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Biomedical subjects

D C Martin

Publications and source records attributed to D C Martin.

At least 55 records · Page 3Linked to original sources
PubMed1997

An information infrastructure for long-term care.

Emerging trends promise to alter the way long-term care is practiced. These include: changing regulation of the nursing home industry with emphasis on outcome and assessment, a trend in medical informatics away from expert systems and toward on-line decision support and reminder systems, and the application of industrial statistical quality management techniques to the realm of human services. Emerging standards such as the Arden Syntax and Unified Medical Language Systems and technologies such as Rapid Application Development Tools will facilitate the use of modern computing to mold and implement these converging trends.

Abstracting and Indexing↗
PubMed1996

Inhibition of SV40 T antigen-induced hepatocellular carcinoma in TIMP-1 transgenic mice.

The potential of tissue inhibitors of metalloproteinases (TIMPs) to inhibit neoplastic progression has been postulated from studies of genetically manipulated cells. To investigate whether the TIMP-1 expressed in a host tissue suppresses cancer in vivo and to identify the affected stages, we developed transgenic mice with constitutive overexpression or reduction of TIMP-1 in the liver. In double transgenic experiments, the TIMP-1 lines were crossed with a second transgenic line which expresses the Simian Virus 40t/T antigen (TAg). This viral oncogene leads to heritable development of hepatocellular carcinomas with a 100% incidence. Effects of TIMP-1 coexpression on the TAg-induced neoplasms were determined at the tissue and cellular level. Here, we report that overexpression of hepatic TIMP-1 blocked the development of TAg-induced hepatocellular carcinomas. High TIMP-1 levels inhibited not only the later stages in tumor development (growth and angiogenesis), but also events associated with tumor initiation (altered hepatocyte cytology and tissue architecture). We further show that an antisense-mediated reduction of TIMP-1 resulted in a more rapid tumor initiation and progression. These data demonstrate that intrinsic TIMP-1 levels contribute to a tissue's susceptibility to viral oncogene-induced tumorigenesis.

Animals↗
PubMed1996

The risk for and severity of bleeding complications in elderly patients treated with warfarin. The National Consortium of Anticoagulation Clinics.

OBJECTIVE: To determine whether increasing age is associated with an increased risk for bleeding during warfarin treatment. DESIGN: Combined retrospective and prospective cohort studies. SETTING: 6 anticoagulation clinics. PATIENTS: 2376 patients receiving warfarin for various indications. MEASUREMENTS: Bleeding events categorized as minor (resulting in no costs or consequences), serious (requiring testing or treatment), life-threatening, or fatal. RESULTS: 812 first bleeding events (4 fatal, 33 life-threatening, 222 serious, and 553 minor) occurred during 3702 patient-years. Age was inversely related to the mean warfarin dose and dose-adjusted prothrombin time ratio. The unadjusted incidence of minor bleeding complications did not vary according to age group: 18.0 per 100 patient-years for patients younger than 50 years of age, 21.5 for patients 50 to 59 years of age, 24.0 for patients 60 to 69 years of age; 23.5 for patients 70 to 79 years of age, and 16.3 for patient 80 years of age and older. The unadjusted incidence of serious bleeding complications also did not vary according to age group: 9.3 per 100 patient-years for patients younger than 50 years of age, 7.1 for patients 50 to 59 years of age, 6.6 for patients 60 to 69 years of age, 5.1 for patients 70 to 79 years of age, and 4.4 for patients 80 years of age and older. The unadjusted incidence of life-threatening or fatal complications combined was significantly higher among the oldest patients: 0.75 per 100 patient-years for patients younger than 50 years of age, 0.97 for patients 50 to 59 years of age, 1.10 for patients 60 to 69 years of age, 0.68 for patients 70 to 79 years of age, and 3.38 for patients 80 years of age and older. Patients 80 years of age and older had a relative risk of 4.5 (95% CI, 1.3 to 15.6) compared with patients younger than 50 years of age. After adjustment for the intensity of anticoagulation therapy and the deviation in the prothrombin time ratio using Cox and Poisson regression, age was not generally associated with the occurrence of bleeding; relative risk estimates ranged from 0.99 to 1.03 per year of age (lower-bound 95% CI, 0.97 to 1.01; upper-bound 95% CI, 1.00 to 1.09). The single exception was life-threatening and fatal complications in patients 80 years of age or older (relative risk, 4.6 [CI, 1.2 to 18.1]). CONCLUSIONS: Age did not appear to be an important determinant of risk for bleeding in patients receiving warfarin, with the possible exception of age 80 years or older. The intensity of anticoagulation therapy and the deviation in the prothrombin time ratio were much stronger predictors of risk for bleeding.

