The impact of different hair-removal behaviours on the biophysical and biochemical characteristics of female axillary skin.

OBJECTIVE: The impact of hair removal on the biophysical and biochemical characteristics of human axillary skin is not fully understood. This study investigated the effect of different hair-removal techniques on biophysical parameters and the concentrations of key inflammatory biomarkers in the axillae of female Thai subjects. Axillary hair was removed by shaving, plucking or waxing. METHODS: Following a 2-week washout phase without hair removal, subjects underwent visual assessment for erythema and skin dryness in one (randomized) axilla, then, hair was removed from the axilla by shaving, plucking or waxing according to each subject's established habit. Erythema and dryness were assessed again 30 min after hair removal, and buffer scrubs collected from depilated and non-depilated axillae and analysed for inflammatory cytokines; after a further 48 h, erythema, dryness and post-inflammatory hyperpigmentation (PIHP) were assessed in the depilated axilla. Biophysical assessments (skin hydration, barrier integrity, elasticity and roughness) were made in depilated and non-depilated axillae. RESULTS: All three hair-removal techniques induced an increase in axillary erythema and skin dryness. Shaving was associated with significantly less erythema (P < 0.01), but significantly greater skin dryness (P < 0.05) versus the other techniques 30 min after hair removal. There were no between-technique differences in PIHP or biophysical parameters. Interleukins IL-1α and IL-1RA concentrations increased, and IL-8 concentration decreased following hair removal by each technique. CONCLUSION: This is the first study to identify the principal cytokines associated with the inflammatory process triggered by axillary hair removal. A single hair-removal treatment did not appear to induce PIHP or further biophysical changes to the skin.

OBJECTIF: L'impact de l'épilation sur les caractéristiques biophysiques et biochimiques de la peau axillaire humaine n'est pas entièrement compris. Cette étude a examiné l'effet de différentes techniques d'épilation sur les paramètres biophysiques et les concentrations de biomarqueurs inflammatoires clés dans les aisselles de sujets thaïlandais de sexe féminin. Les aisselles ont été épilées par rasage, à la pince ou à la cire. MÉTHODES: Après une phase de sevrage de 2 semaines sans épilation, les sujets ont subi une évaluation visuelle de l'érythème et de la sécheresse cutanée dans une aisselle (randomisé), puis l'aisselle a été épilée par rasage, à la pince ou à la cire selon l'habitude établie de chaque sujet. L'érythème et la sécheresse ont été évalués à nouveau 30 minutes après l'épilation, et des frottis tampons ont été prélevés dans les aisselles épilées et non épilées et analysés pour détecter les cytokines inflammatoires; puis, après 48 heures, l'érythème, la sécheresse et l'hyperpigmentation post-inflammatoire (PIHP) ont été évalués dans les aisselles épilées. Des évaluations biophysiques (hydratation cutanée, intégrité de la barrière cutanée, élasticité et rugosité de la peau) ont été réalisées sur les aisselles épilées et non épilées. RÉSULTATS: Les trois techniques d'épilation ont entraîné une accentuation de l'érythème axillaire et de la sécheresse de la peau. Le rasage a été associé à un érythème nettement moins important (P < 0,01), mais à une sécheresse cutanée nettement plus importante (P < 0,05) par rapport aux autres techniques 30 min après l'épilation. Aucune différence entre les techniques n'a été observée en ce qui concerne le PIHP ou les paramètres biophysiques. Les concentrations en interleukines IL-1α IL-1RA ont augmenté, et la concentration en IL-8 a diminué après l'épilation par chaque technique. CONCLUSION: Cette étude est la première à identifier les cytokines principales associées au processus inflammatoire déclenché par l'épilation des aisselles. Une seule épilation n'a pas semblé entraîner de PIHP ou d'autres modifications biophysiques de la peau.

VIP and muscarinic synergistic mucin secretion by salivary mucous cells is mediated by enhanced PKC activity via VIP-induced release of an intracellular Ca2+ pool.

