bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Activities of Garenoxacin (BMS-284756) against
Streptococcus pneumoniae
, Viridans Group Streptococci, and
Enterococcus faecalis
Compared to Those of Six Other Quinolones
Authors: Grohs Patrick , Houssaye Serge , Aubert Agnès , Gutmann Laurent , Varon Emmanuelle
Published: October 2003

The activity of garenoxacin, a new quinolone, was determined in comparison with other quinolones against different strains of
S. pneumoniae
, viridans group streptococci (VGS), and
Enterococcus faecalis
. Strains were quinolone-susceptible clinical isolates and quinolone-resistant strains with defined mechanisms of resistance obtained from either clinical isolates or derivatives of
S. pneumoniae
R6. Clinical quinolone-susceptible strains of
S. pneumoniae
, VGS and
E. faecalis
showed garenoxacin MICs within a range of 0.03 μg/ml to 0.25 μg/ml. Garenoxacin MICs increased two- to eightfold when one mutation was present in the ParC quinolone resistance-determining region (QRDR), fourfold when one mutation was present in the GyrA QRDR (
S. pneumoniae
), 8- to 64-fold when two or three mutations were associated in ParC and GyrA QRDR, and 2,048-fold when two mutations were present in both the GyrA and ParC QRDRs (
Streptococcus pneumoniae
). Increased active efflux had a moderate effect on garenoxacin MICs for
S. pneumoniae
and VGS. Against
S. pneumoniae
, garenoxacin behaved like moxifloxacin and sparfloxacin, being more affected by a single
gyrA
mutation than by a single
parC
mutation. Although garenoxacin was generally two- to fourfold more active than moxifloxacin against the different wild-type or mutant strains of
S. pneumoniae
, VGS, and
E. faecalis
, it was two- to fourfold less active than gemifloxacin. At four times the respective MIC for each strain, the bactericidal effect of garenoxacin, observed at 6 h for
S. pneumoniae
and at 24 h for
S. oralis
and
E. faecalis
, was not influenced by the presence of mutation either in the ParC or in both the ParC and GyrA QRDRs.
Analysis of Daptomycin Efficacy and Breakpoint Standards in a Murine Model ofEnterococcus faecalisandEnterococcus faeciumRenal Infection
Authors: Alder Jeff , Li Tongchaun , Yu Donghui , Morton Larry , Silverman Jared , Zhang Xi-Xian , Critchley Ian , Thorne Grace
Published: October 2003

Daptomycin efficacy against clinical isolates ofEnterococcus faecalis,Enterococcus faecium, and a lab-derived daptomycin-resistant isolate ofE. faecaliswas investigated in a mouse model of renal infection. The daptomycin MICs against these enterococci ranged from 0.5 to 50 μg/ml. The objective of this study was to determine the relationship between the MICs of drugs againstE. faecalisandE. faeciumand the level of daptomycin exposure needed to evaluate the drug's efficacy. Correlating the required therapeutic exposures of mice with the exposures achieved clinically allowed us to project enterococcal breakpoint values. Mice pretreated with carrageenan were infected intravenously with 3 × 108to 4 × 108CFU ofE. faecalisorE. faecium. Daptomycin (5 to 50 mg of drug/kg of body weight) or saline control was administered 4 h postinfection and continued once daily for 2 days (three total doses). On day 4, infected kidneys were harvested, homogenized, and dilution plated. Efficacy was defined as a ≥2-log10(99%) reduction in bacterial burden in infected kidneys. At clinically relevant dosages and exposures (area under the curve, 400 to 600 μg · hr/ml), daptomycin demonstrated similar and marked efficacy against all clinical enterococcal isolates tested. Daptomycin achieved efficacy with comparable doses against both vancomycin-sensitive (MIC, ≤4 μg/ml) and -resistant enterococcal strains tested. Efficacy was also established against the lab-derived daptomycin-resistantE. faecalisisolate. In this murine renal infection model, clinically relevant exposures of daptomycin were effective againstE. faecalisandE. faeciumstrains for which MICs were ≤8 μg/ml. These murine efficacy data for daptomycin, along with surveillance data and human pharmacokinetic exposures achieved, suggest a breakpoint concentration value of ≤8 μg/ml (susceptible) and ≥16 μg/ml (resistant) for daptomycin againstE. faeciumandE. faecalis.
In Vitro Activity of TD-6424 againstStaphylococcus aureus
Authors: Pace John L. , Krause Kevin , Johnston Deborah , Debabov Dmitri , Wu Terry , Farrington Lesley , Lane Cassie , Higgins Deborah L. , Christensen Burt , Judice J. Kevin , Kaniga Koné
Published: October 2003

TD-6424, a rapidly bactericidal agent with multiple mechanisms of action, is more potent in vitro and more rapidly bactericidal than currently available agents against methicillin-susceptible and methicillin-resistantStaphylococcus aureus. TD-6424 produces a postantibiotic effect with a duration of 4 to 6 h against these organisms. The results suggest potential efficacy against susceptible and resistant strains ofS. aureus.
First
Streptococcus agalactiae
Isolates Highly Resistant to Quinolones, with Point Mutations in
gyrA
and
parC
Authors: Kawamura Yoshiaki , Fujiwara Hiromitsu , Mishima Noriko , Tanaka Yuko , Tanimoto Ayako , Ikawa Shiro , Itoh Youko , Ezaki Takayuki
Published: October 2003

Three isolates of
Streptococcus agalactiae
highly resistant to multiple fluoroquinolones were isolated in Japan. Compared with susceptible strains of
S. agalactiae
, these quinolone-resistant strains had double point mutations within the quinolone resistance-determining regions of
gyrA
and
parC
; Ser-81 was changed to Leu (TCA → TTA) in the amino acid sequence deduced from
gyrA
, and Ser-79 was changed to Phe (TCC → TTC) in the amino acid sequence deduced from
parC
. Comparative sequence analysis revealed the possibility of gene transfer between
S. agalactiae
and another beta-hemolytic streptococcus,
Streptococcus difficile
.
Inhibition of the Complement Membrane Attack Complex bySchistosoma mansoniParamyosin
Authors: Deng Jiusheng , Gold Daniel , LoVerde Philip T. , Fishelson Zvi
Published: October 2003

