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PubMed1995

Solution structure of a brodimoprim analogue in its complex with Lactobacillus casei dihydrofolate reductase.

Two-dimensional (2D) double-quantum-filtered correlation spectroscopy (DQF-COSY), total correlation spectroscopy (TOCSY), nuclear Overhauser effect spectroscopy (NOESY), and rotating-frame NOESY (ROESY) spectra were used to assign essentially all the protons in a 1:1 complex of Lactobacillus casei dihydrofolate reductase formed with an analogue of the antibacterial drug brodimoprim [2,4-diamino-5-(3',5'-dimethoxy-4'-bromobenzyl)pyrimidine]. The analogue has a 4,6-dicarboxylic acid side chain substituted on the 3'-O position designed to interact with the Arg 57 and His 28 residues in L. casei dihydrofolate reductase; it binds a factor of 10(3) more tightly to the enzyme than does the parent compound. Thirty-eight intermolecular and 11 intramolecular NOEs were measured involving the bound brodimoprim-4,6-dicarboxylic acid analogue. These provided the distance constraints used in conjunction with an energy minimization and simulated annealing protocol (using Discover from Biosym Ltd.) to dock the brodimoprim analogue into dihydrofolate reductase. In calculations where side chains and backbone fragments for binding-site residues were allowed flexibility, 90% of the 40 calculated structures had reasonable covalent geometry and none of them had NOE distance violations of greater than 0.36 A. The conformations of the aromatic rings in the bound ligand were well-defined in all the structures, with torsion angles tau 1 = -153 degrees +/- 4 degrees (C4-C5-C7-C1') and tau 2 = 53 degrees +/- 4 degrees (C5-C7-C1'-C2'): the aromatic rings of the ligand occupied essentially the same space in all the calculated structures (root mean square deviation value 1.83 A). Inclusion of the electrostatic interactions into the energy minimizations indicated that structures in which the 4,6-dicarboxylate group of the ligand interacts with the side chains of Arg 57 and His 28 are of low energy. Significant differences in side-chain and backbone conformations were detected between binding-site residues in the enzyme complexes with the brodimorpim analogue and methotrexate.

Amino Acid Sequence↗

PubMed2003

Effects of sucrose oleate and sucrose laureate on in vivo human stratum corneum permeability.

PURPOSE: The purpose of this work was to 1) investigate the effect of sucrose esters (sucrose oleate and sucrose laureate in water or in Transcutol, TC) on the stratum corneum (SC) barrier properties in vivo and 2) examine the impact of these surfactant-like molecules on the in vivo percutaneous penetration of a model penetrant 4-hydroxybenzonitrile (4-HB). METHODS: Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and transepidermal water loss measurements were used to evaluate the sucrose oleate- and sucrose laureate-induced biophysical changes in SC barrier function in vivo. In addition. the effect of the enhancers on 4-HB penetration was monitored in vivo using ATR-FTIR spectroscopy in conjunction with tape-stripping of the treated site. RESULTS: Treatment of the skin with 2% sucrose laureate or sucrose oleate in TC significantly increased the extent of 4-HB penetration relative to the control. Furthermore, when skin treated with these formulations was examined spectroscopically, the C-H asymmetric and symmetric stretching bands of the lipid methylene groups were characterized by 1) decreased absorbances and 2) frequency shifts to higher wavenumbers. These effects on the SC lipids and 4-HB penetration were more pronounced for sucrose laureate when combined with TC. CONCLUSIONS: A combination of sucrose esters (oleate or laureate) and TC is able to temporally alter the stratum corneum barrier properties, thereby promoting 4-HB penetration. These molecules are worthy of further investigation as potential candidates for inclusion in transdermal formulations as penetration enhancers.

Adult↗

PubMed2004

A meta-analysis of the timing of chest irradiation in the combined modality treatment of limited-stage small cell lung cancer.

