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[Morphologic studies of the pathogenesis of ligneous conjunctivitis].

The cases of ligneous conjunctivitis published since 1964 are presented in a review of the literature. A total of 84 cases have been described. The predominance of this disease in women is lower than was previously thought. Ligneous conjunctivitis tends to occur more frequently in children. However, it is not a "disease of little girls". Two cases are described in the present paper, including pathomorphological studies. In both cases, neutrophilic granulocytes were studied by electron microscopy. The results are compared with a control case and with corresponding reports in the literature. The number of granules in the neutrophilic granulocytes was significantly reduced in both cases. In one of the cases studied the granules were increased in size. These findings support the hypothesis that ligneous conjunctivitis could be the result of a lowered resistance associated with a disturbance of wound healing.

Biopsy↗

Convection warmers--not just hot air.

We sought to determine whether the forced air convection warmers (nine Bair Huggers, Augustine Medical, and one Warm Touch, Mallinkrodt Medical) used in our operating theatres could be a source of microbial pathogens. Agar plates were placed directly in the air stream of the warmers. Four of these grew potentially pathogenic organisms. When the warmers were set to blow through perforated blankets, no growth occurred. Three of the warmers were swabbed and sites of colonisation were found in their hoses. After fixing a microbial filter to the end of the hose, organisms were no longer detectable. We conclude that these warming devices are a potential source of nosocomial infection. They should only be used in conjunction with perforated blankets, should have their microbial filters changed regularly and their hoses sterilised. The inclusion of a microbial filter into the nozzle of the hose could be incorporated into the design of the warmer.

Air Microbiology↗

Transcriptional regulation of ferric citrate transport in Escherichia coli K-12. Fecl belongs to a new subfamily of sigma 70-type factors that respond to extracytoplasmic stimuli.

Transcription of the ferric citrate transport system of Escherichia coli K-12 is repressed by Fe(2+)-Fur and activated by ferric citrate. Ferric citrate does not have to enter the cytoplasm; it initiates a signal transduction mechanism by binding to the outer membrane receptor FecA. Presumably, a conformational change is transmitted in a TonB-dependent manner to the FecR protein. FecR activates FecI, and FecI activates transcription of the fecABCDE transport genes. In this communication, FecI was isolated after cloning fecI downstream of an ideal ribosome-binding site. Overexpressed FecI formed inclusion bodies which were solubilized and purified in active form using a mild detergent. FecI, in conjunction with RNA polymerase core enzyme, directed transcription from the fecA promoter in an in vitro run-off transcription assay. Furthermore, FecI retarded the electrophoretic mobility of a specific 75 bp DNA fragment located upstream of fecA. An in vivo competition experiment between the fecA promoters of wild-type and mutant strains identified the nucleotide positions 2747, 2749, 2751 and 2753, located within the 75 bp fragment, as important for FecI-induced transcription. Mobility band shift of fecA promoter DNA caused by cell lysates required growth of cells in the presence of ferric citrate and expression of FecA, FecI and FecR. These data support the previous assignment of FecI, based on sequence homologies, to a new subfamily of eubacterial RNA polymerase sigma 70 factors that respond to extra-cytoplasmic stimuli and regulate extracytoplasmic functions.

Bacterial Proteins↗

Detection of primary breast carcinoma with a dedicated, large-field-of-view FDG PET mammography device: initial experience.