Mucin secretion by salivary mucous glands is mediated predominantly by parasympathetic acetylcholine activation of cholinergic muscarinic receptors via increased intracellular free calcium ([Ca2+]i) and activation of conventional protein kinase C isozymes (cPKC). However, the parasympathetic co-neurotransmitter, vasoactive intestinal peptide (VIP), also initiates secretion, but to a lesser extent. In the present study, cross talk between VIP- and muscarinic-induced mucin secretion was investigated using isolated rat sublingual tubuloacini. VIP-induced secretion is mediated by cAMP-activated protein kinase A (PKA), independently of increased [Ca2+]i. Synergistic secretion between VIP and the muscarinic agonist, carbachol, was demonstrated but only with submaximal carbachol. Carbachol has no effect on cAMP ± VIP. Instead, PKA activated by VIP releases Ca2+ from an intracellular pool maintained by the sarco/endoplasmic reticulum Ca2+-ATPase pump. Calcium release was independent of phospholipase C activity. The resultant sustained [Ca2+]i increase is additive to submaximal, but not maximal carbachol-induced [Ca2+]i. Synergistic mucin secretion was mimicked by VIP plus either phorbol 12-myristate 13-acetate or 0.01 µM thapsigargin, and blocked by the PKC inhibitor, Gö6976. VIP-induced Ca2+ release also promoted store-operated Ca2+ entry. Synergism is therefore driven by VIP-mediated [Ca2+]i augmenting cPKC activity to enhance muscarinic mucin secretion. Additional data suggest ryanodine receptors control VIP/PKA-mediated Ca2+ release from a Ca2+ pool also responsive to maximal carbachol. A working model of muscarinic and VIP control of mucous cell exocrine secretion is presented. Results are discussed in relation to synergistic mechanisms in other secretory cells, and the physiological and therapeutic significance of VIP/muscarinic synergism controlling salivary mucous cell exocrine secretion.

Melt-rich channel observed at the lithosphere-asthenosphere boundary.

The lithosphere-asthenosphere boundary (LAB) separates rigid oceanic plates from the underlying warm ductile asthenosphere. Although a viscosity decrease beneath this boundary is essential for plate tectonics, a consensus on its origin remains elusive. Seismic studies identify a prominent velocity discontinuity at depths thought to coincide with the LAB but disagree on its cause, generally invoking either partial melting or a mantle dehydration boundary as explanations. Here we use sea-floor magnetotelluric data to image the electrical conductivity of the LAB beneath the edge of the Cocos plate at the Middle America trench offshore of Nicaragua. Underneath the resistive oceanic lithosphere, the magnetotelluric data reveal a high-conductivity layer confined to depths of 45 to 70 kilometres. Because partial melts are stable at these depths in a warm damp mantle, we interpret the conductor to be a partially molten layer capped by an impermeable frozen lid that is the base of the lithosphere. A conductivity anisotropy parallel to plate motion indicates that this melt has been sheared into flow-aligned tube-like structures. We infer that the LAB beneath young plates consists of a thin, partially molten, channel of low viscosity that acts to decouple the overlying brittle lithosphere from the deeper convecting mantle. Because this boundary layer has the potential to behave as a lubricant to plate motion, its proximity to the trench may have implications for subduction dynamics.

Axillary skin: biology and care.

In skin care, the axilla is a biologically unique site requiring specialized attention and care. This area of skin is often subject to hair removal techniques, such as shaving and plucking. These procedures damage the skin leading to erythema and dryness in the short term, and in some cases, post-inflammatory hyperpigmentation (PIHP) in the long term. This study will (i) briefly review the biology and unique properties of axillary skin, and (ii) describe the characteristics of the irritation and damage induced by contemporary skin care habits and resolution of these responses by the use of efficacious skin moisturizing technology. With respect to the latter, we propose that there are five groups of compounds, defined according to their mechanism of action, which are particularly relevant to the care of damaged axillary skin.

Role of calcium and PKC in salivary mucous cell exocrine secretion.