The objective of this study was to determine whether initial combined chemoradiation results in superior 1-, 2-, and 3-year survivals in the treatment of limited-stage small cell lung cancer versus sequential or split-course therapy. Using a prospective meta-analysis protocol outlining study inclusion criteria, literature search strategy, and statistical procedures, data from all available randomized controlled trials addressing the above-noted objective were pooled using a fixed effects model (Peto). Results were expressed as summary odds ratios (ORp), and statistical tests for data heterogeneity were performed prior to calculation of ORps. Odds ratios greater than 1.0 favored the experimental arm versus control (i.e., early chest irradiation). If statistical heterogeneity was demonstrated, sensitivity analyses were performed by previously described methods to evaluate possible sources of heterogeneity across the included studies. Pooling data from eight randomized controlled trials enrolling over 1,500 patients showed that early integration of chest radiotherapy with systemic chemotherapy increases overall survival by 34%-216%, depending on the end point of interest. Etoposide (E) plus cisplatin (P) in conjunction with chest irradiation appears to offer the greatest increase in survival versus delayed or split-course radiation therapy and non-EP-containing drug schedules. The available randomized trial data support early concurrent chest radiotherapy and systemic chemotherapy in the form of E and P in the management of limited-stage small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2003

Conformational changes in SP-B as a function of surface pressure.

X-ray reflectivity of bovine and sheep surfactant-associated protein B (SP-B) monolayers is used in conjunction with pressure-area isotherms and protein models to suggest that the protein undergoes changes in its tertiary structure at the air/water interface under the influence of surface pressure, indicating the likely importance of such changes to the phenomena of protein squeeze out as well as lipid exchange between the air-water interface and subphase structures. We describe an algorithm based on the well-established box- or layer-models that greatly assists the fitting of such unknown scattering-length density profiles, and which takes the available instrumental resolution into account. Scattering-length density profiles from neutron reflectivity of bovine SP-B monolayers on aqueous subphases are shown to be consistent with the exchange of a large number of labile protons as well as the inclusion of a significant amount of water, which is partly squeezed out of the protein monolayer at elevated surface pressures.

Animals↗

PubMed1990

Transmembrane cytoskeletal modulation in preterminal growing axons: I. Arrest of bulk and organelle transport in goldfish retinal ganglion cell axons regenerating in vitro by lectins binding to sialoglycoconjugates.

Goldfish retinal ganglion cell (RGC) axons regenerating in vitro exhibit a novel mode of axoplasmic transport that entails a rapid bidirectional bulk redistribution of axoplasm, "packaged" as protruding varicosities and non-protruding phase-dense inclusions (Koenig et al.: J. Neurosci. 5:715-729, 1985; Edmonds and Koenig Brain Res. 406:288-293, 1987). We have used phase-contrast video microscopy to study transmembrane effects of surface-binding lectins on bulk transport and transport of single visible organelles in RGC axons. Our findings show that certain lectins which crosslink sialoglycoconjugates, such as wheat germ agglutinin (WGA) and the more specific sialic acid-binding lectin Limax flavus agglutinin (LFA), induce a rapid inhibition of transport activity. The LFA-induced inhibition of transport can be reversed by appropriate simple sugar haptens, and can also be antagonized by pretreatment with cytochalasin D. One of the consequences of LFA binding is an increase in RITC-conjugated phalloidin fluorescence staining of preterminal axons. The latter observation in conjunction with the antagonistic action of cytochalasin D suggests that one possible explanation for the transmembrane arrest of transport induced by crosslinking of surface sialoglycoconjugates may involve a polymerization and/or reorganization of the actin filament network which hinders translocation of mobile axoplasmic components.

Animals↗

PubMed1994

Recent developments in heterologous protein production in Escherichia coli.

During the past three to four years, remarkable progress has been made in our understanding of protein folding, protein translocation across biological membranes, and the role of molecular chaperones in these processes. In conjunction with recent developments in Escherichia coli expression systems, this understanding has led to an improved capability to accumulate proteins in a soluble form, secrete proteins from the cell cytoplasm, accumulate proteins in the cytoplasmic membrane, and direct proteins to the outer membrane of the cell for surface display. These advances suggest that E. coli should now be considered seriously for applications that, only a few years ago, would have been thought beyond the scope of this organism.