Larvae and adults of the parasitic blood flukeSchistosoma mansoniare resistant to killing by human complement. An earlier search by Parizade et al. for a schistosome complement inhibitor identified a 94-kDa surface protein which was named SCIP-1 (M. Parizade, R. Arnon, P. J. Lachmann, and Z. Fishelson, J. Exp. Med. 179:1625-1636, 1994). Following partial purification and analysis by mass spectrometry, we have determined SCIP-1 to be a surface-exposed form of the muscle protein paramyosin. As shown by immunofluorescence, anti-paramyosin antibodies label the surface of live schistosomula and adult worms. Like SCIP-1, purified native paramyosin reacts with a polyclonal rabbit anti-human CD59 antiserum, as shown by Western blot analysis. Also, the human complement components C8 and C9 bind to recombinant and native paramyosin. Analysis of paramyosin binding to fragments of C9 generated by thrombin or trypsin has demonstrated that paramyosin binds to C9 at a position located between Gly245 and Arg391. Paramyosin inhibited Zn2+-induced C9 polymerization and poly-C9 deposition onto rabbit erythrocytes (ER). In addition, paramyosin inhibited lysis of ERand of sensitized sheep erythrocytes by human complement. Finally, anti-paramyosin antibodies enhanced in vitro killing of schistosomula by normal and C4-depleted human complement. Taken together, these findings suggest that an exogenous form ofS. mansoniparamyosin inhibits activation of the terminal pathway of complement and thus has an important immunomodulatory role in schistosomiasis.
Type 1 Fimbriae ofSalmonella entericaSerovar Typhimurium Bind to Enterocytes and Contribute to Colonization of Swine In Vivo
Authors: Althouse Carrie , Patterson Sheila , Fedorka-Cray Paula , Isaacson Richard E.
Published: October 2003

Salmonella entericaserovar Typhimurium strain 798 is a clinical isolate from a pig and is known to be able to cause persistent, asymptomatic infections. This strain also is known to exist in two phenotypes (adhesive and nonadhesive to enterocytes) and can switch between the two phenotypes at a rate consistent with phase variation. Cells in the adhesive phenotype are more readily phagocytosed by leukocytes than nonadhesive cells. Once in a leukocyte, adhesive-phase cells survive while nonadhesive-phase cells die. In the present study, nonadhesive mutants were obtained with the transposon TnphoA. A nonadhesive mutant was selected for study and was shown by electron microscopy not to produce fimbriae. The gene encoding the adhesin was cloned and sequenced. Based on its sequence, the adhesin was shown to be FimA, the major subunit of type 1 fimbriae. The nonadhesive mutant was attenuated in its ability to colonize both mouse and pig intestines, but remained capable of systemic spread in mice. The nonadhesive mutant was phagocytosed to the same extent as parental cells in the adhesive phase and then survived intracellularly. These results demonstrated that type 1 fimbriae were important for attachment to enterocytes and promoted intestinal colonization. However, they were not important in promoting phagocytosis or intracellular survival.
Growth Phase-Dependent Response ofHelicobacter pylorito Iron Starvation
Authors: Merrell D. Scott , Thompson Lucinda J. , Kim Charles C. , Mitchell Hazel , Tompkins Lucy S. , Lee Adrian , Falkow Stanley
Published: October 2003

Iron is an essential nutrient that is often found in extremely limited available quantities within eukaryotic hosts. Because of this, many pathogenic bacteria have developed regulated networks of genes important for iron uptake and storage. In addition, it has been shown that many bacteria use available iron concentrations as a signal to regulate virulence gene expression. We have utilized DNA microarray technology to identify genes of the human pathogenHelicobacter pylorithat are differentially regulated on a growth-inhibiting shift to iron starvation conditions. In addition, the growth phase-dependent expression of these genes was investigated by examining both exponential and stationary growth phase cultures. We identified known iron-regulated genes, as well as a number of genes whose regulation by iron concentration was not previously appreciated. Included in the list of regulated factors were the known virulence genescagA,vacA, andnapA. We examined the effect of iron starvation on the motility ofH. pyloriand found that exponential- and stationary-phase cultures responded differently to the stress. We further found that while growing cells are rapidly killed by iron starvation, stationary-phase cells show a remarkable ability to survive iron depletion. Finally, bioinformatic analysis of the predicted promoter regions of the differentially regulated genes led to identification of several putative Fur boxes, suggesting a direct role for Fur in iron-dependent regulation of these genes.
Simultaneous Variation of the Immunodominant Outer Membrane Proteins, MSP2 and MSP3, duringAnaplasma marginalePersistence In Vivo
Authors: Brayton Kelly A. , Meeus Patrick F. M. , Barbet Anthony F. , Palmer Guy H.
Published: October 2003

Vector-borne bacterial pathogens persist in the mammalian host by varying surface antigens to evade the existing immune response. To test whether the model of surface coat switching and immune evasion can be extended to a vector-borne bacterial pathogen with multiple immunodominant surface proteins, we examinedAnaplasma marginale, a rickettsia with two highly immunogenic outer membrane proteins, major surface protein 2 (MSP2) and MSP3. The simultaneous clearance of variants of the two most immunodominant surface proteins ofA.marginalefollowed by emergence of unique variants indicates that the switch rates and immune selection for MSP2 and MSP3 are sufficiently similar to explain the cyclic bacteremia observed during infection in the immunocompetent host.
The Influence of Bradycardia and Normofrequent Ventricular Pacing on Myocardial Blood Flow and Energy Demand in Rats
Authors: Schneider Hans-Jürgen , Pfeiffer Dietrich , Hagendorff Andreas
Published: October 2003

