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Microbial colonization of human ileal conduits.

Morphological and microbiological techniques were used to locate and identify the microorganisms that colonized the human ileal conduits in 17 different patients from 5 days after surgery up to as many as 16 years of service as a urine conduit. The ecological sequence of this colonization assumes some practical importance because the ascending growth of pathogenic organisms in this essentially open, unvalved urinary tract diversion system leads to the development of life-threatening pyelonephritis. Extensive examination of the microvillus surfaces of the ilea of five accident victims by both transmission and scanning electron microscopy showed that these tissue surfaces were not colonized by bacteria, even in the absence of prophylactic antibiotic therapy, and that these surfaces were not occupied by adherent microorganisms after several years of service as a urine conduit, even when the skin surface stoma and the conduit contents were heavily colonized by bacteria and yeasts. During the initial period (10 days) of postoperative antibiotic therapy, the mucus and urine within the conduit were largely colonized by yeasts. A mixed population of yeasts and gram-positive cocci subsequently developed in the conduit itself, and gram-positive cocci were seen to be avidly adherent to epidermal cells at the stoma. As antibiotic protection was gradually withdrawn, gram-negative organisms became a part of the mixed microbial flora of the conduit contents, and some of the potentially pathogenic organisms of this group (e.g., Escherichia spp., Proteus spp., Pseudomonas spp., etc.) were isolated from patients with pyelonephritis that appeared to come from the ileal conduit.(ABSTRACT TRUNCATED AT 250 WORDS)

Bacteria↗

Oral clearance and pathogenic oropharyngeal colonization in the elderly.

The elderly have an increased incidence of oropharyngeal colonization with respiratory pathogens, a well-known risk factor for the development of pneumonia. Changes in the oral milieu may occur secondary to decreased salivary production and abnormalities in swallowing. These abnormalities, common in the elderly, may result in impaired clearance of organisms, allowing pathogenic colonization. To test this hypothesis, we performed a prospective cross-sectional analysis of 75 elderly institutionalized patients and measured oral clearance using (99m)Tc-human serum albumin (HSA) administered to the oropharynx. Oropharyngeal cultures, salivary cell populations, elastase activity, and clinical parameters were measured simultaneously. Retention of radiolabel ranged from 100% to 2.3% over 120 min of observation. Clearance in the oropharynx was significantly decreased in those patients who had oropharyngeal colonization with gram-negative bacilli (GNB), Staphylococcus aureus (SA), or yeast compared with those demonstrating normal flora by 95% confidence intervals. Decreased clearance was also seen in patients on antidepressants by 95% confidence levels. The absolute number of salivary lymphocytes/ml and buccal cells/ml was increased in colonized patients versus noncolonized persons (mean +/- SEM, 128 x 10(3) +/- 49 x 10(3), 25.4 +/- 11.6 x 10(3)). Elastase activity was elevated in patients who had GNB compared with patients without GNB (mean +/- SEM, 10.6 nM +/- 5.7, versus 2.2 nM +/- 1.2, p = 0.036). We conclude that a decrease in salivary clearance of potentially pathogenic organisms may be a major risk factor for the development of colonization in the elderly.

Aged↗

Serological study of responses to selected pathogens causing respiratory tract infection in the institutionalized elderly.

In a prospective 2-year study, serological responses to selected pathogens were analyzed in 224 episodes of fever attributable to respiratory tract infection (51.8%) or of unknown source (48.2%) in 131 residents of two long-term-care facilities. A serological response was identified in 45 episodes (20.1%): Chlamydia pneumoniae (14 episodes), Haemophilus influenzae type b (1), influenza virus type A (14), respiratory syncytial virus (RSV;2), parainfluenza virus type 3 (7), C. pneumoniae and H. influenzae (3), C. pneumoniae and influenza virus type A (2), C. pneumoniae and RSV (1), and C. pneumoniae and parainfluenza virus type 3 (1). No serological responses to Chlamydia psittaci, Chlamydia trachomatis, parainfluenza virus types 1 and 2, influenza virus type B, or Mycoplasma pneumoniae were seen. Vaccination did not affect the duration of fever in those residents with serologically confirmed influenza A. Serologically confirmed C. pneumoniae infection was detected in 9.4% of all febrile episodes. Serological responses to a second agent were detected in 33% of the patients with C. pneumoniae infections, and these dual infections were associated with an underlying malignancy (P = .02). C. pneumoniae should be recognized as a potential pathogen when choosing empirical antimicrobial therapy for respiratory tract infection in residents of long-term-care facilities.