Bacterial Proteins↗

PubMed2004

Electrokinetics of the amphifunctional metal/electrolyte solution interface in the presence of a redox couple.

Double layers (DL) at amphifunctionally electrified interfaces, such as that of an oxidized metal in an aqueous electrolyte solution, arise from coupling between ionic and electronic surface-charging processes. The electronic component enters the double-layer formation in the well-known situation where a potential is externally applied. In that case, the DL is fully or partly polarized depending on the possibility of interfacial electron transfer, that is, a faradaic process. This paper reports on the conjunction of the chemical/electrochemical processes at the interface in the case where the solution contains a redox-active couple. This makes it possible to polarize/depolarize a DL without invoking any external circuit. Streaming potential data obtained for the gold/(Fe(CN)6(3-)/Fe(CN)6(4-), KNO3) electrolyte interface are analyzed in terms of a recently developed theory which takes into account reversible bipolar faradaic depolarization, the inherent nonlinearity of the lateral field, and the effects of flow on the rate of the faradaic reactions. It appears that the theory largely overestimates the bipolar currents, leading to physically unrealistic zeta-potentials. A careful analysis of monopolar voltammetric data reveals quasi-reversible behavior of the redox couple under the typical convective conditions and electrolyte compositions met in electrokinetic experiments. Inclusion of reduced reversibility (the extent of which is position-dependent under the streaming-potential measurement conditions) leads to a consistent set of zeta-potentials which compare well to the values for the background electrolyte.

Journal Article↗

PubMed2005

Dystonia-causing mutant torsinA inhibits cell adhesion and neurite extension through interference with cytoskeletal dynamics.

Early onset torsion dystonia is a movement disorder inherited as an autosomal dominant syndrome with reduced penetrance. Symptoms appear to result from altered neuronal circuitry within the brain with no evidence of neuronal loss. Most cases are caused by loss of a glutamic acid residue in the AAA+ chaperone protein, torsinA, encoded in the DYT1 gene. In this study, torsinA was found to move in conjunction with vimentin in three cell culture paradigms-recovery from microtubule depolymerization, expression of a dominant-negative form of kinesin light chain and respreading after trypsinization. Co-immune precipitation studies revealed association between vimentin and torsinA in a complex including other cytoskeletal elements, actin and tubulin, as well as two proteins previously shown to interact with torsinA-the motor protein, kinesin light chain 1, and the nuclear envelope protein, LAP1. Morphologic and functional differences related to vimentin were noted in primary fibroblasts from patients carrying this DYT1 mutation as compared with controls, including an increased perinuclear concentration of vimentin and a delayed rate of adhesion to the substratum. Overexpression of mutant torsinA inhibited neurite extension in human neuroblastoma cells, with torsinA and vimentin immunoreactivity enriched in the perinuclear region and in cytoplasmic inclusions. Collectively, these studies suggest that mutant torsinA interferes with cytoskeletal events involving vimentin, possibly by restricting movement of these particles/filaments, and hence may affect development of neuronal pathways in the brain.

Actins↗

PubMed2006

A thiamin-bound, pre-decarboxylation reaction intermediate analogue in the pyruvate dehydrogenase E1 subunit induces large scale disorder-to-order transformations in the enzyme and reveals novel structural features in the covalently bound adduct.

