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Biomedical subjects

M E Fritz

Publications and source records attributed to M E Fritz.

At least 19 recordsLinked to original sources

Pharmacokinetics of midazolam administered by continuous intravenous infusion to intensive care patients.

OBJECTIVE: To determine the pharmacokinetics of continuously infused midazolam in patients during intensive care. DESIGN: Descriptive trial. SETTING: General ICU in a Swiss hospital. SUBJECTS: Eight critically ill patients requiring mechanical ventilation. INTERVENTIONS: To achieve an appropriate level of long-term sedation, the rate of iv infusion of midazolam in ICU patients was adjusted individually to between 6 and 15 mg/hr. Blood samples were taken during and after the continuous infusion of midazolam. MEASUREMENTS: Measurements included plasma concentration time profiles of midazolam and pharmacokinetic parameters, such as elimination half-life, clearance, and volume of distribution. RESULTS: The elimination half-life was prolonged (mean 5.4 vs. 2.3 hrs) and the volume of distribution was larger (3.1 vs. 0.9 L/kg) in patients vs. healthy volunteers. The clearance did not differ between groups (6.3 vs. 4.9 mL/min/kg in patients vs. volunteers, respectively). CONCLUSIONS: The increased volume of distribution in our critically ill patients is the major determinant for the observed slower elimination of midazolam. It is unlikely that the hepatic metabolism of midazolam was impaired in these patients.

Adult

Dental implants: a review.

The present article is a review presenting an update on the field of dental implants since the World Workshop in Clinical Periodontics in July 1989. Areas that are discussed include following: 1. Biomaterials and the implant interface, and the interaction of these with the environment. 2. Periodontal considerations including data supporting a perimucosal seal of implant to soft tissue and discussion of the endosseous interface between the bone and the implant. 3. Newer techniques of diagnostic imaging and their determination of bone types are related to the future practice of dental implants. 4. Implant selection and the surgical techniques involved in implant placement. 5. Current ideas of implant prosthodontics, implant maintenance, and the treatment of implant failures. 6. Finally, the use of dental implants in the United States and Sweden.

Dental Implantation, Endosseous

Multicenter evaluation of tetracycline fiber therapy: I. Experimental design, methods, and baseline data.

The study design and baseline characteristics of a multicenter trial to test the effectiveness and safety of locally delivered tetracycline for treatment of adult periodontitis are described. Local delivery was provided by 0.5 mm diameter ethylene vinyl acetate copolymer fibers loaded 25% with tetracycline hydrochloride which were placed into periodontal pockets and maintained by an adhesive for 10 (+/- 2) days. A total of 113 subjects (56 male and 57 female; mean age 49.3 yr) at five centers participated in the study. Subjects were selected who had 4 nonadjacent teeth with 6-10 mm pockets that bled on probing. The selected sites in each subject were randomly assigned to 4 test groups: tetracycline fiber, control fiber, scaling with root planing, or untreated. A balanced experimental design was thereby established in which each subject contributed equally by providing 4 clinically comparable sites for evaluation. To provide a more specific model for testing periodontitis therapy, gingivitis was treated prior to the initiation of the study by prophylaxis with supragingival calculus removal and home care instruction. Clinical response variables measured were pocket depth reduction, attachment level gain and bleeding on controlled-force probing measured at baseline, 30 d, and 60 d. Levels of 6 bacterial species selected as probable periodontal pathogens were measured by DNA probe analysis of plaque samples. The design of this study provided several unique analytical opportunities. Controls included a comparison with conventional treatment, analysis of vehicle effects, and effects at untreated sites. Comparison of the test group with controls permitted evaluation of the principal variables that could effect interpretation of results.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Multicenter evaluation of tetracycline fiber therapy: II. Clinical response.

