PubMed Health⌕ Search

Biomedical subjects

M Thompson

Publications and source records attributed to M Thompson.

At least 109 records · Page 6Linked to original sources
PubMed2000

Efficacy testing of recombinant human immunodeficiency virus (HIV) gp160 as a therapeutic vaccine in early-stage HIV-1-infected volunteers. rgp160 Phase II Vaccine Investigators.

A phase II efficacy trial was conducted with recombinant human immunodeficiency virus (HIV) type 1 envelope glycoprotein gp160 (rgp160) in 608 HIV-infected, asymptomatic volunteers with CD4+ cell counts >400 cells/mm3. During a 5-year study, volunteers received a 6-shot primary series of immunizations with either rgp160 or placebo over 6 months, followed by booster immunizations every 2 months. Repeated vaccination with rgp160 was safe and persistently immunogenic. Adequate follow-up and acquisition of endpoints allowed for definitive interpretation of the trial results. There was no evidence that rgp160 has efficacy as a therapeutic vaccine in early-stage HIV infection, as measured at primary endpoints (50% decline in CD4+ cell count or disease progression to Walter Reed stage 4, 5, or 6) or secondary endpoints. A transient improvement was seen in the secondary CD4 endpoint for the vaccination compared with the placebo arm, but this did not translate into improved clinical outcome.

AIDS Vaccines↗
PubMed2000

Five giant leaps toward integrating health care delivery and ways to drive organizations to leap or get out of the way.

The article argues that incremental improvement of, or "tinkering" with, health care delivery is taking too long and leaves unacceptable gaps in health care quality and service. It lists five common types of quality improvement "leaps" that have proven across studies to improve the integration of care during hospital and emergency department discharge, to bring mental health and substance abuse treatment into primary care, and to allow better management of chronic diseases. It also lists five key tasks that organizations need to accomplish in order to make such leaps and then describes four ways that consumers, employers, consumer advocates, and investors force the stubborn "bullfrogs" to take a big jump forward.

California↗
PubMed2000

Lactulose-mannitol intestinal permeability test in children with diarrhea caused by rotavirus and cryptosporidium. Diarrhea Working Group, Peru.

BACKGROUND: The relationship between intestinal permeability and acute secretory diarrheal syndromes caused by rotavirus and Cryptosporidium parvum in infants less than 36 months of age was studied using the lactulose-mannitol excretion assay. METHODS: An oral solution containing 0.4 g/kg lactulose and 0.1 g/kg mannitol was administered to 15 infants with rotavirus, 7 with Cryptosporidium infection and a control group of 7 with secretory diarrhea admitted to the Oral Rehydration Unit of the National Children's Hospital in Lima, Peru. Urinary sugar excretion was measured using an enzymatic spectrophotometric method. The ratio of urinary excretion of lactulose to mannitol was used to measure intestinal mucosal permeability, with higher ratios indicative of increased intestinal permeability. Infants in all three groups were retested 20 days after the initial test. RESULTS: The (mean +/- SE) lactulose:mannitol (L:M) excretion ratios during the acute phase (day 1) of diarrhea in infants with rotavirus or Cryptosporidium and control infants were 0.67 +/- 0.1, 0.76 +/- 0.16, and 0.26 +/- 0.04, respectively. In the convalescent phase (day 20) the ratios were 0.19 +/- 0.02, 0.28 +/- 0.05, and 0.29 +/- 0.07, respectively. Significant reductions in L:M ratios were noted in rotavirus patients between days 1 and 20 (paired t-test; P < 0.01), Cryptosporidium patients between days 1 and 20 (paired t-test; P < 0.05), and between control subjects on day 1 and rotavirus patients on day 1 and Cryptosporidium patients on day 1 (unpaired t-tests; P < 0.05 for both). There were no significant differences in control subjects between days 1 and 20, control subjects and rotavirus patients on day 20, or control subjects and Cryptosporidium patients on day 20. CONCLUSIONS: The results indicate that increased intestinal permeability caused by rotavirus or cryptosporidium infections in Peruvian infants less than 36 months of age is a significant but reversible phenomenon. The temporal relationship observed in the current study and the contribution of such alterations in intestinal mucosal integrity to the burden of diarrheal disease and the development of malnutrition in developing countries is discussed.