Age Factors↗
PubMed1996

A comparative study of ovarian and pelvic wall-infiltrating endometriosis.

STUDY OBJECTIVE: To compare the histology of ovarian endometriomas (OE) with that of pelvic wall-infiltrating endometriosis (PWIE) in an attempt to elucidate their histopathologic and clinical differences. DESIGN: Retrospective histologic study. SETTING: University-affiliated hospital. SUBJECTS: Randomly selected tissue samples of 10 cases each of OE and PWIE. Interventions. Immunoperoxidase and Masson's trichrome stains were applied to the samples to determine the presence of myofibroblasts and collagen, respectively. MEASUREMENTS AND MAIN RESULTS: All cases of OE showed changes suggestive of type 3 collagen deposition and myofibroblast proliferation. All cases of PWIE showed changes suggestive of type 1 collagen deposition and extensive smooth muscle metaplasia. The endometrial glands and stroma of OE tended to be on the inside lining of the chocolate cyst and did not freely intermix with native ovarian collagen. The lesions of PWIE, however, showed endometrial glands and stroma mixing freely with the native pelvic wall collagen. CONCLUSIONS: These findings suggest two different mechanisms for the pathogenesis of OE and PWIE and offer a rationale for using different surgical approaches to the different sites. Ovarian endometriosis is a lesion within the ovary with a response compatible with recent metastasis, whereas PWIE appears to be a metaplastic reaction.

Coloring Agents↗
PubMed1996

Overutilization of acute-care beds in Veterans Affairs hospitals.

The authors tested the hypothesis that the Department of Veterans Affairs (VA) hospitals would have substantial overutilization of acute care beds and services because of policies that emphasize inpatient care over ambulatory care. Reviewers from 24 randomly selected VA hospitals applied the InterQual ISD* (Intensity, Severity, Discharge) criteria for appropriateness concurrently to a random sample of 2,432 admissions to acute medical, surgical, and psychiatry services. Reliability of hospital reviewers in applying the ISD* criteria was tested by comparing their reviews with those of a small group of expert reviewers. Validity of the ISD* criteria was tested by comparing the assessments of master reviewers with the implicit judgments of panels of nine physicians. The physician panels validated the ISD* admission criteria for medicine and surgery (74% agreement with master reviewers, kappa > 0.4), whereas the psychiatry criteria were not validated (66% agreement, kappa 0.29). Hospital reviewers reliably used all three criteria sets (> 83% agreement with master reviewers, kappa > 0.6). Rates of nonacute admissions to acute medical and surgical services were > 38% as determined by the hospital and master reviewers and by the physician panels. Nonacute rates of continued stay were > 32% for both medicine and surgery services. Similar rates of nonacute admissions and continued stay were found for all 24 hospitals. Reasons for nonacute admissions and continued stay included lack of an ambulatory care alternative, conservative physician practices, delays in discharge planning, and social factors such as homelessness and long travel distances to the hospital. Using criteria that the authors showed to be reliable and valid, substantial overutilization of acute medicine and surgical beds was found in a representative sample of VA hospitals. Correcting this situation will require changes in physician practice patterns, development of ambulatory care alternatives to inpatient care, and modification of current VA policies determining eligibility for care.

Acute Disease↗
PubMed1995

Spermidine attenuation of volatile anesthetic inhibition of glutamate-stimulated [3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine ([3H]MK-801) binding to N-methyl-D-aspartate (NMDA) receptors in rat brain.

