Embolic coronary occlusion after the arterial switch procedure.
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Coronary Thrombosis↗
Biomedical subjects
J M Baron
Publications and source records attributed to J M Baron.
Drug metabolism in the skin.
The skin performs a wide range of active metabolic functions including xenobiotic metabolism involving metabolizing enzymes specific to the skin. In this review we focus on the role of drug metabolism: (i) in allergic reactions to substances of low molecular weight; (ii) in cutaneous vitamin A and D3 metabolism and its modulation; (iii) in the interaction of transport and metabolic enzymes in skin cells; and (iv) on novel tools for the measurement of drug metabolism in various compartments of the human skin.
Drug Hypersensitivity↗
Modulation of P450 CYP3A4-dependent metabolism by P-glycoprotein: implications for P450 phenotyping.
Some compounds used for phenotyping of cytochrome P450s are substrates of P-glycoprotein (pgp). It is likely that in these cases, the level of pgp modulates the metabolism of in vivo probes. To address this important issue, we have analyzed the effects of pgp on CYP3A4-mediated reactions in two newly established cell lines (3A4/HR/MDR(-) and 3A4/HR/MDR(+)), which express CYP3A4 in the absence and presence of pgp, respectively. In cultured cells, the presence of pgp increased the apparent K(m) for the 6beta-hydroxylase activity of CYP3A4 toward testosterone and cortisol by a factor of 1.7 and 4, respectively. These steroids are poor and good substrates of pgp, respectively, and cortisol 6beta-hydroxylase has been frequently used as an in vivo probe for CYP3A4. Interestingly, we also found that pgp modulated the inhibition of CYP3A4-mediated metabolism by several compounds in intact cells. Although quinidine inhibited testosterone 6beta-hydroxylase activity in membranes or in intact cells that expressed recombinant CYP3A4 in the absence of pgp, low concentrations of this compound increased CYP3A4 activity in intact cells that expressed pgp. These results imply that pharmacokinetic drug-drug interactions involving CYP3A4 can be influenced by pgp.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Study of three patients with thrombotic thrombocytopenic purpura exchanged with solvent/detergent-treated plasma: is its decreased protein S activity clinically related to their development of deep venous thromboses?
Solvent/detergent treated plasma (S/DP) has reduced protein S activity (about 0.5 units/mL) as compared with fresh frozen plasma (FFP). When used as replacement fluid for repetitive therapeutic plasma exchange (PEX), e.g., in patients with thrombotic thrombocytopenic purpura (TTP), S/DP could lead to lowered protein S levels and, possibly, risk of hypercoagulable complications. We describe three patients with TTP who had low functional protein S (FPS) levels during PEX for TTP. Each developed one or more deep vein thromboses (DVTs) while receiving 100% S/DP or 50% S/DP and 50% cryosupernatant plasma (CSP) as replacement fluid. FPS levels rose when 100% CSP was substituted for S/DP. Our observations suggest that use of S/DP alone or in 50% combination with CSP as replacement fluid in PEX for TTP may lead to difficulty in maintaining safe FPS levels. Determination of risk of resulting clinically significant thrombotic events requires further study.
Adult↗
Solid facial edema preceding a diagnosis of retro-orbital B-cell lymphoma.
Persistent solid facial edema is a rare condition of unknown cause. Although acute facial edema has been associated with numerous disease processes such as infections, neoplasms, immune disorders, inflammation, neuropathic processes, drugs, mechanical obstructions, and trauma, solid facial edema has most often been associated with acne vulgaris. We report the first case, to our knowledge, of solid facial edema preceding a diagnosis of a subcutaneous scalp and orbital/periorbital B-cell lymphoma.
Aged↗
Analysis of tumor cell evolution in a melanoma: evidence of mutational and selective pressure for loss of p16ink4 and for microsatellite instability.
