Transesophageal echocardiography--an overview.
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Aortic Dissection↗
Biomedical subjects
R Wolf
Publications and source records attributed to R Wolf.
Virtual doctors--ready for launching.
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Global Health↗
Cigarette smoking, sexually transmitted diseases, and HIV/AIDS.
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HIV Infections↗
A century of the synthesis of dapsone: its anti-infective capacity now and then.
BACKGROUND: Although dapsone was first synthesized in 1908, a quarter of a century was to pass before it was used in the treatment of bacterial infections. Dapsone was, however, too toxic for humans (because of the excess dosage which was administered at that time) and was thus considered to be of no value in the treatment of common bacterial infections. Since the early 1950s, dapsone has been recognized as being uniquely effective against a number of noninfectious, inflammatory diseases and, today, this is its main indication. Thus, the reason why dapsone was first introduced into medicine, namely the treatment of bacterial infections, has been set aside and its main current applications are the treatment of noninfectious, inflammatory, autoimmune, and bullous diseases. OBJECTIVE: To study the anti-infective capacity of dapsone against common bacterial infections. As many patients who receive dapsone for the treatment of noninfectious, inflammatory diseases have a concomitant bacterial infection or a superinfection of their skin disease, we thought that, if dapsone proved to be effective against common bacterial infections, it may obviate the need for an additional antimicrobial drug in these patients. METHODS: Three bacterial ATCC> strains (Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli) were tested by a macrodilution minimal inhibitory concentration (MIC) test for dapsone. Dapsone concentrations were between 0.06 and 1125 microg/mL. RESULTS: Even the highest concentration of dapsone of 1125 microg/mL did not inhibit bacterial growth. CONCLUSIONS: Our results indicate that dapsone has no antibacterial effects whatsoever. Even at very high concentrations, it does not suppress the growth of most susceptible strains of bacteria. The story of dapsone (i.e. the long time that elapsed between its synthesis to its use for the chemotherapy of infectious diseases) will not repeat itself this time.
Dapsone↗
Recurrent aphthous stomatitis and smoking.
BACKGROUND: Several studies have reported cigarette smoking to have a beneficial protective effect on recurrent aphthous stomatitis (RAS). In this study, we evaluated once again the incidence of smoking in RAS patients compared with controls. This study differs from most previous ones in that the patients were diagnosed by direct observation of active lesions by a dermatologist. METHODS: Thirty-four patients with RAS who were seen at the dermatology clinic during a period of 2 years were compared with 115 outpatients with other skin diseases and 20 healthy hospital personnel who had no history of aphthae, with regard to their smoking habits. RESULTS: Among the 34 patients with RAS, 8.8% were active smokers compared with a significantly higher percentage (25.2%) among the control subjects. CONCLUSIONS: In agreement with others, we found a negative epidemiologic association between smoking and RAS. This finding can be used to clarify the cause and pathogenesis of the disease, and possibly to identify better treatment or preventive options than those currently available.
Adult↗
The relationship between Helicobacter pylori IgG antibody and autologous serum test in chronic urticaria.
BACKGROUND: In chronic urticaria, suspicious factors are Helicobacter pylori (HP) infection and autoimmunity, as well as other etiologic agents. Autologous serum injection is the first step to identify autoimmune urticaria. Our study was performed to determine the prevalence of HP infection in patients with chronic urticaria, and to evaluate the results of autologous serum testing in chronic urticaria patients who had HP antibodies. METHODS: HP immunoglobulin G (IgG) antibody was defined by an immunochromatographic method in 61 chronic urticaria patients and 15 healthy persons. Autologous serum testing was performed in 32 chronic urticaria patients. RESULTS: HP IgG antibody was found to be positive in 41% of chronic urticaria patients and 26% of healthy controls (chi2= 7.82, P= 0.005). Autologous serum testing was positive in 40% of chronic urticaria patients who had HP IgG antibody. This ratio was 14.3% in chronic urticaria patients who did not have HP IgG antibody (chi2 = 9.23, P= 0.002). CONCLUSIONS: In this study, autologous serum testing was found to highly positive in chronic urticaria patients with HP IgG antibody, but the relationship between autoimmunity and HP infection requires further investigations.
Antibodies, Bacterial↗
Effects of lithium carbonate (Li2CO3) on in-vitro-cultured normal human skin explants.
