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Biomedical subjects

M L Miller

Publications and source records attributed to M L Miller.

At least 127 records · Page 7Linked to original sources
PubMed1990

Development and validation of the Penn State Worry Questionnaire.

The present report describes the development of the Penn State Worry Questionnaire to measure the trait of worry. The 16-item instrument emerged from factor analysis of a large number of items and was found to possess high internal consistency and good test-retest reliability. The questionnaire correlates predictably with several psychological measures reasonably related to worry, and does not correlate with other measures more remote to the construct. Responses to the questionnaire are not influenced by social desirability. The measure was found to significantly discriminate college samples (a) who met all, some, or none of the DSM-III-R diagnostic criteria for generalized anxiety disorder and (b) who met criteria for GAD vs posttraumatic stress disorder. Among 34 GAD-diagnosed clinical subjects, the worry questionnaire was found not to correlate with other measures of anxiety or depression, indicating that it is tapping an independent construct with severely anxious individuals, and coping desensitization plus cognitive therapy was found to produce significantly greater reductions in the measure than did a nondirective therapy condition.

Adult↗
PubMed1990

Intravenous nitroglycerin-induced heparin resistance: a qualitative antithrombin III abnormality.

An ability of intravenous nitroglycerin to interfere with the anticoagulant properties of intravenous heparin would have profound clinical implications. To investigation nitroglycerin-heparin interactions, the following pilot study was performed. Patients (N = 18) admitted to the coronary care unit with a diagnosis of either acute myocardial infarction or unstable angina were divided into four treatment groups: (1) intravenous nitroglycerin and intravenous heparin; (2) intravenous nitroglycerin alone; (3) intravenous heparin alone; or (4) neither intravenous nitroglycerin nor intravenous heparin. Serial determinations of activated partial thromboplastin time (APTT), serum heparin concentration, antithrombin III (ATIII) antigen (ATA), and ATIII activity (ATC) were obtained over a 72-hour period. Overall, patients receiving intravenous nitroglycerin did not differ significantly from other patients in APTT, heparin dose, heparin concentration, ATA, ATC, or ATA/ATC ratio (ATR). However, patients receiving intravenous nitroglycerin at a rate exceeding 350 micrograms per minute had a lower APTT (p less than 0.05), lower ATC (p = 0.02), higher ATR (p = 0.004), and a larger heparin dose requirement than patients receiving lower infusion rates. ATR correlated directly (r = 0.91; p less than 0.05) and ATC inversely (r = -0.78; p less than 0.05) with the intravenous nitroglycerin dose. Serum heparin concentration did not correlate with the intravenous nitroglycerin dose. Intravenous nitroglycerin-induced heparin resistance occurs at a critical nitroglycerin dose. A nitroglycerin-induced qualitative ATIII abnormality may be the underlying mechanism.

Adult↗
PubMed1990

Ibuprofen suspension in the treatment of juvenile rheumatoid arthritis. Pediatric Rheumatology Collaborative Study Group.

Ninety-two children with juvenile rheumatoid arthritis were randomly assigned to treatment in a multicenter, double-blind, 12-week trial designed to compare the efficacy and safety of a liquid formulation of ibuprofen at a dosage of 30 to 40 mg/kg/day versus those of aspirin at a dosage of 60 to 80 mg/kg/day. No significant intergroup differences in response rates or in the amount of improvement in articular indexes of disease activity were observed. More children treated with aspirin discontinued treatment early because of adverse reactions. After this trial, 84 additional patients with juvenile rheumatoid arthritis entered a 24-week, multidose (30, 40, and 50 mg/kg/day), open trial of ibuprofen suspension. Favorable response rates for the three groups were similar, and continued improvement was observed throughout the 24-week period. A dose-response relationship was observed with respect to adverse reactions of the upper gastrointestinal tract. We conclude that ibuprofen suspension is an effective nonsteroidal antiinflammatory drug and that its tolerability in children is acceptable.

Adolescent↗
PubMed1990

Accelerated expression of anti-Sm and Y2 idiotype differ in dependence on T cell subsets in MRL/+ mice.