Fluid and exocrine secretion of mucins by salivary mucous glands is regulated predominantly by parasympathetic activation of muscarinic receptors. A direct role for subsequent putative signaling steps, phospholipase C (PLC), increased intracellular calcium ([Ca(2+)](i)), and isoforms of protein kinase C (PKC) in mediating muscarinic exocrine secretion has not been elucidated, and these are potential therapeutic targets to enhance mucin secretion in hyposalivary patients. We found that muscarinic-induced mucin secretion by rat sublingual tubulo-acini was dependent upon PLC activation and the subsequent increase in [Ca(2+)](i), and further identified a transient PKC-independent component of secretion dependent upon Ca(2+) release from intracellular stores, whereas sustained secretion required entry of extracellular Ca(2+). Interactions among carbachol, PKC inhibitors, phorbol 12-myristate 13-acetate, and thapsigargin to modulate [Ca(2+)](i) implicated conventional PKC isoforms in mediating sustained secretion. With increasing times during carbachol perfusion of glands, in situ, PKC-α redistributed across glandular membrane compartments and underwent a rapid and persistent accumulation near the luminal borders of mucous cells. PKC-ß1 displayed transient localization near luminal borders, whereas the novel PKCs, PKC-δ or PKC-ε, displayed little or no redistribution in mucous cells. Collective results implicate synergistic interactions between diacylglycerol (DAG) and increasing [Ca(2+)](i) levels to activate cPKCs in mediating sustained muscarinic-induced secretion.

Certification of standard reference materials containing bitter orange.

A suite of three dietary supplement standard reference materials (SRMs) containing bitter orange has been developed, and the levels of five alkaloids and caffeine have been measured by multiple analytical methods. Synephrine, octopamine, tyramine, N-methyltyramine, hordenine, total alkaloids, and caffeine were determined by as many as six analytical methods, with measurements performed at the National Institute of Standards and Technology and at two collaborating laboratories. The methods offer substantial independence, with two types of extractions, two separation methods, and four detection methods. Excellent agreement was obtained among the measurements, with data reproducibility for most methods and analytes better than 5% relative standard deviation. The bitter-orange-containing dietary supplement SRMs are intended primarily for use as measurement controls and for use in the development and validation of analytical methods.

Sorafenib induces apoptosis of AML cells via Bim-mediated activation of the intrinsic apoptotic pathway.

Raf/MEK/Erk signaling is activated in the majority of acute myeloid leukemias (AMLs), providing rationale for targeting this pathway with therapeutic intent. We investigated growth-inhibitory and proapoptotic effects of sorafenib in AML. Our studies demonstrated that sorafenib significantly inhibited the phosphorylation levels of Raf downstream target proteins MEK1/2 and Erk, induced apoptosis and inhibited colony formation in AML cell lines and in primary AML samples. Mechanistically, treatment with sorafenib resulted in upregulation of proapoptotic Bim, accompanied by an increase in Bad, Bax and Bak protein levels and decreased Mcl-1, X-linked inhibitor of apoptosis and surviving levels, which mainly led to the activation of the intrinsic apoptotic pathway. Silencing of Bim protein expression significantly abrogated sorafenib-induced apoptosis, suggesting a critical function of Bim in the activation of the intrinsic mitochondrial pathway induced by sorafenib. Importantly, sorafenib also modulated phospho-Erk, Bim, Bax and Mcl-1 levels in samples procured from patients in an ongoing Phase I clinical trial of sorafenib in AML. Combination of sorafenib with cytarabine or the novel small molecule Bcl-2 inhibitor ABT-737 synergistically induced cell death in AML cell lines. Our results strongly suggest potential activity of sorafenib as a novel mechanism-based therapeutic agent in AML.

Survivorship of the St Georg Sled medial unicompartmental knee replacement beyond ten years.

