Zinc import mediated by AdcABC is critical for colonization of the dental biofilm by Streptococcus mutans in an animal model.

Trace metals are essential to all domains of life but toxic when found at high concentrations. Although the importance of iron in host-pathogen interactions is firmly established, contemporary studies indicate that other trace metals, including manganese and zinc, are also critical to the infectious process. In this study, we sought to identify and characterize the zinc uptake system(s) of Streptococcus mutans, a keystone pathogen in dental caries and a causative agent of bacterial endocarditis. Different than other pathogenic bacteria, including several streptococci, that encode multiple zinc import systems, bioinformatic analysis indicated that the S. mutans core genome encodes a single, highly conserved, zinc importer commonly known as AdcABC. Inactivation of the genes coding for the metal-binding AdcA (ΔadcA) or both AdcC ATPase and AdcB permease (ΔadcCB) severely impaired the ability of S. mutans to grow under zinc-depleted conditions. Intracellular metal quantifications revealed that both mutants accumulated less zinc when grown in the presence of a subinhibitory concentration of a zinc-specific chelator. Notably, the ΔadcCB strain displayed a severe colonization defect in a rat oral infection model. Both Δadc strains were hypersensitive to high concentrations of manganese, showed reduced peroxide tolerance, and formed less biofilm in sucrose-containing media when cultivated in the presence of the lowest amount of zinc that support their growth, but not when zinc was supplied in excess. Collectively, this study identifies AdcABC as the major high affinity zinc importer of S. mutans and provides preliminary evidence that zinc is a growth-limiting factor within the dental biofilm.

Evaluation of the role of polyelectrolyte deposition conditions in growth factor release.

Polyelectrolyte multilayer coatings were prepared from solutions of poly(methacrylic acid) and poly-l-histidine. Bone morphogenetic protein 2 (BMP-2) was adsorbed onto the surface of anodized titanium and polyelectrolyte multilayer coatings were built up on top of the BMP-2. The effect of deposition conditions on coating properties and preosteoblast response was measured by comparing coatings prepared under natural conditions to those prepared from solutions at pH = 6.0 and solutions containing 0.1 M NaCl. High levels of BMP-2 release were achieved, with coatings prepared from pH = 6.0 solutions releasing 86 ng cm-2 and coatings prepared from solutions containing 0.1 M NaCl releasing 114 ng cm-2 over 25 days. Enhanced preosteoblast differentiation was observed on coatings prepared from modified solutions; however, this increased differentiation was apparent for BMP-2-eluting and control coatings. Additionally, a positive relationship between surface roughness and differentiation was observed, which may account for increased differentiation for systems that do not release BMP-2.

Pseudo-outbreak of Mycobacterium abscessus Infection Caused by laboratory contamination .

OBJECTIVE: To investigate the cause(s) of an increased incidence of clinical cultures growing Mycobacterium abscessus at a hospital in Florida. DESIGN: Outbreak investigation. SETTING: University-affiliated, tertiary-care hospital. METHODS: A site visit was done during the first week of September 2006. We reviewed the medical records of patients from whom M. abscessus was recovered during the period from January 1, 2003, through June 30, 2006. We collected environmental samples from various sites and evaluated specimen processing procedures in the microbiology laboratory. Isolates of M. abscessus recovered from the environment and from 12 randomly selected patients who sought medical care in 2006 were compared by pulsed-field gel electrophoresis (PFGE). Follow-up case surveillance was continued through March 31, 2007. RESULTS: Specimens from 143 patients obtained from various anatomical sites grew M. abscessus on culture in 2005-2006, compared with specimens from 21 patients in 2003-2004. The 12 isolates from patients that were selected for molecular typing had indistinguishable PFGE patterns. Observations revealed no major breaches in the processing of mycobacterial specimens in the laboratory. Isolates grew only after prolonged incubation (mean +/- SD, 45 +/- 15 days) in test tubes containing diagonally oriented Middlebrook and Cohn 7H10 agar or Lowenstein-Jensen medium. Environmental samples obtained from the inside of the specimen incubator grew M. abscessus on culture. A test tube containing diagonally oriented, uninoculated Middlebrook and Cohn 7H10 agar that was incubated in the same incubator as clinical specimens grew M. abscessus with a PFGE pattern that matched the pattern of the patient isolates. Cases of M. abscessus infection decreased to baseline after the hospital changed suppliers of mycobacterial media and cleaned the incubator. CONCLUSIONS: Although the source was never confirmed, our investigation suggests that this was a pseudo-outbreak of M. abscessus infection that resulted from contamination of mycobacterial cultures during incubation. Our findings emphasize the need for guidance on the disinfection of specimen incubators.