Animals↗
PubMed2000

Increased cardiomyocyte intracellular calcium during endotoxin-induced cardiac dysfunction in guinea pigs.

Septic shock is a complex pathophysiologic state characterized by circulatory insufficiency, multiple system organ dysfunction, and frequent mortality. Although profound cardiac dysfunction occurs during sepsis, the pathogenesis of this dysfunction remains poorly understood. To determine whether abnormalities in intramyocyte calcium accumulation might contribute to the development of cardiac dysfunction, we measured myocyte intracellular calcium during peak cardiac dysfunction after an endotoxin challenge. Intraperitoneal administration of Escherichia coli lipopolysaccharide 4 mg/kg to adult guinea pigs resulted in significantly impaired cardiac performance (Langendorff preparation) 18 h after challenge compared with control. This included diminished left ventricular pressure development (56 +/- 7 versus 95 +/- 4 mm Hg, p < 0.05), maximal rate of left ventricular pressure rise (998 +/- 171 versus 1784 +/- 94 mm Hg/s, p < 0.05) and left ventricular pressure fall (1014 +/- 189 versus 1621 +/- 138 mm Hg/s, p < 0.05). Assay of intracellular calcium in fura-2AM-loaded cardiac myocytes demonstrated increased intracellular calcium concentration in myocytes obtained from lipopolysaccharide-challenged animals compared with controls (234 +/- 18 versus 151 +/- 6 nM, p < 0.05). Inhibition of calcium-release channel (ryanodine receptor) opening by administration of dantrolene prevented the increase in intracytoplasmic calcium (159 +/- 8 versus 234 +/- 18 nM, p < 0.05) and partially ameliorated systolic and diastolic ventricular dysfunction. These data indicate that abnormalities of intracellular calcium contribute to the development of endotoxin-induced myocardial dysfunction.

Animals↗
PubMed2000

Can patient demand for pharmaceuticals be moderated?

OBJECTIVE: Ask health plan members whether they would consider switching to a less costly medication or alternative treatment if their physician asked. SAMPLE & SETTING: Random sample of 265 members of Kaiser Permanente in Northern California. DESIGN: A telephone survey asked participants to respond to three vignettes tailored to either men and women age 18 to 39, women age 40-80, or men age 40-80. MAIN RESULTS: If asked to do so by their doctors, most young adults (77%) said they would be open to switching to a less expensive allergy medicine, most women over age 40 (60%) said they would try a less expensive blood pressure medication, and most men over age 40 (68%) said they would meet with a behavioral specialist and try other steps before taking ViagraAE. In open feedback, participants said they would be most receptive if the recommendation came from a trusted physician, if given the freedom to choose otherwise, and the alternative was equally effective and convenient. About one-third of participants expressed reservations or said they would definitely refuse substitution. These refusers were significantly less satisfied with the health plan, less satisfied with their primary care doctor, less trusting of Kaiser physicians in general, and in poorer health (as indicated in one or more vignettes). CONCLUSIONS: Moderating patients' demand for pharmaceuticals can begin by physicians skillfully asking patients to consider a more cost-effective alternative to expensive medications when one is available.

Adolescent↗
PubMed2000

Asking women to see nurses or unfamiliar physicians as part of primary care redesign.