The crystal structure of the E1 component from the Escherichia coli pyruvate dehydrogenase multienzyme complex (PDHc) has been determined with phosphonolactylthiamin diphosphate (PLThDP) in its active site. PLThDP serves as a structural and electrostatic analogue of the natural intermediate alpha-lactylthiamin diphosphate (LThDP), in which the carboxylate from the natural substrate pyruvate is replaced by a phosphonate group. This represents the first example of an experimentally determined, three-dimensional structure of a thiamin diphosphate (ThDP)-dependent enzyme containing a covalently bound, pre-decarboxylation reaction intermediate analogue and should serve as a model for the corresponding intermediates in other ThDP-dependent decarboxylases. Regarding the PDHc-specific reaction, the presence of PLThDP induces large scale conformational changes in the enzyme. In conjunction with the E1-PLThDP and E1-ThDP structures, analysis of a H407A E1-PLThDP variant structure shows that an interaction between His-407 and PLThDP is essential for stabilization of two loop regions in the active site that are otherwise disordered in the absence of intermediate analogue. This ordering completes formation of the active site and creates a new ordered surface likely involved in interactions with the lipoyl domains of E2s within the PDHc complex. The tetrahedral intermediate analogue is tightly held in the active site through direct hydrogen bonds to residues His-407, Tyr-599, and His-640 and reveals a new, enzyme-induced, strain-related feature that appears to aid in the decarboxylation process. This feature is almost certainly present in all ThDP-dependent decarboxylases; thus its inclusion in our understanding of general thiamin catalysis is important.

Amino Acid Substitution↗

PubMed2004

Health related virtual communities and electronic support groups: systematic review of the effects of online peer to peer interactions.

OBJECTIVE: To compile and evaluate the evidence on the effects on health and social outcomes of computer based peer to peer communities and electronic self support groups, used by people to discuss health related issues remotely. DESIGN AND DATA SOURCES: Analysis of studies identified from Medline, Embase, CINAHL, PsycINFO, Evidence Based Medicine Reviews, Electronics and Communications Abstracts, Computer and Information Systems Abstracts, ERIC, LISA, ProQuest Digital Dissertations, Web of Science. SELECTION OF STUDIES: We searched for before and after studies, interrupted time series, cohort studies, or studies with control groups; evaluating health or social outcomes of virtual peer to peer communities, either as stand alone interventions or in the context of more complex systems with peer to peer components. MAIN OUTCOME MEASURES: Peer to peer interventions and co-interventions studied, general characteristics of studies, outcome measures used, and study results. RESULTS: 45 publications describing 38 distinct studies met our inclusion criteria: 20 randomised trials, three meta-analyses of n of 1 trials, three non-randomised controlled trials, one cohort study, and 11 before and after studies. Only six of these evaluated "pure" peer to peer communities, and one had a factorial design with a "peer to peer only" arm, whereas 31 studies evaluated complex interventions, which often included psychoeducational programmes or one to one communication with healthcare professionals, making it impossible to attribute intervention effects to the peer to peer community component. The outcomes measured most often were depression and social support measures; most studies did not show an effect. We found no evidence to support concerns over virtual communities harming people. CONCLUSIONS: No robust evidence exists of consumer led peer to peer communities, partly because most peer to peer communities have been evaluated only in conjunction with more complex interventions or involvement with health professionals. Given the abundance of unmoderated peer to peer groups on the internet, research is required to evaluate under which conditions and for whom electronic support groups are effective and how effectiveness in delivering social support electronically can be maximised.

Clinical Trials as Topic↗

PubMedDate not supplied

Gender differences in processing information for making self-assessments of health.

OBJECTIVE: This study proposes that women's greater inclusiveness of various sources of information when making self-assessed health (SAH) judgments accounts for the finding that SAH is a weaker predictor of mortality in women than in men. METHODS: Data from a sample of 830 elderly residents of a retirement community and a 5-year mortality follow-up study were used to examine the bases for women's and men's reports of negative affect (NA) and judgments of SAH. The degree to which each health-related measure accounts for the SAH-mortality association in each gender group was examined. RESULTS: The findings support two possible explanations for the lower accuracy of SAH as a predictor of mortality among women: 1) In both men and women, NA is associated with poorer SAH, but in men, NA is more closely linked to serious disease in conjunction with other negative life events, whereas in women, NA reflects a wider range of factors not specific to serious disease. 2) Men's SAH judgments reflect mainly serious, life-threatening disease (eg, heart disease), whereas women's SAH judgments reflect both life-threatening and non-life-threatening disease (eg, joint diseases). CONCLUSIONS: Women's SAH judgments and NAs are based on a wider range of health-related and non-health-related factors than are men's. This difference can explain gender differences in the accuracy of SAH judgments and may be related to other documented differences in women's physical and mental health and illness behavior. The findings emphasize the need to study the bases of NA and other self-evaluations separately for women and men.