PURPOSE: To prospectively assess a dedicated, large field of view positron emission tomography (PET) mammographic device for imaging primary breast carcinoma. MATERIALS AND METHODS: Institutional review board approval was obtained for this study, and all patients provided written informed consent prior to participation. Subjects were recruited from a cohort of patients in whom diagnostic mammography and/or ultrasonography demonstrated lesions that were highly suggestive of malignancy. Twenty-three patients who met the inclusion criteria were subsequently imaged by using a dedicated PET mammography unit that was developed in conjunction with the Thomas Jefferson National Accelerator Facility (Newport News, Va). One hour after administration of 2.0-2.5 mCi (74.0-93.5 MBq) of fluorodeoxyglucose, 5-minute PET mammography of the affected breast was performed. Images were processed and reconstructed in the transverse craniocaudal and coronal planes. For each lesion, image-guided core-needle biopsy was performed immediately after PET mammography. Conventional mammography results and histologic findings were correlated with PET mammography images. The sensitivity, specificity, negative predictive value, and positive predictive value of PET mammography for demonstrating malignant lesions were calculated. RESULTS: PET mammography demonstrated 20 focal abnormalities, of which 18 were malignant and two were benign. Both benign lesions represented areas of fat necrosis. Three of 20 malignant lesions demonstrated at conventional mammography were not demonstrated at PET mammography. The overall sensitivity of PET mammography for malignancy was 86% (95% confidence interval: 65%, 95%), with a positive predictive value of 90% (95% confidence interval: 70%, 97%). The calculated specificity was 33% (95% confidence interval: 2%, 79%), and the negative predictive value was 25% (95% confidence interval: 1%, 70%). CONCLUSION: These pilot data suggest that PET mammography can demonstrate small primary breast malignancies.

Adenocarcinoma↗

Combination erythropoietin-hydroxyurea therapy in sickle cell disease: experience from the National Institutes of Health and a literature review.

Erythropoietin is being used more widely in the management of sickle cell disease (SCD, inclusive of homozygous sickle beta, SS, and compound heterozygous sickle beta thalassemia, Sbeta0 thal), often in conjunction with hydroxyurea (HU). Herein, we summarize the published experience with erythropoietin use in SCD, in 39 patients (SS, n = 30; Sb0 thal, n = 9) who were treated between 1990 and 1996; and in 13 patients with sickle syndromes (SS, n = 12, compound heterozygous SC disease, n = 1) who were treated with erythropoietin or darbepoietin at the National Institutes of Health (NIH) since 2002. The dose range of erythropoietin for SCD in the published series, at a median of > 200 U/Kg/dose, is higher than that used in end-stage renal disease. The median duration of erythropoietin therapy was > or =3 months, with minimal reported side-effects. At the NIH, the median age of sickle syndrome patients who received erythropoietin or darbepoietin (both referred to as EPO in the NIH series) was 51 (24 to 70) years; 12/13 patients had sickle-associated pulmonary hypertension. Eleven out of the 13 patients were treated with both HU and EPO for > 4 months (median of 11 months on EPO) without complication. Of the 13 patients, five (all SS) with pulmonary hypertension were given EPO for reticulocytopenia (< 100,000/mL) on HU; 5/13 patients (all SS), with pulmonary hypertension, were given EPO and HU concurrently, in the light of an estimated glomerular filtration rate of < 80 mL/minute. Three of the 13 patients (2 SS, 1 SC) were treated with EPO for miscellaneous reasons. Hematologic responses, detailed herein, suggest that EPO therapy may allow more aggressive HU dosing in high-risk SCD patients and in the setting of mild renal insufficiency, common to the aging sickle cell population. Furthermore EPO appears to be safe in SCD, particularly when used in conjunction with HU. We outline our current therapeutic strategy for EPO use in SCD.

Anemia, Sickle Cell↗

Cystinosis with crystal-induced synovitis and arthropathy.

A clinically and experimentally verified intermediary form of cystinosis is described. A 30-year old patient has been examined initially for eye complications confined to the frontal segment of the eye on the cornea and conjunctiva. The joint disease received no attention despite the fact that the motor apparatus of the patient was involved from her childhood. As regards the arthrology, the disease can be classed among crystal-induced synovitis and arthropathy. The lesion of the tubular apparatus of the kidney, which cannot transform vitamin D into its active form, represents an important factor in the genesis of osteoporosis. A description of the intermediary from of cystinosis with eye, kidney and joint symptoms was not found in the literature.

