Differences between prolonged weaning patients from medical and surgical intensive care units.

BACKGROUND: It is not clear whether patients entering a specialized, interdisciplinary weaning unit from surgical or medical intensive care units (ICU) distinguish substantially. The purpose of the present study was to assess differences in patients with prolonged weaning being referred from surgical and medical ICU. METHODS: Data collected from April 2013 to April 2014 was conducted for retrospective analysis. Mortality rates, demographic data, clinical, and microbial differences in 150 patients with prolonged weaning were assessed (80 surgical and 70 medical). RESULTS: Surgical ICU referrals tended to be older (70.7 ± 11.3 vs. 67.3 ± 12.3, P = 0.051) and had fewer underlying pulmonary diseases (45% vs. 60%, P = 0.067). Sodium values at the time of referral to the weaning unit were significantly higher in surgical (147.1 ± 9.6) vs. medical (141.3 ± 6.7 mmol/l) patients (P < 0.001). Each 10-unit increase in sodium at the time of referral to the weaning unit was associated with a 2.5-day (95% CI -0.4, 5.4; P = 0.09) prolongation of stay in the weaning unit. Although significant differences in microbiological agents from tracheal aspiration were seen, the infection rate on the weaning unit was similar in both groups. There was no difference in weaning unit mortality between surgical and medical ICU patients (18% vs. 23%; P = 0.41). CONCLUSION: Few differences were found between patients being referred to a specialized weaning unit from surgical vs. medical ICUs. Besides differences in microbiological characteristics of tracheal secretions, there were also differences in sodium levels, which appear to influence on treatment duration.

Towards a Common Understanding of the Health Sciences.

OBJECTIVE: The aim of health sciences is to maintain and improve the health of individuals and populations and to limit disability. Health research has expanded astoundingly over the last century and a variety of scientific disciplines rooted in very different scientific and intellectual traditions has contributed to these goals. To allow health scientists to fully contextualize their work and engage in interdisciplinary research, a common understanding of the health sciences is needed. The aim of this paper is to respond to the call of the 1986 Ottawa Charter to improve health care by looking both within and beyond health and health care, and to use the opportunity offered by WHO's International Classification of Functioning, Disability and Health (ICF) for a universal operationalization of health, in order to develop a common understanding and conceptualization of the field of health sciences that account for its richness and vitality. METHODS: A critical analysis of health sciences based on WHO's ICF, on WHO's definition of health systems and on the content and methodological approaches promoted by the biological, clinical and socio-humanistic traditions engaged in health research. RESULTS: The field of health sciences is presented according to: 1) a specification of the content of the field in terms of people's health needs and the societal response to them, 2) a meta-level framework to exhaustively represent the range of mutually recognizable scientific disciplines engaged in health research and 3) a heuristic framework for the specification of a set of shared methodological approaches relevant across the range of these disciplines. CONCLUSION: This conceptualization of health sciences is offered to contextualize the work of health researchers, thereby fostering interdisciplinarity.

[Noninvasive Mechanical Ventilation in Acute Respiratory Failure]. / Nicht-invasive Beatmung als Therapie der akuten respiratorischen Insuffizienz.

The non-invasive ventilation (NIV) is widespread in the clinical medicine and has attained meanwhile a high value in the clinical daily routine. The application of NIV reduces the length of ICU stay and hospitalization as well as mortality of patients with hypercapnic acute respiratory failure. Patients with acute respiratory failure in context of a cardiopulmonary edema should be treated in addition to necessary cardiological interventions with continuous positive airway pressure (CPAP) or NIV. In case of other forms of acute hypoxaemic respiratory failure it is recommended the application of NIV to be limited to mild forms of ARDS as the application of NIV in severe forms of ARDS is associated with higher rates of treatment failure and mortality. In weaning process from invasive ventilation the NIV reduces the risk of reintubation essentially in hypercapnic patients. A delayed intubation of patients with NIV failure leads to an increase of mortality and should therefore be avoided. With appropriate monitoring in intensive care NIV can also be successfully applied in pediatric patients with acute respiratory insufficiency. Furthermore NIV can be useful within palliative care for reduction of dyspnea and improving quality of life. The aim of the guideline update is, taking into account the growing scientific evidence, to outline the advantages as well as the limitations of NIV in the treatment of acute respiratory failure in daily clinical practice and in different indications.

A novel application for assessing diaphragmatic function by ultrasonic deformation analysis in noninvasively ventilated healthy young adults.

