Chronic low level physical activity as a determinant of high density lipoprotein cholesterol and subfractions

Physical activity has been associated with reduced risk of coronary heart disease. A mechanism for the reduced risk may be through increased high density lipoprotein cholesterol (HDL-C) and subfractions, in particular HDL2-C. Research associated with increased physical activity investigating HLD-C have assessed the effects of intense aerobic activity. The current research evaluated the relationship between low intensity, long duration activity to HDL-C and subfractions in 35 active postal carriers. Measurements of physical activity via the Large Scale Integrated monitor and reported miles walked, and lipoproteins were assessed at 3-month intervals over a 1-year period. Reported miles walked/day (5.3) was significantly correlated with HLD2-C (r = 0.50, P = 0.003) and approached significance for HDL-C (r = 0.29, P = 0.06). The Large Scale Integrated measures were correlated with HDL-C (r = 0.44, P = 0.008) and HDL2-C (r = 0.44, P = 0.007). Controlling for either age, alcohol consumption, body mass index, or leisure time activity did not reduce the relationship between reported miles walked or Large Scale Integrated readings and HDL2-C, suggesting that the increased HDL-C was the result of long duration, low intensity physical activity.     

Long-term course of epilepsy in a large cohort of intellectually disabled patients.

This study was designed to describe the course of epilepsy (in terms of seizure frequency) and to assess the variables (antiepileptic therapy regimens and others) correlated to improvement. Seizure frequency (categories: seizure free, more than one seizure/year, monthly seizures, weekly seizures and daily seizures) and antiepileptic medication were retrospectively compared between 1992 and 2002 in a large cohort of 550 inpatients with chronic epilepsy and different degrees of intellectual disability or multiple handicaps. RESULTS: Seizure frequency decreased significantly (p<0.001). 218 of the 394 patients (55.3%) not seizure free in 1992 improved (changed into a better frequency category). The improvement rate was marginally higher in patients who had undergone a medication change (p=0.08). A high seizure frequency in 1992 (p=0.016) and older age (p=0.006), but not epilepsy syndrome or degree of intellectual disability, were predictors for improvement (stepwise logistic regression analysis). 56.4% of the improved patients were on combinations of two AEDs (17.4%, monotherapy; 20.2%, triple therapy). The most frequent therapy regimens in the improved patients were lamotrigine/valproate (48 patients), carbamazepine/phenobarbital (21) and carbamazepine only (19). Lamotrigine/valproate was effective in all kinds of epileptic syndromes. Most patients on lamotrigine had serum concentrations above 10microg/ml, approximately one half had dosages above 200mg/day. The rate of seizure freedom increased from 28.4 to 37.6%. The 84% of the patients seizure free in 1992 remained seizure free. Predictors for seizure freedom in 2002 were higher age (stepwise logistic regression, p<0.0005) and seizure freedom in 1992 (p<0.0005). CONCLUSIONS: Substantial improvement can be achieved even in intellectually disabled patients with chronic epilepsy. Although the rate of seizure freedom is reduced in comparison with a non-ID population, once seizure freedom has been achieved it is most likely to continue. For a majority of this patient population, monotherapy may not be sufficient. Lamotrigine/valproate appears to be a major therapeutic innovation.     

Digital mammography. ROC studies of the effects of pixel size and unsharp-mask filtering on the detection of subtle microcalcifications

We investigated the spatial resolution requirement and the effect of unsharp-mask filtering on the detectability of subtle microcalcifications in digital mammography. Digital images were obtained by digitizing conventional screen-film mammograms with a 0.1 X 0.1 mm2 pixel size, processed with unsharp masking, and then reconstituted on film with a Fuji image processing/simulation system (Fuji Photo Film Co., Tokyo, Japan). Twenty normal cases and 12 cases with subtle microcalcifications were included. Observer performance experiments were conducted to assess the detectability of subtle microcalcifications in the conventional, the unprocessed digital, and the unsharp-masked mammograms. The observer response data were evaluated using receiver operating characteristic (ROC) and LROC (ROC with localization) analyses. Our results indicate that digital mammograms obtained with 0.1 X 0.1 mm2 pixels provide lower detectability than the conventional screen-film mammograms. The detectability of microcalcifications in the digital mammograms is improved by unsharp-mask filtering; the processed mammograms still provide lower accuracy than the conventional mammograms, however, chiefly because of increased false-positive detection rates for the processed images at each subjective confidence level. Viewing unprocessed digital and unsharp-masked images in pairs resulted in approximately the same detectability as that obtained with the unsharp-masked images alone. However, this result may be influenced by the fact that the same limited viewing time was necessarily divided between the two images.     

