Cost-effectiveness of a real-time spatiotemporal mapping surveillance system for meticillin-resistant Staphylococcus aureus prevention.

OBJECTIVES: An infection surveillance system based on a hospital's digital twin [4D-Disease Outbreak Surveillance System (4D-DOSS)] is being developed in Singapore. It offers near-real-time infection surveillance and mapping capabilities. This early economic modelling study was conducted, using meticillin-resistant Staphylococcus aureus (MRSA) as the pathogen of interest, to assess the potential cost-effectiveness of 4D-DOSS. METHODS: A Markov model that simulates the likelihood of MRSA colonization and infection was developed to evaluate the cost-effectiveness of adopting 4D-DOSS for MRSA surveillance from the hospital perspective, compared with current practice. The cycle duration was 1 day, and the model horizon was 30 days. Probabilistic sensitivity analysis was conducted, and the probability of cost-effectiveness was reported. Scenario analyses and a value of information analysis were performed. RESULTS: In the base-case scenario, with 10-year implementation/maintenance costs of 4D-DOSS of $0, there was 68.6% chance that 4D-DOSS would be cost-effective. In a more pessimistic but plausible scenario where the effectiveness of 4D-DOSS in reducing MRSA transmission was one-quarter of the base-case scenario with 10-year implementation/maintenance costs of $1 million, there was 47.7% chance that adoption of 4D-DOSS would be cost-effective. The value of information analysis showed that uncertainty in MRSA costs made the greatest contribution to model uncertainty. CONCLUSIONS: This early-stage modelling study revealed the circumstances for which 4D-DOSS is likely to be cost-effective at the current willingness-to-pay threshold, and identified the parameters for which further research will be worthwhile to reduce model uncertainty. Inclusion of other drug-resistant organisms will provide a more thorough assessment of the cost-effectiveness of 4D-DOSS.

Histamine H(2) receptors mediate the inhibitory effect of histamine on human eosinophil degranulation.

The effect of histamine on human eosinophil degranulation and the receptor mediating such effect were studied in vitro using the complement C5a-mediated eosinophil peroxidase (EPO) release model. Following pre-treatment with 5 microg ml(-1) cytochalasin B(CB), C5a induced a concentration-dependent release of EPO from eosinophils isolated from healthy donors. Histamine (0.1-50 microM), but not L-histidine, inhibited concentration-dependently C5a-induced EPO release with IC(50) (95% CI) of 0.6 microM (0.3-1.2 microM) and maximal inhibition of approximately 60%. A similar effect was seen with the selective H(2) agonists dimaprit (IC(50) (95% CI)=6.9 microM (3.2-10.6 microM)) and amthamine (IC(50) (95% CI)=0.4 microM (0.2-0.7 microM)). Neither the selective H(1) agonist 6-(2-(4-imidazolyl)ethylamino)-N-(4-trifluoromethylphenyl) heptanecarboxamide(HTMT), nor the selective H(3) agonists imetit (up to 100 microM) had any significant effect. The inhibition by histamine was reversed by cimetidine (0.1-30 microM) and other H(2) antagonists, but not the H(1) antagonist mepyramine (1.0- 100 microM), nor the H(3) antagonist thioperamide (1.0-100 microM). Cimetidine (1-30 microM) shifted to the right the dimaprit log dose-response curve, producing a pA(2) value of 5.9 and Schild's plot slope of 0.98, thus confirming simple competitive antagonism. Histamine (10-100 microM) increased intracellular level of adenosine 3',5'-cyclic monophosphate, which was completely abolished by cimetidine (30 microM), but not mepyramine or thioperamide. The cyclic AMP analogue - dibutyryl cyclic AMP - also inhibited degranulation (IC(50) approximately 300 microM). The cyclic AMP phosphodiesterase(PDE) IV inhibitor rolipram (10 microM) synergistically enhanced the inhibition of EPO release by histamine. These results suggest that histamine, via stimulation of H(2) receptors and a consequent elevation of intracellular levels of cyclic AMP, inhibits human eosinophil degranulation.

Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release.