There have been several reports of good survivorship and excellent function at ten years with fixed-bearing unicompartmental knee replacement. However, little is known about survival beyond ten years. From the Bristol database of over 4000 knee replacements, we identified 203 St Georg Sled unicompartmental knee replacements (174 patients) which had already survived ten years. The mean age of the patients at surgery was 67.1 years (35.7 to 85) with 67 (38.5%) being under 65 years at the time of surgery. They were reviewed at a mean of 14.8 years (10 to 29.4) from surgery to determine survivorship and function. There were 99 knees followed up for 15 years, 21 for 20 years and four for 25 years. The remainder failed, were withdrawn, or the patient had died. In 58 patients (69 knees) the implant was in situ at the time of death. Revision was undertaken in 16 knees (7.9%) at a mean of 13 years (10.2 to 21.6) after operation. In seven knees (3.4%) this was for progression of arthritis, in three (1.5%) for wear of polyethylene, in four (2%) for tibial loosening, in two (1%) for fracture of the femoral component and in two (1%) for infection. Two knees (1%) were revised for more than one reason. The mean Bristol knee score of the surviving knees fell from 86 (34 to 100) to 79 (42 to 100) during the second decade. Survivorship to 20 years was 85.9% (95% CI 82.9% to 88.9%) and at 25 years was 80% (95% CI 70.2% to 89.8%). Satisfactory survival of a fixed-bearing unicompartmental knee replacement can be achieved into the second decade and beyond.

Hidden blood loss following hip and knee arthroplasty. Correct management of blood loss should take hidden loss into account.

Following total hip arthroplasty (THA) and total knee arthroplasty (TKR) only the 'visible' measured blood loss is usually known. This underestimates the 'true' total loss, as some loss is 'hidden'. Correct management of blood loss should take hidden loss into account. We studied 101 THAs and 101 TKAs (with re-infusion of drained blood). Following THA, the mean total loss was 1510 ml and the hidden loss 471 ml (26%). Following TKA, the mean total loss was 1498 ml. The hidden loss was 765 ml (49%). Obesity made no difference with either operation. THA involves a small hidden loss, the total loss being 1.3 times that measured. However, following TKA, there may be substantial hidden blood loss due to bleeding into the tissues and residual blood in the joint. The true total loss can be determined by doubling the measured loss.

Effect of antiperspirants on whole body sweat rate and thermoregulation.

It is well established that the evaporation of sweat from the human body surface is the main mechanism by which heat balance is maintained following a rise in body core temperature. Since the introduction of the first brand name antiperspirant in the United States during the early 1900s, antiperspirant products designed to control underarm wetness have grown to represent one of the largest cosmetic categories in most global markets. However, although axillary sweating only constitutes less than 1% of whole body sweat rate, consumers, particularly in hot countries, have begun to articulate the concern that antiperspirants may interfere with the body's natural cooling process. To investigate this, we undertook carefully designed experiments that measured the effects of axillary antiperspirant application on whole body sweat rate and body core temperature, following a regimen of exercise-induced heat stress in a hot environment in human volunteers. Our data show clearly that although antiperspirant prevents sweat production in the axillary area, this does not impact the ability of the body to thermoregulate following a rise in body core temperature. Thus, recent consumer questioning over this aspect of antiperspirant use appears to be unwarranted.

Lateral unicompartmental knee replacement survivorship and clinical experience over 21 years.

We describe 88 knees (79 patients) with lateral unicompartmental osteoarthritis which had been treated by the St Georg Sled prosthesis. At a mean follow-up of nine years (2 to 21) 15 knees had revision surgery, nine for progression of arthritis, six for loosening, four for breakage of a component and four for more than one reason. Six patients complained of moderate or severe pain at the final follow-up. Only five knees were lost to follow-up in the 21-year period. We performed survivorship analysis on the group using revision for any cause as the endpoint. At ten years the cumulative survival rate was 83%, and at 15 years, when ten knees were still at risk, it was 74%. Based on our clinical results and survival rate the St Georg Sled may be considered to be a suitable unicompartmental replacement for isolated lateral compartment osteoarthritis.

Development and deployment of an internet-based data management system for use by the Asthma Clinical Research Network.

