[Anesthetic incompatibility--rare, but dangerous].
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Biomedical subjects
Publications and source records attributed to J M Baron.
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Non-hereditary photodermatoses with well-known trigger factors and idiopathic light eruptions occur quite frequently during childhood and are at least temporarily associated with a marked impairment of quality of life in affected patients and their parents. Thus, it is crucial that the involved specialties are familiar with acquired UV-associated disorders in order to guarantee a quick diagnosis and effective therapy. Additionally, the recurrence of photodermatoses associated with potentially severe long-term complications has to be prevented. This requires a stringent prophylaxis that can only succeed after age-adapted instruction of the patient and parents.
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The importance of P-glycoprotein (P-gp) in the pharmacokinetics of amisulpride and the effects of a P-gp inhibitor cyclosporine A (CsA) was investigated both, in vitro and in vivo. In vitro and in vivo results indicated amisulpride as a substrate of P-gp. Amisulpride was not metabolized by rat liver microsomes. Open field behavior showed time dependent abolishment in locomotion by amisulpride (50 mg kg(-1)). Co-administration of CsA (50 mg kg(-1)) resulted in a higher and significantly longer antipsychotic effect (24 h after drug administration). Accordingly, the area under concentration-time curve in serum and brain was higher in CsA co-treated rats (13.5 vs. 29.8 micromol h l(-1) for serum and 2.16 vs 2.98 micromol h l(-1) for brain tissue) while renal clearance was not affected. These results pointed to a pharmacokinetic drug interaction between CsA and amisulpride most likely caused by inhibition of P-gp.
Primary cutaneous B cell lymphomas have a high recurrence rate after treatment with surgery and/or local radiation therapy. Two men are described in whom radiotherapy-relapsing cutaneous B-cell lymphomas were successfully treated with the monoclonal anti-CD20 antibody rituximab. Both patients had a complete response with no recurrence at follow-up at 17 and 24 months for the large B-cell lymphoma of the leg and the follicle centre cell lymphoma, respectively. These are two of the few cases in the literature showing that rituximab is an effective and well-tolerated treatment for radiotherapy-relapsing primary cutaneous B cell lymphoma.
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Allergy to human seminal fluid is a rare but potentially life-threatening disorder. Acute symptoms range from local reactions to generalized symptoms. A 30-year-old woman experienced vulvovaginal itching, erythema and swelling as well as generalized urticaria and angioedema of the neck and face after unprotected sexual intercourse. A scratch test with undiluted seminal fluid and the detection of specific IgE antibodies revealed a type I allergy to seminal fluid. Risk factors and therapeutic options are discussed.
Interactions between low molecular weight compounds with cells of the skin result in reactions with different proteins which enable the uptake, metabolism and efflux of these compounds. It is unlikely, that small molecular weight compounds can achieve pharmacological concentrations within cells by diffusion alone. The pattern of influx proteins of keratinocytes is different from that of hepatocytes. If the balance between these systems is disturbed, the skin may become unable to function as a protective organ which can result in diseases including cancer or-more frequently-allergic contact dermatitis. Recent investigations of the sensitization to fragrances and p-phenylenediamine are discussed. An improved understanding of the metabolism of low molecular weight compounds can lead to new therapeutic strategies. One example is the introduction of photodynamic therapy with topical applied porphyrin precursors.
Because of their variable application, microarrays are currently used in different areas of research and development, such as skin pharmacology and allergology. Microarrays are plane carriers, on whose surface a variety of known DNA-molecules and proteins were immobilised. Transcripts can be detected by cDNA- and oligonucleotid-arrays and proteins of activated genes can be discovered using antibody microarrays. Detection of allergen-specific IgE from human serum can be performed using allergen chips. Since many details of the molecular mechanism and pathogenesis of skin cancer and inflammatory skin diseases and the effect of xenobiotics on cells of the human skin are still not known, array-technologies are a powerful tool to identify novel marker genes and offer the possibility of develop new therapeutic strategies as well as prognosis- and diagnosis-systems.
Coronary artery brachytherapy may require treatment of lesions longer than a single source length. A treatment option is tandem positioning of the single source. This study presents relative dosimetric measurements of a cardiovascular brachytherapy source and the dosimetric characteristics in the junction region of tandem treatments. Measurements were carried out using a Novoste Beta Cath 90Sr/90Y 40 mm beta source in a plastic water phantom. Radiochromic MD-55-2 film, calibrated using both 6 MV photon and 6 MeV electron beams from a linear accelerator, was used as the dosimeter. Dose distributions around a single source and in the junction region of tandem irradiation were measured. Measurements of the near field dose as close as 1.2 mm from the source are presented. Significant over- or underdoses in the junction region of tandem irradiation were quantified. At a radial distance of 2 mm from the longitudinal axis of the source, the dose value in the middle of the junction region, normalized to the dose at 2 mm midline single source, was about 182% for a 2-seed overlap and 16% for a 2-seed gap, respectively. Dose distributions in the junction region as a function of source overlap and radial distance have fairly high gradients and exhibit characteristic patterns. The fraction of prescription dose was found to have a sigmoidal dependence on overlap size, for radial distances ranging between 1.2 and 3 mm. The parameters of these sigmoids, quantified as functions of radial distance, could be used to provide quick and reasonable over/underdose estimates, given any potential overlap or gap in the junction area, with an uncertainty within 10%.