We investigated the role of MRl T cells in the induction of anti-Sm antibodies and Y2 idiotype. Four injections of Sm antigen in Freund's complete adjuvant were required to induce peak amounts of specific anti-Sm antibody in young BALB/c and MRL/+ mice. The Y2 idiotype was expressed in MRL/+ mice but not in BALB/c mice. Expression of both anti-Sm, predominantly IgG2a heavy chain, and Y2 idiotype was augmented in MRL/+ mice after two injections of Sm if, prior to immunization, mice received splenic T cells from naive MRL/lpr or immunized, but not naive MRL/+ mice. These results suggest that the lpr gene contributes to the ability of autoimmune T cells to augment the anti-Sm antibody response. Treatment of primed MRL/+ donor T cells with anti-CD4, but not anti-CD8, antibodies and complement removed the ability to augment anti-Sm antibody production. In contrast, augmentation of Y2 idiotype production was abrogated by pretreatment of donor T cells with either anti-CD4 or anti-CD8. These results suggest that, while MRL/+ CD4+ T cells play an important role in anti-Sm antibody production, additional interaction between CD4+ and CD8+ T cells augments Y2 expression.

Animals↗
PubMed1990

Thrombotic thrombocytopenic purpura in a patient with AIDS.

Thrombotic thrombocytopenic purpura (TTP) has only recently been documented in association with human immunodeficiency virus infection. The authors present the clinical, laboratory, and pathologic features of a unique case of secondary thrombotic thrombocytopenic purpura occurring in a patient with AIDS, including the immunohistologic characterization of the vascular thrombi. They also review 12 previously reported cases of thrombotic thrombocytopenic purpura associated with human immunodeficiency virus infection.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Prevention of venous thrombosis after total knee arthroplasty. Comparison of antithrombin III and low-dose heparin with dextran.

In a prospective, randomized trial, we compared the efficacy of a combination of antithrombin III and heparin with that of dextran 40 as prophylaxis against venous thrombosis after total knee arthroplasty. Ascending venography identified thrombosis in about one-third of the patients who received the combination of antithrombin III and heparin, compared with about four-fifths of those who received dextran (p less than 0.001). In both groups, the patients who had venous thrombosis had a significantly lower concentration of antithrombin III postoperatively than those who did not have thrombosis. Venous thrombosis occurred in all patients in whom the concentration of antithrombin III was less than 65 per cent postoperatively. These findings demonstrated that, after total knee replacement, the combination of antithrombin III and heparin effectively reduces the incidence of postoperative venous thrombosis and is significantly better than dextran. Furthermore, the findings suggested a relationship between postoperative deficiency of antithrombin III and the occurrence of thrombotic complications.

Adult↗
PubMed1989

Evidence for insulin-like growth factor-I regulation of chick aortic elastogenesis.

The potential role of insulin-like growth factor-I (IGF-I) as a modulator of chick aortic embryogenesis was examined. Studies were designed to investigate the in vivo relationships between embryonic IGF-I serum concentrations, liver and aortic IGF-I mRNA steady-state levels and the inception and perpetuation of aortic elastogenesis. In addition to aortic tissue, elastogenesis was measured in heart and lung tissues in order to compare the responses of functionally unique elastin-containing tissues to the developmental appearance of IGF-I in embryonic serum. Our results demonstrate that the induction of aortic tropoelastin mRNA steady-state levels coincides with a major increase in serum IGF-I concentration. This is not the case with either lung or heart elastogenic responses. All three tissues examined (aorta, lung, and heart) exhibited different developmental patterns of tropoelastin mRNA steady-state levels during the embryonic ages studied (8- through 10-day). Only aortic tropoelastin mRNA levels paralleled the rise and fall of IGF-I serum levels. Steady-state levels of liver IGF-I mRNA peaked one day (9-day) prior to detectable IGF-I serum levels but otherwise mirrored the gradual, but steady decrease in IGF-I serum levels through 16-day. Aortic tissue also expresses IGF-I mRNA beginning at 8-day and continuing throughout the embryonic ages examined (16-day). Although the relative levels of aortic IGF-I mRNA are very low in comparison to corresponding mRNA levels in liver, the fact that IGF-I mRNA is transcribed in the aorta points to the possibility that autocrine and/or paracrine mechanisms of IGF-I action may be operative in aortic elastogenesis.

