The effect of increasing risk and challenge in the school playground on physical activity and weight in children: a cluster randomised controlled trial (PLAY).

BACKGROUND: To investigate whether changing the play environment in primary schools to one that includes greater risk and challenge increases physical activity and reduces body mass index (BMI). SUBJECTS/METHODS: A 2-year cluster randomised controlled trial was undertaken in 16 New Zealand schools (years 1-8). Intervention schools (n=8) redesigned their play environments to encourage imaginative and independent free play by increasing opportunities for risk and challenge (for example, rough-and-tumble play), reducing rules and adding new playground components (for example, loose parts). Control schools (n=8) were asked to not change their play environment. A qualified playworker rated all school play environments at baseline and 1 year. Primary outcomes were moderate-to-vigorous physical activity (7-day accelerometry) and BMI z-score, collected in 840 children at baseline, 1 and 2 years. Data were analysed using generalised estimating equations. RESULTS: Multiple changes were made to the school play environments resulting in a significant difference in overall play evaluation score between intervention and control schools of 4.50 (95% confidence interval: 1.82 to 7.18, P=0.005), which represents a substantial improvement from baseline values of 19.0 (s.d. 3.2). Overall, schools liked the intervention and reported many benefits, including increased physical activity. However, these beliefs did not translate into significant differences in objectively measured physical activity, either as counts per minute (for example, 35 (-51 to 120) during lunch break) or as minutes of moderate-to-vigorous physical activity (0.4, -1.1 to 2.0). Similarly, no significant differences were observed for BMI, BMI z-score or waist circumference at 1 or 2 years (all P>0.321). CONCLUSIONS: Altering the school play environment to one that promoted greater risk and challenge for children did not increase physical activity, nor subsequently alter body weight. Although schools embraced the concept of adding risk and challenge in the playground, our findings suggest that children may have been involved in different, rather than additional activities.

When does a human being die?

For most of human history there has been no particular importance of establishing the exact time of a person's death, only whether the person is alive or dead. With modern medical advances, however, more precise answers are looked for. For a definition of death to succeed is important that it is a universal definition and that under it, all human beings are correctly identified as alive or dead. This article initially examines the most commonly proposed positions on when a human being dies those of cardiopulmonary death, whole brain death, brainstem death and higher brain death and for each describes scenarios that provide counter-intuitive results. Intuition is used as a benchmark as this is what our patients most commonly use. The second part of the article seeks to establish a more robust definition of death. We argue that death is an event that takes place at a set point in time, when the collection of bodily processes that maintains homoeostasis finally cease. Based upon defining 'human being' as being in possession of human DNA and Olsen's Animalism, the model is applicable to a full lifespan and maintains personal identity throughout the course of life. That this conclusion will interfere with clinical practice concerning organ transplantation is considered, but countered with the argument that there has been a conflation of the normative question of timing of organ retrieval for transplantation with the metaphysical question of what is death.

Implementation of a quality improvement programme to support advance care planning in five hospitals across a health region.

OBJECTIVES: Advance care planning (ACP) can help patients with a terminal illness to prepare for the end of their lives. This report describes a regional service improvement initiative to increase the identification of hospital inpatients at this stage in their illnesses and to increase the number of such patients who are offered the opportunity to start the process of ACP. METHODS: Data were collected prospectively over a 7 month period from four acute hospital trusts and a specialist cancer centre in the South-West London region. Each unit identified a specific patient population who were screened for eligibility to engage in the process of ACP. Data concerning the reasons for eligibility, the suitability for discussion and the various reasons why patients did not complete the process, were recorded. RESULTS: Over a 7 month period 1980 patients were screened and 559 (28.2%) were found to be potentially eligible for an ACP discussion. Of these 227/559 (40.6%) were deemed suitable for a discussion by medical staff. The majority of these patients (195/227; 86%) were offered the opportunity to undergo ACP discussions and 144/195 (73.8%) agreed to begin the process of ACP. CONCLUSIONS: This report shows that a targeted approach can result in increased uptake in the number of patients who engage in ACP. However, systematic identification of potentially eligible patients requires a significant investment of clinical time and resources.

Measuring physical activity and sedentary behaviors in women with young children: a systematic review.

