Measurement of regional substrate utilization rates by emission tomography.

Emission tomography can be used to monitor, in vivo and regionally, the utilization of metabolic substrates labeled with positron-emitting radioisotopes produced by a cyclotron. The concept was validated by measuring brain glucose utilization with carbon--11-labeled glucose in rhesus monkeys.

A novel metallo-beta-lactamase, Mbl1b, produced by the environmental bacterium Caulobacter crescentus.

Caulobacter crescentus 101123 possesses a gene (Mbl1b) encoding a metallo-beta-lactamase with 32% amino acid identity to the L1 metallo-beta-lactamase from Stenotrophomonas maltophilia. The gene was cloned into an expression vector and the enzyme, Mbl1b, was expressed in Escherichia coli. Mbl1b was purified. Catalytic properties for several antibiotics were determined. The enzyme exhibits Michaelis-Menten kinetics for imipenem, meropenem and nitrocefin but substrate inhibition kinetics with cefoxitin, cefaloridine, penicillin G and ampicillin. A homology model predicts Mbl1b has the same structural fold as other metallo-beta-lactamases with a detailed structure very similar to L1 but whereas L1 is a homotetramer, Mbl1b is monomeric. The main differences between Mbl1 and L1 are in the N-terminal region.

Determination of radionuclide concentrations with positron CT scanning (PETT): concise communication.

A series of experiments was undertaken to evaluate the response of a positron emission transverse tomograph (PETT) to measured radionuclide concentrations similar to those encountered in human studies. The correlation between the response of the imaging system (mean PETT number/min), and the concentration of the radioactivity producing the output data, was linear with a computed sensitivity of 2720 PETT number/min, per micronCi/ml, per picture element, for a radionuclide (100% beta+) contained in either of two phantoms and imaged with a reduction of 1.5 cm. It was concluded that the output data are essentially independent of the imaged object's physical dimensions for the range of 18-28-cm diam and faithfully reflect the regional radioactivity concentration within the object, provided valid attenuation correction is achieved and the sampled area is not compromised by the imaging system's limitations of spatial resolution.

Design and performance characteristics of a whole-body positron transaxial tomograph.

A whole-body positron-emission transaxial tomograph (PETT III) is described in detail and evaluated in terms of resolution, accuracy, and efficiency. The PETT III utilizes annihilation coincidence detection to provide spatial resolution; high sensitivity is achieved by using 48 Nal(tl) detectors set in a hexagonal array with a multiple-coincidence logic. The assumptions and approximations made in the reconstruction and their effect on image quality are discussed. Phantom studies shows the depth-independent resolution and response of PETT III, as well as its ability to recover activity distribution quantitatively in the cross section measured. Images obtained with patients and normal volunteers show the potential clinical utility of PETT III.

Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria.

OBJECTIVE: To investigate the antibiotic and biocide susceptibilities of clinical isolates of rarely encountered Gram-negative, non-fermenting bacteria. METHODS: Thirty Gram-negative non-fermenting bacterial strains were isolated from blood cultures of oncology patients. These were studied for their resistance to 11 antibiotics. Their susceptibilities to seven biocides used in hospitals were also examined. RESULTS: Isolates of Stenotrophomonas maltophilia and Ochrobactrum anthropi were generally resistant to at least five of the antibiotics, whereas isolates of Comamonas acidivorans, Flavobacterium oryzihabitans, Aeromonas hydrophila, Sphingobacterium spiritivorum, Acinetobacter junii and Acinetobacter lwoffi were generally sensitive to at least nine of the antibiotics. Trovafloxacin and trimethoprim-sulfamethoxazole were the most effective antibacterial agents tested, with 0% and 7%, respectively, of isolates being resistant, whereas 63% of isolates were resistant to aztreonam. Some isolates, sensitive to meropenem and/or ceftazidime in vitro, possessed very high MBC/MIC ratios for these beta-lactams. Two out of three biocides used in hospital pharmacies showed lethal activity towards all strains tested when used at less than one-third of their recommended in-use concentration. Proceine 40 failed to give a 5 log reduction in bacterial cell number for the isolates tested when used at its "in-use" concentration. A concentration of > 500 mg/L chlorhexidine was required to achieve a 5 log reduction for the same isolates. CONCLUSIONS: We have examined the antibiotic susceptibilities of non-fermenting Gram-negative bacterial strains isolated from immunocompromised patients. Despite being sensitive to certain antibiotics in vitro, some isolates were still able to cause serious bacteremia. We have also reported for the first time the susceptibilities of non-fermenting Gram-negative bacteria to common biocides used in hospital infection control, and have shown that some strains are able to persist at the "in-use" concentration of particular biocides. It is therefore important to study further this particular group of organisms, and, in particular, to examine whether there exists a link between resistance to antibiotics and resistance to biocides.

Factors associated with hospital-specific cesarean birth rates.