Data management system development for the first Asthma Clinical Research Network (ACRN) study began at the data coordinating center (DCC) in May 1995 with the requirement for delivery of a production system by November 1995. Special methods had to be used to establish an internet local area network (LAN), place clinical client systems, and achieve an accelerated software development cycle. The development of a fully integrated data management system prior to the start of the study was not possible. Therefore an early analysis focused on identifying discrete groupings of data management functions that would allow development of distinct database modules to provide specific functionality such as subject randomization, subject registration, and data entry. The modules were categorized as either being associated with clinical centers or the DCC so that the clinical center modules could be developed and delivered to meet the start date of the study. In the second phase of development during the relatively slow patient-enrollment period, the DCC functional modules were delivered discretely over time. While at the time this development model was a necessity due to limited DCC resources, it continues to be used today as it permits the DCC to implement studies more rapidly and efficiently for the ACRN. This paper describes the methodologies used to develop an internet-based LAN, establish clinical center client systems, establish DCC client and server operations, and develop a data management system. It describes the circumstances that contributed to the development of these systems and the special methodologies developed. The technical aspects of the data management system and LAN are presented as well as a description of the requirements and constraints analysis used to develop the hardware and software systems.

Modem remote support of pulmonary-function testing and quality control systems.

The data coordinating center (DCC) of the Asthma Clinical Research Network (ACRN) is responsible for the support of 11 pulmonary-function testing systems and two quality control systems. Pulmonary-function data from these systems are used as outcome indicators in studies conducted by the ACRN. Each of these systems is composed of a spirometer, a personal computer for data acquisition from the spirometer, a modem, and a printer. These systems are located at six clinical centers nationwide. An analysis conducted at the beginning of the first ACRN protocol identified the following requirements: (1) standard pulmonary-function testing, (2) standard methacholine-challenge testing, (3) the ability to handle simultaneous multiple protocols as well as have data from non-ACRN subjects, (4) the ability to separate data from different protocols as well as separate ACRN and non-ACRN data, (5) the ability to transmit data from the remote clinical centers to the DCC, (6) the ability to ensure quality data and to report on those results, and (7) the ability to provide remote support.

Chronic pediatric asthma and chiropractic spinal manipulation: a prospective clinical series and randomized clinical pilot study.

OBJECTIVES: The first objective was to determine if chiropractic spinal manipulative therapy (SMT) in addition to optimal medical management resulted in clinically important changes in asthma-related outcomes in children. The second objective was to assess the feasibility of conducting a full-scale, randomized clinical trial in terms of recruitment, evaluation, treatment, and ability to deliver a sham SMT procedure. STUDY DESIGN: Prospective clinical case series combined with an observer-blinded, pilot randomized clinical trial with a 1-year follow-up period. SETTING: Primary contact, college outpatient clinic, and a pediatric hospital. PATIENTS: A total of 36 patients aged 6 to 17 years with mild and moderate persistent asthma were admitted to the study. OUTCOME MEASURES: Pulmonary function tests; patient- and parent- or guardian-rated asthma-specific quality of life, asthma severity, and improvement; am and pm peak expiratory flow rates; and diary-based day and nighttime symptoms. INTERVENTIONS: Twenty chiropractic treatment sessions were scheduled during the 3-month intervention phase. Patients were randomly assigned to receive either active SMT or sham SMT in addition to their standardized ongoing medical management. RESULTS: It is possible to blind the participants to the nature of the SMT intervention, and a full-scale trial with the described design is feasible to conduct. At the end of the 12-week intervention phase, objective lung function tests and patient-rated day and nighttime symptoms based on diary recordings showed little or no change. Of the patient-rated measures, a reduction of approximately 20% in beta(2) bronchodilator use was seen (P =.10). The quality of life scores improved by 10% to 28% (P <.01), with the activity scale showing the most change. Asthma severity ratings showed a reduction of 39% (P <.001), and there was an overall improvement rating corresponding to 50% to 75%. The pulmonologist-rated improvement was small. Similarly, the improvements in parent- or guardian-rated outcomes were mostly small and not statistically significant. The changes in patient-rated severity and the improvement rating remained unchanged at 12-month posttreatment follow-up as assessed by a brief postal questionnaire. CONCLUSION: After 3 months of combining chiropractic SMT with optimal medical management for pediatric asthma, the children rated their quality of life substantially higher and their asthma severity substantially lower. These improvements were maintained at the 1-year follow-up assessment. There were no important changes in lung function or hyperresponsiveness at any time. The observed improvements are unlikely as a result of the specific effects of chiropractic SMT alone, but other aspects of the clinical encounter that should not be dismissed readily. Further research is needed to assess which components of the chiropractic encounter are responsible for important improvements in patient-oriented outcomes so that they may be incorporated into the care of all patients with asthma.

