Shrub changes with proximity to anthropogenic disturbance in boreal wetlands determined using bi-temporal airborne lidar in the Oil Sands Region, Alberta Canada.

In this study, we used bi-temporal airborne lidar data to compare changes in vegetation height proximal to anthropogenic disturbances in the Oil Sands Region of Alberta, Canada. We hypothesize that relatively low-impact disturbances such as seismic lines will increase the fragmentation of wetlands, resulting in shrub growth. Bi-temporal lidar data collected circa 2008 and 2018 were used to identify correspondence between the density of anthropogenic disturbances, wetland shape complexity and changes in vegetation height within >1800 wetlands near Fort McKay, Alberta, Canada. We found that up to 50% of wetlands were disturbed by anthropogenic disturbance in some parts of the region, with the highest proportional disturbance occurring within fens. Areas of dense anthropogenic disturbance in bogs resulted in increased growth and expansion of shrubs, while we found the opposite to occur in fens and swamps during the 10-year period. Up to 30% of bogs had increased shrubification, while shrub changes in fens and swamps varied depending on density of disturbance and did not necessarily correspond with shrub growth. As wetland shapes became increasingly elongated, the prevalence of shrubs declined between the two time periods, which may be associated with hydrological drivers (e.g. elongated may indicate surface and ground-water discharge influences). The results of this study indicate that linear disturbances such as seismic lines, considered to have relatively minimal impacts on ecosystems, can impact proximal wetland shape, fragmentation and vegetation community changes, especially in bogs.

Primary surgical management of anterior pelvic organ prolapse: a systematic review, network meta-analysis and cost-effectiveness analysis.

BACKGROUND: Anterior compartment prolapse is the most common pelvic organ prolapse (POP) with a range of surgical treatment options available. OBJECTIVES: To compare the clinical effectiveness and cost-effectiveness of surgical treatments for the repair of anterior POP. METHODS: We conducted a systematic review of randomised controlled trials comparing surgical treatments for women with POP. Network meta-analysis was possible for anterior POP, same-site recurrence outcome. A Markov model was used to compare the cost-utility of surgical treatments for the primary repair of anterior POP from a UK National Health Service perspective. MAIN RESULTS: We identified 27 eligible trials for the network meta-analysis involving eight surgical treatments tested on 3194 women. Synthetic mesh was the most effective in preventing recurrence at the same site. There was no evidence to suggest a difference between synthetic non-absorbable mesh, synthetic partially absorbable mesh, and biological mesh. The cost-utility analysis, which incorporated effectiveness, complications and cost data, found non-mesh repair to have the highest probability of being cost-effective. The conclusions were robust to model inputs including effectiveness, costs and utility values. CONCLUSIONS: Anterior colporrhaphy augmented with mesh appeared to be cost-ineffective in women requiring primary repair of anterior POP. There is a need for further research on long-term effectiveness and the safety of mesh products to establish their relative cost-effectiveness with a greater certainty. TWEETABLE ABSTRACT: New study finds mesh cost-ineffective in women with anterior pelvic organ prolapse.

Loss of hypothalamic corticotropin-releasing hormone markedly reduces anxiety behaviors in mice.

A long-standing paradigm posits that hypothalamic corticotropin-releasing hormone (CRH) regulates neuroendocrine functions such as adrenal glucocorticoid release, whereas extra-hypothalamic CRH has a key role in stressor-triggered behaviors. Here we report that hypothalamus-specific Crh knockout mice (Sim1CrhKO mice, created by crossing Crhflox with Sim1Cre mice) have absent Crh mRNA and peptide mainly in the paraventricular nucleus of the hypothalamus (PVH) but preserved Crh expression in other brain regions including amygdala and cerebral cortex. As expected, Sim1CrhKO mice exhibit adrenal atrophy as well as decreased basal, diurnal and stressor-stimulated plasma corticosterone secretion and basal plasma adrenocorticotropic hormone, but surprisingly, have a profound anxiolytic phenotype when evaluated using multiple stressors including open-field, elevated plus maze, holeboard, light-dark box and novel object recognition task. Restoring plasma corticosterone did not reverse the anxiolytic phenotype of Sim1CrhKO mice. Crh-Cre driver mice revealed that PVHCrh fibers project abundantly to cingulate cortex and the nucleus accumbens shell, and moderately to medial amygdala, locus coeruleus and solitary tract, consistent with the existence of PVHCrh-dependent behavioral pathways. Although previous, nonselective attenuation of CRH production or action, genetically in mice and pharmacologically in humans, respectively, has not produced the anticipated anxiolytic effects, our data show that targeted interference specifically with hypothalamic Crh expression results in anxiolysis. Our data identify neurons that express both Sim1 and Crh as a cellular entry point into the study of CRH-mediated, anxiety-like behaviors and their therapeutic attenuation.