Aged↗

Comparative genomic analyses of the vibrio pathogenicity island and cholera toxin prophage regions in nonepidemic serogroup strains of Vibrio cholerae.

Two major virulence factors are associated with epidemic strains (O1 and O139 serogroups) of Vibrio cholerae: cholera toxin encoded by the ctxAB genes and toxin-coregulated pilus encoded by the tcpA gene. The ctx genes reside in the genome of a filamentous phage (CTXphi), and the tcpA gene resides in a vibrio pathogenicity island (VPI) which has also been proposed to be a filamentous phage designated VPIphi. In order to determine the prevalence of horizontal transfer of VPI and CTXphi among nonepidemic (non-O1 and non-O139 serogroups) V. cholerae, 300 strains of both clinical and environmental origin were screened for the presence of tcpA and ctxAB. In this paper, we present the comparative genetic analyses of 11 nonepidemic serogroup strains which carry the VPI cluster. Seven of the 11 VPI(+) strains have also acquired the CTXphi. Multilocus sequence typing and restriction fragment length polymorphism analyses of the VPI and CTXphi prophage regions revealed that the non-O1 and non-O139 strains were genetically diverse and clustered in lineages distinct from that of the epidemic strains. The left end of the VPI in the non-O1 and non-O139 strains exhibited extensive DNA rearrangements. In addition, several CTXphi prophage types characterized by novel repressor (rstR) and ctxAB genes and VPIs with novel tcpA genes were found in these strains. These data suggest that the potentially pathogenic, nonepidemic, non-O1 and non-O139 strains identified in our study most likely evolved by sequential horizontal acquisition of the VPI and CTXphi independently rather than by exchange of O-antigen biosynthesis regions in an existing epidemic strain.

Amino Acid Sequence↗

Scored antibody reactivity determined by immunoblotting shows an association between clinical manifestations and presence of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. Valaisiana in humans.

An immunoglobulin G immunoblot was developed with antigenic extracts of Borrelia burgdorferi sensu stricto, B. garinii, B. afzelii, and B. valaisiana genospecies and was reacted with sera from patients with neuroborreliosis, acrodermatitis, and Lyme arthritis. A detailed analysis of the reactivities of the protein bands was performed, and a two-step scoring procedure was selected to determine the preferential reactivity of sera to one particular genospecies. The discriminative potential of 5 proteins (12-kDa, 16-kDa, 18-kDa, OspA, and 66-kDa proteins) was used as a rapid first-step scoring method, followed by scoring of 14 additional protein bands if necessary. The advantage of this procedure is the low percentage of serum samples with inconclusive results for one of the four species (10% for patients with neuroborreliosis, 6% for patients with acrodermatitis chronica atrophicans, and 6% for patients with Lyme arthritis). Among 31 serum samples from patients with neuroborreliosis, 16 were more reactive to B. garinii, 7 were more reactive to B. afzelii, 3 were more reactive to B. valaisiana, and 2 were more reactive to B. burgdorferi sensu stricto. Of 31 serum samples from patients with acrodermatitis, 26 showed a higher level of reactivity to B. afzelii. Of 34 serum samples from patients with Lyme arthritis, 21 were more reactive to B. burgdorferi sensu stricto, 10 were more reactive to B. afzelii, and 1 was more reactive to B. valaisiana. Our results suggest an organotropism of Borrelia species and provide some evidence of a pathogenic potential of B. valaisiana in humans.

Antibodies, Bacterial↗

The use of mucolysed induced sputum for the identification of pulmonary pathogens associated with human immunodeficiency virus infection.

