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Biomedical subjects

M Frederick

Publications and source records attributed to M Frederick.

16 recordsLinked to original sources
PubMed2000

Evaluation of treatment efficacy of Raynaud phenomenon by digital blood pressure response to cooling. Raynaud's Treatment Study Investigators.

Our previous studies have suggested that digital blood pressure response to cooling could provide a measure of the efficacy of treatments that are administered to patients with Raynaud phenomenon (RP). This method was used on 158 primary RP patients participating in a multicenter, randomized clinical trial that compared the efficacy of sustained-release nifedipine with temperature biofeedback in the treatment of RP. A pill placebo and electromyography served as controls. The response to local finger cooling was measured at 30 degrees, 20 degrees, 15 degrees and 10 degrees C in a temperature-controlled room under standardized conditions. The results showed that, at the 15 degrees C and 10 degrees C local cooling temperatures, the patients in the nifedipine group had a higher mean digital systolic blood pressure, a higher relative digital systolic blood pressure (RDSP), a smaller proportion of subjects with RDSP < 70% and a smaller proportion of subjects with a zero reopening pressure than the patients in the three other treatment groups. These results were statistically significant at 10 degrees C, the nifedipine group being significantly different from all others (p < 0.05); no significant difference was found between the three other treatment groups.

Blood Pressure↗
PubMed1999

Identification and cDNA cloning of headpin, a novel differentially expressed serpin that maps to chromosome 18q.

Differential display was used to identify a novel serpin (headpin) underexpressed in squamous cell cancers of the oral cavity. Headpin cDNA encoding a complete open reading frame was cloned and sequenced. Headpin is expressed in normal oral mucosal tissue, skin, and cultured keratinocytes. Using Northern analysis and relative reverse-transcription polymerase chain reaction (relative RT-PCR), downregulation of headpin mRNA expression was demonstrated in oral cavity squamous carcinomas. Northern blot analysis identified a 3. 3-kb headpin mRNA transcript. Headpin is a 391-amino-acid protein with a theoretical molecular weight of 44 kDa. Hinge region homology at the reactive site loop suggests that headpin belongs to the inhibitory class of serine protease inhibitors. Headpin was mapped to 18q21.3/18q22. This region includes the ovalbumin serpins (ov-serpins) maspin, SCCA1, SCCA2, and PAI-2. Furthermore, 18q is recognized as a region for frequent loss of heterozygosity (LOH) in head and neck cancer and other malignancies.

Amino Acid Sequence↗
PubMed1999

Behavioral and pharmacologic interventions: the Raynaud's Treatment Study.

The Raynaud's Treatment Study (RTS) exemplified clinical trials with treatments that differ qualitatively both in their modes and in their methods of delivery. The RTS compared finger-temperature biofeedback to slow-release nifedipine, a calcium channel blocker, in patients with primary Raynaud's disease. Factors influencing the study design were the nature of the interventions and control measures of the protocol, the possibility of perceived differences by the patients between the treatments once the final protocol was developed, and concern on the part of the investigators over the fact that the primary endpoint was self-reported. This paper presents the final statistical model: a double parallel design with both a placebo group and a nonspecific behavioral control group.

Biofeedback, Psychology↗
PubMed1998

Adenovirus-mediated p53 gene transfer in patients with advanced recurrent head and neck squamous cell carcinoma.

PURPOSE: Standard therapies of head and neck squamous cell carcinoma (HNSCC) often cause profound morbidity and have not significantly improved survival over the last 30 years. Preclinical studies showed that adenoviral vector delivery of the wild-type p53 gene reduced tumor growth in mouse xenograft models. Our purpose was to ascertain the safety and therapeutic potential of adenoviral (Ad)-p53 in advanced HNSCC. PATIENTS AND METHODS: Patients with incurable recurrent local or regionally metastatic HNSCC received multiple intratumoral injections of Ad-p53, either with or without tumor resection. Patients were monitored for adverse events and antiadenoviral antibodies, tumors were monitored for response and p53 expression, and body fluids were analyzed for Ad-p53. RESULTS: Tumors of 33 patients were injected with doses of up to 1 x 10(11) plaque-forming units (pfu). No dose-limiting toxicity or serious adverse events were noted. p53 expression was detected in tumor biopsies despite antibody responses after Ad-p53 injections. Clinical efficacy could be evaluated in 17 patients with nonresectable tumors: two patients showed objective tumor regressions of greater than 50%, six patients showed stable disease for up to 3.5 months, and nine patients showed progressive disease. One resectable patient was considered a complete pathologic response. Ad-p53 was detected in blood and urine in a dose-dependent fashion, and in sputum. CONCLUSION: Patients were safely injected intratumorally with Ad-p53. Objective antitumor activity was detected in several patients. The infectious Ad-p53 in body fluids was asymptomatic, and suggests that systemic or regional treatment may be tolerable. These results suggest the further investigation of Ad-p53 as a therapeutic agent for patients with HNSCC.

