Fosphenytoin: worth the cost?
Explore the source record for details and available documents.
Anticonvulsants↗
Biomedical subjects
M H Miller
Publications and source records attributed to M H Miller.
Surgical results in malignant glaucoma refractory to medical or laser therapy.
We investigated the surgical results in 25 patients identified with malignant (ciliary block) glaucoma. Four of these patients (16%) had successful outcomes following laser treatment alone. Nineteen patients (76%) underwent microsurgery for glaucoma refractory to conventional medical and/or laser therapy and are the subjects of this study. Core vitrectomy was successful in 4 of 6 pseudophakic patients (67%) and in 1 of 4 phakic patients (25%). Combined cataract extraction and vitrectomy had a higher success rate in patients undergoing posterior capsulectomy at the time of surgery (5 of 6 patients; 83%) compared with those patients left with an intact posterior capsular bag (1 of 4 patients; 25%). Intracapsular cataract extraction was successful in 1 of 2 patients (50%). We conclude that surgical vitrectomy in the presence of an intact posterior capsule may preclude the surgical resolution of aqueous misdirection. In eyes with pre-existing cataract, we recommend combined lens extraction, primary posterior capsulectomy and surgical vitrectomy for the surgical management of phakic malignant glaucoma.
Adult↗
In vitro activities of ciprofloxacin and rifampin alone and in combination against growing and nongrowing strains of methicillin-susceptible and methicillin-resistant Staphylococcus aureus.
We characterized the effects of ciprofloxacin and rifampin alone and in combination on Staphylococcus aureus in vitro. The effects of drug combinations (e.g., indifferent, antagonistic, or additive interactions) on growth inhibition were compared by disk approximation studies and by determining the fractional inhibitory concentrations. Bactericidal effects in log-phase bacteria and in nongrowing isolates were characterized by time-kill methods. The effect of drug combinations was dependent upon whether or not cells were growing and whether killing or growth inhibition was the endpoint used to measure drug interaction. Despite bactericidal antagonism in time-kill experiments, our in vitro studies suggest several possible explanations for the observed benefits in patients treated with a combination of ciprofloxacin and rifampin for deep-seated staphylococcal infections. Notably, when growth inhibition rather than killing was used to characterize drug interaction, indifference rather than antagonism was observed. An additive bactericidal effect was observed in nongrowing bacteria suspended in phosphate-buffered saline. While rifampin antagonized the bactericidal effects of ciprofloxacin, ciprofloxacin did not antagonize the bactericidal effects of rifampin. Each antimicrobial prevented the emergence of subpopulations that were resistant to the other.
Anti-Infective Agents↗
Aggressive, socially disruptive and antisocial behaviour associated with fronto-temporal dementia.
BACKGROUND: Research suggests an association between frontal and temporal injury and antisocial conduct. We studied the frequency of antisocial behaviours in fronto-temporal dementia (FTD) where pathology is anterior frontal-temporal, compared with Alzheimer's disease (AD) where pathology is primarily posterior temporal-parietal. METHOD: The presence of antisocial conduct was compared in 22 FTD versus 22 AD subjects. All FTD patients had anterior frontal or temporal hypoperfusion with single photon emission computed tomography, whereas those with AD had posterior temporal-parietal hypoperfusion. RESULTS: Ten FTD and one AD subject showed antisocial behaviours, which included assault, indecent exposure, shoplifting and hit-and-run driving. Three FTD subjects were arrested. This difference was highly significant (P = 0.004). CONCLUSIONS: Degeneration of frontal and temporal lobes predisposes to antisocial behaviour. This study supports a relationship between frontal-temporal dysfunction and certain types of antisocial activities.
Aggression↗
A method for representing search results in three dimensions.
This paper presents a new method for representing results of an information retrieval search in a three dimensional environment. Aside from the fact that users find 3-D interfaces visually appealing, there are strong practical reasons for developing 3-D representations of search results. Traditional information retrieval systems present results in ordered lists which are difficult to browse, and exclude useful information. The current method employs a multivariate statistical method called Local Latent Semantic Indexing (LLSI) to create meaningful local dimensions in which to view search results. A prototype Internet-ready system is described which utilizes Virtual Reality Modeling Language (VRML) to display search results. Preliminary tests of this system with a small collection of MEDLINE articles are very encouraging.