The variation in hospital-specific cesarean birth rates was examined using a multiple regression analysis in a national data base of deliveries in 1977. This data base included 222,285 singleton births in 282 hospitals representing all regions of the United States. The 32 independent variables included measures of medical risk, technologic sophistication, demographic characteristics and economic incentives. The incidences of medical risk factors, nonwhite race and ratio of obstetricians to fertile women were associated positively with hospital-specific cesarean delivery rates. Participation in health maintenance organizations and numbers of deliveries were correlated negatively with those rates. Hospital-specific cesarean delivery rates were not associated with technologic sophistication, malpractice premiums or reimbursement differences between routes of delivery. Pay source stratified models explained 45-63% of the variation in the hospital-specific cesarean rates. Sensitivity analysis revealed that even a 50% change in the incidence of any independent variable would change the cesarean delivery rate by less than 2%.

Pathways to long-term geriatric hospital care.

This paper describes the pathways that are taken to long-term geriatric hospital care. Information was collected for 160 people currently receiving such care, and it was found that 110 different pathways were taken to a long-term geriatric bed. The most commonly experienced accommodation settings were acute hospital care, and living in the community with some form of disability but no domiciliary services, which were also the most frequent ways of beginning the pathways. The ends of the pathways were characterized by acute hospital care, short-term geriatric or convalescent care and rest or residential care. Domiciliary services had been used by less than half of the sample, and many of these appeared to have been receiving only a minimal level of support. This paper also examines the role of the assessment and rehabilitation unit, and seeks to comment on how services designed to reduce the demand for long-term geriatric care have been used.

A study of the recipients of district nursing services in Christchurch.

This paper reports on a study of the patients and the services provided by the Nurse Maude District Nursing Association in Christchurch. The 1149 recipients were predominantly elderly, 80.8% being over 65, 68.8% female and long term patients with musculoskeletal disorders comprising more than one-third of the principal diagnoses. Services were provided to 26 per 1000 of the elderly population, which is close to suggested guidelines. This rate increased markedly with age. Ten percent of patients utilised 40% of the nursing time. They may be considered as borderline cases for whom community care with community support services was an acceptable and efficient alternative to long term hospital care.

General practitioner prescribing rates and costs.

This study was undertaken to determine whether the relationship between availability (population/GP) and utilisation (services/person) shown in previous work also applied to general practitioner prescribing rates and costs. Pharmaceutical pricing office records of payments to pharmacists were used as a data base. Calculated rates of prescribing and costs for 1978/79 showed a wide variation between health districts ranging from 9.0 prescription items and $40.18 per capita in Whangarei, to 5.8 items and $26.83 in Invercargill. These rates were highly correlated with both availability and utilisation, thus indicating that the wide inequality in distribution of general practitioners is associated with an equivalent maldistribution of pharmaceutical expenditure. In 1978/79 each general practitioner on average issued 16315 prescriptions at a cost of $72 934. These findings have important cost and policy implications with the projected surplus of medical manpower seeking entry to general practice.

Determinants of hospital use: a cross-diagnostic analysis.

This article estimates the effects of personal, clinical, physician, and hospital characteristics in a simultaneous equations model of length of stay and ancillary services use for five narrowly defined medical and surgical conditions. These are tonsillectomy and adenoidectomy, gastroenteritis and colitis, inguinal hernia, coronary heart disease, and cholelithiasis. The data are derived from a sample survey of medical and financial records of patients discharged from any of 63 New England short-term general hospitals during the period July 1, 1969 through June 30, 1970. The results confirm the importance of a simultaneous equations formulation of utilization analysis and of inclusion of detailed measures of severity. Length of stay and ancillary services are significantly interrelated for all five conditions, corroborating results of a previous study of obstetric cases. Results for patient's employment status and value of time, attending physician specialty and mode of practice, and hospital size, control, and nature of teaching activities were less conclusive, but suggest differential effects across diagnoses, thus emphasizing the importance of a diagnostic-specific approach to utilization analysis.

Measurement of regional cerebral blood volume by emission tomography.

The technique of positron emission tomography was used to measure cerebral blood volume (CBV) in 10 normal right-handed human volunteers following inhalation of trace quantities of cyclotron-produced, 11C-labeled carbon monoxide. In scans obtained 4 cm above the orbitomeatal line, CBV was 4.3 ml per 100 gm of tissue, whereas in scans obtained 8 cm above the orbitomeatal line, CBV was significantly less (3.3 ml per 100 gm; p less than 0.001). This difference reflects the greater proportion of gray matter in the lower scan. Furthermore, the CBV was significantly larger (p less than 0.001) in the left cerebral hemisphere in the tomographic scans obtained 4 cm above the orbitomeatal line. These scans include the region of the superior surface of the temporal lobe (planum temporale), which is thought to be larger in individuals with left cerebral dominance for speech. This observation is the first in vivo demonstration of a structural correlate of a known functional difference in the cerebral hemispheres of man.

A TEM-2beta-lactamase encoded on an active Tn1-like transposon in the genome of a clinical isolate of Stenotrophomonas maltophilia.

