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PubMed2006

A morphogenetic wave of p27Kip1 transcription directs cell cycle exit during organ of Corti development.

The molecular mechanisms coordinating cell cycle exit with cell differentiation and organogenesis are a crucial, yet poorly understood, aspect of normal development. The mammalian cyclin-dependent kinase inhibitor p27(Kip1) is required for the correct timing of cell cycle exit in developing tissues, and thus plays a crucial role in this process. Although studies of p27(Kip1) regulation have revealed important posttranscriptional mechanisms regulating p27(Kip1) abundance, little is known about how developmental patterns of p27(Kip1) expression, and thus cell cycle exit, are achieved. Here, we show that during inner ear development transcriptional regulation of p27(Kip1) is the primary determinant of a wave of cell cycle exit that dictates the number of postmitotic progenitors destined to give rise to the hair cells and supporting cells of the organ of Corti. Interestingly, transcriptional induction from the p27(Kip1) gene occurs normally in p27(Kip1)-null mice, indicating that developmental regulation of p27(Kip1) transcription is independent of the timing of cell cycle exit. In addition, cell-type-specific patterns of p27(Kip1) transcriptional regulation are observed in the mature organ of Corti and retina, suggesting that this mechanism is important in differential regulation of the postmitotic state. This report establishes a link between the spatial and temporal pattern of p27(Kip1) transcription and the control of cell number during sensory organ morphogenesis.

Animals↗
PubMed2002

Co-ordinating retinal histogenesis: early cell cycle exit enhances early cell fate determination in the Xenopus retina.

The laminar arrays of distinct cell types in the vertebrate retina are built by a histogenic process in which cell fate is correlated with birth order. To explore this co-ordination mechanistically, we altered the relative timing of cell cycle exit in the developing Xenopus retina and asked whether this affected the activity of neural determinants. We found that Xath5, a bHLH proneural gene that promotes retinal ganglion cell (RGC) fate, ( Kanekar, S., Perron, M., Dorsky, R., Harris, W. A., Jan, L. Y., Jan, Y. N. and Vetter, M. L. (1997) Neuron 19, 981-994), does not cause these cells to be born prematurely. To drive cells out of the cell cycle early, therefore, we misexpressed the cyclin kinase inhibitor, p27Xic1. We found that early cell cycle exit potentiates the ability of Xath5 to promote RGC fate. Conversely, the cell cycle activator, cyclin E1, which inhibits cell cycle exit, biases Xath5-expressing cells toward later neuronal fates. We found that Notch activation in this system caused cells to exit the cell cycle prematurely, and when it is misexpressed with Xath5, it also potentiates the induction of RGCs. The potentiation is counteracted by co-expression of cyclin E1. These results suggest a model of histogenesis in which the activity of factors that promote early cell cycle exit enhances the activity of factors that promote early cellular fates.

Animals↗
PubMed1997

Measurements of exit dose profiles in 60Co beams with a conventional portal film system.

An important step in the verification of the reliability of portal films as in vivo dosemeters is the evaluation of the agreement between exit dose profiles and optical density profiles measured on the portal film. To test the possibilities of a conventional portal film system in 60Co beams suitable for head and neck irradiation, we verified the agreement between relative exit doses (measured by ionization chamber) and relative optical densities, on cubic homogeneous phantoms, on an homogeneous "step" phantom and on a cubic phantom including air and aluminium inhomogeneities. The optical density profiles were corrected with the appropriate sensitometric curves. For an homogeneous phantom 10.8 cm thick and with the film in contact with the phantom, the agreement was found to be excellent with a mean deviation of 0.8% and a maximum deviation of 1.5%. The agreement was worse when the air gap between the exit surface of the phantom and the portal film was increased (with an air gap equal to 15 cm the maximum deviation was 4%), and when the thickness of the phantom was increased (for a thickness of 14.4 cm the maximum deviation was 3.1%). The agreement was found to be acceptable for the "step" phantom too, with a mean deviation around 1% and a maximum deviation within 2% (air gap equal to zero). When air and aluminium inhomogeneities were incorporated into the phantom a maximum deviation of 6% and a mean deviation less than 3% were found. Furthermore, the relative optical density profiles show an underestimate of measured off-axis exit dose values under a high density inhomogeneity and a small overestimate under a low density inhomogeneity. Results suggest the possibility of using conventional portal films for exit relative dosimetry in head and neck irradiation with 60Co beams if the air gap is kept as small as possible.