Affect↗

PubMed2000

Surfactant for meconium aspiration syndrome in full term infants.

OBJECTIVES: To evaluate the effect of surfactant administration in the treatment of term infants with meconium aspiration syndrome. SEARCH STRATEGY: Searches were made using Medline (1985 to January 2000) (MeSH terms: pulmonary surfactant and meconium aspiration; limits: age groups, newborns; publication type, clinical trials), previous reviews including cross-references, abstracts, conference and symposia proceedings, expert informants, and journal hand searching in the English language. Authors were directly contacted to provide additional data. SELECTION CRITERIA: Randomized controlled trials which evaluated the effect of surfactant administration in term infants with meconium aspiration syndrome are included in the analysis. DATA COLLECTION AND ANALYSIS: Data regarding clinical outcomes including duration of assisted ventilation, duration of supplemental oxygen, pneumothorax, intraventricular hemorrhage (any grade and severe IVH), chronic lung disease, treatment with extracorporeal membrane oxygenation (ECMO), and mortality were excerpted from the reports of the clinical trails by the reviewers. Data analysis was done in accordance with the standards of the Cochrane Neonatal Review Group. MAIN RESULTS: Two randomized controlled trials met inclusion criteria. Findlay (1996) reports a decrease in the risk of pneumothorax (relative risk 0.09, 95% CI 0.01, 1.54, risk difference -0.25, 95% CI -0.45, -0.05). Both Findlay (1996) and Lotze (1998) report a decrease in the number of infants receiving extracorporeal membrane oxygenation. The meta-analysis supports a significant reduction in the risk of requiring extracorporeal membrane oxygenation (typical relative risk 0.64, 95% CI 0.46, 0.91 typical risk difference -0.17, 95% CI -0.30, -0.04). No difference was noted in overall mortality (typical relative risk 1.86 95% CI 0.35, 9.89, typical risk difference 0.02 95% CI -0.03, 0.07). REVIEWER'S CONCLUSIONS: In infants with meconium aspiration syndrome, surfactant administration may reduce the severity of respiratory illness and decrease the number of infants with progressive respiratory failure requiring support with ECMO. The relative efficacy of surfactant therapy compared to, or in conjunction with, other approaches to treatment including inhaled nitric oxide, liquid ventilation, and high frequency ventilation remains to be tested.

Humans↗

PubMed1995

Immuno-gold localization of hepatotoxins in cyanobacterial cells.

A polyclonal antibody against the potent hepatotoxic cyclic peptide microcystins and nodularins was used in conjunction with immuno-gold labelling to localize the toxins in three strains of cyanobacteria. Ultrastructurally, there were no major differences between unicellular Microcystis aeruginosa strain PCC 7820 (toxin-producing strain) and M. aeruginosa strain UTEX 2063 (non-toxin-producing strain), except that M. aeruginosa PCC 7820 cells had a sheath. The thickness of the sheath was about 12 nm and was distinguishable from the cell wall at the ultrastructural level only when the specimen was stained en bloc with uranyl acetate. Microcystins and nodularin were found in M. aeruginosa PCC 7820 and Nodularia spumigena strain L-575 respectively, but not in nontoxic M. aeroginosa UTEX 2063. In M. aeruginosa PCC 7820 cells, microcystin was found primarily in the thylakoid area and nucleoid, with smaller amounts in the cell wall and sheath. Only nonspecific labelling was found in other cellular inclusions, such as polyhedral bodies, cyanophycin granules and membrane-limited inclusions. In strain N. spumigena L-575, nodularin was found in both vegetative cells and heterocysts with a distribution similar to that in M. aeruginosa PCC 7820.