Adenoviridae↗
PubMed1997

Cytokine-induced cytotoxic function expressed by lymphocytes of the innate immune system: distinguishing characteristics of NK and LAK based on functional and molecular markers.

Several molecular events are now identifiable during the activation, recognition, and killing by natural killer (NK) cells that are distinct from those differentiated in response to cytokines during the generation of lymphokine-activated killer (LAK) cells or during lymphocyte proliferation. Because LAK and MHC-unrestricted killing activities also include the prototypic NK targets as part of their broad recognition spectra, accurate identification of the complete function being studied is critical. In many publications, past and present, only NK-sensitive target cells were used (K562, Molt-4, others), and, therefore, the results do not necessarily indicate whether the effectors are NK or have differentiated into LAK cells. Such a consideration becomes critical when the effectors are grown in interleukin-2 (IL-2), and an attempt is made to define receptor recognition, signal transduction pathways, and specificity at the molecular level. In some instances, effector cells are likely to have stopped, therefore merely expressing NK activity, and have also acquired LAK function. The identified receptors may not have been unique to NK cells or NK function. Not until the targets employed are also confirmed to be NK sensitive, and the effectors do not kill NK-resistant targets can the results of molecular studies be proposed to represent aspects unique to NK. Reports of the use of IL-2-expanded NK clones are most likely providing data concerning the biology of LAK and not of classic NK. The classic NK activity surveying our blood apparently performs an important function, including the ability to respond rapidly to certain cytokines and to acquire additional functions and receptors for use in destroying a vast array of target cells. It is critical for scientists to appreciate the functional distinctions and to identify the molecules and pathways unique to each of these curious cytolytic systems.

Biomarkers↗
PubMed1995

Differences in participation in experimental drug trials among persons with AIDS.

To measure participation in experimental drug trials among persons with acquired immunodeficiency syndrome (AIDS), we interviewed 4,604 persons at least 18 years of age who were reported to have AIDS to 11 state and city health departments in the United States. Ten percent reported that they were currently in a trial. Current enrollment differed significantly (p < 0.05) by race/ethnicity (blacks, 5%; whites, 14%; Hispanics, 15%), gender (women, 7%; men, 11%), exposure mode (injection drug use, 5%, men who have sex with men, 14%), annual household income (< $10,000, 8%, > or = $10,000, 14%), education (< 12 years, 6%; > or = 12 years, 12%), health care (no regular care, 1%, public care, 8%; private care, 17%), and time since AIDS diagnosis (< or = 6 months, 9%; > 6 months, 12%). Adjusting for all factors and time since AIDS diagnosis, blacks (adjusted odds ratio [AOR] = 0.35, 95% confidence interval [CI] 0.26, 0.47), persons with less than 12 years of education (AOR = 0.71, CI 0.53, 0.96), and those without regular health care (AOR = 0.24, CI 0.10, 0.61) remained less likely to be in a trial. Blacks, those with less than 12 years of education, and persons without regular health care were less likely than other persons with AIDS to be currently enrolled in AIDS trials. To increase enrollment of these persons, researchers must address barriers to participation for these groups.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Interleukin-1 production in tumor cells of human melanoma surgical specimens.