Adult↗

[Bacterial conjunctivitis: most prevalent pathogens and their antibiotic sensitivity].

INTRODUCTION: Bacterial conjunctivitis is a self-limiting process, but topical antibiotic treatment is recommended to eradicate the pathogen and reduce symptom duration. Since this treatment is usually empirical and prior cultures are not normally taken, the etiological agents involved in the process are unknown. PATIENTS AND METHODS: A total of 596 conjunctival exudates from pediatric outpatients with a diagnosis of acute conjunctivitis in Medical Area 6 of Madrid, Spain, were studied over 3 years (from 2000 to 2002 inclusive). The patients were divided into three age groups: group 1 (infants), group 2 (2- to 6-year-olds) and group 3 (7- to 14-year-olds). RESULTS: A total of 428 bacteria were isolated. The most prevalent bacteria were Haemophilus influenzae (44.8 %) and Streptococcus pneumoniae (30.6 %) followed by Staphylococcus aureus (7.5 %), S. viridans (7.2 %), Moraxella catarrhalis (6.8 %) and Enterobacteriaceae (4.2 %). In 56 exudates (15.1 %), two or more bacteria were isolated and S. pneumoniae 1 H. influenzae were found in 8.1 % of the cases. By age group, S. aureus was significantly more prevalent (p < 0.0001) in group 3 than in groups 1 and 2. Isolation of Enterobacteriaceae, S. viridans and non-fermentative Gram negative bacilli was significantly more frequent (p < 0.05) in group 1 and isolation of S. pneumoniae (p < 0.05) was significantly more frequent in group 2. S. pneumoniae showed the greatest level of resistance to antibiotics used in eye drops and ophthalmic ointments. Ciprofloxacin, chloramphenicol and rifampin were active in the most prevalent pathogens. CONCLUSIONS: The most prevalent bacteria were H. influenzae and S. pneumoniae. The most active antibiotics in these pathogens were ciprofloxacin, chloramphenicol and rifampin.

Adolescent↗

Laboratory studies in chronic conjunctivitis.

Conjunctival cultures and scrapings for cytological examination were done in 852 cases of chronic conjunctivitis. Bacteria were recovered in 464. Of these, Staphylococcus sp were isolated in 91%; their etiologic importance over normal flora is questionable. Important cytological findings included atypical epithelium (three cases), Halberstaedter-Prowazek inclusion bodies (two), and eosinophils (104). Epithelial degenerative changes were common (585 cases). Crystals (105) and microorganisms (283) were other frequent findings. Active infection seems to be an uncommon cause of chronic conjunctivitis. Cultures are important in avoiding unnecessary antibiotic therapy when no organism is present. Cytological examination can be a helpful diagnostic adjunct in selected cases and is to be recommended especially in chronic follicular conjunctivitis, possible drug toxicity or allergy, dry eye states, and other atypical clinical presentations.

Bacteria↗

Ara-C cytokinetic studies in normal tissues in vivo.

The importance of including normal tissues in the design of cytokinetic-based chemotherapeutic schedules is becoming increasingly apparent. However, the lack of rapid analytical techniques to obtain quantitative cytokinetic data on target subpopulations in heterogenous normal tissues, such as the gastrointestinal and hematopoietic system, has limited the inclusion of these tissues in therapy design. Once target subpopulations are identified and/or discriminated, flow cytometry in conjunction with radioactivity measurements by liquid scintillation counting can be used to rapidly obtain quantitative cytokinetic data during drug therapy. The present paper reviews our current cytokinetic techniques and the applications and limitations of these techniques in the analysis of Ara-C-induced perturbations in the small intestine and hematopoietic system. Cell cycle information both prior to and 30 hrs following a single Ara-C treatment was obtained in the intestinal crypts and femoral marrow population using radioactive precursor uptake and flow cytometric techniques. In addition, the relationship between crypt cell survival and animal lethality following Ara-C treatment was determined to better understand the impact of a damage to a regenerative population on the "clinical endpoint" of animal survival. Understanding the principles behind the normal tissue toxicity which occurs during multidose treatment will hopefully allow modulation of this toxicity through the rational design of optimal chemotherapeutic schedules.