The early morphological changes induced by lithium carbonate, a well-known psoriasis-provoking drug, were studied on cultured skin. Normal human skin from patients undergoing mastectomy was cultured in the presence of 3 mM, 6 mM and 10 mM of Li2CO3 for 4 days. The morphological changes were then evaluated by three observers in a blind manner and their reports were matched and collated. The cultured skin in the presence of Li2CO3 showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia. Another striking finding was intercellular oedema and vacuolar alteration with formation of small cavities in the upper dermis. There was no evidence of parakeratosis or any other histological characteristic of psoriasis, except hyperproliferation of the epidermis. Based on our knowledge of mechanisms of lithium action, we proposed two competitive explanations for its action on the epidermis: i) that lithium acts directly on dividing cells of the epidermis; and ii) that it acts indirectly by altering epidermal barrier function. Although we lack definite proof, we suggest that the observed morphological changes, in particular the non-specific stimulus to epidermal proliferation, are the primary events which initiate the process that will ultimately lead to the development of psoriasis in a predisposed patient.
Cells, Cultured↗
Efficacy, cardiac safety and tolerability of sertindole: a drug surveillance.
Sertindole is a novel atypical antipsychotic, which has shown efficacy in the treatment of positive and negative symptoms of schizophrenia in phase II and III studies. Furthermore, these studies have demonstrated tolerability and a favourable side-effect profile. In contrast to classical antipsychotics, sertindole was not associated with extrapyramidal symptoms (EPS). We report drug surveillance data in 34 comorbid and comedicated sertindole treated patients suffering from different psychotic disorders. The drug surveillance consisted of two distinct phases: inpatient treatment and outpatient follow-up. Clinical global impression (severity and improvement of illness), psychotic symptoms, side-effects, and blood parameters have been carefully documented. With special respect to cardiac safety electrocardiograms (ECGs) have been recorded twice (during sertindole treatment and during treatment with an antipsychotic different from sertindole). Recommended ECG-parameters for assessment of the proarrhythmic risk of a drug have been calculated (QTc-, QTc2-interval; QT-, QTc-dispersion). The majority of patients (n = 29) have been treated previously with several typical and/or atypical antipsychotics. We observed a clinical response to sertindole treatment in 29 patients (85%). Both positive and negative symptoms improved with sertindole and no severe side-effects have been documented. EPS occurred at placebo level. A mean QTc-interval prolongation of 19.7 ms (4.7%) has been detected. None of the patients developed clinical or electrocardiographic evidence of cardiac dysrhythmia during sertindole treatment, or other clinical evidence of cardiac abnormalities. In summary, sertindole did show efficacy for positive and negative symptoms together with a favourable side-effect profile. No evidence for an increased proarrhythmic risk has been found.
Adult↗
Tissue-specific expression of a type I adenylyl cyclase rescues the rutabaga mutant memory defect: in search of the engram.
Most attempts to localize physical correlates of memory in the central nervous system (CNS) rely on ablation techniques. This approach has the limitation of defining just one of an unknown number of structures necessary for memory formation. We have used the Drosophila rutabaga type I Ca(2+)/CaM-dependent adenylyl cyclase (AC) gene to determine in which CNS region AC expression is sufficient for memory formation. Using pan-neural and restricted CNS expression with the GAL4 binary transcription activation system, we have rescued the memory defect of the rutabaga mutant in a fast robust spatial learning paradigm. The ventral ganglion, antennal lobes, and median bundle are likely the CNS structures sufficient for rutabaga AC- dependent spatial learning.
Adenylyl Cyclases↗
Hepatic microvascular responses to ischemia-reperfusion in low-density lipoprotein receptor knockout mice.
The overall objective of this study was to determine whether genetically induced hypercholesterolemia alters the inflammatory and microvascular responses of mouse liver to ischemia-reperfusion (I/R). The accumulation of rhodamine 6G-labeled leukocytes and the number of nonperfused sinusoids (NPS) were monitored (by intravital microscopy) in the liver of wild-type (WT) and low-density lipoprotein receptor-deficient (LDLr(-/-)) mice for 1 h after a 30-min period of normothermic ischemia. Plasma alanine transaminase (ALT) levels were used to monitor hepatocellular injury. Microvascular leukostasis as well as increases in NPS and plasma ALT were observed at 60 min after hepatic I/R in both WT and in LDLr(-/-) mice; however, these responses were greatly exaggerated in LDLr(-/-) mice. Pretreatment of LDLr(-/-) mice with gadolinium chloride, which reduces Kupffer cell function, attenuated the hepatic leukostasis, NPS, and hepatocellular injury elicited by I/R. Similar protection against I/R was observed in LDLr(-/-) mice pretreated with antibodies directed against tumor necrosis factor-alpha, intercellular adhesion molecule-1 (ICAM-1), or P-selectin. These findings indicate that chronic hypercholesterolemia predisposes the hepatic microvasculature to the deleterious effects of I/R. Kupffer cell activation and the leukocyte adhesion receptors ICAM-1 and P-selectin appear to contribute to the exaggerated inflammatory responses observed in the postischemic liver of LDLr(-/-) mice.