We describe a system for diagnosis of pulmonary disease in the human immunodeficiency virus-infected patient using induced sputum and other diagnostic procedures. This system has been successfully used at San Francisco (Calif) General Hospital for more than 2 years. It utilizes outpatient facilities and reduces the need for bronchoscopy. Sputum induced by inhalation of 3% saline mist, mucolysed, concentrated by centrifugation, and stained by a rapid modified Giemsa stain was the first diagnostic specimen examined in 404 episodes of suspected human immunodeficiency virus-associated pulmonary disease in 358 patients. Pneumocystis carinii was found in 222 (55%) sputum specimens. In 118 episodes in which the sputum did not contain P carinii, bronchoscopy with transbronchial biopsy and/or bronchoalveolar lavage was performed and P carinii was found in 50 (42%). These 118 bronchoscopy results, as well as evaluation of the subsequent clinical course of those patients who accounted for 64 episodes of lung disease and who did not have bronchoscopy following examination of nondiagnostic induced sputum, indicated a range of sensitivity for detection of P carinii in induced sputum of 74% to 77% and a negative predictive value of 58% to 64%. Mycobacteria were recovered from 11 (6%) of the induced sputum and 6 (12%) of the bronchoscopic specimens containing P carinii. However, only oral or environmental fungi were recovered from P carinii-containing induced sputum or bronchoscopic specimens. For those patients in whom P carinii was not detected, only the bronchoscopic specimens were cultured for Mycobacteria and fungi. Potentially pathogenic Mycobacteria and fungi were recovered from 16 (23.5%) and 34 (50%), respectively, of these P carinii-negative specimens. Analysis of these results, obtained under routine practice conditions, indicates that bronchoscopy should be reserved for those patients whose induced sputum examinations do not show P carinii and that mycobacterial and fungal cultures be performed only on bronchoscopic specimens in which P carinii is not detected.

Acquired Immunodeficiency Syndrome↗

Digenic inheritance of mutations in SPG7 and AFG3L2 causes motor neuron and cerebellar disorders.

BACKGROUND: Biallelic SPG7 mutations cause one of the most common forms of hereditary spastic paraplegia (HSP). Several reports have suggested that heterozygous SPG7 variants may also play a role in HSP, but also in amyotrophic lateral sclerosis (ALS). However, it remains controversial whether heterozygous SPG7 mutations are pathogenic on their own, or if other mechanisms are at play. We recently provided evidence for non-Mendelian inheritance in spastic paraplegia 7 (SPG7), as heterozygous carriers of SPG7 mutations often also carried mutations in other disease-related genes, including AFG3L2, more frequently than expected by chance. Given that SPG7 and AFG3L2 encode interacting subunits of the mitochondrial m-AAA protease complex, we hypothesized that combined heterozygous mutations in these genes may act synergistically to disrupt mitochondrial function and contribute to disease. In this study, we aimed to examine whether digenic heterozygous mutations in SPG7 and AFG3L2 can lead to a spectrum of neurodegenerative disorders. METHODS: We first analyzed genome and exome sequencing data of 6644 unrelated individuals including 4817 motor neuron disorder (MND) and ataxia patients and 1827 controls. We next analyzed an additional 18,748 exome data from rare disease cohorts to further examine the occurrence of variants in SPG7 and AFG3L2. RESULTS: Among the first 4817 MND and ataxia patients, we identified a total of 6 patients, 4 of whom were unrelated, who carried potentially pathogenic variants in both SPG7 and AFG3L2, in contrast to none in 1827 unrelated controls. Further analysis of the 18,748 additional patients with rare disease, as well as a comprehensive literature review, identified 6 more patients, 5 of whom were unrelated, who had digenic mutations in SPG7 and AFG3L2. In the two families we identified, digenic mutations in SPG7 and AFG3L2 perfectly segregated with the disease. The 12 patients reported here exhibited predominant signs of motor neuron and cerebellar involvement. CONCLUSIONS: Our findings demonstrate that digenic inheritance of concurrent heterozygous mutations in SPG7 and AFG3L2 may cause motor neuron and cerebellar disorders. Screening of the entire SPG7 and AFG3L2 genes in genetically undiagnosed cases of MND and spastic ataxia may help to increase the diagnostic yield.

Humans↗

Middle ear mucin glycoprotein: purification and interaction with nontypable Haemophilus influenzae and Moraxella catarrhalis.