Utility of the hypertriglyceridemic waist phenotype in the cardiometabolic risk assessment of youth stratified by body mass index.

BACKGROUND: It is unclear whether the hypertriglyceridemic waist phenotype (HTWP) can be used to identify those at most risk of cardiometabolic disorders. OBJECTIVES: The utility of the HTWP as a useful predictor of cardiometabolic risk in youth stratified by body mass index was assessed. METHODS: Three hundred and eighty-seven children (12-17.5 years) were used within this cross-sectional study. Participants were classified as normal weight or overweight/obese according to the International Obesity Task Force criteria. The HTWP phenotype was defined as having a waist circumference ≥90th percentile for age and gender with concomitant triglyceride concentrations ≥1.24 mmol L(-1) . Cardiometabolic risk profiles were compared using MANCOVA. RESULTS: Normal weight participants with the HTWP had significantly higher levels of C-reactive protein 2.6 ± 0.4 vs. 1.6 ± 0.3 mg L(-1) (P < 0.05) and cardiometabolic risk scores (1.3 ± 0.3 vs. -0.7 ± 0.2 and 2.1 ± 0.4 vs. -0.5 ± 0.2; both P < 0.05) compared with those of a normal weight without the HTWP. Overweight/obese participants with the HTWP had significantly higher C-reactive protein levels (3.5 ± 0.6 vs. 2.6 ± 0.5; P < 0.05) as well as both cardiometabolic risk scores (1.6 ± 0.6 vs. 0.9 ± 0.2 and 2.2 ± 0.6 vs. 0.8 ± 0.2; both P < 0.001) when compared with overweight/obese participants without the HTWP. CONCLUSIONS: The HTWP may serve as a simple and clinically useful approach to identify youth at increased cardiometabolic risk.

Personality dimensions and their relationship with job satisfaction amongst Dutch nurse anaesthetists.

AIM: This study investigates the relationship between personality dimensions and job satisfaction. BACKGROUND: The shortage of nurses, and those voluntarily leaving their jobs, continues to be a problem affecting the delivery of healthcare all over the world, including anaesthesia. If it is found that nurse anaesthetists with certain personality types have high levels of job satisfaction, the information may be helpful for the retention of nurse anaesthetists. METHODS: A questionnaire was distributed amongst Dutch nurse anaesthetists. Factor and multiple regression analyses were performed to reveal personality dimensions and their impact on job satisfaction. RESULTS: Nine hundred and twenty-three questionnaires were completed and analysed (46% response rate). Two personality dimensions -'easy going' and 'orderly'- explained 3.5% of the variance in job satisfaction. CONCLUSION: Personality dimensions as measured with the Myers-Briggs Type Indicator (MBTI) are only minimally relevant in predicting job satisfaction amongst Dutch nurse anaesthetists. IMPLICATIONS FOR NURSING MANAGEMENT: Before using personality traits as a selection tool for retaining employees, it is important to understand the relationship of particular personalities to job satisfaction; it is also important to know which combination of personality traits is likely to create a highly cohesive work group.

High-throughput applicable genomic sex typing of chicken by TaqMan real-time quantitative polymerase chain reaction.

Genetic sex typing of vertebrate animals is an essential technique for research on reproductive phenomena such as sex determination of embryonic tissues. Polymerase chain reaction amplification of genomic DNA segments in the Z and W sex chromosomes has been widely used as a standard laboratory method to determine genetic sex of the chicken (Gallus gallus domesticus). However, conventional protocols for PCR determination of avian sex typically involve tedious steps of genomic DNA isolation, which often require relatively large amounts of tissue samples, and the purity of genomic DNA specimens significantly affects PCR efficiency. Moreover, detection of sex chromosome-specific PCR products by gel electrophoresis is prone to misjudgment caused by amplification of contaminating genomic DNA segments derived from tissue or DNA samples as well as previously generated PCR products. Thus, the credibility of genetic sex typing by conventional PCR-based methods that measure the relative amounts of the end product DNA amplicons critically depends on several experimental steps that are potentially vulnerable to errors. Here, we describe an optimized protocol of chicken genetic sex typing by TaqMan real-time quantitative PCR amplification of markers on the sex chromosomes. This TaqMan sex typing method accurately quantifies relative amounts of the Z and W sex chromosome markers directly from only 0.5 to 2 microL of total blood lysate without nucleic acid purification. The real-time amplification curves of the quantitative PCR reaction readily distinguished truly homozygous (ZZ) and heterozygous (ZW) sex chromosomes from contamination of the sex chromosomal DNA, ensuring highly credible sex determination. Thus, the TaqMan typing of chicken genetic sex has several advantageous features for high-throughput operation compared with conventional methods.