Air↗
PubMed1995

Double-pass measurements of the retinal-image quality with unequal entrance and exit pupil sizes and the reversibility of the eye's optical system.

We have used a modified double-pass apparatus with unequal entrance and exit pupil sizes to measure the optical transfer function in the human eye and have applied the technique to three different problems. First, we confirm that in the eye the double-pass spread function is the cross correlation of the input spread function with the output spread function [J. Opt. Soc. Am. A 12, 195 (1995)]. Consequently, when entrance and exit pupil sizes are equal, phase information is lost from the double-pass images. Second, we show that in double-pass measurements the eye behaves like a reversible optical system. That is, when entrance and exit pupils are equal, the double-pass image results from two passes through an optical system having a transfer function that is the same in both directions. To test for reversibility in the living eye we have used a double-pass apparatus with different exit and entrance pupil sizes (one of them small enough to consider the eye diffraction limited), so that the ingoing and the outgoing transfer functions are different. The measured image quality was unchanged when the pupils were interchanged, i.e., when the first-pass entrance pupil size becomes the second-pass exit pupil size, and vice versa. Third, the technique provides a means for inferring the complete optical transfer function of the eye, including the phase transfer function, and the shape of the point-spread function.

Accommodation, Ocular↗
PubMedDate not supplied

Exit-site care with ciprofloxacin otologic solution prevents polyurethane catheter infection in peritoneal dialysis patients.

OBJECTIVE: Mupirocin ointment and antiseptics are standard cleansing agents in routine exit-site care of peritoneal dialysis (PD) catheters, but these agents have a deleterious effect on polyurethane devices. We assessed the effectiveness of topical use of ciprofloxacin otologic solution for preventing exit-site infection (ESI) in PD patients with polyurethane catheters. DESIGN: Prospective study. SETTING: Service of Nephrology of an acute-care teaching hospital in Galdácano, Bizkaia, Spain. PATIENTS: A total of 164 patients with polyurethane catheters inserted was studied from start of continuous ambulatory PD to the end of a 24-month period. Patients were divided into two groups according to exit-site treatment protocols. INTERVENTION: Patients in group 1 (n = 86) were instructed on daily exit-site care with soap and water only; whereas patients in group 2 (n = 78) cleansed with soap and water, followed by application of a single-dose vial of 0.5 mL ciprofloxacin (1 mg) for application around the insertion site. MAIN OUTCOME MEASURES: Episodes of ESI and peritonitis. RESULTS: There were 67 episodes of ESI among patients in group 1 versus 9 episodes among patients in group 2 (p < 0.05), resulting in a rate of 0.41 and 0.06 episodes per patient-year of exposure, respectively (p < 0.001). Staphylococcus aureus ESI rate was 0.34 in group 1 versus 0.06 in group 2 (p = 0.001). Infections caused by Pseudomonas aeruginosa and other pathogens occurred in 11 patients in group 1 and in no patients in group 2 (p = 0.05). Peritonitis due to S. aureus ESI was significantly less frequent among patients treated with ciprofloxacin (1 vs 9 cases, p = 0.001). Removal of the catheter was necessary in 5 patients in group 1 and in no patients in group 2 (p < 0.05). CONCLUSION: Daily application of ciprofloxacin otologic solution at the exit site of PD patients with polyurethane catheters inserted significantly reduces the rate of ESI caused by S. aureus and other organisms, particularly P. aeruginosa.

Anti-Infective Agents↗
PubMed2000

A comparison study of house entering and exiting behavior of Anopheles vestitipennis (Diptera: Culicidae) using experimental huts sprayed with DDT or deltamethrin in the southern district of Toledo, Belize, C.A.

