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Biomedical subjects

R Wiley

Publications and source records attributed to R Wiley.

16 recordsLinked to original sources

Biomechanical evaluation of a veterinary suture anchor in the canine cadaver pelvis and femur.

A commercially available veterinary suture anchor was tested in the acetabula and femurs of canine cadavers. Size #2 suture anchor constructs were compared to a traditional screw and Teflon spiked washer constructs in a model of coxofemoral luxation repair. The screw/washer constructs failed at a higher maximum load than the #2 anchor constructs. In the acetabulum, significant differences in strength were also found in the position of the implant and in the direction of pull. The constructs in a more caudal position, and constructs pulled 90 degrees to the axis of insertion, failed at higher loads. The predominant mode of failure of the constructs was a suture failure. In the femur, size #5 suture anchors were used in a model of cranial cruciate ligament repair and collateral ligament repair. The anchor constructs failed predominantly by anchor pull-out in the distal femur. The constructs pulled 90 degrees to the axis of insertion were stronger than construcs pulled at 0 degrees to the axis of insertion. Varying the location of the implant in the femur did not affect the maximum load to failure.

Animals↗

Expression of the Th1 chemokine IFN-gamma-inducible protein 10 in the airway alters mucosal allergic sensitization in mice.

Although the preliminary characterization of chemokines and their receptors has been prolific, comparatively little is known about the role of chemokines in the evolution of immune responses. We speculate that the preferential recruitment of a particular immune cell population has implications for the short- and long-term features of an adaptive response. To test this hypothesis, we employed adenovirus-mediated gene transfer to express the Th1-affiliated, CXC chemokine IFN-gamma-inducible protein (IP) 10 in the airways of mice undergoing a mucosal sensitization regimen known to result in a Th2-polarized allergic response. This resulted in a approximately 60-75% inhibition of eosinophils in the bronchoalveolar lavage (BAL); these inflammatory changes were accompanied by enhanced IFN-gamma, ablated IL-4, and, peculiarly, unaltered IL-5 and eotaxin levels in the BAL. The effect of IP-10 expression was shown to be dependent on IFN-gamma, as there was no statistically significant reduction in BAL eosinophilia in IFN-gamma knockout mice subjected to the IP-10 intervention. Flow cytometric analysis of mononuclear cells in the lung revealed a approximately 60% reduction in the fraction of CD4(+) cells expressing T1/ST2, a putative Th2 marker, and a parallel increase in the proportion expressing intracellular IFN-gamma following IP-10 treatment. The effect of IP-10 expression at the time of initial Ag encounter is persistent, as mice rechallenged with OVA following the resolution of acute inflammation exhibited reduced eosinophilia and IL-4 in the BAL. Collectively, these data illustrate that local expression of the chemokine IP-10 can introduce Th1 phenomena to a Th2-predisposed context and subvert the development of a Th2 response.

Adenoviruses, Human↗

The effects of tetanus toxin on the orbicularis oculi muscle.

PURPOSE: Tetanus toxin can cause localized neuromuscular weakness, but it also can produce systemic tetany. The action of tetanus toxin on the orbicularis muscle has not been studied in animals immunized to prevent systemic tetany. Our objective was to determine whether tetanus toxin could be used to treat orbicularis oculi muscle spasms. METHODS: We analyzed the clinical, electrophysiologic, and histopathologic effects of tetanus toxin injected into the orbicularis oculi muscle of rabbits with passive immunity to tetanus toxin. In six rabbits, the orbicularis oculi function in both eyes was assessed clinically, and the baseline orbicularis oculi muscle action potential was measured physiologically with electromyography (EMG). The rabbits then were immunized against tetanus toxin with tetanus immunoglobulin for immediate and definitive immunity. Tetanus toxin was injected into the left orbicularis oculi muscles, leaving the right eyes as controls. Ten days later, the rabbits were again assessed by clinical examination and with EMGs on both the injected side and the noninjected side. The animals were killed at 14 days, and the orbicularis muscle was removed from both sides. The injected and control tissues were examined microscopically for signs of neuromuscular denervation. RESULTS: All six rabbits showed weakness in eye closure on the side injected with tetanus toxin. In addition, four rabbits developed complete ear ptosis on the tetanus toxin injected side because of spread of the toxin to adjacent ear muscles. EMGs showed both a denervation of the orbicularis oculi muscle and a poor blink potential on the side injected with tetanus toxin. Histopathologic studies of the orbicularis oculi muscle injected with tetanus toxin showed angulation of both slow and fast types of muscle fibers compatible with neuromuscular denervation. CONCLUSIONS: Tetanus toxin can cause localized orbicularis oculi weakness, as documented clinically, physiologically, and microscopically, without producing systemic tetany in immunized rabbits. Tetanus toxin may have a potential application in the treatment of blepharospasm and hemifacial spasm.