Animals↗

Inhibition of tetraphenylphosphonium-induced NMR-visible lipid accumulation in human breast cells by chlorpromazine.

The effects of chlorpromazine (CPZ) on the lipid accumulation induced by the cationic lipophilic compound tetraphenylphosphonium chloride (TPP) were examined using proton nuclear magnetic resonance spectroscopy (NMR), lipid extraction and thin layer chromatography (TLC), and electron microscopy (EM). Chlorpromazine at concentrations of 12 or 25 microM significantly reduced the NMR-visible lipid accumulation induced by a 48-h treatment with 6.25 microM TPP in the human breast cell line, HBL-100, without affecting cell viability. TPP caused threefold increases in whole-cell triglyceride levels that were attenuated by the addition of CPZ. Electron micrographs of TPP-treated HBL-100 cells showed that the destruction of mitochondria was accompanied by the accumulation of lipid droplets and myelinoid bodies. The addition of CPZ to TPP-treated cells reduced the occurrence of lipid droplets but not of mitochondrial destruction. Treatment with CPZ, in the presence or absence of TPP, resulted in large cytoplasmic inclusions indicating the inhibition of lysosomal metabolism. The induction and attenuation of NMR-visible lipids in conjunction with concomitant changes in both intracellular lipid droplets and whole-cell triglyceride levels provides evidence that NMR-visible lipids arise from cytoplasmic neutral lipid droplets. The observation that CPZ, a known inhibitor of lysosomal and cytosolic lipid metabolism, attenuates the formation of neutral triglycerides indicates that lysosomal processing may be a major step in the accumulation of NMR-visible lipid in breast cell lines.

Breast↗

Use of complementary and alternative medicine by HIV-infected outpatients in Ontario, Canada.

Little is known about complementary and alternative medicine (CAM) use in Canadian patients with HIV. We sought to determine the prevalence of CAM use by patients attending HIV outpatient clinics in Ontario, Canada, and to compare the characteristics of users and nonusers. Impact of CAM definition on reported utilization rates was also assessed, specifically in relation to the inclusion and exclusion of vitamins, minerals, and multivitamins in CAM definition. In-person interviews were conducted between 1999 and 2001 with 104 HIV-positive outpatients enrolled in the HIV Ontario Observational Database project (HOOD) and attending HIV outpatient clinics in Ontario. Self-reported CAM utilization and demographic data were collected. Clinical data were obtained from medical chart review. Seventy-seven percent of participants reported current CAM use. Inclusion of vitamins and minerals (CAMVIT) increased this estimate to 89%. Nearly all patients used CAM in conjunction with antiretroviral medications. Out of pocket costs ranged from CAD$0 to more than CAD$250 per month. Most patients reported CAM use was beneficial and had improved their overall health. Female gender, HIV risk group, number of prescriptions, and overall number of drugs used were associated with CAM use. CAM use in Canadian patients with HIV is extremely common, with higher use among women. The definition of CAM has a substantial impact both on reported prevalence rates and on predictors of CAM use.

Adult↗

Pseudorabies virus glycoprotein M inhibits membrane fusion.