An investigation of the house entering and exiting behavior of Anopheles vestitipennis Dyar and Knab was undertaken in the Toledo District of Belize, Central America, between March and December of 1998. Three untreated experimental huts were either fitted with exit or entrance interception traps or used as a control for human landing collections. Human landing collections showed that An. vestitipennis exhibited a high level of biting activity shortly after sunset and continued biting at high levels throughout the night. Under unsprayed conditions, the use of exit and entrance interception traps demonstrated that doors, windows, and eaves were the primary mode of entry; whereas, cracks in the walls served a secondary role. The peak entrance time for An. vestitipennis occurred between 6:45 P.M. and 9:45 P.M. and a peak exit time occurred between 11:45 P.M. and 4:45 A.M. Additional trials were conducted after spraying one of the huts with DDT and another with deltamethrin. The excito-repellent properties of deltamethrin did not affect entrance times but did result in a peak exiting behavior that was five hours earlier than under pre-spray conditions. Deltamethrin also exhibited a repellency effect, showing 66% fewer An. vestitipennis entering the hut two weeks post-spray. DDT had an even more powerful repellency effect resulting in a 97% post-spray reduction of An. vestitipennis females entering the hut up to two weeks post-spray. The control hut showed only a 37% reduction in An. vestitipennis as compared to pre-spray conditions.

Animals↗
PubMed2001

Treatment of mycobacterial exit-site infections in patients on continuous ambulatory peritoneal dialysis.

Exit-site infections (ESIs) are frequently due to gram-positive organisms and occasionally to gram-negative organisms. Initial empiric antibiotic therapy is therefore directed against these organisms until culture reports are available. Two cases of ESI associated with Mycobacterium are here reported. The first patient, a 63-year-old man with type 2 diabetes, recently treated for Staphylococcus epidermidis peritonitis, presented with acute purulent drainage at the catheter exit site, accompanied by pain and erythema. No tunnel abscess was identified by ultrasound. Empiric antibiotic therapy was initiated with ofloxacin and vancomycin. A rapid-growing acid-fast bacillus (AFB) noted four days after culture was eventually identified as Mycobacterium fortuitum. Ofloxacin was continued, vancomycin was discontinued, and clarithromycin was added. The ESI initially showed improvement; therapy was therefore continued for several months. However, cultures remained positive for M. fortuitum, and the catheter was removed 5 months after therapy was initiated. The second patient, a 28-year-old woman, presented with severe pain and tenderness at the exit site without erythema or drainage. Empiric therapy with cefazolin, gentamicin, and cephalexin was initiated. Gram-positive cocci and an AFB were identified from the exit-site culture, and antibiotics were initially changed to clarithromycin, trimethoprim/sulfamethoxazole, and ofloxacin. The organisms were subsequently identified as M. chelonae-M. abscessus complex and coagulase-negative Staphylococcus. The patient continued to improve after 3 weeks of antibiotic therapy. However, despite the initial improvement in the ESI, the M. chelonae-M. abscessus complex continued to grow, and amikacin was added intravenously. Despite continued treatment, the ESI did not resolve, and the catheter was removed after 4 months of therapy. Despite unusual exist-site infections with rapidly growing AFBs, both patients continued continuous ambulatory peritoneal dialysis (CAPD) while undergoing treatment for ESI. Catheters were left intact, as improvement was initially seen with no evidence of tunnel infection or peritonitis. Rapid-growing AFB should be considered another possible causative agent for ESI. Two cases of atypical mycobacterial exit-site infection are presented to illustrate the difficulties in managing this complication of peritoneal dialysis. Ofloxacin--or other quinolones--may provide a better spectrum of coverage when choosing empiric therapy in patients presenting with ESI.

Adult↗
PubMed2003

[Incidence of peritonitis and catheter exit site infection in children undergoing automatic continuous cyclic peritoneal dialysis].

