Sertraline and platelet counts in idiopathic thrombocytopenia purpura.
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1-Naphthylamine↗
Biomedical subjects
J Wiener
Publications and source records attributed to J Wiener.
Molecular approaches to prevention and detection of epithelial ovarian cancer.
More than 90% of epithelial ovarian cancers arise from single cells. Malignant transformation can be associated with a number of molecular alterations including upregulation of tyrosine kinases and phosphatases, physiologic activation o ras, mutation of p53, amplification of myc, and increased activity of matrix metalloproteinases 2 and 9. Proliferation of transformed epithelial cells can be enhanced through the persistence of autocrine growth stimulation by TGF-alpha, loss of autocrine growth inhibition by TGF-beta, as well as paracrine growth stimulation by macrophage derived cytokines and OCAF, a novel lyso-phospholipid. Ascites tumor cells retain responsiveness to growth inhibition by TGF-beta which induces apoptosis in malignant ovarian epithelial cells, but not in normal ovarian surface epithelium. Proliferation of surface epithelial cells following ovulation may contribute to the pathogenesis of ovarian cancer. Use of oral contraceptives that suppress ovulation has been associated with reduced risk of ovarian cancer in later life. Retinoids also deserve further evaluation for chemoprevention. Treatment with fenretinide was associated with decreased incidence of ovarian cancer. Additive or synergistic inhibition of ovarian tumor cell proliferation has been observed with TGF-beta in combination with all-trans-retinoic acid. Early detection of ovarian cancer could improve survival. Transvaginal sonography (TVS) and serum markers such as CA-125 have been evaluated in multiple clinical trials. The former lacks adequate specificity, whereas the latter is not sufficiently sensitive. Use of multiple serum markers can improve sensitivity. A combination of CA-125, M-CSF and OVX-1 has detected > 95% of Stage I ovarian cancers. If similar results are obtained with different data sets, multiple serum markers could be used to trigger the performance of TVS, providing a potentially cost effective screening strategy. Prospective trials will be required to demonstrate that screening for early stage ovarian actually impacts on survival.
Diagnosis, Differential↗
A randomized, double-blind, placebo-controlled trial of selective digestive decontamination in a medical-surgical intensive care unit.
A randomized, double-blind, placebo-controlled trial of selective decontamination of the oropharynx and gastrointestinal tract was conducted on 61 intubated patients in a medical-surgical intensive care unit (ICU) to determine the impact on nosocomial pneumonia, other infections, and emergence of colonization or infection with antibiotic-resistant bacteria. Over 8 months, 30 patients received an oral paste and solution containing polymyxin, gentamicin, and nystatin; 31 patients received a placebo paste and solution. At study entry, patients in both groups were seriously ill (mean acute physiologic score, 27.2), frequently had pulmonary infiltrates (73.8%), and were likely to be receiving systemic antibiotics (86.9%). There were no differences between study patients and control patients in these characteristics or in frequency of any nosocomial infection (50% vs. 55%), nosocomial pneumonia (27% vs. 26%), febrile days (2.3 vs. 2.0), duration of antibiotic therapy (14.0 vs. 13.4), or mortality rates (37% vs. 48%). There was no difference in infections caused by antibiotic-resistant gram-negative bacilli, although a trend towards more frequent infection with gentamicin-resistant enterococci was found for study patients. Selective decontamination did not appear to be effective in our very ill medical-surgical ICU patients, although the number of patients in our trial was sufficient to detect only a 50% or greater reduction in pneumonia rates.
Colistin↗
Exercise programmes in the treatment of children with learning disabilities.
Learning disability is characterised by a discrepancy between achievement and assessed intellectual ability. Children with this problem commonly (but not invariably) show impaired motor proficiency, as assessed by such instruments as the Bruininks-Oseretsky Test of motor proficiency. It has been hypothesised that poor motor performance and/or poor social skills lead to exclusion from games, creating a vicious cycle of decreasing participation, decreasing competence, a deterioration of self-worth and increasing social maladjustment. Attempts to break the vicious cycle with programmes designed to enhance motor proficiency have been uniformly unsuccessful. There is limited experimental evidence to support the view that structured physical activity programmes with an embedded social skills training component can be an effective method of enhancing both actual motor ability and self-perception of physical and academic competence. However, a controlled comparison with small-group, academic instruction has shown that, from the educational perspective, a physical activity-based intervention is no more effective than other forms of special attention. The main argument for delivering social skills training through a physical activity programme lies not in a unique impact upon learning disability, but rather in terms of the other well-established long term health benefits of exercise.