The purpose of the present study was to determine the effect of β-blockade-induced bradycardia and normofrequent ventricular pacing (VP) on regional myocardial (MBF) and cerebral blood flow (CBF) as well as on myocardial oxygen consumption (MVO2) using colored microspheres. The MBF at sinus rhythm (SR) was 4.60 ± 1.27 ml/g/min and decreased to 3.80 ± 0.74 ml/g/min (p < 0.05) during β-blockade. The MBF was 5.10 ± 1.88 ml/g/min during VP with β-blockade. The endo-/epicardial MBF ratio during VP was significantly reduced. MVO2 at β-blockade was significantly lower (0.21 ± 0.06 ml/g × min–1, p < 0.05) than at SR (0.47 ± 0.15 ml/g × min–1) and during VP with β-blockade (0.54 ± 0.14 ml/g × min–1). Results: (i) MBF and MVO2 are reduced with decreasing mean arterial pressure (MAP) during β-blockade-induced bradycardia, but MBF and MVO2 are significantly increased during normofrequent VP with β-blockade despite a further reduction in MAP. (ii) The MBF ratio is constant during β-blockade but is significantly lower during normofrequent VP with β-blockade. (iii) CBF remained constant during all experimental conditions. Conclusion: Despite β-blockade, the subendocardium is jeopardized during normofrequent VP by ischemia.
Regional Heterogeneity in Gene Expression Profiles: A Transcript Analysis in Human and Rat Heart
Authors: Sharma Saumya , Razeghi Peter , Shakir Ali , Keneson 2nd Bradley J. , Clubb Fred , Taegtmeyer Heinrich
Published: October 2003

Background: Investigations involving biopsies of human cardiac tissue often assume that myocardial samples from a specific location are representative of the entire heart. Hypothesis: There are significant regional differences in gene expression in the heart. Methods: We used two models. In the first model, seven whole human hearts were cut in 1-cm slices from apex to base and 11 distinct regions were sampled. Full thickness left ventricular tissue was further subdivided equally into an inner, outer, and middle region. In the second model, hearts were removed from adult Sprague-Dawley rats and were divided into 4 regions. Using species-specific quantitative reverse transcriptase-polymerase chain reaction, we measured transcript levels of myosin heavy chain β (MHC-β), glucose transporter 1 (GLUT 1), and atrial natriuretic factor (ANF) in tissue samples from both models. Results: In human heart, there were significant differences in transcript levels between regions. The following patterns could be recognized among the seven hearts. ANF expression was highest in the subendocardial region. MHC-β and GLUT 1 transcript levels were higher in the right ventricle than the left ventricle. As expected, ANF transcript levels were highest in the atria, where MHC-β and GLUT 1 expression was low. Analogous to the human studies, MHC-β and GLUT 1 transcript levels were low in rat atria as compared to ventricles. In rat heart, MHC-β expression was higher in the left ventricle than the right ventricle while GLUT 1 expression was not significantly different between ventricles. Conclusion: Despite the large variability in transcript levels among different regions in human hearts, certain patterns in gene expression emerged suggesting that different anatomical regions of the heart also differ in respect to gene expression.
Primary Vitrectomy in Complicated Rhegmatogenous Retinal Detachment – A Survey of 205 Eyes
Authors: Schmidt J.C. , Rodrigues E.B. , Hoerle S. , Meyer C.H. , Kroll P.
Published: October 2003

Introduction: In a few types of rhegmatogenous retinal detachment (RRD), scleral buckling (SB) has a lower success, and, here, pars plana vitrectomy (PPV) is a good alternative option. This survey reviews the indications and the surgical outcome of primary PPV with internal tamponade. Patients and Methods: We reviewed 205 eyes operated by primary PPV for RRD at the Department of Ophthalmology of the Philipps University Marburg between the years 1990 and 1997. The indications of PPV were: holes greater than 90°; holes posterior to the equator; proliferative vitreoretinopathy grade C; pseudophakic status. Results: A complete reattachment of the retina after absorption of the gas or after silicone oil removal was achieved by 1 operation in 146 eyes (71.2%) and in 195 eyes (95.2%) by a second intervention. Conclusion: Although SB is the standard procedure for the treatment of RRD, complicated cases can be treated successfully with primary PPV.
Is Membrane Extraction in Cases of Exudative Age-Related Macular Degeneration Still Up-to-Date?
Authors: Schmidt Jörg C. , Rodrigues Eduardo B. , Meyer Carsten H. , Kroll Peter
Published: October 2003

Background: Age-related macular degeneration (AMD) is a frequent cause of an irreversible loss of the ability to read. The non-exudative form of AMD has not been therapeutically approached in the past in contrast to the exudative form with choroidal neovascularizations (CNVs). Parafoveal laser coagulation can be applied, and in cases of subfoveal location a pars plana vitrectomy with subretinal resection of the CNV is possible. Material and Methods: Since 1995, we have operated 46 eyes of 45 patients with CNV developing from AMD. Patient ages ranged from 63 to 85 years (mean 71.8 years). Pre- and postoperatively we performed vision tests, fluorescence angiographies with sodium fluorescein and indocyanine green. Follow-up times ranged from 3 to 28 months (mean 12.3 months). Results: Pre-operative vision was 0.10 (range: hand movements to 0.4). Postoperative vision at the end of the follow-up period was 0.12 (range: hand movements to 0.4). Vision at the end of the follow-up was lower in 41%, unchanged in 20% and improved in 39%. In 43 eyes, a non-exudative form of AMD developed. Two eyes had a recurrent CNV, which was removed successfully with a second pars plana vitrectomy. Three patients developed a retinal detachment, which was successfully treated by pars plana vitrectomy, encircling buckle and gas tamponade. Conclusions: We still have to wait for the results of the photodynamic study trials and a randomized study of macular dislocation. Subretinal removal of the CNV by pars plana vitrectomy allows a stabilization of the visual function in most of our cases of AMD. This method inhibits the development of large pseudotumour-like scars. Postoperatively remaining pigment epithelial defects with choroidal atrophies however limit a visual rehabilitation so that reading vision can only be achieved in cases with good pre-operative vision. Long-term results of photodynamic therapy are still lacking and have to show its effectiveness over greater time spans.
Prognostic Factors in Open Globe Injuries
Authors: Cruvinel Isaac David Leonardo , Ghanem Vinícius Coral , Nascimento Maurício Abujamra , Torigoe Marcelo , Kara-José Newton
Published: October 2003

