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R J Anderson

Publications and source records attributed to R J Anderson.

At least 37 records · Page 2Linked to original sources
PubMed2001

Potential transition state phosphoramidate inhibitors of beta-tubulin as antifilarial agents.

Transition state phosphoramidate inhibitors of beta-tubulin were designed as potential antifilarial agents. The reaction of 2-aminobenzimidazole with diisopropyl phosphite and carbon tetrachloride at a low temperature gave the unexpected 1-diisopropoxyphosphoryl-2-aminobenzimidazole, which on heating gave the novel benzimidazole derivative, 2-(diisopropoxyphosphoryl)aminobenzimidazole. Both products were fully characterized and the synthetic procedure to both compounds was optimized. The procedure was used to prepare the related 5-benzoyl-2-(diisopropoxyphosphoryl)aminobenzimidazole and 5-benzoyl-2-(diethoxyphosphoryl)aminobenzimidazole (1d). In a preliminary trial against Brugia pahangi compound 1d was found to have no antifilarial activity. This lack of activity may be attributed to its extreme insolubility and thus low bioavailability. The synthesis of analogous, more soluble, phosphorothioate-substituted benzimidazoles using the same methods may yield compounds with greater antifilarial activity.

Amides↗
PubMed2001

Disease conditions most frequently evaluated among the homeless in Dallas.

Responding to the medical needs of the homeless population across the United States exact large costs on the health care system. To provide effectively for such vulnerable populations, health care systems require creative and efficient strategies of service organization tailored to the specific needs of the homeless. However, such needs often vary by geographic region due to the inherent diversity of the population. Currently, no published medical evaluation of the urban homeless in Texas exists. Therefore, this study examines 93,074 diagnoses given to 20,331 homeless patients seen in a seven-year period in a primary care mobile and fixed clinic system. The most frequent disease conditions evaluated in this cohort of patients are reported. These findings may be useful to clinical site managers and health care planners contemplating an outreach program for the homeless.

Adolescent↗
PubMed2001

Characterization of human liver thermostable phenol sulfotransferase (SULT1A1) allozymes with 3,3',5-triiodothyronine as the substrate.

Sulfotransferase 1A1 (SULT1A1) (thermostable phenol sulfotransferase, TS PST1, P-PST) is important in the metabolism of thyroid hormones. SULT1A1 isolated from human platelets displays wide individual variations not only in the levels of activity, but also in thermal stability. The activity of the allelic variant or allozyme SULT1A1*1, which possesses an arginine at amino acid position 213 (Arg213) has been shown to be more thermostable than the activity of the SULT1A1*2 allozyme which possesses a histidine at this position (His213) when using p-nitrophenol as the substrate. We isolated a SULT1A1*1 cDNA from a human liver cDNA library and expressed both SULT1A1*1 and SULT1A1*2 in eukaryotic cells. The allozymes were assayed using iodothyronines as the substrates and their biochemical properties were compared. SULT1A1*1 activity was more thermostable and more sensitive to NaCl than was SULT1A1*2 activity when assayed with 3,5,3'-triiodothyronine (T(3)). Sensitivities to 2,6-dichloro-4-nitrophenol (DCNP) and apparent K(m) values for SULT1A1*1 and for SULT1A1*2 with iodothyronines were similar. Based on K(m) values, the preferences of these SULT1A1 allozymes for iodothyronine substrates were the same (3,3'-diiodothyronine (3,3'-T(2))>3', 5',3-triiodothyronine (rT(3))>T(3)>thyroxine (T(4))>>3,5-diiodothyronine (3,5-T(2))). SULT1A1*1 activity was significantly higher than the SULT1A1*2 activity with T(3) as the substrate. Potential differences in thyroid hormone sulfation between individuals with predominant SULT1A1*1 versus SULT1A1*2 allozymes are most likely due to differences in catalytic activity rather than substrate specificity.

Alleles↗
PubMed2001

The prevalence of comorbid depression in adults with diabetes: a meta-analysis.

