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Biomedical subjects

G Park

Publications and source records attributed to G Park.

At least 37 records · Page 2Linked to original sources
PubMed2000

Relative contributions of the components of the American College of Rheumatology 20% criteria for improvement to responder status in patients with early seropositive rheumatoid arthritis.

OBJECTIVE: To evaluate factors that influence the responses defined by the American College of Rheumatology (ACR) 20% criteria for improvement in rheumatoid arthritis (RA). METHODS: ACR 20% and 50% response rates were calculated from data collected for the intervals 0-6, 0-12, and 0-24 months for 180 RA patients participating in the Western Consortium of Practicing Rheumatologists long-term observational study of early seropositive RA (mean +/- SD duration of RA at study entry 6.0 +/- 3.4 months). Analyzable cases were patients with paired data for tender and swollen joint counts plus at least 3 of the following criteria: physician's and patient's global assessments of disease activity and patient's score for pain (by visual analog scale), physical function score on the Health Assessment Questionnaire (HAQ), and levels of an acute-phase reactant. Response rates were then recalculated by 3 different methods: 1) using only cases with complete paired data for all criteria, 2) sequentially assuming no improvement in each of the 5 secondary criteria, and 3) substituting grip strength for HAQ scores. RESULTS: Using 464 paired observations for all analyzable cases, ACR 20% (50%) improvement rates were 52.6% (33.0%), compared with 55.6% (34.8%) for 365 paired observations from the cases with complete data. Decreases in ACR response rates when secondary criteria were sequentially set at "no improvement" ranged from 11.7% (pain at 0-6 months) to 1.2% (C-reactive protein at 0-12 months), but these were not statistically different by the kappa statistic. Overall numerical rankings of the relative contributions of the secondary criteria to the ACR 20% or 50% response rates were physician's global assessment, pain, HAQ, patient's global assessment, and acute-phase reactant. Only 7.8% of paired grip strength observations showed > or =20% improvement, compared with 71% of paired HAQ observations. CONCLUSION: The use of all "analyzable" cases (paired data for tender and swollen joint counts plus > or =3 of the 5 secondary criteria) increases the number of subjects and only slightly decreases the ACR response rate compared with analyses limited to cases with complete data. The contributions of the secondary criteria are not statistically different, supporting their equal weighting in the ACR definition of improvement. The ACR 20% response rates are higher when the HAQ, rather than grip strength, is used to measure physical function.

Adult↗
PubMed2000

Basal insulin glargine (HOE 901) versus NPH insulin in patients with type 1 diabetes on multiple daily insulin regimens. U.S. Insulin Glargine (HOE 901) Type 1 Diabetes Investigator Group.

OBJECTIVE: Insulin glargine (HOE 901, 21(A)-Gly-30(B)a-L-Arg-30(B)b-L-Arg human insulin) is a novel recombinant analog of human insulin with a shift in the isoelectric point producing a retarded absorption rate and an increased duration of action that closely mimics normal basal insulin secretion. It recently received approval from the Food and Drug Administration. The aim of this study was to evaluate 2 formulations of insulin glargine for safety and efficacy in the treatment of patients with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a 4-week trial, 256 patients with type 1 diabetes received either NPH insulin or insulin glargine containing 30 microg/ml zinc (insulin glargine[30]) or 80 microg/ml zinc (insulin glargine[80]). Insulin glargine was given subcutaneously once daily at bedtime. NPH insulin was given either once daily (at bedtime) or twice daily (before breakfast and at bedtime), according to the patient's prestudy regimen. The initial doses of insulin glargine and NPH were based on the previous NPH total daily dose. RESULTS: At study end point, insulin glargine-pooled groups had significantly lower fasting plasma glucose (FPG) levels than the NPH insulin group, with adjusted mean FPG levels reduced by 2.2 mmol/l (P = 0.0001). Insulin glargine was superior to NPH insulin in reducing FPG levels in patients who had previously received NPH insulin twice daily but not in patients who had previously received NPH once daily. FPG levels were more stable in patients using insulin glargine than in patients using NPH insulin. A subset of patients (n = 71) underwent hourly overnight plasma glucose measurements. Insulin glargine patients exhibited lower FPG levels after 5:00 A.M.; the difference was significant by 8:00 A.M. The adjusted mean FPG for insulin glargine[30] was 7.8 mmol/l; for insulin glargine[80], 7.3 mmol/l; and for NPH, 10.7 mmol/l. Both formulations of insulin glargine were well tolerated, similar to NPH insulin. CONCLUSIONS: Basal insulin glargine administered once daily for 4 weeks as part of a basal-bolus multiple daily insulin regimen was safe and more effective in lowering fasting plasma glucose levels than NPH in patients with type 1 diabetes.

