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Biomedical subjects

M S McCracken

Publications and source records attributed to M S McCracken.

13 recordsLinked to original sources

The effect of the addition of a polyglutamate motif to RGD on peptide tethering to hydroxyapatite and the promotion of mesenchymal stem cell adhesion.

Mimicking endogenous bone-binding proteins, RGD peptides have been synthesized with polyacidic amino acid domains in order to ionically tether the peptides to bone-like synthetic biomaterials, including hydroxyapatite (HA). However, a direct comparison of unmodified RGD with polyacidic-conjugated RGD has not been performed, and thus a benefit for the acidic domain has not been established. We evaluated the peptide/HA bond of RGD peptides with and without an attached polyglutamate sequence (E(7)), as well as examined mesenchymal stem cell (MSC) adhesion and morphology as they were affected by the conjugated peptide. We found that significantly more E(7)RGD was bound to HA than RGD at all coating concentrations tested, and moreover, more E(7)RGD was retained on the HA surface even after extended washing in serum-free media. Consistent with in vitro results, higher levels of E(7)RGD than RGD remained on HA that had been implanted in vivo for 24 h, indicating that the polyacidic domain improved peptide-binding efficiency. At several peptide concentrations, E(7)RGD increased cell adhesion compared to RGD surfaces, establishing a biological benefit for the E(7) modification. In addition, HA pre-coated sequentially with low-density E(7)RGD (1-10 microg/ml) and serum (FBS) stimulated cell adhesion and spreading, compared to either coating alone, suggesting that an ionic linkage allows for the potential adsorption of serum proteins to unoccupied sites, which may be important for bone formation in vivo. Collectively, these results suggest that tethering peptides to HA via a polyglutamate domain is an effective method for improving the peptide/HA bond, as well as for enhancing MSC adhesion.

Adolescent↗

The additive effect of latanoprost to maximum-tolerated medications with low-dose, high-dose, or no pilocarpine therapy.

OBJECTIVE: To assess the efficacy of latanoprost additive therapy in patients with intraocular pressure (IOP) out of control while taking maximum-tolerated medications and to determine whether pilocarpine therapy has a dose-dependent adverse effect on the efficacy of latanoprost therapy. DESIGN: Noncomparative case series. PARTICIPANTS: Sixty-one eyes of 61 patients with chronic glaucoma with IOP out of control while receiving maximum-tolerated medications were treated with latanoprost additive therapy on a compassionate basis. MAIN OUTCOME MEASURES: Follow-up was up to 22 months with a mean of 13.9 +/- 5.7 months. Kaplan-Meier survival analysis with Mantel-Cox log-rank test was performed to determine the overall success of latanoprost additive therapy and to compare the success rates of high-dose pilocarpine, low-dose pilocarpine, and no pilocarpine therapies. The criterion for success was avoiding glaucoma surgery with IOP decrease of 20% or greater and final IOP less than 22 mmHg. The IOP change and its significance for patients satisfying and failing the criterion for success also were determined to assess the latanoprost additive therapy. In addition, a number of pretreatment variables, including pilocarpine therapy, were analyzed for a significant effect on the efficacy of latanoprost additive therapy using Cox proportional hazards regression analysis. RESULTS: Latanoprost additive therapy significantly lowered mean IOP by 3.9 +/- 5.5 mmHg at 3 months and by 3.5 +/- 5.8 mmHg at 12 months. The cumulative success rate of the latanoprost additive therapy was 70% at 1 month, 42% at 3 months, 40% at 6 months, and 30% at 12 months. Of the variables studied, only increased number of previous incisional glaucoma surgeries and IOP greater than 24 mmHg before latanoprost additive therapy were significant prognostic factors for failure of latanoprost additive therapy. Pilocarpine therapy in any dose had no significant effect. CONCLUSION: This study supports a trial of latanoprost additive therapy before glaucoma surgery in patients with IOP out of control while receiving maximum-tolerated medications irrespective of pilocarpine therapy and the pilocarpine dosage, especially when the number of previous incisional glaucoma surgery is less than three and the IOP is less than 25 mmHg.

Adult↗

Tooth structure loss apical to preparations for fixed partial dentures when using self-limiting burs.