Cerebral responses to noxious thermal stimulation in chronic low back pain patients and normal controls.

Changes in regional cerebral blood flow (rCBF) have previously been demonstrated in a number of cortical and subcortical regions, including the cerebellum, midbrain, thalamus, lentiform nucleus, and the insula, prefrontal, anterior cingulate, and parietal cortices, in response to experimental noxious stimuli. Increased anterior cingulate responses in patients with chronic regional pain and depression to noxious stimulation distant from the site of clinical pain have been observed. We suggested that this may represent a generalized hyperattentional response to noxious stimuli and may apply to other types of chronic regional pain. Here these techniques are extended to a group of patients with nonspecific chronic low back pain. Thirty-two subjects, 16 chronic low back pain patients and 16 controls, were studied using positron emission tomography. Thermal stimuli, corresponding to the experience of hot, mild, and moderate pain, were delivered to the back of the subject's right hand using a thermal probe. Each subject had 12 measurements of rCBF, 4 for each stimulus. Correlation of rCBF with subjective pain experience revealed similar responses across groups in the cerebellum, midbrain (including the PAG), thalamus, insula, lentiform nucleus, and midcingulate (area 24') cortex. These regions represented the majority of activations for this study and those recorded by other imaging studies of pain. Although some small differences were observed between the groups these were not considered sufficient to suggest abnormal nociceptive processing in patients with nonspecific low back pain.

Venous angioma adjacent to the root entry zone of the trigeminal nerve: implications for management of trigeminal neuralgia.

Detection of a venous angioma at the root entry zone is important for surgical planning, so that the neurosurgeon will be aware that both veins and arteries may require microvascular decompression. In selected cases, alternative treatment may be indicated to avoid the potential surgical complication of a venous infarct. Trigeminal neuralgia typically occurs in the middle-aged to elderly population, usually the result of compression of the trigeminal nerve at its root entry zone by an ectatic, aging artery or, less commonly, a regional vein [1, 2, 3]. When associated with a venous angioma at the root entry zone, trigeminal neuralgia usually presents at a younger age [4, 5, 6]. We review the imaging examinations and clinical data of five patients with trigeminal neuralgia who had a venous angioma adjacent to the root entry zone of the trigeminal nerve, and discuss how the imaging findings affected their management.

Electronic prescribing in ambulatory practice: promises, pitfalls, and potential solutions.

OBJECTIVE: To examine advantages of and obstacles to electronic prescribing in the ambulatory care environment. DATA SOURCES: MEDLINE and International Pharmaceutical Abstract searches were conducted for the period from January 1980 to September 2000. Key words were electronic prescribing, computerized physician order entry, prior authorization, drug utilization review, and consumer satisfaction. In September 2000, a public search engine (www.google.com) was used to find additional technical information. In addition, pertinent articles were cross-referenced to identify other resources. DATA EXTRACTION: Articles, symposia proceedings, and organizational position statements published in the United States on electronic prescribing and automation in healthcare are cited. DATA SYNTHESIS: Electronic prescribing can eliminate the time gap between point of care and point of service, reduce medication errors, improve quality of care, and increase patient satisfaction. Considerable funding requirements, segmentation of healthcare markets, lack of technology standardization, providers' resistance to change, and regulatory indecisiveness create boundaries to the widespread use of automated prescribing. The potential solutions include establishing a standardizing warehouse or a router and gaining stakeholder support in implementation of the technology. CONCLUSIONS: Electronic prescribing can provide immense benefits to healthcare providers, patients, and managed care. Resolution of several obstacles that limit feasibility of this technology will determine its future.