The influence of spermidine, a polyamine agonist, on volatile anesthetic inhibition of N-methyl-D-aspartate (NMDA) receptor activation, as indicated by glutamate stimulation of [3H]MK-801 ([3H](5D,10S)-(+)-methyl-10,11-dihydro-5H- dibenzo[a,d]cyclohepten-5,10-imine) binding, was studied in rat brain. Spermidine reserved the inhibition caused by four volatile anesthetics (enflurane, halothane, methoxyflurane and chloroform) at the same concentrations (EC50 approximately 3 microM) at which it potentiated glutamate opening of the NMDA ion channel. The anesthetics had no effect on the direct stimulation of channel opening by spermidine, which occurred at concentrations of spermidine greater than 30 microM in the absence of receptor agonist. In these actions, spermidine closely resembled the allosteric co-agonist glycine. The present results suggest that anesthetic action on NMDA receptors involves a set of sites on the channel complex that is distinct from the recognition sites for glutamate, glycine, and channel blockers, and are consistent with the idea that blockade of NMDA receptors contributes to the development of the anesthetic state.

Anesthetics, Inhalation↗
PubMed1995

Breaking the matches in a paired t-test for community interventions when the number of pairs is small.

There is considerable interest in community interventions for health promotion, where the community is the experimental unit. Because such interventions are expensive, the number of experimental units (communities) is usually small. Because of the small number of communities involved, investigators often match treatment and control communities on demographic variables before randomization to minimize the possibility of a bad split. Unfortunately, matching has been shown to decrease the power of the design when the number of pairs is small, unless the matching variable is very highly correlated with the outcome variable (in this case, with change in the health behaviour). We used computer simulation to examine the performance of an approach in which we matched communities but performed an unmatched analysis. If the appropriate matching variables are unknown, and there are fewer than ten pairs, an unmatched design and analysis has the most power. If, however, one prefers a matched design, then for N < 10, power can be increased by performing an unmatched analysis of the matched data. We also discuss a variant of this procedure, in which an unmatched analysis is performed only if the matching 'did not work'.

Health Promotion↗
PubMed1995

Volatile anesthetics and glutamate activation of N-methyl-D-aspartate receptors.

Several studies have indicated important functional interactions between volatile anesthetics and the N-methyl-D-aspartate (NMDA) class of glutamate receptors. In the present study, we examined the effects of diethyl ether, chloroform, methoxyflurane, halothane, enflurane, and isoflurane on (1) glutamate activation of the NMDA receptor complex, including glycine reversal of anesthetic action, as revealed by [3H]-(5R, 10S)-(+)methyl-10,11-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine, dizocilpine (MK-801) binding to the cation channel, and (2) [3H]cis-4-( phosphonomethyl)piperidine-2-carboxylic acid (CGS 19755) binding to the glutamate recognition site of the NMDA receptor In agreement with previous studies, glutamate increased the binding of 1 nM [3H]MK-801, measured after a 1-hr incubation at 37 degrees, by up to several hundred fold. This stimulation was blocked by glutamate antagonists and potentiated by glycine with an EC50 of approximately 0.03 muM. Glycine also had a direct stimulatory effect on [3H]MK-801 binding at much higher concentrations ( > or = 10 muM). All of the anesthetics examined depressed glutamate stimulation of [3H]MK-801 binding in a concentration-dependent manner with the following order of potency: halothane > or = enflurane > methoxyflurane > chloroform > diethyl ether. This inhibition of [3H]MK-801 binding was observed at concentrations that are routinely attained in the cerebrospinal fluid during surgical anesthesia. Moreover, the inhibition was reversed rapidly following removal of the anesthetics from the assay medium. Inclusion of glycine in the incubation medium markedly attenuated anesthetic-induced inhibition of glutamate-sensitive [3H]MK-801 binding with an EC50 of between 0.1 and 1 muM. Thus, this reversal by glycine correlated with its potentiating as opposed to its direct stimulatory, effect on NMDA receptors. Anesthetic inhibition of [3H]MK-801 binding could not be overcome by raising the glutamate concentration (i.e. the interaction did not appear to be competitive with respect to glutamate) unless glycine was present. Binding of [3H]CGS 19755 to the glutamate recognition site was also inhibited by each of the anesthetics examined. However, with the exception of chloroform, all of the anesthetics were more potent inhibitors of glutamate-stimulated [3H]MK-801 binding than they were of [3H]CGS 19755 binding. [3H]CGS 19755 binding saturation curves in the presence of halothane and enflurane indicated a decrease in the density of [3H]-CGS 19755 binding sites with no change in binding affinity (i.e. the inhibition did not appear to be competitive). These findings support the idea that anesthetic drugs disrupt NMDA receptor transmission through multiple allosteric effects on the receptor-channel activation mechanisms and the glutamate binding site.

