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Biomedical subjects

J Alderman

Publications and source records attributed to J Alderman.

At least 19 recordsLinked to original sources
PubMed2005

Therapeutic benefit of eletriptan compared to sumatriptan for the acute relief of migraine pain--results of a model-based meta-analysis that accounts for encapsulation.

A novel model-based meta-analysis was used to quantify the dose-response relationship of sumatriptan and eletriptan for the proportion of patients that achieve migraine pain relief up to 4 h after treatment. The proportion of patients that became pain free was also evaluated. This analysis includes some unique features, allowing comparison of sumatriptan and eletriptan doses that have not been directly compared in a head to head study and also permitting comparison between the two drugs at multiple time points up to 4 h after treatment. Because the analysis allows comparison of response to blinded sumatriptan with that to marketed sumatriptan and contains timepoints as early as 0.5 h, it is especially suited to detection of possible effects of encapsulation on sumatriptan's therapeutic effectiveness and thus was employed to assess this also. Data from 19 randomized placebo controlled clinical trials were jointly analysed using a random-effects logistic regression model. The results of this analysis show a significant clinical benefit of eletriptan 40 mg compared to sumatriptan 100 mg at any point in time up to 4 h after treatment. The benefit of eletriptan 40 mg is greatest around 1.5-2 h after treatment with an absolute difference at 2 h of 9.1% (7.4-11.5%) more patients achieving pain relief and 7.3% (5.8-8.6%) more patient achieving pain free when compared to sumatriptan 100 mg. An absolute benefit of more than 5% of patients is maintained from 45 min up to 4 h after treatment for pain relief and from 1.5 h up to 4 h for pain free. Eletriptan 20 mg was superior to sumatriptan 50 mg and similar to sumatriptan 100 mg for pain relief while it was similar to sumatriptan 50 mg for pain free. The benefit of eletriptan 20 mg when compared to sumatriptan 50 mg is greatest around 1.5-2 h after treatment with an absolute difference at 2 h of 5.0% (2.9-8.1%) more patients achieving pain relief. An absolute benefit of more than 3% of patients was maintained from 1 h up to 3 h after treatment. No significant difference was found between eletriptan 20 mg and sumatriptan 50 mg for the fraction of patients that became pain free. No significant effect of encapsulation of sumatriptan was found on the time course of response up to 4 h after treatment when compared to commercial sumatriptan.

Capsules↗
PubMed2001

Ion chromatography on-chip.

On-chip separation of inorganic anions by ion-exchange chromatography was realized. Micro separation channels were fabricated on a silicon wafer and sealed with a Pyrex cover plate using standard photolithography, wet and dry chemical etching, and anodic bonding techniques. Quaternary ammonium latex particles were employed for the first time to coat the separation channels on-chip. Owing to the narrow depths of the channels on the chip, 0.5-10 microm, there were more interactions of the analytes with the stationary phase on the chip than in a 50-microm I.D. capillary. With off-chip injection (20 nl) and UV detection, NO2-, NO3-, I-, and thiourea were separated using 1 mM KCl as the eluent. The linear ranges for NO2- and NO3- are from 5 to 1000 microM with the detection limits of 0.5 microM.

Chromatography, Ion Exchange↗
PubMed2001

On-chip definition of picolitre sample injection plugs for miniaturised liquid chromatography.

The fabrication of components for a miniaturised liquid chromatography system on silicon has recently been reported by our research group [J. Cap. Electrophoresis Microchip Technol. 6 (1999) 33; Analyst 125 (2000) 25]. To date, inlet and outlet connection ports, separation micro-channels (20-200 microm in width, 0.5-10 microm in depth, 15-60 cm in length), and an intersection for picolitre injection have been etched on a silicon wafer and then sealed with a Pyrex cover plate on which platinum electrodes for on-chip detection have been patterned. The platinum electrodes have been used for the amperometric detection of phenol, using 20 nl off-chip injection. In this work we present our latest results obtained with on-chip pressure driven picolitre injection, designed to realize the full capabilities of this micro-LC system. The injection volume is dependent on the micro-channel depth, width, and also on the intersection length, allowing injection in the low nanolitre to picolitre range.

Chromatography, High Pressure Liquid↗
PubMed2001

Predictors of success with the use of donor sperm.