Animals↗
PubMed1989

Effects of protein level, methionine supplementation and carbohydrate type of the diet on liver lipid and plasma free threonine contents in the lactating rat.

Eight groups of 13-15 female rats were fed purified diets after littering. Four groups received a low protein (8% casein) diet (groups 8) and the others, a normal protein (20% casein) diet (groups 20). Carbohydrates were supplied either as starch (groups S) or as starch plus 40% fructose (groups F). Half the animals received a 0.4% methionine supplementation (groups M). Four or five dams per group were sacrificed on days 2, 7 and 14 after littering. The diet intake was increased by methionine supplementation, substitution of starch for fructose and increased protein content, mainly during the second week of lactation. This influenced weight variation of the dams and litter growth. On all days, the plasma levels of cholesterol esters, triglycerides and phospholipids were positively correlated with the dietary protein level. On days 7 and 14, the liver neutral lipid content was increased in rats fed the low protein diets supplemented with methionine (groups 8SM and 8FM) and the normal protein diets containing 40% fructose (groups 20F and 20FM). The plasma free threonine content was positively correlated with the protein level in the diet. On day 14, rats fed a low protein diet had a threonine deficiency, except those in groups 8S and 8F. The plasma free threonine content of these rats was not reduced, possibly due to an impaired utilization of this amino acid. The liver lipidosis observed during lactation, in contrast to that observed during growth with a low protein diet, was not due to a threonine deficiency.

Animals↗
PubMed1989

Comparative histomorphometric changes in SENCAR mouse epidermis in response to multiple treatments with complete and stage-specific tumor promoting agents.

Responses of various cells of the epidermis and dermis to topically applied agents have been implicated in the mechanism of multistage mouse tumorigenesis. These responses have been discussed almost entirely in the context of a single promoter treatment, although tumor expression is dependent on multiple applications. Responses of keratinocytes, epidermal dendritic non-keratinocytes and dermal leukocytes were therefore recorded following multiple topical applications of the potent complete tumor-promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). In order to assess the importance of the response of individual cell types to the mechanisms and stages of promotion, responses to TPA were compared with those to agents with low complete promoting activity, but significant activity in individual stages of multistage promotion models. These included 4-O-methyl-TPA, a stage 1 promoting agent, mezerein and n-dodecane, stage 2 promoting agents of apparently different mechanism of action, and ethyl phenylpropiolate (EPP), a highly inflammatory stage 3 promoting agent. In agreement with previous findings, TPA induced a persistent epidermal hyperplasia and an increase in dark keratinocytes, although a similar finding was made for EPP and n-dodecane. The response to n-dodecane was significantly delayed, however, and that to EPP was accompanied by focal epidermal destruction and inflammation. The response to n-dodecane contrasted with that found for mezerein, supporting the suggestion that their mechanisms of action are distinct. Multiple treatments of 4-O-methylTPA caused no increase in dark cells, and mezerein induced no increase in numbers of pyknotic cells, whereas increases were expected in both cases on the basis of single dose experiments. Of the agents examined, only TPA induced a decrease in pale dendritic epidermal cells in the absence of marked toxicity, supporting the previous proposal that prolonged effects on this cell type are important in the promotion process. Some degree of persistent dermal leukocyte infiltration was observed with all agents excepting 4-O-methylTPA, although the extent of the response and its cellular characteristics appeared strongly dependent on the agent applied. In the case of TPA small mononuclear cells, neutrophils and macrophages all provided significant contributions to the total infiltrate. A similar phenomenon was observed with n-dodecane and EPP, with an additional increase in eosinophils which was not observed with TPA. Mezerein differed from both TPA and n-dodecane in inducing a significant increase only in eosinophils. As reported previously for single applications, prolonged TPA application caused a change in morphology and a considerable decrease in numbers of Thy-1+ epidermal dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetone↗
PubMed1989

Immunologic characterization of lymphocytic leukemias. Methodologic and immunophenotypic considerations.