Alanine Transaminase↗
Context generalization in Drosophila visual learning requires the mushroom bodies.
The world is permanently changing. Laboratory experiments on learning and memory normally minimize this feature of reality, keeping all conditions except the conditioned and unconditioned stimuli as constant as possible. In the real world, however, animals need to extract from the universe of sensory signals the actual predictors of salient events by separating them from non-predictive stimuli (context). In principle, this can be achieved if only those sensory inputs that resemble the reinforcer in their temporal structure are taken as predictors. Here we study visual learning in the fly Drosophila melanogaster, using a flight simulator, and show that memory retrieval is, indeed, partially context-independent. Moreover, we show that the mushroom bodies, which are required for olfactory but not visual or tactile learning, effectively support context generalization. In visual learning in Drosophila, it appears that a facilitating effect of context cues for memory retrieval is the default state, whereas making recall context-independent requires additional processing.
Animals↗
Triggered psoriasis.
There are conflicting reports in the literature concerning the use of antimalarials in psoriatic patients with arthropathy or coexisting systemic lupus erythematosus. On the basis of a review of 18 publications in English, it was estimated that up to 18% of patients with psoriasis would develop an exacerbation of their disease following antimalarial therapy. In contrast to lithium and beta-blockers, antimalarials do not induce psoriasis de novo, but they only trigger already existing psoriasis, via a pharmacologic mechanism, probably due to an alteration of the activity of enzymes involved in the epidermal proliferation process. The chemical structure of the antimalarials is very similar to dansylputrescine, a potent transglutaminase (TGase) inhibitor. We suggested therefore that antimalarials trigger psoriasis through the modulation of the TGase activity. To verify this hypothesis, we examined the effect of hydroxychoroquine sulphate (HCQS) on cultured human skin and on TGase activity in vitro. Significant changes of epidermal morphology were seen in all explants cultured in the presence of HCQS. HCQS showed a concentration-dependent inhibition of TGase activity. We suggest that HCQS caused an initial break in the barrier function of the epidermis by inhibiting TGase activity; this was followed by a physiologic response of the epidermis aimed at barrier restoration. This rather non-specific stimulus to epidermal proliferation is probably sufficient to trigger psoriasis in predisposed individuals. Drug eruption is an age-old but timeless and fascinating subject. Of particular interest are those drug eruptions that may mimic idiopathic skin diseases. Apart from their obvious practical importance they are also of theoretical interest, because they provide an opportunity to investigate possible pathogenic mechanisms of the mimicked disease. In this paper, I would like to review briefly the characteristics of drug-induced psoriasis, and then propose a hypothesis concerning the pathogenesis of this phenomenon. In all, we found 258 reported cases of drug-induced psoriasis [1]. The drugs mainly involved are the antimalarials, lithium, beta blockers, and a large group of miscellaneous drugs. Three out of the four groups of drugs (lithium, beta blockers and miscellaneous drugs) can both induce or trigger psoriasis with almost equal frequency, namely they induce psoriasis de novo or they exacerbate an already existing psoriasis in 30-50% of the reported cases. Only one group of drugs, the antimalarials is an exception. In contrast to lithium and beta blockers, antimalarials do not induce psoriasis de novo, but only trigger already existing psoriasis. There are only three reported cases of psoriasis induced by antimalarials in patients who did not have the disease previously. Of these three patients, one had a seronegative arthritis and a family history of psoriasis, and, as stated by the author, there is evidence that the patient had pre-existing latent psoriasis. We believe that the other two cases may also have had latent psoriasis. That antimalarial drugs only trigger latent psoriasis and do not induce psoriasis de novo can be suspected from the fact that psoriasis cleared up completely after withdrawal of the drug in only 30% of patients on antimalarials, as compared with more than 60% of those receiving lithium and nearly 50% of those receiving beta blockers. This is probably also why the incubation period of the cases induced by antimalarial drugs is much shorter than that of lithium and beta blockers. Possibly, in triggered psoriasis (as in antimalarials) the drug only sets off with a chain of pathologic events previously programmed and ready to be set off, whereas in true drug-induced cases (as in some cases of lithium and betablockers) the drug is supposed to cause more profound changes and, therefore, more time is needed for these changes to occur.
Adrenergic beta-Antagonists↗
Recurrent, multiple, calcified soft tissue metastases from osteogenic sarcoma without pulmonary involvement.
Osteosarcoma (osteogenic sarcoma) metastasizes primarily to the lung. With the introduction of neoadjuvant chemotherapy as part of the treatment, the overall and disease-free survival rates have dramatically improved. In this case report, a young man with multiple soft tissue and bone metastases, including a rare large bone-forming retroperitoneal metastasis, is described. Despite the extensive extrapulmonary metastases, the patient did not develop pulmonary metastases in the 4 years following initial presentation of the primary tumour.
