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Biomedical subjects

J C Price

Publications and source records attributed to J C Price.

At least 55 records · Page 3Linked to original sources

Noise reduction in PET attenuation correction by maximum likelihood histogram sharpening of attenuation images.

UNLABELLED: A new method for PET transmission data processing was developed and found to reduce transmission noise in 18F-FDG cardiac emission images. This method is based on a model that describes the measured attenuation image histogram as some unknown true underlying histogram, blurred by noise. METHODS: Emission data from an elliptical phantom (cardiac insert) and three humans were reconstructed using transmission data of varying duration with varying levels of smoothing. Biases and noise levels (cardiac sector analysis) were evaluated for the phantom (simulated replicates) and human emission images. RESULTS: The estimated attenuation histograms typically displayed three distinct peaks corresponding to air, lung and soft tissue without a priori assumptions of the underlying mu values. This method effectively sharpened the histogram peaks and performed well for the phantom and human data. For intermediate transmission noise levels, biases in the phantom sector values were <4%. The human sector results were more variable but consistent with the phantom results. Noise reduction (approximately 30%) was demonstrated across all smooth levels for the phantom data. CONCLUSION: This histogram sharpening method introduces only small bias in the cardiac sector values while achieving an increase in effective transmission scan time of 50-100%. Alternatively, histogram sharpening permits less transmission data smoothing without increased noise.

Algorithms↗

[The assessment of basement membrane in cancer of the floor of the mouth and larynx].

An immunohistochemical method using a monoclonal antibody to collagen type IV was employed to assess the basement membrane (BM) deposition in 36 cases of cancer of the floor of the mouth and in 32 cases of cancer of the larynx. The BM deposition was scored as extensive or limited, and compared to degree of histologic differentiation of tumor and to 3-year survival rate for patient and regional metastasis. There were 42 cases with extensive and 26 with limited BM deposition between cancer of the floor of the mouth and cancer of the larynx were found. Statistical analysis did not show a relationship between BM deposition of either cancer and the survival of patients or with regional metastasis, however a little better results was obtained for patients with extensive BM deposition. Poorly differentiated carcinoma of the floor of the mouth had a tendency to limited BM deposition.

Antibodies, Monoclonal↗

Advantages of mandibular reconstruction with the titanium hollow screw osseointegrating reconstruction plate (THORP).

Alloplastic reconstruction following segmental mandibulectomy is a simple way to maintain mandibular segmental relationships, partially preserving form and function for many patients. This study is a retrospective review of 40 patients who had mandibular reconstruction with metal plates over a 6-year period (April 1986 through August 1992). The results of reconstruction with titanium hollow-screw osseointegrating reconstruction plates (THORP [n = 12]) and solid screw (SS) steel and titanium plates (n = 28) are compared. One THORP has been removed as compared to 14 SS plates. While the improved results with THORP may be attributable in part to its advanced design, the success of soft-tissue reconstruction and tumor extirpation are important factors in the early outcome seen in this series. Longer follow-up is needed to determine if THORP can serve as a permanent implant. THORP is the authors' method of choice for alloplastic mandibular reconstruction.

Adult↗

Development and evaluation of sustained-release ibuprofen-wax microspheres. II. In vitro dissolution studies.

A modified USP paddle method using minibaskets was used to study the effects of various formulations on in vitro dissolution of ibuprofen microspheres. Formulations containing waxes such as paraffin or ceresine wax without modifiers exhibited very slow dissolution profiles and incomplete release, which did not improve with increased drug loading or the preparation of smaller microspheres. The addition of modifiers such as stearyl alcohol and glyceryl monostearate greatly increased the dissolution rate, with 20% (w/w) near the optimum for predictable dissolution. Higher drug loading and decreased microsphere size increased the dissolution rate from microspheres containing modifier. Optimum formulations contained ceresine wax or microcrystalline wax and stearyl alcohol as a modifier, with a drug content of 17%. An increase in the encapsulation dispersant concentration had little effect on the dissolution profiles. The dissolution data from narrow size fractions of microspheres indicated spherical matrix drug release kinetics; the 50% dissolution time decreased with the square of the microsphere diameter. With appropriate modifiers, wax microsphere formulations of drugs with solubility characteristics similar to those of ibuprofen can offer a starting basis for predictable sustained release dosage forms.

Delayed-Action Preparations↗

SPECT quantification of [123I]iomazenil binding to benzodiazepine receptors in nonhuman primates: I. Kinetic modeling of single bolus experiments.