STATEMENT OF PROBLEM: Burs with guide pins may be used to limit the depth of tooth preparation for fixed partial dentures. The effects of guide pins on tooth structure apical to the finish line after tooth preparation for fixed partial dentures has not been recorded. PURPOSE: This in vitro study recorded loss of tooth structure within 1.0 mm apical to the finish line of teeth prepared with straight cylinder and tapered cylinder self-limiting burs and one conventional bur. MATERIAL AND METHODS: Forty-five extracted human teeth were randomly divided into three groups. The facial surface of each tooth was prepared with two types of diamond burs with guide pins and a conventional diamond for the control. The surface was profiled before and after tooth preparation. Profiled surfaces were analyzed and the groups were compared using analysis of variance and the Tukey-Kramer HSD test (alpha = 0.05). RESULTS: No significant difference was recorded between the control group and the group prepared with a round-ended tapered cylinder self-limiting pin. However, there was a statistically significant difference between the control and cylindrical pin groups, and between the two groups prepared with self-limiting diamonds. CONCLUSION: This study revealed abrasion apical to the finish line of the preparation in all groups. The cylindrical guide pin group exhibited the greatest loss of tooth surface.

Analysis of Variance↗

Demineralization effects of 10 percent carbamide peroxide.

OBJECTIVES: The purpose of this in vitro study was to measure the amount of calcium lost from enamel exposed to a 10% carbamide peroxide solution. METHODS: Nine teeth (3 incisors, 2 premolars, 4 molars) were sectioned to serve as paired test and control specimens. Each tooth half was coated with wax, leaving a uniform 3 mm x 4 mm window of exposed enamel. Test specimens were placed in culture tubes with 1.00 ml of deionized water and 0.02 ml of 10% carbamide peroxide for 6 h; controls were exposed to water alone. Calcium concentrations in the solutions were measured using a Perkin-Elmer 5100 atomic absorption spectrophotometer. RESULTS: Teeth exposed to carbamide peroxide lost an average of 1.06 micrograms/mm2 of calcium. This amount of loss was significantly greater than controls (p < 0.001), according to ANOVA. For comparison, teeth were exposed to a cola beverage for 2.5 min, the time equivalent of drinking a 16 oz. beverage. The amount of calcium lost from these teeth was also about 1 microgram/mm2. CONCLUSIONS: Teeth exposed to 10% carbamide peroxide lost calcium. However, the amount of loss was small, and may not be clinically significant.

Analysis of Variance↗

The reporting of statistical techniques in otolaryngology journals.

The domain of this study is the reporting of statistical analyses in the otolaryngology literature during 1983 and 1984. Fewer than ten basic statistical procedures accounted for more than 90% of the statistical techniques reported. Implications for authors, journals, and educators are discussed. We offer suggestions for imparting statistical skills that may be helpful in curriculum design, residency training, and continuing medical education planning.

Humans↗

Sizing of a vesicle drug formulation by quasi-elastic light scattering and comparison with electron microscopy and ultracentrifugation.

Quasi-elastic light scattering has been used for the sizing of a vesicle formulation. Porcine insulin was encapsulated in a vesicle preparation containing cholesterol, dipalmitoylphosphotidylcholine, digalactosyl digycerides, and dipalmitoylphosphotidylglycerol in a 40:40:15:5 ratio. The measurement requires less than 15 min to obtain mean size and distribution information and can be operated in a quality control environment. Advantages and limitations of quasi-elastic light scattering are described and this method is compared to electron microscopy and ultracentrifugation.

Chemistry, Pharmaceutical↗

Development of a short-term model of decalin inhalation nephrotoxicity in the male rat.

