Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes.

A device providing frequent, automatic, and non-invasive glucose measurements for persons with diabetes has been developed: the GlucoWatch biographer. This device extracts glucose through intact skin via reverse iontophoresis where it is detected by an amperometric biosensor. The biographer can provide glucose readings every 20 min for 12 h. The performance of this device was evaluated in two large clinical studies in a controlled clinical environment (n=231), and the home environment (n=124). Accuracy of the biographer was evaluated by comparing the automatic biographer readings to serial finger-stick blood glucose (BG) measurements. Biographer performance was comparable in both environments. Mean difference between biographer and finger-stick measurements was -0.01 and 0.26 mmol l(-1) for the clinical and home environments, respectively. The mean absolute value of the relative difference was 1.06 and 1.18 mmol l(-1) for the same studies. Correlation coefficient (r) between biographer and finger-stick measurements was 0.85 and 0.80 for the two studies. In both studies, over 94% of the biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low BG levels. Biographer accuracy is relatively constant over all rates of BG changes, except when BG decreases more than 10 mmol l(-1) h(-1), which occurred for only 0.2% of points in the home environment study. Biographer precision, as measured by CV%, is approx. 10%. Skin irritation, characterized by erythema and edema, was either non-existent or mild in >90% of subjects and resolved in virtually all subjects without treatment in several days.

Plasminogen activator inhibitor type 2 contains mRNA instability elements within exon 4 of the coding region. Sequence homology to coding region instability determinants in other mRNAs.

Plasminogen activator inhibitor type 2 (PAI-2) is a serine protease inhibitor that inhibits urokinase. Constitutive and regulated PAI-2 gene expression involves post-transcriptional events, and an AU-rich mRNA instability motif within the 3'-untranslated region of PAI-2 mRNA is required for this process (Maurer, F., Tierney, M., and Medcalf, R. L. (1999) Nucleic Acids Res. 27, 1664-1673). Here we show that instability determinants are present within various exons of the PAI-2 coding region, most notably within exon 4. Deletion of exon 4 from the full-length PAI-2 cDNA results in a doubling in the half-life of PAI-2 mRNA, whereas a 28-nucleotide region within exon 4 contains binding sites for cytoplasmic proteins. Inducible stabilization of PAI-2 mRNA in HT-1080 cells treated with phorbol ester and tumor necrosis factor does not alter the binding of proteins to the exon 4 instability determinant, but resulted in a transient increase in the binding of factors to the AU-rich RNA instability element. Hence, PAI-2 mRNA stability is influenced by elements located within both the coding region and the 3'-untranslated region and that cytoplasmic mRNA binding factors may influence steady state and inducible PAI-2 mRNA expression. Finally a 10-nucleotide region flanking the exon 4 protein-binding site is homologous to instability elements within five other transcripts, suggesting that a common coding region determinant may exist.

The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor.

The GlucoWatch (Cygnus, Inc, Redwood City, CA, USA) biographer provides automatic, frequent and noninvasive blood glucose measurements for up to 12 h. The device extracts glucose through intact skin where it is measured by an amperometric biosensor. Clinical trials in a variety of environments have shown that the biographer provides accurate and precise glucose measurements when compared with serial fingerstick blood glucose measurements. Mean difference between these measurements was 0.26 mmol/L in the home environment (r = 0.80). Over 94% of biographer readings were in the clinically acceptable A+B region of the Clarke Error Grid. A slight positive bias is observed for the biographer readings at low glucose levels. Biographer precision, as measured by coefficient of variation (CV)%, is approximately 10%. The low glucose alert function of the biographer was able to detect up to 75% of hypoglycaemic episodes with a low false alert level. Skin irritation, characterized by erythema and oedema was either nonexistent or mild in over 87% of subjects and resolved in virtually all subjects without treatment in several days. The GlucoWatch biographer has been shown to be a safe and effective method to track glucose level trends and patterns, which should enable improved glycaemic control for many patients.