Immunophenotyping has become an important adjunct to the routine morphologic and cytochemical evaluation of leukemias. The development and refinement of immunologic techniques applicable to the general clinical pathology laboratory and the commercial availability of lineage-specific monoclonal antibodies have enhanced this technology as a diagnostic tool. Lymphoid leukemias, in particular, can be accurately identified and subclassified according to their immunologic characteristics, as defined by lymphocyte differentiation antigens. Immunophenotypic classification has also been demonstrated to have prognostic significance for certain acute and chronic lymphoid leukemias. This review considers current immunotyping methods, characteristics of the antibody probes used, and the immunophenotypic characteristics of the acute and chronic lymphoid leukemias.

Antibodies, Monoclonal↗
PubMed1989

Antithrombin III/low-dose heparin in the prevention of deep-vein thrombosis after total knee arthroplasty. A preliminary report.

This preliminary report outlines the rationale for a new approach to deep-vein thrombosis (DVT) prophylaxis in total knee arthroplasty (TKA) patients and describes preliminary hematologic and venographic findings. A protocol was employed to (1) document a series of hematologic events surrounding cemented TKA and the alterations of these events by the study drugs and (2) compare the safety and efficacy of a regimen of antithrombin III/low-dose heparin (ATIII/LDH) to that of low-molecular-weight dextran (LMWD) in the prevention of DVT after TKA. Using a dosage regimen of 3000 units of ATIII as a loading dose followed postoperatively by 2000 units daily combined with 5000 units of LDH twice daily, a prospective randomized study of patients treated by cemented TKA was performed. The ATIII/LDH regimen was compared with LMWD (10 ml/kg x 12 hours loading dose followed by 7 ml/kg x 24 hours maintenance dose). The rate of DVT after TKA in 42 patients was 25% (5/20) for the ATIII/LDH group versus 82% (18/22) for the LMWD group (p less than 0.001). Bleeding complications were minimal and comparable for each group. Hematologic studies demonstrated that quantitative and functional ATIII levels decreased after TKA and that preoperative loading with ATIII prevented levels from falling below 100%. Studies of clot formation (fibrinopeptide A) and plasmin activity (fibrinopeptides B beta 15-42 and 1-42) in 34 patients suggest some reduction in procoagulant activity in patients in the ATIII/LDH group. These findings indicate that the combination of ATIII and LDH may offer superior protection from DVT than does LMWD.

Antithrombin III↗
PubMed1988

Autoimmune CD4+ T cells interfere with immune tolerance to a thymic-independent antigen.

The ability of autoimmune T cell subsets to interfere with tolerization of B cells can be studied by using thymic-independent Ag. We have defined an abnormality within the CD4+ T cell compartment in young NZB and MRL-lpr/lpr mice by studying tolerance of spleen and B cells to the thymic independent Ag, fluorescein-Brucella abortus. Tolerization of spleen cells is defective in MRL-lpr/lpr mice, but not MRL-+/+ or C3H.lpr mice, suggesting that the defect requires both the autosomal MRL background and the lpr gene to be present. T enriched cells from NZB mice and from MRL-lpr/lpr mice (but not MRL-+/+ or C3H.lpr mice) reverse tolerance in spleen cells from [NZB X DBA/2]F1 and C3H/HeJ mice, respectively. This interference is removed by treatment with anti-CD4 antibody and C. Supernatants from cultured T cells of NZB and MRL-lpr/lpr mice also prevent tolerance in spleen cells of [NZB X DBA/2]F1 and MRL-+/+ mice, respectively, unless CD4+ cells are removed prior to T cell culture. Removal of T cells from NZB and MRL-lpr/lpr spleen cells allows normal tolerization of B cells, which is abrogated by the addition of syngeneic T cells or cultured T cell supernatants. This effect also depends on the presence of CD4+ T cells. These studies show that in MRL-lpr/lpr mice, through interaction of the lpr and MRL background genes in a T cell subset, and in NZB mice, CD4+ T cells interfere with B cell tolerance to a thymic-independent Ag.

