'Stat' workflow modifications to expedite care after needlestick injuries.

BACKGROUND: Post-exposure prophylaxis (PEP) for human immunodeficiency virus (HIV) is recommended to start within hours of needlestick injuries (NSIs) among healthcare workers (HCWs). Delays associated with awaiting the results of testing from the source patient (whose blood was involved in the NSI) can lead to psychological consequences for the exposed HCW as well as symptomatic toxicities from empiric PEP. AIMS: After developing a 'stat' (immediate) workflow that prioritized phlebotomy and resulting of source patient bloodwork for immediate handling and processing, we retrospectively investigated whether our new workflow had (i) decreased HIV order-result interval times for source patient HIV bloodwork and (ii) decreased the frequency of HIV PEP prescriptions being dispensed to exposed HCWs. METHODS: We retrospectively analysed NSI records to identify source patient HIV order-result intervals and PEP dispensing frequencies across a 6-year period (encompassing a 54-month pre-intervention period and 16-month post-intervention period). RESULTS: We identified 251 NSIs, which occurred at similar frequencies before versus after our intervention (means 3.54 NSIs and 3.75 NSIs per month, respectively). Median HIV order-result intervals decreased significantly (P < 0.05) from 195 to 156 min after our intervention, while the proportion of HCWs who received one or more doses of PEP decreased significantly (P < 0.001) from 50% (96/191) to 23% (14/60). CONCLUSION: Using a 'stat' workflow to prioritize source patient testing after NSIs, we achieved a modest decrease in order-result intervals and a dramatic decrease in HIV PEP dispensing rates. This simple intervention may improve HCWs' physical and psychological health during a traumatic time.

A re-evaluation of modelling of the current flow between electrodes: consideration of blood flow and wounds.

Electrical stimulation has been used for exercise, healing wounds, relieving pain, and strengthening muscle. The assumption is that current will flow predictably between electrodes and, therefore, there will be predictability in the clinical response to electrical stimulation. This may not be the case. The present investigation shows that considerable channelling of current occurs when the skin is heated or when there is a wound between the electrodes. By studying current movement in nutrient agar (a homogenous medium), blood agar and layered blood and nutrient agar to simulate areas of increased blood flow, it was found that areas of high or low resistance, especially in the surface layer, caused significant current movement toward (low resistance area) or away (high resistance area) from those areas. When a resister model was used to measure dispersion characteristics of current in a three-dimensional array, it was shown that if even a single resister value was lowered by 20% in the upper layer, current sinking occurred in all three layers of the array. The results seem to imply that where the tissue is non homogeneous due to injury or inflammation, electrode design or current delivery systems need to be modified appropriately to have the intended effect of the electrical stimulation.

Dietary forage and nonfiber carbohydrate contents influence B-vitamin intake, duodenal flow, and apparent ruminal synthesis in lactating dairy cows.

The objective of this experiment was to quantify intakes, duodenal flows, and ruminal apparent synthesis (AS) of B-vitamins in lactating dairy cows fed diets varying in forage and nonfiber carbohydrate (NFC) contents. Eight (4 primiparous and 4 multiparous) ruminally and duodenally cannulated Holstein cows were assigned to 4 dietary treatments in a replicated 21-d period, 4 x 4 Latin square design with a 2 x 2 factorial treatment arrangement. Diets, fed as TMR, contained (DM basis) 2 levels of forage (35 and 60%) and 2 levels of NFC (30 and 40%). The forage portion of the diets contained 50% corn silage, 33% alfalfa hay, and 17% grass hay. Soybean hulls and beet pulp (2:1) and corn meal and ground barley (2:1) were included to achieve desired NFC concentrations. No supplemental B-vitamins were fed. B-vitamin AS was calculated as the amount of a specific B-vitamin flowing to the duodenum minus its daily orts-corrected intake. Dry matter and organic matter intakes were higher for cows fed the 35% forage diets and the 40% NFC diets. Increasing dietary forage content decreased ruminal AS of pyridoxine, folic acid, and B12. Increasing dietary NFC content increased ruminal AS of nicotinic acid, nicotinamide, niacin, pyridoxal, B6, and folic acid but decreased AS of B12. Across diets, amounts of B-vitamins synthesized were highest for niacin, followed by riboflavin, B12, thiamin, B6, and folic acid. Biotin AS values were negative for all diets, suggesting either no ruminal synthesis or that destruction by ruminal microflora was greater than synthesis. B-vitamin intake, duodenal flow, and ruminal synthesis are influenced by dietary forage and NFC contents.