Tumorigenesis and tumor progression can be considered an evolutionary process. In order to deduce information on the mutational and selective pressures during melanoma progression we performed microsatellite analysis at 42 autosomal and two X-linked loci in a microdissected primary melanoma and its nine metastases. Loss of heterozygosity at locus D9S259 was the only genetic change observed in all metastases. The pattern of loss of heterozygosity at loci D9S162 and D9S171 within the region of common loss on chromosome 9p21 which encompasses the tumor suppressor gene p16ink4 enabled the distinction of four genetically different tumor cell populations. Three cell lineages showed homozygous loss of the p16ink4 gene, which evolved independently in each tumor cell population within the primary tumor. Additional allele losses could be demonstrated at markers D14S53 and DXS998. The fourth lineage did not demonstrate loss of heterozygosity at loci D9S162 and D9S171 and contained the wild type p16ink4 gene but was characterized by abundant microsatellite instability. The evolutionary approach towards tumorigenesis and tumor progression used in this study thus confirms the role of p16ink4 inactivation for melanoma progression but not for melanoma initiation; it suggests the existence of additional putative tumor suppressor genes located on 9p as well as on the long arm of chromosome 14 and shows that microsatellite instability may represent an alternative pathway of tumor cell evolution in malignant melanoma.
Carrier Proteins↗
Cytochrome P450 isoenzyme mRNA expression pattern in human urinary bladder malignancies and normal urothelium.
This study was designed to analyze the cytochrome P450 isoenzyme mRNA expression pattern of transitional cell carcinomas of the bladder (N = 19) and normal urothelium (N = 10). In addition, biopsies from normal urothelium (N = 32) taken at the time of transurethral resection of bladder cancer in eight patients from surrounding histologically normal urothelium also were characterized concerning their specific cytochrome P450 mRNA expression pattern. A total of 13 of 19 of the analyzed tumor specimens (68%) revealed expression of cytochrome P450 1B1. Cytochrome P450 4B1 and 1A1 mRNA expression were detected in 79% (15 of 19) and 53% (10 of 19) of the tumor specimens, with no correlation between tumor stage and grade of the neoplasm. Biopsies from macroscopically and histologically normal urothelium from tumor-invaded bladders also showed expression of cytochrome P450 1B1 in 75% (24 of 32), 4B1 in 62.5% (20 of 32), and 1A1 in 50% (16 of 32). Furthermore, a 75% homology concerning cytochrome P450 1B1 and 4B1 mRNA expression was observed between the bladder tumor and the biopsies from this bladder. The polymerase chain reaction analysis of normal urothelium from normal bladders that do not harbor a neoplasm revealed CYP450 mRNA expression for CYP450 1A1 in 6 of 10; 1B1 in 5 of 10; 4B1 in 6 of 10; 2D6 in 2 of 10; and 2E1 in 2 of 10. According to our data, CYP450 1B1 mRNA expression is not tumor-specific. The present findings are the first to compare CYP450 expression in bladder cancer with biopsies from the same tumor-bearing bladder, and they indicate that, from the enzymatic point of view, bladder cancer also is a panurothelial field disease present in even normal urothelium.
Aged↗
Therapeutic plasma exchange for the acute management of the catastrophic antiphospholipid syndrome: beta(2)-glycoprotein I antibodies as a marker of response to therapy.
We describe two patients with the catastrophic antiphospholipid syndrome associated with elevation of beta(2)-glycoprotein I antibodies and fulminant thrombotic diatheses. Both patients were treated with therapeutic plasma exchange (TPE), which resulted in a marked decrease in antibody titer accompanied by an improved clinical outcome in one patient (IgG antibody). In the second patient, the outcome was poor despite TPE (IgA antibody). There were no significant complications of TPE in either case. Because of the fulminant nature of the catastrophic antiphospholipid syndrome, we conclude that a trial of TPE is warranted for the acute management. Further studies are needed to clarify which patients may benefit from this treatment.
Amputation, Surgical↗
HPV 18-induced pigmented bowenoid papulosis of the neck.