Comparison of subacute rehabilitative care with outpatient primary medical care.

PURPOSE: Prior rehabilitation outcome studies have had many weaknesses. but they gradually observe a lack of long-term benefits from inpatient care alone. The goal of this study was to measure the additive effect of outpatient, subacute rehabilitation (compared with usual outpatient primary medical care) for adults diagnosed with a disabling disorder in four major diagnostic groups (nervous, circulatory, musculoskeletal and injury). METHOD: A randomized clinical trial was conducted to determine the effects of outpatient, subacute rehabilitative care on: (1) physical function; (2) health; (3) well being; (4) family function; and (5) social support. Patients hospitalized for the first time with a disabling condition (n = 180) were provided inpatient rehabilitation and then were randomly assigned to either outpatient, subacute rehabilitation at home (n = 90) or to usual outpatient follow-up (n = 90) in which only primary care medical services were provided. To compare the two groups, univariate analyses of covariance were conducted for the outcome variables. RESULTS: The major finding of this study was that of no significant effect of the intervention on any outcome variable. CONCLUSIONS: Based on current study results, we conclude that any long term additive benefit of outpatient, subacute rehabilitation may not be detectable across disability categories and may require closer evaluation in studies with a more homogeneous population than in the current study. Providing complex follow-up case management services to all clients is apparently not beneficial and might better be provided using selection criteria based on need. Future studies should determine if services are more effective when provided to those with the most unmet rehabilitative needs. Further outpatient, subacute care rehabilitation studies should address the specific needs of the patients and be adapted individually to those needs.

Defective fluid secretion and NaCl absorption in the parotid glands of Na+/H+ exchanger-deficient mice.

Multiple Na(+)/H(+) exchangers (NHEs) are expressed in salivary gland cells; however, their functions in the secretion of saliva by acinar cells and the subsequent modification of the ionic composition of this fluid by the ducts are unclear. Mice with targeted disruptions of the Nhe1, Nhe2, and Nhe3 genes were used to study the in vivo functions of these exchangers in parotid glands. Immunohistochemistry indicated that NHE1 was localized to the basolateral and NHE2 to apical membranes of both acinar and duct cells, whereas NHE3 was restricted to the apical region of duct cells. Na(+)/H(+) exchange was reduced more than 95% in acinar cells and greater than 80% in duct cells of NHE1-deficient mice (Nhe1(-/-)). Salivation in response to pilocarpine stimulation was reduced significantly in both Nhe1(-/-) and Nhe2(-/-) mice, particularly during prolonged stimulation, whereas the loss of NHE3 had no effect on secretion. Expression of Na(+)/K(+)/2Cl(-) cotransporter mRNA increased dramatically in Nhe1(-/-) parotid glands but not in those of Nhe2(-/-) or Nhe3(-/-) mice, suggesting that compensation occurs for the loss of NHE1. The sodium content, chloride activity and osmolality of saliva in Nhe2(-/-) or Nhe3(-/-) mice were comparable with those of wild-type mice. In contrast, Nhe1(-/-) mice displayed impaired NaCl absorption. These results suggest that in parotid duct cells apical NHE2 and NHE3 do not play a major role in Na(+) absorption. These results also demonstrate that basolateral NHE1 and apical NHE2 modulate saliva secretion in vivo, especially during sustained stimulation when secretion depends less on Na(+)/K(+)/2Cl(-) cotransporter activity.

Nonoperative treatments for sciatica: a pilot study for a randomized clinical trial.

