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Biomedical subjects

John Martin

Publications and source records attributed to John Martin.

45 records · Page 3Linked to original sources

Effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus: a retrospective review of randomly selected medical records.

BACKGROUND: The antihyperglycemic effects of pioglitazone hydrochloride and rosiglitazone maleate are well documented. The results of clinical trials and observational studies have suggested, however, that there are individual differences in the effects of these drugs on blood lipid levels. OBJECTIVE: The present study evaluated the effects of pioglitazone and rosiglitazone on blood lipid levels and glycemic control in patients with type 2 diabetes mellitus. METHODS: This was a retrospective review of randomly selected medical records from 605 primary care practices in the United States in which adults with type 2 diabetes received pioglitazone or rosiglitazone between August 1, 1999, and August 31, 2000. The outcome measures were mean changes in serum concentrations of triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glycosylated hemoglobin (HbA1c) values. RESULTS: Treatment with pioglitazone was associated with a reduction in mean TG of 55.17 mg/dL, a reduction in TC of 8.45 mg/dL, an increase in HDL-C of 2.65 mg/dL, and a reduction in LDL-C of 5.05 mg/dL. Treatment with rosiglitazone was associated with a reduction in mean TG of 13.34 mg/dL, an increase in TC of 4.81 mg/dL, a reduction in HDL-C of 0.12 mg/dL, and an increase in LDL-C of 3.56 mg/dL. With the exception of HDL-C, the differences in mean changes in lipid parameters between treatment groups were statistically significant (P < 0.001, pioglitazone vs rosiglitazone). Reductions in HbA1c were statistically equivalent between treatments (1.04% pioglitazone, 1.18% rosiglitazone). CONCLUSIONS: Treatment with pioglitazone was associated with greater beneficial effects on blood lipid levels than treatment with rosiglitazone, whereas glycemic control was equivalent between the 2 treatments.

Adult↗

Detecting cholangiocarcinoma in patients with primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a progressive cholestatic liver disease associated with cholangiocarcinoma. Brush cytology and serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9 [CA19-9]) have been used to diagnose cholangiocarcinoma, but there are few data comparing their effectiveness. METHODS: The effectiveness of brush cytology, carcinoembryonic antigen, and CA19-9 for the diagnosis of cholangiocarcinoma was retrospectively studied by review of patients with primary sclerosing cholangitis. Receiver operator curves were used to identify cutoff points for carcinoembryonic antigen and CA19-9. RESULTS: Of 692 patients with primary sclerosing cholangitis screened, adequate follow-up was obtained in 333, 44 (13%) of whom had a diagnosis of cholangiocarcinoma. Three hundred eighteen brush cytology specimens were obtained in 151 patients; serum carcinoembryonic antigen and CA19-9 levels were obtained in 144 and 55 patients, respectively. The overall sensitivity and specificity of brush cytology were, respectively, 46.4% (95% CI [27.5, 64.5]) and 100% (95% CI [97.2, 100]). A carcinoembryonic antigen >5.2 ng/mL had a sensitivity of 68.0% (95% CI [47.5, 83.9]) and specificity of 81.5% (95% CI [73.9, 87.7]). A CA19-9 >180 U/mL had a sensitivity of 66.7% (95% CI [34.9, 87.7]) and specificity of 97.7% (95% CI [88.2, 99.9]). In the subset of patients in which all 3 tests were obtained, (n = 45, cholangiocarcinoma = 8) the combination of an abnormal carcinoembryonic antigen or CA19-9 had the highest sensitivity: 100% (95% CI [65.1, 100.0]) with a specificity of 78.4% (95% CI [63.1, 89.7]). The combination of a positive brush cytology or an abnormal CA19-9 had a sensitivity and specificity of, respectively, 87.5% (95% CI [50.0, 99.4]) and 97.3% (95% CI [86.2, 99.9]). CONCLUSIONS: Screening patients with primary sclerosing cholangitis for cholangiocarcinoma with CA19-9 and carcinoembryonic antigen is reasonable, but the ideal intervals at which to obtain these tests and the cost-effectiveness require further study.