Current evidence indicates that women with young children are less active than women without children. In this review the authors investigated the methods of measuring physical activity employed in studies of women with young children (aged 1-5 years) and the associated challenges in measurement. Articles from databases (MEDLINE, OVID, CINAHL, Google Scholar) and manual searches were limited to English peer-reviewed journals published from 1990 to 2010. Studies that included measurement of physical activity in samples of women with young children were selected. Measurement properties were extracted, and original reliability and validity articles were reviewed for physical activity measurement tools used by 15 samples. The evidence base was dominated by self-report measurement tools, many of which assessed leisure-time physical activity only. Use of motion sensors to assess physical activity in this population was limited. It is likely that much of the habitual physical activity performed by women with young children has not been captured by self-report measures. Further investigation should be undertaken using tools that capture adequately all health-enhancing physical activity among women with young children.

Video capsule endoscopy in peutz-jeghers syndrome: a blinded comparison with barium follow-through for detection of small-bowel polyps.

BACKGROUND AND STUDY AIMS: Video capsule endoscopy has shown promise for the surveillance of significant small-bowel polyps in patients with Peutz-Jeghers syndrome. In this study the yield of significant small-bowel polyps by capsule endoscopy was compared to the yield of these polyps by barium follow-through in adults with Peutz-Jeghers syndrome. PATIENTS AND METHODS: A total of 19 adults with Peutz-Jeghers syndrome who were undergoing surveillance underwent both capsule endoscopy and barium follow-through examinations, and the number of small-bowel polyps of at least 1 cm in diameter that were detected was recorded for each method. The two methods were assessed in terms of comfort and convenience for the patients and their preferred future surveillance method, using a questionnaire. RESULTS: Capsule endoscopy detected a median of four significant small-bowel polyps while barium follow-through detected a median of one (P = 0.008). There was a trend towards more participants having at least one significant small-bowel polyp detected by capsule endoscopy than was the case with barium follow-through, though capsule endoscopy seemed to be less reliable for accurate sizing of polyps that were at the limit of clinical significance. Most participants expressed a preference for capsule endoscopy for future surveillance. CONCLUSIONS: Capsule endoscopy should replace barium follow-through for the surveillance of small-bowel polyps in adults with Peutz-Jeghers syndrome, but the findings of this study should be interpreted with caution until a more reliable means of sizing polyps by capsule endoscopy is available.

Pedometer steps in primary school-aged children: a comparison of school-based and out-of-school activity.

While studies of the physical activity habits of New Zealand children have been carried out, the findings have been restricted by the use of proxy and self-report measures and limited to total overall daily activity. Objective measurement of children's in-school and out-of school physical activity using pedometry is likely to provide more accurate data on habitual daily activity. To date, no such data are available for New Zealand children. In the present study, children from school years 1-6 (girls, n=46; boys, n=45) at a New Zealand primary school wore a Yamax Digiwalker SW-200 pedometer to record school-based and out-of-school steps over a 3-day period. Mean daily steps for the overall sample were 14 333 (S.D.=4110). Boys (X=15 606; S.D.=4601) were significantly more active than girls (X=13 031; S.D.=3079) (p=.00). Mean steps were also significantly higher in older age groups for both boys (p=.03) and in particular, girls (p=.00). Of note, for the overall sample, steps taken out of school made up 52.4% of total daily steps. Girls (53.6%) and boys (51.3%) took a similar proportion of their overall daily steps outside of the school environment. While a significant difference was found between the most and least active tertiles in steps taken during both during school hours (p=.00) and outside of school hours (p=.00), the most active third of the sample completed significantly more of their daily steps outside of school (55.1%) than did their least active (46.7%) counterparts (p=.00). These results suggest that physical activity outside of the school environment is a key contributor to a child's overall level of physical activity, reinforcing the need for interventions targeting the family and community as well as the school environment.

Development of a psychometrically valid and reliable sports nutrition knowledge questionnaire.