To determine whether IL-1 alpha and/or IL-1 beta protein is expressed by human melanoma tumor in vivo, we first analyzed nine human melanoma cell lines and optimized the in situ detection of these proteins. Three of the melanoma cell lines stained positively for both IL-1 alpha and IL-1 beta using immunohistochemistry (IHC). THe specificity of IHC was confirmed by the ability of purified recombinant IL-1 alpha and IL-1 beta protein to abolish the staining after being adsorbed by their respective antibodies before use in IHC. The three positively staining cell lines were also the only lines to demonstrate IL-1 production by western blot analysis as well as IL-1 secretion by ELISA. Next we examined 29 surgically obtained melanoma tumor specimens (6 primary and 23 metastases) that had been formalin fixed and paraffin embedded. Using the same anti-IL-1 antibodies, 5 of 23 metastatic tumors stained positively. None of the 6 primary lesions stained for either IL-1 alpha or IL-1 beta. Comparison of staining pattern performed on serially sectioned tissue using preimmune serum and antibodies against S-100 protein, melanoma-associated antigen (HMB-45), and CD68 (kappa P1), which recognizes monocyte-macrophage cell lineage, demonstrates for the first time that IL-1 protein is produced by human melanoma tumor cells in vivo. These findings provide the basis for examination of what may be a previously unrecognized biologically distinct subset of patients.

Analysis of Variance↗
PubMed1994

Completion rates of clients discharged from drug and alcohol treatment programs in Washington State.

OBJECTIVES: The primary goal of this study was to analyze completion rates of clients in drug and alcohol abuse treatment programs in Washington State and to assess the factors associated with treatment completion. A secondary goal was to examine the utility of a state information system as a source of evaluative data. METHODS: Analyses were conducted of 5827 client records contained in the Washington State Substance Abuse Monitoring System, representing a census of public clients discharged during the last quarter of 1990 from all state-funded alcohol and drug treatment programs in four treatment modalities. Logistic regression was performed to determine the independent predictors of treatment completion. RESULTS: Completion rates were highest for intensive inpatient alcohol treatment (75%) and lowest for intensive outpatient drug programs (18%). Factors associated with treatment completion included screening at a referral assessment center, education, age, ethnicity, and existence of a secondary drug problem. CONCLUSIONS: The fit between clients and treatment programs may be an important factor explaining why some clients complete treatment and others drop out. State client information systems are an important source of data for analyzing treatment completion and other outcomes.

Adolescent↗
PubMed1994

Risk behaviors of persons with heterosexually acquired HIV infection in the United States: results of a multistate surveillance project.

To describe past risk behaviors among persons with heterosexually acquired human immunodeficiency virus (HIV) infection, we interviewed 497 persons > or = 18 years of age with heterosexually acquired HIV infection reported to 11 state and city health departments in the United States. Thirty-nine percent of persons reported using noninjection drugs in the past 5 years; noninjection drug use was highest among men whose sex partners injected drugs (53%). Sixteen percent of all persons used crack, and 17% were classified as potential alcoholics; among men, 29% were classified as potential alcoholics. Of the 49% of men who reported paying a woman for sex, 86% did so multiple times. Most persons had multiple sex partners in the past 5 years; however, 35% of the women had only one sex partner. Thirty-four percent of the women and 50% of the men had been treated for a sexually transmitted disease in the past 10 years. Seventy-four percent of the women and 68% of the men had never used condoms in the 5 years before they knew they were HIV positive. Among these people with heterosexually acquired HIV, noninjection drug use was common, many men have paid someone for sex, and many women have not had multiple sex partners. These findings have important implications for the types of prevention programs that can most successfully lessen the spread of HIV among heterosexuals.

Adult↗
PubMed1993

The Dietary Intervention Study in Children (DISC): dietary assessment methods for 8- to 10-year-olds.