Current distribution under electrodes in relation to stimulation current and skin blood flow: are modern electrodes really providing the current distribution during stimulation we believe they are?

Carbonized rubber electrodes were tested extensively when they were first developed 30 years ago, but modern carbonized rubber electrodes have not received the type of scrutiny that the first electrodes received. Modern electrodes differ from the original electrodes in that they come with a self-adhesive electrode gel called hydrogel as part of their composition. The present study was undertaken to examine the current distribution and impedance characteristics of five brands of carbonized rubber electrodes and to examine the current distribution between electrodes during electrical stimulation in six subjects. Several different electrode sizes were tested between 3 and 10 cm. The current flow between the electrodes was determined by measuring the voltage across the skin on human subjects in 15 discrete locations between the electrodes. Blood flow was also measured between the electrodes with a laser Doppler flow meter to assess the physiological effect of current distribution on the skin at several skin temperatures. The results of these studies showed that at low currents, such as is used in TENS, very little current is actually applied through the skin due to the high impedance of the electrodes. At current levels normally used for electrical stimulation for functional movement, while current flow is better in most electrodes, it is very uneven, resulting in high current density in the centre of the electrodes and a fall off of at least 50% in current intensity at the edges of the electrode. There was very little difference in current density between small and large electrodes due to the high current density in the centre. Skin blood flow altered the movement of current between the electrodes and also may contribute to electrode performance. The implication of these studies is that electrode design needs to be altered for better current distribution, especially at low stimulation currents.

Modified differential display technique that eliminates radioactivity and decreases screening time.

Several techniques are available that detect variations in gene expression between cellular populations. These include subtractive hybridization (SH), differential colony hybridization (DCH) and mRNA differential display, all based on the analysis of mRNA. The first two techniques, however, are limited because they require large amounts of mRNA for SH or several rounds of screening for DCH. Differential display overcomes both of these limitations. However, the conventional differential display technique is plagued by false positives and is labor intensive. The identification of genes that are truly differentially expressed, therefore, becomes a formidable task. We describe a modified differential display technique that overcomes the limitations of the conventional technique. This new technique eliminates a source of false positives, decreases the time required to screen a set of primers and reduces the use of radioactivity.

Administration of silica or monoclonal antibody to Thy-1 prevents low-dose streptozotocin-induced diabetes in mice.

Multiple injections of low doses of streptozotocin induce an experimental diabetes in mice. We have analyzed in two inbred strains whether the development of hyperglycaemia can be influenced by administration of macrophage-toxic silica particles or by a monoclonal antibody to Thy-1.2. Mice received streptozotocin (30 or 40 mg/kg) on five consecutive days (day 0-day 4) and in addition either silica particles (starting at day 0) or anti-Thy-1.2 (starting at day -2 or -3). In both strains mice receiving streptozotocin alone became hyperglycaemic within two weeks. Additional treatment with silica almost fully prevented diabetes development. Anti-Thy-1.2 administration was similarly effective in C57B1/Ks and partially protective in C57BL/6 mice. Histological analysis of pancreatic islets showed that a large fraction of beta cells had been spared from destruction by this treatment. The data indicate a role for both macrophages and Thy-1 positive cells in the pathogenesis of low-dose streptozotocin-induced diabetes.

Pulmonary alveolar hemorrhage in systemic lupus erythematosus.

Pulmonary alveolar hemorrhage (PAH) is a rare and often fatal presenting feature of systemic lupus erythematosus (SLE). Reported mortality rates are extremely high, 70% to 90%. Death frequently occurs within the first several days of the hemorrhage. The hospital records of all inpatients with PAH and SLE between April 1986 and May 1991 at the Hospital of the University of Pennsylvania were reviewed. The complete resolution of PAH and the 75% survival rate found in this study is in marked contrast to previous reports. This experience suggests that patients with PAH and SLE may have a better prognosis than previously reported.