The present range of sports nutrition knowledge questionnaires have inadequate psychometric validation, and few are up to date in a rapidly changing discipline. The purpose of this study was to design a sports nutrition questionnaire that satisfied acceptable psychometric criteria of validity (content and construct) and reliability (test-retest). The questionnaire was designed by an expert panel of six sports dietitians and distributed to five groups, selected for their expected variation in sports nutrition knowledge. Dietitians, university business staff and nutrition students received questionnaires via e-mail. The response rates obtained were 21.3% (n = 49), 34.4% (n = 33), and 72.0% (n = 18), respectively. University business and fitness students completed questionnaires during class time. Response rates were 52.3% (n = 23) and 75.4% (n = 49), respectively. The questionnaire was administered a second time to the business staff and the dietitians to assess test-retest reliability. Two methods were used: 1, Pearson's product-moment correlation; and 2, a percentage calculation of questions answered in an identical manner on both test occasions. Reliability was acceptable with Method 1 yielding acceptable values (r = 0.74-0.93), aside from the fluid sub-category (r = 0.52). Method 2 showed good test-retest concordance with 81.2% duplication of responses of all questions. Construct validity was high, as indicated by significant mean knowledge score differences between the groups (p = 0.0001). Dietitians and nutrition students achieved significantly greater mean scores than the remaining groups. The findings of this study indicate that the questionnaire is suitably valid and reliable to be used in research and practice to determine sports nutrition knowledge.

Objectively-measured physical activity in New Zealand workers.

To date, no objective measurements of New Zealanders' physical activity have been reported. The relative contribution of work time activity to total daily physical activity by gender and occupational category has also not been measured objectively in any population. The present study reports such data using pedometer steps counts to quantify both work and non-work physical activity in a sample of New Zealand adult workers in six different occupational categories over a three-day period. Females (9943+/-3855 steps) had slightly higher, but not significantly different (F=0.084(1,179)1, p=0.772) daily step counts than males (9766+/-3965 steps). Using the 10 000 steps a day criterion, 57% of the sample were considered at least low-active. Analysis of variance was used to identify between group (occupational) differences in workplace physical activity (F=11.189(5,175), p<0.001), non-work physical activity (F=2.596(5.175), p=0.027), and total physical activity (F=6.265(5,175), p<0.001). Tukey post hoc comparisons showed significant differences with retail and blue collar workers achieving higher activity levels in comparison to the other occupational categories in work and total physical activity. Odds ratios were calculated to find the odds of being in the top half of activity classification for work and non-work physical activity by tertile splits of work time, active transportation use, sport and exercise participation, television and computer viewing, and passive recreation. Active transportation and passive recreation were related to increased odds of higher work pedometer steps. For non-work pedometer values, television and computer use increased the likelihood of being in the lowest activity group, while sport and exercise participation were associated with increased activity levels.

Cancer surveillance in longstanding ulcerative colitis: endoscopic appearances help predict cancer risk.

BACKGROUND AND AIMS: The risk of colorectal cancer is increased in ulcerative colitis (UC). Patients with UC have diverse colonoscopic appearances. Determining colonoscopic markers for cancer risk could allow patient risk stratification. PATIENTS AND METHODS: Following on from an earlier study which demonstrated a correlation between inflammation severity and neoplasia risk, a case control study was performed to look for colonoscopic markers of colorectal neoplasia risk in UC. Each patient with neoplasia detected between 1988 and 2002 was matched with two non-dysplastic colitic controls. Data were collected on post-inflammatory polyps, scarring, strictures, backwash ileitis, a shortened, tubular, or featureless colon, severe inflammation, and normal looking surveillance colonoscopies. RESULTS: Cases (n = 68) and controls (n = 136) were well matched. On univariate analysis, cases were significantly more likely to have post-inflammatory polyps (odds ratio (OR) 2.14 (95% confidence interval 1.24-3.70)), strictures (OR 4.22; 1.08-15.54), shortened colons (OR 10.0; 1.17-85.6), tubular colons (OR 2.03; 1.00-4.08), or segments of severe inflammation (OR 3.38; 1.41-10.13), and less likely to have had a macroscopically normal looking colonoscopy (OR 0.40; 0.21-0.74). After multivariate analysis, a macroscopically normal looking colonoscopy (OR 0.38; 0.19-0.73), post-inflammatory polyps (2.29; 1.28-4.11), and strictures (4.62; 1.03-20.8) remained significant. The five year risk of colorectal cancer following a normal looking colonoscopy was no different from that of matched general population controls. CONCLUSIONS: Macroscopic colonoscopic features help predict neoplasia risk in UC. Features of previous/ongoing inflammation signify an increased risk. A macroscopically normal looking colonoscopy returns the cancer risk to that of the general population: it should be possible to reduce surveillance frequency to five years in this cohort.

Pancolonic indigo carmine dye spraying for the detection of dysplasia in ulcerative colitis.