OBJECTIVE: To estimate the odds and prevalence of clinically relevant depression in adults with type 1 or type 2 diabetes. Depression is associated with hyperglycemia and an increased risk for diabetic complications; relief of depression is associated with improved glycemic control. A more accurate estimate of depression prevalence than what is currently available is needed to gauge the potential impact of depression management in diabetes. RESEARCH DESIGN AND METHODS: MEDLINE and PsycINFO databases and published references were used to identify studies that reported the prevalence of depression in diabetes. Prevalence was calculated as an aggregate mean weighted by the combined number of subjects in the included studies. We used chi(2) statistics and odds ratios (ORs) to assess the rate and likelihood of depression as a function of type of diabetes, sex, subject source, depression assessment method, and study design. RESULTS: A total of 42 eligible studies were identified; 20 (48%) included a nondiabetic comparison group. In the controlled studies, the odds of depression in the diabetic group were twice that of the nondiabetic comparison group (OR = 2.0, 95% CI 1.8-2.2) and did not differ by sex, type of diabetes, subject source, or assessment method. The prevalence of comorbid depression was significantly higher in diabetic women (28%) than in diabetic men (18%), in uncontrolled (30%) than in controlled studies (21%), in clinical (32%) than in community (20%) samples, and when assessed by self-report questionnaires (31%) than by standardized diagnostic interviews (11%). CONCLUSIONS: The presence of diabetes doubles the odds of comorbid depression. Prevalence estimates are affected by several clinical and methodological variables that do not affect the stability of the ORs.

Adult↗
PubMed2000

Sulfation of iodothyronines by human sulfotransferase 1C1 (SULT1C1)*.

Sulfation is an important component of human thyroid hormone metabolism. The role of the human sulfotransferase 1C1 (SULT1C1) is not known. Because SULT1C1 is present in the adult thyroid, intra-thyroidal sulfation of thyroid hormones and their metabolites might occur. We tested this hypothesis by determining the ability of recombinant human SULT1C1 to catalyze iodothyronine sulfation. Apparent K(m) values for 3,3',5-triiodothyronine (T(3)), 3, 3'-diiodothyronine (3,3'-T(2)), 3',5',3-triiodothyronine (rT(3)), and 3,3',5,5'-tetraiodothyronine (T(4)) with SULT1C1 were 28.7, 10.3, 10.2, and 59.3 microM, respectively. Thermal stability and responses to inhibitors also were tested with T(3) as the substrate. Enzyme aliquots were measured simultaneously to determine SULT1C1 substrate preferences at optimal iodothyronine concentrations. SULT1C1 activity obtained with T(3) was used as 100%, and the activities with 3,3'-T(2), rT(3), T(4), and 3,5-diiodothyronine (3, 5-T(2)) were 614, 314, 25, and 4%, respectively. We report for the first time the characterization of human SULT1C1 with T(3) and the preferences of the enzyme for various iodothyronines. The presence of SULT1C1 in the adult thyroid gland raises the possibilities that the enzyme can contribute to intraglandular thyroid hormone processing and iodide reutilization.

Animals↗
PubMed2000

DeltaguaBA attenuated Shigella flexneri 2a strain CVD 1204 as a Shigella vaccine and as a live mucosal delivery system for fragment C of tetanus toxin.

The DeltaguaBA Shigella flexneri 2a vaccine candidate, CVD 1204, was evaluated as a delivery system for the non-toxic C-terminal of tetanus toxin (fragment C), either as a polypeptide expressed in the bacteria or as a DNA vaccine. CVD 1204 was transformed with plasmid pTETnir15 which encodes the fragment C gene (tetC) under the control of the inducible prokaryotic nir15 promoter or a DNA vaccine plasmid pcDNA3tetC which encodes tetC under the eukaryotic hCMV promoter. Guinea pigs immunised intranasally (i.n.) with either recombinant strain mounted a secretory immune response against S. flexneri 2a Lipopolysaccharide (LPS) and were protected against ocular challenge with wild-type S. flexneri 2a. Both strains were effective in eliciting a serum IgG response against fragment C in guinea pigs following i.n. immunisation. Furthermore, serum from guinea pigs immunised with CVD 1204(pTETnir15) contained tetanus toxin neutralising antibodies. These results demonstrate that this S. flexneri 2a vaccine candidate can serve as a vehicle for the delivery of foreign antigens to the systemic immune system while retaining its capacity to serve as a mucosal Shigella vaccine.