Bacterial Toxins↗

PubMed1993

Comparative trial of prednisone plus aspirin versus aspirin alone in the treatment of anticardiolipin antibody-positive obstetric patients.

OBJECTIVE: We compared the use of aspirin alone with combined therapy (prednisone plus aspirin) in antiphospholipid antibody-positive obstetric patients with prior adverse pregnancy outcome. STUDY DESIGN: Thirty-nine patients meeting specific laboratory and clinical inclusion criteria were randomized to receive either combined therapy (prednisone plus low-dose aspirin, n = 17) or aspirin alone (n = 22). The daily aspirin dose was 81 mg; prednisone was begun at 20 mg/day and increased or decreased on the basis of observed changes in serial antibody levels. Perinatal outcomes were compared between groups. Evaluation of treatment-related maternal complications and serial antibody titers was also accomplished. RESULTS: Thirty-four randomized subjects were evaluable (prednisone plus low-dose aspirin, n = 12 vs aspirin only, n = 22); no perinatal losses were observed in the study cohort. Preterm delivery was experienced by significantly more patients receiving prednisone plus low-dose aspirin than aspirin only (8/12 vs 3/22, respectively; p = 0.003), and prednisone exposure appeared to be an independent risk factor for preterm birth. CONCLUSIONS: The use of prednisone therapy in conjunction with low-dose aspirin does not appear to improve outcome and may provoke obstetric complications in antiphospholipid antibody-positive patients.

Adult↗

PubMed1999

[30-day mortality after heart surgery: a pilot project of the Working Party of Directors of Hospital Cardiology Departments].

BACKGROUND AND OBJECTIVE: 30-day mortality after operation is generally accepted as a central standard of quality, especially in regard to cardiac operations. The Working Party of Directors of Hospital Cardiology Departments (Arbeitsgemeinschaft Leitender Kardiologischer Krankenhausärzte, ALKK) in Germany set up a pilot project to analyse whether by direct communication with patients by a database centre the expenditure incurred in collecting complete data can be decisively reduced and full documentation of outcome can in this way be obtained even for a large multi-centre patient cohort. PATIENTS AND METHODS: Between 1.6.1997 and 31.3.1998, data were consecutively collected by questionnaire on all patients registered for a cardiac operation at 85 of the 135 ALKK centres. The questionnaire included data about each patient and the indication for operation as well as the estimate of operative risk, assigned to one of five risk categories by the referring cardiologist either alone or in conjunction with the cardiac surgeon. RESULTS: Until 30.9.1998, the data were obtained on 11,349 patients who had given informed consent (response rate 99.99%), including survival figures. 824 (7.3%) patients had not undergone the planned cardiac surgery, 134 having died before the data of operation. The 30-day postoperative mortality, obtained in 99.99% of the 10,525 patients, was 3.92%. The operative mortality was lowest, at 3.73%, for aortocoronary bypass only (n = 7932), highest for aortocoronary bypass plus valvular operation (n = 785), at 8.04%. There was good agreement between the cardiologists' preoperative risk assessment and the observed mortality. CONCLUSIONS: The 30-day mortality after cardiac operation can be obtained almost completely and with reasonable expenditure even for a large patient cohort. The results confirm that hospital mortality data definitely understate the overall operative risk. The methodology used in this pilot project, namely the inclusion of information from the patients by questionnaire, can also be applied to clinical results in other areas.

Adult↗

PubMed2004

Clinical outcomes of stents versus balloon angioplasty in non-acute coronary artery disease. A meta-analysis of randomized controlled trials.