The safety and efficacy of periodontal disease treatment by intrapocket placement of tetracycline (TC) fibers was investigated in a 60-day multicenter study conducted by selecting 4 sites in each subject with 6-10 mm pockets that bled on probing. Sites were randomly assigned to 1 of 4 test groups: TC fiber therapy, scaling, control fiber (fibers without drug), or untreated. TC fibers and control fibers were placed to fill the pocket and were maintained with a cyanoacrylate adhesive for 10(+/- 2) d. Scaling was performed for a minimum of 5 min under local anesthesia. Following initial tooth cleaning procedures, pocket depth, attachment level and bleeding on controlled-force probing were measured at baseline and at 30 d, and 60 d following therapy. Analysis of data from 107 subjects who had complete clinical data sets indicated that TC fiber therapy significantly decreased pocket depth, increased attachment level, and decreased bleeding on controlled-force probing to a greater extent than observed in all other test groups including scaling. These effects were greater than, and in addition to, effects that occurred due to prophylaxis and improved home care. No serious adverse side-effects attributed to TC fiber therapy were observed. No TC fiber-treated sites abscessed and superinfection was not noted. A transient redness at fiber removal was seen at 21% of the sites. Although fibers were placed without anesthesia, mild pain on initial placement was infrequent (19%) and abated rapidly. The results indicate that TC fiber placement provides a safe and effective means for treatment of periodontal infections.

Adult

Inhibition of human periodontal prostaglandin E2 synthesis with selected agents.

Considerable evidence has demonstrated the importance of PGE2 synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE2 synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE2 synthesis in periodontal tissues. The apparent IC50 values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE2 synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence of 3H-arachidonic acid for 45 min at 37 degrees C. Inhibitors were tested at 10(-10)-10(-4) M and at zero concentration to measure conversion of 3H-arachidonate to 3H-PGE2. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE2 was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE2 present in the sample to correct for antibody capture recovery. The apparent IC50 values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE2/min/mg tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid

Clinical management of keratoconus. A multicenter analysis.

The clinical management of 746 eyes in 417 patients referred for keratoconus from January 1984 through January 1988 was retrospectively analyzed. In 357 patients, 554 eyes (74%) did not require surgery and were managed with contact lenses or spectacles, 156 eyes (21%) in 137 patients either underwent penetrating keratoplasty (PK) (140 eyes) or surgery was recommended (16 eyes), and 36 eyes (4%) in 34 patients underwent epikeratoplasty. Comparing baseline and final examination findings, the nonsurgical group showed a significant improvement in average best-corrected visual acuity from 20/30 to 20/25, the PK group from 20/70 to 20/25, and the epikeratoplasty group from 20/40 to 20/30. Average keratometry was unchanged in the nonsurgical group, but decreased by 10.7 diopters (D) for the PK group and 6.5 D for the epikeratoplasty group. Corneal cylinder was unchanged in the nonsurgical group, whereas there was a reduction of the percentage of eyes with indeterminant cylinder from 55 to 2% in the PK group and from 36 to 0% in the epikeratoplasty group. Previous contact lens history, best-corrected visual acuity of 20/50 or worse, and average keratometry of 55 D or greater at baseline were associated with a significant risk for PK. No baseline variables were associated with significant risk for epikeratoplasty, suggesting that this group was similar to the nonsurgical group, except for contact lens intolerance. The nonsurgical management of keratoconus continues to play a predominant role in the management of this disorder in a referral population.

Adolescent

Osseo-integrated implant treatment of a patient with rapidly progressive periodontitis. A case report.

The case report presented describes placement of osseointegrated fixtures in a patient with a probable history of rapidly progressive periodontitis. A 12-year history is presented. The post-operative sequelae of placing fixtures in a fully edentulous maxilla and partially edentulous mandible were the worst seen by the Implant Team at Emory University. The hypothesis presented is that patients with aggressive forms of periodontal disease should be subjected to appropriate mechanical and antimicrobial therapy to produce a healthy oral flora before any implants are placed.

Adult

Full circle or forward.

In the early 70s when a parent with abuse problems named Jolly K. sought help to stop her abusive behavior, there were no services for parents. Today, nearly two decades later, there has not been much improvement with regard to the provision of services for parents. Our belief is that the dichotomy which occurred early in the field's development between those who were for the child, and those (such as Parents Anonymous) who sought to provide services to parents and were presumed to be for the parent and implicitly against the child is largely responsible for an ever more punitive approach to the problem. The solution lies in shifting our focus away from the exclusive mandate to protect the child towards support for the family unit. Such a shift should include expanding the knowledge base of the field by the inclusion of information from fields such as alcoholism, spouse abuse, and eating disorders, as well as by advocating for services which support the family. Research into the part that neuro-chemistry plays in violence should also be undertaken. The impetus for change within the field cannot come from the child protective services (CPS) system, which, as a creature of the law, can only be reactive, not pro-active. Professionals working outside the CPS system must take responsibility for change if it is to occur.