OBJECTIVE: This study was undertaken to assess the effect of multiple factors that influence the success rate and time to conception among couples undergoing donor sperm insemination. STUDY DESIGN: A retrospective analysis of 960 cycles of frozen donor sperm insemination was performed at the University of Florida. Cycle pregnancy rates and cumulative probability of pregnancy were compared using several variables. RESULTS: The pregnancy rate was 12.1% per treatment cycle, and the cumulative probability of pregnancy exceeded 80% for the entire cohort. Seventy percent of pregnancies resulted in a liveborn infant. Age had a profound impact on the cycle pregnancy rate. The cycle pregnancy rates for women younger than 30 years, between the ages of 30 and 35 years, between the ages of 35 and 40 years, and older than 40 years were 15.8%, 14.6%, 8.2%, and 0%, respectively. There was a trend toward higher cycle pregnancy rates in women with prior pregnancies versus women without prior pregnancies of 14.4% and 12.3%, respectively. Parity had no effect on the cycle pregnancy rate or the cumulative probability of pregnancy. There was a trend toward higher cumulative probability of pregnancy in women whose partners were azoospermic versus oligospermic. There was no difference in pregnancy rates obtained with the Percoll wash gradient versus the Isolate gradient. At >20 million total motile sperm per insemination, there was no threshold above which the pregnancy rate was improved. CONCLUSION: The most significant influence on pregnancy rates in the donor sperm insemination program at the University of Florida was maternal age. Nulligravidity and a diagnosis of mild oligospermia in the man may have a negative impact on pregnancy rates.

Adult↗
PubMed1999

Contrast-enhanced ultrasound for guidance of local tumor ablation.

The objective was to assess the efficacy of sonography with and without contrast medium enhancement in guiding and monitoring percutaneous ethanol ablation of tumors in an animal model. VX-2 carcinoma was implanted into the thighs of New Zealand white rabbits and examined by grey-scale ultrasound, color, power, and pulse Doppler, before and after injection of 95% ethanol into the tumors. Injections of ethanol were guided by ultrasound to sites of tumor vascularity, until all tumor vascularity had been obliterated. Microbubble contrast medium or saline was injected i.v. prior to each of the ultrasonic interrogations. Arteriography was performed before and after ablation. Selected tumor samples were submitted for histologic examination. Contrast enhanced tumor vascularity over saline controls in all cases. In some, incompletely ablated foci of tumor could only be identified with contrast medium enhancement. Arteriography showed complete ablation of all but 1 tumor. We conclude that ultrasound enhanced by contrast better shows the presence or absence of tumor vascularity. Ultrasound enhanced by contrast might offer an accurate means of guiding and monitoring percutaneous ethanol injection for tumor ablation.

Albumins↗
PubMed1999

Managing irritable bowel syndrome.

IBS is a functional gastrointestinal disorder in which the patient has chronic or recurrent gastrointestinal symptoms (diarrhea, constipation or abdominal pain and bloating) that are unexplained by any structural or biochemical abnormalities. Research has demonstrated no causal relationship between psychosocial factors and the development of IBS. IBS cannot be diagnosed through radiologic, endoscopic or laboratory studies because the symptoms are not explained by structural or chemical abnormalities. One of the most important components of treatment is the development of an effective provider patient relationship. Behavioral treatments may be helpful in select patients. Dietary management can also reduce symptoms if the patient can identify foods that trigger them.

Adaptation, Psychological↗
PubMed1999

A reexamination of the angiotoxicity of superselective injection of DMSO in the swine rete embolization model.

BACKGROUND AND PURPOSE: There are a variety of embolization applications for non-adhesive, liquid agents. We reevaluated the potential microvascular angiotoxicity of superselective infusions of dimethyl sulfoxide (DMSO) using very long infusion rates in a previously described animal model. METHODS: Twenty-six swine underwent percutaneous femoral puncture for superselective catheterization of the artery of the rete while being continuously monitored for ECG and intraarterial pressure. Two volumes (0.5 or 0.8 mL) and three durations (30, 60, and 90 seconds) of superselective infusion of DMSO were used to evaluate the effect of a single-dose rate within an ipsilateral rete. Contralateral control infusions of normal saline were also administered. Acute hemodynamic and angiographic outcomes were assessed. After recovery, follow-up angiography and sacrifice were performed at either 10 or 28 days. Brains and retia were harvested for gross and microscopic histopathologic evaluation. RESULTS: No significant hemodynamic alterations occurred acutely. Twenty-three of the 24 infused retia showed variable acute vasospasm that typically was mild to moderate in severity and transient (10 to 20 minutes). Follow-up angiography at sacrifice always showed normal retial arterial anatomy. No adverse clinical sequelae were noted. Gross inspection of brains showed no evidence of infarction or subarachnoid hemorrhage. Microscopic histopathologic examination of retia showed mostly nonspecific changes in both exposed and control samples. Possible causal histotoxicity was seen in four retia (three of four exposed to higher dose rates), in which involvement was limited to one to three retial arteries. CONCLUSION: Lower total dose and dose rates of superselective infusion of DMSO into the retial microarterial network resulted in substantially less angiotoxicity than that found in a previous study, as defined by clinical, angiographic, gross, and histopathologic criteria.