Purposes: To evaluate the main factors related to visual outcome after open globe injuries (excluding intraocular foreign bodies). Methods: Retrospective study analyzing consecutive ocular lacerations, primarily repaired in this institution, between January 1993 and January 2000. Of the 364 cases, 283 (77.75%) lacerations were statistically analyzed, correlating the preoperative variables with the postoperative visual acuity (VA). Excluded from this study were all patients with less than 6 months of follow-up, previous ocular surgery, unreliable information on VA, intraocular foreign bodies and endophthalmitis. When a bilateral injury was detected, only 1 eye was randomly chosen. Results: It was observed, after statistical analysis (multivariate analysis), that the most important factors related to postoperative poor VA (less than 20/100) were: the length of the laceration, the elapsed time between the injury and the surgery and the presence or absence of vitreous loss, cataract (lens damage), hyphema, laceration posterior to rectus muscle insertion and retinal detachment. Conclusion: With this study, it was possible to point out the most important factors related to visual prognosis in open globe injuries. The results found are similar to results previously reported.
Ocular Involvement in Leukemia – A Study of 288 Cases
Authors: Reddy S.C. , Jackson N. , Menon B.S.
Published: October 2003

Two hundred and eighty-eight newly diagnosed cases of leukemia (164 males and 124 females, 167 adults and 121 children, 245 acute and 43 chronic, 151 myeloid and 137 lymphoid), aged between 6 weeks and 78 years, were examined for eye changes in the oncology wards within 2 days of diagnosis before starting chemotherapy. Ocular lesions were present in 102 patients (35.4%) – retinal vascular changes in 91 (31.6%); infiltration of ocular tissues in 5 (1.7%), and neuro-ophthalmic signs in 6 (2.1%) cases. Some of the patients had more than one ocular lesion in one or both eyes. The eye changes were seen more often in adults (49.1%) than in children (16.5%), and in myeloid leukemia (41.0%) than in lymphoid leukemia (29.2%). Eye symptoms were present in 29 patients (10%) at initial diagnosis. Since ocular lesions were detected in many asymptomatic leukemia patients, eye examination should be included as a part of routine evaluation at initial diagnosis in these patients.
Asymptomatic Cytomegalovirus Retinitis after Cardiac Transplantation
Authors: Erakgun Tansu , Afrashi Filiz , Nalbantgil Sanem , Ozbaran Mustafa , Mentes Jale
Published: October 2003

Purpose: To determine the prevalence and the risk factors of cytomegalovirus (CMV) retinitis after cardiac transplantation in visually asymptomatic patients. Methods: Ophthalmoscopic examinations including fundus fluorescein angiography were performed in asymptomatic patients who had cardiac transplantation at Ege University Hospital between April 1998 and June 2002 to screen for evidence of diagnostic CMV retinitis lesions to determine the prevalence in this population. Results: Thirteen patients (aged 40 ± 12.6) who had cardiac transplantation underwent ophthalmoscopic examination 2–50 months (23.5 ± 16.2 months; mean ± SD) after transplantation. All recipients had positive serology to CMV before transplantation. During the study period, 3 patients developed asymptomatic CMV reactivation. One patient developed CMV disease (pneumonia). All of the patients were visually asymptomatic during the study period. Two patients (15%) had a history of diabetes mellitus and chronic severe arterial hypertension. Seven recipients (53%) had been heavy cigarette smokers and 3 patients (23%) had hyperlipidemia. Two (15%) of 13 patients with arterial hypertension and diabetes had evidence of asymptomatic active CMV retinitis. These patients were treated with intravenous ganciclovir. Conclusions: Active cytomegalovirus retinitis lesions were found in 2 (15%) of 13 cardiac transplantation patients who had no visual symptoms. We think that the patients with systemic microvascular risk factors such as diabetes, hypertension and smoking should be screened closely for the development of CMV retinitis after cardiac transplantation even if the patients have no visual symptoms.
Transient Raise of Endothelin-1 Plasma Level and Reduction of Ocular Blood Flow in a Patient with Optic Neuritis
Authors: Haufschild Timo , Shaw Sidney G. , Kaiser Hedwig J. , Flammer Josef
Published: October 2003

Purpose: To analyze how far an ischemic component might have been involved in optic neuritis. Methods: Case report: a 32-year-old man with symptoms characteristic for optic neuritis underwent extensive clinical, laboratory/serological and vascular examination for systemic associations and vascular involvement. Results: The patient was found to have a temporary ocular blood flow dysregulation and increased plasma endothelin-1 levels which decreased after the acute phase of the optic nerve. Conclusions: We conclude that there might be an ischemic component in this patient with optic neuritis and hypothesize that this ischemic component is at least in part due to a temporarily increased endothelin-1 level.
Treatment Failures and Relapses in Onychomycosis: A Stubborn Clinical Problem
Authors: Arrese Jorge E. , Piérard Gérald E.
Published: October 2003