Adult↗

A compilation of soybean ESTs: generation and analysis.

Whole-genome sequencing is fundamental to understanding the genetic composition of an organism. Given the size and complexity of the soybean genome, an alternative approach is targeted random-gene sequencing, which provides an immediate and productive method of gene discovery. In this study, more than 120000 soybean expressed sequence tags (ESTs) generated from more than 50 cDNA libraries were evaluated. These ESTs coalesced into 16928 contigs and 17336 singletons. On average, each contig was composed of 6 ESTs and spanned 788 bases. The average sequence length submitted to dbEST was 414 bases. Using only those libraries generating more than 800 ESTs each and only those contigs with 10 or more ESTs each, correlated patterns of gene expression among libraries and genes were discerned. Two-dimensional qualitative representations of contig and library similarities were generated based on expression profiles. Genes with similar expression patterns and, potentially, similar functions were identified. These studies provide a rich source of publicly available gene sequences as well as valuable insight into the structure, function, and evolution of a model crop legume genome.

Contig Mapping↗

Validity and accuracy of a risk calculator in predicting periodontal disease.

BACKGROUND: Research on the pathobiology of periodontal diseases has increased our knowledge of these diseases and is fostering a transition from the repair model to the medical or wellness model of periodontal care. Successful application of the wellness model depends on an accurate and valid assessment of disease risk, as well as institution of risk reduction as an integral part of prevention and treatment. A computer-based risk assessment tool has been developed. METHODS: The authors reviewed clinical records and radiographs of 523 subjects enrolled in the Veterans Affairs Dental Longitudinal Study to evaluate the validity of risk prediction using the computer-based tool. Data from baseline examinations was entered into the risk calculator, and a risk score on a scale from 1 (lowest risk) to 5 (highest risk) was calculated for each subject to predict periodontal deterioration. Actual periodontal status in terms of alveolar bone loss (determined from digitized radiographs) and tooth loss (determined from clinical records) was assessed at years 3, 9 and 15. The authors determined the statistical strength of the association between risk prediction and actual outcome. RESULTS: The risk scores were strong predictors of periodontal status, as measured by alveolar bone loss and loss of periodontally affected teeth. Risk scores consistently ranked risk score groups from least to most bone loss and tooth loss. Compared with a risk score of 2, the relative risk of tooth loss was 3.2 for a risk score of 3, 4.5 for a risk score of 4 and 10.6 for a risk score of 5. CONCLUSIONS AND PRACTICE IMPLICATIONS: Use of the risk assessment tool over time may result in more uniform and accurate periodontal clinical decision-making, improved oral health, reduction in the need for complex therapy, reduction in health care costs and a hastening of the transition from a repair model to a wellness model of care.

Alveolar Bone Loss↗

Induction of metalloproteinases by glomerular mesangial cells stimulated by proteins of the extracellular matrix.

Human glomerular mesangial cells (HMC) are embedded in the mesangial matrix (MM) and control its turnover through a dynamic equilibrium between synthesis and degradation. Degradation is controlled by matrix metalloproteinases (MMP), whose activity has been causally implicated in the progression of glomerular disease. In other systems, MMP secretion may be directly affected by exposure to specific matrix proteins. The present study, therefore, investigated the effect of different matrix components on the adherence of HMC and on their secretion and activation of the gelatinases MMP2 and MMP9. HMC adhered strongly (quantified using crystal violet staining) to collagen IV and collagen I (P < 0.01, relative to binding to control, bovine serum albumin (BSA)-coated wells) and to a lesser extent to gelatin IV and fibronectin (P < 0.05). Binding to vitronectin and laminin was not statistically different to control wells. After the addition of these matrix proteins (0.1 microg/ml to 100 microg/ml) to growth-arrested HMC for 72 h, zymography of the conditioned medium established that only fibronectin and collagens I and IV dose-dependently increased latent (72 kD) MMP2 secretion and activation. Fibronectin, however, also induced the secretion of MMP9. Membranes from HMC that had been co-cultured with fibronectin for 72 h were prepared to investigate whether the activation of MMP2 in this system was due to the action of membrane-type (MT)-MMP. When incubated with latent MMP2 for times up to 24 h, these membranes activated the enzyme in a time- and dose-dependent manner. The results demonstrate that specific matrix components increased the secretion of MMP2 and MMP9 from HMC. In addition, MT-MMP activity, selectively induced by fibronectin, was implicated in the activation of the secreted proteinases.