Administration, Intranasal↗
PubMed2000

Common issues in medical professionalism: room to grow.

PURPOSE: Much of the respect and trust that society grants to physicians is based on the expectation of upholding professional values. We performed this study to assess responses to common challenges to medical professionalism and to ascertain physician satisfaction with training in professionalism. METHODS: A self-administered questionnaire containing six challenges to professionalism (acceptance of gifts, conflict of interest, confidentiality, physician impairment, sexual harassment, and honesty) with multiple-choice responses was mailed to 528 medical students and 779 house officers at the University of Colorado Health Sciences Center and to 900 randomly selected Colorado physicians. Information about previous exposure to the issue depicted in the scenarios and satisfaction with, and site of, previous education in medical professionalism was obtained. An independent panel selected the best or acceptable answers to the challenges. RESULTS: In all, 961 evaluable responses were received. More than 40% of physicians reported experience with four of the six challenges. The frequency of the best or acceptable answers to the six scenarios ranged from 12% to 86%. Best or acceptable responses were more common in physicians than in house officers, and in house officers than in medical students (P < 0.001). Practice setting and specialty type had only modest effects. The physician impairment scenario was the most challenging: Only 12% of physicians provided the best answer. Most (73%) respondents reported having 10 or fewer hours of formal course work in professionalism, and many (40%) were dissatisfied with their training in professionalism. CONCLUSIONS: While everyday challenges to professionalism are commonly encountered by trainees and practicing physicians, many practitioners are dissatisfied with their training in this area and were unable to provide an acceptable answer to these challenges.

Adult↗
PubMed2000

A longitudinal study of visual function in carriers of X-linked recessive retinitis pigmentosa.

OBJECTIVE: This study was carried out to evaluate the progression of visual function impairment in carriers of X-linked recessive retinitis pigmentosa. We also assessed the relationship between the retinal findings at presentation and the extent of deterioration. DESIGN: Observational, retrospective, case series. PARTICIPANTS: Twenty-seven carriers of X-linked recessive retinitis pigmentosa. METHODS: Each carrier was clinically categorized into one of four grades (grades 0 through 3) depending on the presence or absence of a tapetal-like retinal reflex and the extent of peripheral pigmentary degeneration. A complete ophthalmologic examination was performed and data for visual acuity, visual field area, and electroretinographic measurements were collected on the most recent visit in both eyes. These were then compared with similar data obtained on their initial visits. MAIN OUTCOME MEASURES: A comparison of visual function was carried out between the initial visit and the most recent visit on each carrier. The visual acuity was measured with Snellen's acuity charts. The visual fields to targets V-4-e and II-4-e were planimeterized and used for the analysis. The electroretinographic (ERG) measures used were light-adapted single-flash b-wave amplitudes and 30-Hz red flicker for cone function, dark-adapted maximal b-wave amplitudes, and response to a low intensity blue-flash for rod function. RESULTS: None of the 11 carriers with a tapetal-like reflex only (grade 1) showed any significant change in visual acuity or fields as compared with 3 of 7 (43%) carriers with diffuse peripheral pigmentary findings (grade 3) who showed significant deterioration in visual acuity in at least one eye, and 6 of 7 (86%) who showed a significant decrease in visual field area with at least one target size in at least one eye. By comparison, only 1 of 10 carriers with a grade 1 fundus finding demonstrated a significant decrease in maximal dark-adapted ERG function as compared with 5 of 6 (83%) carriers with grade 3 in response to a single-flash stimulus and with 4 of 5 (80%) carriers in response to a single-flash blue stimulus. For the single-flash photopic response, none of the 10 carriers with grade 1 showed any significant deterioration, whereas 2 of 4 (50%) with grade 3 did show such deterioration. The ERG responses for carriers with grade 2 were in between the extent of decrease in ERG amplitudes of those in carriers with grades 1 and 3. CONCLUSIONS: In our cohort of X-linked retinitis pigmentosa carriers, those with only a tapetal-like retinal reflex at presentation had a better prognosis to retain visual function than those with peripheral retinal pigmentation. These data are useful in counseling such carriers as to their visual prognosis.