Adolescent↗
Early and late cognitive event-related potentials mark stages of HIV-1 infection in the drug-user risk group.
HIV-1 (Human immunodeficiency virus) infection of the brain causes delays in auditory event-related potential (ERP) components. We recorded auditory ERPs from 38 former parenteral drug users (PDUs) at three stages of HIV-1 infection: seronegative; seropositive; stage II; and seropositive, stage IV. There were five response conditions: Go Nogo, Count, Simple Response, Simple Count, and Ignore. P3 peak latencies were significantly delayed and P3 amplitudes were significantly reduced for all seropositives, including asymptomatics, when compared to PDU seronegative controls. In contrast, the P1 and N1 peak latency measures were delayed only for seropositives with acquired immunodeficiency syndrome (AIDS) qualifying illnesses. There was a significant negative correlation between the CD4 count and the latency of P1, N1, and the MMN. Also, increased P1 and N1 amplitudes correlated with indices of disease progression (Choice RT and CD4 counts, respectively). The results extend previous findings by clarifying the pattern of auditory ERP markers of disease progression. Early, as well as late, brain involvement caused by HIV-1 is marked by delays and decreased amplitudes in cognitive components. In addition, late brain involvement is marked by delays and increased amplitudes in specific, automatic, and/or obligatory components.
AIDS Dementia Complex↗
Looking out and looking in: some reflections on 'body talk' in the consulting room.
In this paper, I use illustrations from analytic work with one patient to suggest that we reconsider and extend the meaning which we give to the term 'psychosomatic'. It should include patients who come for analysis with severe anxieties about their bodies which may not necessarily take the form of an actual organic bodily illness. Using contemporary analytic thinking in this field, I have tried to look at what we mean by the term 'psychosomatic' and to make some attempt to differentiate it from the term 'hysteria'. Hysterical symptoms may sometimes mask earlier and more profound psychosomatic troubles, but may need to be analysed before the core split between psyche and soma may be approached. A useful way of bypassing difficult overlaps in diagnostic terminology when thinking about the way in which patients use the body in the consulting room, can be to make a distinction between body talk and body language. Body talk I have described as a primitive mode of communication which is a precursor to actual talking and which for some patients can come to be a substitute for talking, thinking and reflecting. When this happens, it suggests a very early fundamental rupture between body and mind where certain deintegration/reintegration experiences have inhibited growth and the body continues to function in an archetypal fashion. I hypothesize that body talk is a consequence of the kind of preverbal communication between mother and baby where there may have been a bad fit in terms of vitality affects. In later life, this can manifest itself in the form of 'body' or psychosomatic problems which cannot be put into words but are often recognizable through the quality of the interpersonal transference dynamics. Body language, on the other hand, is an essential and unique component in every patient's communication about him or herself. Our sense impressions of a patient can teach us much about the psychic meaning of body-based responses through observing with our eyes, our nose, as well as through our ears. Whilst we may all regress into body talk when under stress, body language may be said to be more integrated at all points with verbal communications and therefore it suggests some capacity to symbolize. In the transference/countertransference dynamics, there is less evidence of discomfort or dissonance between what the patient is 'saying' and what they seem to be 'doing', than there was in the earlier body talk.
Adult↗
Growth properties and receptor expression in vascular smooth muscle cells from hypertensive rats.
The objective of this study was to evaluate the growth properties and receptor expression in aorta-ring derived smooth muscle cells (SMCs) cultured from control (WKY) and spontaneously hypertensive rats (SHR). SHR-SMCs exhibited a 3-4 day lag period before migrating. In addition, SHR-SMCs had a significantly higher growth rate, shorter population doubling time and higher saturation density level characteristics that were retained at higher passage levels. beta-adrenergic and angiotensin (All) receptors were measured using iodocyanopindolol (ICYP) and [3H]-All, respectively. All receptor expression was similar in both WKY and SHR-SMC cultures. WKY-SMCs exhibited little ICYP binding (Bmax 8.27 +/- 2.0 fmol/mg) while SHR-SMC binding capacity was 8 fold higher (Bmax 65 +/- 9.2 fmol/mg). In addition, the responsiveness of the beta-receptor, as assessed by adenylyl cyclase stimulation, was similar for WKY and SHR-SMCs. These data suggest that factors regulating SMC receptor expression in vitro are selective since All and adrenergic receptor densities exhibit different responses to hypertension.