Effect of acetaminophen on the accuracy of glucose measurements obtained with the GlucoWatch biographer.

BACKGROUND: Improved glycemic control significantly reduces long-term microvascular complications of diabetes mellitus associated with chronic hyperglycemia. The GlucoWatch biographer is designed to facilitate intensive diabetes management by providing automatic, frequent, and noninvasive glucose readings up to three times per hour for as long as 12 hours. METHODS: The device extracts glucose through intact skin using reverse iontophoresis and measures the extracted glucose with an electrochemical biosensor. A clinical trial was performed to assess the effect of acetaminophen, a potential interference for traditional blood glucose meters, on the accuracy of the GlucoWatch biographer in adult subjects with diabetes (n = 18). One thousand milligram doses of acetaminophen were administered to subjects in two groups: one to achieve Cmax (peak acetominophen concentration) at the time of biographer calibration and the other to achieve Cmax during the measurement period. The biographer readings were compared to serial fingerstick blood glucose measurements. RESULTS: Time profiles over 9 hours show close tracking of the biographer glucose results with fingerstick blood glucose measurements for all groups. The mean difference between the two measurements is between 8 and 12 mg/dL for all groups. The mean absolute value of the relative difference is less than 20%, and more than 93% of the points were in the clinically acceptable (A+B) region of the Clarke Error Grid. No statistically significant differences were found for any accuracy measurement across all groups. CONCLUSIONS: The GlucoWatch Biographer provides frequent measurements of glucose over a 12-hour period with high accuracy. No effect of therapeutic dosage of acetaminophen on the accuracy of the glucose readings was found.

An investigation into modification of personality hardiness in staff nurses.

Responsibilities of nurse educators include assisting nurses to adjust to a rapidly changing healthcare environment and demonstrating how these efforts are effective. In this article, the authors describe a study that measures the effects of teaching hardiness, a characteristic encompassing commitment, control, and challenge, to newly employed hospital nurses. The authors believe the study results indicate that instruction in hardiness is possible and may have an impact on morale.

Effect of growth hormone replacement on wound healing in healthy older men.

The secretion of growth hormone, an important anabolic agent, declines with aging. We hypothesize that growth hormone levels (measured as insulin-like growth factor-1) correlate with postoperative tissue repair in otherwise healthy, elderly persons. The goal was to determine whether growth hormone supplementation can improve wound healing in this circumstance. We conducted a randomized controlled double-blind trial of 6 months of growth hormone replacement or placebo in 28 healthy older men (>69 years of age) with low baseline plasma insulin-like growth factor-1. Growth hormone doses were adjusted to elevate insulin-like growth factor-1 to levels expected in younger adults. Wound healing was tested by implanting 10 cm expanded polytetrafluoroethylene porous tubes for 10 days, then measuring the content of collagen (as hydroxyproline), DNA, and total protein. Hydroxyproline content was 15% greater in the wounds of the growth hormone group (n = 13) compared with the placebo group (n = 15), (4.52 +/- 0.94 versus 3.92 +/- 0.78 microg/cm; p = 0.04). Therefore, healthy older men who took growth hormone had enhanced reparative collagen deposition during the wound healing process. This action may be clinically useful after selected surgery or trauma in the elderly.

Growth hormone replacement in healthy older men improves body composition but not functional ability.