Adult↗
PubMed2000

Direct and indirect costs associated with the onset of seropositive rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To examine the direct and indirect costs of rheumatoid arthritis (RA) during the first year of disease. METHODS: As part of a longitudinal observational study, 150 patients with seropositive RA of 5.9 +/- 2.9 mo duration were recruited through the Western Consortium of Practicing Rheumatologists. Subjects completed questionnaires about health care services and resources utilized and about the number of days of usual activity lost as a result of RA during the 6 month period prior to enrolment. RESULTS: Study participants had active RA as evidenced by mean tender and swollen joint counts of 24.9 +/- 13.5 and 20.6 +/- 11.6, respectively, and moderate functional impairment reflected by a mean Health Assessment Questionnaire (HAQ) score of 1.24 +/- 0.7. The average total direct cost of RA was $200/month. Health care visits, medications, and radiographs accounted for 78% of the total direct cost, while expenditures for hospitalizations accounted for only 3.5% of the total. The average number of days of usual activity lost per month because of RA was 3.8 +/- 7.7, translating into an average indirect cost of $281/month. Of the 95 subjects who were gainfully employed prior to disease onset, 12 were disabled and 5 were on sick leave as a result of RA, corresponding to a work disability rate of 18%. Work disabled subjects reported significantly lower total household incomes and higher HAQ disability and global disease activity scores than subjects who continued working. CONCLUSION: In this group of patients with seropositive RA substantial costs, both direct and indirect, were incurred during the first year of disease.

Arthritis, Rheumatoid↗
PubMed1999

Long-acting insulin analogs.

Once daily injection of existing intermediate/long-acting insulin preparations does not provide a 24-h basal insulinemia in most patients. High variability, pronounced insulin peaks, and (as a result) a high risk of nocturnal hypoglycemia only poorly simulate normal physiology. One principle to prolong insulin action is the shift of the isoelectric point of insulin towards neutral. One example is HOE 901, which shows in healthy volunteers a constant peakless profile over the entire 24-h clamp period. In 4-week trials in comparison to NPH insulin, significant lower fasting plasma glucose levels were achieved with lower rates of nocturnal hypoglycemia. Another principle to prolong insulin action is the use of soluble fatty acid acylated insulins that are bound to albumin after absorption. The combination of long- and short-acting insulins might provide the tools towards the final goal of achieving sustained normoglycemia in diabetic patients.

Acylation↗
PubMed1999

Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American College of Rheumatology 20% improvement criteria or the Disease Activity Score in patients with early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS). METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation. RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values. CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.