Animals↗
Cell growth regulation in epithelial ovarian cancer.
BACKGROUND: As in the case of other epithelial neoplasms, most ovarian cancers arise from single clones of cells that have undergone multiple genetic alterations. A comparison of normal and malignant ovarian epithelium has identified several differences in growth regulation by peptide growth factors, protooncogenes, and tumor suppressor genes. METHODS: Recent articles and abstracts have been reviewed. RESULTS: The malignant ovarian epithelial phenotype has been associated with (1) autocrine growth stimulation by transforming growth factor-alpha, (2) loss of autocrine growth inhibition by transforming growth factor-beta, (3) mutation or amplification of ras in 2-12% of cases, (4) amplification of myc in 23% of specimens, (5) expression of fms in 56% of cases with potential autocrine stimulation by macrophage colony stimulating factor, (6) paracrine stimulation by macrophage products including interleukin-1, interleukin-6 and tumor necrosis factor, (7) overexpression of c-erbB-2 (HER-2/neu) in 30% of cases, and (8) mutation with consequent overexpression of p53 in 50% of advanced ovarian cancers. A poor clinical prognosis is associated with expression or overexpression of the epidermal growth factor receptor, fms, and HER-2/neu. Antibodies against the extracellular domain of the HER-2/neu gene product p185 inhibit the growth of tumor cells that overexpress HER-2/neu and are associated with marked decreases in diacylglycerol levels. The intracellular kinase domain is required for growth inhibition. Antibodies that inhibit growth stimulate phosphorylation of intracellular substrates. Ricin A chain monoclonal antibody conjugates that react with p185 also inhibit the growth of tumor cells that overexpress p185. The intracellular kinase region is not required for immunotoxin-mediated killing. Coexpression of HER-2/neu and the epidermal growth factor receptor has been observed in 65% of epithelial ovarian cancers and in a limited number of normal tissue from a fraction of donors. CONCLUSIONS: Multiple alterations in growth factors, protooncogenes and growth factors have been detected in different epithelial ovarian cancers. Inappropriate signalling from receptor tyrosine kinases may be particularly important for ovarian oncogenesis. Drugs that affect tyrosine kinase and phosphatase activity deserve attention as potential therapeutic agents for ovarian cancer. The extracellular domains of the HER-2/neu gene product p185 and the epidermal growth factor receptor may provide useful targets for serotherapy.
Carcinoma↗
Isolation and characterization of cerebral resistance vessel endothelium in culture.
Organ-derived endothelia have been shown to exhibit distinct patterns of morphology and growth responsiveness in vitro. This report describes the development, cloning and establishment of long-term serial cultures of rat vascular endothelial cells derived from cerebrocortical resistance vessels (small arteries and arterioles). Modification of our previous published technique for establishing resistance vessel-derived smooth muscle cells (RV-SMC) resulted in enhanced levels of endothelial outgrowth from collagenase-treated microvessel fragments. Although primary culture growth consisted predominantly of SMC, subsequent subcultivation of these cultures revealed the presence of distinct endothelial cell clusters within the SMC monolayer. Serial cloning of these isolates resulted in a homogeneous population of cells with the characteristic endothelial cobblestone growth pattern and positive immunofluorescence for factor VIII-related antigen. Previously established RV-SMC frozen stocks provided an additional source for obtaining resistance vessel endothelial cells. This was made possible by the slow proliferation rate of early-passage RV-SMC and their inability to withstand freezing procedures. Endothelial cells from both preparations were identical and designated resistance vessel derived endothelial cells RV-EC. Upon long-term cultivation (> P15), confluent RV-EC cultures expressed spontaneous multicellular cord development that stained positive for factor VIII-related antigen. Cell growth studies demonstrated that RV-EC were capable of significant growth when maintained in serum-free conditions. Growth kinetics using serum-free conditioned medium demonstrated mitogenic activity indicating the presence of an autocrine growth factor. Increase growth responsiveness was also noted in RV-EC when treated with a variety of peptide growth factors. These results indicate that resistance vessel endothelium can be successfully isolated and maintained in long-term serial cultures. Furthermore, the availability of cultured EC and SMC from this unique microvascular site will enable examination of cerebrovascular endothelial-smooth muscle cell interactions in vitro and may help to elucidate the mechanisms of altered vascular function in disease states.
