MSCRAMM--targeted vaccines and immunotherapy for staphylococcal infection

Hospital-acquired infections are associated with prolonged hospitalization and an increase in both healthcare costs and resources. Advances in sophisticated medical procedures, an increase in the number of immunocompromised patients, and the continued emergence of resistance to conventional antibiotic therapy has created a need for alternative strategies to prevent and treat infectious bacterial diseases. Immunoprevention and immunotherapy targeting microbial surface components recognizing adhesive matrix molecule (MSCRAMM) proteins are viable approaches to potentially impede bacterial adherence, eliminate colonization, and minimize hematogenous dissemination, thereby halting the inception and progression of infection. This review summarizes several investigative efforts where staphylococcal MSCRAMM proteins are being utilized in the design of subunit vaccines and in the development of innovative therapeutic strategies that could be implemented following the onset of infection to manage severe and life-threatening disease.     

The process for continuous improvement of the TNM classification

The TNM classification is a worldwide benchmark for reporting the extent of malignant disease and is a major prognostic factor in predicting the outcome of patients with cancer. The objectives for cancer staging were defined by the International Union Against Cancer (UICC) TNM Committee almost 50 years ago and are still broadly applicable today. To keep pace with the modern demands of evidence-based practice, the UICC introduced a structured process for introducing changes to the TNM classification. The elements of the TNM process were determined to include the development of unambiguous criteria for the information and documentation required to consider changes in the classification, establishment of a well-defined process for the annual review of relevant literature, formation of site-specific expert panels, and the participation of experts from all over the world in the TNM review process. Communication between the oncology community and those involved in the TNM classification was established as being essential to the success of the process. The process, which was introduced in 2002, will be tested over the next 3-4 years and evaluated. In addition to the formal process, individual initiative, involvement by the national staging committees, and group consensus are required. Furthermore, increased involvement by the experts should improve the understanding and dissemination of the TNM classification.     

Patient-centered communication

OBJECTIVE: To investigate patient preferences for a patient-centered or a biomedical communication style. DESIGN: Randomized study. SETTING: Urgent care and ambulatory medicine clinics in an academic medical center. PARTICIPANTS: We recruited 250 English-speaking adult patients, excluding patients whose medical illnesses prevented evaluation of the study intervention. INTERVENTION: Participants watched one of three videotaped scenarios of simulated patient-physician discussions of complementary and alternative medicine (CAM). Each participant watched two versions of the scenario (biomedical vs. patient-centered communication style) and completed written and oral questionnaires to assess outcome measurements. MEASUREMENTS AND MAIN RESULTS: Main outcome measures were 1) preferences for a patient-centered versus a biomedical communication style; and 2) predictors of communication style preference. Participants who preferred the patient-centered style (69%; 95% confidence interval [CI], 63 to 75) tended to be younger (82% [51/62] for age < 30; 68% [100/148] for ages 30-59; 55% [21/38] for age > 59; P < .03), more educated (76% [54/71] for postcollege education; 73% [94/128] for some college; 49% [23/47] for high school only; P= .003), use CAM (75% [140/188] vs. 55% [33/60] for nonusers; P= .006), and have a patient-centered physician (88% [74/84] vs. 30% [16/54] for those with a biomedical physician; P < .0001). On multivariate analysis, factors independently associated with preferring the patient-centered style included younger age, use of herbal CAM, having a patient-centered physician, and rating a "doctor's interest in you as a person" as "very important."CONCLUSIONS: Given that a significant proportion of patients prefer a biomedical communication style, practicing physicians and medical educators should strive for flexible approaches to physician-patient communication.     

A case series of 72 neonates with renal vein thrombosis. Data from the 1-800-NO-CLOTS Registry

Neonatal renal vein thrombosis (RVT) is a well-recognized clinical entity which is associated with serious morbidity. However, current information regarding RVT has been restricted to case reports and small case series. In this study, it was our objective to describe patient demographics, clinical presentation, location and risk factors of RVT. For our study design, we looked at a case series of 72 neonates with RVT referred to the 1-800-NO-CLOTS consultation service between 9/1996 and 8/2001. Data on age, gender, associated conditions, prothrombotic disorders, family history, location of the thrombosis, diagnostic techniques, and treatment were prospectively recorded using a standardized form. Our results show that RVT affected males (65%, CI 52-76%) significantly more often than females (35%, CI 24-48%). Median age at presentation was 2 days (0-21 days). RVT was unilateral in 72% (left side: 67%,CI 49-81%; right side: 33%, CI 19-51%), and bilateral in 28%. The majority (83%) had at least one associated condition: Prematurity (54%), central venous lines (17%), a diabetic mother (13%), asphyxia (6%), infections (6%). Prothrombotic testing was performed in 21 neonates. Activated protein C resistance was found in 8 children (38%), other defects in three. This is the largest case series of neonatal RVT to date. Data from the study show that i) male infants are affected twice as often as females and ii) there appears to be a left-sided predominance of neonatal RVT. Neonatal RVT is only infrequently associated with the presence of a catheter as compared to thrombosis at other sites. The majority of infants have associated conditions with prematurity being most frequent. A small subset of neonates were screened for prothrombotic abnormalities and 50% of the children screened were positive.     