Angiography, Digital Subtraction↗
PubMed1998

Development of a capacitive immunosensor: a comparison of monoclonal and polyclonal capture antibodies as the primary layer.

There is widespread interest in capacitance immunosensor systems which directly detect antigen binding to immobilized antibody. Our system comprises an active biolayer of antibodies bound to a silicon--silicon dioxide--silicon nitride (Si-SiO2-Si3N4) surface. As with other groups, our system initially gave poorly reproducible responses on addition of antigen. We mechanically degraded the Si-SiO2-Si3N4 surface, and the responses on addition of transferrin were monitored. The mechanical degradation allowed the affinity reaction to be 'seen' capacitively. Once the system was established, a comparison of capture antibodies was performed to establish the most effective biolayer. Three affinity reactions were examined: (a) 1D2A4, monoclonal antibody (mAb) to human transferrin, as the capture layer; (b) polyclonal goat anti-human transferrin antibody (PcAb) as the capture layer; and (c) 1D2A4 with transferrin (Tf) prebound as the capture layer. There was no response to addition of transferrin where 1D2A4 was the capture layer. Addition of transferrin when the polyclonal antibody was used as the primary layer resulted in a drop in measured capacitance. Addition of goat anti-human transferrin antibody to a device with 1D2A4 plus transferrin as the capture layer also resulted in a measured capacitance decrease. There is a difference in dielectric/blocking effectiveness between the monoclonal and polyclonal antibodies.

Animals↗
PubMed1998

Sertraline treatment of children and adolescents with obsessive-compulsive disorder or depression: pharmacokinetics, tolerability, and efficacy.

OBJECTIVE: To evaluate the pharmacokinetics, safety, and efficacy of sertraline in children (6 to 12 years old) and adolescents (13 to 17 years old). METHOD: Children (n = 29) and adolescents (n = 32) with major depression, obsessive-compulsive disorder (OCD), or both received a single dose of 50 mg of sertraline followed, 1 week later, by 35 days of sertraline treatment as follows: (1) either a starting dose of 25 mg/day titrated to 200 mg/day in 25-mg increments or (2) a starting dose of 50 mg/day titrated to 200 mg/day in 50-mg increments. Sertraline and desmethylsertraline pharmacokinetics were determined approximately weekly, and efficacy measures were assessed before drug administration and at the end of treatment. RESULTS: Mean area under the plasma concentration-time curve (AUC), peak plasma concentration (Cmax), and elimination half-life (t1/2) for sertraline and desmethylsertraline were similar to previously reported adult values. No titration-dependent pharmacokinetic or safety differences were seen. While Cmax and AUC0-24 were greater for children versus adolescents, these differences disappeared after parameters were normalized for body weight. Sertraline was well tolerated in both children and adolescents, with adverse experiences similar to those previously reported by adult patients. Efficacy measurements indicated improvement (p < .001) in depression and OCD symptomatology. CONCLUSIONS: Sertraline can be safely administered to pediatric patients using the currently recommended adult titration schedule.

1-Naphthylamine↗
PubMed1997

Technical feasibility and performance studies of a 0.009-inch nitinol microguidewire for potential neuroendovascular applications.

RATIONALE AND OBJECTIVES: The authors conduct technical feasibility and performance studies on a new 0.009-inch nitinol microguidewire for potential neuroendovascular applications. METHODS: In vivo microcatheterizations of brachiocephalic arteries were performed in four pigs using the 0.009-inch nitinol microguidewire with a commonly used microcatheter and compared with the performance of commercially available microguidewires. Vessels catheterized using the 0.009-inch wire were evaluated by histopathological analysis. A standardized, bench-top method of evaluating basic mechanical properties of microguidewires also was used to compare the 0.009-inch nitinol microguidewire with two commonly used microguidewires. RESULTS: The 0.009-inch microguidewire had similar steerability, tractability, torque control, and distal tip flexibility to the commonly used microguidewires in the in vivo simulations. Bench top testing showed the 0.009-inch microguidewire to have comparable distal tip flexibility and objective mechanical properties to the commonly used microguidewires. CONCLUSIONS: The comparable subjective and objective mechanical properties of the 0.009-inch nitinol microguidewire to that of commonly used microguidewires further establishes the possibility of clinical implementation.

