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.

Bistatic-radar observation of long-period, directional ocean-wave spectra with loran a.

Bistatic-radar scattering from medium- to long-wavelength (80 to 200 meters) ocean waves has been observed with the use of loran A (1.85 megahertz) transmissions and a receiver located 280 kilometers away. The received echoes have been converted into a time-delay, Doppler-frequency map in which the effects of anisotropies in the ocean-wave spectra are clearly shown. The distribution of the echoes in delay-Doppler space is consistent with Bragg scattering from trains of dispersed ocean waves.

Bistatic-radar detection of lunar scattering centers with lunar orbiter I.

Continuous-wave signals transmitted from Lunar Orbiter I have been received on Earth after they have been reflected from the surface of the moon. The frequency spectrum of the reflected signals is used to locate discrete, heterogeneous, scattering centers on the lunar surface. The scattering centers are probably distinguished from the surrounding terrain by a higher surface reflectivity. Continuous-wave bistatic radar could provide an important new method for the study and mapping of planetary surfaces.

Second-order scattering from the sea: ten-meter radar observations of the Doppler continuum.

Ten-meter radar observations of the sea have been used to study second-order interactions between waves in electromagnetic scattering from the sea. Techniques of coherent, pulsed radar provide echo frequency spectra from several range intervals. The echo spectra are resolved with an analysis window of a few millihertz. These spectra show a clear second-order echo continuum which appears as sidebands about the first-order Bragg scattering lines. Up to one-half of the total echo power has been observed in these sidebands. The principal characteristics of these sidebands vary with time, apparently in response to the sea state. The form of the echo spectra is consistent with the results of perturbation theory computations based on Rice's method.

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.

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.

Sequence of three cDNAs encoding an alkaline midgut trypsin from Manduca sexta.

We have purified trypsin from the midgut of Manduca sexta and shown it has an alkaline pH optimum of 10.5. In order to clone the midgut trypsin, a DNA probe was generated using the polymerase chain reaction (PCR) with template isolated from a midgut cDNA library phage stock, a mixture of degenerate primers synthesized to code for the highly conserved region around the active site serine found in trypsins, and the T7 sequencing primer. Three different trypsin cDNAs were isolated each of which encodes a preproenzyme of 256 amino acids with a putative signal sequence of 17 amino acids, an activation peptide of seven amino acids and a mature trypsin of 232 amino acids. The encoded midgut trypsins contain the highly conserved residues, Asp, His, Ser, involved in catalysis in serine proteases, along with the residues which define the trypsin specificity pocket. Sequence comparisons show that all sequences are similar to other invertebrate and vertebrate serine proteases, but they differ in that two of the three encoded trypsins have an odd number of cysteines. Northern analysis localizes the trypsin mRNA to the middle third of the midgut. A large number of arginines (19, 20 and 21) are encoded by the three cDNAs which may stabilize the trypsin, by remaining protonated, in the alkaline midgut of M. sexta.

Purification, characterization and cDNA sequence of an alkaline chymotrypsin from the midgut of Manduca sexta.

The chymotrypsin in the midgut of Manduca sexta has been purified, characterized and the cDNA encoding the protein has been cloned. The enzyme exists as a monomer of approx. 24 kDa and shows maximal activity between pH 10.5 and 11.0. Kinetic studies reveal that the Michaelis constant (Km) for the synthetic substrate N-succinyl-Ala-Ala-Pro-Phe p-nitroanilide varies only slightly between pH 7.5 and 11.5 and the Dixon plot shows a kinetically significant pKa at 9.2. The specificity of the purified enzyme was determined to be the peptide bond on the carboxyl side of tyrosine, phenylalanine, tryptophan, histidine, leucine, threonine and glycine. The protease is inhibited by TPCK, PMSF, chymostatin and DFP. A 1 kilobase chymotrypsin cDNA clone was isolated and sequenced. The cDNA sequence encodes a preproenzyme with a putative 17 amino acid signal sequence, a 41 amino acid activation peptide and a mature enzyme of 235 amino acids. The isolated clone encodes the highly conserved active site residues (His, Asp, Ser) and specificity pocket residues present in bovine chymotrypsinogen B. Northern analysis localizes the mRNA for the chymotrypsin to the anterior and middle third of the midgut.

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.

The pathogenesis of Munchausen syndrome. A review and case report.

The authors present a case of Munchausen syndrome notable for an extended premorbid length and lack of early identifiable antisocial behavior. The patient's life history has been reconstructed, and an integrated psychobiological evaluation of the patient is given including neuroanatomical, neurohormonal, and neuropsychological assessments. Frontotemporal cerebral atrophy and lack of thyroid-stimulating hormone response to thyroid-releasing hormone infusion were found. Although self-object losses did appear to precipitate the Munchausen syndrome in a step-wise fashion, it appears that central nervous system deterioration might have been related to the development of the disorder.

Expert systems. Assisting formulary decision making in the ambulatory setting.

