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Education ?

Medical School Score Rankings
University of North Carolina (1991)
Top 25%

Awards & Distinctions ?

American Board of Internal Medicine

Publications & Research

Dr. Naylor has contributed to 11 publications.
Title Reduction of Amputation Rates Among Alaska Natives with Diabetes Following the Development of a High-risk Foot Program.
Date March 2005
Journal International Journal of Circumpolar Health

OBJECTIVE: The prevalence of diabetes is increasing rapidly among Alaska's Indian, Eskimo and Aleut populations. Approximately half the Native people with diabetes have no road access to hospitals or physicians, presenting a challenge in the attempt to prevent lower extremity amputation as a complication. In late 1998 funding became available for diabetes prevention and treatment among Native Americans. The tribal health corporations in Alaska decided to use a portion of this funding to implement a high-risk foot program to decrease the amputation rate. PROGRAM DESIGN: The program initially involved a surgical podiatrist who provided training to local staff and performed preventive and reconstructive surgery on several patients with impending amputations. The program then provided training for a physical therapist to become a certified pedorthist. This individual established the long-term maintenance phase of the program by conducting diabetic foot clinics routinely at the Alaska Native Medical Center, a referral center in Anchorage. He also travels to other regions of the state to provide training for village and hospital-based health care providers and to conduct field clinics. A system was established in a common database management program to track the patients' foot conditions. Patient education is emphasized. RESULTS: The overall amputation incidence among all Alaska Native patients with diabetes decreased from 7.6/1,000 in the pre-program period (1996 to 1998) to 2.7/1,000 in the post-program period (1999-2001) (p<.001). The rate among Aleuts, who previously had the highest amputation incidence, decreased from 17.4/1,000 to 3.1/1,000 over the same time periods (p<.001). Among people who had had diabetes at least 10 years, the overall amputation incidence decreased from 16.4/1,000 to 6.8/1,000 (p=.021); among Aleuts the rate fell from 24.5/1,000 to 2.6/1,000 (p=.01). CONCLUSIONS: Though longer follow-up is needed, these data suggest that even in populations living in isolated regions, diabetic amputations can be prevented by a coordinated system to identify high-risk feet and provide preventive treatment and education in the context of a comprehensive diabetes management program in an integrated health system.

Title Diabetes Among Alaska Natives: a Review.
Date March 2004
Journal International Journal of Circumpolar Health

This review summarizes the published information on diabetes mellitus and gestational diabetes among Alaska Natives. The most recently published age-adjusted prevalence was 28.3/1000 in 1998. There is evidence of a steadily increasing prevalence, documented both by cross sectional screening studies and patient registry methods. The overall incidence rates in 1986-1998 of lower extremity amputation (6.1/1000) and renal replacement therapy (2.1/1000) appear to be lower than those in other Native American populations in the United States. Incidence of stroke and MI in 1986-1998 varied widely by ethnic group and gender with Eskimo women having the highest rate of stroke (19.6/1000), and Aleut men the highest rate of MI (14/1000). The overall mortality among diabetic Alaska Native people in 1986-1993 (43.2/1000) was somewhat lower than that in other US diabetic populations, with heart disease being the most common cause of death. A high rate of gestational diabetes (6.7%) was reported in one region in 1987-88, but this appeared to decline following nutritional education intervention. In screening studies, the prevalence of abnormal glucose tolerance has been found to be positively associated with body mass index and negatively associated with daily seal oil or salmon consumption and higher levels of physical activity. Observations on the prevalence and relationships among other factors in the insulin resistance syndrome are summarized. Suggestions for prevention of diabetes and further studies are presented.

Title The Inhalation Toxicology, Genetic Toxicology, and Metabolism of Difluoromethane in the Rat.
Date March 1997
Journal Fundamental and Applied Toxicology : Official Journal of the Society of Toxicology