A transient transfection-fusion assay was established to investigate membrane fusion mediated by pseudorabies virus (PrV) glycoproteins. Plasmids expressing PrV glycoproteins under control of the immediate-early 1 promoter-enhancer of human cytomegalovirus were transfected into rabbit kidney cells, and the extent of cell fusion was quantitated 27 to 42 h after transfection. Cotransfection of plasmids encoding PrV glycoproteins B (gB), gD, gH, and gL resulted in formation of polykaryocytes, as has been shown for homologous proteins of herpes simplex virus type 1 (HSV-1) (A. Turner, B. Bruun, T. Minson, and H. Browne, J. Virol. 72:873-875, 1998). However, in contrast to HSV-1, fusion was also observed when the gD-encoding plasmid was omitted, which indicates that PrV gB, gH, and gL are sufficient to mediate fusion. Fusogenic activity was enhanced when a carboxy-terminally truncated version of gB (gB-008) lacking the C-terminal 29 amino acids was used instead of wild-type gB. With gB-008, only gH was required in addition for fusion. A very rapid and extended fusion was observed after cotransfection of plasmids encoding gB-008 and gDH, a hybrid protein consisting of the N-terminal 271 amino acids of gD fused to the 590 C-terminal amino acids of gH. This protein has been shown to substitute for gH, gD, and gL function in the respective viral mutants (B. G. Klupp and T. C. Mettenleiter, J. Virol. 73:3014-3022, 1999). Cotransfection of plasmids encoding PrV gC, gE, gI, gK, and UL20 with gB-008 and gDH had no effect on fusion. However, inclusion of a gM-expressing plasmid strongly reduced the extent of fusion. An inhibitory effect was also observed after inclusion of plasmids encoding gM homologs of equine herpesvirus 1 or infectious laryngotracheitis virus but only in conjunction with expression of the gM complex partner, the gN homolog. Inhibition by PrV gM was not limited to PrV glycoprotein-mediated fusion but also affected fusion induced by the F protein of bovine respiratory syncytial virus, indicating a general mechanism of fusion inhibition by gM.

Alphaherpesvirinae↗

Strategies for searching medical natural language text. Distribution of words in the anatomic diagnoses of 7000 autopsy subjects.

Computerized indexing and retrieval of medical records is increasingly important; but the use of natural language versus coded languages (SNOP, SNOMED) for this purpose remains controversial. In an effort to develop search strategies for natural language text, the authors examined the anatomic diagnosis reports by computer for 7000 consecutive autopsy subjects spanning a 13-year period at The Johns Hopkins Hospital. There were 923,657 words, 11,642 of them distinct. The authors observed an average of 1052 keystrokes, 28 lines, and 131 words per autopsy report, with an average 4.6 words per line and 7.0 letters per word. The entire text file represented 921 hours of secretarial effort. Words ranged in frequency from 33,959 occurrences of "and" to one occurrence for each of 3398 different words. Searches for rare diseases with unique names or for representative examples of common diseases were most readily performed with the use of computer-printed key word in context (KWIC) books. For uncommon diseases designated by commonly used terms (such as "cystic fibrosis"), needs were best served by a computerized search for logical combinations of key words. In an unbalanced word distribution, each conjunction (logical and) search should be performed in ascending order of word frequency; but each alternation (logical inclusive or) search should be performed in descending order of word frequency. Natural language text searches will assume a larger role in medical records analysis as the labor-intensive procedure of translation into a coded language becomes more costly, compared with the computer-intensive procedure of text searching.

Abstracting and Indexing↗

Isolation of Chlamydia psittaci from nasal and conjunctival exudate of a domestic cat.

A feline strain of Chlamydia psittaci was isolated in tissue culture from nasal and conjunctival swabs from a free range domestic cat with bilateral conjunctivitis and rhinitis, living in the Liverpool area of the UK. The isolate was identified as C psittaci on the basis of its characteristic inclusion morphology in cell culture and by means of specific indirect immunofluorescence with known C psittaci specific antiserum. The isolate could be differentiated from other chlamydiae of non-feline origin by its amino acid nutritional requirements.

Animals↗

Ocular rosacea in childhood.