In this article, the author reviews the application of a computer-assisted decision support system to their formulary decision-making process. Basic information is presented describing expert systems, which are a type of computer-assisted decision support system, and their advantages and disadvantages. A specific example of an expert system, 'RXPERT', is described. 'RXPERT' is a prototype expert system that models the decision-making process for an ambulatory (nonhospital) formulary. This formulary is the underpinning of the prescription drug benefit programme for the nearly 1 million residents of Saskatchewan, Canada. In the current formulary decision process, each drug product is evaluated by 2 separate committees, with the third and final decision resting with the Ministry of Health. The first committee, the Drug Quality Assessment Committee (DQAC), comprises members with expertise in medicine, pharmacology, clinical pharmacy, pharmaceutics, statistics, and regulatory processes. The DQAC evaluates information from the drug manufacturer and other independent sources, and makes an initial assessment with respect to clinical aspects of alternative therapies and generic interchangeability. The committee then makes its recommendation to the Saskatchewan Formulary Committee (SFC). The SFC reviews the recommendation of the DQAC and considers the administrative and economic implications of accepting the product for the patient, the programme, and healthcare professionals' practice. The SFC either reaffirms the recommendation of the DQAC or modifies it based on further review, and forwards its recommendation to the Ministry of Health. Finally, the Ministry of Health reviews the evaluation and determines the drug's formulary status.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

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.

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.

Averaged electrode voltages used to identify nonfunctioning electrodes in cochlear implants: case study.

We present the case of an adult male whose internal cochlear implant unit failed. Several months elapsed following initial stimulation with the implant before the problem was identified and corrected. The sequence of the failure and its detection are detailed. Following reimplantation, the patient did not initially report improved sound quality. However, within a week of the initial stimulation of the second device, he reported being able to identify environmental sounds, and speech began to sound the way he remembered it before he lost his hearing. We suggest a method of detection that might improve the early identification of a nonfunctioning device or of nonfunctioning individual electrodes. Knowledge of specific nonfunctioning electrodes is important in device adjustment, especially for young children.

Cochlear implantation in the senior citizen age group using the Nucleus 22-channel device.

Cochlear implantation has become a recognized beneficial method of assisting in the rehabilitation of the profoundly deaf individual. The only device that is currently approved by the Food and Drug Administration for implantation in children and adults in the United States is the Nucleus 22-channel device. Since 1988, the Nucleus is the only device that has been implanted at the Mayo Clinic, Rochester, Minnesota. Fifty-six patients ranging in age from 3 to 85 have received implants. Twenty-five (45%) were over 55 and 14 (25%) were 65 or older. All of the patients over 55 are currently using their implants. Several of the patients over 65 are continuing to be gainfully employed. The benefits, complications, and results are addressed.

Comparison of home glucose monitoring with the oral glucose tolerance test to detect gestational glucose intolerance.

BACKGROUND: Recent evidence suggests that infant morbidity is increased among women who have abnormal prenatal glucose screening tests but who do not have gestational diabetes mellitus (GDM). These women fall into a diagnostic gray zone and historically have not been treated. METHODS: Forty-eight pregnant women with abnormal oral glucose challenge test results performed self-monitored blood glucose (SMBG) testing seven times per day for 1 week before undergoing a diagnostic 100-g oral glucose tolerance test (OGTT). At delivery, perinatal complications and birthweights were recorded. Results of SMBG tests for women with normal OGTTs were correlated with infant birthweights. RESULTS: Thirteen infants (37%) were found to be large for gestational age (LGA). Significant correlation was found between increasing birthweight and increasing average fasting SMBG values (P < .001), increasing percentage of SMBG values above 120 mg/dL (6.7 mmol/L) (P < .01), and increasing average SMBG values (P < .016). CONCLUSIONS: Maternal home glucose values at 28 weeks correlate with the risk of LGA infant births among women in the diagnostic gray zone. Women with average fasting SMBG values > 95 mg/dL (5.3 mmol/L) are at increased risk for giving birth to LGA infants and may be more likely to exhibit complications usually associated with GDM.

VLSI processors for signal detection in SETI.

The objective of the Search for Extraterrestrial Intelligence (SETI) is to locate an artificially created signal coming from a distant star. This is done in two steps: (1) spectral analysis of an incoming radio frequency band, and (2) pattern detection for narrow-band signals. Both steps are computationally expensive and require the development of specially designed computer architectures. To reduce the size and cost of the SETI signal detection machine, two custom VLSI chips are under development. The first chip, the SETI DSP Engine, is used in the spectrum analyzer and is specially designed to compute Discrete Fourier Transforms (DFTs). It is a high-speed arithmetic processor that has two adders, one multiplier-accumulator, and three four-port memories. The second chip is a new type of Content-Addressable Memory. It is the heart of an associative processor that is used for pattern detection. Both chips incorporate many innovative circuits and architectural features.

Facsimile (fax) technology.

Fax technology is the transmission of text and graphic data between two locations via telephone lines. The advantages of this technology include the speed with which a document can be sent anywhere in the world and the decreased cost versus traditional courier and Telex services. Several different types of machines exist, but standard operating parameters are set by the Consultative Committee for International Telephone and Telegraph (CCITT). There are four categories of machines, called Groups, which aid in classifying the various fax units. Group 3 machines are the most common comprising about 75% of the market. Standard features vary between and within groups, depending on the manufacturer and model. Features such as polling, document broadcasting, security levels, and computer linkage are discussed. The healthcare industry has been slow to adopt fax technology. Applications in hospital pharmacy are the main focus of attention of some hospital administrators and directors of pharmacy. A few studies have shown decreased medication order turnaround time after implementation of a fax-based pharmacy order system. However, problems such as order clarity and legibility, elevated nursing expectations and increased use of paper can decrease its usefulness. Overall, facsimile technology will find a place in the healthcare arena and may become an integral part of the modern pharmacy department.