AIMS: To evaluate whether stents as compared to balloon angioplasty reduce mortality in patients with non-acute coronary artery disease. METHODS AND RESULTS: We identified randomized controlled trials comparing stents to balloon angioplasty for the treatment of non-acute coronary artery disease by searching major medical databases from 1979 to March 2002. Two independent reviewers selected and extracted data from trials that had to report data on death and myocardial infarction. Nineteen trials, with a total of 8004 patients, fulfilled our inclusion criteria. For 1000 patients treated with stents rather than balloon angioplasty, 3 (95% CI 0-6), 5 (95% CI 0-9), and 6 (95% CI -1-12) additional lives were saved at 30 days, 6 and 12 months. At 12 months, for 1000 patients treated with stents rather than balloon angioplasty 46 (95% CI 25-66) additional target vessel revascularizations were avoided, but 25 (95% CI 15-34) additional bleeding complications with need for blood transfusion or surgical intervention occurred. In sensitivity analysis 11 (95% CI 2-20) and 2 (95% CI -4-7) deaths were avoided per 1000 patients treated with stents rather than PTCA in trials that routinely used compared to trials that did not use glycoprotein IIb/IIIa inhibitors. CONCLUSION: In non-acute coronary disease stents may reduce overall mortality, but this benefit seems to be limited to stents used in conjunction with glycoprotein IIb/IIIa inhibitors. Stents compared to PTCA reduce target vessel revascularizations, but increase the risk of bleeding complications.

Angioplasty, Balloon, Coronary↗

PubMed1997

Heterotopic ossification as a complication of toxic epidermal necrolysis.

The development of heterotopic ossification (HO) as a complication of toxic epidermal necrolysis (TEN) has not been previously reported. TEN, also known as Lyell's syndrome, is a rare but serious skin disorder that typically occurs after the administration of drugs, especially sulfonamides, barbiturates, phenytoin, and nonsteroidal anti-inflammatory agents. TEN is characterized by the development of large fluid-filled bullae with separation of large sheets of skin. Complications of TEN can include extensive denudation of skin with dehydration and electrolyte abnormalities, gastrointestinal hemorrhage, acute tubular necrosis, secondary infection of denuded skin, pneumonia, bacterial conjunctivitis, keratitis, and septic infarcts of internal organs. We report a case of HO in a patient with TEN after treatment with trimethoprim-sulfamethoxazole. A 49-year-old man developed an erythematous rash, bullae, fever, and extensive skin loss consistent with a diagnosis of TEN. He was intubated for complications of TEN (pneumonia) and maintained on bed rest for several weeks. In addition, he developed HO that resulted in multiple joint contractures. He was treated with aggressive range of motion by physical therapy, surgical resection of the HO followed by radiation to both elbows, right hip, and right knee. Postoperative outpatient rehabilitation enabled improved function in his mobility and activities of daily living. HO is known to occur after spinal cord and brain injuries and burns. It has not been reported to occur after TEN. Our experience with this case suggests that HO may merit inclusion into the list of complications of TEN.

Anti-Infective Agents↗

PubMed1983

The black thyroid associated with minocycline therapy. A local manifestation of a drug-induced lysosome/substrate disorder.

Two cases of black discoloration of the thyroid are reported, each in a young woman treated for acne; the first with minocycline alone, the second with tetracycline and minocycline. Light microscopy showed numerous brown granules in the cytoplasm of the follicular epithelium, with large brown deposits in the colloid, including, in Case 2, numerous crystalline forms. The association between drug therapy and pigment accumulation (in conjunction with animal experiments) was taken to indicate some form of causal relationship, and minocycline residues were anticipated. Histochemical studies indicated that the granules were lipofuscin and electron microscopy showed an increase in phagolysosomes but no novel structures. There was no evidence for persisting minocycline, or its derivatives, although these could not be excluded. The black thyroid appears to be a disorder at lysosome/substrate level, induced by drug action, particularly by minocycline, and manifested by an accumulation of heterogeneous intracellular material with the histochemical and electron microscopic appearances of lipofuscin.

Acne Vulgaris↗