PURPOSE: Noninvasive pressure support ventilation is intended to relieve the load on respiratory muscles and to prevent exhaustion. This includes continuous positive airway pressure (CPAP) as well as pressure support ventilation (PSV). Speckle tracking echocardiography (STE) allows quantification of tissue deformation by tracing characteristic grayscale patterns, independent of the acquisition angle. The aim of the present study was to assess the applicability of using STE as a way to investigate diaphragm movement using deformation analysis as a parameter for respiratory workload. MATERIALS AND METHODS: Healthy male subjects (n = 13, 27 ±â€Š7 years) were treated while in a seated supine position with the following respirator settings: regular breathing, 5 mbar CPAP, CPAP + 5 / + 10 / + 15 mbar PSV. A 2 - 4 MhZ M5S phased array sector transducer was used on a Vivid E 9 (GE, Horton, Norway) to visualize the diaphragm. The inspiratory peak transverse strain was measured as a parameter of maximal inspiratory muscle workload and compared to the M-mode-based fractional thickening (FT). RESULTS: Both the FT and the transverse strain increased significantly under CPAP and PSV. The transverse strain correlated well with the FT (r = 0.753; p < 0.001). CONCLUSION: The results measured by STE were comparable to the M-mode-based measurements. The capturing of a larger diaphragmatic sample area and movement tracking possibly lead to higher precision compared to one-dimensional M-mode. The use of STE in patients might provide a reproducible, bedside method to analyze the respiratory workload. Due to the larger sampling area, it might prove superior to mere M-mode acquisition.

Perfusion of microvascular free flaps in head and neck reconstruction after prior neck dissection and irradiation.

Microvascular free flaps are frequently used for head and neck reconstruction after prior neck dissection (ND) and neck irradiation (RTX). The aim of this study was to investigate the influence of ND and RTX on flap perfusion as a critical factor for flap success. Overall, 392 patients reconstructed with a microvascular fasciocutaneous flap (FF) or perforator flap (PF) in the head and neck region between 2011 and 2020 were analysed retrospectively. Flap perfusion measured intraoperatively and postoperatively with the O2C tissue oxygen analysis system was compared between patients who had received neither ND nor RTX (controls), patients who had received ND but no RTX (ND group), and patients who had received both ND and RTX (ND+RTX group). Intraoperative and postoperative flap blood flow was decreased in FFs in ND group patients compared to controls (median 66.3 AU vs 86.0 AU, P = 0.023; median 73.5 AU vs 93.8 AU, P = 0.045, respectively). In the multivariable analysis, these differences showed a tendency to persist (P = 0.052 and P = 0.056). Flap success rates were similar in control patients, ND patients, and ND+RTX patients (98.7%, 94.0%, and 97.6%, respectively). Flap perfusion is not reduced in FFs and PFs in patients who have undergone ND or ND and RTX. This indicates that neck dissection and neck irradiation should not be contraindications for microvascular free flap reconstruction.

Identification of risk factors for postoperative delirium in patients following intraoral reconstruction with microvascular free flaps: a matched-pair analysis.

Postoperative delirium (POD) following microvascular head and neck reconstruction negatively impacts patient outcomes, and only a few risk factors have been identified. The aim of this study was to identify additional risk factors for POD after intraoral reconstruction with microvascular free flaps. Data from 377 patients who underwent intraoral microvascular free flap reconstruction between 2011 and 2019 were analysed retrospectively. Preoperative, intraoperative, and postoperative variables were compared between 40 patients with POD and 40 patients without POD who were matched for previously identified risk factors (i.e., sex, age, American Society of Anesthesiologists class, preoperative arterial hypertension, tracheotomy, operation time, and blood transfusion). A multivariable regression analysis was then performed to identify risk factors associated with POD. POD occurred in 50 (13.3%) of the 377 cases studied; the median time of onset was postoperative day 2. Excessive preoperative alcohol consumption (odds ratio 9.22, 95% confidence interval 1.09-77.97; P = 0.041) and postoperative transplant revision (odds ratio 25.72, 95% confidence interval 1.26-525.43; P = 0.035) were identified as risk factors for POD. The identification of patients at high risk of POD based on these two risk factors may allow early adjustment of diagnostic and therapeutic modalities to improve outcomes and reduce healthcare costs.

Transient expression of OCT4 is sufficient to allow human keratinocytes to change their differentiation pathway.