OBJECTIVE: To gauge women's flexibility about seeing a nurse or an unfamiliar physician, to assess their interest in telephone visits, and to identify the characteristics of women who are least flexible. STUDY DESIGN: Telephone surveys, focus groups, and in-person interviews with women. PATIENTS AND METHODS: A random, demographically stratified sample of 1500 English-speaking female members of a health maintenance organization (ages 18-80 years) completed a 20-minute telephone survey (with a 72% response rate). A random subgroup of 500 women were asked about care preferences during acute illness and routine visit scenarios. Women (n = 242) from the full sample with a chronic illness were asked about their openness to telephone visits and care managers. Qualitative information was gathered from 10 focus groups and 75 in-person interviews. RESULTS: Most women (72%) were open to seeing a different physician for a minor acute illness, but they were less so (35%) for a routine checkup. If their physician was not available, the majority said they would be willing to see a registered nurse for the flu (72%) or a nurse-practitioner for a checkup (64%). Half (59%) of the chronically ill women were comfortable with telephone visits, and one third (37%) were "very interested" in care managers. Across scenarios, approximately one third of the women were strongly committed to seeing only their regular physician. They were more likely to be middle-aged or older, to have lower health plan satisfaction and perceived coordination of care, and to recall rude encounters with clinicians. CONCLUSION: The flexibility of most women regarding redesigned models of healthcare is encouraging. More attention needs to be paid, however, to education of women about multidisciplinary roles, enhancement of coordination of care, and customization of care to match patients' preferences.

Adolescent↗
PubMed1999

A phase II safety and efficacy study of amprenavir in combination with zidovudine and lamivudine in HIV-infected patients with limited antiretroviral experience. Amprenavir PROAB2002 Study Team.

OBJECTIVE: To determine the safety and efficacy of amprenavir (APV) in combination with lamivudine (3TC) and zidovudine (ZDV). DESIGN: Multicenter, randomized, partially blinded trial. SETTING: Nine study sites in the United States and Europe. PATIENTS: A group of 84 HIV-infected subjects with no prior 3TC or protease inhibitor therapy experience, CD4 cell count > or = 150 x 10(6) cells/l, and plasma HIV RNA > 10000 copies/ml. INTERVENTIONS: 3TC/ZDV with one of three doses of APV (900, 1050, or 1200 mg) versus 3TC/ZDV with 1050 mg placebo. All medications were dosed twice daily. The 1050 mg placebo and the APV 1050 mg dose were administered blinded. After 12 weeks, APV 1050 mg was substituted for 1050 mg placebo in the control group and the blind was maintained. MAIN OUTCOME MEASURES: Reduction in plasma HIV RNA from baseline; proportion of subjects with plasma HIV RNA < 400 copies/ml; and an increase in CD4 cell count from baseline. RESULTS: During the initial 12-week study period, APV/3TC/ZDV-treated subjects had greater viral suppression than the group receiving two nucleosides. By 48 weeks, 89% of subjects in the group taking the highest APV dose (1200 mg) had plasma HIV RNA < 400 copies/ml while 42% of the 900 mg group and 60% of the 3TC/ZDV group (1050 mg APV added at week 12) had plasma HIV RNA < 400 copies/ml using an as-treated analysis. By 60 weeks, 86% of subjects in the APV 1200 mg group had plasma HIV RNA < 400 copies/ml in the as-treated analysis, while 25% (900 mg), 43% (1050 mg), and 20% (1200 mg) of subjects had viral load <400 copies/ml in a strict intent-to-treat analysis owing to treatment discontinuations. Median CD4 cell count increases at week 60 were highest for the three treatment groups who received APV throughout the study, by intent-to-treat and as-treated analyses. The most common adverse events considered to be possibly drug related were nausea, rash, oral paresthesia, diarrhea, and fatigue. CONCLUSIONS: Treatment with APV, dosed at 1200 mg twice daily in combination with 3TC/ZDV, resulted in sustained viral suppression. This combination represents a potent alternative initial antiretroviral regimen for protease inhibitor-naive individuals.

Adult↗
PubMed1999

Interactions of HIV-1 TAR RNA with Tat-derived peptides discriminated by on-line acoustic wave detector.

The human immunodeficiency virus type I is strongly regulated at the transcriptional level through the interaction of an 86-amino acid protein (Tat) with a viral messenger RNA transcript. Accordingly, the binding of this protein and other cellular factors to the RNA has constituted a significant target for the development of anti-HIV drugs. In the present work, we describe the detection of the binding of two Tat-derived peptides, of 12 and 40 amino acids in length, with chemically synthesized RNA by an acoustic wave sensor. Immobilization of the nucleic acid to the sensor surface, which was incorporated in an on-line system, was effected using the biotin-neutravidin interaction. As expected, the changes in series resonance frequency and motional resistance for the two peptides indicate reversible interactions in both cases that can be further characterized by the calculation of kinetic off-rates. Of particular interest is the nature of the two frequency-based signals, which are in opposite directions for the two peptides. These results together with those obtained for the surface interactions of neutravidin and biotinylated RNA confirm that the thickness shear mode sensor, mass-response model involving the well-known Sauerbrey expression is invalid when applied to operation in liquids.