Fischer 344 male rats and C57BL/6 male mice were exposed 'continuously' (22 hr/day, 7 days/wk) for 20, 28 or 35 days to a model compound, decalin, at 0, 25, 62.5 or 125 ppm. Fischer 344 female rats were exposed 'continuously' to decalin at 0 or 125 ppm for 28 days. No histopathological changes were observed in selected organs of female rats or male mice exposed to up to 125 ppm decalin for 28 or 35 days, respectively. However, kidney lesions were observed in all three test groups of male rats after 20, 28 and 35 days' exposure. The nephrotoxicity was characterized by the formation of hyaline droplets in the cytoplasm of proximal convoluted tubule epithelial cells, by the presence of granular casts at the outer zone of the medulla, and by chronic nephrosis. These changes were time and dose dependent and were identical to the renal toxicity that has been reported to occur in male rats following 90 days of continuous exposure to decalin by inhalation. No histopathological effects were observed in the heart, liver, lung or nasal turbinates of male rats. Our results indicate a sex and species specificity for the kidney toxicity. This leads to questions with regard to the appropriateness of using the male rat to assess the potential inhalation toxicity of volatile hydrocarbons. By producing nephrotoxicity in less than 90 days, decalin may now be used to examine, in a well-defined manner, the effect on nephrotoxicity of variables such as dose, exposure regimen, sex, species, and route of exposure. Data from these studies can be used to ascertain whether or not the male rat is an appropriate test animal for predicting potential human nephrotoxic responses to volatile chemicals such as perfumes and perfume raw materials.

Administration, Inhalation↗

Morphogenesis of decalin-induced renal alterations in the male rat.

Adult male Fischer 344 rats were killed after 5, 12, 19 or 31 days' 'occupational' (6 hr/day, 5 days/wk), 'semi-continuous' (22 hr/day, 5 days/wk) or 'continuous' (22 hr/day, 7 days/wk) exposure to 125 ppm decalin vapour. Control rats were exposed to filtered air. Kidney sections were evaluated to determine the nature and time-course of development of decalin-induced lesions. The development of renal lesions was characterized by a specific sequence of light microscopically evident alterations. The extent of the alterations was dependent on time and exposure regimen. Severe exacerbation of the spontaneous protein accumulation (hyaline droplets) routinely observed in the kidneys of control male rats was present in kidneys of all decalin-exposed animals at day 5, and was considered to be the primary morphological alteration associated with decalin exposure. The following sequelae of the hyaline droplet response were observed: the variable occurrence of light microscopically evident proximal convoluted tubule (PCT) epithelial cell degeneration/necrosis, presumably a reflection of cellular injury associated with excessive protein accumulation; the occurrence of granular casts at the junction of the inner and outer bands of the outer zone of the medulla secondary to PCT epithelial cell injury; chronic nephrosis, occurring secondary to tubular obstruction by granular casts. This triad of lesions (hyaline droplet accumulation, granular cast formation and chronic nephrosis) lends specificity to the decalin response and establishes a potential mechanistic relationship with other chemicals that induce these effects.

Administration, Inhalation↗

Determination of total and encapsulated insulin in a vesicle formulation.

A method for the determination of the amount of insulin in a vesicle formulation was developed. Samples were treated with anion exchange resin to quantitatively remove the insulin outside the vesicle walls. Encapsulated insulin was released from vesicles by disruption with a surfactant and the amount released was determined by reversed-phase HPLC. Recovery of insulin from the vesicle matrix was 99, 97, and 98% for vesicle solutions spiked with 1.0, 0.5, and 0.2 U/mL of insulin, respectively. The sample preparation steps resulted in removal of greater than 99.5% of the unencapsulated insulin; 98% recovery of the vesicles from the resin; 97% recovery of the encapsulated insulin from the resin; and greater than 99% disruption of the vesicles by the surfactant. Precision of the measurements for the amounts of total and encapsulated insulin was 2.7 and 3.3% relative standard deviations, respectively, for insulin levels of 0.7 U/mL.

Animals↗

High-performance liquid chromatographic determination of lipids in vesicles.

Accurate quantitation of the four lipid components in a vesicle formulation has been accomplished by selectively changing the high-performance liquid chromatographic mobile phase composition to arrive at an optimal separation requiring less than 10 min. A systematic approach to selection of the mobile phase conditions has minimized the number of experiments required to achieve the necessary separation. Relative standard deviations between one and four percent are obtained for the four lipid components. Accuracy, as measured by recovery experiments for spiked vesicle formulations, varies between one and two percent of target levels at the nominal lipid concentrations investigated.

Cholesterol↗

A technique for monitoring respiratory responses in guinea pigs.

A piezoelectric crystal was used to detect respiration rates and pulmonary retractions of guinea pigs in response to intratracheal administration of histamine. Voltage output from the crystal was displayed on a recorder for visual processing and interfaced to a microcomputer for automatic data processing. Using intratracheal instillation of histamine, this system accurately reproduced the visual observations of respiratory responses in guinea pigs.

Animals↗