Klebsiella pneumoniae ST307 with OXA-181: threat of a high-risk clone and promiscuous plasmid in a resource-constrained healthcare setting.

INTRODUCTION: Klebsiella pneumoniae with OXA-48-like enzymes were introduced into Tshwane Tertiary Hospital (TTH) (Pretoria, South Africa) during September 2015, causing nosocomial outbreaks. METHODS: PCR methodologies and WGS were used to characterize K. pneumoniae with carbapenemases (n = 124) from TTH (July 2015-December 2016). RESULTS: PCR was used to track K. pneumoniae ST307 with OXA-181 among 60% of carbapenemase-positive isolates in different wards/units over time and showed the transmission of IncX3 plasmids to other K. pneumoniae clones. WGS identified different ST307 clades: 307_OXA181 (consisting of two lineages, A and B) with OXA-181 on IncX3 plasmids (named p72_X3_OXA181) and clade 307_VIM with VIM-1 on IncFII plasmids. Clade 307_OXA181 lineage B was responsible for the rapid increase and transmission of OXA-181 K. pneumoniae in various wards/units throughout TTH, while the numbers of clade 307_OXA181 lineage A and clade 307_VIM remained low. Separate outbreaks were due to K. pneumoniae ST17 and ST29 with p72_X3_OXA181 plasmids. CONCLUSIONS: The high-risk clone K. pneumoniae ST307 with OXA-181 rapidly spread to different wards/units despite infection and prevention measures. ST307 clades and lineages seemingly acted differently in outbreak situations. This study also highlighted the threat of promiscuous plasmids such as p72_X3_OXA181.

Impact of FDG PET on the management of TBC treatment. A pilot study.

UNLABELLED: The aim of this study is to assess the potential impact of double-phase FDG PET versus routine staging in HIV-negative patients suffering from tuberculosis. PATIENTS, METHODS: 16 consecutive patients suffering from tuberculosis underwent contrast-enhanced CT and double-phase FDG PET imaging (45 min, 120 min). Early (E) and delayed (D) SUVmax values were determined for all identified lesions and % change in SUV calculated (DeltaSUV). RESULTS: Seven patients presented with lung lesions on PET as well as CT (mean SUVmaxE 8.2, mean SUVmaxD 11.1, (p = 0.002), DeltaSUV 35%. In two patients, lesions were judged as non-active on CT. In nine patients, 18 sites of LN involvement were identified on both early and delayed FDG PET images (mean SUVmaxE 6.3, mean SUVmaxD 7.9, (p = 0.0001), DeltaSUV: 25%). 9 out of 18 sites of LN involvement, occurring in five patients, were missed on CT. In four of these five patients, sites of LN involvement were the only sites of extra-pulmonary involvement identified. In 6 out of 16 patients, pleural involvement was identified, respectively in 5 on FDG PET and in 6 on CT imaging (mean SUVmaxE 1.3, mean SUVmaxD 1.7, (p = 0.06), DeltaSUV 21%). In 4 patients, osseous involvement was identified by both FDG PET and CT (mean SUVmaxE 7.2, mean SUVmaxD 10.7, (p = 0,06), DeltaSUV 45%). Finally, in 3 patients, joint involvement was identified on both FDG PET as well as on CT imaging (mean SUVmaxE 4.7, mean SUVmaxD 5.2, DeltaSUV 23%). FDG PET did not identify CT-additional sites of involvement that would have resulted in a prolonged treatment. CONCLUSION: In HIV-negative patients suffering from tuberculosis, FDG PET images suggested a more extensive involvement by Mycobacterium tuberculosis when compared to contrast enhanced CT.

Superior mesenteric artery syndrome: a rare etiology of upper intestinal obstruction in adults.

The superior mesenteric artery (SMA) syndrome is an atypical cause of high intestinal obstruction in adults. Formerly considered controversial, this syndrome has now been recognized as a real clinical entity which results from extrinsic compression of the third portion of the duodenum by reduction of the angle formed between the SMA and the aorta, usually favoured by rapid and dramatic weight loss. We report a case observed in a 25-year-old female. The abdominal scan provided the diagnosis. Laparoscopic duodenojejunostomy provided cure after failure of initial conservative treatment.