A survey of selected Internet pharmacies in the United States.

OBJECTIVE: To determine whether differences in the provision of pharmacy services exist among different types of Internet pharmacies. DESIGN: Survey of selected pharmacies with a presence on the Internet. Data were abstracted onto a data collection form for further analysis. Data collection was limited to 3 weeks. SETTING: U.S.-based Internet pharmacies that allow patients to purchase prescription medications online. Pharmacies were identified using a metasearch engine with the search terms "Internet pharmacy" and "Internet pharmacist." INTERVENTION: Survey. MAIN OUTCOME MEASURES: Comparisons of availability of 10 commonly used products representing a variety of product categories, prescription verification methods, and privacy issues; and determinations of site navigability, drug information and provider access, and payment methods. Sites were categorized as "chain pharmacy extensions," "mail order pharmacies," "independent pharmacy extensions," and "online pharmacies." RESULTS: Thirty-three sites were reviewed. There was significant variation among the four types of pharmacies selling prescriptions over the Internet. Most pharmacies provided all of the drugs in the survey. Patients were required to provide their own prescription at 88% of the sites, and 75% of sites used mail or fax to verify prescription integrity. More than 50% of sites had privacy policies posted, and 64% used cookies. Chain pharmacy extensions required completion of an average of 10.2 pages to order drugs versus 2.4 to 4 pages for all other site types. Drug information was written at an eighth-grade reading level at 36% of the sites. More than two-thirds of the sites provided a toll-free telephone for a health care professional. Nearly 80% of the sites accepted health insurance, and 95% accepted credit cards; however, only 40% used a secure transmission mechanism for patient or payment information. CONCLUSION: Internet pharmacies provide varying levels of service. Policies regarding the use of the Internet for obtaining medications should focus on improving the privacy of consumer information and ensuring the secure transmission of financial information.

Cochlear implantation after labyrinthectomy.

OBJECTIVE: The goal was to report a method used for intraoperative ear selection for cochlear implantation using electrical brainstem response. Initial patient response and the longer-term results of cochlear implantation after labyrinthectomy were compared. STUDY DESIGN: This was a specific retrospective review of a single case of cochlear implantation after labyrinthectomy. SETTING: The study involved a tertiary referral center in both an ambulatory and a hospital setting. PATIENT: The study involved a report of a single patient who was evaluated for a possible cochlear implant and successfully underwent cochlear implantation. INTERVENTIONS: A case study of a profoundly deaf individual is presented, including the diagnostic measures used to determine the candidacy for cochlear implantation, the ear selected, and the rehabilitation. MAIN OUTCOME MEASURES: Both early (3 months) and later (14 months) postoperative results clearly demonstrate that a cochlear implant in a patient with a previous labyrinthectomy can be beneficial. RESULTS: The early and later results after cochlear implantation are compared in a single case study. CONCLUSION: This case study demonstrates that there is improvement in sound awareness, speech recognition, and communication after cochlear implantation in a previously labyrinthectomized ear.

MR imaging response of brain metastases after gamma knife stereotactic radiosurgery.