Burnout, psychosomatic symptoms and job satisfaction among Dutch nurse anaesthetists: a survey.

BACKGROUND: To meet the increasing demand for healthcare providers, it is crucial to recruit and retain more nurse anaesthetists (NAs). The majority of NAs in the Netherlands are >45 years old, and retaining them in their jobs is very important. This study investigates the relationships among burnout, physical health and job satisfaction among Dutch NAs. METHODS: Two thousand NAs working in Dutch hospitals were invited to participate in this online questionnaire. We tested the relationships among burnout, psychosomatic symptoms, sickness absence, perceived general health and job satisfaction. RESULTS: Nine hundred and twenty-three questionnaires were completed and analysed (46% response rate). Burnout and psychosomatic symptoms were negatively associated with job satisfaction, and predicted 27% of job satisfaction. Perceived general health was positively and sickness absence was negatively related to job satisfaction. Older NAs had a higher incidence of burnout than their younger counterparts. CONCLUSIONS: The results confirmed the importance of a healthy psychosocial work environment for promoting job satisfaction. To prevent burnout, further research is necessary to determine the factors causing stress. These findings may also apply to anaesthesiologists who share many tasks and work in close cooperation with NAs.

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition.

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies.

Discriminating work context factors in the working environment of Dutch nurse anesthetists.

With an ever increasing number of patients and more demanding health care system it is important to keep nurse anesthetists as mentally and physically fit as possible. Especially with a shortage of nurse anesthetists it is important to know which work context factors are important for maintaining a healthy balance between the nurse anesthetist and his work environment. This study is the first to determine which work context factors of nurse anesthetists are most relevant for a healthy work environment. A questionnaire survey, containing work related items, was distributed among all nurse anesthetists working in Dutch hospitals. All together 882 questionnaires (response rate 44%) were completed and analyzed, including factor analysis for the discriminating work context factors. Four discriminating work context factors (career/rewards, relation with supervisor, task contents and social environment) were found to be relevant, explaining 48% of the variance in work context. All four work context factors are considered to be job resources, although not hospital related. Supervisors (head nurses) interpret these work context factors differently from nurse anesthetists, which can result in dissatisfaction of the latter group. Nurse anesthetists participate more in sub-functions and activities in larger peripheral and academic anesthesia departments. Smaller anesthesia departments require nurse anesthetists to be more flexible and perform many different functions within the anesthesia domain.

Exogenous application of platelet-leukocyte gel during open subacromial decompression contributes to improved patient outcome. A prospective randomized double-blind study.

BACKGROUND: Platelet-leukocyte gel (PLG) is being used during various surgical procedures in an attempt to enhance the healing process. We studied the effects of PLG on postoperative recovery of patients undergoing open subacromial decompression (OSD). METHODS: PLG was produced from platelet-leukocyte-rich plasma (P-LRP), prepared from a unit of whole blood. Forty patients were included in the study. Self-assessed evaluations, using the American Shoulder and Elbow Surgeons scoring system of activities of daily living (ADL), joint instability, pain levels, pain medications, and clinical evaluations for range of motion were conducted. RESULTS: Platelet and leukocyte counts were significantly increased in the P-LRP compared to baseline counts. Treated patients demonstrated decreased visual analog scales for pain and used significantly less pain medication, had an improved range of motion during passive forward elevation, external rotation, external rotation with arm at 90 degrees abduction, internal rotation, and cross body adduction compared to control patients (p < 0.001). No differences in the instability score were observed between the groups. Furthermore, treated patients performed more ADL (p < 0.05). CONCLUSION: In the PLG-treated group, recovery was faster and patients returned earlier to daily activities and also took less pain medication than control subjects.