Location and Setting of the Mars InSight Lander, Instruments, and Landing Site.

Knowing precisely where a spacecraft lands on Mars is important for understanding the regional and local context, setting, and the offset between the inertial and cartographic frames. For the InSight spacecraft, the payload of geophysical and environmental sensors also particularly benefits from knowing exactly where the instruments are located. A ~30 cm/pixel image acquired from orbit after landing clearly resolves the lander and the large circular solar panels. This image was carefully georeferenced to a hierarchically generated and coregistered set of decreasing resolution orthoimages and digital elevation models to the established positive east, planetocentric coordinate system. The lander is located at 4.502384°N, 135.623447°E at an elevation of -2,613.426 m with respect to the geoid in Elysium Planitia. Instrument locations (and the magnetometer orientation) are derived by transforming from Instrument Deployment Arm, spacecraft mechanical, and site frames into the cartographic frame. A viewshed created from 1.5 m above the lander and the high-resolution orbital digital elevation model shows the lander is on a shallow regional slope down to the east that reveals crater rims on the east horizon ~400 m and 2.4 km away. A slope up to the north limits the horizon to about 50 m away where three rocks and an eolian bedform are visible on the rim of a degraded crater rim. Azimuths to rocks and craters identified in both surface panoramas and high-resolution orbital images reveal that north in the site frame and the cartographic frame are the same (within 1°).

Standardization of natural mycolic acid antigen composition and production for use in biomarker antibody detection to diagnose active tuberculosis.

Mycobacterium tuberculosis, the causative agent of tuberculosis, is characterized by the abundance of species specific, antigenic cell wall lipids called mycolic acids. These wax-like molecules all share an identical, amphiphilic mycolic motif, but have different functional groups in a long hydrophobic hydrocarbon mero-chain that divide them into three main classes: alpha-, keto- and methoxy-mycolic acids. Whereas alpha-mycolic acids constitutively maintain an abundance of around 50%, the ratio of methoxy- to keto-mycolic acid types may vary depending on, among other things, the growth stage of M. tuberculosis. In human patients, antibodies to mycolic acids have shown potential as diagnostic serum biomarkers for active TB. Variations in mycolic acid composition affect the antigenic properties and can potentially compromise the precision of detection of anti-mycolic acids antibodies in patient sera to natural mixtures. We demonstrate this here with combinations of synthetic mycolic acid antigens, tested against TB patient and control sera. Combinations of methoxy- and α-mycolic acids are more antigenic than combinations of keto- and α-mycolic acids, showing the former to give a more sensitive test for TB biomarker antibodies. Natural mixtures of mycolic acids isolated from mature cultures of M. tuberculosis H37Rv give the same sensitivity as that with synthetic methoxy- and α-mycolic acids in combination, in a surface plasmon resonance inhibition biosensor test. To ensure that the antigenic activity of isolates of natural mycolic acids is reproducible, we cultured M. tuberculosis H37Rv on Middlebrook 7H10 solid agar plates to stationary growth phase in a standardized, optimal way. The proportions of mycolic acid classes in various batches of the isolates prepared from these cultures were compared to a commercially available natural mycolic acid isolate. LC-MS/MS and NMR data for quantitation of mycolic acids class compositions show that the variation in batches is small, suggesting that the quality of the results for anti-mycolic acid antibody detection in the TB patients should not be affected by different batches of natural mycolic acid antigens if prepared in a standard way.

Altered insulin secretory responses to glucose in subjects with a mutation in the MODY1 gene on chromosome 20.