Animals↗

Longitudinal assessment of the dose consistency of botulinum toxin type A (BOTOX) for cervical dystonia.

Botulinum toxin type A (BoNT/A) is the principal therapy for patients with cervical dystonia. Repeated treatments over many years are required in most cases. This retrospective review evaluates the dose of BoNT/A used to treat cervical dystonia and the interval between treatments during a 2-year observation period. Outcomes data were abstracted from the medical records of 172 patients at 3 different sites who had received BoNT/A between January and December 1998. A total of 1059 treatments were assessed. Mean per-treatment doses throughout the 2-year study ranged from 241.80 to 254.07 units. The mean interval between treatments was 108.48 days during the first year of observation and 114.14 days during the second year. These findings indicate that doses of and intervals between BoNT/A treatments for cervical dystonia were consistent throughout 2 years of observation.

Adult↗

Morphology of the turtle accessory optic system.

Neural signals of the moving visual world are detected by a subclass of retinal ganglion cells that project to the accessory optic system in the vertebrate brainstem. We studied the dendritic morphologies and direction tuning of these brainstem neurons in turtle (Pseudemys scripta elegans) to understand their role in visual processing. Full-field checkerboard patterns were drifted on the contralateral retina while whole-cell recordings were made in the basal optic nucleus in an intact brainstem preparation in vitro. Neurobiotin diffused into the neurons during the recording and was subsequently localized in brain sections. Neuronal morphologies were traced using appropriate computer software to analyze their position in the brainstem. Most labeled neurons were fusiform in shape and had numerous varicosities along their processes. The majority of dendritic trees spread out in a transverse plane perpendicular to the rostrocaudal axis of the nucleus. Neurons near the brainstem surface were often oriented tangential to that surface, whereas more cells at the dorsal side of the nucleus were oriented radial to the brainstem surface. Further analysis of Nissl-stained neurons revealed the largest neurons are located in the rostral and medial portions of the nucleus although neurons are most densely packed in the middle of the nucleus. The preferred directions of the visual responses of the neurons in this sample did not correlate with their morphology and position in the nucleus. Therefore, the morphology of the cells in the turtle accessory optic system appears dependent on its position within the nucleus while its visual responses may depend on the synaptic inputs that contact each cell.

Animals↗

Cancer cluster investigations: use of a hybrid approach in a rural county.

A rural community expressed concern about a perceived excess of kidney and pancreatic cancer coupled with contamination of drinking water with atrazine, benzene, ethylene dibromide, and nitrate. Incidence and mortality for these two cancers were compared to what might be expected. A literature review was conducted for risk factors for kidney and pancreatic cancer as well as for the effects of the above 4 chemicals on these 2 cancers. Interviews with cases or surrogates ascertained chemical and risk factor exposures for these 2 cancers. Chemical exposures found in the public drinking water supply were evaluated as to their carcinogenicity. Hospital cases were compared to cases in the cancer registry. No statistically significant increases in kidney and pancreatic cancer incidence or mortality were found. The major risk factor found in the literature for these 2 cancers was smoking. Most of the cases were smokers and the chemicals found in the drinking water were not found to pose a risk for these 2 cancers. This approach provided considerable information, suggested prevention options and additional research, and is recommended for responding to cancer cluster concerns originating in the community (reactive approach). A proactive approach to cancer cluster surveillance and research was also used and is recommended for state or large local health departments.

Cluster Analysis↗