A constitutively expressed beta-lactamase gene from a clinical isolate of Stenotrophomonas maltophilia, J675Ia, has been cloned. Its DNA sequence is almost identical to that of bla(TEM2) (one nucleotide change) and the expressed enzyme is a Bush type 2a penicillinase with an amino acid sequence identical to that of TEM-2. The bla(TEM) gene was present within a novel Tn1/Tn3-type transposon in the genome of isolate J675Ia and the transposon was able to mobilize bla(TEM) on to the broad host-range conjugative plasmid, R388. When transferred to an Escherichia coli recipient, R388::Tn conferred high-level ampicillin resistance. This represents the first identification of a TEM beta-lactamase in S. maltophilia and the first evidence that this important clinical pathogen is able to act as a reservoir for mobile beta-lactamase genes in the hospital environment.

A multislice positron emission computed tomograph (PETT IV) yielding transverse and longitudinal images.

We designed, built, and tested a positron emission tomograph (PETT IV) capable of providing seven slices of the human body simultaneously. PETT IV utilizes a moving hexagonal array of 48 scintillation detectors placed around the subject. Each detector consists of a cylindrical activated sodium iodide crystal optically coupled to two photomultiplier tubes. The multislice capability is achieved by comparing the light outputs of the two photomultiplier tubes in each detector. The images are displayed either as transverse or as longitudinal tomographic sections. This system provides high sensitivity and resolution, and permits rapid and accurate three-dimensional imaging of the head and body.

Plasmid location and molecular heterogeneity of the L1 and L2 beta-lactamase genes of Stenotrophomonas maltophilia.

An approximately 200-kb plasmid has been purified from clinical isolates of Stenotrophomonas maltophilia. This plasmid was found in all of the 10 isolates examined and contains both the L1 and the L2 beta-lactamase genes. The location of L1 and L2 on a plasmid makes it more likely that they could spread to other gram-negative bacteria, potentially causing clinical problems. Sequence analysis of the 10 L1 genes revealed three novel genes, L1c, L1d, and L1e, with 8, 12, and 20% divergence from the published strain IID 1275 L1 (L1a), respectively. The most unusual L1 enzyme (L1e) displayed markedly different kinetic properties, with respect to hydrolysis of nitrocefin and imipenem, compared to those of L1a (250- and 100-fold lower k(cat)/K(m) ratios respectively). L1c and L1d, in contrast, displayed levels of hydrolysis very similar to that of L1a. Several nonconservative amino acid differences with respect to L1a, L1b, L1c, and L1d were observed in the substrate binding-catalytic regions of L1e, and this could explain the kinetic differences. Three novel L2 genes (L2b, L2c, and L2d) were sequenced from the same isolates, and their sequences diverge from the published sequence of strain IID 1275 L2 (L2a) by 4, 9, and 25%, respectively. Differences in L1 and L2 gene sequences were not accompanied by similar divergences in 16S rRNA gene sequences, for which differences of <1% were found. It is therefore apparent that the L1 and L2 genes have evolved relatively quickly, perhaps because of their presence on a plasmid.

Characterization, cloning and sequence analysis of the inducible Ochrobactrum anthropi AmpC beta-lactamase.

Ochrobactrum anthropi is resistant to most cephalosporins and penicillins due, at least in part, to the inducible expression of a single beta-lactamase. The beta-lactamase gene has been cloned and sequenced. It encodes an AmpC-type class 1 serine active-site enzyme that hydrolyses mainly cephalosporins and is resistant to inhibition by clavulanic acid. Expression of the ampC gene is inducible via a typical AmpR regulator, which is encoded upstream of ampC. Inducible expression is retained following cloning of O. anthropi ampR-ampC into Escherichia coli, confirming that the signal for AmpR activation in O. anthropi is the same as that used in the Enterobacteriaceae. This is the first reported example of an AmpC beta-lactamase outside of the gamma-subdivision of the bacterial kingdom. Genomic searches of other non-gamma-subdivision bacteria revealed a homologous ampR-ampC cluster in the plant symbiont, Sinorhizobium meliloti.

Design considerations for a positron emission transverse tomograph (PETT V) for imaging of the brain.

Imaging of the brain by positron emission tomography can be optimized for sensitivity by dedicating the design of the tomograph to this application. We have designed a multislice positron emission tomograph (PETT V) for imaging the human brain and the whole body of small experimental animals. The detector system of PETT V consists of a circular array of 48 NaI(Tl) scintillation detectors, each fitted with two photomultiplier tubes, with one dimensional positioning capability. Suitable sampling is achieved by rotation of the circular array of detectors and by a wobbling motion of the detector circle. The proposed system is capable of providing seven slices simultaneously, with a spatial resolution in the plane of the slice from 7 to 15 mm and with slice thicknesses of 7 and 14 mm. The minimum scanning time is 1 sec. The estimated overall sensitivity of PETT V is 350,000 counts/sec/mCi in a 20 cm diameter phantom for a resolution of approximately 1.5 x 1.5 cm. The system is under construction.