major colorectal surgery. The preoperative protocol for major colorectal surgery was indicated in 542 patients (98.2%) and its variant for patients allergic to beta-lactam antibiotics was used in 10 patients (1.8%). The postoperative pharmacotherapeutic protocol assigned depended on whether a central venous line (317 patients; 57.4%) or only peripheral venous access (235 patients; 42.6%) was used. CONCLUSIONS: Each clinical unit has a duty to carry out and update consensus protocols (always based on the best scientific evidence available) that can be used in the processes managed in that unit. The use of these protocols shows a high degree of acceptance among physicians and nurses, allowing clinical practice to be standardized and healthcare processes to be homogenized.

Colorectal Surgery↗
PubMed2006

Brief report: the Ego Identity Process Questionnaire: factor structure, reliability, and convergent validity in Dutch-speaking late adolescents.

The reliability and validity of a Dutch version of the Ego Identity Process Questionnaire (EIPQ) were evaluated. In Study 1, the instrument was found to exhibit a clear factor structure and acceptable reliability. Using Confirmatory Factor Analysis, both a model with two process factors (Commitment, Exploration) and a model with four content factors (Ideological Commitment, Ideological Exploration, Interpersonal Commitment, Interpersonal Exploration) evidenced a good fit once direction of wording was taken into account. In Study 2, moderate convergence was observed between Commitment and Exploration, and continuous measures of identity statuses and identity styles. The results of both studies combined indicated that the Dutch version of the EIPQ may be recommended as a research tool with college students.

Adolescent↗
PubMed2006

Shuttling mechanism of ion transfer at the interface between two immiscible liquids.

The transfers of hydrophilic ions between aqueous and organic phases are ubiquitous in biological and technological systems. These energetically unfavorable processes can be facilitated either by small molecules (ionophores) or by ion-transport proteins. In absence of a facilitating agent, ion-transfer reactions are assumed to be "simple", one-step processes. Our experiments at the nanometer-sized interfaces between water and neat organic solvents showed that the generally accepted one-step mechanism cannot explain important features of transfer processes for a wide class of ions including metal cations, protons, and hydrophilic anions. The proposed new mechanism of ion transfer involves transient interfacial ion paring and shuttling of a hydrophilic ion across the mixed-solvent layer.

Journal Article↗