PURPOSE: To characterize the magnetic resonance (MR) imaging response of brain metastases after gamma knife stereotactic radiosurgery and determine whether imaging features and tumor response rates correlate with local tumor control and survival. MATERIALS AND METHODS: Serial MR examinations were performed in 48 patients (25 men, 23 women; mean age, 58 years) with 78 lesions. Pretreatment and follow-up enhancing lesion volumes and imaging features were assessed. Rates of response to stereotactic radiosurgery were calculated. Prognostic imaging features affecting local control and survival were analyzed. RESULTS: Local tumor control was achieved in 66 (90%) of 73 metastases at 20 weeks after stereotactic radiosurgery; 61% maintained local control at 2 years. A homogeneous baseline enhancement pattern and initial good response rate (> 50% lesion volume reduction) predicted local control. Five metastases demonstrated a transient volume increase after treatment. The median survival time after stereotactic radiosurgery was 53 weeks and correlated with systemic disease burden and primary tumor type. CONCLUSION: Baseline homogeneous tumor enhancement and initial good response correlate with local control. Initial lesion growth does not preclude local control and may represent radiation-related change. Recognition of these serial MR imaging findings may guide image interpretation and influence treatment in patients with stereotactic radiosurgery-treated metastases.

alpha2-adrenoceptors modulate NMDA-evoked responses of neurons in superficial and deeper dorsal horn of the medulla.

Extracellular single unit recordings were made from neurons in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in 21 male rats anesthetized with urethan. NMDA produced an antagonist-reversible excitation of 46 nociceptive as well as nonnociceptive neurons. Microiontophoretic application of a preferential alpha2-adrenoceptor (alpha2AR) agonist, (2-[2, 6-dichloroaniline]-2-imidazoline) hydrochloride (clonidine), reduced the NMDA-evoked responses of 86% (6/7) of nociceptive-specific (NS) neurons, 82% (9/11) of wide dynamic range (WDR) neurons, and 67% (4/6) of low-threshold (LT) neurons in the superficial dorsal horn. In the deeper dorsal horn, clonidine inhibited the NMDA-evoked responses of 94% (16/17) of NS and WDR neurons and 60% (3/5) of LT neurons. Clonidine facilitated the NMDA-evoked responses in 14% (1/17) of NS, 9% (1/11) of WDR, and 33% (2/6) of LT neurons in the superficial dorsal horn. Idazoxan, an alpha2AR antagonist, reversed the inhibitory effect of clonidine in 90% (9/10) of neurons, whereas prazosin, an alpha1-adrenoceptor antagonist with affinity for alpha2BAR, and alpha2CAR, were ineffective. We suggest that activation of alpha2ARs produces a predominantly inhibitory modulation of the NMDA-evoked responses of nociceptive neurons in the medullary dorsal horn.

The role of H2-receptor antagonists in the pathogenesis of nosocomial pneumonia in mechanically ventilated patients.

We conducted a computerized MEDLINE search and selected controlled studies and meta-analyses correlating the frequency of nosocomial pneumonia (NP) with the administration of histamine2-receptor antagonists (H2RAs) as stress ulcer prophylaxis in critically ill patients. Although such a correlation does exist, the literature supports the theory that gastric bacterial overcolonization through alkalinization by H2RAs is not a risk factor for NP in critically ill patients. Further well-designed studies are necessary to resolve the issue and clarify the role of H2RAs in the pathogenesis of NP.

Therapeutic-interchange program for oral histamine H2-receptor antagonists.

A therapeutic-interchange (TI) program for oral histamine H2-receptor antagonists at a hospital is described. In 1992 the pharmacy and therapeutics committee at a large teaching hospital accepted cimetidine as the preferred oral H2 antagonist. However, the program to promote cimetidine met with little success. The manufacturer of nizatidine then offered the hospital that drug at a reduced cost relative to all other members of the drug class. The committee recommended including nizatidine on the formulary; implementing a TI program so that when an order for an oral H2 antagonist was written nizatidine would be dispensed; deleting cimetidine and ranitidine tablets from the formulary; and retaining cimetidine and ranitidine oral liquid and i.v. formulations. The program was approved by the medical executive committee and was implemented in August 1994. Extensive efforts to inform the pharmacy, medical, and nursing staffs about the program were undertaken, and the pharmacy established mechanisms for monitoring compliance. Two months into the program, 97% of eligible patients were receiving nizatidine. Actual cost savings in the first four months exceeded $40,000. In July 1997 the same program was applied to famotidine, which had replaced nizatidine as the most cost-effective H2 antagonist. A successful TI program for oral H2 antagonists was achieved by gaining physician support for the program, educating providers, monitoring compliance, and responding to changes in drug costs.