We describe the case of a 53-year-old man in whom pigmented bowenoid papulosis developed on the skin of the neck. By polymerase chain reaction with general primers for genital human papillomaviruses (HPV) and subsequent restriction enzyme cleavage we could demonstrate HPV 18-related DNA in two biopsy specimens of the pigmented papules. To our knowledge, this report represents the first case of HPV 18-induced extragenital bowenoid papulosis of the neck.
Biopsy↗
First two cases of immune hemolytic anemia associated with ceftizoxime.
BACKGROUND: Second- and third-generation cephalosporins have been associated with immune-mediated hemolytic reactions. This report discusses two patients who developed clinically significant extravascular hemolysis while receiving the third-generation cephalosporin ceftizoxime (Ceftizox). This is believed to be the first time hemolysis has been described in patients receiving this drug. STUDY DESIGN AND METHODS: Immunologic workup of drug-dependent antibodies was performed on blood samples using drug-coated and immune complex methodologies. Antibody classes and titers were analyzed. RESULTS: Both the patients' sera contained anti-ceftizoxime that reacted with red cells only when ceftizoxime was added to the sera ("immune complex" method). The patients recovered without complications following discontinuation of the drug. Each patient had IgM and IgG drug-dependent antibodies. The drug-induced antibodies from each patient cross-reacted with cefotaxime, which is structurally similar to ceftizoxime, but cross-reacted either weakly or not at all with ceftriaxone, which has a more complex side chain. CONCLUSION: This report describes the first cases of immune hemolytic anemia associated with ceftizoxime. In drug-induced hemolytic reactions, prompt recognition and discontinuation of the drug may be important factors in reducing the chance of serious sequelae.
Adult↗
Cytochrome P450 1B1: a major P450 isoenzyme in human blood monocytes and macrophage subsets.
In this study, cytochrome P450 (CYP; EC 1.14.14.1)-dependent activities and P450 isoenzyme patterns were determined in human monocytes and macrophages, which play a major role in antigen processing including small molecular weight compounds which cause contact dermatitis or drug-allergic reactions. Using reverse transcriptase-polymerase chain reaction (RT-PCR) we determined the mRNA expression of eight CYPs (1A1, 1A2, 1B1, 2B6/7, 2E1, 3A3/4, 3A7 and 4B1) in human blood monocytes and macrophage subsets 27E10 and RM3/1. To study the influence of known P450 inducers, monocytes were incubated in vitro with ethanol, dexamethasone, cyclosporin A (CSA), benzanthracene (BA), phenobarbital (PB), lipopolysaccharide (LPS) and 12-O-tetradecanoyl-phorbol-13-acetat (TPA) for 24 hr. Percoll density gradient isolated monocytes as well as the pro-inflammatory macrophage subtype 27E10 expressed 1B1, 2E1 and 2B6/7. On the other hand, in the anti-inflammatory macrophage subtype RM3/1, predominantly 1B1 and to some extent 2B6/7 were found. Treatment with cyclosporin A, phenobarbital, benzanthracene or ethanol resulted in induction of the expression of 3A3/4. CYP1B1 was the predominant isoenzyme in all monocytes and macrophages. In monocytes purified by adherence or induced by benzanthracene, lipopolysaccharide or 12-O-tetradecanoyl-phorbol-13-acetat, 1A1 was also expressed. Northern blot analysis confirmed the presence of CYP1B1 in monocytes and macrophages, a presence which was also demonstrated on the protein level by immunoblot and by immunohistochemical staining of the cells. The expression of several CYPs in monocytes/macrophages suggests that these cells may be important in the metabolism of small molecular weight compounds, which play a role in allergic contact dermatitis and drug reactions. Of particular interest is the remarkably strong expression of the recently identified dioxin inducible CYP1B1, known to be present in a wide range of malignant tumors.
Aryl Hydrocarbon Hydroxylases↗
Clinical value of acute rest technetium-99m tetrofosmin tomographic myocardial perfusion imaging in patients with acute chest pain and nondiagnostic electrocardiograms.