Anesthetics, Inhalation↗
PubMed1995

Utilization of transgenic mice in the study of matrix degrading proteinases and their inhibitors.

The extracellular matrix (ECM) acts as both a structural scaffold and an informational medium. Its dynamic status is determined by cells that secrete its constituent molecules and, in most cases, also secrete enzymes that catalyze degradation of these molecules. A stasis between ECM degrading enzymes and their inhibitors maintains the integrity of the matrix. While controlled ECM remodelling is fundamental to several normal processes, uncontrolled disruption underlies diverse pathological conditions. Transgenic mice with specific modulations or a total lack of expression of certain metalloproteinases, serine proteinases or their inhibitors have been generated to elucidate endogenous expression patterns, identify regulatory elements of these genes, and study the physiological consequences of their deregulated expression. With these models we enhance our understanding of the role of proteinases and their inhibitors in diverse normal processes and pathologies including mammary gland development, hemostasis, emphysema and cancer.

Animals↗
PubMed1995

Coexpression of 5-HT2A and 5-HT4 receptors coupled to distinct signaling pathways in human intestinal muscle cells.

BACKGROUND & AIMS: The type and function of 5-hydroxytryptamine (5HT) receptors on intestinal muscle cells in humans are not known. 5-HT receptors were characterized pharmacologically and by radioligand binding. METHODS: Contraction, relaxation, inositol 1,4,5-triphosphate (IP3) and adenosine 3',5'-cyclic monophosphate (cAMP) formation, and 5-HT binding were measured in dispersed muscle cells and in cells in which only one receptor type was preserved by selective receptor protection. RESULTS: 5-HT binding was completely inhibited by 5-HT and partially by 5-HT2A (ketanserin), 5-HT4 (SDZ-205,557), and 5-HT1p (N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide; 5-HTP-DP) receptor antagonists. 5-HT caused contraction that was inhibited by ketanserin and augmented by SDZ-205,557 and 5-HTP-DP. In the presence of ketanserin, 5-HT caused relaxation of cholecystokinin-contracted cells that was inhibited by SDZ-205,557 and 5-HTP-DP. 5-HT increased IP3, which was inhibited by ketanserin, and cAMP, which was inhibited by SDZ-205,557 and 5-HTP-DP. In cells with only 5-HT2A receptors, 5-HT caused contraction only, and residual binding was inhibited by ketanserin. In cells with only 5-HT4/5-HT1p receptors, 5-HT caused only relaxation and residual binding was inhibited by SDZ-205,557 and 5-HTP-DP. CONCLUSIONS: 5-HT2A receptors mediating contraction and 5-HT4 receptors mediating relaxation coexist on human intestinal muscle cells. The 5-HT4 receptors are closely similar or identical to 5-HT1p receptors.

4-Aminobenzoic Acid↗
PubMed1995

Optimal survey design for community intervention evaluations: cohort or cross-sectional?

Community intervention evaluations that measure changes over time may conduct repeated cross-sectional surveys, follow a cohort of residents over time, or (often) use both designs. Each survey design has implications for precision and cost. To explore these issues, we assume that two waves of surveys are conducted, and that the goal is to estimate change in behavior for people who reside in the community at both times. Cohort designs are shown to provide more accurate estimates (in the sense of lower mean squared error) than cross-sectional estimates if (1) there is strong correlation over time in an individual's behavior at time 0 and time 1, (2) relatively few subjects are lost to followup, (3) the bias is relatively small, and (4) the available sample size is not too large. Otherwise, a repeated cross-sectional design is more efficient. We developed methods for choosing between the two designs, and applied them to actual survey data. Owing to drop-outs and losses to followup, the cohort estimates were usually more biased than the cross-sectional estimates. The correlations over time for most of the variables studied were also high. In many instances the cohort estimate, although biased, is preferred to the relatively unbiased cross-sectional estimate because the mean squared error was smaller for the cohort than for the cross-sectional estimate. If these results are replicated in other data, they may result in guidelines for choosing a more efficient study design.

Cohort Studies↗
PubMed1995

Association of Chlamydia trachomatis immunoglobulin gamma titers with dystrophic peritoneal calcification, psammoma bodies, adhesions, and hydrosalpinges.

