[Searching for a controlled madness. How artists were fascinated by images of schizophrenics].
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Biomedical subjects
Publications and source records attributed to G Graf.
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The purpose of this study was to evaluate the effects of an intervention on pharmacists' behaviors, knowledge, and attitudes related to skin cancer prevention counseling. Fifty-four pharmacy sites (N = 178 pharmacists) were randomly assigned to the intervention or control condition. Intervention consisted of video-based training, prompts installed in the pharmacy to promote pharmacist-patient discussions on the topic, and group-based feedback on previous week's counseling rates. Outcomes were measured using a mailed survey. The proportion of patients counseled at post-test was significantly higher among intervention subjects, adjusting for pretest values. Similar results were found for pharmacists' skin cancer knowledge and self-rated expertise, but not for counseling-related attitudes. The intervention was successful. If implemented on a wide scale, large segments of the U.S. population would be exposed to skin cancer prevention advice.
OBJECTIVES: This study evaluated the effects of an intervention on rates of skin cancer prevention counseling by pharmacists. METHODS: Fifty-four pharmacies were randomly assigned to intervention or control conditions. Intervention consisted of training, feedback, and prompts. Counseling rates before and after the intervention were obtained from study confederates. RESULTS: At pretest, the proportions of control and intervention sites providing counseling at least once were 7.4% and 0%, respectively (NS). At posttest, these proportions were 3.7% and 66.7%, respectively (P < .001). CONCLUSIONS: The results indicated that the intervention was successful and that pharmacists can play an important role in educating the public about skin cancer prevention strategies.
The main aspects of the development of veterinary toxicology from the time of foundation of the veterinary college in Berlin 1790 up to 1945 are being described. The first toxicological experiments were made in 1821. The teaching of veterinary toxicology in Berlin began in 1872 and the foundation of the Department of Pharmacology as a part of Small Animal Clinic was in 1886. The historical development may be divided in four periods. In the first, from 1821-1830, acute and chronical intoxications were examined. The second period, from 1831-1870, has been determined by experimental drug toxicology and the beginning of environmental toxicology. In 1935 were the foundation of an independent Department of Pharmacology and Toxicology and in this time the toxicological research reached an internationally important level.
Since the early twenties several institutes of the Veterinary College in Berlin were involved in the development of microchemical analyzing methods for doping-alkaloids and clinical studies in doped race horse. This research made it possible to build national acting structures against the abuse of doping in race horses, which soon became a model for similar activities in other countries, for instance Greece, Japan and the United States. Concerning the results of their research, the scientists of the Veterinary College in Berlin have got an enormous part in fighting against doping in race horses in Germany. In the year 1943 the second world war led to a stagnation of the development of spectroscopical methods and clinical investigations of this field.
BACKGROUND: The transition from remifentanil intraoperative anesthesia to postoperative analgesia must be planned carefully due to the short duration of action (3-10 min) of remifentanil hydrochloride, a potent, esterase-metabolized mu-opioid agonist. This study compared the efficacy and safety of transition regimens using remifentanil or morphine sulfate for immediate postoperative pain relief in patients who had surgery under general anesthesia with remifentanil/propofol. METHODS: One hundred fifty patients who had received open-label remifentanil and propofol for intraoperative anesthesia participated in this multicenter, double-blind, double-dummy study and were randomly assigned to either the remifentanil (R) group or the morphine sulfate (M) group. Twenty minutes before the anticipated end of surgery, the propofol infusion was decreased by 50%, and patients received either a placebo bolus (R group) or a bolus of 0.15 mg/kg morphine (M group). At the end of surgery, the propofol and remifentanil maintenance infusions were discontinued and the analgesic infusion was started: either 0.1 microg x kg(-1) x min(-1) remifentanil (R group) or placebo analgesic infusion (M group). During the 25 min after tracheal extubation, remifentanil titrations in increments of 0.025 microg x kg(-1) x min(-1) and placebo boluses (R group), or 2 mg intravenous morphine boluses and placebo rate increases (M group) were administered as necessary at 5-min intervals to control pain. Patients received the 0.075 mg/kg intravenous morphine bolus (R group) or placebo (M group) at 25 and 30 min after extubation, and the analgesic infusion was discontinued at 35 min. From 35 to 65 minutes after extubation, both groups received 2-6 mg open-label morphine analgesia every 5 min as needed. RESULTS: Successful analgesia, defined as no or mild pain with adequate respiration (respiratory rate [RR] > or =8 breaths/min and pulse oximetry > or = 90%), was achieved in more patients in the R group than in the M group (58% vs. 33%, respectively) at 25 min after extubation (P < 0.05). The median remifentanil rate for successful analgesia was 0.125 microg x kg(-1) x min(-1) (range, 0.05-0.23 microg x kg(-1) x min(-1)), and the median number of 2-mg morphine boluses used was 2 (range, 0-5 boluses). At 35 min after extubation, > or = 74% of patients in both groups experienced moderate to severe pain. Median recovery times from the end of surgery were similar between groups. Transient respiratory depression, apnea, or both were the most frequent adverse events (14% for the R group vs. 6% for the M group; P > 0.05). CONCLUSIONS: Remifentanil provided safe and effective postoperative analgesia when administered at a final rate of 0.05-0.23 microg x kg(-1) x min(-1) in the immediate postextubation period. Remifentanil provided more effective postoperative analgesia than did intraoperative treatment with morphine (0.15 mg/kg) followed by morphine boluses (< or = five 2-mg boluses). The effects of remifentanil dissipated rapidly after ending the infusion, and alternate analgesia was required. Further studies are underway to define transition regimens that will improve postoperative analgesia in patients receiving anesthesia with remifentanil.