In this study, we describe a simple system in which human keratinocytes can be redirected to an alternative differentiation pathway. We transiently transfected freshly isolated human skin keratinocytes with the single transcription factor OCT4. Within 2 days these cells displayed expression of endogenous embryonic genes and showed reduced genomic methylation. More importantly, these cells could be specifically converted into neuronal and contractile mesenchymal cell types. Redirected differentiation was confirmed by expression of neuronal and mesenchymal cell mRNA and protein, and through a functional assay in which the newly differentiated mesenchymal cells contracted collagen gels as efficiently as authentic myofibroblasts. Thus, to generate patient-specific cells for therapeutic purposes, it may not be necessary to completely reprogram somatic cells into induced pluripotent stem cells before altering their differentiation and grafting them into new tissues.

ISCoS-WHO collaboration. International Perspectives of Spinal Cord Injury (IPSCI) report.

OBJECTIVE: The objective of this study was to describe the projects, the International Spinal Cord Society (ISCoS) has in cooperation with the World Health Organization (WHO) for the benefit of individuals with spinal cord injury (SCI) worldwide. SETTING: International METHODS: Collaboration between ISCoS and WHO can be divided into (A) building capacity for better SCI education and prevention programs; (B) improving classification systems for use of data in SCI research, the International Classification of External Cause of Injury (ICECI), the International Classification of Diseases (ICD) and the International Classification of Functioning, Disability and Health (ICF); and (C) improving the evidence base for SCI through the report, International Perspectives on Spinal Cord Injury (IPSCI). The objectives of the IPSCI report are first to summarize information on SCI, in particular the science and epidemiology, the services, interventions and policies that are relevant and 'the lived experience' of persons with SCI across the full spectrum of life and throughout the world; second, to document all aspects of the science and experience of SCI to identify gaps between what exists and what is required; and third to make recommendations based on this evidence, with a clear perception of feasible goals and targets, that are consistent with the aspirations and goals of inclusion and full participation as expressed in the UN Convention of the Rights of Persons with Disabilities. FUTURE COOPERATION: ISCoS and WHO will continue to join forces in areas where they can make the greatest difference, especially in prevention and educational issues worldwide.

External ventricular and lumbar drainage-associated meningoventriculitis: prospective analysis of time-dependent infection rates and risk factor analysis.

BACKGROUND: Data on time-dependency of external ventricular drainage (EVD)- and lumbar drainage (LD)-associated meningoventriculitis (MV) are scarce and discussions on the subject are controversial; no data exist for infection rates (IR) relative to drainage-days. For this reason, we conducted an observational study to determine time-dependent IRs and to perform a risk factor analysis. PATIENTS AND METHODS: All patients (n = 210) requiring an EVD or LD during an 18-month period in 2007 and 2008 were enrolled and characterized. Data on type and duration of drainage, ICP measurement, number of drainage manipulations, hospital stay and time point of MV were analysed statistically. RESULTS: A total of 34 MV cases were reported with 17 for each kind of drainage accounting for an IR of 7.5 and 24.7 MV/1000 EVD- and LD-days, respectively. Of these, 28/34 MV (82%) occurred within the first 12 days, and IRs were highest between days 4 and 9. Longer drainage duration (>5 and >9 days, respectively) was correlated with a significant lower risk of MV (p = 0.03; p < 0.001). In this study, significant risk factors for MV were LD [vs. EVD, OR: 2.3 (1.1-4.7); p = 0.01], a previous MV [OR: 7.0 (2.1-23.3); p = 0.002], and neoplasm [OR: 11.6 (3.4-39); p = 0.001]. Simultaneous drainage, ICP and a previous drainage showed no influence on infection. CONCLUSION: To the best of our knowledge, this study is the first to provide data on time dependency of EVD- and LD-associated MV-IR based on drainage-days. However, because of the limited scale of our study, it would be desirable to confirm these results in a more powerful larger study. In conclusion, we recommend that future efforts should be made to better identify preventable risk factors as well as to define time periods of higher risk for the difficult-to-diagnose MV infection as a first step in profiling high risk patients.

Lessons from loricrin-deficient mice: compensatory mechanisms maintaining skin barrier function in the absence of a major cornified envelope protein.