Alloys↗
PubMed1997

Desipramine pharmacokinetics when coadministered with paroxetine or sertraline in extensive metabolizers.

In vitro studies have shown that fluoxetine and paroxetine are more potent inhibitors of cytochrome CYP2D6 than sertraline. The pharmacokinetics of desipramine when coadministered with the selective serotonin reuptake inhibitors (SSRIs) paroxetine and sertraline were studied in 24 healthy male volunteers (CYP2D6 extensive metabolizers). Desipramine (50 mg/day) was administered for 23 days in each phase of the crossover study with a 7-day drug-free period between phases. In addition, subjects were randomly assigned to receive concomitant paroxetine (20 mg/day on days 8 through 17 followed by 30 mg/day on days 18 through 20) or sertraline (50 mg/day on days 8 through 17 and 100 mg/day on days 18 through 20). SSRI treatments were switched between phases. After 10 days of coadministration at the lower dose, mean desipramine maximum concentration in plasma (Cmax) relative to baseline increased from 37.8 to 173 ng/mL (+358%) with paroxetine versus from 36.1 to 51.9 ng/mL (+44%) with sertraline; the mean desipramine 24-hour area under the concentration-time curve (AUC[24]) increased from 634 to 3,305 ng x h/mL (+421%) with paroxetine versus from 611 to 838 ng x h/mL (+37%) with sertraline; and the mean desipramine trough value (C0) increased from 18.5 to 113 ng/mL (+511%) with paroxetine versus from 18.3 to 21.8 ng/mL (+19%) with sertraline (all increases, p < 0.001). An approximately 10-fold increase in the Cmax and AUC(24) of paroxetine and an approximately 2-fold increase in these parameters for sertraline occurred simultaneously with the desipramine concentration changes. Thus, when coadministered with 50 mg/day desipramine, sertraline had significantly less pharmacokinetic interaction than paroxetine with desipramine at the recommended starting dosages of 50 mg/day and 20 mg/day, respectively.

1-Naphthylamine↗
PubMed1997

Sertraline does not inhibit cytochrome P450 3A-mediated drug metabolism in vivo.

The in vivo effect of sertraline on oxidative drug metabolism mediated by cytochrome P450 (CYP) 3A was assessed by coadministration with alprazolam, carbamazepine, and terfenadine in three separate studies. Sertraline at doses of 50 to 200 mg/day for 10 to 20 days did not alter the pharmacokinetics of these CYP3A substrates/drugs.

1-Naphthylamine↗
PubMed1996

Changes in stroke distance in response to haemorrhage in a swine model.

OBJECTIVE: To determine, using an animal model of blood loss, (1) if stroke distance, derived non-invasively from the time integral of the maximum velocity of red cells in the aorta, changed to a greater extent than heart rate and mean arterial pressure (MAP), which are recognised to be unreliable indicators of blood loss; (2) if changes in stroke distance reflected changes in stroke volume derived from thermodilution cardiac output measurements. METHODS: Eight anaesthetised swine had baseline measurements of heart rate, MAP, stroke volume, and stroke distance and were then exsanguinated at a rate of 1 ml/kg/min. Percentage changes from baseline of heart rate, MAP, stroke volume, and stroke distance were compared after 10, 20, and 30 ml/kg blood loss. The animal's blood was then reinfused at the rate of 2 ml/kg/min for 15 min, followed by normal saline 1 ml/kg/min. Percentage changes from baseline measurement of stroke volume and stroke distance over the whole experiment were evaluated by regression analysis. RESULTS: Heart rate, MAP, and stroke distance changed +7.9%, -22.5%, and -18.1% respectively (from baseline values) after 10 ml/kg blood loss; +23.2%, -44.0%, and -47.4% after 20 ml/kg blood loss; and +55.7%, -62.0%, and -69.8% after 30 ml/kg blood loss. Regression analysis of percentage changes in stroke volume and stroke distance from their baseline values at experimental time zero is stroke volume = 1.014 x stroke distance -2.156, r = 0.92, n = 54, P < 0.0001. CONCLUSIONS: (1) At maximal blood loss, stroke distance changes to a greater extent than heart rate and MAP. (2) Changes in stroke distance reflected changes in stroke volume but with less variability at lower values. Stroke distance may be a more useful measure of blood loss than heart rate and MAP.

Animals↗