Thrombopoietin (TPO) is the major regulator of platelet production in vivo and is the ligand for the MPL receptor. In an effort to determine the distribution of TPO and MPL in the different hematopoietic cell types and in various types of tissue, we examined the mRNA expression of this ligand-receptor pair in two series of human leukemia-lymphoma cell lines and of solid tumor cancer cell lines using northern blot and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. At the northern blot mRNA level, 8/15 (53%) megakaryocytic and 3/11 (27%) erythroid leukemia cell lines expressed MPL mRNA; except for one positive monocytic cell line, the remaining 78 pre B-cell, B-cell, plasma cell, T-cell, NK cell, myeloid, monocytic and Hodgkin/anaplastic large cell lymphoma (ALCL)-derived cell lines were negative. No MPL message was detected in any of the 23 solid tumor cell lines established from 21 different tumors. In order to examine whether a low level of MPL expression could be detected, 51 leukemia cell lines were investigated with the RT-PCR technique. By this technique, MPL message was seen in many more cell types: 13/26 (50%) of non-erythromegakaryocytic cell lines and in nearly all megakaryocytic (14/15, 93%) and erythroid (10/11, 91%) cell lines. Thus, the highest expression of MPL clearly occurs in cells with megakaryocytic differentiation; furthermore, expression of MPL appears to be restricted to hematopoietic cell types. TPO mRNA expression was examined by RT-PCR and found in 9/11 (82%) of the solid tumor cell lines (derived from colon, endometrium, kidney, liver, ovary, retinoblastoma and urinary bladder cancers). Among the leukemia-lymphoma cell lines, TPO mRNA was detected by RT-PCR in most plasma cell, myeloid, megakaryocytic and erythroid cell lines, but not in pre B-cell, B-cell or T-/NK-cell lines. The results reported here extend the observations of MPL and TPO expression in normal cells to the whole spectrum of hematological cell types and to an array of different tissue types, both exemplified by their malignant counterparts.
Thrombopoietin (TPO) is a major regulator of megakaryocytopoiesis both in vivo and in vitro. TPO initiates its biological effects by binding to the c-MPL receptor, which is a member of the hematopoietin receptor superfamily. To define the regulation of the MPL receptor, six continuous human leukemia cell lines with megakaryocytic properties were treated with the phorbol ester 12-myristate 13-acetate (PMA), TPO and transforming growth factor (TGF)-beta 1, a cytokine known to possess inhibitory effects. We used Northern blotting and flow cytometry analysis to determine MPL mRNA and protein levels. An increase of MPL mRNA and protein expression was observed in 2/6 PMA-exposed cell lines. There is no evidence from this study that TPO or TGF-beta 1 cause any decrease or increase in MPL expression. MPL upregulation triggered by PMA was accompanied by signs of induced differentiation such as increase in CD41, CD42 and CD61 expression, increase in cell size and cessation of proliferation. These data demonstrate that MPL can be upregulated in differentiating megakaryocytic cells via stimulation of protein kinase C, the intracellular target of PMA and a key kinase in one of the second messenger signal transduction pathways. These findings further the understanding of the regulation of this molecule, a cytokine receptor that, together with its ligand TPO, appears to represent a crucial element in megakaryocytopoiesis.