Differences in platelet growth factor release and leucocyte kinetics during autologous platelet gel formation.

Three commercial systems for whole blood separation were compared to obtain the buffy coat composed of platelet-rich plasma (BC-PRP) and leucocytes . These samples of the buffy coat were used to make a platelet gel (PG), which was used to measure platelet growth factor (PGF) release, to perform a white blood cell (WBC) count and to measure myeloperoxidase (MPO) release from WBCs. Aliquots of whole blood obtained from ten volunteers were distributed either to a blood cell separator (The Electa Cell-Separator, E-CS) or to a tabletop centrifuge (Gravitational Platelet Sequestration System, GPS) to prepare the BC-PRP. The third system combines the BC-PRP production by E-CS with a micro porous filter (Autologous Growth Factor filter, AGF) to enrich for the BC-PRP. Autologous thrombin was used to activate the BC-PRP and to prepare the PG and subsequently to degranulate the platelet concentrate. Platelet-derived growth factor-AB and transforming growth factor-beta1 were present in high levels after thrombin activation of the E-CS or GPS prepared samples. However, the AGF prepared samples released their growth factors before thrombin activation. The WBCs were significantly increased with each of the three systems. Contrary to the AGF, no leucocyte degranulation occurred with the E-CS or GPS prepared samples, based upon the low MPO concentrations in the BC-PRP. The three types of apparatus had different harvesting capacities for collecting the enriched platelets and the release of high concentrations of PGF. When the E-CS and GPS, but not the AGF, were used, low levels of MPO were maintained in the PG, which potentially contributes to antimicrobial properties of platelet gel at the site of application.

Platelet gel and fibrin sealant reduce allogeneic blood transfusions in total knee arthroplasty.

BACKGROUND: Total knee arthroplasty (TKA) is often associated with a considerable amount of post-operative blood loss, necessitating the transfusion of allogeneic blood, which can add to the complications. Optimization of strategies to reduce the need for blood transfusion is desired. This study was designed to evaluate the efficacy of autologous platelet gel and fibrin sealant in unilateral TKA. METHODS: Consecutive patients were operated on and assigned to the study and control groups. Study group patients (n = 85) were operated on according to our standard TKA protocol, with the application of autologous platelet gel and fibrin sealant on the wound tissues at the end of surgery. Eighty patients were operated on according to the same protocol, but without the use of platelet gel and fibrin sealant, and served as the control group. All blood transfusions, occurrence of wound leakage, wound healing disturbances and incidences of post-operative infections were recorded. RESULTS: Patients in the treatment group had a significantly higher post-operative haemoglobin level (11.3 vs. 8.9 g/dl, respectively) and a decreased need for allogeneic blood products (0.17 vs. 0.52 units, respectively) than those in the control group (P < 0.001). The incidences of wound leakage and wound healing disturbance were significantly less (P < 0.001) in patients managed with platelet gel and fibrin sealant. Four patients in the control group, who received blood products, developed wound infection. The hospital stay was decreased by 1.4 +/- 1.5 days for patients in the treatment group (P < 0.001). CONCLUSION: Peri-operatively applied platelet gel and fibrin sealant may reduce the incidence of allogeneic blood transfusions and complications associated with TKA.

Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction.

Patients with postinfective irritable bowel syndrome and Trichinella spiralis-infected mice share many features including visceral hypersensitivity and disordered motility. We assessed enterochromaffin (EC) numbers and serotonin transporter (SERT) using National Institute of Health (NIH) female mice studied for up to 56 days post-T. spiralis infection. The effects of steroid treatment and the T-cell dependence of the observed responses were assessed by infection of hydrocortisone-treated or T-cell receptor knock out [TCR (betaxdelta) KO] animals. Enterochromaffin cell density in uninfected animals increased from duodenum 10.0 cells mm-2 (5.9-41.0) to colon 61.8. (46.3-162) cells mm-2 P<0.0001. Infection increased duodenal and jejunal counts which rose to 37.3 (22-57.7) cells mm-2 and 50.6 (7-110.8) cells mm-2, respectively, at day 14. Infection significantly reduced jejunal SERT expression, with luminance values falling from 61.0 (45.1-98.3) to a nadir of 11.6 (0-36.0) units at day 9, P<0.001. Specific deficiencies in all T cells reduced EC hyperplasia and abrogated infection-induced mastocytosis. Thus infection induced inflammation increases EC numbers, as has been reported in PI-IBS, and reduces SERT. This may increase mucosal 5HT availability and contribute to the clinical presentation of PI-IBS.