Nontypable Haemophilus influenzae and Moraxella catarrhalis are important pathogens in children and adults. The mechanisms of their adherence to the epithelial cell surface and colonization are not clear. For the pathogen to adhere to the epithelial cell, it must first attach to and penetrate the mucus barrier. Mucin glycoproteins of the mucus layer generally are thought to be involved in bacterial attachment. To understand the precise mechanisms of middle ear mucin-bacterial interactions, we used an overlay binding assay with a highly purified middle ear mucin and outer membrane proteins of both nontypable H. influenzae and M. catarrhalis. Outer membrane proteins P2 and P5 were identified as the major components that medicate the binding between nontypable H. influenzae and human middle ear mucin. Moreover, the 57 kDa protein, CD, of the outer membrane protein of M. catarrhalis was found to be the only protein binding human middle ear mucin. Finally, it appears that a protein-oligosaccharide interaction is responsible for binding because asialo-mucin does not bind to either of the bacteria. Knowledge of the specific bacterial-mucin interaction may provide an understanding of the bacterial-epithelial cell colonization. Conversely, comprehension of this interaction between bacteria and purified mucin may be a strategy to prevent colonization of potential pathogens that cause otitis media and sinusitis in children.

Amino Acids↗

Secretory immunoglobulin A in tears:functions and changes during contact lens wear.

INTRODUCTION: Secretory immunoglobulin A (sIgA) is the predominant immunoglobulin in tears. The role of sIgA in defending the eye against pathogens has not been established clearly. There have been conflicting reports about the effect of contact lens wear on the concentration of sIgA in tears. This study was conducted to elucidate the role of sIgA in ocular defence and to determine the effect of contact lens wear on sIgA concentration. METHODS: Tears were collected from contact lens wearers and non-wearers using micro-capillary tubes. The concentration of sIgA was evaluated using an in-house ELISA. The specificity of sIgA to a strain of P. aeruginosa was examined using a fluorescent assay and the ability of neutrophils to phagocytose sIgA coated bacteria were assessed by plate counts. RESULTS: Tears contained sIgA that reacted to P. aeruginosa. P. aeruginosa coated with sIgA was phagocytosed by the neutrophils. The level of sIgA and the level of sIgA specific to P. aeruginosa in the tears of contact lens wearers were significantly reduced. CONCLUSIONS: These results indicate that contact lens wear significantly alters the level of sIgA in tears which may lead to changes in the ability of the ocular surface to defend itself against potential pathogens.

Journal Article↗

CD4+ T-cell-directed antibody responses are maintained in patients with psoriasis receiving alefacept: results of a randomized study.

BACKGROUND: Alefacept, human LFA-3/IgG(1) fusion protein, selectively reduces memory-effector (CD45RO(+)) T cells, a source of the pathogenic mediators of psoriasis. OBJECTIVE: To evaluate the effect of alefacept on immune function, T-cell-dependent humoral responses to a neoantigen (PhiX174) and recall antigen (tetanus toxoid) were assessed. METHODS: Patients with psoriasis were randomized to the control group or to receive alefacept (7.5 mg intravenously weekly for 12 weeks). The alefacept group received PhiX174 immunizations at weeks 6, 12, 20, and 26 and tetanus toxoid at week 21; control subjects received PhiX174 at weeks 6 and 12 and tetanus at week 10. RESULTS: Mean anti-PhiX174 titers were comparable in both groups. There was no difference in the percentage of responders (anti-PhiX174 IgG >/=30% of the total anti-PhiX174) between the alefacept group and the control group (86% and 82%, respectively; P =.73). The percentage of patients with anti-tetanus toxoid titer increases >/=2 times baseline also was similar (alefacept, 89%; control 91%). CONCLUSION: A single 12-week course of alefacept did not impair primary or secondary antibody responses to a neoantigen or memory responses to a recall antigen. The selective immunomodulatory effect of alefacept against a potentially pathogenic T-cell subset is associated with maintenance of a significant aspect of immune function (antibody response) to fight infection and respond to vaccinations.

Adult↗

Optic neuritis in multiple sclerosis.