Thrombopoietin (TPO) is a recently characterized growth and differentiation factor for megakaryocytes and platelets exerting its effects via the receptor MPL. We examined the expression of MPR on the cell surface of a panel of 43 myelomonocytic, erythroid and megakaryocytic leukemia cell lines and 21 primary acute myeloid leukemia (AML) cases by flow cytometry. With few exceptions MPL was found on all 32 erythroid/megakaryocytic cell lines and on all 11 growth factor-dependent myelomonocytic cell lines, albeit at variable percentages and intensities per cell population (with a 10% cut-off level for positivity still 30/43 cell lines scored as MPL positive). The majority of the primary AML samples (including all seven M6/M7 cases) expressed the MPL protein regardless of the morphological and immunological subtype (13/21 cases had >10% MPL-positive cells). Recombinant TPO overexpressed in hamster cells induced a mitogenic response in seven cell lines (one growth factor-independent and six factor-dependent lines) and in 3/21 AML specimens (two AML M2, one AML M7) as measured by 3H-thymidine incorporation. Expression of MPL clearly did not correlate with response to TPO. For further detailed studies of the interaction of TPO with other cytokines we used the AML M7-derived M-07e cells as an informative indicator cell line for which both murine and human TPO acted as a very potent mitogen in a dose-dependent fashion (3- to 11-fold proliferation increase relative to medium alone). This growth factor-dependent cell line which is normally cultured in conditioned medium containing several cytokines could be grown in long-term culture supplemented only with TPO. Co-incubation of M-07e with various cytokines and TPO showed additive proliferative effects for interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) and synergistic responses for stem cell factor (SCF), interferon (IFN)-alpha, and to a lesser extent for IFN-gamma and tumor necrosis factor (TNF)-alpha. Erythropoietin (EPO), IL-1, IL-6, IL-11 and leukemia inhibitory factor (LIF), know as megakaryocytic maturation-inducing molecules, were not substantially effective, neither singly nor in combination with TPO, with regard to cell growth. Transforming growth factor (TGF)-beta1 antagonized the inductive effect of TPO on M-07e cell growth. Addition of TPO to cultures of megakaryocytic cell lines failed to significantly alter the ploidy distribution and the differentiation marker immunoprofile of the cells indicating a lack of maturation-inducing effects in this model system. In summary, TPO represents an efficient in vitro potentiator of megakaryocytic leukemia proliferation of at least some primary cases or cell lines. While TPO seems to be the major physiological regulator of megakaryocytopoiesis, the present data suggest also some proliferative effects on certain leukemia cells, apparently on non-megakaryocytic leukemia cells as well, thus assigning to TPO a possible pathobiological role in leukemogenesis which would be of clinical relevance. Our data show that the response to TPO is not restricted to cells committed to the megakaryocytic differentiation pathway as we could demonstrate TPO-responsive megakaryocytic and non-megakaryocytic cell lines; thus, these cell lines represent powerful tools in such analyses. Consequently, this new cytokine needs to be properly examined so we can get a clear understanding of the clinical possibilities and dangers.
Adnexal torsion, although infrequent, may have a devastating effect on the future reproductive performance of adolescents and young women. However, clear variables predicting a favorable operative outcome have not yet been identified. In this retrospective study the authors analyzed the charts of 72 adolescent girls hospitalized for acute lower abdominal pain. In 13 cases (18%) torsion of the adnexa was found and six of them ended with reproductive compromise expressed by either adnexectomy or salpingectomy. We have found that in the cases of adnexal torsion, the time factor, from admission until final diagnosis and treatment, was the only significant variable affecting the operative results. A shorter time until the operation, resulted in less harm to the reproductive organs involved. Therefore, we conclude that whenever an adnexal torsion is suspected, a quick diagnostic laparoscopy followed by an operative procedure when needed, may contribute to better reproductive performance in the future.