BACKGROUND AND AIMS: Colonoscopic surveillance for cancer in longstanding extensive ulcerative colitis relies heavily on non-targeted mucosal biopsies. Chromoendoscopy can aid detection of subtle mucosal abnormalities. We hypothesised that routine pancolonic indigo carmine dye spraying would improve the macroscopic detection of dysplasia and reduce the dependence on non-targeted biopsies. PATIENTS AND METHODS: One hundred patients with longstanding extensive ulcerative colitis attending for colonoscopic surveillance underwent "back to back" colonoscopies. During the first examination, visible abnormalities were biopsied, and quadrantic non-targeted biopsies were taken every 10 cm. Pancolonic indigo carmine (0.1%) was used during the second colonoscopic examination, and any additional visible abnormalities were biopsied. RESULTS: Median extubation times for the first and second colonoscopies were 11 and 10 minutes, respectively. The non-targeted biopsy protocol detected no dysplasia in 2904 biopsies. Forty three mucosal abnormalities (20 patients) were detected during the pre-dye spray colonoscopy of which two (two patients) were dysplastic: both were considered to be dysplasia associated lesions/masses. A total of 114 additional abnormalities (55 patients) were detected following dye spraying, of which seven (five patients) were dysplastic: all were considered to be adenomas. There was a strong trend towards statistically increased dysplasia detection following dye spraying (p = 0.06, paired exact test). The targeted biopsy protocol detected dysplasia in significantly more patients than the non-targeted protocol (p = 0.02, paired exact test). CONCLUSIONS: No dysplasia was detected in 2904 non-targeted biopsies. In comparison, a targeted biopsy protocol with pancolonic chromoendoscopy required fewer biopsies (157) yet detected nine dysplastic lesions, seven of which were only visible after indigo carmine application. Careful mucosal examination aided by pancolonic chromoendoscopy and targeted biopsies of suspicious lesions may be a more effective surveillance methodology than taking multiple non-targeted biopsies.

The epidemiology of medically attended sport and recreational injuries in Queensland.

The Queensland Sport and Recreation Injury Survey (QSRIS) is a retrospective study describing the annual incidence of injuries in the state of Queensland, Australia, resulting from sport and recreational activity involvement. Data were collected by means of a computer-assisted-telephone-interview (CATI) survey of a representative sample of Queenslanders in the spring of 2000. The sample produced a total of 1337 respondents aged 18 to 94 years. The survey asked information regarding medically attended, non-fatal injuries resulting from sport and recreational activities in the past 12 months. Of the 1337 individuals surveyed, 191 of the respondents reported one or more injuries that required medical attention resulting in a total of 222 Injuries. This represents an overall rate of 1,666 medically attended injuries per 10,000 people. Among those reporting a sport or recreational injury, the most common types of injuries were a strained/pulled muscle (30.9%), sprained/torn ligament (24.1%), and fracture (12.6%). The most common bodily locations of injuries were the shoulders (13.0%) and knees (12.5%). Results detail the nature and type of injury, medical professional attending to the injury and the nature of the sport or recreational activity that led to the reported injury, highlighting the number of injuries associated with general fitness activities achieved through high participation rates and low injury rates. This remains an area of much needed attention given the promotional push towards raising the levels of physical activity at a population level.

Changes in cytoplasmic calcium determine the secretory response to extracellular cations in human parathyroid cells: a confocal microscopy study using FM1-43 dye.

Whether activation of the calcium receptor (CaR) modulates secretory events was investigated by real-time fluorescence and confocal microscopy using fura 2 and FM1-43 fluorescent dye. Two paradigms were used: human parathyroid cells, which are stimulated by a step from a high to a low extracellular calcium concentration ([Ca(2+)](ext)), and rMTC6-23 cells, a rat medullary thyroid carcinoma cell line whose secretion is stimulated by an increase in [Ca(2+)](ext). Parathyroid cells were dispersed from parathyroid adenomas removed from 18 patients with primary hyperparathyroidism. In both cell types, incubation with FM1-43 (2 microM) resulted in staining of the plasma membranes, which was rapidly increased following changes in [Ca(2+)](ext) known to stimulate secretion. A high [Ca(2+)](ext) and lanthanum (La(3+)) decreased the membrane-associated FM1-43 fluorescence. Prolonged incubation (5-30 min) in the presence of FM1-43 resulted in accumulation of the dye in the cytoplasm, its granular distribution suggesting targeting of the secretory compartment. These data suggest that FM1-43 fluorescence is determined by: (i) changes in cell membrane surface area associated with secretion-associated events, (ii) displacement/quenching by extracellular cations and (iii) endocytosis of the dye. In parathyroid cells, a rise in FM1-43 fluorescence occurred during incubation in a high (inhibitory) [Ca(2+)](ext) if the cytoplasmic calcium concentration ([Ca(2+)](i)) was decreased by the calcium chelator BAPTA/AM [bis-(o-aminophenoxy)ethane-N,N,N',N'-tetra-acetic acid tetrakis(acetoxymethyl ester)] (10-50 microM). Alternatively, the expected rise in FM1-43 fluorescence did not occur during incubation in a low (stimulatory) [Ca(2+)](ext) if [Ca(2+)](i) was increased by addition of the calcium ionophore A23187 (10-25 microM). These data suggest that [Ca(2+)](i), rather than the absolute value of [Ca(2+)](ext), is the main modulator of secretion from parathyroid cells.