Emission pattern of high-energy pions: A new probe for the early phase of heavy-Ion collisions

The emission pattern of charged pions has been measured in Au+Au collisions at 1 GeV/nucleon incident energy. In peripheral collisions and at target rapidities, high-energy pions are emitted preferentially towards the target spectator matter. In contrast, low-energy pions are emitted predominantly in the opposite direction. The corresponding azimuthal anisotropy is explained by the interaction of pions with projectile and target spectator matter. This interaction with the spectator matter causes an effective shadowing which varies with time during the reaction. Our observations show that high-energy pions stem from the early stage of the collision whereas low-energy pions freeze out later.

Evidence for a Soft Nuclear Equation-of-State from Kaon Production in Heavy-Ion Collisions.

The production of pions and kaons has been measured in 197Au+197Au collisions at beam energies from 0.6 to 1.5A GeV with the kaon spectrometer at SIS/GSI. The K+ meson multiplicity per nucleon is enhanced in Au+Au collisions by factors up to 6 relative to C+C reactions, whereas the corresponding pion ratio is reduced. The ratio of the K+ meson excitation functions for Au+Au and C+C collisions increases with decreasing beam energy. This behavior is expected for a soft nuclear equation-of-state.

Randomized prospective study of the impact of three needleless intravenous systems on needlestick injury rates.

OBJECTIVE: To determine the impact of three needleless intravenous systems on needlestick injury rates. DESIGN: Randomized controlled trial. SETTING: 1,000-bed tertiary-care Midwestern hospital. PARTICIPANTS: Nursing personnel from general medical, general surgical, and intensive-care units. INTERVENTIONS: From June 1992 through March 1994, a metal blunt cannula (MBC), two-way valve (2-way), and plastic blunt cannula (PBC) were introduced into three study areas, and needlestick injury rates were compared to three control areas using traditional needled devices. RESULTS: 24 and 29 needlestick injuries were reported in study and control areas. Intravenous-therapy-related injuries comprised 45.8% and 57.1% of injuries in each area. Thirty-seven percent and 20.7% of study and control area needlestick injuries were considered to pose a high risk of bloodborne infection. The 2-way group had similar rates of total and intravenous-related needlestick injuries compared to control groups. The PBC group had lower rates of total and intravenous-related needlestick injuries per 1,000 patient-days (rate ratios [RR], 0.32 and 0.24; 95% confidence intervals [CI95], 0.12-0.81 and 0.09-0.61; P = .02 and P = .003, respectively) and per 1,000 productive hours worked (RR, 0.11 and 0.08; CI95, 0.01-0.92 and 0.01-0.69; P = .03 and P = .005, respectively) compared to controls. CONCLUSIONS: Needlestick injuries continued in study areas despite the introduction of needleless devices, and risks of bloodborne pathogen transmission were similar to control areas. The PBC device group noted lower rates of needlestick injuries compared to controls, but there were problems with product acceptance, correct product use, and continued traditional device use in study areas. Low needlestick injury rates make interpretations difficult. Further studies of safety devices are needed and should attempt greater control of worker behavior to aid interpretation.

Identification of a novel 5-HT(1) binding site in rat spinal cord.

High affinity, specific [(3)H]5-hydroxytryptamine (5-HT) binding to spinal cord synaptosomes was examined to identify the 5-HT receptor subtypes present. Computer nonlinear regression analysis of competition studies employing 8-OH-DPAT indicated that this 5-HT(1A) selective agonist demonstrated high affinity competition (K(i = 1.3 nM)) for 24.6 +/- 0.7% of the total [(3)H]5-HT binding sites. Competition studies employing the 5-HT(1B) selective agonist RU24969, in the presence of 100 nM 8-OH-DPAT, indicated that RU24969 demonstrated high affinity (K(i = 1.1 nM)) competitive inhibition for 26.2 +/- 1.4% of all [(3)H]5-HT binding sites. Neither 5-HT(1C), 5-HT(1D), 5-HT(2) nor 5-HT(3) selective compounds demonstrated any high affinity competition for the residual 49% of specific [(3)H]5-HT binding. Therefore, three major classes of [(3)H]5-HT binding sites could be demonstrated in spinal cord synaptosomes: 5-HT(1A), 5-HT(1B) and a novel [(3)H]5-HT binding site which respectively represented 25, 26 and 49% of spinal cord synaptosomal [(3)H]5-HT binding. Further studies focusing on the function of the latter binding site are needed to determine if the presently identified novel binding site is the major 5-HT(1) receptor subtype present in spinal cord.

