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Biomedical subjects

Adrian Lee

Publications and source records attributed to Adrian Lee.

24 records · Page 2Linked to original sources

Temporal dermoids: three cases and a modified treatment algorithm.

Congenital orbitofacial dermoids can be segregated into frontotemporal, orbital, and nasoglabellar regions. Although 10% to 45% of nasoglabellar dermoids present with sinus tracts and occasional intracranial extension, it is rare for frontotemporal dermoids to do so. Frontotemporal dermoids typically manifest as superficial, slow-growing masses that are treated by simple excision. In this retrospective review of 24 patients with congenital orbitofacial dermoids, the authors noted three cases of temporal dermoids with sinus tracts and bony involvement. All three patients were female, with an average presenting age of 4.2 years. Two lesions appeared on the left and one on the right. Each lesion involved the sphenotemporal suture, requiring debridement of the outer cranial table to prevent recurrence. In light of their experience, the authors offer an amendment to the current treatment algorithm for congenital orbitofacial dermoids. A congenital frontotemporal dermoid with a sinus tract should have preoperative radiological evaluation with computed tomography or magnetic resonance imaging to define the pathological anatomy. If bony invasion exists, aggressive exposure and resection of at least the outer cranial table is necessary to prevent recurrence. Temporal dermoids may represent a distinct entity that requires a separation classification from frontotemporal dermoids.

Adolescent↗

Gastric transitional zones, areas where Helicobacter treatment fails: results of a treatment trial using the Sydney strain mouse model.

Current combination therapies cure Helicobacter pylori infection in 75 to 85% of cases. However, many treatment failures are not explained by antibiotic resistance. Our goal was to explore treatment failures under in vivo conditions by using the H. pylori Sydney strain (SS1) mouse model. Mice infected with H. pylori (SS1) were treated with monotherapies or combination therapies used in human trials. Bacterial levels and distribution of organisms within the stomach were assessed 24 h after treatment to determine clearance and location of treatment failures and 29 days after treatment to determine cure rates. Except for treatment with metronidazole, mono- and dual therapies did not cure infection but resulted in decreases in bacterial levels and differences in distribution within the stomach. In cases of treatment failure when clarithromycin was used, omeprazole and dual therapy with omeprazole and amoxicillin resulted in organisms being cleared from the antrum, but organisms remained in the antrum-body transitional zone. The triple therapies of OMC and bismuth subcitrate, metronidazole, and tetracycline were successful in eradicating infection. Except for metronidazole monotherapy and triple therapy with OAC, there was good correlation between the Sydney strain mouse model and humans with respect to the success of antimicrobial therapy. The antrum-body transitional zone was identified as a sanctuary site in treatment failure. This could result from antimicrobial agents not functioning effectively at this site or bacteria in this location expressing products that protect them against antimicrobial agents. This is the first demonstration of a possible sanctuary site as a reason for failure of therapy.

Amoxicillin↗

Growth phase-dependent response of Helicobacter pylori to iron starvation.

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 pathogen Helicobacter pylori that 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 genes cagA, vacA, and napA. We examined the effect of iron starvation on the motility of H. pylori and 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.

Base Sequence↗

Gene expression profiling of Helicobacter pylori reveals a growth-phase-dependent switch in virulence gene expression.

The global pattern of growth-phase-dependent gene expression of Helicobacter pylori during in vitro culture was analyzed by using a high-density DNA microarray. To detect consistent coordinated gene expression in this bacterium, temporal changes in transcription were assessed in two independent time courses. Cluster analysis of the expression profiles highlighted a major switch in gene expression during the late log-to-stationary phase transition that we have termed the Log-Stat switch. Statistical analysis of the genes that were significantly induced or repressed during the Log-Stat switch revealed that many of these genes were related to virulence. Among these, expression of the genes for the neutrophil activating protein (napA) and the major flagellin subunit (flaA) were significantly induced. Additionally, the expression of a number of genes involved in iron homeostasis changed dramatically at this switch; the gene for the iron-storage protein, pfr, was induced, while the genes for two putative iron uptake proteins, fecA and frpB, were significantly repressed. These data suggest that the late log phase may correspond to the most virulent phase of growth in H. pylori and may be intimately related to its pathogenesis. The use of microarrays to analyze the kinetics of the transcriptional response of a bacterial pathogen to a changing environment has enabled the discovery of previously unappreciated relationships between genes by elucidation of coordinated gene expression profiles.

Flagella↗

In vivo behavior of a Helicobacter pylori SS1 nixA mutant with reduced urease activity.

Helicobacter pylori mutants devoid of urease activity fail to colonize the gastric mucosa of mice; however, the effect of decreased levels of urease on colonization has not been examined. The nixA gene, required for full urease activity, encodes a cytoplasmic membrane nickel transporter that imports nickel ions and leads to incorporation of nickel ions into apourease. A nixA mutant of the Sydney strain of H. pylori (SS1) was constructed by disruption of the nixA gene with a kanamycin resistance cassette. This mutant retained only half the urease activity of the wild-type (wild-type) SS1 strain. C57BL/6j (n = 75) and BALB/c (n = 75) mice were inoculated independently with the wild-type or the nixA strain. The level and distribution of colonization were assessed by bacterial colony counts and histological grading at 4, 12, and 24 weeks postinfection. Colonization levels of the nixA strain in BALB/c mice were significantly lower compared with SS1 (P = 0.005), while colonization in C57BL/6j mice was similar for both the wild-type and mutant strains. Subtle differences in colonization of the different regions of the stomach, determined by microscopic grading, were observed between wild-type SS1 and the nixA strain in BALB/c mice. On the contrary, when C57BL/6j (n = 35) and BALB/c (n = 35) mice were coinfected with the wild-type and nixA strains simultaneously, the nixA mutant failed to colonize and was outcompeted by the wild-type SS1 strain, which established normal levels of colonization. These results demonstrate the importance of the nixA gene for increasing the fitness of H. pylori for gastric colonization. Since nixA is required for full urease activity, the decreased fitness of the nixA mutant is likely due to reduced urease activity; however, pleiotropic effects of the mutation cannot be completely ruled out.

Animals↗

Individual finger strength: are the ulnar digits "powerful"?

This study determined the test-retest reliability of a grip device that measures the contribution of individual fingers to grip strength and described the pattern of contribution in subjects without hand pathology. Subjects repeated a set of three maximal grip efforts on two occasions separated by two to seven days. Intraclass correlation reliability coefficients were high (>0.75) for eight out of ten strength measures. The percentage contributions of the index, middle, ring, and small fingers to grip were approximately 25%, 35%, 25%, and 14%, respectively. Grip and finger strengths were highly correlated. Anthropometric measures of body size or finger length were moderately correlated with strength measures. These data suggest that there is a predictable pattern by which individual fingers contribute to overall grip strength, which is partially related to body size. The ulnar side of the hand contributes to the smaller proportion of overall grip (approximately 60% radial, 40% ulnar). The clinical utility of finger strength measures should be explored.

Adult↗