Adolescent↗
PubMed2000

Mild renal failure is associated with adverse outcome after cardiac valve surgery.

The present study was performed to ascertain whether the presence of mild renal failure (defined as a serum creatinine concentration of 1. 5 to 3.0 mg/dL) is an independent risk factor for adverse outcome after cardiac valve surgery. An extensive set of preoperative and postoperative data was collected in 834 prospectively evaluated patients undergoing cardiac valve surgery at 14 Veterans Affairs Medical Centers. Univariate and multivariable analyses were performed to determine whether an independent association of mild renal dysfunction with adverse outcomes was present. Patients with mild renal failure had significantly greater 30-day mortality rates (P = 0.001; 16% versus 6%) and frequency of postoperative bleeding (P = 0.023; 16% versus 8%), respiratory complications (P = 0.02, 29% versus 16%), and cardiac complications (P = 0.002; 18% versus 7%) than patients with normal renal function (serum creatinine <1.5 mg/dL) when controlling for multiple other variables. The presence of a serum creatinine concentration of 1.5 to 3.0 mg/dL is significantly and independently associated with adverse outcomes after cardiac valve surgery.

Age Factors↗
PubMed2000

Procedural experience and comfort level in internal medicine trainees.

BACKGROUND: The American Board of Internal Medicine (ABIM) has recommended a specific number of procedures be done as a minimum standard for ensuring competence in various medical procedures. These minimum standards were determined by consensus of an expert panel and may not reflect actual procedural comfort or competence. OBJECTIVE: To estimate the minimum number of selected procedures at which a majority of internal medicine trainees become comfortable performing that procedure. DESIGN: Cross-sectional, self-administered survey. SETTING: A military-based, a community-based, and 2 university-based programs. PARTICIPANTS: Two hundred thirty-two internal medicine residents. MEASUREMENTS: Survey questions included number of specific procedures performed, comfort level with performing specific procedures, and whether respondents desired further training in specific procedures. The comfort threshold for a given procedure was defined as the number of procedures at which two thirds or more of the respondents reported being comfortable or very comfortable performing that procedure. RESULTS: For three of seven procedures selected, residents were comfortable performing the procedure at or below the number recommended by the ABIM as a minimum requirement. However, residents needed more procedures than recommended by the ABIM to feel comfortable with central venous line placement, knee joint aspiration, lumbar puncture, and thoracentesis. Using multivariate logistic regression analysis, variables independently associated with greater comfort performing selected procedures included increased number performed, more years of training, male gender, career goals, and for skin biopsy, training in the community-based program. Except for skin biopsy, comfort level was independent of training site. A significant number of advanced-year house officers in some programs had little experience in performing selected common ambulatory procedures. CONCLUSION: Minimum standards for certifying internal medicine residents may need to be reexamined in light of house officer comfort level performing selected procedures.

Adult↗
PubMed2000

Human red blood cell hemolysate is a potent mitogen for renal tubular epithelial cells.

Conditions associated with intravascular hemolysis are often complicated by acute renal failure which is characterized by renal vasoconstriction and tubular injury. However, the effects of human red blood cell (RBC) hemolysate on renal tubular epithelial cell function have not been well characterized. We therefore measured the effect of distilled water-lysed human RBCs on cultured LLC-PK1 cell function. We found that human RBC hemolysate produced a marked effect to promote LLC-PK1 3H-thymidine uptake that was several-fold higher than that produced by maximal concentrations of several known growth factors. Partial purification of human RBC hemolysate by sequential centrifugation and passage over a column that removes low molecular weight substances each significantly reduced, but did not totally eliminate, the effect of human RBC hemolysate to promote 3H-thymidine uptake. Exposure of LLC-PK1 cells to horse myoglobin also stimulated 3H-thymidine incorporation in LLC-PK1 cells. A reducing agent (ascorbic acid) decreased the effect of horse myoglobin and of human RBC hemolysate to promote LLC-PK1 mitogenesis. Ascorbic acid also decreased the methemoglobin content of human RBC hemolysate. The effect of human RBC hemolysate to increase LLC-PK1 incorporation of 3H-thymidine could also be significantly decreased by either of two inhibitors of tyrosine kinase. These results suggest that there are several components of human RBC hemolysate that promote LLC-PK1 3H-thymidine incorporation. One of these components appears to be methemoglobin that exerts its effect via a tyrosine kinase signal transduction pathway.