Computer Graphics↗
Predictive value of several signs of infection as surrogate markers for mortality in a neutropenic guinea pig model of Pseudomonas aeruginosa sepsis.
Infected, neutropenic animals are used as experimental models to evaluate the relative efficacies of antimicrobial agents and host-pathogen-antibiotic interactions. In the past, these models used death as the study end point. Because of the concern about use of death as an end point, we evaluated the accuracy with which various signs of infection predicted mortality in a neutropenic guinea pig model of treated and untreated Pseudomonas aeruginosa sepsis. The potential surrogate markers studied included ruffled fur, respiratory distress, diarrhea, hunched posture, lethargy, abnormal neurologic movements (twitching, paralysis of a limb), inappetence for > 48 h, the inability to ambulate, and the inability of a supine animal to stand. In addition, we evaluated whether percentage of weight loss or change in daily food and water consumption were predictive of mortality. Animals were inspected for these signs at least every 4 h during the day and every 8 h in the evening. In treated and untreated animals, 100% of subjects that were unable to ambulate or to rise from the supine position died (positive predictive value for death was 100% for either sign). Guinea pigs that could not rise from a supine position expired between 1 and 8 h after this sign was observed. Those that could not ambulate died between 4 and 40 h after that sign was observed. In treated and untreated animals, none of the survivors manifested either sign of disease (100% specificity for each sign). However, 59% of untreated and 69% of treated animals that were ambulatory were found dead at the next observation period, underscoring the rapidity with which this infection progresses to death when it enters its final stage. No other signs of infection distinguished animals that survived or died. Thus, the inability of neutropenic, infected guinea pigs to rise from a supine position and the inability to ambulate were the only signs that accurately predicted death and, therefore, are the only signs that can be used as surrogates for death in this experimental model of P. aeruginosa sepsis.
Animals↗
Aqueous and vitreous penetration of ciprofloxacin following different modes of systemic administration.
The overall importance of the peak or the mean serum concentrations as predictors of ocular drug penetration is unknown. To address this fundamental question with an agent which shows promise as adjunctive therapy in the treatment of endophthalmitis, we studied the penetration of ciprofloxacin into the aqueous and vitreous humors following three different modes of systemic administration. New Zealand white rabbits received either a single bolus dose (40 mg kg-1), three intermittent doses of 13.33 mg kg-1 evenly spaced over an 8 hr period, or a continuous infusion of 40 mg kg-1 over an 8 hr period. Pharmacokinetic analysis was performed using RSTRIP II, a non-linear, least square regression model analysis program. The serum area under the concentration-time curve (AUC) values for each mode of drug administration were similar: 32.9 micrograms hr ml-1 for single dose, 31.9 micrograms hr ml-1 for intermittent dose, and 33.8 micrograms hr ml-1 for continuous infusion modes. The percentage penetration into the aqueous and vitreous were also similar; 30.5% and 6.5% for a single dose, 31.6% and 7.4% for intermittent doses and 30.0% and 7.5% for continuous infusion. The penetration into the aqueous and vitreous humors was not influenced by mode of administration. As with other quinolones we have studied, elimination rates were similar for the central and peripheral compartments in the post-distributive phase. Vitreous humor ciprofloxacin concentrations achieved were below that which inhibits most Staphylococcus epidermidis, the most common isolate in patients with post-operative endophthalmitis.
Animals↗
Seasonal differences in biochemical parameters of bone remodelling.
AIMS: To compare bone remodelling parameters in late autumn and early spring in 20 post-menopausal women. METHODS: The parameters measured were serum osteocalcin and its apparent degree of carboxylation (measured by hydroxyapatite binding), total and bone specific alkaline phosphatase and urinary bone resorption markers, (pyridinoline and deoxypyridinoline). RESULTS: Serum osteocalcin concentrations were lower in autumn than in spring but the degree of carboxylation was similar. Total and bone specific alkaline phosphatase activities in serum were higher in autumn than in spring. These results support previous observations. However, notable and previously unreported changes in urinary bone resorption markers were observed. Pyridinoline concentrations were lower and deoxypyridinoline higher in autumn compared with spring. The ratio of pyridinoline:deoxypyridinoline was therefore very different between the seasons. CONCLUSIONS: The results clearly demonstrate that seasonal changes in these variables of bone remodelling must be taken into consideration when designing, reporting or analysing studies of bone metabolism in vivo.