Adult↗
Video-assisted thoracoscopy.
New therapeutic modalities for disorders of the pediatric spine must include video-assisted thoracoscopy. The endoscopic approach to the spine has involved an evolutionary approach. What began as an isolated drainage of a vertebral abscess was continued as a method of single discectomy; release of the annulus fibrosis with or without ligation of segmental vessels; rib resection for costoplasty; rib harvesting for intervertebral fusion; and most recently, insertion of correctional implants and fusion.
Adolescent↗
Antifungal sponsored supplements.
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Antifungal Agents↗
The in vitro effect of hydroxychloroquine on skin morphology in psoriasis.
BACKGROUND: In earlier papers, we suggested that the aggravation of psoriasis by antimalarial drugs (analogous to hypolipidemic drugs) could be initiated by a break in the epidermal barrier. We suggested that these drugs exerted their effect by inhibiting epidermal transglutaminase activity, and supported this hypothesis by demonstrating the effect of hydroxychloroquine sulfate (HCQS) on the morphology of cultured skin and on liver transglutaminase activity. In the present article, we describe, for the first time, the morphologic changes induced by HCQS on cultured skin of psoriatic patients. METHODS: Uninvolved (apparently normal) skin explanted from the back of two psoriatic patients was cultured in the presence of 9.2 and 13.8 mM of HCQS for 3 days. The morphologic changes were evaluated in a blind manner. The experiment was repeated twice. RESULTS: Significant changes in the epidermal morphology of psoriatic skin cultured in the presence of HCQS, compared with skin cultured without the presence of the drug, were observed. The most striking changes were enhanced and irregular keratinization and dermo-epidermal detachment and cleft formation. No parakeratosis or other characteristics of psoriasis were observed. CONCLUSIONS: The first changes caused by HCQS on the cultured skin of psoriatic patients are not characteristic of psoriasis, and include hyperproliferation and enhanced and irregular keratinization. The present experimental study gives further support to the hypothesis that HCQS causes an initial break in the barrier function of the epidermis (probably by inhibiting transglutaminase activity), which is followed by a physiologic response of the epidermis aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation is probably sufficient to trigger psoriasis, in vivo, among genetically predisposed patients.
Antimalarials↗
Prick test and protein contact dermatitis.
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Animals↗
Effects of gemfibrozil on in vitro cultured normal human skin explants.
BACKGROUND: Several lipid-lowering agents, when given topically, show a profound effect on skin morphology. Because of low bioavailability of these drugs for keratinocytes, the incidence is extremely low clinically. The most appropriate way to study the effect of hypolipidemic drugs on keratinocytes is by artificial exposure of the skin to high drug concentrations. OBJECTIVE: To study the effects of gemfibrozil on the morphology of in vitro cultured normal human skin explants. As gemfibrozil induces barrier disruption by inhibiting epidermal sterologenesis, essential for a competent permeability barrier, it is interesting to investigate the morphologic changes associated with this phenomenon. Studying the epidermal changes induced by lipid-lowering agents is important, not only because it might lead to a better understanding of the effects of these drugs on keratinocytes, but as it might also unlock the door to a wider knowledge of the pathomechanism of disorders of cornification. METHODS: Normal human skin from patients undergoing mastectomy was cultured in the presence of 2, 5, and 10 mM of gemfibrozil for 4 days The morphologic changes were evaluated by three blinded observers. Their reports were matched and collated. RESULTS: The cultured skin in the presence of gemfibrozil showed cell crowding of keratinocytes in the lower part of the epidermis, indicating epidermal hyperplasia and increased proliferation. Intercellular edema with the formation of small cavities in the epidermis, intracellular edema, and vacuolar alteration of keratinocytes in the upper portion of the epidermis were also observed. The intensity of these changes tended to parallel the gemfibrozil concentration. Some dermo-epidermal detachments did not correlate with the gemfibrozil concentration, but rather with tissue characteristics peculiar to each explant. CONCLUSIONS: The morphologic changes caused by gemfibrozil to normal human skin were not characteristic of psoriasis, and included intracellular and intercellular edema in the upper portion of the epidermis and cell crowding, indicating epidermal hyperplasia in the lower portion of the epidermis. The present experimental study gives further support to the hypothesis that hypolipidemic drugs cause an initial break in the barrier function of the epidermis, followed by a physiologic epidermal response, aimed at barrier restoration. This rather nonspecific stimulus to epidermal proliferation may trigger psoriasis in predisposed patients.
Cells, Cultured↗