Analysis of Variance↗
PubMed2000

Alternative/complementary medicine: wider usage than generally appreciated.

OBJECTIVE: To test the hypothesis that there is substantial use of a practitioner of alternative/complementary medicine by patients traditionally considered to be underserved. DESIGN: Cross-sectional, self-administered survey study. SETTINGS: Three university hospital-affiliated general ambulatory clinics serving patients of different socioeconomic status and racial origin. SUBJECTS: Five hundred and thirty-six (93% of those attending) consecutive clinic attendees. OUTCOME MEASURES: Past use and desired future use of one or more practitioners of five modalities of alternative/complementary medicine and willingness to pay for these modalities out-of-pocket. RESULTS: Past usage and desired future usage of one or more practitioners of alternative/complementary medicine was comparable at the three clinic sites despite wide differences in socioeconomic status and willingness/ability to pay out-of-pocket for these services. Multivariable analyses revealed lower self-rated health status and female gender (both p < 0.006) but not income, race, age or education as independent, significant predictors of use of a practitioner of alternative/complementary medicine. CONCLUSION: Usage of alternative/complementary medicine is not confined to any well-circumscribed socioeconomic group and is common in patients often considered to be underserved. Self-assessed lower health status is significantly and independently associated with use of a practitioner of alternative/complementary care.

Adolescent↗
PubMed2000

Evidence for Rho protein regulation of renal tubular epithelial cell function.

BACKGROUND: Rho proteins are small guanine 5'-triphosphate (GTP)-binding proteins felt to be important regulators of several aspects of cell function, including the organization of the actin cytoskeleton. The effects of Rho proteins on the regulation of renal tubular epithelial cell function are not known. METHODS: Selected bacterial toxins that inhibit Rho protein function were used to examine the effect of Rho in cultured renal tubular epithelial cells. RESULTS: Clostridium difficile toxin A significantly and dose dependently inhibited LLC-PK(1) cell (3)H-thymidine uptake and healing of small wounds made in confluent monolayers, and it induced apoptosis. A second Clostridium difficile toxin (toxin B) that acted via a different receptor also impaired LLC-PK(1) thymidine uptake and wound healing, and it induced apoptosis. A third bacterial toxin, C3 toxin from Clostridium botulinum, also impaired LLC-PK(1) thymidine uptake and stimulated apoptosis in LLC-PK(1) cells. Since Rho inhibition disrupted organization of the actin cytoskeleton, we examined the effects of another agent that disrupted the actin cytoskeleton (cytochalasin D) and found significant dose-dependent effects that impaired LLC-PK1 thymidine uptake and wound healing and that induced apoptosis. The effects of toxin A and cytochalasin D to induce apoptosis were not associated with significant changes in expression of Bcl-2, BAD, or BAK proteins and were significantly attenuated by a pancaspase inhibitor. CONCLUSIONS: Our results suggest that Rho proteins are important endogenous regulators of several aspects of renal tubular epithelial cell function, including proliferation, migration, and apoptosis. Further studies are needed to clarify the cellular mechanisms of Rho regulation of renal epithelial cell function.

ADP Ribose Transferases↗
PubMed2000

Recognition of patient referral desires in an academic managed care plan frequency, determinants, and outcomes.