OBJECTIVES: The dietary assessment methods used in the Dietary Intervention Study in Children (DISC) are described and the rationale, validity, and/or general usefulness of each are discussed. DESIGN: DISC is the first multicenter, randomized, clinical trial to study the feasibility and long-term efficacy, safety, and acceptability of a fat-moderately diet in 8- to 10-year-old prepubescent children with moderately elevated plasma low-density lipoprotein cholesterol (LDL-C) levels. Final data collection for the original study (DISC I) occurred December 1, 1993; continued intervention and follow-up (DISC II) will extend beyond 1997. SETTING: Six clinical centers across the country participate in DISC. SUBJECTS: Preadolescent boys and girls with fasting LDL-C levels between the 80th and 98th age-specific and sex-specific percentiles established by the Lipid Research Clinics were eligible for the study. The feasibility phase included 140 children who were then enveloped into the full-scale trial. Baseline dietary data for 652 randomized children in the full-scale trial and 6-month results for the feasibility cohort are reported. INTERVENTIONS: Dietary assessment involved several elements: (a) determining eligibility based on consumption of more than 30% of energy from total fat, (b) monitoring adherence to and adequacy of the intervention diet, (c) evaluating acceptability of the diet in the intervention group, and (d) determining appropriate foods for the intervention diet. Methods are described for each purpose. MAIN OUTCOME MEASURES: LDL-C differences between the two groups and differences in total and saturated fat intakes as calculated from three 24-hour recalls were the primary outcome measures. Six-month dietary differences in the feasibility group are reported. STATISTICAL METHODS: Baseline group means and 6-month differences in dietary intake are reported for the full-scale trial and feasibility study, respectively. RESULTS: Baseline mean intake from three dietary recalls for the intervention (n = 328) and control (n = 324) groups, respectively, were as follows: energy = 1,759 kcal and 1,728 kcal; total energy from fat = 33.3% and 34.0%; total energy from saturated fat = 12.5% and 12.7%; and total dietary cholesterol = 209 mg and 195 mg. After 6 months of intervention, percentage of energy from total fat and saturated fat was reduced by 5.1% (P = .004) and 2.9% (P < .001), respectively, in this feasibility subset (n = 73) of the intervention group. Essentially no change in these parameters occurred in the control group (n = 67), which demonstrates a measurable difference in reporting between groups. APPLICATIONS/CONCLUSIONS: Results illustrate the feasibility of implementing a variety of dietary assessment methods among preadolescent children without relying primarily on parental reports.

Child↗
PubMed1993

Sociodemographics and HIV risk behaviors of bisexual men with AIDS: results from a multistate interview project.

OBJECTIVE: To describe the sociodemographic characteristics and sexual and drug use behaviors of men with AIDS who engage in bisexual activity. METHODS: We interviewed 2120 men aged > or = 18 years who were reported with AIDS in 11 states and cities. Men were considered bisexual if they reported having had sex with a man and a woman in the previous 5 years. RESULTS: Of the 2020 men with AIDS who reported being sexually active in the previous 5 years, 1150 (57%) had had male partners only, 522 (26%) had had female partners only and 348 (17%) had had both. White men were least likely to report bisexual behavior (15%; 161 out of 1071). Men of Latin American descent were most likely to report bisexual behavior (24%; 37 out of 155), especially those born outside the United States who had lived there for < or = 10 years (38%; 11 out of 29). Bisexual Latin American men, regardless of birthplace, were more likely to be currently married than all other bisexual men (22 versus 7%; P < 0.05). HIV risk behaviors differed between men reporting bisexual and those reporting exclusively homosexual or heterosexual activity. Injecting drug use in the previous 5 years was more common among bisexual than homosexual men (12 versus 6%; P < 0.05). Bisexual men were more likely (P < 0.05) to have received money for sex (11%) than homosexual (4%) or heterosexual men (4%). This difference was even greater among injecting drug users receiving money for sex: bisexual (29%), homosexual (13%), heterosexual (3%). CONCLUSIONS: Demographics and HIV risk behaviors of bisexual men with AIDS differ from those of homosexual and heterosexual men with AIDS. These findings indicate that special efforts are needed to prevent sexual transmission of HIV among bisexual men.

Acquired Immunodeficiency Syndrome↗
PubMed1991

Hemorrhagic events during therapy with recombinant tissue-type plasminogen activator, heparin, and aspirin for acute myocardial infarction. Results of the Thrombolysis in Myocardial Infarction (TIMI), Phase II Trial.