Difluoromethane (HFC32) is under development as a replacement for chlorofluorocarbons (CFCs) in some refrigeration applications. It has been evaluated by standard studies of toxicity, developmental toxicity, and genotoxicity. In addition, the metabolism and disposition of HFC32 was investigated and a physiologically based pharmacokinetic (PB-PK) model constructed. Inhalation of HFC32 (up to 50,000 ppm) caused no organ-specific effects, but resulted in slight maternal toxicity to the pregnant rat and rabbit and some fetotoxicity to the rat. HFC32 did not sensitize the heart to adrenaline. The pharmacokinetics of [14C]difluoromethane (10,000 to 50,000 ppm/6 hr) revealed that about 2.1% of the inhaled HFC32 was absorbed and that steady state blood levels were achieved within 2 hr and were proportional to dose. Carbon dioxide was the major metabolite of HFC32 at all exposure levels. Carbon monoxide was not detected. The in vivo data were used to validate a PB-PK model to describe the uptake and metabolism of HFC32. Absorption and distribution are adequately described using rat blood:air and tissue:air partition coefficients. Metabolism, which was linear across the dose range, was described by a first order rate constant (Kf = 8.98 hr-1). Of the absorbed HFC32, about 63% was metabolized at all doses; however, when metabolism was expressed as a percentage of the inhaled dose it was much lower, being about 1.4% of the HFC32 entering the airways. Overall, the results indicate that HFC32 is of very low toxicity and should be an acceptable alternative to CFCs.

Title Metabolism and Disposition of Difluoromethane (hfc32) in the Mouse.
Date December 1996
Journal Human & Experimental Toxicology

1. Difluoromethane (HFC32) is under development as a replacement for chlorofluorocarbons (CFCs) in some refrigeration applications. 2. The metabolism and disposition of [14C]-difluoromethane ([14C]-HFC32) was determined in male Swiss mice as a consequence of a single 6 h inhalation exposure to atmospheres of 10 000 p.p.m. 3. Of the inhaled dose, about 1-2% was recovered in expired air, urine, faeces and carcass suggesting that systemic absorption of this hydrofluorocarbon from the alveolar air space of the lung into blood is poor. Upon cessation of exposure the majority of the systemically absorbed HFC32 was exhaled within 1 h. 4. Carbon dioxide was a major metabolite of HFC32. Carbon dioxide measured post-exposure accounted for about 0.3% of the inhaled dose. Urinary and faecal excretion of non-volatile metabolites accounted for about 0.34% and 0.07% of the inhaled dose, respectively. 5. Carbon monoxide could not be detected. 6. Total metabolism, measured as the sum of the radioactivity recovered in urine, faeces, as carbon dioxide and that retained in the carcass, amounted to about 0.8% of the inhaled dose, equivalent to 64% of the total radioactivity recovered. 7. Analysis of a range of tissues at 4 days post-exposure showed a relatively uniform distribution of radioactivity with the highest concentration in the lung, liver and kidney. There was no evidence of a specific retention in any organ or tissue.

Title Further Evidence That the Blood/brain Barrier Impedes Paraquat Entry into the Brain.
Date December 1995
Journal Human & Experimental Toxicology

The distribution of the non-selective herbicide paraquat was examined in the brain following subcutaneous administration of 20 mg kg-1 paraquat ion containing [14C]paraquat to male adult rats in order to determine whether paraquat crosses the blood/brain barrier. Following administration, [14C]paraquat reached a maximal concentration in the brain (0.05% of administered dose) within the first hour and then rapidly disappeared from the brain. However, 24 h after administration of the herbicide, about 13% of the maximal recorded concentration of paraquat remained in the brain (1.6 nmol g-1 wet weight) and could not be removed by intracardiac perfusion. Using measurements of [14C]paraquat in dissected brain regions and using quantitative autoradiography we demonstrated an asymmetrical distribution in and around the brain at 30 min (maximal concentration) and 24 h after administration. Most of the paraquat was associated with five structures, two of which, the pineal gland and linings of the cerebral ventricles lie outside the blood/brain barrier whilst the remaining three brain areas, the anterior portion of the olfactory bulb, hypothalamus and area postrema do not have a blood/brain barrier. Overall, the distribution of [14C]paraquat in the brain 24 h after systemic administration was highly correlated to the blood volume. These data indicate that any remaining paraquat in the brain 24 h after systemic administration is associated with elements of the cerebro-circulatory system, such as the endothelial cells that make up the capillary network and that there is a limited entry of paraquat into brain regions without a blood/brain barrier.(ABSTRACT TRUNCATED AT 250 WORDS)

Title Identification and Quantification of Fluorine-containing Metabolites of 1-chloro-2,2,2-trifluoroethane (hcfc133a) in the Rat by 19f-nmr Spectroscopy.
Date May 1995
Journal Drug Metabolism and Disposition: the Biological Fate of Chemicals