The aim of this study was to find out the clinical aspects of peritonitis and catheter exit site infection in children undergoing continuous cyclic peritoneal dialysis. The incidence of peritonitis and catheter related infections were reviewed in 8 children on continuous cyclic peritoneal dialysis over a mean period of 14.9+/-15.8 months. Peritonitis occurred in 4 children. There were 14 episodes of peritonitis. The mean time from starting dialysis to the first episode of peritonitis was 1.9+/-1.0 months. The incidence of peritonitis was 1 episode in 9 treatment months. Gram-negative organisms (Enterococcus spp.) were responsible for the majority of episodes (35.7%) of peritonitis and gram-positive bacteria mainly caused the catheter exit site infections (Staphylococcus epidermidis). The incidence of catheter exit site infection was one episode in 8 treatment months. Recurrent peritonitis was present in 1 case. Most patients with dialysis-related peritonitis and catheter exit site infection responded to antibiotic therapy. Catheter was replaced in 2 patients. The mortality rate was 2 out of 8 patients but none of the deaths were related to peritonitis. Patients with exit site infection had 7 times higher risk than those without developing peritonitis.

Adolescent↗
PubMed2004

Bed-exit alarms. A component (but only a component) of fall prevention.

Patient falls are a common cause of morbidity, nonfatal injuries, and trauma-related hospitalizations in the United States. Sometimes, they're even fatal. Falls typically occur either while the patient is getting into or out of bed or shortly after the patient has exited the bed. One means of helping to reduce the number of patient falls is the bed-exit alarm. Such alarms can be either built-in devices incorporated into the beds themselves or stand-alone units consisting of a portable control unit and a pressure- or position-sensitive sensor. They can serve as an "early warning system" alerting nursing staff when patients attempt to leave their beds unassisted. However, bed-exit alarms do not themselves prevent falls--a fact that is not always clearly understood. To be effective, they need to be implemented with care and with a clear understanding of their limitations. In this article, we describe the types of stand-alone bed-exit alarms currently available on the market and provide guidance to facilities on how to implement them effectively. We also review the elements of an effective fall-prevention program and recount one hospital's success in reducing patient falls. We are in the process of conducting a comparative evaluation of a number of bed-exit alarms, which will be published in an upcoming issue of Health Devices.

Accidental Falls↗
PubMedDate not supplied

Exit-site infections by non-diphtheria corynebacteria in CAPD.

Non-diphtheria corynebacteria species cause disease in risk populations such as immunocompromised patients and patients with indwelling medical devices. Despite reports of exit-site infection and peritonitis caused by non-diphtheria corynebacteria, these organisms are frequently dismissed as contaminants. During a 10-year observation period, we prospectively identified 8 cases of exit-site/tunnel infections caused by 2 different species of corynebacteria (Corynebacterium striatum in 5 and C. jeikeium in 3 cases). Four patients experienced a second episode of exit-site infection 3 months (2 cases), 25 months, and 40 months, respectively, after termination of an oral cephalosporin therapy of 4 to 6 weeks' duration. Non-diphtheria corynebacteria accounted for 9% of all exit-site infections during the study period. All catheter-related infections healed; no catheter had to be removed. The diagnosis of catheter-related non-diphtheria corynebacteria infection may be suspected when Gram stain shows gram-positive rods and with colony morphology and commercial biochemical identification systems. Susceptibility of non-diphtheria corynebacteria to antibiotics may vary, especially in C. jeikeium. Virtually all Corynebacterium species are sensitive to vancomycin. Empirical antibiotic therapy with vancomycin should be initiated while antibiotic susceptibility testing is being carried out. Oral cephalosporin may be an alternative treatment regimen for exit-site infections if sensitive. This study highlights the importance of non-diphtheria corynebacteria as emerging nosocomial pathogens in the population of end-stage renal disease patients on on continuous ambulatory peritoneal dialysis.

Adult↗
PubMed2004

Bed exit alarms.