The role of adenosine A3 receptors on human eosinophil degranulation and superoxide anion (O2-) release was studied in vitro using the complement fragment C5a as the main stimulus and employing a number of selective agonists and antagonists. In the presence of cytochalasin B (CB), C5a induced a dose-dependent release of the granular eosinophil peroxidase (EPO), but not O2-, whereas in the absence of CB O2- , but not EPO, was released. C5a-induced EPO release was inhibited dose-dependently by the selective A3 agonist N6-(3-iodobenzyl)-5'-N-methylcarbamoyladenosine (IB-MECA) and to a lesser extent by the less-selective N6-2-(4-amino-3-iodophenyl) ethyladenosine (APNEA). The IC50 (95% CI) for IB-MECA was 6.8 microM (3.1-12.0 microM). At concentrations up to 100 microM, neither adenosine nor the selective A1 agonist N-cyclopentyladenosine (CPA) and the selective A2 agonist 2-[[2-[4-(2-carboxyethyl)phenyl]ethyl]amino]-N-ethylcarboxamidoadenosine (CGS 21680) had any significant effect. The inhibitory effect of IB-MECA was almost completely abolished by pre-treatment with 1 microM of the selective A3 antagonist 9-chloro-2-(2-furyl)-5-phenylactylamino[1,2,4]triazolo[1,5-c]quina zoline (MRS 1220), but not the selective A1 antagonist 1,3-dipropyly-8-cyclopentylxanthine (DPCPX) or the selective A2 antagonist 3,7-dimethyl-1-propargylxanthine (DMPX). IB-MECA also significantly inhibited C5a-induced O2- release with IC50 (95% CI) of 9.5 microM (4.6-13.1 microM) whereas adenosine and the A1 agonist CPA potentiated this effect at low concentrations. The potentiation appeared to be a result of their direct O2- release from these cells, probably mediated via A1 receptors. The inhibition by IB-MECA was selectively reversed by MRS 1220. These results show that the A3 receptors on human eosinophils mediate inhibition of both degranulation and O2- release and suggest a therapeutic potential for A3 agonists in diseases such as asthma in which activated eosinophils are involved.

Infection by Rhodococcus equi in a patient with AIDS: histological appearance mimicking Whipple's disease and Mycobacterium avium-intracellulare infection.

Rhodococcus equi pneumonia with systemic dissemination is being reported increasingly in immunocompromised patients. This is the first case report of disseminated R equi infection with biopsy documented involvement of the large intestine. The patient was a 46 year old male with AIDS who was diagnosed with cavitating pneumonia involving the left lower lobe. R equi was isolated in culture from the blood and lung biopsies. Subsequently, the patient developed anaemia, diarrhoea, and occult blood in the stool. Colonoscopy revealed several colonic polyps. Histological examination of the colon biopsies showed extensive submucosal histiocytic infiltration with numerous Gram positive coccobacilli and PAS positive material in the histiocytes. Electron microscopy showed variably shaped intrahistiocytic organisms which were morphologically consistent with R equi in the specimen. Disseminated R equi infection may involve the lower gastrointestinal tract and produce inflammatory polyps with foamy macrophages which histologically resemble those seen in Whipple's disease and Mycobacterium avium-intracellulare infection.

Treatment of urinary incontinence in cystic fibrosis.

BACKGROUND: Urinary incontinence (UI) is a newly recognised problem in cystic fibrosis. Whilst prevalence is well documented, there are no reports of assessment and treatment of the problem. METHODS: A previous study reports the prevalence of UI in women with CF to be 51/75 (68%). Nineteen women subsequently requested help for the problem and were referred to a physiotherapist specialising in women's health. A digital assessment was performed to measure pelvic floor muscle strength and endurance. An individualised programme of pelvic floor muscle exercises (PFME) was taught based on the assessment. A questionnaire addressed issues of assessment and treatment. RESULTS: 12 women were assessed. The median (range) age, FEV1% predicted and BMI were 20.9 (19.3-46.1) years, 45.9 (14.8-82.7) and 20.5 (16.1-26.0), respectively. The median strength of the pelvic floor muscle was moderate (Oxford Scale grade 3) with a hold time (endurance) of 5 s. At reassessment (median time 13.1 weeks), there was an improvement in endurance (P = 0.04), with no change in strength. This was supported by a subjective improvement in symptoms. Patients found the exercises were difficult to perform, difficult to fit into their treatment programme and adherence was poor. CONCLUSIONS: PFME are effective at improving endurance and reducing leakage over the short-term. Women are reluctant to be assessed and the CF team should provide support and encouragement with treatment. Long-term outcome and the mechanisms of UI in this group of patients need further evaluation.

Diagnostic value of the portable chest x-ray technic in pulmonary edema.