The therapeutic outcome of onychomycoses is uncertain. Comparative short-term efficacy studies on antifungals abound and report contradictory findings. Few unbiased follow-up studies have scrutinized the long-term outcome. Basically, none of the current antifungals can guarantee cure in all instances. In addition, relapses are not rare. The causes of therapeutic failure in onychomycoses are multiple. The most important are the lack of diagnostic accuracy, inadequate antifungal choice or delivery modality, and presence of dormant conidia, sequestrated mycelium pockets or resistant fungal species. The concept of fungicidal drug derived from selected in vitro studies appears irrelevant in clinical practice.
High Iron and Low Ascorbic Acid Concentrations in the Dermis of Atopic Dermatitis Patients
Authors: Leveque Nathalie , Robin Sophie , Muret Patrice , Mac-Mary Sophie , Makki Safwat , Humbert Philippe
Published: October 2003

Background: Atopic dermatitis (AD) is a chronic inflammatory skin disease in which reactive oxygen species (ROS) may be involved. Iron catalyses ROS formation and ascorbic acid (AA) scavenges these species. Objective: The aim of this work was to determine iron and AA levels in AD patients’ dermis and to compare their concentrations with those of healthy volunteers’ dermis. Methods: Five AD patients and 5 healthy subjects (controls) were enrolled in this study. Iron and AA were collected from human dermis by microdialysis and assessed by atomic absorption spectrometry and gas chromatography-mass spectrometry, respectively. Results: The AD dermis demonstrated higher iron concentrations (44.3 ± 4.6 µg/l) compared to controls (21.8 ± 1.2 µg/l) as well as a significantly lower concentration of AA (46.7 ± 0.6 vs. 176.8 ± 14.5 µg/ml, respectively). Conclusion: These results suggest that iron and AA dermis levels could be indicators of inflammatory tissues and might be implicated in dermatological diseases such as AD.
Estrogen Dermatitis: A Dendritic-Cell-Mediated Allergic Condition
Authors: Yotsumoto Shinichi , Shimomai Koji , Hashiguchi Takaki , Uchimiya Hiroshi , Usuki Kazunari , Nishi Masayuki , Kanekura Takuro , Kanzaki Tamotsu
Published: October 2003

Background: Most estrogen dermatitides are induced by local or systemic contact dermatitis where dendritic cells are central, and tamoxifen has a blocking effect on dendritic cells. Methods: We present 5 cases of estrogen dermatitis in which the clinical features were prurigo, urticaria, acneiform eruption and annular erythema. Results: Tamoxifen was effective in 3 of 4 cases. Three of 4 biopsy specimens showed the formation of Langerhans cell nests in the epidermis and hair follicles and perivascular infiltration of CD4+ and CD8+ lymphocytes in the dermis. Conclusion: These results suggest that a dendritic-cell-mediated allergic mechanism is involved in estrogen dermatitis.
Evaluation of Medium-Dose UVA1 Phototherapy in Localized Scleroderma with the Cutometer and Fast Fourier Transform Method
Authors: de Rie M.A. , Enomoto D.N.H. , de Vries H.J.C. , Bos J.D.
Published: October 2003

Purpose: To evaluate the efficacy of medium-dose UVA1 phototherapy in patients with localized scleroderma. Method: A controlled pilot study with medium-dose UVA1 (48 J/cm2) was performed. The results were evaluated by means of a skin score and two objective methods for quantifying sclerosis (cutometer and fast Fourier transform method). Patients were treated 4 times a week for 5 weeks. The follow-up period was 12 weeks. Results: All patients responded to therapy. Skin score and cutometer results showed improvement of skin elasticity of treated skin compared to control skin. Fast Fourier transform measurements showed no change in bundle orientation ratio and spacing. Conclusion: We concluded that treatment for 12 weeks 4 times a week with medium-dose UVA1 may be a beneficial therapy and a well-tolerated treatment modality for localized scleroderma (morphea). After 12 weeks, improvement of skin sclerosis can be detected by skin score and cutometer measurements but not by the fast Fourier transform method.
Local Pathogenic Bacteria in Allergic Rhinitis: A Novel Concept of Its Pathogenesis
Authors: Glück Ulrich , Gebbers Jan-Olaf
Published: October 2003

Background: It is still unclear to what extent microorganisms are involved in the pathogenesis of allergic rhinitis. Objective: Therefore, we examined the mucosal colonization with potential pathogenic bacteria (PPB) of the nasal cavity in allergic and nonallergic subjects. Methods: In an open prospective study of 389 office workers (297 men, mean age 42.5 years, and 92 women, mean age 36.7 years), bacterial swabs were taken selectively from both nasal cavities. Standard skin tests for various aeroallergens and negative control tests were conducted in parallel in these subjects. Results: In the 389 subjects, we found positive skin tests in 58 (15%); 37 of these revealed a high level of sensitivity, whilst the other 21 persons had low to moderate levels. Ninety percent of the 58 sensitive persons had PPB in their nasal cavity while only 36% (119) of the remaining 331 subjects with negative skin tests were shown to have PPB in nasal cultures (p < 0.001). Sixty-four percent of the sensitized subjects with PPB were found to have more than 2 PPB species and a positive correlation with the intensity of the skin reaction. In contrast, only 18% (22) of the 119 nonallergic test persons with PPB had more than 1 PPB species. Conclusions: This finding of an unusually high frequency of nasal PPB in subjects with positive skin tests to aeroallergens may indicate an involvement of PPB in the pathogenesis of allergic rhinitis. Yet, further data are still lacking to support this novel concept.
Three-Dimensional Conformal Radiotherapy for Treatment of Extensive Juvenile Angiofibroma: Report on Two Cases
Authors: Beriwal Sushil , Eidelman Anthony , Micaily Bizhan
Published: October 2003