OBJECTIVE: To determine whether growth hormone replacement in older men improves functional ability. DESIGN: Randomized, controlled, double-blind trial. SETTING: General community. PATIENTS: 52 healthy men older than 69 years of age with well-preserved functional ability but low baseline insulin-like growth factor 1 levels. INTERVENTION: Growth hormone (0.03 mg/kg of body weight) or placebo given three times a week for 6 months. MEASUREMENTS: Body composition, knee and hand grip muscle strength, systemic endurance, and cognitive function. RESULTS: The participants' mean age was 75.0 years (range, 70 to 85 years). At 6 months, lean mass had increased on average by 4.3% in the growth hormone group and had decreased by 0.1% in the placebo group, a difference of 4.4 percentage points (95% CI, 2.1 to 6.8 percentage points). Fat mass decreased by an average of 13.1% in the growth hormone group and by 0.3% in the placebo group, a difference of 12.8 percentage points (CI, 8.6 to 17.0 percentage points). No statistically or clinically significant differences were seen between the groups in knee or hand grip strength or in systemic endurance. The mean Trails B score in the growth hormone group improved by 8.5 seconds, whereas scores in the placebo group deteriorated by 5.0 seconds, a difference of 13.5 seconds (CI, 3.1 seconds to 23.9 seconds; P = 0.01). However, the growth hormone group's score on the Mini-Mental Status Examination deteriorated by 0.4, whereas the placebo group's score improved by 0.2, a difference of 0.6 (P = 0.11). The two treatment groups had almost identical scores on the Digit Symbol Substitution Test (P > 0.2). Twenty-six men in the growth hormone group had 48 incidents of side effects, and 26 placebo recipients had 14 incidents of side effects (P = 0.002). Dose reduction was required in 26% of the growth hormone recipients and in none of the placebo recipients (P < 0.001). CONCLUSIONS: Physiologic doses of growth hormone given for 6 months to healthy older men with well-preserved functional abilities increased lean tissue mass and decreased fat mass. Although body composition improved with growth hormone use, functional ability did not improve. Side effects occurred frequently.

Insulin-like growth factor 1 and functional status in healthy older men.

OBJECTIVE: To determine if insulin-like growth factor 1 (IGF-1) is associated with strength and functional ability in healthy older men. DESIGN: Cross-sectional study. SETTING: San Francisco Department of Veterans Affairs Medical Center. PARTICIPANTS: One hundred four ambulatory community-dwelling men. MEASUREMENTS: Serum IGF-1 levels were obtained. Measured variables included strength of the knee flexors and extensors, handgrip, score on the Physical Performance Test, body composition, and three tests of cognitive function. RESULTS: The subjects' mean age was 75.5 +/- 4.9 (SD) years (range 70-94 years), and their mean IGF-1 level was 134.7 +/- 43.6 ng/mL. The univariate association of age with the variables was much stronger than the univariate association of IGF-1 with the same variables. In multivariable models, age, but not IGF-1, was associated with the variables. CONCLUSION: In this study of healthy older men, age is the most important variable in predicting functional decline. There was no association of IGF-1 levels to functional status independent of age.

Ethics in Japanese health care: a perspective for clinical nurse specialists.

Bioethical issues relevant to nurses in Japan are described in this article. Significant Japanese values and behavior patterns, the impact of religion on ethical concerns, patient and family roles in illness, and relationships with the physician are described. Within this context, Japanese nursing involvement in ethics and selected ethical issues are explored with examples.

Required technology breakthroughs to assume widely accepted biosensors.

Silicon microsensors have been very successful over the last decade in a wide variety of applications. Although commercialization of silicon-based biosensors has been slow, careful applications of microfabrication technologies to the development of biosensors will drive the formation of many new markets. The most promising high-volume, emerging markets include clinical analysis, health care, and environmental. For example, the worldwide sales of clinical sensors are expected to reach several hundreds of millions by 2000, whereas the total worldwide market for biosensors is forecast to reach $1 billion by the year 2000. In this article, an overview of current and potential markets is presented with an emphasis on technological barriers to overcome before biosensors will become more widely accepted. We start by explaining the relative success of physical sensors compared to biosensors. Subsequently, we review several biosensor approaches and techniques and their associated problems. Finally, the markets that these sensors are meant to serve are analyzed.

Clinical nurse specialists in transition.

Much attention is given to the development of the clinical nurse specialist role in an institution. This article is written for the seasoned Clinical Nurse Specialist who experiences a change in nursing administration. It describes dilemmas, identifies dynamics, and offers practical suggestions for surviving and thriving during a transition period.