Brain Chemistry

Elevated serum levels of soluble Tac peptide in adult T-cell leukemia: correlation with clinical status during chemotherapy.

Adult T-cell leukemia associated with human T-cell leukemia virus type I (HTLV-I) is characterized by a clonal expansion of a CD4-positive subset of T lymphocytes that constitutively express high numbers of interleukin-2 receptors and that frequently infiltrate the skin; osteolytic bone lesions, and hypercalcemia. Using an enzyme-linked immunosorbent assay (ELISA) test, we measured the level of soluble Tac peptide, one chain of the human interleukin-2 receptor, in the serum of 50 patients with adult T-cell leukemia (38 Japanese and 12 American patients), 8 patients with other hematologic malignancies, 8 asymptomatic HTLV-I-antibody-positive carriers, and 17 normal controls. The serum level of soluble Tac peptide (geometric mean U/mL, 95% CI) was elevated at presentation in all patients with adult T-cell leukemia (16,461; 819 to 330,896) when compared with normal controls (238; 112 to 502), patients with other hematologic malignancies (1302; 475 to 3569), and healthy HTLV-I antibody-positive carriers (490; 115 to 2086). The highest levels were seen in patients (n = 33) with acute (32,154; 2587 to 399,598) compared with chronic (5464; 661 to 45,156) disease (n = 14). Serum levels of Tac peptide also tended to be more elevated in patients with adult T-cell leukemia with hypercalcemia (32,072; 2461 to 417,908) compared with normocalcemic patients (13,885; 496 to 388,436). Serial measurements of soluble Tac peptide levels in serum were done in four patients with adult T-cell leukemia during chemotherapy and the levels reflected disease activity. These observations suggest that the measurement of soluble Tac peptide levels in patients with adult T-cell leukemia is useful as a noninvasive measure of tumor burden and will help in the diagnosis of the disease and management of these patients.

Acute Disease

Soluble Tac peptide is present in the urine of normal individuals and at elevated levels in patients with adult T cell leukaemia (ATL).

The T lymphocyte-derived lymphokine interleukin 2 and the cell-associated receptor for this molecule play major roles in the activation and regulation of the human immune response. An enzyme-linked immunosorbent assay has been developed to measure quantitatively a soluble form of one component of the human interleukin 2 receptor, namely the Tac peptide. In the present studies, soluble Tac peptide was measured in the urine of normal individuals (mean = 92 U/ml), a level not significantly different (0.01 less than P less than 0.05) from the corresponding serum concentrations (mean = 175). The urinary Tac peptide had a molecular weight of 40-45 kD by sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis and specifically bound interleukin 2. Elevated levels of urinary Tac peptide were found in four patients with adult T cell leukaemia who also had elevated serum levels of Tac peptide. Thus, urine may represent a valuable source of lymphokine-binding proteins that may serve as important markers of immunological activation.

Adult

Epikeratoplasty. The surgical correction of aphakia, myopia, and keratoconus.

Thirty-five patients have had 39 consecutive epikeratoplasty procedures (12 adult aphakic, 9 pediatric aphakic, 12 myopic, and 6 keratoconic eyes) by the same surgeon, using commercially prepared lenticules. The lenticule remained totally clear in 85% of eyes. Two lenticules were removed due to infection and scarring; four lenticules had minimal scarring and did not require removal. Spectacle-corrected acuity was worse than one line from the preoperative spectacle-corrected acuity in 58% of the adult aphakic eyes; however, 75% were 20/50 or better postoperatively. Fifty percent were within 2 diopters (D) of emmetropia and 92% within 3 D. All pediatric aphakic patients showed an improvement in best-corrected acuity, and 83% of eyes at 6 months were within 2 D of emmetropia; by 1 year a 3.4-D average myopic shift had occurred. Two of the six eyes (33%) using the original myopia technique were within 2 D of emmetropia, whereas five of the six eyes (83%) with the current technique are within this range. Spectacle-corrected acuity in the entire current myopia group has either improved by one or more lines or has remained unchanged. Five of the six keratoconic eyes had 20/40 or better spectacle-corrected and 20/25 contact lens-corrected acuity postoperatively; average corneal flattening was 6 D. Persistent epithelial defect and irregular astigmatism were the principal factors in delay in visual recovery.