Development of doxorubicin resistant rat prostate cancer cell lines.

BACKGROUND: One possible mechanism of chemotherapeutic resistance in patients with metastatic prostate cancer is the overexpression of P-glycoprotein. Additional tumor models are necessary to study this phenomenon. MATERIALS AND METHODS: Doxorubicin resistant rat prostate cancer cell lines were developed by increasing doxorubicin levels in cell culture. RESULTS: The MDR lines (AT3B-1, AT3B-2, MLLB-1, and MLLB-2) were more resistant to vinblastine compared to controls. When P-glycoprotein was blocked, the AT3 MDR lines demonstrated efflux activity. Injection of AT3 MDR lines into rats followed by doxorubicin treatment produced larger tumors compared to the parental controls. CONCLUSIONS: MDR rat prostate cancer cells were developed. AT3B-1 and AT3B-2 cell lines have drug efflux pump ability, whereas the MLLB-1 and MLLB-2 may not, suggesting alternative key mechanisms other than P-glycoprotein overexpression. These new cell lines are being used to study chemotherapy resistance in prostate cancer.

A high-fat diet does not influence the growth of the Dunning R3327-H transplantable prostate adenocarcinoma.

BACKGROUND: The etiology of prostate cancer is currently a mystery. Several epidemiological studies suggest a link between dietary fat and prostate cancer. In vitro and in vivo studies support this evidence. Using the Dunning model of rat prostate cancer we hypothesized that a high-fat diet (20%) would increase the growth of the R3327-H tumor. MATERIALS AND METHODS: R3327-H tumors were implanted subcutaneously into male Copenhagen rats which were fed diets with 5 or 20% total fat. Tumors were allowed to grow for 16 weeks; they were then excised and weighed. The initial and final weights of the rats were also recorded. RESULTS: Statistical analysis revealed the level of dietary fat was a positive predictor of weight gain (p < 0.01). No effect on tumor growth was seen when compared to dietary fat, fiber type, or the interaction of fat and fiber. DISCUSSION: Growth of the R3327-H tumor, when implanted subcutaneously, is not affected by the level of dietary fat.

Examination of the DNA methylation properties in nontumorigenic and tumorigenic breast epithelial cell lines.

Molecular changes in the progressive state of tumorigenesis often include altered patterns of DNA methylation. Utilizing a series of breast epithelial cell lines, the overall 5-methylcytosine content in genomic DNA demonstrated an overall decrease when comparing two malignant cell lines (MCF-7 and T47D) with a mortal cell line (MCF 1 2M) and several derivative cell lines of the immortalized MCF10 cultures (MCF10A,-2A, -5A, A1neoT2, and 139B6). Further investigation on the methylation status of these cells lines indicated no difference in DNA methyltransferase activity, both at a protein and mRNA levels, in the nontumorigenic cell lines examined while activity was 3-10 fold higher in the tumorigenic lines (MCF7, T47D, SkBr3, MB-MDA-231, -468). Examination of the CpG island in the 5' promoter region of the estrogen receptor gene indicates that this region is unmethylated in the mortal and immortal nontumorigenic lines as well as the tumorigenic lines examined, with the exception of the estrogen receptor negative breast cell line MB-MDA-468 which appears to be partially methylated at this site. These results indicate methylation of this CpG island does not account for the inactivation of the estrogen receptor gene in immortalized nontumorigenic breast cells, suggesting another mechanism of transcriptional inactivation of ER in this environment.

The effect of castanospermine on the metastatic properties of prostate cancer cells.

BACKGROUND: Most deaths from prostate cancer result from the metastatic spread of the disease. Castanospermine has been shown to inhibit tumor growth and metastasis in mouse and rat models. We hypothesized that castanospermine might inhibit metastasis in the Dunning model of rat prostate adenocarcinoma by interfering with the metastatic properties of tumor cells. MATERIALS AND METHODS: We examined the cytotoxicity of castanospermine toward the metastatic MAT-LyLu and nonmetastatic AT. 1 cell lines and its effects on cell motility and adhesion to endothelial cells. We assessed castanospermine's effects on in vivo metastasis in Copenhagen rats. RESULTS: Castanospermine was not cytotoxic toward the MAT-LyLu and AT. 1 cell lines at concentrations through 10 micrograms/mL, nor did it significantly affect cell motility, adhesion to endothelial cells, or in vivo metastasis. CONCLUSIONS: Within the Dunning model, castanospermine did not appear to significantly affect cell characteristics related to metastatic potential.