Aged↗
Sequential parenteral and oral ciprofloxacin regimen versus parenteral therapy for bacteremia: a pharmacoeconomic analysis.
OBJECTIVE: To compare, in patients with gram-negative bacteremia, a course of parenteral antibiotic therapy alone with initial parenteral therapy followed by oral ciprofloxacin in terms of the length of hospitalization, clinical effectiveness, toxicity, and cost. DESIGN: A prospective, controlled, randomized, open trial in select hospitalized patients. SETTING: Large metropolitan teaching hospital. PATIENTS: Fifty hospitalized patients with proven gram-negative bacteremia were randomized to receive either oral ciprofloxacin (group 1) following a 72-hour initial intravenous antibiotic regimen or to continue parenteral therapy alone (group 2). To compare the length of hospitalization, an additional group of 50 hospitalized patients with bacteremia (not enrolled in the study, group 3) were analyzed. INTERVENTION: Parenteral antibiotics for 72 hours followed by continuation of a parenteral regimen or oral ciprofloxacin 750 mg bid. MAIN OUTCOME MEASURES: Clinical response, toxicity, and length of hospitalization. RESULTS: Clinical resolution was comparable in the 24 group 1 patients receiving intravenous antibiotics followed by oral ciprofloxacin (83%), the 26 group 2 patients receiving parenteral therapy alone (77%), and the 50 comparison patients (76%). There was little toxicity noted in any group, and the initial parenteral antibiotic regimens were similar. The mean numbers of hospital days on antibiotics were 9.1, 11.2, and 10.6 days in groups 1,2, and 3, respectively (p < 0.05 for group 1 vs. group 2 or 3), and the lengths of hospitalization were 9.8, 15.7, and 12.1 days, respectively (p < 0.05 for group 1 vs. group 2 or 3). Shortening the length of hospitalization and days of antibiotic therapy was associated with a cost savings of up to $78 000 for group 1 patients. CONCLUSIONS: Parenteral therapy for 72 hours followed by oral ciprofloxacin significantly shortened both the number of hospital days taking antibiotics and the length of stay compared with parenteral therapy alone. Both regimens were equally effective and safe in the therapy of gram-negative bacteremia, and initial parenteral therapy followed by oral ciprofloxacin was cost-effective.
Administration, Oral↗
Admissions and student concerns.
Explore the source record for details and available documents.
Curriculum↗
Tobramycin uptake in Escherichia coli membrane vesicles.
The uptake of tobramycin was measured in Escherichia coli membrane vesicles prepared in KMES [K(+)-2-(N-morpholino)ethanesulfonic acid] buffer at pH 6.6. Uptake occurred in vesicles energized with ascorbic acid and phenazine methosulfate, in which the electrical potential (delta psi) was -120 mV, but not in vesicles energized with D-lactate (delta psi = -95 mV). The addition of nigericin to vesicles energized with D-lactate did not induce tobramycin uptake despite an increase in delta psi to -110 mV. However, when delta psi was increased or decreased by the addition of nigericin or valinomycin, respectively, uptake in vesicles energized with ascorbic acid and phenazine methosulfate was stimulated or inhibited, respectively, confirming studies with whole cells showing that uptake of aminoglycosides is gated by delta psi rather than by proton motive force (delta microH+) or delta pH. N-ethylmaleimide prevented uptake, suggesting that the aminoglycoside transporter is a cytoplasmic membrane protein with accessible sulfhydryl groups. The observation that uptake is gated in vesicles as well as in whole cells suggested that diffusion occurs through a voltage-gated channel. In vesicles preloaded with tobramycin, no efflux occurred after the addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone. In susceptible cells, aminoglycosides themselves decreased the magnitude of delta psi. We propose a mechanism of aminoglycoside-induced killing in which aminoglycosides themselves close the voltage-gated channel by decreasing the magnitude of delta psi. Channel closure causes aminoglycosides accumulated prior to the fall in delta psi to be trapped, which in turn causes irreversible uptake and subsequent bactericidal effects.
