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Biomedical subjects

C Brown

Publications and source records attributed to C Brown.

At least 361 records · Page 20Linked to original sources

Bryostatin 1: a potential anti-leukemic agent for chronic myelomonocytic leukemia.

Bryostatin 1 is a macrocyclic lactone which activates protein kinase C (PKC), and is able to induce maturation in cells from some cases of acute myelogenous leukemia. This paper reports that bryostatin inhibits the spontaneous in vitro proliferation of chronic myelomonocytic leukemia cells (CMMoL) in semi-solid medium at concentrations between 10(-8) and 10(-10) M. Growth inhibition was equivalent to or greater than that seen with phorbol-12-myristate-13-acetate. Bryostatin acted primarily as a cytotoxic agent, rather than as a cytostatic agent. The spontaneous in vitro proliferation of CMMoL cells is due to autocrine or paracrine secretion of granulocyte-macrophage colony-stimulating factor (GM-CSF). Bryostatin 1 actually increased GM-CSF secretion by CMMoL cells while inhibiting their proliferation. Bryostatin 1 also increased tumor necrosis factor alpha (TNF alpha) secretion by CMMoL cells, and in 2/5 cases the cytotoxic effect of bryostatin 1 on fresh CMMoL cells could be substantially reversed by the addition of antibody to TNF alpha to the culture medium. Bryostatin 1 may produce a cytotoxic effect on CMMoL cells in part by increasing the secretion of, or sensitivity to, TNF alpha, and may have therapeutic potential in CMMoL.

Antineoplastic Agents↗

Using bed scales in the neonatal intensive care unit.

Using bed scales in the intensive care nursery enables a nursing staff to weigh neonates efficiently. More important, it helps nurses provide continuous respiratory support, thermal control, and decrease negative stimulation for critically ill or premature neonates.

Beds↗

Specialist versus general practitioner treatment of problem drinkers.

The efficacy of specialist versus general practitioner (GP) treatment of problem drinkers was assessed in a randomised controlled trial. 40 problem drinkers referred consecutively to a specialist alcohol clinic by their GP were, after assessment, randomly allocated to either GP or specialist clinic treatment groups. All subjects received initial advice and counselling in the clinic about their drinking. The specialist clinic group received continued care from the clinic including, if necessary, admission to hospital. Patients in the GP group were returned to the care of the GP who was contacted and supported by the specialist. After 6 months of follow-up, there were significant reductions in alcohol consumption and alcohol-related problems in both groups. No significant difference was found between the two groups with respect to the main outcome measures. No differential treatment effect was found with the more severely dependent drinkers. The findings show that after an initial detailed assessment and advice session, the treatment provided by GPs is at least as effective as that from a specialist clinic with respect to improvements in drinking behaviour and alcohol-related problems. After initial assessment and advice, specialist clinics should encourage GPs to become more involved in the subsequent care of problem drinkers. Such a practice should be based on the individual patient's needs and the adequacy of support offered to GPs.

Adult↗

Differentiation and growth modulation of chronic myelogenous leukemia cells by bryostatin.

We have examined the ability of bryostatin 1 (bryo), an activator of protein kinase C, to induce differentiation of chronic myelogenous leukemia (CML) cells obtained from peripheral blood. Bryo induced a prompt and persistent macrophage-like differentiation, as evidenced by functional, morphological, and immunological criteria. Differentiated cells remained viable for at least 21 days with little change in cell number. CML cell cultures treated in semisolid medium with bryo showed diffuse infiltration with single macrophages, as well as discrete macrophage, mixed, and granulocytic colonies. Supernatants of suspension cultures of bryo-treated CML cells contained granulocyte-macrophage colony-stimulating factor (GM-CSF) by enzyme-linked immunosorbent assay. Furthermore, colony formation could be significantly inhibited by the addition of antibodies to GM-CSF. Prolonged liquid culture of CML cells in bryo reduced colony-forming unit, granulocyte-macrophage content. Bryo-induced differentiation was associated with a decrease in lactoferrin, a marker of granulocyte differentiation, and an increase in both c-fms and interleukin-1 beta RNA, both of which are expressed by monocytes/macrophages. These data demonstrate that bryostatin 1 is capable of inducing macrophage-like differentiation in maturing CML cells. Furthermore, bryostatin induces secretion of GM-CSF by such cells in suspension and semisolid medium and also promotes clonal extinction of granulocyte-macrophage progenitors. Bryostatin may be a possible therapeutic agent for CML.

