Experiences with the shikimate-pathway enzymes as targets for rational drug design.

The background and current context of work on the shikimate-pathway enzymes as potential targets for anti-bacterial, anti-fungal and anti-parasitic drugs is reviewed. Recent work on the third enzyme of the pathway, dehydroquinase, which occurs in two structurally and mechanistically distinct forms, is used to illustrate the present state of studies into rational drug design.

Assessment of fetal status in multiple gestation pregnancies using interphase FISH.

The use of fluorescence in situ hybridization (FISH) for women with multiple gestation pregnancies has been evaluated. Women were referred for chromosome analysis because of advanced maternal age, abnormal ultrasound findings or a positive family history and/or prior to fetal reduction. FISH was successfully applied to all specimens obtained by amniocentesis or chorionic villus sampling (CVS). Based on FISH results, fetal-fetal contamination of specimens following CVS was 11.5% in twin pregnancies and 16% in triplet or higher multiples. FISH detected trisomy 21 in three cases with no false negatives or positives. Whereas FISH may provide rapid and useful assessment of fetal status in decision-making regarding fetal reduction, the present study also highlighted the obstetrical difficulty of ensuring a sample representative of each fetus following CVS in addition to the possibility of not identifying clinically significant chromosome aberrations using currently available FISH probes.

Evidence-based practice for enteral feedings: aspiration prevention strategies, bedside detection, and practice change.

Nurses questioned the hospital policy of using blue dye in all enteral feedings. A project team gathered and disseminated information from the literature and national practice benchmarks. Hospital policy and nursing practice were revised according to the evidence-based information.

The implementation of bedside bladder ultrasound technology: effects on patient and cost postoperative outcomes in tertiary care.

RESEARCH PROBLEM: The purpose of this study was to determine the effect of ultrasound assessment of bladder volume on patient and cost outcomes for patients needing postoperative catheterization. RESEARCH METHODS: Prospective descriptive and quasi-experimental designs were used with patients having general surgery (N = 50) and patients having orthopaedic surgery (N = 103), respectively. Four outcomes were measured: number of catheterizations over the hospitalization period, infection rates, cost, and patient and provider satisfaction. RESULTS: Accuracy of the technology ranged from .76 to .97 (p = .01). Catheterizations were avoided in 38% (in the "Due to Void" category) and in 81% (in the "Void with Residual" category) of patients in the general surgery group. Patients in the orthopaedic surgery group having ultrasound experienced 1.68 and the standard catheterization group, 1.96 catheterizations, throughout hospitalization. This difference was not statistically significant. UTI rates from admission to 30 days after discharge were 4% and 13% of patients in the ultrasound and standard orthopaedic groups, respectively, and 17% of patients in the general surgical population. Based on acquisition catheter cost, approximately 3 years of ultrasound machine use would be needed to recover the acquisition cost for each machine. The satisfaction rate with the technology was 93% of patients and 97% of nurses. In postoperative patients, bedside bladder ultrasound is accurate, is effective in decreasing numbers of catheterizations, reduces cost over time, and provides high patient and provider satisfaction.

The role of the rehabilitation physician in the postacute continuum.

Compared to just 10 years ago, the US health care terrain looks much different today. In 1985, hospitals were the hub of a bustling delivery system that focused on acute care services and undervalued primary or preventive care. Health insurance benefits created incentives for consumers to use hospitals where their care was fully reimbursed, and discouraged office visits for which there were hefty copayments. Today, admissions into acute care hospitals are screened by none other than those same primary care physicians. These gatekeepers often have more authority over patient services and referrals than do the specialists and the hospitals. Financial incentives have made a 180 degrees shift, now motivating consumers to use outpatient care and office visits to satisfy the majority of their health care needs. Moreover, there are currently health care providers actively delivering a wide range of treatments and services that were not available or "covered" a decade ago. The migration of treatment out of hospitals into the vast frontier of postacute care has revolutionized our thinking about how patients receive treatment, in what locations, and by whom. This article describes the trends in financing and in clinical innovation that have contributed to the expansion of postacute alternatives. The factors that most clearly contribute to new opportunities facing rehabilitation physicians in postacute care are discussed, as are the added competencies required of those who choose to take a leadership role in the postacute delivery system. A case study of one model "managed care system" where the rehabilitation specialists are driving the care is presented. The future for rehabilitation specialists who are positioned to participate in setting the standards for high-quality postacute and chronic care in a future marketplace dominated by managed care is discussed.

In vitro recording of raphe unit activity: evidence for endogenous rhythms in presumed serotonergic neurons.

The spontaneous activity of single neurons in the nucleus raphe dorsalis was recorded in vitro in mouse brain slices. The neurons displayed the slow and regular discharge pattern characteristic of raphe neurons recorded in vivo. When magnesium ion was added to increase the medium concentration to 20-30 mM for the purpose of inhibiting all synaptic transmission, raphe neurons continued to display the same discharge pattern and rate. The data suggest that the steady rhythmic firing of nucleus raphe dorsalis neurons is generated by an intracellular pacemaker mechanism.

Thallous ion activation of p-nitrophenylphosphatase of rat myometrium plasma membrane.

Addition of thallous ion (Tl+) inhibited the spontaneous mechanical activity of rat myometrium in K-free Krebs solutions with an I50 value of 30 microM. The corresponding value for I50 for similar inhibition by addition of K+ was 150 microM. Tl+ as well as K+-activated p-nitrophenylphosphatase (PNPPase) of isolated rat myometrium plasma membrane vesicles. Half maximal activation was caused by 0.47 mM Tl+ or 1.6 mM K+. Maximal enzyme activities obtained using Tl+ and K+ were comparable. The Km values for the substance p-nitrophenylphosphatase using Tl+ (1.24 mM) and K+ (1.46 mM) were also similar. Activation by either ion was inhibited by ouabain, Na+, inorganic phosphate, and vanadate (V +5). The results suggest that Tl+ can substitute for K+ for activation of the Na-K pump of rat myometrium plasma membrane.

Emergence of spontaneous alternation in the kitten.

Two studies are reported that describe the development of spontaneous alternation in the kitten. The first indicates that 3- and 4-week-old kittens do not alternate whereas animals 5 weeks and older do alternate. The second suggests that inability to discriminate maze arms is an unlikely explanation for the lack of alternation among the youngest animals. The approximate simultaneity between the onset of alternation (described here) and the maturation of the kitten hippocampus (described by others) is taken as support for the notion that hippocampal maturation may be related to the development of spontaneous alternation.

Developmental changes in open-field behavior in the kitten.

Seventy-eight kittens from 3 to 7 weeks of age were studied in an open-field arena. Three major age-dependent changes were noted: (1) the number of floor squares entered was markedly higher for 5- and 6-week-olds than for younger animals, and slightly lower for 7-week-olds than for 5- and 6-week-olds; (2) the tendency to backtrack from 1 square to a just-vacated square decreased with age, the largest change occurring between 4 and 5 weeks of age; (3) the within-session decrement in locomotion was largest for 3-week-old kittens but was smallest for 4-week-olds and increased monotonically with age thereafter. The results suggest a possible role of hippocampal maturation.