Action Potentials↗

Differences in apparent contrast in yellow and white light.

The purpose of this study was to investigate suprathreshold contrast perception in white and yellow light. The contrast of black-on-white letters was adjusted to match the perceived contrast of yellow-on-yellow letters presented simultaneously on a video display. At lower contrasts (7-15%), the apparent contrast of yellow letters was slightly enhanced compared to black-on-white letters (mean enhancement = 23%), but this effect diminished with increasing contrast. The slight enhancement in yellow light was independent of letter size, and could not be explained by luminance differences between yellow and white displays. This effect may relate to the subjective improvement often reported when wearing yellow (blue-blocking) lenses.

Adult↗

Switching from forward-looking infrared to night vision goggles: transitory effects on visual resolution.

Helmet-mounted displays under development for rotary- and fixed-wing aircraft will allow the user to switch electronically between forward-looking infrared (FLIR) and night vision goggle (NVG) sensors. These sensor transitions potentially involve large changes in display luminance which could transiently impair visual resolution and performance. The purpose of this study was to identify the display luminances which produce a transient reduction in vision when switching from a higher luminance (i.e., FLIR) to a lower luminance (i.e., NVG) display. A letter recognition task was used to assess the effect of luminance adaptation on visual resolution in five subjects. A significant reduction in letter recognition was observed in the first second after switching from simulated FLIR to simulated NVG's when the FLIR luminance was > or = 10 fL. By varying letter size, contrast, and exposure time, the magnitude and duration of visual loss after switching from a bright (49.2 fL) FLIR display were determined. The visual loss lasted up to 4 s, and included a 2x reduction in visual acuity, and a 3x reduction in contrast sensitivity. Large differences in sensor display luminance should be avoided to maintain high levels of visual performance and aviation safety. Design features or training may be necessary to achieve a proper balance between FLIR and NVG luminances which optimize performance and safety without sacrificing the quality of the sensor image.

Adult↗

Toxicity of alkyldihydrofurans to metabolically active organs in the mouse.

Alkylfurans inflict toxicity in several mammalian species to lung, liver and kidney. Organ specificity of the alkylfurans is a sensitive function of the nature of the alkyl group. To determine if this toxicity requires an aromatic ring in the compound, we synthesized 4-methyl-2,3-dihydrofuran, 4-ethyl-2,3-dihydrofuran and 4-pentyl-2,3-dihydrofuran and determined their toxicity to lung, liver and kidney in mice. Lung damage was evaluated by light microscopy and the incorporation of [14C]thymidine into lung DNA. The results indicated that 4-methyl-2,3-dihydrofuran and 4-ethyl-2,3-dihydrofuran were toxic to the lung whereas 4-pentyl-2,3-dihydrofuran did not produce lung toxicity. Histological examination of liver sections revealed that 4-ethyl-2,3-dihydrofuran induced vacuolar degeneration of hepatocytes. Kidney toxicity was evaluated by light microscopy and determining plasma urea levels. Both 4-ethyl-2,3-dihydrofuran and 4-pentyl-2,3-dihydrofuran exhibited kidney toxicity, while equimolar doses of 4-methyl-2,3-dihydrofuran did not damage the kidney. A quantitative comparison of the nephrotoxicity of 4-pentyl-2,3-dihydrofuran with the corresponding aromatic compound 3-pentylfuran was made. We also sought to determine if renal injury resulting from these 2 agents is related to their oxidative metabolism. Uptake of organic ions by kidney slices and plasma urea nitrogen levels were used to assess renal function. 3-Pentylfuran caused greater renal injury than an equimolar dose of 4-pentyl-2,3-dihydrofuran. Phenobarbital pretreatment protected mice against 3-pentylfuran-induced nephrotoxicity. Cotreatment with piperonyl butoxide did not affect renal injury resulting from 3-pentylfuran. N-octylimidazole significantly reduced 3-pentylfuran-induced nephrotoxicity as well as that caused by 4-pentyl-2,3-dihydrofuran. These results point to metabolic activation as a basis for the nephrotoxicity induced by both compounds.