PURPOSE: To describe the clinical characteristics and treatment response of ocular rosacea in the pediatric population. DESIGN: Retrospective case series. METHODS: The clinic charts of consecutive pediatric cases of ocular rosacea were evaluated over a 34-month period. Minimal diagnostic inclusion criteria were the presence of posterior eyelid inflammation including meibomian gland inspissation and lid margin telangiectasis, in conjunction with conjunctival injection or episcleritis. RESULTS: Six patients ranged from 3 to 12 years of age at presentation. All shared a long history of ocular irritation and photophobia. Five patients (83%) were female and had bilateral involvement. Eyelid telangiectases and meibomian gland disease were present in all cases. Three patients (50%) had sterile corneal ulcers. Only two patients (33%) had cutaneous involvement at the time of diagnosis. All patients experienced significant improvement with a combination of oral antibiotics (doxycycline or erythromycin), with or without topical antibiotics (erythromycin or bacitracin) or topical steroids (fluorometholone). CONCLUSION: Ocular rosacea in children may be misdiagnosed as viral or bacterial infections. Unlike in adults, associated cutaneous changes are uncommon. Most disease is bilateral, although involvement may be asymmetric. Response to conventional treatment is excellent, although long-term treatment may be necessary to prevent relapses.

Anti-Bacterial Agents↗

Compliance with American Academy of Pediatrics and American Public Health Association illness exclusion guidelines for child care centers in Maryland: who follows them and when?

BACKGROUND: In 1992, the American Academy of Pediatrics and the American Public Health Association jointly published guidelines for temporary exclusion of sick children from child care. However, little is known about key stakeholders' compliance with these guidelines. OBJECTIVES: The purpose of this work was to compare pediatricians', parents', and child care providers' compliance with American Academy of Pediatrics guidelines and determine predictors for higher rates of compliance. METHODS: We conducted a cross-sectional survey of 215 randomly selected Maryland pediatricians, 223 parents, and 192 child care providers from 22 Baltimore, Maryland, child care centers from January to July 2004. Questionnaires contained the following 6 case vignettes depicting common child care illnesses: upper respiratory infection, conjunctivitis, gastroenteritis, mild febrile illness, tinea capitis, and atopic dermatitis. The instrument measured the correctness of exclusion and inclusion decisions (using American Academy of Pediatrics/American Public Health Association guidelines as gold standard) according to varying levels of fever, disease severity (eg, clear versus yellow eye discharge), familiarity with the child, and parent work schedule flexibility. RESULTS: Response rates were 71% for pediatricians, 56% for parents, and 85% for child care providers. Guideline compliance was higher for pediatricians (74%) than for child care providers (60%) and parents (61%). Only 23% of pediatricians and parents and 29% of child care providers reported familiarity with American Academy of Pediatrics/American Public Health Association guidelines by name. In general, child care providers and parents had lower false-negative rates (allowed fewer children to attend who met criteria for exclusion) than pediatricians, suggesting that pediatricians may underexclude. Child care providers and parents correctly excluded in 65%-98% of cases requiring exclusion, whereas pediatricians correctly excluded 31%-86% of cases requiring exclusion, depending on the vignette. Yet pediatricians were much more specific about which children met criteria (pediatricians correctly included 61%-93% of cases requiring inclusion versus child care providers and parents who correctly included 20%-75% of such cases), suggesting that child care providers and parents may overexclude. Compliance rates varied significantly by stakeholder, vignette (disease), level of fever, and disease severity but did not vary with the stakeholder's familiarity with the child or the flexibility of the parent's work schedule. CONCLUSIONS: Pediatricians, parents, and child care providers were unfamiliar with American Academy of Pediatrics/American Public Health Association illness exclusion guidelines by name but moderately compliant with them. When noncompliant, child care providers and parents generally overexcluded, and pediatricians underexcluded. Stakeholder- and disease-specific predictors for noncompliance gleaned from this study suggest how educational interventions aiming to increase guideline compliance could be individually tailored to child care providers, parents, and pediatricians.

Academies and Institutes↗