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Postoperative analgesia provided by epidurally administered sufentanil and/or morphine was evaluated in 45 patients recovering from major gynecologic surgery. At the first complaint of pain in the Postanesthesia Care Unit, patients received a single epidural bolus of 30 micrograms sufentanil (group A), 5 mg morphine (group B), or 30 micrograms sufentanil plus 3 mg morphine (group C) in a randomized blinded fashion. Analgesic efficacy was assessed throughout the 24-h study period with 10-cm visual analog scales. The need for additional postoperative analgesia (patient-controlled analgesia, 1 mg of morphine every 6 min as necessary) and the incidence of adverse effects were also assessed. Patients receiving sufentanil (groups A and C) had significantly faster onset of analgesia than did patients given morphine alone (group B, P less than 0.05). Group B subjects experienced the longest duration of analgesia (B vs A and C, P less than 0.05) and required significantly less patient-controlled analgesia (morphine) than patients in group A (P less than 0.05). No patient developed clinically significant respiratory depression or excessive sedation, and there were no intergroup differences in incidence of pruritus or nausea (P value not significant). The data indicate that a mixture of sufentanil and morphine provides either a more rapid onset of epidural analgesia or reduced patient-controlled analgesia narcotic requirement than respective doses of each agent administered alone.
To determine the lowest effective dose of epidural sufentanil given for analgesia, 41 patients undergoing elective abdominal gynecologic surgery during continuous epidural anesthesia (lidocaine 2%) were randomly assigned to one of four postoperative treatment groups. Patients received an epidural bolus of either 25 (group A), 40 (group B), 55 (group C), or 70 micrograms (group D) sufentanil in 10 mL of saline. They were evaluated for the next 8 h using a 10-cm visual analogue scale. Except for two individuals in group A, all patients achieved a visual analogue scale score of 1 cm or less during the study interval. The onset of analgesia was most rapid in the two higher dose groups (A vs C and D; P less than 0.05). Pairwise comparison between groups showed a significant difference in the time needed to achieve maximum pain relief between the lowest and highest treatment groups (A vs D; P less than 0.05). Duration of analgesia was also significantly longer in groups C and D than in group A (208.0 +/- 21.1 and 224.0 +/- 14.7 vs 140.0 +/- 10.7 min; P less than 0.05). There were no differences among groups with regard to mean respiratory rate, level of sedation, 24-h narcotic requirements, or incidence of nausea, vomiting, and pruritus (P = NS). A single patient in group D suffered profound respiratory depression within seconds of administration. We conclude that, in patients recovering from lower abdominal surgery, a single 40-55-micrograms epidural bolus of sufentanil provides 3-3.5 h of effective analgesia, and that larger doses are not warranted.
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The exact regional correlation of findings of facial bone scans, planar or SPECT, to dental orthopan X-ray films (OPT) is difficult because of the very different projection techniques. To improve correlative imaging in this regard a projection algorithm was developed that uses SPECT data of the skull for reconstructing an orthopan tomoscintigraphic projection. Fourteen conventional SPECT slices of the upper and lower jaws were obtained during bone scanning. All mandibular slices were superimposed resulting in a horseshoe shaped structure, while was marked by an ROI which was divided into segments. All 14 SPECT slices were then masked by this segmental ROI, thereby marking the teeth-carrying bone in all slices. The information from this horseshoe like ROI is then transformed into lines. Line by line arrangement results in an orthopan projection, the orthopan tomoscintigram. This new display allows 1:1 true scale superimposition with the X-ray OPT and markedly facilitates correlative imaging.
Gated SPECT (GASPECT) during radionuclide ventriculography (RNV) is a time-consuming procedure requiring extended hard- and software. Furthermore, the procedure suffers from poor count statistics. Our method tries to overcome these difficulties by exploiting the count summation effect of Fourier analysis. The sine and cosine coefficients of the first harmonic are extracted from the gated views and reconstructed. This, in fact, results in an improvement of the count statistics by a factor of four combined with a tremendous reduction of disc space requirements. Using short-axis slices, bull's-eye plots of the amplitude and phase of the left ventricle are calculated. Cardiac functions and localization and extent of any malfunction are documented three-dimensionally without superposition.
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The taxonomy of the family Pasteurellaceae has remained controversial despite investigations of biochemistry, serology, and nucleic acid relatedness. In an attempt to resolve some of this confusion, we have partially sequenced the 16S rRNAs of seven members of the family, representing all three genera. The sequences were aligned, similarity scores calculated, and single, average and complete linkage cluster analysis of the resulting distance matrix performed. In this way, an evolutionary branching pattern of these closely related species was reconstructed, and the approximate phylogenetic position of the family determined. Actinobacillus (Haemophilus) actinomycetemcomitans clustered with Haemophilus instead of Actinobacillus, supporting transfer of this species to the genus Haemophilus. Thus cluster analysis of phylogenetic relatedness was found to be particularly useful for studying closely related organisms, and could be performed using a microcomputer.