These case reports describe the application of three-dimensional conformal radiotherapy for the treatment of extensive juvenile angiofibroma. The affected areas included the pterygomaxillary fossa, infratemporal fossa, orbit, middle cranial fossa and maxillary sinus. Three-dimensional conformal radiotherapy was used to deliver the tumor dose of 3,800–4,140 cGy. The radiation dose to the surrounding normal structures including the optic nerve, optic chiasm, spinal cord, parotid and brain was limited. The tumor showed an excellent clinical and radiological response in both patients. There was no appreciable late toxicity. In conclusion, three-dimensional conformal radiotherapy provides several advantages over conventional radiotherapy in the treatment of extensive juvenile angiofibroma.
Maternal Hypertensive Disorders Are an Independent Risk Factor for the Development of Necrotizing Enterocolitis in Very Low Birth Weight Infants
Authors: Bashiri Asher , Zmora Ehud , Sheiner Eyal , Hershkovitz Reli , Shoham-Vardi Ilana , Mazor Moshe
Published: October 2003

Objective: The purpose of this study was to compare complications and outcome of preterm neonates weighing ≤1,500 g who developed necrotizing enterocolitis (NEC) to neonates without NEC. Study Design: During January, 1995 to December, 1998, 211 live preterm neonates were born with birth weight ≤1,500 g. A cross sectional prospective study was designed and two groups were defined: 17 neonates who developed NEC and 194 without NEC. Multiple logistic regression analysis was performed to determine independent risk factors for the development of NEC. Results: The prevalence of NEC was 8% (17/211). The following complications were found to be significantly higher among mothers of neonates with NEC: mild pre-eclampsia (11.8 vs. 2.6%, p = 0.04); severe pre-eclampsia (35.5 vs. 12.9%, p = 0.01); chronic hypertension (29.4 vs. 5.7%, p < 0.001) and low birth weight (968 ± 233 vs. 1,123 ± 257 g, p = 0.02). In contrast, mean maternal age, mean gestational age at delivery and parity were not significantly different between the groups. A multivariate analysis including the following factors: maternal hypertensive disorders, pregestational diabetes mellitus, birth weight and gestational age at delivery, found only maternal hypertensive disorders to be independent risk factors for NEC (OR = 5.21, 95% CI 1.64–16.58). Conclusions: Maternal hypertension is an independent risk factor for the development of NEC in preterm neonates weighing <1,500 g. Thus, maternal vascular disorders may play an important role in the pathophysiology of NEC.
Transabdominal Amnioinfusion Treatment of Severe Oligohydramnios in Preterm Premature Rupture of Membranes at Less than 26 Gestational Weeks
Authors: De Santis Marco , Scavo Maria , Noia Giuseppe , Masini Lucia , Piersigilli Fiammetta , Romagnoli Costantino , Caruso Alessandro
Published: October 2003

Objective: To evaluate the efficacy of transabdominal amnioinfusion on feto-neonatal and maternal morbidity and feto-neonatal mortality. Methods: We studied 71 patients with preterm premature rupture of membranes (pPROM) at <26 weeks of gestational age. Thirty-four patients were managed expectantly and 37 underwent serial transabdominal amnioinfusion with saline every 7 days in case of persistent oligohydramnios. Results: Latency period pPROM delivery, week of delivery (26.0 vs. 22.4, p < 0.001), neonatal weight (922 vs. 602, p < 0.01) and the percentage of intrauterine fetal survival were higher in treated than in control groups (64.8 vs. 32.3%, p < 0.01). In amnioinfusion-treated patients, we did not note a higher rate of complications from infection during both pregnancy and puerperium. In the amnioinfusion group, fluid loss within 6 h after infusion is the main variable in predicting pulmonary hypoplasia and neonatal survival. Conclusions: Our data suggest that amnioinfusion seems to be a low fetal and maternal risk technique that modifies the natural history of pPROM, improving fetal intrauterine stay and survival.
Acupuncture Conversion of Fetal Breech Presentation
Authors: Habek Dubravko , Čerkez Habek Jasna , Jagušt Mirjana
Published: October 2003

Aim: The aim of this study was to assess the value of acupuncture (AP) in the conversion of fetal breech presentation into vertex presentation. Patients and Methods: A randomized prospective controlled clinical study included 67 pregnant women with fetal breech presentation: 34 women with singleton pregnancies treated with manual AP (urinary bladder 67, Zhiyin) and a control group which included 33 women with singleton pregnancies without AP treatment. The AP treatment lasted 30 min a day, and was conducted during and after 34 weeks of pregnancy with simultaneous cardiotocography. Results: The success rate of the AP correction of fetal breech presentation is 76.4% (26 women), and spontaneous conversion without AP in vertex presentation is observed in 15 women (45.4%; p < 0.001). Conclusions: We believe that AP correction of fetal malpresentation is a relatively simple, efficacious and inexpensive method associated with a lower percentage of operatively completed deliveries, which definitely reflects in improved parameters of vital and perinatal statistics.
Abnormal Umbilical Cord Dopplers May Predict Impending Demise in Fetuses with Sacrococcygeal Teratoma
Authors: Olutoye Oluyinka O. , Johnson Mark P. , Coleman Beverly G. , Crombleholme Timothy M. , Adzick N. Scott , Flake Alan W.
Published: October 2003