The aim of this work was to study the feasibility and reproducibility of in vivo measurement of benzodiazepine receptors with single photon emission computerized tomography (SPECT) in the baboon brain. Arterial and brain regional activities were measured for 420 min in three baboons after single bolus injection of the benzodiazepine antagonist [123I]iomazenil. Data were fit to a three-compartment model to derive the regional binding potential (BP), which corresponds to the product of the receptor density, (Bmax) and affinity (1/KD). Regional BP values (from 114 in striatum to 241 in occipital) were in good agreement with values predicted from in vitro studies. Constraining the regional volume of distribution of the nondisplaceable compartment to the value measured during tracer constant infusion experiments in baboons (Laruelle et al., 1993) improved the identifiability of the rate constants. Each experiment was repeated to investigate the reproducibility of the measurement. The regional average reproducibility was 10 +/- 5%, expressed as coefficient of variation (CV). Results of equilibrium analysis at peak uptake were in good agreement with results of kinetic analysis. Empirical counts ratio methods were found to be poorly sensitive to benzodiazepine receptor density. These studies suggest the feasibility of quantitative measurement of benzodiazepine receptors by kinetic analysis of SPECT data and the inadequacy of empirical methods of analysis, such as counts ratios, to evaluate differences in receptor density.

Animals↗

Measurement of benzodiazepine receptor number and affinity in humans using tracer kinetic modeling, positron emission tomography, and [11C]flumazenil.

Kinetic methods were used to obtain regional estimates of benzodiazepine receptor concentration (Bmax) and equilibrium dissociation constant (Kd) from high and low specific activity (SA) [11C]flumazenil ([11C] Ro 15-1788) positron emission tomography studies of five normal volunteers. The high and low SA data were simultaneously fit to linear and nonlinear three-compartment models, respectively. An additional inhibition study (pretreatment with 0.15 mg/kg of flumazenil) was performed on one of the volunteers, which resulted in an average gray matter K1/k2 estimate of 0.68 +/- 0.08 ml/ml (linear three-compartment model, nine brain regions). The free fraction of flumazenil in plasma (f1) was determined for each study (high SA f1: 0.50 +/- 0.03; low SA f1: 0.48 +/- 0.05). The free fraction in brain (f2) was calculated using the inhibition K1/k2 ratio and each volunteer's mean f1 value (f2 across volunteers = 0.72 +/- 0.03 ml/ml). Three methods (Methods I-III) were examined. Method I determined five kinetic parameters simultaneously [K1, k2, k3 (= konf2Bmax), k4, and konf2/SA] with no priori constraints. An average kon value of 0.030 +/- 0.003 nM-1 min-1 was estimated for receptor-rich regions using Method I. In Methods II and III, the konf2/SA parameter was specifically constrained using the Method I value of kon and the volunteer's values of f2 and low SA (Ci/mumol). Four parameters were determined simultaneously using Method II. In Method III, K1/k2 was fixed to the inhibition value and only three parameters were estimated. Method I provided the most variable results and convergence problems for regions with low receptor binding. Method II provided results that were less variable but very similar to the Method I results, without convergence problems. However, the K1/k2 ratios obtained by Method II ranged from 1.07 in the occipital cortex to 0.61 in the thalamus. Fixing the K1/k2 ratio in Method III provided a method that was physiologically consistent with the fixed value of f2 and resulted in parameters with considerably lower variability. The average Bmax values obtained using Method III were 100 +/- 25 nM in the occipital cortex, 64 +/- 18 nM in the cerebellum, and 38 +/- 5.5 nM in the thalamus; the average Kd was 8.9 +/- 1.0 nM (five brain regions).

Adult↗

Complications and early outcome of anterior craniofacial resection.