Diagnostic applications of cardiac multislice CT with sixteen-row scanner: state of the art

Coronary angiography is nowadays the diagnostic standard in the evaluation of coronary artery anatomy, in the identification of stenoses and in the follow-up of revascularization procedures (PTCA-stenting, bypass). The limitations of such technique in terms of invasivity and high cost has targeted research efforts towards the development of non invasive diagnostic tools. Technological evolution in the field of helical CT has provided 2, 4, 8 and 16 detector-row multislice scanners characterized by progressive improvements in terms of spatial and temporal resolution that have made them increasingly suitable for the analysis of moving structures with high quality anatomic detail. The main cardiologic applications of multislice CT include coronary calcium scoring, the evaluation of coronary vascular anatomy and disease, follow-up of revascularization procedures (stenting, bypass), and the evaluation of cardiac walls and chambers. The aim of this paper is to describe the applications of sixteen detector-row multisclice CT in non invasive evaluation of cardiac and coronary diseases.     

Diffuse, micronodular lung disease. The high-resolution CT approach. A pictorial essay

Careful HRCT evaluation of the preferential distribution of micronodular lesions within the secondary lobule provides a fundamental contribution in the correct interpretation of the different associated patterns. This paper suggests a modern diagnostic algorithm that, together with clinical-anamnestic data and additional imaging features, is able to provide a definitive diagnosis or to reduce the possible differential diagnoses.     

Effects of short-chain fructo-oligosaccharides on glucose and lipid metabolism in mild hypercholesterolaemic individuals

BACKGROUND: The intake of 10 g/day of short-chain-fructo-oligosaccharides (sc-FOS) has been shown to increase significantly bifidus counts and to produce high amounts of short-chain fatty acids (SCFA), presumed to influence glucose and lipid metabolism. AIM: To evaluate the effects of moderate intake of sc-FOS on glucose and lipid metabolism in individuals with mild hypercholesterolaemia. Design: A randomized double-blind sequential cross-over study. SUBJECTS AND METHODS: Thirty subjects of both genders (20 M/10 F), mean age 45.5+/-9.9 years (M+/-SD), BMI 26.6+/-2.2 kg/m(2), with plasma cholesterol >5.17 and <7.76 mmol/l and plasma triglycerides <3.45 mmol/l, participated in the study. The study was performed after a wash-out period of 1 month and a run-in period of 1 month to stabilize patients on a standard diet (CHO 50%, fat 30%, protein 20%, fibre 20 g/day) plus placebo (maltodextrine plus aspartame 15 g/day). At the end of run-in, subjects were randomly assigned to receive sc-FOS (Actilight) (10.6g/day) or placebo (maltodextrine plus aspartame 15 g/day) with tea and/or coffee for a duration of 2 months and thereafter switched to the other treatment for additional 2 months. Plasma glucose, total and lipoprotein (VLDL, LDL, HDL) cholesterol and triglyceride concentrations were measured in the fasting state at the end of run-in and of each treatment period. At the end of the two treatment periods, patients consumed a standard test meal (protein 15%, carbohydrate 34%, fat 51%, kJ 3988) 1h after the administration of 5.3g of sc-FOS or placebo; plasma glucose, insulin, free fatty acid (FFA) and triglyceride responses to the test meal were evaluated. RESULTS: No significant difference in fasting parameters was detected between the two treatments. After sc-FOS and placebo plasma cholesterol levels were, respectively, 6.47+/-0.70 and 6.44+/-0.78 mmol/l (n.s.) and plasma triglycerides were 1.53+/-0.71 and 1.56+/-0.53 mmol/l (n.s.). No significant differences were observed in cholesterol and triglyceride content of VLDL, LDL and HDL and in plasma Apo A1 levels; conversely, fasting plasma Lp(a) concentrations were significantly increased after sc-FOS (37+/-38 vs. 33+/-35 mg/dl; P<0.005). Postprandial responses of glucose, FFA and triglycerides were not significantly different between sc-FOS and placebo, while postprandial insulin response (incremental area) was significantly reduced after sc-FOS compared to placebo (14,490+/-7416 vs. 17,760+/-7710 pmol/l x 300 min; P<0.02). CONCLUSIONS: A moderate intake of sc-FOS has no major effects on lipid metabolism, both in the fasting and in the postprandial period, in individuals with mild hypercholesterolaemia. A small but significant increase of Lp(a) concentrations was observed with sc-FOS consumption together with a reduction of the postprandial insulin response; however, the clinical relevance of these small effects is unclear.     

The use of formic acid to embellish amyloid plaque detection in Alzheimer's disease tissues misguides key observations

We compared our heat pretreatment method to the widely used formic acid pretreatment technique to immunohistochemically detect amyloid in control and Alzheimer's disease brain tissues. Both methods detected amyloid in plaques, neurons, ependymal cells, circulating monocytes, vascular smooth muscle and endothelial cells. Although there were no observable differences in the intensity of the amyloid labeling in these cell types using both pretreatment methods, there were considerable differences in the intensity of amyloid immunolabeling in the plaques. The formic acid produced much more intense amyloid labeling in the plaques than the heat method. With the heat method, the intensity of the amyloid labeling in the plaques was similar to that detected in nearby neurons suggesting a neuronal origin of plaques. Conversely, the intensity of the amyloid in nearby neurons and plaques was drastically different using the formic acid suggesting unique origins of amyloid. The obvious benefits of formic acid for increasing the sensitivity of amyloid plaque immunolabeling may artifactually emphasize plaques over amyloid-containing cells during analyses.     

Aggressive nutrition of the very low birthweight infant

We propose an approach to nutrition of the VLBW infant that aims at minimizing the interruption of nutrient uptake engendered by premature birth. Our approach is aggressive in that it goes beyond current practice in several key aspects. The gap in nutrient intakes between the proposed aggressive approach and current practice will most likely disappear over the next few years as today's aggressive practice becomes tomorrow's standard practice. As the gap diminishes, so will the threat that nutritional deprivation poses to growth and development of VLBW infants.