Objective: To identify factors predictive of fetal demise in fetuses with sacrococcygeal teratoma (SCT). Method: The recent management of monochorionic twins discordant for a large SCT and a singleton with a large SCT were reviewed. Results: Serial fetal echocardiography and ultrasonography with Doppler flow measurements documented rapid growth of the SCT in both cases with a relatively modest increase in combined cardiac output. No placentomegaly or hydrops was observed at any time. In both fetuses with SCT, evolution of abnormal umbilical artery waveforms was observed with the ultimate development of reversed end-diastolic umbilical arterial flow that was followed by sudden fetal demise. Conclusion: Death in these 2 fetuses with large SCTs in the absence of placentomegaly/hydrops or hemodynamic changes suggestive of evolving high-output failure suggests a previously unrecognized mechanism of death in fetuses with large rapidly growing SCTs. In these cases, fetal demise may only be heralded by abnormal umbilical artery waveforms that progress to the premorbid observation of reversed diastolic umbilical artery blood flow. Umbilical artery waveform analysis should be closely monitored with other hemodynamic parameters in fetuses with large SCTs. In such fetuses, depending on the gestational age, abnormalities in umbilical artery waveform should be considered indications for early delivery or in utero intervention to prevent fetal demise.
Comparison of Magnetic Resonance Imaging and Ultrasonography in the Prenatal Diagnosis of Congenital Thoracic Abnormalities
Authors: Matsuoka Shozo , Takeuchi Kyousuke , Yamanaka Yoshihiko , Kaji Yasushi , Sugimura Kazuro , Maruo Takeshi
Published: October 2003

Objectives: To evaluate prenatal MRI in the diagnosis of fetal thoracic abnormalities and to determine whether MRI provides useful information in addition to that of ultrasonography (US). Methods: Ultrafast MR scanning was performed in 7 pregnant women in whom US was suspicious of fetal congenital anomalies of the thorax [3 cases of congenital diaphragmatic hernia (CDH), 3 cases of chylothorax and 1 case of congenital cystic adenomatoid malformation (CCAM) type III]. The presence, position, size and characteristics of the congenital lesions were determined and compared with postnatal diagnoses. Results: The MRI diagnoses were 3 cases of CDH, 2 of chylothorax and one each of esophageal atresia and CCAM type III. The results of MRI were in agreement with those of US in 6 cases and in disagreement in 1 case of esophageal atresia. Final diagnoses were confirmed at surgery or autopsy in all fetuses. Combined use of MR and US imaging enabled a correct diagnosis in 5 cases and led to an error in the diagnosis of 1 fetus with bronchial stenosis, which had been diagnosed as CCAM type III by US and MRI. MRI led to a correct diagnosis in 1 fetus with esophageal atresia, in whom US had been equivocal in the prenatal diagnosis. Conclusion: MRI helped further characterize the fetal thoracic lesions and confirmed or changed the prenatal diagnosis based on US. MRI seems to be powerful in the prenatal diagnosis of thoracic lesions that are atypical or complicated by multiple abnormalities.
New Diagnostic Avenues in Inflammatory Bowel Diseases
Authors: Schreyer Andreas G. , Gölder Stefan , Seitz Johannes , Herfarth Hans
Published: October 2003

The modalities for diagnostic imaging in patients with inflammatory bowel disease (IBD) have dramatically changed in the last decade. Several years ago the only methods to assess the small bowel were conventional enteroclysis or a small bowel ‘follow through’. Nowadays, wireless capsule endoscopy as well as magnetic resonance imaging (MRI) with virtual endoscopy represent new evolving methods to depict and assess the small bowel. This article describes these recently introduced methods in the diagnostic assessment of the small bowel and discusses the clinical significance based on the current literature.
Excretory-Secretory Products Secreted by Paragonimus westermani Delay the Spontaneous Cell Death of Human Eosinophils through Autocrine Production of GM-CSF
Authors: Shin Myeong Heon , Seoh Ju-Young , Park Hae-Young , Kita Hirohito
Published: October 2003

Background: Eosinophils play important roles in tissue inflammatory responses associated with helminth infections. Excretory-secretory products (ESP) produced by tissue-invasive helminths contain a large quantity of proteolytic enzymes that can modulate the host’s immune responses. However, little is known regarding the roles of worm-derived products that are responsible for eosinophilic inflammatory responses in helminth infections. Objective: In the present study, we investigated whether ESP produced by Paragonimus westermani, which cause pulmonary or extrapulmonary paragonimiasis in human beings, regulates both cell survival and death of human eosinophils. Methods: The ESP was obtained from P. westermani newly excysted metacercariae (PwNEM). Eosinophils were purified from peripheral blood of healthy donors, and the purified eosinophils were incubated with or without the ESP secreted by PwNEM. The viability of eosinophils was assessed by staining with propidium iodide using the flow cytometer. Results: When eosinophils were incubated with a low concentration of the ESP produced by PwNEM, which totally consists of proteolytic enzymes, eosinophil cell death was delayed compared with results for cells incubated with medium alone. In fact, the ESP at a low concentration stimulated eosinophils to produce detectable levels of GM-CSF that can delay eosinophil cell death. In contrast, eosinophil cell death was dose-dependently accelerated when cells were incubated with high concentrations of the ESP. To see whether the dose-dependent biphasic survival effect of the ESP on eosinophils is primarily due to the protease activity contained in the ESP, a high dose of the ESP was treated with heat at 56°C for 30 min before being added to eosinophils. Attenuating protease activity in a high dose of the ESP by heat treatment reversed the ESP-afforded eosinophil cell death. This prolonged survival of eosinophils induced by the heated ESP was remarkably inhibited by anti-GM-CSF-neutralizing mAb and Jak2 kinase inhibitor AG-490. Conclusion: These results suggest that the proteases in the ESP secreted by PwNEM are able to regulate eosinophil survival through the autocrine production of GM-CSF. Thus, the enhanced eosinophil survival induced by Paragonimus-secreted products may contribute to the elicitation of eosinophilic inflammatory responses at the worm-infected lesion in human paragonimiasis.
Eosinophil Count in Nasal Mucosa Is More Suitable than the Number of ICAM-1-Positive Nasal Epithelial Cells to Evaluate the Severity of House Dust Mite-Sensitive Allergic Rhinitis: A Clinical Correlation Study
Authors: Klaewsongkram Jettanong , Ruxrungtham Kiat , Wannakrairot Pongsak , Ruangvejvorachai Preecha , Phanupak Praphan
Published: October 2003