Acute-Phase Reaction↗
PubMed1999

Patient self-report tender and swollen joint counts in early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: To determine the correlation between patient self-report joint counts and standard physician joint counts, and to compare pictorial (Mannequin) and text (Rapid Assessment of Disease Activity in Rheumatology, RADAR) formats for obtaining patient self-reports. METHODS: Baseline patient self-report joint counts were mailed and completed by 60 patients with early rheumatoid arthritis (RA) one day before and one day after being examined by a physician. Twenty-seven were randomized to the Mannequin tender and Mannequin swollen joint counts; 33 were randomized to the RADAR tender and swollen joint counts. Agreement between patient and physician self-report joint counts, diagnostic characteristics, and test-retest reliability of patient self-report joint counts was computed. Stepwise regression analyses were performed to identify predictors of patient-physician differences in total joint count. RESULTS: Means and standard deviations of paired patient and physician total joint counts were not different for Mannequin or RADAR forms. Spearman correlations were moderate (0.58 to 0.69 for Mannequin, 0.37 to 0.58 for RADAR). Agreement (intraclass correlations) was 0.65 for the Mannequin and 0.56 for the RADAR forms. Patient test-retest reproducibility was moderate for RADAR tenderness (0.58) and high (r>0.90) for RADAR swollen and both Mannequin forms. Level of patient education predicted patient-physician differences on the RADAR swollen joint counts (p = 0.003), but was not significant in Mannequin forms, suggesting that education was not a factor in accurate completion of Mannequin forms. CONCLUSION: Both pictorial and text format patient self-report joint counts are significantly correlated with physician joint counts. In addition to moderately high patient test-retest reproducibility, this suggests that patient self-reports in both formats may yield accurate measures of improvement in disease activity.

Adult↗
PubMed1998

Subchronic toxicity of benzothiophene on rats following dietary exposure.

The systemic and neurobehavioral effects of benzo[b]thiophene (routinely referred to as benzothiophene) were studied in rats following 13-wk oral exposure. Male (170 +/- 16 g) and female (146 +/- 12 g) Sprague-Dawley rats (10 animals per group) were fed diet containing 0.5, 5, 50, or 500 ppm benzothiophene for 13 wk. Control animals were given rat feed plus vehicle (corn oil) only. No clinical signs of toxicity and neurobehavioral effects were observed using screening tests that included cage-side observations, righting reflex, open field activities, and forelimb and hindlimb grip strength. Elevated serum aspartate aminotransferase activity and bilirubin level were observed in highest dose females. Except for a statistically significant decrease in hematocrit in the highest dose males, benzothiophene exerted no marked effects on hematological parameters. Benzothiophene exposure did not result in alterations in hepatic alkaline phosphatase activity, or the typical hepatic phase I (aniline hydroxylase, ethoxyresorufin O-deethylase, pentoxyresorufin O-dealkylase, aminopyrine N-demethylase) and phase II (UDP-glucuronosyltransferase, glutathione S-transferase) drug-metabolizing enzyme activities. No significant elevation in urinary ascorbic acid, protein, and N-acetylglucosaminidase activity was detected in the treated animals. Peribiliary fibrosis was the most significant histological change and occurred in the liver of females in the 50 and 500 ppm groups. Mild epithelial hyperplasia in the renal pelvis was detected in the majority of 5 and 50 ppm females, with epithelial hyperplasia in the urinary bladder observed in the 50 ppm females. In males, increased incidence and severity of mild binucleation of hepatocytes and mild thickening of the basement membrane in kidney cortex were observed at 500 ppm. Benzothiophene was not detected in the urine of high-dose animals at the termination of the experiment. Based on the kidney, hepatic, and hematocrit changes, the no-observed-adverse-effect level (NOAEL) in the diet was determined to be 0.5 ppm (0.04 mg/kg/d) for females and 50 ppm (3.51 mg/kg/d) for males.

Animals↗
PubMed1998

Tumor cell cytotoxicity of a novel metal chelator.

We have synthesized a novel six-coordinate metal chelator from the triamine cis-1,3,5-triaminocyclohexane by the addition of a 2-pyridylmethyl pendant arm on each nitrogen, which we term tachpyr. The experiments described here were designed to explore whether this compound exhibits potential antitumor activity. When added to MBT2 or T24 cultured bladder cancer cells, tachpyr was profoundly cytotoxic, with an IC50 of approximately 4.6 micromol/L compared with 70 micromol/L for desferioxamine. To explore the mode of action of tachpyr, several metal complexes were prepared, including Fe(II), Ca(II), Mn(II), Mg(II), Cu(II), and Zn(II) tachpyr complexes. Of these, the Zn(II), Cu(II), and Fe(II) complexes were without toxic effect, whereas the Ca(II), Mn(II), and Mg(II) complexes remained cytotoxic. To further probe the role of Zn(II) and Cu(II) chelation in the cytotoxicity of tachpyr, sterically hindered tachpyr derivatives were prepared through N-alkylation of tachpyr. These derivatives were unable to strongly bind Fe(III) or Fe(II) but were able to bind Zn(II) and Cu(II). When added to cells, these sterically hindered tachpyr derivatives were nontoxic, consistent with a role of iron depletion in the cytotoxic mechanism of tachpyr. Further, the addition of tachpyr to proliferating cultures resulted in an early and selective inhibition of ferritin synthesis, an iron storage protein whose translation is critically dependent on intracellular iron pools. Taken together, these experiments suggest that tachpyr is a cytotoxic metal chelator that targets intracellular iron, and that the use of tachpyr in cancer therapy deserves further exploration.