The epidermal cornified cell envelope (CE) is a complex protein-lipid composite that replaces the plasma membrane of terminally differentiated keratinocytes. This lamellar structure is essential for the barrier function of the skin and has the ability to prevent the loss of water and ions and to protect from environmental hazards. The major protein of the epidermal CE is loricrin, contributing approximately 70% by mass. We have generated mice that are deficient for this protein. These mice showed a delay in the formation of the skin barrier in embryonic development. At birth, homozygous mutant mice weighed less than control littermates and showed skin abnormalities, such as congenital erythroderma with a shiny, translucent skin. Tape stripping experiments suggested that the stratum corneum stability was reduced in newborn Lor(-/-) mice compared with wild-type controls. Isolated mutant CEs were more easily fragmented by sonication in vitro, indicating a greater susceptibility to mechanical stress. Nevertheless, we did not detect impaired epidermal barrier function in these mice. Surprisingly, the skin phenotype disappeared 4-5 d after birth. At least one of the compensatory mechanisms preventing a more severe skin phenotype in newborn Lor(-/-) mice is an increase in the expression of other CE components, such as SPRRP2D and SPRRP2H, members of the family of "small proline rich proteins", and repetin, a member of the "fused gene" subgroup of the S100 gene family.

[Intensive care medicine as a component of the compulsory medical curriculum. Evaluation of a pilot curriculum at the University Hospital Aachen]. / Intensivmedizin als Bestandteil des Pflicht-Curriculums: Evaluation eines Pilot-Curriculums am Universitätsklinikum Aachen.

BACKGROUND: In order to provide early achievement of practical experience during medical education, the medical faculty of the university Aachen has developed a new medical school curriculum which was offered in 2003 for the first time. In this curriculum anaesthesiology became a compulsory subject with practical training both in the operation theatre and in emergency medicine. Accordingly, a practical course in the field of intensive care medicine has also been designed with respect to the planned schedule and personnel resources. This course was evaluated by both students and teaching staff in a written, anonymous form as a quality control. METHODS: A dedicated course was developed for medical students of the 8th and 9th semesters. In this course comprised of 6 students and lasting 1 week, practical training is provided by intensive care physicians and accompanied by theoretical lessons focusing on the definition, diagnosis, therapy and prophylaxis of sepsis, essentials of mechanical ventilation and patient presentation at the bedside during daily rounds. On the last day of training students were required to present patients by themselves thereby recapitulating the acquired knowledge. In the summer semester 2007 this intensive care training course was offered for the first time. All participating 83 students and 23 physicians involved in teaching evaluated the course with marks from 1 to 6 according to the standard German school grading system using an online questionnaire. RESULTS: Students rated the course with 1.6+/-0.7 (mean +/- SD) for comprehensibility, with 1.6+/-0.7 for structural design, and with 1.7+/-0.7 for agreement between teachers. They graded their personal learning success with 1.7+/-0.7. With a cumulative mark of 1.7+/-0.6, the course was ranked as 1 of the top 3 courses of the medical faculty from the very beginning. The majority of the teaching staff (80%) appreciated the focus on few selected teaching subjects. However, comprehensibility, structural design, agreement between teachers and personal learning success were graded one mark worse than by the students. CONCLUSIONS: According to the results, efficiency and acceptance of intensive care training courses were high. Major criteria for the high grading were a limited number of participants, the focus on few subjects, and a clear structural design. However, according to several personal notes from the students, simulation-based sessions and written teaching material might further improve success of this course.

The ICF as a conceptual platform to specify and discuss health and health-related concepts.

BACKGROUND: The World Health Organization's International Classification of Functioning, Disability and Health (ICF) has provided a new foundation for our understanding of health, functioning, and disability. As a content-valid, comprehensive and universally applicable health classification, it serves as a platform to clarify and specify health-related concepts that are frequently used in the medical literature. The health concepts to which we refer are: well-being, health status, quality of life (QoL) and health-related quality of life (HRQoL). OBJECTIVE: The aim of this paper is to use the ICF as a conceptual platform to specify and discuss health-related concepts. METHODS: The ICF entities health and health-related domains and functioning will be used as starting point to reach the objective of the paper. Health domains refer to domains intrinsic to the person as a physiological and psychological entity, such as mental functions, seeing functions, and mobility. Health-related domains are not part of a person's health but are so closely related that a description of a person's lived experience of health would be incomplete without them. Examples of health-related domains are work, education, and social activities. Functioning refers to all health and health-related domains within the ICF. RESULTS: Well-being is made up of health, health-related, and non-health-related domains, such as autonomy and integrity. Health state is a health profile that results from collecting together health domains. Functioning states is a profile that results from collecting both health and health-related domains. Health status is a summary measure of health state. Functioning status is a summary measure of functioning state. QoL is the individual's perceptions of how the life is going in health, health-related, and non-health domains. HRQoL is the individual's perceptions of how the life is going in health and health-related domains. DISCUSSION: "HRQoL is to QoL as functioning is to well-being". The ICF represents a standardized and international basis for the operationalization of health based on its health domains. It refers to the more restricted concepts of health state and health status. The ICF is also the basis for the operationalization of functioning based on all health and health-related domains contained therein. The authors argue that functioning is an operationalization of health from a broader perspective. It refers to an operational concept of health in terms of a set of health domains ('under the skin') and health-related domains ('outside the skin') that consider the individual person not only as a biological but also as a social entity. Health from this perspective refers to the broader notion of functioning state and functioning status. Nevertheless, the ICF provides more than a basis for the operationalization of health and functioning. The ICF also contains contextual factors.