C2-Ceramide increases cytoplasmic calcium concentrations in human parathyroid cells.

Effects of extracellular calcium ([Ca(2+)](ext)) on parathyroid cells are mainly due to the activation of a plasma membrane calcium receptor (CaR) coupled with release of intracellular calcium. In addition, high [Ca(2+)](ext) activates the sphingomyelin pathway in bovine parathyroid cells, generating ceramides and sphingosine. This study explored the direct effects of synthetic ceramides on [Ca(2+)](i) in human parathyroid cells. Cells from five parathyroid adenomas removed from patients with primary hyperparathyroidism were dispersed and maintained in primary culture. Intracellular calcium concentration ([Ca(2+)](i)) [Ca(2+)](i) was monitored using standard quantitative fluorescence microscopy in Fura-2/AM-loaded cells. Laser scanning microscopy was used to monitor the intracellular distribution of a fluorescent ceramide analogue (BODIPY-C5). After addition of 10 microM C2-ceramide (N-acetyl-d-erythro-sphingosine), [Ca(2+)](i) increased rapidly (30-60 s) to a peak three times above basal levels in 70% of cells (37/55 cells in four experiments). This effect appeared to be due to release of Ca(2+) from intracellular stores rather than Ca(2+) entry from the extracellular medium. C2-responsive cells had a smaller [Ca(2+)](i) response to subsequent stimulation with the CaR agonist-neomycin (1 mM). These responses were specific to C2 since C6-ceramide (N-hexanoyl-d-erythro-sphingosine) did not affect basal [Ca(2+)](i) nor the responses to an increase in [Ca(2+)](ext) and to neomycin. C5-BODIPY generated intense perinuclear fluorescence, suggesting targeting of the ceramides to the Golgi apparatus. These data demonstrate that endogenous generation of ceramides has the potential to modulate changes in [Ca(2+)](i) and secretion in response to [Ca(2+)](ext) in human parathyroid cells.

Thimerosal increases the responsiveness of the calcium receptor in human parathyroid and rMTC6-23 cells.

Parathyroid cells express a plasma membrane calcium receptor (CaR), which is stimulated by a rise in extracellular calcium concentration ([Ca2+]ext). A decreased sensitivity to [Ca2+]ext occurs in adenomatous parathyroid cells in patients with primary hyperparathyroidism, but the underlying functional mechanism is not yet fully understood. This study explored whether CaR responsiveness is influenced by increasing the affinity of IP3 receptors--a major signalling component of other G-protein-coupled receptors. The sulphydryl reagent thimerosal was used to increase the responsiveness of IP3-receptors. Quantitative fluorescence microscopy in Fura-2-loaded cells was used to investigate the effects of thimerosal on the cytoplasmic calcium concentrations ([Ca2+]i) in human parathyroid cells and to compare its effects in a rat medullary thyroid carcinoma cell line (rMTC6-23) also expressing CaR. During incubation in Ca(2+)-free medium, thimerosal 5 microM induced a rapid sustained rise in [Ca2+]i in human parathyroid cells and no further [Ca2+]i increase appeared in response to the CaR agonist Gd3+ (100 microM). Thimerosal 1 microM induced only slow and minimal changes of basal [Ca2+]i and allowed a rapid response to Gd3+ 20 nM (a concentration without effect in control cells). The slope of the thimerosal-induced [Ca2+]i responses was steeper following exposure to CaR agonists. In the presence of 1 mM [Ca2+]ext, thimerosal (0.5 microM) induced a sharp increase in [Ca2+]i to a peak (within 60 s), followed either by return to basal [Ca2+]i or by a plateau of slightly higher amplitude. Similar results were obtained using rMTC6-23 cells. Thimerosal increases the responsiveness to CaR agonists through modulation of the sensitivity of the IP3 receptor in both parathyroid and rMTC6-23 cells.