Acoustics↗
PubMed1999

Calcium antagonists improve cardiac mechanical performance after thermal trauma.

Burn trauma initiates a pathophysiologic cascade, which includes cardiac dysfunction and intramyocyte calcium accumulation. This study examined the hypothesis that therapeutic interventions which limit intracellular cardiac Ca(2+) accumulation after burn trauma will improve cardiac function. Guinea pigs were anesthetized (methoxyflurane), burned over 43% of total body surface area, and fluid resuscitated (FR) for 24 h. Burn guinea pigs were randomly divided into three groups: Group 1, FR alone, Group 2, FR plus dantrolene (10 mg/kg body wt, IV, 30 min, 8 and 22 h postburn), a drug which inhibits the Ca(2+) release channel (ryanodine receptor) of the cardiac sarcoplasmic reticulum, and Group 3, FR plus diltiazem (0.20-0.22 mg/kg given IV as a slow infusion over 6 h postburn), a drug which specifically blocks Ca(2+) slow channels; sham burn guinea pigs were given vehicle (Group 4), dantrolene (Group 5), or diltiazem (Group 6) as described above (respective controls). Cardiac dysfunction was impaired in fluid-treated burns (Group 1) compared to sham burns (Group 4) as indicated by reduced developed left ventricular pressure (LVP) (86 +/- 2 vs 52 +/- 3 mm Hg, P < 0.05), rate of LVP rise, (+dP/dt max, 1379 +/- 64 vs 909 +/- 44 mm Hg/s, P < 0.05), and LVP fall (-dP/dt max, 1184 +/- 31 vs 881 +/- 40 mm Hg/s, P < 0.05), and time to peak pressure (110 +/- 2 vs 102 +/- 2 ms, P < 0.05). In addition, [Ca(2+)](i) rose in cardiomyocytes harvested from fluid-treated burns (Group 1, 307 +/- 29 nM) compared to vehicle-treated controls (Group 4, 152 +/- 6 nM, P < 0.05). Neither calcium antagonist altered ventricular function or [Ca(2+)](i) in sham burns (Groups 5 and 6). In contrast, antagonists given after burn injury reduced cardiomyocyte [Ca(2+)](i) (Group 2, dantrolene-treated burns: 196 +/- 8 nM, and Group 3, diltiazem treated burns: 216 +/- 8 nM) and improved cardiac performance compared to that measured in burns given FR alone. Our data suggest that calcium antagonists given after burn trauma restored intracellular Ca(2+) homeostasis, decreased cardiac cell injury, and improved cardiac contractile function.

Animals↗
PubMed1999

The time course of metabolites in human plasma after 6-[(18)F]fluoro-l-m-tyrosine administration.

For the investigation of intracerebral dopamine metabolism, 6-[(18)F]fluoro-l-m-tyrosine (FmT) has been proposed as an alternative tracer that, unlike 6-[(18)F]fluoro-l-dopa, is not subjected to O-methylation. We have studied the time course of FmT and its labelled metabolites in plasma after intravenous injection into humans, employing a method that we have developed and validated to analyze labelled metabolites of FmT in plasma. The study population comprised 38 subjects, 14 of whom were taking an aromatic amino acid decarboxylase inhibitor (carbidopa), and obtained arterialized venous blood samples at various times after an intravenous injection of between 185 and 370 MBq of FmT. The major metabolite of FmT present in plasma was 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The time course of the fraction of radioactivity in plasma attributable to FmT was fitted well by the decay of two exponential functions. The fast component of the decay accounted for 40%-50% of the radioactivity and had a half-life of about 5 min. The slow component of the decay had a half-life of about 6 h in the subjects not taking carbidopa and 20 h in the patients taking carbidopa. When the total available FmT was calculated for each individual subject and expressed as a proportion of total radioactivity, this quantity did not differ significantly from that determined from the corresponding population mean. There was significantly more (15% on average) FmT available over the course of the 2-h experiment in the group pretreated with carbidopa. Our results demonstrate that the major metabolite in plasma after an intravenous injection of FmT is 6-[(18)F]fluoro-3-hydroxyphenylacetic acid. The clearance of FmT from plasma compares well with the clearance of intravenously administered levodopa. Carbidopa increases significantly the availability of FmT in plasma. These results verify, in a large number of human subjects, earlier analyses of FmT metabolism in other species. We validate a population-derived approach that can adequately describe the time course of FmT in plasma, alleviating the need for metabolite analysis.