Antineoplastic Agents↗

The American College of Rheumatology criteria for the classification and reporting of osteoarthritis of the hand.

Clinical criteria for the classification of symptomatic idiopathic (primary) osteoarthritis (OA) of the hands were developed from data collected in a multicenter study. Patients with OA were compared with a group of patients who had hand symptoms from other causes, such as rheumatoid arthritis and the spondylarthropathies. Variables from the medical history, physical examination, laboratory tests, and radiographs were analyzed. All patients had pain, aching, or stiffness in the hands. Patients were classified as having clinical OA if on examination there was hard tissue enlargement involving at least 2 of 10 selected joints, swelling of fewer than 3 metacarpophalangeal joints, and hard tissue enlargement of at least 2 distal interphalangeal (DIP) joints. If the patient had fewer than 2 enlarged DIP joints, then deformity of at least 1 of the 10 selected joints was necessary in order to classify the symptoms as being due to OA. The 10 selected joints were the second and third DIP, the second and third proximal interphalangeal, and the trapeziometacarpal (base of the thumb) joints of both hands. Criteria derived using the "classification tree" method were 92% sensitive and 98% specific. The "traditional format" classification method required that at least 3 of these 4 criteria be present to classify a patient as having OA of the hand. The latter sensitivity was 94% and the specificity was 87%. Radiography was of less value than clinical examination in the classification of symptomatic OA of the hands.

Adult↗

The duration of orthodontic treatment with and without extractions: a pilot study of five selected practices.

Contemporary orthodontic practice is diverse, both in the variety of clinical problems treated and in the methods used. Practices differ with respect to their patient composition as well as in many variables relative to treatment protocols. Such heterogeneity makes it difficult to make valid generalizations concerning the characteristics of orthodontic treatment procedures or outcomes; yet data and methods are required for assessment of issues of efficacy and utility. The frequency of orthodontic extractions is an objective criterion that distinguishes practices and may also be related to differences in treatment outcome variables, such as duration. Following a telephone survey to estimate extraction rates in the practices of 238 Michigan orthodontists, five practices with very high or low reported rates were chosen for this pilot study. Our primary aim was to determine whether a systematic relationship existed between the relative frequency of extraction treatments and the duration of active appliance therapy. Records of 438 patients from these practices were examined. The extraction rates of the practices ranged from a low of 25% to a high of 84%. Treatment duration was affected by several variables, such as the number of arches treated, the number of treatment phases, and the practice selected. When the data for all five practices were pooled, and all of the extraction versus nonextraction treatments were compared, the mean durations of treatment were 31.2 and 31.3 months, respectively. Data from individual practices, however, indicated that extraction treatment in each of the practices was of longer duration than nonextraction therapy. These differences in duration were 3.0, 6.6, 2.4, 3.0, and 7.3 months in the five practices.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Successful use of pooled sera to determine HIV-1 seroprevalence in Zaire with development of cost-efficiency models.

To determine the accuracy and cost efficiency of pooling sera prior to HIV-1 testing, sera from 8,000 Kinshasa factory workers and their spouses were screened individually (2.44% seropositive) and in 800 pools of 10 sera each. There were no false-negative or false-positive pools, resulting in a calculated seroprevalence estimate of 2.42%. Further testing of all sera in positive pools can identify HIV-positive individuals. These applications were modeled to compare the cost-efficiency of pooling with individual testing under different conditions. The results suggest that pooling provides an alternative test format for use in both developing and industrialized countries when the seroprevalence and/or the marginal cost of obtaining a sample are sufficiently low. For our cohort, testing only the pools for seroprevalence estimation resulted in a 78% cost saving compared with individual testing; pooling with subsequent identification of individual seropositives represented a 56% cost reduction.

Acquired Immunodeficiency Syndrome↗

Identification of Bacillus anthracis by using monoclonal antibody to cell wall galactose-N-acetylglucosamine polysaccharide.