Renal function and Ca(2+) currents after dye-labeling identification of renal sympathetic neurons.

The present study was performed to determine whether renal efferent sympathetic neurons could be identified using a retrograde neuronal tracer without compromising renal function and whether the labeling and identification procedure alters Ca(2+) currents and neuromodulation of those neurons. Renal sympathetic and superior cervical ganglion (SCG) neurons were labeled with the fluorescent retrograde tracer fast blue. Renal function studies made 1 wk after labeling revealed that renal hemodynamics and fluid and electrolyte excretion were similar between the dye-injected (left) kidney and the control (right) kidney under control conditions and after hemorrhage. After volume expansion, urine flow in the dye-injected kidney was slightly, but significantly, less than that of the control kidney, whereas urinary sodium excretion increased by approximately ninefold in both kidneys. Patch-clamp studies of SCG neurons in 10 mM external Ca(2+) revealed that peak currents were not affected by the presence of the dye or a 1-min exposure to ultraviolet (UV) light. Neither maximal norepinephrine-induced Ca(2+) current inhibition nor the sensitivity to norepinephrine was affected by the dye or 1-min UV exposure. Facilitation protocols revealed that G protein modulation of Ca(2+) currents remained intact in dye-labeled UV-exposed neurons. This study demonstrates that a retrograde fluorescent dye technique to identify renal sympathetic neurons does not compromise renal function and the presence of the dye label or UV exposure has no effect on Ca(2+) currents and neuromodulation in these neurons. Isolation of single identified renal sympathetic neurons coupled with patch-clamp techniques represents a tool to investigate the role of individual current systems in the modulation of excitability in these neurons, which play an important role in the control of renal hemodynamics and excretory function and in the pathogenesis of hypertension.

Transitional changes in membrane potential and intracellular [Ca2+] in rat basophilic leukemia cells.

Using whole-cell current-clamp measurements we have found that thapsigargin-mediated activation of store-regulated Ca2+ entry in rat basophilic leukemia cells is accompanied by complex changes in membrane potential. These changes consisted of: (i) an initial slow, small depolarization, (ii) a transitional change in potential to a depolarized value and (iii) transitional changes between a hyperpolarized and a depolarized potential. These complex changes in potential can be explained by the interaction between the endogenous inwardly rectifying K+ conductance and the generation of a small inward current. To investigate the possible influence of these changes of potential on [Ca2+]i, single cell measurements of fura2 fluorescence were undertaken alone or in combination with current-clamp measurements. Thapsigargin-mediated activation of the store-regulated Ca2+ entry pathway was accompanied by a marked increase of [Ca2+]i. During this increase, transient, abrupt declines in [Ca2+]i were detected in approximately 60% of the cells investigated. These changes of [Ca2+]i are consistent with the observed changes of membrane potential recorded under current-clamp.

Primary and adaptive changes of A-type K+ currents in sympathetic neurons from hypertensive rats.

The A-type K+ current (IA) of superior cervical ganglion neurons acutely isolated from spontaneously hypertensive (SHR) and age-matched Wistar-Kyoto (WKY) rats was compared under whole cell voltage clamp. Activation parameters were similar in each strain. Steady-state inactivation was shifted approximately -6 mV in SHR, where one-half inactivation occurred at -81 mV vs. -75 mV in WKY rats. The shift was not present in prehypertensive SHR but remained in adult enalapril-treated SHR and, therefore, may represent a primary alteration of IA properties. IA amplitudes evoked from physiological potentials were similar, despite inactivation of a greater fraction of the current in the SHR. Comparing maximal IA densities revealed that current density is elevated in the SHR, which compensates for the inactivation shift. Current density decreased with age in WKY neurons but did not significantly decline in SHR neurons unless hypertension was prevented with enalapril. Thus adult SHR neurons may retain a high IA density as an adaptive response to offset potential hyperexcitability resulting from the hyperpolarized IA inactivation.