PURPOSE: To review the clinical features, natural history, potential pathogenic mechanisms, differential diagnosis, and management of optic neuritis in multiple sclerosis. METHODS: Relevant literature regarding optic neuritis in multiple sclerosis from 1970 to the present was reviewed. RESULTS: Optic neuritis is an acute inflammatory optic neuropathy. It is the most common type of optic neuropathy causing acute visual loss in young adults (peak age at 30-40 years), especially among women. Patients usually present with an acute reduction of visual acuity, orbital pain exacerbated by eye movements, dyschromatopsia, and an afferent papillary defect, with or without swelling of the optic nerve head. Visual field testing most often reveals central defects, but others, such as centrocecal, can also occur. Magnetic resonance image (MRI) scanning of the brain should be undertaken in all cases of acute optic neuritis for diagnostic and prognostic purposes. The brain lesions of multiple sclerosis are commonly seen as T2 ovoid high-signal white matter lesions on MRI scans of the brain located in perivenular regions perpendicular to ventricles with variable enhancement. For atypical presentations of optic neuritis, additional laboratory tests, such as cerebrospinal fluid analysis, serologic tests, and visual evoked potentials, prove to be useful in the diagnosis and subsequent management of the patient. The recommended treatment for optic neuritis is intravenous steroids, as shown in the Optic Neuritis Treatment Trial (ONTT). CONCLUSION: Optic neuritis is often the initial presentation of multiple sclerosis. Recent advances in the understanding of the immune basis for multiple sclerosis has led to earlier and more effective treatment of this disease.

Brain↗

The intracellular status of Streptococcus pyogenes: role of extracellular matrix-binding proteins and their regulation.

Streptococcus pyogenes (group A streptococci, GAS) is an important and exclusively human pathogen. Adherence to and internalization into host cells significantly contributes to the pathogenesis of GAS infections. The adherence mechanism is a two-step process in which host extracellular matrix (ECM) proteins act as prime targets. GAS may express more than a dozen different microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) that attach to fibronectin or collagen. One of them, protein F1/SfbI binds fibronectin and mediates adherence of GAS to host cells. Bound fibronectin acts as a bridging molecule towards host cell integrins, which in turn initialize the uptake process that leads to GAS internalization. In their safe intracellular niche GAS can persist protected from antibiotics and host defense, a scenario currently discussed in the context of treatment failure, asymptomatic GAS carriers and recurrent GAS infections. Patients with such low grade infections represent the main GAS reservoir from which the bacteria are spread in the general population. Due to their important function, expression of GAS MSCRAMMs is under control of several "stand alone" transcriptional regulators and two-component signal transduction systems. Several regulator genes are organized together with MSCRAMM genes on one of two potential pathogenicity islands, act together in a growth phase-dependent regulatory network and are expressed in a strain-specific manner. A detailed understanding of these mechanisms is crucial, since interference with MSCRAMM function alone or in conjunction with specific manipulations of regulators is an attractive goal for novel anti-infective strategies.

Adhesins, Bacterial↗

Expression of Toll-like receptors (TLR) and responsiveness to TLR agonists by polarized mouse uterine epithelial cells in culture.

The objective of the present study was to examine the expression of Toll-like receptors (TLRs) by mouse uterine epithelial cells and to determine if stimulation of the expressed TLR induces changes in cytokine and/or chemokine secretion. Using RT-PCR, the expression of TLRs 1-6 by mouse uterine epithelial cells was demonstrated, with TLRs 7-9 expressed only periodically. In the absence of pathogen-associated molecular patterns, polarized uterine epithelial cells constitutively secrete interleukin (IL) 1A, cysteine-cysteine ligand (CCL) 2, IL6, granulocyte-macrophage colony-stimulating factor 2 (CSF2), tumor necrosis factor A (TNFA), CSF3, and IL8 in vitro, with levels of cytokines/chemokines secreted into the apical compartment being significantly greater than those released into the basolateral compartment. When added to the apical surface for 48 h before analysis, the TLR2-agonist Pam3Cys-Ser-(Lys)4 and TLR1/6-agonist peptidoglycan increased epithelial cell apical secretion of IL1A, CCL2, and IL6 and apical/basolateral bidirectional secretion of CSF2, TNFA, CSF3, and IL8 when compared to controls. The TLR3-agonist poly (I:C) significantly increased bidirectional secretion of CCL2, IL6, TNFA, and CSF2 and basolateral secretion of CSF3. Lastly, the TLR4-agonist lipopolysaccharide increased bidirectional secretion CCL2, CSF2, TNFA, CSF3, and IL8 and apical secretion of IL6. These results indicate that mRNAs for Tlr1 through Tlr6 are expressed by uterine epithelial cells and that treatment with specific TLR agonists alters the expression of key chemokines and proinflammatory cytokines that contribute to the defense of the uterus against potential pathogens.