Acute effects of cholecystokinin tetrapeptide on brain stem auditory evoked potentials in healthy volunteers.

This study investigated the effects of continuous slow intravenous infusion of cholecystokinin tetrapeptide (CCK-4) on brain stem auditory evoked potentials (BSAEP) in healthy subjects. Twenty-four subjects, 15 females and 9 males, were assigned to infusion with either placebo or CCK-4 in a randomized, double-blind, parallel group design. BSAEPs, mood, physical symptoms, and vital signs were assessed once before infusion and at 10 min and 40 min after the onset of infusion. In the 16 subjects (N = 8, CCK-4; N = 8, placebo) CCK-4, compared to placebo, delayed peak I latency during early infusion, slowed the latencies of peaks III and V, and decreased the amplitude of peak III throughout the infusion. No significant treatment differences were observed with respect to symptoms, mood, or cardiovascular measures. These preliminary findings suggest that CCK-4 may interfere with information processing in the brain stem auditory pathways and that prolonged intravenous CCK-4 administration may be a useful challenge paradigm for investigating CCK's modulatory role on brain stem mechanisms mediating anxiety and panic in humans.

Health effects on nearby residents of a wood treatment plant.

OBJECTIVES: The aim of the study was to evaluate the health status of nearby residents of a wood treatment plant who had sustained prolonged low-level environmental exposure to wood processing waste chemicals. METHODS: A population of 1269 exposed residents who were plaintiffs or potential plaintiffs in a lawsuit against the wood treatment plant were evaluated by questionnaire for a health history and symptoms. A representative sample of 214 exposed subjects was included in the analysis. One hundred thirty-nine controls were selected from 479 unexposed volunteers and matched to the exposed subjects as closely as possible by gender and age. Subjects and controls completed additional questionnaires and were evaluated by a physician for medical history and physical examination, blood and urine testing, neurophysiological and neuropsychological studies, and respiratory testing. Environmental sampling for wood processing waste chemicals was carried out on soil and drainage ditch sediment in the exposed neighborhood. RESULTS: The exposed subjects had significantly more cancer, respiratory, skin, and neurological health problems than the controls. The subjective responses on questionnaires and by physician histories revealed that the residents had a significantly greater prevalence of mucous membrane irritation, and skin and neurological symptoms, as well as cancer. (Exposed versus unexposed, cancer 10.0% versus 2.08%, bronchitis 17.8% versus 5.8%, and asthma by history 40.5% versus 11.0%) There were significantly more neurophysiologic abnormalities in adults of reaction time, trails A and B, and visual field defects. CONCLUSIONS: Adverse health effects were significantly more prevalent in long-term residents near a wood treatment plant than in controls. The results of this study suggest that plant emissions from wood treatment facilities should be reduced.

QT interval in children with sensory neural hearing loss.

Long QT syndrome was first described in children with congenital sensory neural hearing loss (SNHL). The deafness was attributed to abnormalities in potassium ion channels of the inner ear. Similar channels are present in the heart and its dysfunction causes long QT syndrome. Whether congenital SNHL is associated with prolonged QT is unknown. This study examined 52 patients (median age 8.35 years, range 0.21-17.42 years) with SNHL and compared them to 63 healthy children (median age 10.2 years; range 0.67-19 years). An observer, who was blinded from the presence or absence of SNHL, measured QT, QTc intervals and dispersions from a standard 12-lead electrocardiogram. To assess the cardiac autonomic enervation, power spectral analysis of heart rate variability was determined using a 24-hour ambulatory heart rate monitor and was expressed as high (HF) to low frequency (LF) ratio. Left ventricular size and functions were evaluated by using two-dimensional echocardiography. The medians (and ranges) of QT intervals were 340 ms (230-420 ms) in patients and 320 ms (240-386 ms) in the control group (P < 0.01). The QTc was longer in patients with SNHL (median 417 ms, range 384-490 ms) than in controls (median 388 ms, range 325-432 ms, P < 0.001). QT dispersions in SNHL were higher (median .038 ms, range 00-11 ms) than controls (median 27 ms, range 00-52 ms, P < 0.001). T wave inversion (n = 16) and alternans (n = 3) occurred in patients with SNHL. Heart rates were similar in both groups. Some deaf patients (n = 8) had dizzy episodes with a QTc > 440 ms. The HF:LF ratio was 1.32 (0.516-2.33) in deaf patients and 1.428 (0.67-2.3) in the control group (P > 0.1). Left ventricular size and functions were similar and normal in deaf patients and controls. In children, congenital SNHL is associated with a prolonged QT interval.