OBJECTIVES: To assess the feasibility of patient recruitment, the ability of patients and clinicians to comply with study protocols, and the use of data collection instruments to collect cost-effectiveness data, and to obtain variability estimates for sample-size calculations for a full-scale trial. STUDY DESIGN: Prospective, observer-blinded, pilot randomized clinical trial. SETTING: Primary contact chiropractic and medical clinics. PATIENTS: Ages 20 to 65 years, with low back-related radiating leg pain (sciatica). OUTCOME MEASURES: Self-report questionnaires were administered at baseline and 3 and 12 weeks after randomization. The measures included leg and back pain severity, frequency and bothersomeness of symptoms, leg/back disability, medication use, global improvement, satisfaction, and health care utilization. INTERVENTIONS: Medical care, chiropractic care, and epidural steroid injections. RESULTS: A total of 706 persons were screened by phone to determine initial eligibility. Of these, over 90% of those persons contacted did not meet the entrance criteria. The most common reason for disqualification was that the duration of the complaint was longer than 3 months. Twenty patients were randomized into the study. All 3 groups showed substantial improvements in the main patient-rated outcomes at the end of the 12-week intervention phase. For leg pain, back pain, frequency and bothersomeness of leg symptoms, and Roland-Morris disability score, the percent improvement varied from 50% to 84%, and the corresponding effect sizes ranged from 0.8 to 2.2. Bothersomeness of leg symptoms was the most responsive outcome associated with the largest magnitude of effect size. All within-group changes from baseline were statistically significant (P <.01). No between-group comparisons were planned or performed because of the insufficient sample size and high risk of committing type I and type II errors. CONCLUSIONS: Pilot studies such as these are important for the determination of the feasibility of conducting costly, larger scale trials. Recruitment for a full-scale study of sciatica of 2 to 12 weeks duration is not feasible, given the methods used in this pilot study. Our results do indicate, however, that there are substantial numbers of patients with sciatica more chronic in nature who would be interested in participating in a similar study. In addition, collaboration with a local health maintenance organization would likely facilitate clinician referrals and optimize the recruitment process. Patient and provider compliance was high in the pilot study, which indicates that most study protocols are feasible. Additionally, we were able to collect complete outcomes data, including those regarding health care use. A suggested modification by investigators and outside consultants has resulted in the replacement of the medication group with a minimal intervention control group (ie, self-care advice). As a result, a second pilot study of patients with sciatica of more than 4 weeks duration has been planned before a full-scale trial is attempted.

Severe impairment of salivation in Na+/K+/2Cl- cotransporter (NKCC1)-deficient mice.

The salivary fluid secretory mechanism is thought to require Na(+)/K(+)/2Cl(-) cotransporter-mediated Cl(-) uptake. To directly test this possibility we studied the in vivo and in vitro functioning of acinar cells from the parotid glands of mice with targeted disruption of Na(+)/K(+)/2Cl(-) cotransporter isoform 1 (Nkcc1), the gene encoding the salivary Na(+)/K(+)/2Cl(-) cotransporter. In wild-type mice NKCC1 was localized to the basolateral membranes of parotid acinar cells, whereas expression was not detected in duct cells. The lack of functional NKCC1 resulted in a dramatic reduction (>60%) in the volume of saliva secreted in response to a muscarinic agonist, the primary in situ salivation signal. Consistent with defective Cl(-) uptake, a loss of bumetanide-sensitive Cl(-) influx was observed in parotid acinar cells from mice lacking NKCC1. Cl(-)/ HCO(3)(-) exchanger activity was increased in parotid acinar cells isolated from knockout mice suggesting that the residual saliva secreted by mice lacking NKCC1 is associated with anion exchanger-dependent Cl(-) uptake. Indeed, expression of the Cl(-)/ HCO(3)(-) exchanger AE2 was enhanced suggesting that this transporter compensates for the loss of functional Na(+)/K(+)/2Cl(-) cotransporter. Furthermore, the ability of the parotid gland to conserve NaCl was abolished in NKCC1-deficient mice. This deficit was not associated with changes in the morphology of the ducts, but transcript levels for the alpha-, beta-, and gamma-subunits of the epithelial Na(+) channel were reduced. These data directly demonstrate that NKCC1 is the major Cl(-) uptake mechanism across the basolateral membrane of acinar cells and is critical for driving saliva secretion in vivo.

Program review of community residential care.

This article provides an overview of the Department of Veterans Affairs Community Residential Care Program and summarizes key literature about programs developed in the United States. Descriptive data for 1995 and 1996 are provided to assist program planners in comparing and contrasting client characteristics and services. The authors conclude that, in addition to being cost effective, the residential care program strengthens relationships between the health care facility and the community it serves.