Animals↗

Primary lymphoma of the central nervous system. A report of 20 cases and a review of the literature.

Twenty patients with primary non-Hodgkin's lymphoma of the central nervous system (CNS) were seen at Vanderbilt and its affiliated hospitals between 1974 and 1986. Histologically, the most common subtypes were large, noncleaved cell lymphoma and immunoblastic lymphoma of B cells. However, multiple histologies were identified. Lesions most commonly involved the frontal lobes and/or deep nuclei. Positive cerebrospinal fluid cytology was rare at initial presentation. Seventeen patients were treated with surgical biopsy or resection followed by whole brain radiotherapy at a median dose of 5,000 cGy (range: 3,000-5,600 cGy). Seven patients have been followed for less than 12 months since diagnosis. Of the remaining patients, 7 (54%) survived at least 1 year. The extent of surgery performed, dose of radiotherapy administered, subclass of lymphoma diagnosed, or location(s) of involvement within the CNS did not influence survival. Treatment rarely caused a dramatic improvement in performance status despite objective signs of response. New treatment strategies are needed to improve the management of these tumors.

Adult↗

Patterns of change in functional status in extended care.

Most investigators and policymakers assume that the functional abilities of long-term care patients are stable over time. If short-run fluctuations in functional ability occur, then reimbursement and quality control systems based on case mix will have to account for whatever changes can be reasonably expected. However, the probability that the functional status of an extended-care patient will decline, improve, remain constant, or fluctuate over the short run is unknown. Analysis of 191 Veterans Administration extended-care patients over 12 weeks reveals that patient functional status is unstable in some wards and that patients in wards providing a higher level of care are more likely to be unstable and to be discharged in an improved condition. These findings suggest that nursing homes operating under case-mix reimbursement systems will find skilled patients to be more attractive than other nursing home patients. Variability in dependency is related to patient turnover. Turnover rates can be used to adjust patient assessments for expected variability in dependency. Adjusted dependency scores should be used in long-term care reimbursement systems for planning quarterly staffing requirements and for quality control systems based on patient outcomes.

Activities of Daily Living↗

Prospective randomized controlled study of ciprofloxacin versus imipenem-cilastatin in severe clinical infections.

In a randomized prospective study, 66 patients with serious bacterial infections--mainly lower respiratory tract infections--were treated with either imipenem plus cilastatin (32 patients) or ciprofloxacin (34 patients); 30 patients in each group were evaluable for efficacy. Substantial underlying disease was present in most of the patients; pathogens isolated prior to treatment (77 isolates) consisted mainly of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae, and streptococci. Of the etiologic bacteria, 67% were eradicated by ciprofloxacin treatment and 79% by imipenem therapy; however, two patients (6.7%) failed in the ciprofloxacin group, and six patients (20%) did not respond to imipenem treatment (P = 0.25). All patients with therapeutic failures suffered from severe fatal underlying diseases, which had substantial impact on the outcome of treatment. Therapeutic drug monitoring in the ciprofloxacin patients revealed higher concentrations in serum at days 4 and 8 in comparison with day 1 of treatment, indicating that steady-state conditions were reached between days 1 and 4. The total number of side effects was relatively high--eight imipenem patients (25%) and six ciprofloxacin patients (18%) had reactions. Treatment had to be discontinued due to adverse reactions for three ciprofloxacin patients and two imipenem patients. Major side effects in both groups were gastrointestinal and central nervous system-related symptoms. In terms of clinical and bacteriological efficacy and safety, there was no statistical difference between the two groups, and both groups gave good to excellent results for bacterial infections that were difficult to treat.

Adolescent↗

Comparative pharmacokinetics of new quinolones.