The ability of the portable chest x-ray film to define the amount of physiologic shunting and the severity of noncardiogenic pulmonary edema was evaluated in thirty-seven observations of eleven patients. Ten of the eleven patients were suffering from acute respiratory failure. The radiologic assessment of the amount of pulmonary edema and the severity of left ventricular failure were compared with the physiologic shunt fraction, tracer-measured lung water, and pulmonary arterial wedge pressure. The radiologic scores for edema did not predict the shunt fraction or tracer measurements of lung water. The radiologic score for congestive failure correlated with the wedge pressure but not well enough to be clinically useful. Five per cent of the x-ray results were false-positive and 11 per cent false-negative. Results indicate that the portable chest x-ray technic does not provide quantitative information regarding cardiopulmonary function. It is especially hazardous to accept an x-ray diagnosis of congestive failure as the cause of pulmonary edema.

Benign chondroblastoma of talus demonstrated by skeletal scanning.

A patient with a benign condroblastoma of the talus bone is described. A review of the pathogenesis and more common sites of predilection of this unusual tumor is presented. This is the first case, to our knowlege, shown by labeled phosphate scanning.

The perfect gap: when are midline diastemas aesthetically acceptable?

To close or not close a midline diastema is a very significant issue. Ultimately, such decisions are subjective. The role of the dentist is to help patients understand the various fundamental geometric laws of aesthetics. When the relative balance and harmony of the distributed space are properly proportioned and conform to the laws of nature, either scenario is acceptable. Simple proportions using the Golden Rectangle can be used to help patients assess their individual choice.

The classification of smile patterns.

Although "smile therapy" is still in its infancy, society has already placed a great demand on dentists to evaluate and treat smiles. The smile classification scheme and vocabulary presented in this article will aid in discussions between patient and dentist regarding esthetic treatment.

Effect of wortmannin on human eosinophil responses in vitro and on bronchial inflammation and airway hyperresponsiveness in Guinea pigs in vivo.

Many mediators activate eosinophils via transduction pathways involving the enzyme phosphatidylinositol 3-kinase. The initial investigation of wortmannin, a specific inhibitor of PI3-kinase, was of its effect on human and guinea pig eosinophil superoxide (O(2)(-)) release and degranulation in vitro. Subsequently, the effect on allergen- and Sephadex-induced bronchial inflammation and airway hyperresponsiveness (AHR) in vivo in guinea pigs was investigated. Wortmannin potently inhibited complement C5a-induced O(2)(-) generation and eosinophil peroxidase (EPO) release from human eosinophils, with 50% inhibition produced by a 1-10 nM concentration. Both aerosol allergen challenge of sensitized guinea pigs and intravenous injection of Sephadex beads in normal guinea pigs caused, in 24 h, significant eosinophilia and increased EPO activity in bronchoalveolar lavage fluid (BALF) and AHR to intravenous acetylcholine and histamine. In the allergic model, intranasal pretreatment with wortmannin had no effect on BALF eosinophilia, but dose dependently inhibited BALF EPO activity. At 1 mg/kg, the drug abolished the AHR to histamine, but not acetylcholine. In the Sephadex model, the drug significantly inhibited all three parameters (eosinophilia, increased EPO activity, and AHR to both spasmogens). These results show that wortmannin is a potent inhibitor of human eosinophil degranulation and that when administered intranasally can prevent AHR in allergen-challenged guinea pigs, probably by inhibiting eosinophil degranulation, but not their accumulation in BALF. This may be relevant to the possible clinical utility of wortmannin in conditions involving eosinophilic inflammation and AHR.

Desulfuromonas palmitatis sp. nov., a marine dissimilatory Fe(III) reducer that can oxidize long-chain fatty acids.