Guanidine extracts of crude Bacillus anthracis cell wall were used to vaccinate BALB/c mice and to develop monoclonal antibody (MAb) to vegetative cell surface antigens. Two hybridomas selected during this study produced immunoglobulin M immunoglobulins, which appear to be directed to an epitope associated with the galactose-N-acetyl-D-glucosamine polysaccharide. Both demonstrated specificity in their binding to purified B. anthracis cell wall, o-stearoyl-polysaccharide conjugates, and intact, nonencapsulated vegetative cells. The interaction of the MAbs with purified polysaccharide was inhibited by 0.5 M galactose and lactose but not by N-acetylglucosamine, glutamate, glycine, or glycerol. Inhibition by glucose or sucrose was approximately 75% of that seen with galactose. Electron microscopy showed that both MAbs interacted with the cell wall of vegetative cells as well as with the cortex of spores. Neither MAb reacted with encapsulated vegetative cells, such as those from infected guinea pigs, nor did they react with intact spores. After conjugation to fluorescein isothiocyanate, the MAbs stained intensely all B. anthracis strains tested, whereas with two exceptions, none of the strains of 20 other Bacillus spp. was stained. The exceptions, strains of Bacillus cereus, could be differentiated from B. anthracis by being beta-hemolytic on blood agar.

Acetylgalactosamine↗

Limiting care: is CPR for everyone?

Current research on the efficacy of CPR in specific patient groups may lead to the withholding of CPR in groups that statistically show minimal success. Prognosticative factors that indicate minimal-at-best success with CPR include age greater than 70, dysrhythmias such as asystole and electromechanical dissociation, sepsis, metastatic cancer, GI hemorrhage, and acute stroke. Although physicians are under no legal or ethical obligation to provide futile treatments, how one defines a treatment as "futile" is unclear. As a patient advocate, the nurse acts to ensure the autonomous patient is fully informed, freely consenting, and actively directing his/her own health care. End-of-life decisions regarding health care must be based on the patient's goals, which will be revealed through the moral discourse among health care professionals, patients, and their loved ones.

Beneficence↗

Measurement of anterior-posterior displacement of the knee. A comparison of the results with instrumented devices and with clinical examination.

Thirteen subjects who had normal knees and fifteen patients who had a chronic rupture of the anterior cruciate ligament were tested in order to compare the measurements of tibiofemoral displacement as recorded by four commercial devices: the Acufex knee-signature system, the Genucom knee-analysis system, the Medmetric KT-1000 arthrometer, and the Stryker knee-laxity tester. Anterior and posterior displacement were measured at forces of eighty-nine newtons (twenty pounds) and 133 newtons (thirty pounds). We found significant differences in reproducibility of measurement among the devices. The Acufex, Medmetric, and Stryker devices had more reproducible measurements, and they could be used to identify 80 to 90 per cent of the normal subjects and anterior cruciate-deficient patients. The Genucom device had poorer reproducibility of measurement, and it tended to register greater differences in displacement between the right and left knees of normal subjects.

Adult↗

[First intention treatment of arterial hypertension. Effectiveness and safety of perindopril].

Inhibitors of the angiotensin conversion enzyme (ICE) represent an effective and well tolerated therapeutic class, for the treatment of arterial hypertension. The antihypertensive efficacy or perindopril, an ICE active in one single daily dose, is at least equal to that of reference antihypertensive drugs administered at usual doses. The possibility of occurrence of some side-effects while using ICE, has resulted in a particular attention in evaluating the safety of perindopril. First, the renal function was monitored. During essential hypertension, no significant variation of the creatininemia was observed with long-term administration of the drug (12 months). In elderly hypertensive patients or patients with chronic renal insufficiency, the glomerular filtration is also preserved, except during rare occurrences of decreased creatinine clearance, especially after adjunction of hydrochlorothiazide. A discrete elevation of the kaliemia without clinical significance is observed when perindopril is used as a single drug. Reports of symptomatic hypotension with perindopril are rare (0.2%), even in situations of water and sodium depletion. Among other side-effects of ICE, cough, more recent, was thoroughly investigated. Its frequency was determined during a double blind trial comparing perindopril (1.2%) with captopril (2.4%). It was also evaluated during a long-term study concerning 632 hypertensive patients (391 patients treated in 1 year); its incidence is the 2.9 p. cent and it resulted in discontinuation of the treatment in 8 cases. In this study, 36 patients interrupted the treatment prematurily because of an adverse reaction (5.7%). Finally no harmful drug interaction was reported. The favorable tolerance profile of perindopril is combined with a beneficial effect on the functional and structural modifications of the heart and large vessels related to hypertension.