Adolescent

The use of blade implants in a selected population of partially edentulous adults. A 15-year report.

In order to provide longitudinal data for endosteal bladevent implants, a continuing study is being conducted from an original group of 49 implants in 32 patients placed 15 years ago. The present work evaluated 26 of these bladevent implants in 18 patients. Three basic patterns were observed 15 years postoperatively: (1) In 13 of 26 implants, there was clinical and radiographic evidence of health; (2) in 13 of 26 implants, there was a radiolucency 2- to 3-mm square around the neck and shoulder of the implants, along with sulcular depths capable of being probed and evidence of bleeding on probing; and (3) two implants showed evidence of settling deeper into the bone. These results indicate that bladevent endosteal implants can be maintained in the mouth for up to 15 years, and 50% can be free from periodontal disease.

Adult

An analysis of the cellular requirements for the production of soluble interleukin-2 receptors in vitro.

Following activation in vitro, peripheral blood mononuclear cells (PBMC) express cell-associated interleukin-2 receptors (IL-2R) and also release soluble IL-2R into culture supernatants. The present studies were undertaken to define which normal cells were responsible for the release of soluble IL-2R in vitro. Both cell-associated and soluble IL-2R were quantitatively measured with a "sandwich" enzyme-linked immunoassay employing two monoclonal antibodies. PBMC were separated into populations of surface immunoglobulin-negative cells (T cells and monocytes) and surface immunoglobulin-positive cells (B cells and monocytes), and the T-cell population was further separated into OKT4-positive (OKT4+) cells and OKT4-negative (OKT4-) cells. Following activation with phytohemagglutinin, pokeweed mitogen, and the monoclonal antibody OKT3, large amounts of soluble IL-2R were released by PBMC, unseparated T cells, OKT4+ T cells, and OKT4- T cells. The population containing B cells and monocytes made small but readily detectable amounts of soluble IL-2R when stimulated with these T-cell mitogens; likely the result of contaminating T cells in the population. However, when highly purified B cells were stimulated with Staphylococcus aureus Cowan and recombinant IL-2, they also released small amounts of soluble IL-2R. The release of soluble IL-2R by T cells appeared monocyte dependent when OKT3, but not phytohemagglutinin, was employed for activation, and monocytes themselves released no detectable IL-2R under the conditions employed. These studies define the cellular requirements for the release of soluble IL-2R in vitro and demonstrate that such receptors are released by B cells, T cells, and both OKT4+ and OKT4- T-cell subsets.

B-Lymphocytes

The production of soluble and cellular interleukin-2 receptors by cord blood mononuclear cells following in vitro activation.

Cord blood mononuclear cells (CBMC) were investigated for their capacity to generate both cellular and soluble, supernatant interleukin-2 receptors (IL-2R) following cellular activation in vitro. Soluble IL-2R were measured in cell-free supernatants and in detergent-solubilized cell extracts with a "sandwich" enzyme-linked immunosorbent assay. CBMC and adult peripheral blood mononuclear cells were activated with phytohemagglutinin or the murine monoclonal antibody OKT3. CBMC and adult peripheral blood mononuclear cells generated cellular and soluble IL-2R in response to both activators. Peak values for supernatant IL-2R were observed on day 7, while peak values of cell-associated IL-2R occurred on day 5, followed by a decline on day 7. With the exception of supernatant IL-2R production induced by OKT3 stimulation, CBMC produced IL-2R in amounts comparable to adult mononuclear cells. Cord blood plasma also contained amounts of IL-2R comparable to that found in adult sera/plasma. Thus, CBMC appear largely immunocompetent with regard to the expression of IL-2R.

Adult

Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro.

With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R released from either the HTLV I-positive T cell line HUT 102B2 or normal phytohemagglutinin-activated PBMC demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.

Cell Division