OBJECTIVES: We sought to evaluate the clinical use and cost-analysis of acute rest technetium-99m (Tc-99m) tetrofosmin single-photon emission computed tomographic (SPECT) myocardial perfusion imaging in patients with chest pain and a normal electrocardiogram (ECG). BACKGROUND: Current approaches used in emergency departments (EDs) for treating patients presenting with chest pain and a nondiagnostic ECG result in poor resource utilization. METHODS: Three hundred fifty-seven patients presenting to six centers with symptoms suggestive of myocardial ischemia and a nondiagnostic ECG underwent Tc-99m tetrofosmin SPECT during or within 6 h of symptoms. Follow-up evaluation was performed during the hospital period and 30 days after discharge. All entry ECGs, SPECT images and cardiac events were reviewed in blinded manner and were not available to the admitting physicians. RESULTS: By consensus interpretation, 204 images (57%) were normal, and 153 were abnormal (43%). Of 20 patients (6%) with an acute myocardial infarction (MI) during the hospital period, 18 had abnormal images (sensitivity 90%), whereas only 2 had normal images (negative predictive value 99%). Multiple logistic regression analysis demonstrated abnormal SPECT imaging to be the best predictor of MI and significantly better than clinical data. Using a normal SPECT image as a criterion not to admit patients would result in a 57% reduction in hospital admissions, with a mean cost savings per patient of $4,258. CONCLUSIONS: Abnormal rest Tc-99m tetrofosmin SPECT imaging accurately predicts acute MI in patients with symptoms and a nondiagnostic ECG, whereas a normal study is associated with a very low cardiac event rate. The use of acute rest SPECT imaging in the ED can substantially and safely reduce the number of unnecessary hospital admissions.
Electrocardiography↗
Effects of magnesium sulfate infusion upon clotting parameters in patients with pre-eclampsia.
The objectives of this study were to evaluate the possible mechanisms involved in prolongation of bleeding time in pre-eclamptic patients receiving a magnesium sulfate infusion to prevent convulsions. Eighteen pre-eclamptic patients near term or at term (4 cases 33 to 35 weeks; the remainder > 36 weeks) were studied. Fifteen of them received magnesium sulfate infusion; 3 did not and served as controls. Bleeding time (modified Ivy method with Surgicutt), platelet count, platelet aggregation pattern, as well as serum arachidonic acid metabolites [thromboxane B2 (TxB2) and 6-Keto-prostaglandin F1 alpha (6-Keto-PGF1 alpha)] werde done on admission to the labor floor (before magnesium infusion) and repeated at discontinuation of the infusion, 12-24 hours postpartum; the controls received the second test 24 hours postpartum. Thirteen of 15 patients receiving magnesium sulfate had an increase in bleeding time from an average of 6 minutes 31 seconds to 11 minutes 56 seconds, an 82% rise (p < 0.004). In 2 there was a decrease. Among the 3 controls the averages were 6 minutes 38 seconds and 6 minutes 3 seconds. The total magnesium given ranged from 52.5 to 145 grams. Platelet counts averaged 251,000/mm3 (range 145,000-519,000). Platelet aggregation pattern done in 11 patients and was normal and unchanged after magnesium in 10 of the patients with increased bleeding time and one control. TxB2 and 6-Keto-PGF1 alpha levels did not change significantly either after magnesium administration (688 and 135 pgm/ml, to 654 and 117) or in controls (695 and 230 pgm/ml, to 445 and 225). Likewise, the ratio of these 2 substances did not change in either group (6.3 to 6.6, and 4.2 to 2.2). There was no correlation between duration of infusion or total magnesium given and directions of small changes observed. This study confirms a prior preliminary observation that magnesium sulfate infusion, as currently used to prevent eclamptic convulsions, induces a significant prolongation of bleeding time. This effect is mediated neither by changes in platelets count or aggregation pattern, nor by changing the level or ratios of serum arachidonic acid metabolites (TxB2 and 6-Keto-PGF1 alpha). Further studies are needed to clarify the mechanism of this clinically important observation of increased bleeding following magnesium sulfate infusion.