Animals↗

Identification of arthritis-related gene clusters by microarray analysis of two independent mouse models for rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease affecting approximately 1% of the population worldwide. Previously, we showed that human T-cell leukemia virus type I-transgenic mice and interleukin-1 receptor antagonist-knockout mice develop autoimmunity and joint-specific inflammation that resembles human RA. To identify genes involved in the pathogenesis of arthritis, we analyzed the gene expression profiles of these animal models by using high-density oligonucleotide arrays. We found 1,467 genes that were differentially expressed from the normal control mice by greater than threefold in one of these animal models. The gene expression profiles of the two models correlated well. We extracted 554 genes whose expression significantly changed in both models, assuming that pathogenically important genes at the effector phase would change in both models. Then, each of these commonly changed genes was mapped into the whole genome in a scale of the 1-megabase pairs. We found that the transcriptome map of these genes did not distribute evenly on the chromosome but formed clusters. These identified gene clusters include the major histocompatibility complex class I and class II genes, complement genes, and chemokine genes, which are well known to be involved in the pathogenesis of RA at the effector phase. The activation of these gene clusters suggests that antigen presentation and lymphocyte chemotaxis are important for the development of arthritis. Moreover, by searching for such clusters, we could detect genes with marginal expression changes. These gene clusters include schlafen and membrane-spanning four-domains subfamily A genes whose function in arthritis has not yet been determined. Thus, by combining two etiologically different RA models, we succeeded in efficiently extracting genes functioning in the development of arthritis at the effector phase. Furthermore, we demonstrated that identification of gene clusters by transcriptome mapping is a useful way to find potentially pathogenic genes among genes whose expression change is only marginal.

Animals↗

[Prospective cohort study on the relationship between pathogenic bacteria in the nasal middle meatus and acute bacterial respiratory infection in children].

OBJECTIVE: To study the relationship between pathogenic bacteria in the nasal middle meatus and acute bacterial respiratory infection in children. METHODS: Three hundred and twenty eight children with respiratory infection (mean age 8 years) were included into the prospective cohort study. The mucosal fluid specimens from the nasal middle meatus were collected under an endoscope for bacterial culture. The patients with bacterial culture positive were defined as the Exposed group and those with bacterial culture negative as the Non-exposed group. The grouping of the patients was blinded to the patients, patients' parents and physicians. Both groups received anti-virus and symptomatic treatments, without antibiotic administration. Five days later, the patients were evaluated as to whether they had bacterial infection based on the leucocyte count and CRP results. RESULTS: Of the 328 patients, 168 had a positive nasal bacterial culture. The incidence of bacterial respiratory infection in the Exposed group [51.2% (86/168)] was significantly higher than in the Non-exposed group [13.1% (21/160)] (P < 0.01). The relative risk of bacterial respiratory infection occurrence in patients with nasal bacterial culture positive was 3.9002. CONCLUSIONS: The children with respiratory infection who had potential pathogenic bacteria in the nasal middle meatus were more prone to develop bacterial respiratory infection.

Acute Disease↗

Effects of subantimicrobial-dose doxycycline in the treatment of moderate acne.