OBJECTIVE: To determine the frequency and determinants of provider nonrecognition of patients' desires for specialist referral. DESIGN: Prospective study. SETTING: Internal medicine clinic in an academic medical center providing primary care to patients enrolled in a managed care plan. PARTICIPANTS: Twelve faculty internists serving as primary care providers (PCPs) for 856 patient visits. MEASUREMENTS AND MAIN RESULTS: Patients were given previsit and postvisit questionnaires asking about referral desire and visit satisfaction. Providers, blinded to patients' referral desire, were asked after the visit whether a referral was discussed, who initiated the referral discussion, and whether the referral was indicated. Providers failed to discuss referral with 27% of patients who indicated a definite desire for referral and with 56% of patients, who indicated a possible desire for referral. There was significant variability in provider recognition of patient referral desire. Recognition is defined as the provider indicating that a referral was discussed when the patient marked a definite or possible desire for referral. Provider recognition improved significantly (P <.05), when the patient had more than one referral desire, if the patient or a family member was a health care worker and when the patient noted a definite desire versus a possible desire for referral. Patients were more likely (P <.05) to initiate a referral discussion when they had seen the PCP previously and had more than one referral desire. Of patient-initiated referral requests, 14% were considered "not indicated" by PCPs. Satisfaction with care did not differ in patients with a referral desire that were referred and those that were nor referred. CONCLUSIONS: These PCPs frequently failed to explicitly recognize patients' referral desires. Patients were more likely to initiate discussions of a referral desire when they saw their usual PCP and had more than a single referral desire.

Colorado↗
PubMed2000

Attenuated Shigella flexneri 2a vaccine strain CVD 1204 expressing colonization factor antigen I and mutant heat-labile enterotoxin of enterotoxigenic Escherichia coli.

A multivalent live oral vaccine against both Shigella spp. and enterotoxigenic Escherichia coli (ETEC) is being developed based on the hypothesis that protection can be achieved if attenuated shigellae express ETEC fimbrial colonization factors and genetically detoxified heat-labile toxin from a human ETEC isolate (LTh). Two detoxified derivatives of LTh, LThK63 and LThR72, were engineered by substitution-serine to lysine at residue 63, or lysine to arginine at residue 72. The genes encoding these two derivatives were cloned separately on expression plasmids downstream from the CFA/I operon. Following electroporation into S. flexneri 2a vaccine strain CVD 1204, coexpression of CFA/I and LThK63 or LThR72 was demonstrated by Western blot analysis, GM(1) binding assays, and agglutination with anti-CFA/I antiserum. Hemagglutination and electron microscopy confirmed surface expression of CFA/I. Guinea pigs immunized intranasally on days 0 and 15 with CVD 1204 expressing CFA/I and LThK63 or LThR72 exhibited high titers of both serum immunoglobulin G (IgG) and mucosal secretory IgA anti-CFA/I; 40% of the animals produced antibodies directed against LTh. All immunized guinea pigs also produced mucosal IgA (in tears) and serum IgG anti-S. flexneri 2a O antibodies. Furthermore, all immunized animals were protected from challenge with wild-type S. flexneri 2a. This prototype Shigella-ETEC hybrid vaccine demonstrates the feasibility of expressing multiple ETEC antigens on a single plasmid in an attenuated Shigella vaccine strain and engendering immune responses against both the heterologous antigens and vector strain.

Animals↗
PubMed2000

Depression and poor glycemic control: a meta-analytic review of the literature.

OBJECTIVE: Depression is common among patients with diabetes, but its relationship to glycemic control has not been systematically reviewed. Our objective was to determine whether depression is associated with poor glycemic control. RESEARCH DESIGN AND METHODS: Medline and PsycINFO databases and published reference lists were used to identify studies that measured the association of depression with glycemic control. Meta-analytic procedures were used to convert the findings to a common metric, calculate effect sizes (ESs), and statistically analyze the collective data. RESULTS: A total of 24 studies satisfied the inclusion and exclusion criteria for the meta-analysis. Depression was significantly associated with hyperglycemia (Z = 5.4, P < 0.0001). The standardized ES was in the small-to-moderate range (0.17) and was consistent, as the 95% CI was narrow (0.13-0.21). The ES was similar in studies of either type 1 or type 2 diabetes (ES 0.19 vs. 0.16) and larger when standardized interviews and diagnostic criteria rather than self-report questionnaires were used to assess depression (ES 0.28 vs. 0.15). CONCLUSIONS: Depression is associated with hyperglycemia in patients with type 1 or type 2 diabetes. Additional studies are needed to establish the directional nature of this relationship and to determine the effects of depression treatment on glycemic control and the long-term course of diabetes.

Adult↗