Bed-exit alarms alert caregivers that a patient who should not get out of bed unassisted is doing so. These alarms can help reduce the likelihood of falls and can promote speedy assistance to patients who have already fallen. But as we described in our May 2004 Guidance Article on bed-exit alarms, they don't themselves prevent falls. They are only effective if used as part of an overall fall-prevention program and with a clear understanding of their limitations. This Evaluation examines the effectiveness of 16 bed-exit alarms from seven suppliers. Our ratings focus primarily on each product's reliability in detecting bed-exit events and alerting caregivers, its ability to minimize nuisance alarms (alarms that sound even though the patient isn't leaving the bed or that sound while a caregiver is helping the patient to leave the bed), and its resistance to deliberate or inadvertent tampering. Twelve of the products use pressure-sensor-activated alarms (mainly sensor pads placed on or under the mattress); three use a cord that can attach to the patient's garment, alarming if the cord is pulled loose from the control unit; and one is a position-sensitive alarm attached to a leg cuff. All the products reliably detect attempted or successful bed exits. But they vary greatly in how effectively they alert staff, minimize nuisance alarms, and resist tampering. Ease of use and battery performance also vary for many units. Of the pressure-sensor units, three are rated Preferred. Those units meet most of our criteria and have no significant disadvantages. Five of the other pressure-sensor products are Acceptable, and the remaining four are Not Recommended. All three cord-activated alarms are rated Acceptable, as is the patient-worn alarm.

Accident Prevention↗
PubMed2005

[Effect of estradiol on stimulated theophylline and prolactin Ca2+ exit from intracellular stores of pig oocytes].

Effect of estradiol on stimulated theophylline and prolactin Ca2+ exit from intracellular stores of pig oocytes was investigated using fluorescent dye chlortetracycline. It was shown that in the presence of estradiol neithert theophylline nor prolactin stimulated Ca2+ exit from intracellular stores of oocytes. Unlike, the common action oftheophylline and prolactin, also in the presence of estradiol, stimulated Ca2+ exit from intracellular stores. Inhibition of protein kinase C inhibits Ca2+ exit from intracellular stores in common action of theophylline and prolactin. These data suggest an obvious influence of estradiol on Ca2+ exit from intracellular stores of pig oocytes stimulated by theophylline and prolactin.

Animals↗
PubMed1991

Grading of exit sites cannot predict peritonitis in patients on CAPD.

Grading of exit sites was performed at 265 routine outpatient visits of 28 patients starting CAPD between January 1988 and February 1990, with a total observation time of 398.5 months to December 1990. Six patients had no peritonitis episode. The remaining 22 patients suffered from 43 peritonitis episodes. Fifty-eight per cent of these were caused by Staphylococcus epidermidis. Eighty-six per cent of the examinations of exit sites of patients with peritonitis episodes showed 0 to 1 point on an arbitrary grading scale of up to 9 points. Staphylococcus aureus was found after bacterial culture from exit site smears in 3 cases. All were adequately treated. None of these cases showed any peritonitis episodes with this bacteria. No relationship could be found between the grading of the exit site at routine outpatient clinic visits and the appearance of a peritonitis episode. Grading of exit sites is of clinical importance but cannot predict the appearance of peritonitis.

Adolescent↗
PubMed1991

A comparison of the effects of two antiseptic agents on Staphylococcus epidermidis colony forming units at the peritoneal dialysis catheter exit site.

Peritonitis is the most common complication of peritoneal dialysis (PD). Staphylococcus epidermidis (S. epi), a common skin organism, is the microorganism that is identified is the majority of episodes of peritonitis. The PD catheter breaks the natural skin barrier and allows a periluminal migration of bacteria from the skin surface into the sterile peritoneal cavity. Exit site care is routinely performed to decrease the colony counts of microorganisms on the skin surrounding the PD catheter. Research data is limited to support any of the currently used protocols for exit site care. This study compared the effect of two antiseptic agents, povidone-iodine (P-I) and chlorhexidine gluconate (CG), on S. epi colony forming units (cfu) at the PD catheter exit site over a 24 hour period. Because the distribution of the research data was markedly non-normal, a descriptive approach was used to interpret the data. Results showed that there was no difference between P-I and CG immediately after exit site care. All patients had zero growth at Time I. One trend that emerged was that at 24 hours after exit site care with P-I, more patients (54%) had S. epi cfu than did patients (15%) cleaned with CG.

Adult↗
PubMed2006

A new function of Skp1 in the mitotic exit of budding yeast Saccharomyces cerevisiae.