Alkylation↗
PubMed1997

Inhibitors of 25-hydroxyvitamin D3-1alpha-hydroxylase: thiavitamin D analogs and biological evaluation.

Six A-ring analogs of 1alpha,25-dihydroxyvitamin D3 (1, 1alpha,25-(OH)2-D3) 3-deoxy-3-thia-1alpha,25-(OH)2-D3 (3), 3-deoxy-3-thia-1alpha,25-(OH)2-D3-3alpha-oxide (6), 3-deoxy-3-thia-1alpha,25-(OH)2-D3-3beta-oxide (7) and the 5,6-trans counterparts 5, 8, and 9, respectively--were tested for their ability to inhibit 25-hydroxy-D3-1alpha-hydroxylase (1-OH-ase) in vitro in mitochondria isolated from kidneys of vitamin D deficient chicks. The six analogs were also evaluated in terms of their ability to bind to the chicken intestinal nuclear receptor (VDR) in comparison to the natural hormone 1alpha,25-(OH)2-D3. Analog 7 is not only the best inhibitor of the 1-OH-ase but it also binds effectively to the chick intestinal receptor. It is established that vitamin D analogs must have a 1alpha oxygen group for effective inhibition of the 1-OH-ase. This functional group is also needed for effective binding to the chick intestinal VDR.

Animals↗
PubMed1997

The subchronic toxicity of acridine in the rat.

The subchronic toxicity of acridine was investigated in rats following dietary exposure at 0, 1, 10, 100 and 500 ppm for 13 weeks. The growth rate and food consumption were not affected by treatment and no clinical signs of toxicity were observed. There was a slight but significant decrease in spleen weight, both in absolute terms and as a percent of body weight, in the 500 ppm males and a slight increase in absolute thymus weight in the females of the same dose group. Both hepatic ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-dealkylase (PROD) activities were slightly, but significantly, elevated in females in the 500 ppm dose group. No haematological or other biochemical changes were observed. Females also displayed dose-related increases in inorganic phosphate and uric acid levels. Treatment-related histopathological changes were seen in the thyroid, liver and kidney and included hepatic anisokaryosis and vesiculation of nuclei and glomerular adhesions, reticulin sclerosis and nuclear pyknosis in the kidney. Residue data showed a dose-dependent accumulation of acridine in liver, kidney and adipose with the highest concentration being found in the fat of the 500 ppm dose group. Based on these data, the no observable adverse effect level of acridine was judged to be 100 ppm or 12 mg/kg bw/day.

Acridines↗
PubMed1996

A case of Munchausen syndrome with claims of trauma and haemophilia.

A case of Munchausen syndrome presented with both factitious trauma and factitious haemophilia. He was treated inappropriately with factor VIII concentrate before the history of the presenting complaint could be validated. Clinical suspicion remains the most important aid to diagnosis.

Accidents, Traffic↗
PubMed1995

Three-period crossover trial with ambulatory blood pressure monitoring for evaluating antihypertensive therapy.