This study was undertaken to test the hypothesis that the diabetes susceptibility gene on chromosome 20q12 responsible for maturity-onset diabetes of the young (MODY) in a large kindred, the RW family, results in characteristic alterations in the dose-response relationships between plasma glucose concentration and insulin secretion rate (ISR) that differentiate this form of MODY from MODY in subjects with glucokinase mutations. Ten marker-positive subjects and six matched nondiabetic marker-negative subjects from the RW family received graded intravenous glucose infusions on two occasions separated by a 42-h continuous intravenous glucose infusion designed to prime the beta-cell to secrete more insulin in response to glucose. ISR was derived by deconvolution of peripheral C-peptide levels. Basal glucose and insulin levels were similar in marker-negative and marker-positive groups (5.3 +/- 0.2 vs. 5.0 +/- 0.2 mmol/l, P > 0.2, and 86.1 +/- 3.9 vs. 63.7 +/- 12.1 pmol/l, P > 0.1, respectively). However, the marker-positive subjects had defective insulin secretory responses to an increase in plasma glucose concentrations. Thus, as the glucose concentration was raised above 7 mmol/l, the slope of the curve relating glucose and ISR was significantly blunted in the marker-positive subjects (13 +/- 4 vs. 68 +/- 8 pmol.min-1.mmol-1 x 1, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Radiofrequency ablation for colorectal liver metastases.

The management of hepatic metastases from colorectal cancer (HMCRC) is multimodal including chemotherapy, surgical resection, radiation therapy, and focused destruction technologies. Radiofrequency ablation (RFA) is the most commonly used focused destruction technology. It represents a therapeutic option that may be potentially curative in cases where surgical excision is contra-indicated. It also increases the number of candidates for surgical resection among patients whose liver metastases were initially deemed unresectable. This article explains the techniques, indications, and results of radiofrequency ablation in the treatment of hepatic colorectal metastases.

Rapid impact of effective treatment on transmission of multidrug-resistant tuberculosis.

BACKGROUND: Effective treatment for drug-susceptible tuberculosis (TB) rapidly renders patients non-infectious, long before conversion of sputum acid-fast smear or culture to negative. Multidrug-resistant TB (MDR-TB) patients on treatment are currently assumed to remain infectious for months. While the resources required for prolonged hospitalization are a barrier to the scale-up of MDR-TB treatment, the safety of community treatment is clear. OBJECTIVES: To estimate the impact of treatment on infectiousness among MDR-TB patients. METHODS: A series of five human-to-guinea pig TB transmission studies was conducted to test various interventions for infection control. Guinea pigs in adjacent chambers were exposed to exhaust air from a hospital ward occupied by mostly sputum smear- and culture-positive MDR-TB patients. The guinea pigs then underwent tuberculin skin testing for infection. Only the control groups of guinea pigs from each study (no interventions used) provide the data for this analysis. The number of guinea pigs infected in each study is reported and correlated with Mycobacterium tuberculosis drug susceptibility relative to treatment. RESULTS: Despite exposure to presumably infectious MDR-TB patients, infection percentages among guinea pigs ranged from 1% to 77% in the five experiments conducted. In one experiment in which guinea pigs were exposed to 27 MDR-TB patients newly started on effective treatment for 3 months, there was minimal transmission. In four other experiments with greater transmission, guinea pigs had been exposed to patients with unsuspected extensively drug-resistant tuberculosis who were not on effective treatment. CONCLUSIONS: In this model, effective treatment appears to render MDR-TB patients rapidly non-infectious. Further prospective studies on this subject are needed.

A pancreatic metastasis from a colon cancer.

Pancreatic metastases from colorectal cancer are extremely rare. We report the case of a 74-years-old patient presented with a metachronous pancreatic metastasis, which was treated by segmental pancreatectomy. After reviewing literature, diagnosis and management of pancreatic metastasis from colorectal carcinoma are discussed.

Chapter 5 - Detection of antimycolic acid antibodies by liposomal biosensors.