Animals↗
Magnetic resonance abnormalities in HIV infection: a study in the drug-user risk group.
Cognitive impairment is a frequent complication of advanced human immunodeficiency virus-1 (HIV-1) infection. However, structural imaging of the brain has not revealed abnormalities that precede the onset of clinical abnormalities. Cranial magnetic resonance (MR) studies were performed in 28 male subjects with intravenous drug use histories; nine were HIV-1 seronegative, 11 were HIV-1 seropositive but asymptomatic, and eight were seropositive and met symptomatic criteria for acquired immune deficiency syndrome (AIDS). Cortical atrophy, but not the degree of ventricular enlargement or signal abnormalities, was increased in the seropositive group compared with the seronegative group and also differed between asymptomatic seropositive and seronegative patients. An increased level of cortical atrophy may reflect the early impact of HIV-1 infection on the brain.
AIDS Dementia Complex↗
Genetically diverse ceftazidime-resistant isolates from a single center: biochemical and genetic characterization of TEM-10 beta-lactamases encoded by different nucleotide sequences.
Ceftazidime-resistant isolates of Escherichia coli and Klebsiella pneumoniae produced a plasmid-mediated beta-lactamase with a pI of 5.6 with biochemical characteristics comparable to those of the TEM-10 beta-lactamase. Plasmids from the two strains were nonidentical. Both TEM-10 sequences differed from TEM-1 by substitutions of Ser-162 and Lys-237. The nucleotide sequences of the two genes were identical except for three silent nucleotide substitutions corresponding to the nucleotide differences in the Tn2 TEM-1 or Tn3 TEM-1 genes. The original TEM-10 plasmid was identical to that found in the E. coli isolate and coded for a gene that corresponded to the TEM-10 beta-lactamase from Tn2.
Ceftazidime↗
Neuropsychological and neurological manifestations of HIV-1 dementia in drug users.
The cognitive and motor deficits associated with human immunodeficiency virus-1 (HIV-1) infection have been studied using neurological examination and neuropsychological tests. However, drug users with HIV-1 infection generally have been excluded from such studies. Forty-four well-characterized drug users stratified by Centers for Disease Control staging were administered a standardized neurological examination and a battery of neuropsychological tests under single-blind conditions designed to minimize the acute effects of psychoactive substances. The results of the blind neurological examination were consistent with the previously ascertained clinical staging of HIV-1 infection. The pattern of neuropsychological deficits across HIV-1 states was similar to those found in cohorts of homosexual men.
AIDS Dementia Complex↗
Auditory event-related potentials in HIV-1 infection: a study in the drug-user risk group.
Features of event-related potentials (ERPs) may be sensitive and clinically useful markers of central nervous system infection by the human immunodeficiency virus (HIV-1); however, this application has not been studied in the risk group of intravenous drug users. Auditory ERPs generated by an "oddball" paradigm were analyzed for 39 male drug abusers as part of a multimodal assessment. Stage of HIV-1 infection was associated with prolongations of P1, N1, and P3 components of the ERP waveform. Only patients with full acquired immunodeficiency syndrome showed statistically significant increases in waveform prolongations. Specific neuropsychological deficits were not related to waveform latency prolongations.
AIDS Dementia Complex↗
Angiotensin II and atrial natriuretic factor receptor interactions at the blood-brain barrier.