We previously reported that Skp1, a component of the Skp1-Cullin-F-box protein (SCF) complex essential for the timely degradation of cell cycle proteins by ubiquitination, physically interacts with Bfa1, which is a key negative regulator of the mitotic exit network (MEN) in response to diverse checkpoint-activating stresses in budding yeast. In this study, we initially investigated whether the interaction of Skp1 and Bfa1 is involved in the regulation of the Bfa1 protein level during the cell cycle, especially by mediating its degradation. However, the profile of the Bfa1 protein did not change during the cell cycle in skp1-11, which is a SKP1 mutant allele in which the function of Skp1 as a part of SCF is completely impaired, thus indicating that Skp1 does not affect the degradation of Bfa1. On the other hand, we found that the skp1-12 mutant allele, previously reported to block G2-M transition, showed defects in mitotic exit and cytokinesis. The skp1-12 mutant allele also revealed a specific genetic interaction with Deltabfa1. Bfa1 interacted with Skp1 via its 184 C-terminal residues (Bfa1-D8) that are responsible for its function in mitotic exit. In addition, the interaction between Bfa1 and the Skp1-12 mutant protein was stronger than that of Bfa1 and the wild type Skp1. We suggest a novel function of Skp1 in mitotic exit and cytokinesis, independent of its function as a part of the SCF complex. The interaction of Skp1 and Bfa1 may contribute to the function of Skp1 in the mitotic exit.

Cytoskeletal Proteins↗
PubMed1993

Atypical gunshot exit defects to the cranial vault.

Cranial exit wounds typically display external beveling, however, variation has been noted in the literature due to keyhole phenomena and pre-existent fractures. Two cases of atypical exit morphology are presented with features mimicking blunt trauma. In both instances radial fractures created by the exiting impact allowed passage without producing exit beveling. A working knowledge of the biomechanics of bone fracture, radiographs and low power microscopy are essential elements for the proper interpretation of such exit wound fractures.

Adult↗
PubMed2002

MEN, destruction and separation: mechanistic links between mitotic exit and cytokinesis in budding yeast.

Cellular events must be executed in a certain sequence during the cell division in order to maintain genome integrity and hence ensure a cell's survival. In M phase, for instance, chromosome segregation always precedes mitotic exit (characterized by mitotic kinase inactivation via cyclin destruction); this is then followed by cytokinesis. How do cells impose this strict order? Recent findings in budding yeast have suggested a mechanism whereby partitioning of chromosomes into the daughter cell is a prerequisite for the activation of mitotic exit network (MEN). So far, however, a regulatory scheme that would temporally link the initiation of cytokinesis to the execution of mitotic exit has not been determined. We propose that the requirement of MEN components for cytokinesis, their translocation to the mother-daughter neck and triggering of this translocation by inactivation of the mitotic kinase may be the three crucial elements that render initiation of cytokinesis dependent on mitotic exit.

Cell Division↗
PubMed2005

Prenatal three-dimensional ultrasound and magnetic resonance imaging evaluation of a fetal oral tumor in preparation for the ex-utero intrapartum treatment (EXIT) procedure.

Recent attempts at predelivery management of obstructed fetal airways have focused on the EXIT (ex-utero intrapartum treatment) procedure, which allows sufficient time to secure the fetal airway through preservation of uteroplacental gas exchange. We report a fetus with an exophytic oral tumor noted at 34 weeks of gestation. In this case, three-dimensional (3D) ultrasound allowed a complete and interactive evaluation of the tumor and related facial anatomy, and confirmed that access to the fetal airway was unlikely during delivery. Fetal magnetic resonance imaging (MRI) further demonstrated that the tumor originated in the nasopharynx and obstructed the upper airway. Both imaging results led to a final decision to offer an EXIT procedure for the neonate. At 36 weeks' gestation, a successful EXIT procedure was performed to reduce the risk of respiratory distress immediately after birth. This report highlights the value of 3D ultrasound and MRI as essential prerequisites for optimization of the triage process in selecting EXIT candidates.

Adult↗