OBJECTIVE: To evaluate the complications of anterior craniofacial resection and correlate their impact with tumor control status. DESIGN: We conducted a retrospective review of 32 consecutive, operable patients' records seen over a 6-year period, requiring 35 procedures. SETTING: Academic tertiary referral medical center. PARTICIPANTS: Twenty-six patients (81%) had malignant lesions (esthesioneuroblastoma, squamous cell carcinoma, and a group of miscellaneous malignant tumors). Six patients had various benign neoplasms. INTERVENTION: The surgical approach involved bifrontal craniotomy coupled with lateral rhinotomy in 19 cases (61%), facial degloving in 10 cases (32%), a total rhinectomy in one case, and endoscopic sinusectomy without facial incision in two cases. OUTCOME MEASURE: Clinically noted complications and oncologic outcome. RESULTS: There was one avoidable perioperative death indirectly associated with the patient's procedure. Nine patients suffered significant intracranial neurological complications such as tension pneumocephalus and delayed epidural abscess. All of these complications were managed successfully. Of patients with malignant tumors, 13 (52%) are alive with no evidence of disease and one is alive with recurrence after a mean follow-up period of 28.9 months. The 10 patients who succumbed to disease had a mean postoperative survival of 22.9 months. CONCLUSIONS: In contrast to the perspective of only a decade ago, we conclude that craniofacial resection is a relatively safe, versatile, and effective procedure for surgical management of tumors involving the anterior skull base.

Adult↗

Pharmacokinetics of progesterone in ovariectomized rats after single dose intravenous administration.

The pharmacokinetics of progesterone were characterized in ovariectomized female rats. Progesterone was administered intravenously at a dose of 500 micrograms kg-1. Serum progesterone concentrations were determined by radioimmunoassay. Serum concentrations of progesterone were best described by a two-compartment model with elimination from the central compartment. The distribution and elimination phase half-lives were 0.13 +/- 0.024 (mean +/- SD) and 1.21 +/- 0.21 h, respectively. Elimination of the steroid was rapid with a total clearance of 2.75 +/- 0.42 l h-1 kg-1. Progesterone was widely distributed in the rat with a steady state volume of distribution of 2.36 +/- 0.23 l kg-1, a volume of the central compartment of 0.86 +/- 0.24 l kg-1 and a volume of the peripheral compartment of 1.50 +/- 0.19 l kg-1. The results of this study suggest that the ovariectomized female rat is a suitable animal model for examining the pharmacokinetics of progesterone.

Animals↗

Iodine-125 seed implantation as an adjunct to surgery in advanced recurrent squamous cell cancer of the head and neck.

Survival for extensive recurrent squamous cell carcinomas of the head and neck remains poor, with the major cause of death being local recurrence. Surgical implantation of iodine-125 interstitial seeds allows tumoricidal doses of radiation to be delivered to residual tumor while minimizing radiation doses to the surrounding tissues. From 1978 to 1988, 39 implantations were performed on 35 patients for extensive recurrent squamous cell carcinoma of the head and neck. The decision for implantation was based on positive margins or close to resection margins from frozen sections after salvage resection. The determinate 5-year disease-free survival was 41%, with both the overall and no evidence of disease 5-year survivals being 29%. Significant complications occurred in 36% of all cases. This figure increased to 56% when flap reconstruction was required. Possible reasons for this seemingly high complication rate are discussed. Considering the advanced nature of these recurrent carcinomas, surgical resection with iodine-125 seed implantation appears to be an effective method of managing disease that might otherwise be judged unresectable and treated for palliation only.

Actuarial Analysis↗

Effect of drug loading and molecular weight of cellulose acetate propionate on the release characteristics of theophylline microspheres.

Microspheres with 40, 50, and 60% drug loading of anhydrous theophylline core material were prepared by the emulsion-solvent evaporation method. Three different molecular weights of cellulose acetate propionate were used as encapsulating polymers. The geometric mean diameter of the microspheres increased with drug loading for all polymers. Dissolution rate for a given particle size fraction also increased with drug loading for all polymers. Higuchi/Baker-Lonsdale spherical matrix dissolution kinetics were followed by narrow particle size fractions of the microspheres. A linear relationship between the T-50% (time required for 50% of the drug to be released) and the square of microsphere diameter was observed with all three molecular weights of the encapsulants. The slowest drug release was obtained with the high molecular weight polymer, which also produced the smoothest microspheres.

Capsules↗

Development and evaluation of sustained-release ibuprofen-wax microspheres. I. Effect of formulation variables on physical characteristics.

A congealable disperse phase encapsulation method was used to prepare sustained-release ibuprofen-wax microspheres. Microspheres prepared with paraffin wax, such as ceresine and microcrystalline waxes, using polyvinylpyrrolidone (PVP) as dispersant had a tendency to aggregate, but the addition of wax modifiers (stearyl alcohol and glyceryl monostearate) greatly reduced aggregation. Optimum modifier and dispersant concentrations were 20% (w/w) and 5% (w/v), respectively. The particle size distribution of the microspheres was log-normal. An increase in modifier, dispersant concentration, emulsification stirring speed, or temperature shifted the size distribution toward finer particles. Microcrystalline wax required a higher emulsification temperature and produced finer particles than ozokerite wax. The recovery of drug from the different microsphere formulations varied between 71 and 92%. Differential scanning calorimetry (DSC) of the single components and physical mixtures showed endothermic peaks at the respective melting-point ranges. The DSC of the ceresine and microcrystalline wax microspheres was similar to rescans of ternary mixtures of components of the microspheres with less prominent and lower melting temperatures than individual components or physical mixtures.