Background: House dust mite (HDM)-sensitive allergic rhinitis is a perennial rhinitis with persistent nasal inflammation. Currently, there are no reliable parameters to monitor the severity of perennial allergic rhinitis. The purpose of this study was to evaluate correlations between clinical and laboratory parameters in patients with HDM-sensitive allergic rhinitis. Methods: We measured nasal symptoms, did the Dermatophagoides pteronyssinus (Der P) skin prick test (SPT), evaluated the Der P allergen nasal challenge threshold, and laboratory parameters [(1) inflammatory cell count from nasal mucosal scraping specimens: eosinophils and neutrophils and (2) immunocytochemistry: ICAM-1 expression on nasal epithelial cells] in 20 cases of HDM-sensitive allergic rhinitis and performed correlation tests between all parameters. Results:  The wheal diameter induced by Der P SPT was significantly correlated with the Der P allergen nasal challenge threshold (p = 0.001). The number of eosinophils from nasal mucosal scrapping specimens was correlated with the ICAM-1 expression on nasal epithelial cells (p = 0.039), the number of neutrophils from nasal mucosal scrapping specimens (p = 0.001), and nasal stuffiness (p = 0.037) but did not correlate with total nasal symptom scores. Conclusion: Clinical symptoms of HDM-sensitive allergic rhinitis showed a poor correlation with inflammatory parameters. The eosinophil count in nasal mucosa is correlated with ICAM-1 expression and more suitable than ICAM-1 levels to evaluate the severity of HDM-sensitive allergic rhinitis. This study also supports the role of the SPT in the diagnosis of nasal allergy to HDM.
Helicobacter pylori Infection, Vitamin B12 and Homocysteine
Authors: Dierkes Jutta , Ebert Matthias , Malfertheiner Peter , Luley Claus
Published: October 2003

It has been suggested that there is an association between Helicobacter pylori infection, reduced cobalamin absorption and cobalamin status and, consequently, elevated homocysteine levels. This would offer an explanation why H. pylori infection is associated with coronary heart disease. To date, more than 25 studies have been published that either deal with H. pylori infection and homocysteine, H. pylori infection and cobalamin status, or both. The design of these studies differs widely in terms of definition of H. pylori status, measuring cobalamin status, selection of study cohorts and geographical study areas. Therefore, results are fairly inconclusive at present and do not suggest a major role of H. pylori infection in the development of cobalamin deficiency and elevated homocysteine levels.
Sugar Intake, Taste Changes and Dental Health in Crohn’s Disease
Authors: Schütz Tatjana , Drude Clemens , Paulisch Erika , Lange Klaus-Peter , Lochs Herbert
Published: October 2003

Background: An increased intake of sucrose has been reported in patients with Crohn’s disease (CD). Since subclinical zinc deficiency reduces taste perception for sweet, we investigated taste perception, sucrose intake and plasma zinc levels as well as dental status in CD patients. Methods: Carbohydrate intake and plasma zinc levels were assessed in 24 CD patients and 24 age-matched controls (Con). Taste threshold for sucrose, oral hygiene and caries prevalence were evaluated. Results: In CD a higher sucrose intake (CD 107.1 ± 27.7 vs. Con 71.9 ± 13.7 g/day; p < 0.001), a higher taste threshold for sweet (CD 7.31 vs. Con 2.91 g/l; p < 0.001) and lower plasma zinc levels (CD 11.5 ± 1.5 vs. Con 13.5 ± 2.0 µmol/l; p < 0.001) were found. API was poor (CD 85.4 ± 23.6, Con 31.8 ± 24.1, p < 0.001) and correlated with sucrose intake (p < 0.01). Caries prevalence was increased in patients with longer disease (>3 years) (DMFT index: >3 years 15.6 ± 5.7 vs. <3 years 9.5 ± 4.3; p < 0.05). Conclusion: Dental status in CD patients is poor. Both increased sugar consumption and insufficient oral hygiene seem to cause the higher caries prevalence. Obviously, patients with CD belong to a high-risk group, and preventive measures should be taken early in the course of the disease.
Impact of Body Mass Index on Fasting Blood Glucose Concentration among Helicobacter pylori Carriers
Authors: Kyriazanos Ioannis D. , Sfiniadakis Ioannis , Dimakos Panagiotis , Gizaris Vasilios , Datsakis Konstantinos , Dafnopoulou Aggeliki
Published: October 2003

Background/Aims: Despite the fact that Helicobacter pylori (Hp) is regarded as a major gastroduodenal pathogen, it has recently been suggested to be an important factor for non-gastroenterologic conditions such as diabetes mellitus. Accordingly, it seems that Hp infection may have implications in glycemic control and in fasting plasma glucose concentrations. As overnutrition and obesity are directly related to impaired glucose tolerance, the aim of the present study was to determine whether Hp infection leads to alterations in fasting plasma glucose concentrations of Hp carriers and especially in relation to their body mass index. Methods: Serum was obtained from 224 young, male navy recruits. An enzyme-linked immunosorbent assay to detect Hp-specific IgG serum antibodies as well as gastroscopy along with biopsy was used to identify the infected individuals. Serum levels of glucose, urea, creatinine and uric acid were also determined. Non-fasting subjects and persons with abnormal oral glucose tolerance curve test were excluded. Results: Among Hp-positive individuals, obese persons presented with a significantly lower mean blood glucose level than non-obese persons. Obese Hp-contaminated participants had significantly lower mean fasting blood glucose concentrations as well as a significantly smaller percentage of participants with abnormal elevated blood glucose levels than obese participants negative to Hp infection. Conclusions: Our data suggest that obesity in combination with Hp infection may induce an enhanced response to insulin leading to reduced fasting blood glucose levels, among Hp-positive obese persons in comparison to Hp-positive lean persons.