The pharmacokinetic properties of the new quinolones are characterised by a high volume of distribution, long biological half-life, low serum protein binding, elimination mainly by the kidneys, high total and renal clearances, limited biotransformation and a moderate to excellent bioavailability after oral administration. However, each quinolone derivative (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin) possesses individual pharmacokinetic characteristics, which should be considered in the treatment of patients, especially when liver and/or renal dysfunction exists.

Anti-Infective Agents↗

Pharmacokinetics of ciprofloxacin in healthy volunteers after oral and intravenous administration.

The pharmacokinetics of ciprofloxacin was studied in three groups of healthy volunteers comprising a total of 16 males and 16 females (age 21-35 years; body weight 52-80 kg). Single oral doses of 50, 100, 250, 500 and 750 mg were given to fasting subjects. The 250 mg dose was repeated after a breakfast. Intravenous doses of 50, 100 and 200 mg were given by short infusion in a randomized cross-over sequence. Concentrations of the drug in serum and urine were determined by high-performance liquid chromatography and by a microbiological assay. Mean peak concentrations between 0.37 +/- 0.49 mg/l (100 mg dose) and 1.97 +/- 0.50 (750 mg dose) were measured 60-75 min after oral administration. Twelve hours after 750 mg ciprofloxacin, serum concentrations were 0.15 +/- 0.05 mg/l. Taking a breakfast reduced absorption by 15-20% compared to the fasting state, as judged by peak concentrations, AUC and renal excretion. After 200 mg i.v. (20 min infusion period), initial serum concentrations of 4.0 +/- 1.2 mg/l were observed which declined 12 h later to 0.070 +/- 0.025 mg/l. Mean cumulated recovery of ciprofloxacin from urine over 24 h varied between 25.5% and 33.6% of oral doses and between 53.2% and 57.4% of intravenous doses. Two of the three metabolites seen in the chromatograms were identified as M1 and M3 (oxo-ciprofloxacin). Cumulated renal excretion after an oral 250 mg dose was 1.2 +/- 0.4% of M1 and 5.5 +/- 1.6% of M3.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Liquid chromatographic determination of ciprofloxacin and some metabolites in human body fluids.

Two column liquid chromatographic (HPLC) methods for the determination of ciprofloxacin and three metabolites are described. Both use reversed phase chromatography, the stationary phase being Nucleosil 5C18. Method A separates ciprofloxacin, metabolite M1 and another metabolite of unknown structure using fluorometric detection. Method B allows the determinations of metabolite M3 (oxo-ciprofloxacin) in urine by UV absorption. Serum was deproteinised with acetonitrile. Urine was diluted with buffer solution. The detection limit of ciprofloxacin was 0.010 mg/l serum and 0.2 mg/l urine and for the metabolite M3, 1 mg/l urine. Within-batch precision (coefficient of variation) for ciprofloxacin in serum was 0.8 to 2.4% and between-batch precision 4.8 to 9.3%. In urine within-batch precision was 1.7 to 2.1% and between-batch precision 2.4 to 7.2%. Recovery rates of ciprofloxacin from three groups of spiked sera was 94.5 +/- 2.6%, 97.2 +/- 1.1% and 95.0 +/- 1.8% and from urine 99.6%. Results obtained by HPLC (method A) were compared with those from a standard microbiological assay by means of bivariate regression analysis. In 12 subsets of data the slope of the regression line varied from 1.042 to 1.556. Significantly higher results from the microbiological assay were probably due to the presence of microbiologically active metabolites. We conclude that HPLC is the more specific method of determination. The described methods were applied for pharmacokinetic studies and therapeutic drug monitoring.

Biological Assay↗

Effect of inspiratory volume on intrathoracic pressure generated by an L-1 maneuver.

Since each muscle has an optimal length at which it can generate the maximum tension, an optimal inspiratory volume may exist for producing the maximum intrathoracic pressure during the L-1 maneuver. Intrathoracic pressures were measured in eight healthy men after they inspired various volumes of air and performed the L-1 straining maneuver in a 1-G environment. Both the peak and mean intrathoracic pressures increased at greater inspiratory volumes, except for the mean intrathoracic pressure at the highest volumes. The ability to increase intrathoracic pressure with larger inspiratory volumes may improve +Gz tolerance.

Adult↗