OBJECTIVES: To assess the effects of invasive procedures, hemostatic and clinical variables, the timing of beta-blocker therapy, and the doses of recombinant plasminogen activator (rt-PA) on hemorrhagic events. DESIGN: A multicenter, randomized, controlled trial. SETTING: Hospitals participating in the Thrombolysis in Myocardial Infarction, Phase II trial (TIMI II). INTERVENTIONS: Patients received rt-PA, heparin, and aspirin. The total dose of rt-PA was 150 mg for the first 520 patients and 100 mg for the remaining 2819 patients. Patients were randomly assigned to an invasive strategy (coronary arteriography with percutaneous angioplasty [if feasible] done routinely 18 to 48 hours after the start of thrombolytic therapy) or to a conservative strategy (coronary arteriography done for recurrent spontaneous or exercise-induced ischemia). Eligible patients were also randomly assigned to either immediate intravenous or deferred beta-blocker therapy. MEASUREMENTS: Patients were monitored for hemorrhagic events during hospitalization. MAIN RESULTS: In patients on the 100-mg rt-PA regimen, major and minor hemorrhagic events were more common among those assigned to the invasive than among those assigned to the conservative strategy (18.5% versus 12.8%, P less than 0.001). Major or minor hemorrhagic events were associated with the extent of fibrinogen breakdown, peak rt-PA levels, thrombocytopenia, prolongation of the activated partial thromboplastin time (APTT) to more than 90 seconds, weight of 70 kg or less, female gender, and physical signs of cardiac decompensation. Immediate intravenous beta-blocker therapy had no important effect on hemorrhagic events when compared with delayed beta-blocker therapy. Intracranial hemorrhages were more frequent among patients treated with the 150-mg rt-PA dose than with the 100-mg rt-PA dose (2.1% versus 0.5%, P less than 0.001). The extent of the plasmin-mediated hemostatic defect was also greater in patients receiving the 150-mg dose. CONCLUSIONS: Increased morbidity due to hemorrhagic complications is associated with an invasive management strategy in patients with acute myocardial infarction. Our findings show the complex interaction of several factors in the occurrence of hemorrhagic events during thrombolytic therapy.

Aspirin↗
PubMed1991

Selective versus routine predischarge coronary arteriography after therapy with recombinant tissue-type plasminogen activator, heparin and aspirin for acute myocardial infarction. TIMI II Investigators.

To ascertain whether predischarge arteriography is beneficial in patients with acute myocardial infarction treated with recombinant tissue-type plasminogen activator (rt-PA), heparin and aspirin, the outcome of 197 patients in the Thrombolysis in Myocardial Infarction (TIMI) IIA study assigned to conservative management and routine predischarge coronary arteriography (routine catheterization group) was compared with the outcome of 1,461 patients from the TIMI IIB study assigned to conservative management without routine coronary arteriography unless ischemia recurred spontaneously or on predischarge exercise testing (selective catheterization group). The two groups were similar with regard to important baseline variables. During the initial hospital stay, coronary arteriography was performed in 93.9% of the routine catheterization group and 34.7% of the selective catheterization group (p less than 0.001), but the frequency of coronary revascularization (angioplasty or coronary artery bypass surgery) was similar in the two groups (24.4% versus 20.7%, p = NS). Coronary arteriograms showed a predominance of zero or one vessel disease (stenosis greater than or equal to 60%) in both groups (routine catheterization group 73.1%, selective catheterization group 61.3%). During the 1st year after infarction, rehospitalization for cardiac reasons and the interim performance of coronary arteriography were more common in the selective catheterization group (37.9% versus 27.6%, p = 0.007 and 28.6% versus 11.6%, p less than 0.001, respectively); however, the interim rates of death, nonfatal reinfarction and performance of coronary revascularization procedures were similar. At the end of 1 year, coronary arteriography had been performed one or more times in 98.9% of the routine catheterization group and 59.4% of the selective catheterization group (p less than 0.001), whereas death and nonfatal reinfarction had occurred in 10.2% versus 7.0% (p = 0.10) and 8.6% versus 9.0% (p = 0.87), respectively. Because the selective coronary arteriography policy exposes about 40% fewer patients to the small but finite risks and inconvenience of the procedure without compromising the 1 year survival or reinfarction rates, it seems to be an appropriate management strategy.

Aged↗