Antibodies to mycolic acid (MA) antigens can be detected as surrogate markers of active tuberculosis (TB) with evanescent field biosensors where the lipid antigens are encapsulated in liposomes. Standard immunoassay such as ELISA, where the lipid antigen is not encapsulated, but directly adsorbed to the well-bottoms of microtiter plates, does not yield the required sensitivity and specificity for accurate diagnosis of TB. One reason for this is the cross-reactivity of natural anticholesterol antibodies with MAs. MAs are the major cell wall lipids of mycobacteria. Mycobacterial MA has immunomodulatory properties and elicits specific antibodies in TB patients. Liposomes were optimized for their use as carriers both for the presentation of immobilized purified mycobacterial MA on sensor surfaces, and as a soluble inhibitor of antibody binding in inhibition assays. By using an inhibition assay in the biosensor, the interference by anticholesterol antibodies is reduced. Here, we describe the MA carrying capacity of liposomes with and without cholesterol as a stabilizing agent, optimized concentration and size of liposomes for use in the biosensor assay, comparison of the methods for wave-guide and surface plasmon resonance biosensors and how the cholesteroid nature of MA can be demonstrated by the biosensor when Amphotericin B is allowed to bind to MA in liposomes.

Cigar and marijuana use: their relationship in teens.

There is evidence of a substantial increase in teen use of both cigars and marijuana over the last decade. The theoretical concept of sensation seeking suggests a conceptual relationship between teen use of the substances. The hypothesis was that a relationship existed between the use of cigars and marijuana. Data for this study were gathered during the evaluation in a local school district of a teen tobacco-use reduction program. Questionnaire data and focus group results supported the study hypothesis and provided the direction for peer tobacco education to include an emphasis on this significant relationship. Identified associations between use of different substances supplies cues for the school nurse and other health providers to pursue specific areas of substance use practices when assessing students.

Regulation of venous alpha-adrenergic responses in older humans.

Decreased adrenergic responsiveness in human aging could be a result of downregulation mediated by the age-related increase in sympathetic nervous system (SNS) tone. If so, suppression of SNS tone in elderly subjects should upregulate adrenergic responsiveness into the range observed for younger subjects. To test this hypothesis, we examined alpha 1 (phenylephrine)- and alpha 2 (clonidine)-adrenergic agonist-mediated venoconstriction in a group of 15 older healthy subjects (age 59-73 yr) during placebo and when SNS tone was suppressed by guanadrel (15 mg twice daily for 3 wk). During guanadrel compared with placebo 1) there were decreases in plasma norepinephrine (NE) levels (1.47 +/- 0.07 to 0.80 +/- 0.06 nM; P less than 0.001) and in the extravascular NE release rate derived from [3H]NE kinetics (11.8 +/- 1.4 to 6.1 +/- 1.0 nmol.min-1.m-2; P = 0.01), suggesting suppression of SNS tone; 2) there was an augmented clonidine-mediated venoconstriction response [analysis of variance (ANOVA) P = 0.01]; and 3) there was no detectable change in phenylephrine-mediated venoconstriction (ANOVA P = 0.60). When compared with previous results from young subjects, maximal alpha 2-adrenergic venoconstriction during guanadrel was decreased in the elderly compared with the young, although their response appeared to be appropriately upregulated by the decrease in SNS tone. The lack of an age-related decrease in alpha 1-adrenergic venoconstriction, together with the lack of upregulation of this response during guanadrel, suggests that regulation of this alpha 1-adrenergic response is impaired in the older group.

Criteria for the notification of childhood tuberculosis in a high-incidence area of the western Cape Province.

The medical records of 124 children notified from Ravensmead Clinic, Parow, as having tuberculosis during 1987 were reviewed in order to determine the strength of the evidence on which the diagnosis was made. Arranging the diagnostic criteria in an hierarchical manner, as suggested by the World Health Organisation, the cases were categorised as suspect, probable or confirmed. Twenty-five were suspect cases (20%), 89 probable cases (72%) and the remaining 10 confirmed cases (8%). These findings indicated that notifications from the clinic were being made in accordance with internationally accepted practice. The use of the WHO approach for the categorisation of childhood tuberculosis cases is recommended for both clinical and epidemiological purposes.