Recently treatment strategies in advanced malignant melanoma have significantly changed. Due to high response rates (e.g. more than 50% for the Dartmouth-regimen), combination chemotherapy has been the standard therapy in several oncological and dermatooncological centers in the USA and Europe. For the last three years different prospective randomized phase III trials failed to achieve similar results. There was no benefit in overall survival and in response duration in comparison to single agent chemotherapy. Currently, randomized clinical trials seem to be the best approach for the clinical treatment of metastatic melanoma. In this review several novel strategies against malignant melanoma are discussed with focus on the role of single agent chemotherapy and biochemotherapy.
We report two patients with severe congenital factor V deficiency, one of whom also had a factor V inhibitor, who required correction of their coagulopathy prior to surgical procedures. They underwent plasma exchange (PE) with fresh frozen plasma or solvent/detergent treated plasma (S/DP), with achievement of factor V levels satisfactory for hemostasis for their procedures. PE makes it possible to raise factor levels quickly and sufficiently without volume overload. In addition, transient reduction of inhibitor titers by PE may improve the level of correction achievable during the perioperative period. The advent of S/DP promises to provide an added increment of safety in patients exposed to significant volumes of plasma during PE.
Autoimmune thrombocytopenic purpura (ATP) and thrombotic thrombocytopenic purpura (TTP) are each well recognized clinical syndromes which may appear as single episodes or may have chronic relapsing courses. We present four patients negative for human immunodeficiency virus (HIV) infection who appear to have both diagnoses with either concomitant or intermingled episodes, and we review seven additional patients reported in the literature with similar features. All four of our patients are female, two have underlying connective tissue disorders, and their ATP processes came to our attention because of incomplete response of the platelet count to plasma exchange therapy (PEX) during a TTP phase (Cases 1 and 2) or development of thrombocytopenia in the absence of microangiopathy on the background of prior typical TTP episodes (Cases 3 and 4). Recognition of the ATP diagnosis in each case resulted in discontinuation of PEX (Cases 1 and 2) or not instituting PEX (Cases 3 and 4). In each instance, a satisfactory rise in platelet count followed treatment for ATP. Based upon this experience, we conclude that some individuals may have a mixed immune thrombocytopenia syndrome; careful analysis of the mechanism of thrombocytopenia, especially in recurrent episodes and in patients who respond incompletely to PEX for TTP, is important when deciding whether to initiate or continue PEX, or to consider therapies appropriate for other mechanisms of thrombocytopenia.
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Cytochrome P450 enzymes metabolize various endogenous and exogenous small molecular weight compounds. Transport-associated proteins, such as P-glycoprotein, multidrug resistance-associated protein and lung resistance protein are overexpressed in drug-resistant cell lines, as well as in human tumors from various histologic origins, including malignant melanoma. Little is known about the expression and function of cytochrome enzymes and multidrug resistance-associated transport proteins in human skin; therefore, the aim of this study was to analyze the expression pattern of cytochrome enzymes and multidrug resistance-associated transport proteins in proliferating human epidermal keratinocytes under constitutive conditions and after induction with various inducers. Reverse transcription-polymerase chain reaction revealed constitutive expression of cytochromes 1A1, 1B1, 2B6, 2E1, and 3A5 in keratinocytes and showed expression of cytochrome 3A4 after incubation with dexamethasone. The expression of cytochrome 1A1 was enhanced on the mRNA level after induction with benzanthracene. Reverse transcription-polymerase chain reaction analysis of the multidrug resistance-associated transport proteins revealed constitutive expression of multidrug resistance-associated proteins 1 and 3-6, and lung resistance protein in human epithelial keratinocytes and was negative for multidrug resistance 1 and 2. Expression of 1 was seen after induction with dexamethasone. Reverse transcription-polymerase chain reaction results were confirmed by immunoblots which showed expression of cytochromes 1A1, 2B6, 2E1, and 3A, multidrug resistance-associated proteins 1, 3, and 5 as well as multidrug resistance 1 after induction with dexamethasone. Immunohistology showed positive immunofluorescence in skin specimens for cytochromes 1A1, 2B6, 2E1, and 3A and multidrug resistance-associated protein 1 and multidrug resistance 1. Constitutive activity of cytochrome 1A1, 2B, 2E1, and 3A enzymes was measured by catalytic assays. These results show that keratinocytes of the human skin express various transport-associated enzymes and detoxifying metabolic enzymes. Previous studies have revealed that cytochrome enzymes and transport-associated proteins play complementary parts in drug disposition by biotransformation (phase I) and anti-transport (phase III) and act synergistically as a drug bioavailability barrier.
BACKGROUND: Immune hemolytic anemia has been associated with the administration of various antibiotics, including cephalosporins. Presented here is a patient who developed severe acute hemolysis while receiving ceftizoxime (Ceftizox, Fujisawa USA), a third-generation cephalosporin. This is the fourth reported case of hemolysis in association with ceftizoxime. In the previous cases, ceftizoxime was shown to induce hemolysis by the immune-complex mechanism. However, in one of those reports, the concentration of drug used to treat the target RBCs in vitro may not have been optimal. CASE REPORT: The patient's antemortem blood samples were analyzed retrospectively for drug-dependent antibodies by the drug-adsorption and immune-complex methods. Antibody class and titer were evaluated. RESULTS: The patient's sample agglutinated RBCs coated with ceftizoxime as well as uncoated RBCs in the presence of ceftizoxime. The antibodies to ceftizoxime were IgM and IgG. CONCLUSION: This is the first report on both the immune-complex and drug-adsorption mechanisms of ceftizoxime-induced hemolysis. The differential diagnosis of a falling Hct in a patient receiving antibiotics should include drug-related hemolysis; once this diagnosis is considered, management includes the appropriate serologic workup, immediate cessation of the implicated drugs, and possible transfusion support.