OBJECTIVE: To determine if treatment with subantimicrobial-dose (SD) doxycycline hyclate (20-mg tablets taken twice daily) improved clinical outcome, had any detectable effect on skin flora, led to overgrowth or colonization of skin by opportunistic pathogens, or resulted in an increase in antibiotic resistance by the surface skin microflora in patients with moderate acne compared with placebo. DESIGN: Multicenter, double-blind, randomized, placebo-controlled, parallel-group trial. SETTING: Two university-based clinics. SUBJECTS: Adults (N = 51) with moderate facial acne. INTERVENTIONS: Patients were randomized to receive SD doxycycline (Periostat; CollaGenex Pharmaceuticals Inc, Newtown, Pa) or placebo twice daily for 6 months. MAIN EFFICACY OUTCOMES: Primary: changes from baseline in numbers of inflammatory, noninflammatory, and total lesions. Secondary: changes from baseline of individual counts of papules, pustules, and nodules and global assessments of clinical improvement by patient and physician. RESULTS: Forty patients completed 6 months of treatment. At 6 months, the SD doxycycline group had a significantly greater percent reduction in the number of comedones (P<.01), inflammatory and noninflammatory lesions combined (P<.01), and total inflammatory lesions (P<.05) than did the placebo group. They also had significantly greater improvement according to the clinician's global assessment (P =.03). There were no significant differences in microbial counts between groups and no evidence of change in antibiotic susceptibility or colonization by potential pathogens. The treatment was well tolerated. CONCLUSIONS: Twice-daily SD doxycycline treatment significantly reduced the number of inflammatory and noninflammatory lesions in patients with moderate facial acne, was well tolerated, had no detectable antimicrobial effect on the skin flora, and did not result in any increase in the number or severity of resistant organisms.

Acne Vulgaris↗

Peptostreptococcus micros in human periodontitis.

Peptostreptococcus micros is a recognized pathogen in medical infections, and its association with progressive periodontitis was examined in this study. P. micros was isolated from paper-point subgingival samples on anaerobic enriched blood agar plates and identified on the basis of cellular and colonial morphology and selected biochemical tests. In a cross-sectional study involving 907 people with advanced adult periodontitis, 127 with early-onset periodontitis, and 12 with localized juvenile periodontitis, P. micros in these patient groups occurred with a prevalence of 58-63%. In culture-positive patients, P. micros averaged 12-15% of total viable counts. P. micros demonstrated similar occurrence and proportional recovery in all age groups. In a longitudinal study of 91 adult periodontitis patients on maintenance therapy, P. micros demonstrated a significantly higher prevalence in disease-active than in disease-inactive patients (47% vs 14%). Mechanical subgingival debridement and 0.12% chlorhexidine pocket irrigation was unable to eradicate subgingival P. micros from 18 of 22 adult periodontitis patients. In vitro antimicrobial susceptibility testing showed P. micros to be sensitive to therapeutic levels of penicillin, clindamycin and metronidazole. Our findings indicate that P. micros is a potential pathogen in adult periodontitis. The methods for its eradication from subgingival sites remain to be determined.

Adult↗

Abnormalities of glycosphingolipid, sulfatide, and ceramide in the polycystic (cpk/cpk) mouse.

Polycystic kidney disease is a disorder marked by aberrant renal tubular epithelial cell proliferation and transport abnormalities. Sphingolipids are ubiquitous membrane components implicated in several cellular functions including cell membrane sorting, signaling, growth, ion transport, and adhesion. To investigate a potential pathogenic role for sphingolipids in cystic kidney disease, we studied the sphingolipid content and associated enzymatic activities of the kidneys from cpk/cpk mice and their phenotypically normal litter mates. The neutral glycolipids, including glucosylceramide and lactosylceramide, displayed a striking increase in 3-week-old cpk/cpk mice as did the acidic lipid, ganglioside GM3. However, a correspondingly significant decrease in sulfoglycolipid and ceramide concentration was observed in the cpk/cpk kidneys. Glucosylceramide synthase activity was higher in the kidneys of the cpk/cpk mice than in those of the controls. Kinetic analysis of the glucosylceramide synthase revealed the presence of an endogenous activator in the cystic kidney. A marked decrease in sulfotransferase activity was observed in both whole kidney homogenates and in microsomal preparations that was consistent with the decrement in sulfolipid content. The increase in GM3, glucosyl- and lactosylceramide may therefore be the result of impaired sulfolipid synthesis at the 3-week time point. While sulfolipid and glucosylceramide concentrations are not different at 1 and 2 weeks of age, ceramide concentrations in cystic kidneys are significantly reduced compared to kidneys from phenotypically normal mice. These results suggest that sphingolipids may play a potential role in the proliferative and transport abnormalities associated with cystic renal disease and the development of azotemia.

Animals↗