[Weaning ward-different from the ICU?] / Weaningstation ­ was ist anders als auf der ICU?

Weaning from mechanical ventilation is generally not the most urgent topic on many ICUs, because acutely endangered patients are usually the staff's main focus. Nevertheless, even these patients whose underlying problem has been mostly solved-whether it was neurologic, internal or surgical-are in need of a structured weaning strategy. The aim of this weaning "road map" is ventilator independence, decannulation and regaining of muscular strength. Achieving of these aims needs a well-educated team of physicians, nurses, respiratory/physical therapists, logopedists and pychologists. Assessment of patient health status, including respiratory muscle function must be part of the overtaking procedure to be able to focus on the main problem that may be causative for the inability to wean so far. Every weaning unit must be able to organize the future treatment of patients (different ward inside the hospital, rehabilitation) or the transfer into a (ventilated) home care situation.

Skin keratinocytes pre-treated with embryonic stem cell-conditioned medium or BMP4 can be directed to an alternative cell lineage.

OBJECTIVES: In this study, we have investigated whether secreted factors from embryonic stem cells (ESCs) could reprogramme keratinocytes and increase their potential to be directed into alternative cell lineages. MATERIALS AND METHODS: Contact and non-contact co-cultures of skin keratinocytes and murine ESCs were used initially to confirm any reprogramming ability of ESC-conditioned medium (CM). Immunofluoresence was used to assess nuclear expression of octamer-4 (Oct-4), as well as to confirm neuronal protein expression in neuroectodermally directed keratinocytes. Transcript expression changes were evaluated using semiquantitative reverse transcription-polymerase chain reaction. Western blotting, accompanied by densitometry analysis, was used to evaluate protein expression following morphology changes. RESULTS: We found that keratinocytes treated with ESC-CM changed their morphology and were stimulated to express the pluripotency regulator, Oct-4, and its target transcripts, Sox-2, Nanog, Utf1 and Rex-1. We demonstrate that at least one of the reprogramming factors is bone morphogenetic factor-4 (BMP4). Pre-treated keratinocytes could be specifically directed to differentiate into cells of the neuronal lineage. The majority of responsive keratinocytes were the epidermal stem cell population, with a small percentage of transit-amplifying cells also being affected. CONCLUSIONS: Our results suggest that ESC-CM contains a number of factors, including BMP4, which are capable of reprogramming mouse skin keratinocytes to make them more developmentally potent, as evidenced by their ability to be re-differentiated into cells of the neuronal lineage. Our findings also imply a continuum of differentiation within the basal keratinocyte population. An increase in developmental potential combined with directed differentiation could increase the therapeutic relevancy of somatic cells.

TGF alpha and v-fos cooperation in transgenic mouse epidermis induces aberrant keratinocyte differentiation and stable, autonomous papillomas.

To assess the synergistic effect of growth and transcription factor deregulation on carcinogenesis in vivo, mating experiments were performed between transgenic mice expressing human TGF alpha or v-fos exclusively in the epidermis by means of a human keratin K1-based targeting vector (HK1.fos, HK1.TGF alpha and HK1.fos/alpha). While HK1.TGF alpha mice exhibited mild epidermal hyperplasia resulting in a wrinkled appearance, this hyperplasia was significantly increased in HK1.fos/alpha mice which also exhibited a novel opalescent and peeling skin phenotype. HK1.fos/alpha keratinocyte differentiation was considerably deregulated with cornified cells appearing in the granular layer, granular cells in the spinous layer and a sixfold increase in BrdU labeling over normal. In addition, hyperplastic HK1.fos/alpha epidermis exhibited aberrant loricrin, filaggrin and novel K13 expression associated with v-fos expression. Unlike adult HK1.TGF alpha controls, hyperplasia persisted in HK1.fos/alpha adults which also rapidly developed autonomous squamous cell papillomas. These results demonstrate that v-fos and TGF alpha over-expression can cooperate to reprogram keratinocyte differentiation and elicit the early stages of neoplasia. Moreover, TGF alpha over-expression appeared to play an early, initiating role in HK1.fos/alpha papilloma etiology, and a promotion role in the accelerated appearance of v-fos wound-associated preneoplastic phenotypes. However, the stable persistence of HK1.fos/alpha papillomas for up to 12 months, suggests that additional events are required for malignant conversion.