Delayed-Action Preparations↗

Effect of moisture content on compression properties of two dextrose-based directly compressible diluents.

Moisture sorption characteristics and the effect of moisture content on the compression properties of two dextrose-based directly compressible diluents, namely, Emdex (diluent A) and Sweetrex (diluent B) were studied. Both diluents sorbed moisture rapidly at relative humidities greater than 60%. For both the diluents, pressures required to compress tablets to the same relative density decreased with increasing moisture content. Yield pressures calculated from linear Heckel plots obtained from the compression data of both diluents reflected decreasing values with increasing moisture content. Three-way surface profile graphs of moisture content versus tablet parameters such as crushing force, relative density, and compression pressure give a unique overall picture of the compression properties of a diluent and offer the tablet formulator a useful tool for diluent comparison.

Chemical Phenomena↗

Quantification of human opiate receptor concentration and affinity using high and low specific activity [11C]diprenorphine and positron emission tomography.

[11C]Diprenorphine, a weak partial opiate agonist, and positron emission tomography were used to obtain noninvasive regional estimates of opiate receptor concentration (Bmax) and affinity (Kd) in human brain. Different compartmental models and fitting strategies were compared statistically to establish the most reliable method of parameter estimation. Paired studies were performed in six normal subjects using high (769-5,920 Ci/mmol) and low (27-80 Ci/mmol) specific activity (SA) [11C]diprenorphine. Two subjects were studied a third time using high SA [11C]diprenorphine after a pretreatment with 1-1.5 mg/kg of the opiate antagonist naloxone. After the plasma radioactivity was corrected for metabolites, the brain data were analyzed using a three-compartment model and nonlinear least-squares curve fitting. Linear differential equations were used to describe the high SA (low receptor occupancy) kinetics. The k3/k4 ratio varied from 1.0 +/- 0.2 (occipital cortex) to 8.6 +/- 1.6 (thalamus). Nonlinear differential equations were used to describe the low SA (high receptor occupancy) kinetics and the curve fits provided the konf2 product. The measured free fraction of [11C]diprenorphine in plasma (f1) was 0.30 +/- 0.03, the average K1/k2 ratio from the two naloxone studies was 1.1 +/- 0.2, and the calculated free fraction of [11C]diprenorphine in the brain (f2) was 0.3. Using the paired SA studies, the estimated kinetic parameters, and f2, separate estimates of Bmax and Kd were obtained. Bmax varied from 2.3 +/- 0.5 (occipital cortex) to 20.6 +/- 7.3 (cingulate cortex) nM. The average Kd (eight brain regions) was 0.85 +/- 0.17 nM.

Adult↗

Effect of aspartame-derived phenylalanine on neutral amino acid uptake in human brain: a positron emission tomography study.

The possible effects of elevation of the plasma phenylalanine level secondary to the ingestion of aspartame on brain amino acid uptake in human subjects have been investigated by means of positron emission tomography (PET). 1-[11C]Aminocyclohexanecarboxylate [( 11C]ACHC) is a poorly metabolized synthetic amino acid that crosses the blood-brain barrier by the same carrier that transports naturally occurring large neutral amino acids. Quantitative test-retest PET studies were performed on 15 individuals. Seven received two identical baseline scans, whereas eight received a baseline scan followed by a scan performed approximately 40-45 min following ingestion of an orange-flavored beverage containing 34 mg/kg of body weight of the low-calorie sweetener aspartame, a dose equivalent to the amount in 5 L of diet soft drink consumed all at once by the study subjects, weighing an average of 76 kg. The 40-45-min interval was selected to maximize the detection of possible decreases in ACHC uptake resulting from increased competition for the carrier, because the plasma phenylalanine level is known to peak at this time. We observed an 11.5% decrease in the amino acid transport rate constant K1 and a smaller decrease in the tissue distribution volume of ACHC (6%). Under conditions of normal dietary use, aspartame is thus unlikely to cause changes in brain amino acid uptake that are measurable by PET.

Amino Acids↗