Antihypertensive Agents↗

Immune responses associated with early survival after peroral infection with Toxoplasma gondii.

After peroral infection with cysts of Toxoplasma gondii, C57BL/6 mice died and A/J mice survived. To better understand the reasons for this difference in survival, host defenses during acute infection were studied: initial portal of entry of T. gondii contributed to susceptibility as more C57BL/6 mice survived after i.p. than peroral infection (p less than 0.001). Susceptible (C57BL/6) mice had more necrosis and inflammation in their brains, livers, and mesenteric lymph nodes than resistant (A/J) mice. Susceptible mice had less IgM antibody to T. gondii (p less than 0.0005) than resistant mice 7 days after infection, but amounts of IgG antibody to T. gondii were similar. Infection reduced percentages of spleen cells with the Lyt-2+ phenotype in susceptible (p less than 0.02) but not resistant mice; infection decreased percentages of spleen cells with the L3T4+ phenotype similarly in both strains of mice. Spleen cells from infected susceptible mice had greater depression in their blastogenic response to Con A (p less than 0.05) and produced significantly more IFN-gamma in culture with (p = 0.009) or without (p less than 0.05) Toxoplasma Ag than spleen cells from infected resistant mice. Infection increased serum levels of IFN-gamma substantially in susceptible but not resistant mice. Lymphocyte IL-2 production was similar in both groups of mice. Peritoneal macrophages from both strains of mice became activated to inhibit or kill T. gondii by 7 days after infection, but Kupffer cells became activated only in susceptible mice. These results indicate that increased resistance to peroral Toxoplasma infection is likely to be mediated by a number of immune responses acting together. They suggest that increased susceptibility may result from inadequately regulated inflammatory responses that increase tissue destruction.

Animals↗

Passive smoking on commercial airline flights.

In-flight exposure to nicotine, urinary cotinine levels, and symptom self-reports were assessed in a study of nine subjects (five passengers and four attendants) on four routine commercial flights each of approximately four hours' duration. Urine samples were collected for 72 hours following each flight. Exposures to nicotine measured during the flights using personal exposure monitors were found to be variable, with some nonsmoking areas attaining levels comparable to those in smoking sections. Attendants assigned to work in nonsmoking areas were not protected from smoke exposure. The type of aircraft ventilation was important in determining the levels of in-flight nicotine exposure. The environmental tobacco smoke levels that occurred produced measurable levels of cotinine (a major metabolite of nicotine) in the urine of passengers and attendants. Passengers who experienced the greatest smoke exposure had the highest levels of urinary cotinine. Changes in eye and nose symptoms between the beginning and end of the flights were significantly related both to nicotine exposure during the flight and to the subsequent urinary excretion of cotinine. In addition, subjects' perceptions of annoyance and smokiness in the airplane cabin were also related to in-flight nicotine exposure and urinary excretion measures.

Air Pollutants↗

The monoamine oxidase inhibitor-tyramine interaction.

Reports of hypertensive reactions from monoamine oxidase inhibitors (MAOI) began to proliferate in the early 1960s. Asatoor did extensive research and found that the combination of an MAOI and a food containing tyramine resulted in the hypertensive interaction ("the cheese reaction"). Because of the risk of intracerebral hemorrhage and death, clinicians were hesitant to use the MAOIs. Although progress on the metabolic effects of MAOIs has been slow, use of clinical information in addition to analysis of bioactive amine content of foods has allowed the formulation of dietary recommendations, which are thought to be useful clinically in the administration of MAOIs. This has resulted in the gradual return to use of these psychotropic compounds.

Diet↗

The primary structure of a feline class I gene: striking similarity to HLA-A.

The sequence of a feline class I pseudogene and its comparison with class I genes from other species is presented. The gene isolated is a pseudogene because of the presence of four stop codons and two frame shift mutations in the first- and second-domain encoding exons, as well as a mutation in a splice acceptor site in the third intron. By sequence comparison with the other class I sequences determined to date, the FLA pseudogene is most closely related to the HLA-A locus products (88% nucleotide identity.

Amino Acid Sequence↗