Forced choice and ordinal discrete rating assessment of image quality: a comparison.

This study compared a five-category ordinal scale and a two-alternative forced-choice subjective rating of image quality preferences in a multiabnormality environment. 140 pairs of laser-printed posteroanterior (PA) chest images were evaluated twice by three radiologists who were asked to select during a side-by-side review which image in each pair was the "better" one for the determination of the presence or absence of specific abnormalities. Each pair included one image (the digitized film at 100 microns pixel resolution and laser printed onto film) and a highly compressed (approximately 60:1) and decompressed version of the digitized film that was laser printed onto film. Ratings were performed once with a five-category ordinal scale and once with a two-alternative forced-choice scale. The selection process was significantly affected by the rating scale used. The "comparable" or "equivalent for diagnosis "category was used in 88.5% of the ratings with the ordinal scale. When using the two-alternative forced-choice approach, noncompressed images were selected 66.8% of the time as being the "better" images. This resulted in a significantly lower ability to detect small differences in perceived image quality between the noncompressed and compressed images when the ordinal rating scale is used. Observer behavior can be affected by the type of question asked and the rating scale used. Observers are highly sensitive to small differences in image presentation during a side-by-side review.

Mitochondrial cytochrome C oxidase subunit I of Manduca sexta and a comparison with other invertebrate genes.

A cDNA encoding mitochondrial cytochrome c oxidase subunit I (mt COI) from Manduca sexta (Lepidoptera: Sphingidae) was cloned and sequenced. AT (adenine-thymine) content is high and codon usage is biased and likely reflects the role of mt COI in electron transport. The encoded protein is 514 amino acids long, contains seven invariant His residues observed in COIs in all organisms and would be predicted to be composed of 12 transmembrane regions.

Long-term patient self-management of oral anticoagulation.

BACKGROUND: The management of oral anticoagulation is fraught with difficulties. This study assessed a new model of anticoagulation management regarding the ability, safety, and efficacy of patients to self-monitor and self-adjust the dose of their oral anticoagulants guided by a capillary whole-blood prothrombin time (PT) monitor. METHODS: This investigation is a retrospective cohort study of 20 patients compared with 20 matched control patients receiving oral anticoagulation at a tertiary medical institution. RESULTS: Study patients monitored their PTs 2153 times during a mean interval of 44.7 months compared with 1608 PTs in matched control patients during a mean interval of 42.5 months. Study patients made an average of 11.5 dosage changes per patient, contrasted with 22.7 changes per control patient (P < .001). The PTs in study patients were within the recommended therapeutic range in 88.6% (95% confidence interval, 87.2 to 89.9) of the determinations compared with 68.0% (95% confidence interval, 65.7 to 70.3; P < .001) of the determinations made by the matched control patients. In response to the 2153 PTs, study patients made 67 (3.1%) dosage decisions that were considered incorrect based on physician guidelines. None of these changes led to adverse outcomes. There was no significant difference in complication rates between the two groups. CONCLUSIONS: Results from what is the first long-term study of patient self-monitoring of PTs and self-adjustment of the warfarin sodium dosage for oral anticoagulation suggest that patients can successfully measure their own PTs, adjust their own warfarin dosage, and achieve a degree of therapeutic effectiveness at least as good, if not better than patients managed in an anti-coagulation clinic. Larger, prospective, randomized trials are needed to confirm the efficacy and safety of this new approach to therapy and to assess its cost-effectiveness.