Antiparkinson Agents↗
PubMed1999

Simple CPR: A randomized, controlled trial of video self-instructional cardiopulmonary resuscitation training in an African American church congregation.

STUDY OBJECTIVE: Despite the proven efficacy of cardiopulmonary resuscitation (CPR), only a small fraction of the population knows how to perform it. As a result, rates of bystander CPR and rates of survival from cardiac arrest are low. Bystander CPR is particularly uncommon in the African American community. Successful development of a simplified approach to CPR training could boost rates of bystander CPR and save lives. We conducted the following randomized, controlled study to determine whether video self-instruction (VSI) in CPR results in comparable or better performance than traditional CPR training. METHODS: This randomized, controlled trial was conducted among congregational volunteers in an African American church in Atlanta, GA. Subjects were randomly assigned to receive either 34 minutes of VSI or the 4-hour American Heart Association "Heartsaver" CPR course. Two months after training, blinded observers used explicit criteria to assess CPR performance in a simulated cardiac arrest setting. A recording manikin was used to measure ventilation and chest compression characteristics. Participants also completed a written test of CPR-related knowledge and attitudes. RESULTS: VSI trainees displayed a comparable level of performance to that achieved by traditional trainees. Observers scored 40% of VSI trainees competent or better in performing CPR, compared with only 16% of traditional trainees (absolute difference 24%, 95% confidence interval 8% to 40%). Data from the recording manikin confirmed these observations. VSI trainees and traditional trainees achieved comparable scores on tests of CPR-related knowledge and attitudes. CONCLUSION: Thirty-four minutes of VSI can produce CPR of comparable quality to that achieved by traditional training methods. VSI provides a simple, quick, consistent, and inexpensive alternative to traditional CPR instruction, and may be used to extend CPR training to historically underserved populations.

Adult↗
PubMed1999

Ring-substituted 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides with similar patterns of cytotoxicity to the dual topo I/II inhibitor DACA.

A series of ring-substituted analogues of the topoisomerase inhibitor 11-oxo-11H-indeno[1,2-b]quinoline-6-carboxamides was prepared and evaluated. The compounds were prepared by Pfitzinger reaction of the appropriate isatin-7-carboxylic acids and 1-indanones, followed by selective thermal decarboxylation of the resulting tetracyclic diacids, subsequent oxidation of the methylene group with alkaline permanganate under carefully controlled conditions, and 1,1'-carbonyldiimidazole-induced amidation. The compounds were evaluated in a panel of cell lines in culture. The largest increases in cytotoxicity (five to tenfold) were shown by 4-substituted analogues, with the 4-Cl derivative having an IC50 of 8 nM against the Lewis lung carcinoma.

Acridines↗
PubMed1999

High density oligonucleotide and DNA probe arrays for the analysis of target DNA.

The acquisition of sequence, expression and other information concerning genetic material constitutes a crucial component of the modern revolution in molecular biology. One important advance in this area is the development of high density oligonucleotide/DNA microarrays which allows the rapid sequence analysis of genomic target samples in addition to diagnostic possibilities with respect to genetic and infectious disease. In the present article we review protocols for the design of such microarrays and their principles of operation. Together with a look at some recent applications we include brief remarks as to the possibilities for the future.

Animals↗