Studies on the microorganisms living in hydrocarbon-contaminated sediments in San Diego Bay, California led to the isolation of a novel Fe(III)-reducing microorganism. This organism, designated strain SDBY1, was an obligately anaerobic, non-motile, non-flagellated, gram-negative rod. Strain SDBY1 conserves energy to support growth from the oxidation of acetate, lactate, succinate, fumarate, laurate, palmitate, or stearate. H2 was also oxidized with the reduction of Fe(III), but growth with H2 as the sole electron donor was not observed. In addition to various forms of soluble and insoluble Fe(III), strain SDBY1 also coupled growth to the reduction of fumarate, Mn(IV), or S0. Air-oxidized minus dithionite-reduced difference spectra exhibited peaks at 552.8, 523.6, and 422.8 nm, indicative of c-type cytochrome(s). Strain SDBY1 shares physiological characteristics with organisms in the genera Geobacter, Pelobacter, and Desulfuromonas. Detailed analysis of the 16S rRNA sequence indicated that strain SDBY1 should be placed in the genus Desulfuromonas. The new species name Desulfuromonas palmitatis is proposed. D. palmitatis is only the second marine organism found (after D. acetoxidans) to oxidize multicarbon organic compounds completely to carbon dioxide with Fe(III) as an electron acceptor and provides the first pure culture model for the oxidation of long-chain fatty acids coupled to Fe(III) reduction.

Auditory event-related potentials in fetal alcohol syndrome and Down's syndrome children.

Abnormal or borderline electroencephalograms are commonly observed in cases of gross mental retardation. However, fewer studies have focused on the use of event-related responses to aid in the differential diagnosis of developmental cognitive disorders. Fetal alcohol syndrome (FAS) and Down syndrome represent the most common known causes of mental retardation in the Western world. Although Down syndrome is easily diagnosed with a chromosome assay, FAS can be more difficult to diagnose since the diagnostic features are more subjectively based. The present study is the first to characterize auditory event-related potentials (ERPs) in children with FAS and contrast them to subjects with Down syndrome and controls. A passive auditory "oddball-plus-noise" paradigm was utilized to elicit ERPs. Parietal P300 latencies in response to the noise-burst stimuli for the FAS children were significantly longer, as were the P300s from all cortical sites in Down syndrome subjects in response to the both the infrequent tone and noise-burst stimuli when compared with the controls. Frontal P300s in Down syndrome children were significantly larger in amplitude compared to the controls and FAS children in response to the infrequent tone. A discriminant function analysis also revealed that these children could be correctly classified as being either Down syndrome, FAS, or normal controls using measures of latency and amplitude of the P300. These data suggest that an evaluation of ERP characteristics may provide a better understanding of the differences between FAS and Down syndrome children, and prove to be an aid in the early identification of children with FAS. These results demonstrate neurophysiological differences between FAS and Down syndrome, and suggest that P300 amplitude and latency data collected from a passive ERP task may be helpful in the discrimination of developmental cognitive disorders.

Limitations of portable roentgenography of the chest in patients with acute respiratory failure.

The ability of the portable roentgenography of the chest to define the amount of physiologic shunting and the severity of noncardiogenic pulmonary edema was evaluated in 37 observations of 11 patients. Ten of the 11 patients had acute respiratory failure. The roentgenologic assessment of the amount of pulmonary edema and the severity of left ventricular failure was compared with the physiologic shunt fraction, tracer measured lung water and the pulmonary arterial wedge pressure. The roentgenologic scores for edema did not predict the shunt fraction or tracer measured lung water. The roentgenologic score for congestive heart failure correlated with the wedge pressure but not well enough to be clinically useful. Five per cent of the roentgenograms were false-positive and 11 per cent were false-negative. Roentgenologic findings lagged behind physiologic derangements. Thus, the roentgenogram could predict the shunt value of the preceding day. Results indicate that it is hazardous to accept a portable roentgenographic diagnosis of congestive heart failure as a cause of pulmonary edema.

Endoscopic autopsy.

In cases in which the family of the deceased objects to the performance of a conventional autopsy for religious or other reasons, or where there are no forensic pathology facilities in the vicinity of the hospital, postmortem endoscopic examination may be an advantageous and cost-effective substitute for conventional necropsy, especially when the alternative is no postmortem examination at all. To test the reliability of postmortem endoscopy, conventional and endoscopic autopsies were performed on 20 cadavers at the L. Greenberg Institute of Forensic Medicine in Israel. Comparison of the findings of the two procedures showed a very high correlation (100%) for intraperitoneal and thoracic hemorrhages and hepatic, splenic, and diaphragmatic injuries; it showed a slightly lower correlation (60-80%) for mesenteric and retroperitoneal hematomas injuries to the great vessels, blood aspiration, and lung injury. Endoscopy failed to reveal the correct site of injury in the retroperitoneum and posterior aspect of the mediastinum. Collection of body fluids and tissue samples was possible by means of laparoscopy. The technique proved to be relatively accurate, more rapid than conventional autopsy, and left the body virtually intact.