6-Ketoprostaglandin F1 alpha↗
[Prognosis of isolated agenesis of the corpus callosum].
We report preliminary results of a three year follow-up of ten children affected with apparently isolated corpus callosum agenesis (prenatal diagnosis). This population was collected from a multicenter prospective study: annual survey included physical examination, developmental outcome and psychometric evaluation. Febril convulsions appeared to be more frequent than in the general population; developmental outcome was normal at the last evaluation. Follow-up has to be performed up to 10 years to determine more accurately prognosis of isolated corpus callosum agenesis.
Agenesis of Corpus Callosum↗
Routine detection of herpes simplex virus and varicella zoster virus by polymerase chain reaction reveals that initial herpes zoster is frequently misdiagnosed as herpes simplex.
The differential diagnosis of herpes simplex and zoster may require virological confirmation, yet virus typing is not regarded as necessary in routine dermatological assessment. In an attempt to evaluate the clinical benefits of the routine detection of herpes simplex virus (HSV) and varicella zoster virus (VZV), we analysed skin swabs from 110 patients who were diagnosed at the first clinical visit as having herpes simplex (n = 45) or zoster (n = 65). Viruses were typed using the polymerase chain reaction (PCR) with the general primer pair GPHV-RU. PCR analysis showed that at the initial clinical presentation, herpes simplex in these patients was not mistaken for zoster but that zoster was incorrectly diagnosed as herpes simplex in nine cases. Thus these results suggest that initial zoster often mimics herpes simplex, hence routine PCR diagnosis of HSV and VZV or alternative rapid diagnostic approaches may be beneficial in these cases.
Adult↗
Congenital adenomatoid disease of the lung: prenatal diagnosis and perinatal management.
Prenatal ultrasonographic (US) detection of congenital adenomatoid malformation (CAM) was made in 18 fetuses at 17 - 36 weeks' gestation and managed in our institution during a 10-year period (1985-1994). The lesion was left-sided in 13 cases, right-sided in 4, and bilateral in 1. According to Stocker's classification, 12 cases were type I, 4 type II, and 2 type III. The prenatal course was followed with serial US examinations in 13 cases; the size of the lesion was stable in 8 and decreased in 5. Mediastinal shift was usually observed, and amniotic fluid volume was increased in 4 cases. One fetus was aborted. Six infants presented with respiratory distress syndrome and required neonatal surgery; delayed surgery was performed in 9 cases. Spontaneous regression of the lesion was observed on follow-up in 2 cases. Surgery consisted in lobectomy in 8 cases and segmentectomy in 6. The presence of fetal hydrops, type III lesions, and bilateral lung involvement are prenatal factors known to be associated with a poor prognosis. However, this series and a review of the literature suggest that caution should be observed with regard to the initial impression when counseling the parents regarding prognosis.
Cystic Adenomatoid Malformation of Lung, Congenita↗
[Prenatal MRI of the brain. Retrospective study apropos of 34 tests].
We performed 34 antenatal MRI, in utero in 29 foetuses with cerebral malformations depicted by US. For five patients, a second antenatal MRI was performed because of a technical failure or of diagnosis doubt. We considered that MRI is a valuable imaging method. We have observed 2 false negatives (myelomeningocele, gyration abnormality) on MR study (n = 34). MRI is more contributive that US for the etiological diagnosis of ventricular enlargement: 83% versus 46%. MRI depicted corpus callosum agenesis misdiagnosed in 5 patients by US. MR results modified the therapeutic procedure in 37% of our patients. We think that the optimal term to perform MRI study is after 28 weeks gestational age because of the size of the fetus and for the timing of cerebral development. Ventricular dilatation (criteria: occipital horn size more that one centimeter at 25 weeks of term) is the main indication of MR study.
Brain↗
Demonstration of human papillomavirus type 16-related DNA and absence of detectable p53 gene mutations in widespread cutaneous squamous cell carcinomas after oral psoralen with UV-A treatment.
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Aged↗