Nutrient-behavior research with children: methods, considerations, and evaluation.

Diet-behavior research with children formerly focused on effects of diet regimens, as with additive-free diets for hyperactivity. However, an important new area of investigation includes studies of the immediate effects of individual nutrients, such as sugar, on the behavior and cognition of children. Studies of this type use methods from a variety of disciplines. Competence in the fields of nutrition, behavior, neurochemistry, and metabolism is required to perform the studies. Important components of nutrient-behavior studies include the study hypothesis and subject description (including recruitment and selection). Aspects of the food challenge to consider are challenge formulation, dosage, carrier, background dietary variables, and challenge administration schedule. Dependent measures that are used frequently in the studies include observations of behavior, rating scales, activity monitoring, biochemical measures, laboratory tests of performance and attention, tests of cognitive function, and measures of mood. Familiarity with each of the components and use of specific evaluation guidelines will enable nutrition professionals to critically evaluate the studies.

A comparison of learning activity packages and classroom instruction for diet management of patients with non-insulin-dependent diabetes mellitus.

Forty patients were randomly assigned to receive either the individualized learning activity packages or classroom instruction. Effectiveness was evaluated on the basis of fasting plasma glucose, glycosylated hemoglobin, percent of ideal body weight, and knowledge and behavior scores. No significant differences were found between the groups at entry or at the 2-month follow-up. At the 5-month follow-up, the group that received the learning activity packages scored significantly higher on knowledge assessment, significantly increased their behavior score, and decreased their percent of ideal body weight. Patients who received classroom instruction increased their behavior score and exhibited significantly decreased glycosylated hemoglobin levels. Behavior and blood glucose levels were significantly correlated. Although the learning activity packages proved effective in increasing knowledge, no significant improvement was observed in blood glucose levels.

Modeling signal transduction in normal and cancer cells using complex adaptive systems.

As a first approximation, organisms can be defined by the complement of cell types that they possess. Each cell type is defined by its specific collection of signal transduction pathways. While many pathways are common to most cell types (e.g. glycolysis), others are specific to a particular cell type and serve to characterized that cell. Many diseases, including cancer, are characterized by aberrations in general and specific signal-transduction pathways. These pathways are generally intricate and not easily modeled. The formalism of complex adaptive system theory, however, provides the tools by which these pathways can be investigated. By modeling signal-transduction pathways from the viewpoint of complex adaptive systems, a deeper understanding of their intricacies may result. This could eventually lead to novel methods of therapeutic intervention in diseases that arise from aberrant signal transduction.

Cancer as a complex adaptive system.

The second leading cause of death in the USA is cancer. Institutions worldwide are devoting significant resources to the treatment of cancer, and the elucidation of the disease pathway. While great progress has been made in understanding and treating carcinogenesis, many aspects of the disease remain intractable. Throughout the history of science many other disciplines--astronomy, particle physics, etc.--have been advanced when the fundamental ideas governing the discipline were redefined. These redefinitions are often termed 'paradigm shifts'. The new sciences of chaos theory and complexity have led to paradigm shifts in many unrelated disciplines such as economics, meteorology and seismology. Our current understanding of carcinogenesis has resulted from a conventional view of the disease process. In this perception, the mutation of a gene, or several genes, leads to cancer. Applying the formalism of chaos theory and complexity to carcinogenesis, however, leads to a different perception of the disease. If we look closer, cancer can be viewed as a complex adaptive system. Redefining our perception of cancer may lead to a deeper understanding of the disease, and possibly result in novel methods of therapeutic intervention.

[Stabilization in treatment of per- and subtrochanteric fractures of the proximal femur]. / Intramedulläre Kraftträger zur Versorgung der per- und subtrochanteren Femurfraktur.

The incidence of fractures in the trochanteric region is high in the elderly, and early stabilization is required that allows immediate weight bearing. Older patients with low bone quality, limited compliance and strength, and the inability for partial weight-bearing, benefit from intramedullary stabilization of these fractures. The choice of implant and the operative technique depends on the degree of instability in the individual fracture type. Intertrochanteric fractures are frequently combined with subtrochanteric fracture types. Their treatment is still a challenge because of the high degree of instability.