Ascorbic Acid↗
Pharmacokinetics of ofloxacin in serum and vitreous humor of albino and pigmented rabbits.
The purpose of this study was to evaluate the pharmacokinetics of ofloxacin in serum and vitreous humor samples from albino and pigmented rabbits by using a recently described animal model which permits robust estimation of parameter values. The drug was administered to rabbits intravenously, multiple vitreous humor and serum samples were taken from each rabbit, and the vitreous humor and serum samples were assayed by high-pressure liquid chromatography. The pharmacokinetic parameters were determined with RSTRIP, an iterative, nonlinear, weighted, least-squares regression program. Eight New Zealand White rabbits and eight Dutch Belted rabbits (split into single-dose and multiple-dose groups) were investigated in this study. The value of penetration into the vitreous humor of albino rabbits (n = 6) was 32.6% +/- 2.12%, with terminal-elimination half-life values of 3.21 and 2.39 h, respectively, for vitreous humor and serum. In pigmented rabbits after a single dose (n = 3) and with a steady-state concentration of drug in serum (n = 4), penetration values were similar, at 30.4% +/- 2.98% and 30.0% +/- 4.12%, respectively (P > 0.10). Following a single dose of ofloxacin, pigmented animals had elimination half-life values from serum and vitreous humor of 2.64 and 4.32 h, respectively. After steady state was achieved, half-life values for serum and vitreous humor were 3.12 and 6.05 h, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
Albinism↗
Determination of robust ocular pharmacokinetic parameters in serum and vitreous humor of albino rabbits following systemic administration of ciprofloxacin from sparse data sets by using IT2S, a population pharmacokinetic modeling program.
Robust determination of the concentration-time profile of anti-infective agents in certain specialized compartments is often limited by the inability to obtain more than a single sample from such a site in any one subject. Vitreous humor and cerebrospinal fluid are obvious examples for which the determination of concentrations of anti-infective agents is limited. Advances in pharmacodynamics have pointed out the importance of understanding the profiles of drugs in the plasma and in specialized compartments in order to dose the drugs to obtain the best patient outcomes. Advances in population pharmacokinetic modeling hold the promise of allowing proper estimation of drug penetration into the vitreous (or other specialized compartment) with only a single vitreous sample, in conjunction with plasma sampling. We have developed a rabbit model which allows multiple samples of vitreous to be obtained without breaking down the blood-vitreous barrier. We have employed this model to test the hypothesis that robust estimates of vitreous penetration by the fluoroquinolone ciprofloxacin can be obtained from a traditional intensive plasma sampling set plus a single vitreous sample. We studied 33 rabbits which were receiving 40 mg of ciprofloxacin per kg of body weight intravenously as short infusions and from which multiple plasma and vitreous samples were obtained and assayed for ciprofloxacin content by high-performance liquid chromatography. Data were analyzed by the iterative two-stage population modeling technique (IT2S), employing the iterative two-stage program of Forrest et al. (Antimicrob. Agents Chemother. 37:1065-1072, 1993). Two data sets were analyzed: all plasma and vitreous samples versus all plasma samples and the initially obtained single vitreous sample. The pharmacokinetic parameter values identified were used to calculate the percent vitreous penetration as the ratio of the area under the concentration-time curve for the vitreous to that for the plasma. The values identified, 4% penetration for the full data set versus 3% penetration for the single vitreous sample data set, and their corresponding estimates were not statistically significantly different. We conclude that population modeling holds promise for the analysis of penetration of antimicrobiol agents into specialized spaces from which only single samples can be obtained, particularly for patients with whom robust plasma sampling can be performed.
Animals↗
Fibromyalgia syndrome and disease activity in systemic lupus erythematosus.