Data from several laboratories indicate that cerebral endothelial cells possess cell surface receptors for numerous vasoactive agents including angiotensin II (AII) and atrial natriuretic factor (ANF). The intracellular messengers of these receptors as well as possible receptor interactions were explored. ANF increased cGMP 10-fold over basal levels while incubation of the microvessels with AII did not significantly affect the level of this nucleotide. In contrast, AII significantly potentiated the increase in cGMP by ANF. Incubation of cerebral microvessels with AII resulted in a significant increase in the intracellular mediator of PI hydrolysis, 1,2-diacylglycerol (DG). ANF had no affect on DG or on the AII mediated increase of DG. Finally, data at the level of receptor binding indicated that while ANF decreased [3H]angiotensin binding to cerebral microvessels, AII had no effect on the binding of ANF to its receptor. The results of the present study demonstrate that AII can potentiate the regulation of cGMP by ANF and suggest the possibility of receptor interactions in control of blood-brain barrier function.
Angiotensin II↗
Calcium and the impairment of contractions to norepinephrine in aorta isolated from the spontaneously hypertensive rat.
Helical strip contractility from hypertensive (SHR) and normotensive (WKY) rat aortas assessed in the presence of varying calcium concentrations indicated that SHR strips exhibit a higher intrinsic myogenic tone and contract less to norepinephrine (NE) in a physiological calcium concentration compared to controls. Relatively higher isometric tension was developed in the SHR in low calcium (0-0. 27 mM). While control responses were blunted by LaCl3, EGTA, and nifedipine, the SHR strips were unaffected. Addition of procaine significantly enhanced SHR contractility to NE with no effect on control strips. These data suggest that abnormal cytosolic calcium provokes an increase in myogenic tone and an impaired contractile response of aortic smooth muscle cells to NE.
Animals↗
Autonomic receptor interactions in isolated cardiac myocytes from hypertensive rats.
Isolated ventricular myocytes from adult (16 to 20 weeks) spontaneously hypertensive (SHR) and normotensive (WKY) rats were utilized to examine adrenergic and cholinergic receptor expression and interaction. Binding assays were performed using quinuclidinyl benzilate (QNB) and iodocyanopindolol (ICYP) for cholinergic and beta-adrenergic receptors, respectively. In addition, cAMP was measured as an index of adrenergic-cholinergic control of adenylate cyclase. Data from radioligand binding experiments indicated that muscarinic cholinergic receptors were depressed (22%) in SHR myocytes, while beta-adrenergic receptor density was comparable to that of WKY myocytes. Heterologous receptor modulation in isolated myocytes as assessed by displacement analysis with and without guanosine 5'-triphosphate (GTP), showed that carbachol displacement of QNB was shifted five fold to the right in the presence of GTP and that the beta-adrenergic agonist isoproterenol did not prevent the GTP-mediated binding alteration. In contrast, carbachol modulated the GTP-shift of ICYP displacement by isoproterenol and these effects were comparable in both WKY and SHR myocytes. Furthermore, the ability of carbachol to blunt the stimulation of adenylate cyclase by isoproterenol was also comparable in myocytes isolated from adult SHR and control animals. Thus, the observed decrement in muscarinic cholinergic receptor expression did not alter adrenergic-cholinergic interactions as assessed by displacement assays using guanine nucleotides, or the control of cAMP levels. In addition, isolated myocytes provide a useful system for analyzing receptor expression and regulation and how these parameters may be altered in the hypertensive heart.
Adenylyl Cyclases↗
Cerebrovascular angiotensin II receptors in spontaneously hypertensive rats.
The objective of this study was to characterize angiotensin II (AII) receptors in cerebral capillary endothelium and to examine whether the first step in AII responsiveness, namely AII receptor binding, is aberrant in cerebral microvessels obtained from adult spontaneously hypertensive rats (SHR). The binding of [3H]angiotensin II to isolated cerebrocortical microvessels from Sprague-Dawley, Wistar-Kyoto, and SHR rats was used to characterize AII receptors on these vessels. Kinetic experiments yielded an equilibrium-derived Kd (dissociation rate constant/association rate constant) very close to that obtained from Scatchard analysis of saturation binding data. The data indicated that the two normotensive control strains exhibited comparable AII receptor affinity and binding capacity. In contrast, experiments with microvessels from adult SHR indicated a significantly higher Bmax for AII receptors relative to controls. Although experiments assessing functional endothelial alterations in the SHR to AII remain to be performed, the increase in AII receptor number suggests that an abnormality in vascular AII responsiveness may play an important role in this model of hypertension.
Angiotensin II↗