Animals↗
PubMed1988

Isolation, characterization, and long-term culture of fetal bovine tracheal epithelial cells.

Epithelial cells were isolated from fetal bovine trachea by exposing and stripping the mucosal epithelium from the adjacent connective tissue. The tissue was minced and enzymically dissociated in Ca-Mg-free medium containing dispase and dithiothreitol. The stripping procedure and selective trypsinization produced epithelial cell cultures free of fibroblasts. Seeded on plastic, the plating efficiency was 21.5% with a doubling time of 24 h. Dome formation, evidence of occluding junctions and active ion transport characteristic of epithelial cells, was common. Growth of the cells on glass, collagen, and Engelbreth-Holm-Swarm (EHS) substrate demonstrated a striking difference in morphology. Cells grown on EHS presented a more distinctly three-dimensional growth pattern and many more microvilli when compared to cells grown on glass or collagen. The cells retained their epithelioid characteristics through more than 30 passages as shown by the presence of distinct apical and basolateral membranes, tight junctions, and positive keratin staining.

Animals↗
PubMed1988

Long-term implantation of voltammetric oxidase/peroxide glucose sensors in the rat peritoneum.

Methods for designing, fabricating, testing in vitro and in vivo, and improving chronically implantable oxidase/peroxide-type polarographic glucose sensors are described. Voltammetric means to evaluate oxygen supply to the sensor and to measure the nearby microcirculation with hydrogen washout techniques using the implanted glucose sensor are outlined. Because some peritoneally implanted sensors have, perhaps surprisingly, remained functional for months, such devices may prove with further development to be useful as the sensing components in artificial pancreatic beta cells for the control of diabetes.

Animals↗
PubMed1988

Critical comparison of histological and morphometric changes in SENCAR mouse epidermis in response to n-dodecane, 12-O-tetradecanoylphorbol-13-acetate and mezerein.

n-Dodecane, a previously little-studied tumor-promoting agent and mezerein, a diterpenoid natural product, have both been reported to have activity primarily in Stage II of two stage tumor promotion in SENCAR mouse skin. Histological changes in this tissue were therefore investigated in response to these agents in order to determine whether changes could be identified which were common to Stage II promotion by both compounds, and specific in this respect compared to those induced by the complete promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA). All three agents were applied at doses which have previously been found active in multistage tumorigenesis studies in this strain. A single dose of 50 mg dodecane induced no increase in the number of interfollicular cell layers or epidermal thickness, nor any observable inflammation, 6-144 h after application. In contrast, marked increases were predictably observed with TPA and mezerein, maximal responses occurring after 48-72 h. n-Dodecane induced no increase in the number of keratinocytes with dense cytoplasm and increased affinity for basophilic dyes (dark cells), only TPA demonstrating this activity. The alkane likewise did not increase the number of pyknotic basal keratinocytes indicating that toxicity would not account for the low Stage I activity of this agent in the way proposed for mezerein which was the most active in this respect, inducing a significant increase 48 h after treatment. Like TPA and mezerein, n-dodecane induced a significant increase in large intra-mitochondrial densities. Forty-eight to seventy-two hours after application, dodecane induced a significant decrease in the numbers of dendritic epidermal cells, a response which was also observed for TPA and mezerein, although occurring somewhat more rapidly. All three agents appeared to induce these cells to retract their characteristic processes. After four applications of n-dodecane the number of epidermal cell layers and mitotic index were equal to or greater than those observed with TPA. These findings show that in SENCAR epidermis the previously uncharacterized tumor-promoting agent n-dodecane induced essentially no histologic changes in mouse skin in common with mezerein, a second agent with activity primarily in Stage II of two stage tumor promotion, which were not also shown by the complete promoter TPA. The only characteristic specific to Stage II promoting agents therefore remains an inability to induce increased numbers of dark cells. In most other respects dodecane induced responses similar to those observed for TPA, although a distinctly different temporal dependence was noted in several cases.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkanes↗