1-Chloro-2,2,2-trifluorethane (HCFC133a) causes a reduction in testis weight and germinal epithelial cell atrophy in the rat following exposure by inhalation at concentrations of 10,000 ppm and above. Following administration by gavage, an increased incidence of Leydig cell tumors of the testis was seen. The metabolism of HCFC133a has been investigated in respect to the known toxicity of this compound. Male rats were exposed by inhalation to an atmosphere of 50,000 ppm HCFC133a for a period of 6 hr. Analysis of urine, collected during the exposure period and up to 48 hr following exposure, by 19F-NMR spectroscopy identified 2,2,2-trifluoroethanol (TFE; and its beta-glucuronide), trifluoroacetaldehyde (TFAA; as its hydrate and urea adduct), and trifluoroacetic acid (TFA) as fluorine-containing metabolites of HCFC133a. Of the total amount of metabolite eliminated in urine, 83% was excreted within 24 hr postdose, establishing a rapid elimination of metabolites by this route. TFAA, an established testicular toxicant, was the major metabolite accounting for 57% of the total fluorinated metabolites eliminated in urine, whereas TFA and TFE accounted for 29% and 14%, respectively. The presence of these metabolites in urine is consistent with an oxidative route of metabolism of this fluorocarbon.

Title Interrelationships Between the Chemical Structure of Synthetic Entities, Their Platelet Aggregation Inhibitory Potency and Their Cellular Toxicity, Based on in Vitro Experiments.
Date February 1987
Journal Medical Progress Through Technology

Striking relationships were observed, in vitro, between the molecular constitution of synthetic entities, their aggregation-inhibitory potency (as determined in ADP-induced human blood platelet aggregation), and their cellular toxicity (as assessed by their inhibition of cultured mouse fibroblast L-cell growth). Effects exerted on platelets tended to reflect interactions between the molecules' aggregation-inhibitory specific functions and the platelets' corresponding target sites, while fibroblasts were generally more susceptible to the molecular constitution's hydrophobic character. The hyperbolic relationships between concentrations effecting 50% inhibition and slopes of concentration-response curves reflect net activity from both specific and nonspecific receptor site interactions, with the latter being dominant, and indicated that the assays approximated equilibrium systems. Plotting logarithm values of concentrations effecting 50% inhibition against logarithms of reciprocal slopes for concentration response curves yielded multiple regression coefficients of R = 0.97 (platelet aggregation-inhibitory potency) and R = 0.98 (fibroblast growth-inhibitory potency).

Title Relationships Between the Chemical Constitution of Aggregation Inhibitors and Human Blood Platelet Response Profile.
Date June 1984
Journal Biochimica Et Biophysica Acta

Gradually altered synthetic entities were employed as molecular probes, and arachidonic acid, ADP, human alpha-thrombin and the Ca2+ ionophore A23187 as aggregation-inducing agents, in a comprehensive study on the response profile of human blood platelets with an emphasis on the effects of exogenous and increased intracellular Ca2+. Corroborating further previous conclusions, some representative carbamoylpiperidine derivatives, at concentrations effecting substantial inhibition of ADP-induced aggregation, failed to retain that effect when 5.0 mM Ca2+ was introduced into the otherwise identical test medium; reference compounds chlorpromazine and propranolol registered corresponding inhibitory patterns. At increased concentrations the compounds' inhibitory potency was regenerated even in the presence of 5 mM Ca2+. In fact, in sufficiently high concentrations, the compounds were even capable of inhibiting aggregation elicited by 15 microM of the ionophore A23187; so did chlorpromazine and propranolol. Another set of congeners revealed the striking sensitivity of ionophore A23187-induced human blood platelet aggregation to the surface active potencies of inhibitor molecules. The loss in inhibitory potency was directly related to the lesser hydrophobic character of the molecule.

Title Relative Concentrations of Individual Nonsulfated Bile Acids in the Serum and Bile of Patients with Cirrhosis.
Date December 1977
Journal The American Journal of Digestive Diseases

The relative concentrations of individual nonsulfated bile acids were determined in samples of serum and bile obtained simultaneously from 16 patients with biopsy-proven alcoholic cirrhosis. A highly significant (P less than 0.001) correlation was found between the fasting relative concentrations of each of the three major bile acids (cholic, chenodeoxycholic, and deoxycholic) in serum and bile. This relationship persisted after manipulation of bile acid pools produced by feeding of individual bile acids. We conclude that the relative concentrations of individual nonsulfated bile acids in serum accurately reflect those in bile and that measurement of individual serum bile acids may be used for screening and serial determination purposes. In particular, low levels of biliary deoxycholate can be reliably predicted by serum measurements.

Title Biliary Deoxycholate in Patients with Alcoholic Cirrhosis.
Date December 1974
Journal Gastroenterology
Title Gas Chromatograph-minicomputer System. Design and Application to Biomedical Problems.
Date January 1974
Journal Analytical Chemistry

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