Effects of acute nicotine administration on cognitive event-related potentials in tacrine-treated and non-treated patients with Alzheimer's disease.

Earlier studies of cognitive event-related brain potentials (ERPs) reporting diminished amplitudes and delayed latencies of the P300 potential in dementia of the Alzheimer type (DAT), together with independent findings of the P300- and performance-enhancing properties of nicotine in normal adults, stimulated this study to explore the single-dose effects of nicotine on auditory and visual P300s in DAT. Thirteen patients, 6 currently receiving treatment with the cholinesterase inhibitor tacrine (tetrahydroaminoacridine; THA) and the remaining being medication free, were administered 2 mg of nicotine polacrilex under double-blind, randomized, placebo-controlled conditions. Prior to nicotine administration, THA-treated patients exhibited shorter auditory P300 latencies than non-treated patients. Acutely administered nicotine failed to alter auditory P300, but increased the amplitudes of visual P300s in both DAT patient groups. Neither THA treatment nor single-dose nicotine altered behavioural performance in the visual and auditory task paradigms. The results are discussed in relation to nicotinic cholinergic, attentional and cognitive processes in DAT.

Acute nicotine effects on auditory sensory memory in tacrine-treated and nontreated patients with Alzheimer's disease: an event-related potential study.

The auditory mismatch negativity (MMN) event-related brain potential (ERP) reflects the storage of information in acoustic sensory memory. Thirteen patients with Alzheimer's disease (AD), 6 receiving treatment with the cholinesterase inhibitor, tacrine [tetrahydroaminoacridine (THA)], and 7 receiving no treatment, were administered 2 mg of nicotine polacrilex and placebo. MMNs were recorded with 1- and 3-s interstimulus intervals (ISIs) during pre- and post-placebo/nicotine administration. Amplitudes decreased from pre- to post-placebo recordings in nontreated patients but remained stable in THA-treated patients. Comparison of pre- and post-nicotine MMNs found amplitude increases with nicotine in nontreated but not in THA-treated patients. MMN latencies were shortened by nicotine in both treatment groups. These exploratory findings suggest that nicotine-improved strength of acoustic sensory memory traces and speed of acoustic sensory discrimination in AD are differentially affected by chronic tacrine treatment.

Effects of aging on vasopressin production in a kindred with autosomal dominant neurohypophyseal diabetes insipidus due to the DeltaE47 neurophysin mutation.

Postmortem examinations of the hypothalamus of patients with autosomal dominant neurohypophyseal diabetes insipidus (adNDI), which have been reported only on persons dying between the ages of 37-87 yr, reveal the presence of the arginine vasopressin (AVP)-producing parvocellular neurons but the absence of 95% of the expected AVP-producing magnocellular neurons. To determine whether the clinical course of adNDI is compatible with the hypothesis that the neuropathologic findings are attributable to a progressive loss of magnocellular neurons beginning in early life, we performed posterior pituitary magnetic resonance imaging and water deprivation tests, including plasma ACTH measurements, on 17 affected members of a kindred with the deltaE47 neurophysin mutation whose ages ranged from 3 months to 54 yr. Nine adult nonaffected members (ages, 20-56 yr) underwent these tests as controls. All six children undergoing magnetic resonance imaging demonstrated a posterior pituitary hyperintense signal (PPHS). Eight of nine affected adults showed an absent or barely visible PPHS, whereas eight of nine age-matched nonaffected adults produced a normal size PPHS. During water deprivation tests, infants concentrated their urine normally, and a 3-month-old infant produced a high plasma AVP level of 15.7 pmol/liter. By school age, affected children were no longer able to concentrate their urine or prevent hypernatremia. Affected adults became dehydrated; their median plasma AVP level was less than 1.0 pmol/liter, but their median fasting plasma ACTH was 2-fold greater than the level of nonaffected adults (10.0 vs. 5.0 pmol/liter; P = 0.008). These results suggest that adNDI is a progressive disease associated with chronic loss of the magnocellular neurons that supply AVP to the posterior pituitary but preservation of the parvocellular neurons that supply AVP and CRH to the median eminence and stimulate ACTH production during hypernatremia.