To study the effect of fibromyalgia syndrome (FS) on the expression of systemic lupus erythematosus (SLE) and on the measurement of disease activity, we performed a cross-sectional study of subjects with SLE. Eighty-seven subjects were studied and 22 (25.3%), all female, had FS (Yunus' criteria). Disease activity and organ system involvement were assessed using the systemic lupus activity measure (SLAM) and using 10 cm visual analogue scales (VAS) completed by both physician and patient. No significant difference between FS and non-FS groups in the objective measurement of disease activity was present, median (range) SLAM scores being 5 (0-18) and 6 (0-24), respectively (NS). Similarly, expression of SLE, as measured by the prevalence of specific organ system involvement, was similar in the two groups. In contrast the prevalence of glucocorticoid use, antibodies to DSDNA and fulfilling four ACR criteria was higher in the non-FS group. The rating of SLE disease activity was affected by concomitant FS. Physician and patient disease activity VAS correlated significantly with SLAM scores in non-FS subjects (P < 0.001, Spearman analysis), whereas in FS subjects, neither physician nor patient VAS correlated with SLAM scores. We conclude that FS is prevalent in individuals with SLE and does not affect disease expression but may interfere with the rating of disease activity.
Adult↗
Single anticardiolipin measurement in the routine management of patients with systemic lupus erythematosus.
OBJECTIVE: To examine the usefulness of a single measurement of anticardiolipin antibodies (aCL) in systemic lupus erythematosus (SLE) in routine clinical practice. METHODS: All 127 patients with SLE currently followed by our rheumatology unit had an aCL measurement on routine clinic review. Their charts were then reviewed for specific disease manifestations. Basic statistical correlations of the aCL result and the specific disease manifestations were performed, and the clinical utility of the aCL test assessed using Bayesian analysis. RESULTS: aCL was positive (> 2 SD) in 24% and was associated with recurrent fetal loss, thrombosis, cerebrovascular disease, livedo reticularis and digital infarcts. Bayesian analysis showed that a single positive aCL test increased the relative and absolute risk of all the above complications. The criterion of aCL positivity as > 15 units (2 SD) was associated with the highest relative risk. CONCLUSION: A single positive aCL test in routine management of SLE is a useful predictor of important clinical events.
Adult↗
Dangers of direct injection of antimetabolites into filtration blebs.
Explore the source record for details and available documents.
Antimetabolites↗
Does the gender difference in interferon production seen in picornavirus-infected spleen cell cultures from ICR Swiss mice have any in vivo significance?
Splenocyte cultures from female ICR Swiss mice produced greater interferon (IFN) levels, particularly IFN-gamma, than did cultures from males by 12 h post-infection (pi) with the D variant of encephalomyocarditis virus (EMCV-D). This early IFN-gamma is produced by natural killer (NK)-like cells and is dependent on plastic adherent cells and IFN-alpha/beta. In this study, we evaluated the significance of this observation on the innate resistance of ICR Swiss females to EMCV-D-mediated disease. Treatment of females with rabbit anti-mouse IFN-alpha/beta serum rendered them susceptible to the diabetogenicity of EMCV-D. Although sera from both sexes of ICR Swiss mice exhibited peak IFN levels day 3 pi, IFN-gamma was present in the sera of males at only 1 day pi and in the sera of females at days 1-3 pi. Females cleared virus from the circulation by day 2 pi, 1 day earlier than did males. Flow cytometric evaluations of lymphoid cell phenotypes in spleens and pancreata of infected mice revealed that percentages of L3T4+ cells were significantly decreased only in spleens from males at day 1 pi and were diminished along with Ly2+ cells in pancreata of males at 7 days pi, suggesting that T-cell responses were impaired in virus-infected males.
Animals↗
Methotrexate therapy in rheumatoid arthritis: a life table review of 587 patients treated in community practice.
To determine whether methotrexate (MTX) maintains its effectiveness in rheumatoid arthritis (RA) in the setting of community based private rheumatology practice we used life table analysis to review the combined experience of a group of these practices. Of 587 patients with RA who started to take MTX, total termination rate at 70 months was 24.4% with most terminations prompted by drug toxicity. Older age (greater than 65 years) was associated with higher rates of toxicity. Treatment termination rates varied substantially between rheumatologists. We conclude that MTX therapy for RA is well tolerated and maintains effectiveness for at least 70 months.
Adult↗