A double-blind, three-period, crossover trial used 24-hour ambulatory blood pressure monitoring to compare diltiazem controlled diffusion (CD) 300 mg with placebo. Patients with hypertension (N = 43) were randomly assigned to one of four crossover treatment sequences of three treatment periods each. Ambulatory blood pressure was obtained at the end of each 4-week treatment period. Diltiazem CD significantly decreased diastolic and systolic blood pressure at bihourly ambulatory blood pressure evaluations (p < 0.05, all). However, when all ambulatory blood pressure monitoring data were combined into one statistical model, blood pressure reductions were quantifiably similar to those in the overall bihourly analysis, but with a consistent 24-hour antihypertensive effect for both diastolic and systolic blood pressure relative to that with placebo (i.e., parallel blood pressure profiles) and with increased precision. Mean +/- SE changes in diastolic and systolic blood pressure across the 24-hour dosing interval were -5.6 +/- 0.4 mm Hg and -7.6 +/- 0.5 mm Hg, respectively (p < 0.001, both). Therefore, by using a crossover design with ambulatory blood pressure monitoring, we showed diltiazem CD to reduce blood pressure consistently throughout a 24-hour dosing interval in comparison with placebo in patients with hypertension.

Adult↗
PubMed1995

HMSA's HealthPass--a strategy for delivery of preventive services.

Several groups have recommended standards for preventive health care services. Despite this, our health care system contains many obstacles that impede their delivery. Recognizing the need to provide members with appropriate, meaningful, and cost-effective health promotion and disease prevention services, HMSA has created HealthPass. This benefit is now available to 40% of the membership. It offers health promotion, education, and screening services through a formalized network across the state. HealthPass services are integrated with individual physician providers to offer selected periodic evaluations for adults. HMSA's HealthPass was created to promote public health and further enable members to obtain preventive services. HMSA encourages its physician providers to participate in this statewide effort at primary health promotion.

Adolescent↗
PubMed1993

Taxoid side-chain structure determination by electrospray ionization tandem mass spectrometry.

A method to elucidate the side-chain structure of novel taxoids was developed through use of electrospray ionization tandem mass spectrometry. The intact side-chain fragments produced by source fragmentation in the atmosphere-to-vacuum interface were further dissociated in the collision cell of a triple quadrupole mass spectrometer. The distinctive collisionally induced dissociation mass spectra were remarkably informative and gave detailed information on the side-chain functionalities. This technique proved valuable in the characterization of new taxoids produced by yew-tree cell cultures.

Alkaloids↗
PubMed1992

Rapid determination of creatine, phosphocreatine, purine bases and nucleotides (ATP, ADP, AMP, GTP, GDP) in heart biopsies by gradient ion-pair reversed-phase liquid chromatography.

A simple binary solvent method has been developed for the simultaneous determination of creatine (Cr), phosphocreatine (PCr), ATP, ADP, AMP, GTP, GDP, IMP, NAD, inosine, adenosine, hypoxanthine and xanthine. This allows separation of the most important nucleotides present in myocardial biopsies as, for example, in studies using 31P NMR spectroscopy. In NMR spectra ATP and PCr are the only visible high-energy phosphates, therefore the status of other nucleotides and bases cannot be determined. The nucleotides, AMP degradation products, PCr and Cr in pig and rat heart muscle were resolved with 35 mM K2HPO4, 6 mM tetrabutylammonium hydrogensulfate buffer, pH 6.0, and a binary acetonitrile gradient on medium-bore, 250 mm or 125 mm x 3.9-4.6 mm I.D. steel octadecyl-bonded (C18) columns at a flow-rate of 1.5 or 1.0 ml/min. This method, optimized for use with older high-performance liquid chromatography pumps (100 microliters displacement heads), resolves the major porcine and rat myocardial nucleotides and degradation products within 22 min. The amounts found in normoxic porcine muscle are: Cr 9.21 +/- 0.75; hypoxanthine 1.40 +/- 0.14; PCr 7.20 +/- 1.2; IMP 1.34 +/- 0.13; beta NAD 1.82 +/- 0.23; AMP 0.10 +/- 0.04; GDP 0.05 +/- 0.02; ADP 1.23 +/- 0.09; GTP 0.19 +/- 0.01; ATP 4.45 +/- 0.32 mumol/g wet weight. The method, incorporating adenosine tetraphosphate as an internal standard, allows the documentation of changes in both the high-energy phosphates and their degradation products in a single analysis of myocardial samples as small as 200 micrograms (wet weight).

Adenosine Diphosphate↗