Inhibition of retinoid signaling in transgenic mice alters lipid processing and disrupts epidermal barrier function.

To explore the role of retinoids in epidermal development, we recently targeted expression of a dominant-negative, retinoic acid receptor mutant (RAR alpha403) in the epidermis of transgenic mice and observed an unexpected loss of barrier function. In this paper, we demonstrate that transgenic mice expressing the RAR alpha403 transgene show attenuated responsiveness to topical application of all-trans retinoic acid, in agreement with our previous in vitro data. We also show that the vitamin D3 receptor is unaffected in its ability to transactivate in the presence of the dominant-negative RAR alpha403 transgene, indicating that the RAR alpha403 is unlikely to be functioning through a global sequestration of retinoid X receptors. Additionally, we show that the disruption of epidermal barrier function results in a dramatic 4 C drop in mean body surface temperature, probably accounting for the extremely high incidence of neonatal mortality in severely phenotypic pups. Some severely affected pups do survive and show a pronounced hyperkeratosis at postpartum day 4, consistent with previously documented effects of vitamin A deficiency. Biochemical analysis of the severely phenotypic neonates indicates elevated phospholipids and glycosylceramides in the stratum comeum, which results from altered lipid processing. Taken together with previous studies, these data provide strong evidence linking the retinoid-signaling pathway with modulation of lipid processing required for formation of epidermal barrier function.

Identification and localization of label-retaining cells in hamster epithelia.

A subpopulation of basal epithelial cells which retains tritiated thymidine label for extended periods was previously demonstrated in skin and oral mucosae of mice. The present study examined the presence of similar cells in hamsters. Five-day-old hamsters were labeled with tritiated thymidine and the rate at which label was diluted from the basal cells observed. A small percentage of basal cells was found to retain label for up to 69 days. The location of such label-retaining cells ( LRCs ) in the palatal epithelium and in tongue papillae was examined. Thirty and 69 days after labeling, approximately 80% of LRCs in palate were located in the proximal halves of papillae and 80% of LRCs in tongue were positioned basally with approximately 30% of such LRCs occupying positions previously suggested to be stem cell locations. The finding that slowly cycling keratinocytes are related to patterns of tissue architecture is compatible with a function of these cells as epithelial stem cells.

Label-retaining cells in human embryonic and fetal epidermis.

Human embryonic and fetal epidermis was examined and labeling indices (LIs) for basal, intermediate, and periderm cells were determined. The LI for fetal basal cells was 8-11% and the LI for fetal intermediate cells was 7.5-9%. The total fetal epidermal LI was 16-20%, which equaled the basal LI for embryonic epidermis. After 21 days in organ culture, only basal cells in the fetal epidermis labeled with tritiated thymidine, while both basal and intermediate cells in the embryonic epidermis labeled and the total LI for fetal and embryonic epidermal cells was the same as the adult epidermal LI (7%). The LI for periderm decreased with increasing estimated gestational age (EGA) from 9.5% at 49 days EGA to 0.4% at 85 days EGA. A subpopulation of epithelial cells that retained tritiated thymidine label and that have some of the attributes associated with stem cells has been previously demonstrated in rodents. In order to examine human embryonic and fetal epidermis for the presence of such cells, epidermis from various gestational ages were labeled and grown in organ culture for 21 days. The mean percent label-retaining cells (LRCs) for embryonic and fetal epidermis was determined. Approximately 4% of the embryonic and 2% of the fetal epidermal cells retained label for 21 days in organ culture. Embryonic LRCs were found in the basal and suprabasal layers, but fetal LRCs were found only in the basal layer. The presence of LRCs in human embryonic and fetal epidermis suggests that epithelial cell proliferation in these tissues may be regulated via a stem cell pattern of proliferation.