OBJECTIVE: To correlate Chlamydia trachomatis immunoglobulin gamma (IgG) titers with psammoma bodies, dystrophic peritoneal calcification, degree of calcification, adhesions, and hydrosalpinges. DESIGN: This is a prospective single-blinded histologic analysis of tissue and retrospective analysis of historical laboratory and clinical variables. SETTING: Tertiary hospital and private practice patient charts. PATIENTS: Sixty consecutive patients with C. trachomatis IgG titers reported on the coding sheets of a previous study for endometriosis. MAIN OUTCOME MEASURES: The histologic slides were reviewed in a blinded fashion for calcification. Previously used data sheets were reviewed for C. trachomatis IgG titers. Historical data, adhesion scores, hystrosalpingogram findings, and laparoscopic findings were obtained from charts. RESULTS: Dystrophic calcification, psammoma bodies, moderate-to-severe dystrophic calcification and hydrosalpinges were associated with positive C. trachomatis IgG titers. CONCLUSION: This study suggests relationship of C. trachomatis with dystrophic calcification, psammoma bodies, adhesions, and hydrosalpinges. This relationship suggests that C. trachomatis IgG titers can be used as a marker to help determine those infertility patients who might best benefit from hysterosalpingogram or laparoscopy and in clinical studies of endometriosis, infertility, pain, or ovarian cancer. However, there is no current data to suggest a need for therapy on the basis of a positive C. trachomatis IgG titer or of dystrophic peritoneal calcification.

Body Fluids↗
PubMed1995

Anecdotal association of endosalpingiosis with chlamydia trachomatis IgG titers and Fitz-Hugh-Curtis adhesions.

STUDY OBJECTIVE: To correlate Chlamydia trachomatis IgG titers with endosalpingiosis. DESIGN: Prospective, single-blind, histologic analysis of tissue, and retrospective analysis of historical laboratory and clinical variables. SETTING: A tertiary care patient practice. PATIENTS: Sixty consecutive patients with C. trachomatis IgG titers, 28 positive and 32 negative. INTERVENTIONS: The second review of histology slides and charts of these women. MEASUREMENTS AND MAIN RESULTS: One patient was found to have endosalpingiosis. She had Fitz-Hugh-Curtis (FHC) adhesions and a positive C. trachomatis IgG titer, but no endometriosis. CONCLUSIONS: This review confirmed an anecdotal association of endosalpingiosis with positive C. trachomatis IgG titers and FHC adhesions, but failed to demonstrate a statistically significant relationship due to the size of the sample.

Antibodies, Bacterial↗
PubMed1995

Use of algorithmic pathways to develop quality, cost-effective clinical care.

STUDY OBJECTIVES: To analyze the cost of diagnosis and treatment associated with hydrosalpinges and pelvic adhesions using algorithmic pathways. DESIGN: Analysis of six pathways: (1) Chlamydia IgG antibody titer -> hysterosalpingogram -> diagnostic laparoscopy -> in vitro fertilization (IVF); (2) Chlamydia IgG antibody titer -> diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (3) hysterosalpingogram -> diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (4) diagnostic laparoscopy -> therapeutic laparoscopy -> IVF; (5) no treatment; and (6) IVF only. SETTING: A tertiary care practice at a university-associated hospital. PATIENTS: Patients were retrospectively chosen on the basis of availability of results of Chlamydia IgG titers, operative notes from laparoscopy, and hysterosalpingograms (HSGs). All patients identified with these three results available were included. INTERVENTIONS: Determination of results of laparoscopic treatment, IVF, and no therapy (observation only), based on the literature. MEASUREMENTS AND MAIN RESULTS: The theoretical cost to achieve pregnancy for each pathway was calculated by mathematical modeling. The greatest number of pregnancies for the least cost ($18, 883/pregnancy) was from the diagnosis and treatment of adhesions at laparoscopy with no previous screening. The least costly approach to pregnancy for blocked tubes ($26,614/pregnancy) was to start with an HSG. All pathways for adhesions and any screening pathway using HSG for hydrosalpinges were more cost effective than IVF. CONCLUSIONS: These pathways are limited, as they require several assumptions and are based on a tertiary care population. Although HSG and laparoscopy appeared to be the most cost-effective approaches to pregnancy, a primary care group may have a more cost-effective response to the use of Chlamydia trachomatis IgG antibody screening.

Algorithms↗