Bacterial ghosts (BGs)—Advanced antigen and drug delivery system

Bacterial ghosts (BGs) are empty bacterial envelopes of Gram-negative bacteria produced by controlled expression of cloned gene E, forming a lysis tunnel structure within the envelope of the living bacteria. BGs are devoid of cytoplasmic content and possess all bacterial bio-adhesive surface properties in their original state while not posing any infectious threat. BGs are ideally suited as an advanced drug delivery system (ADDS) for toxic substances in tumor therapy. The inner space of BGs can be loaded with either single components or combinations of peptides, drugs or DNA which provides an opportunity to design new types of (polyvalent) drug delivery vehicles. Uptake of BGs loaded with Doxorubicin (Dox) by CaCo2 cells led to effective Dox release from endo-lysosomal compartments and accumulation in the nucleus. Viability and proliferative capacity of the cells were significantly decreased (2–3 orders of magnitude) after internalization of Dox loaded BGs as compared to cells incubated with free Dox. The same effect was observed with leukemia cells. Melanoma cells also revealed a high capability to internalize BGs. These results indicate that BGs are able to target a range of types of cancer. BGs have also been investigated as DNA delivery vectors. Studies show DNA loaded BGs are efficiently phagocytosed and internalized by both professional APCs and tumor cells with up to 82% of cells expressing the plasmid-encoded reporter gene. Our studies with BGs as an ADDS system contribute (i) to optimize drug delivery for the treatment of cancer; (ii) define specific conditions for selection and preparation of BG formulations; (iii) and provide a background for the clinical application of BGs in cancer therapy.     

The neu-oncogene product in serum and tissue of patients with breast carcinoma

BACKGROUND:: A soluble 105 kD neu-related protein is detectable in conditionedmedium from breast cancer cells expressing the neu-oncogeneproduct and in serum of nude mice bearing tumors that overexpressneu-oncogene PATIENTS AND METHODS:: In 100 patients with primary (n - 33) relapse-free (n - 6) andmetastatic (n - 61) breast carcinoma the serum levels of thesoluble new-related protein were investigated by ELISA techniques.Median age was 57 years, range 26–89 years. RESULTS:: The neu-protein serum levels were below 40 HNU/ml (human neu-antigenunit) in 72 patients and 40 or more HNU/ml in 28 patients. In30 patients with primary breast carcinoma, tested before mastectomy,all serum- neu-protein samples were negative. However, 26 of61 metastazised patients (43%) were serum-neu-protein-positive.In disseminated disease (n – 61), serum-neu-protein-positivitywas more likely to be seen in patients with visceral metastases(18/33 – 54%), than in patients with nonvisceral metastases(8/28 – 28%). Furthermore, monitoring of the serum-neu-proteinlevels reflected clinical course. For 53 patients original paraffin-embeddedtumor material was available for studying immunohistochemicalneu-protein expression. In 39/53 (73%) patients immunohistochemicaland ELISA data showed corresponding results. In 27/30 (90%)patients, from whom sera and tissue could be obtained at thesame time at primary mastectomy, results of immunohistochemistryin primary tumor and serum ELISA were negative and mutuallyconfirmatory. However, the other three patients were positivefor immunohistochemical neu-protein expression in primary tumorbut negative for serum-neu-protein expression. CONCLUSIONS:: Our results suggest that patients with advanced breast cancerand an elevated serum-neu-protein level may have a poor clinicaloutcome. This test might be a useful tool for monitoring patientswith advanced breast carcinoma, but not those with early disease.Further prospective studies are warranted to elucidate the questionof whether this test can contribute to determining prognosisand treatment strategies. breast carcinoma, c-erb-B2, HER-2, neu, oncogene, pl85     

Anaphylaxis to isosulfan blue and cross-reactivity to patent blue V: case report and review of the nomenclature of vital blue dyes.

BACKGROUND: Blue dyes used for lymphatic mapping in sentinel lymph node biopsy cause intraoperative anaphylactic reactions in up to 2.7% of patients. With increasing implementation of this technique, the incidence of anaphylaxis to these dyes can be expected to increase. In the literature, the chemically often unrelated and inconsistently designated dyes have been confused, adding to other inconsistencies in the nomenclature. OBJECTIVE: To demonstrate the nomenclature, chemical and physiologic differences, and allergenicity of the various blue dyes used in a medical context. METHODS: We describe a patient with an intraoperative grade IV anaphylactic reaction to isosulfan blue. Immediate-type hypersensitivity was proved by positive skin test reactions and CD63 expression to isosulfan blue and cross-reactivity to patent blue V. RESULTS: A review of the literature clarified the exact nomenclature of the blue dyes and the possible pitfalls of confusing nomenclature in the context of structurally closely related dyes with different allergenic properties. For the detection of type I hypersensitivity, intracutaneous tests are valuable tools. An IgE-mediated mechanism has been shown recently. In most cases, sensitization exists without known previous exposure in a medical context. This may be due to the widespread use of such dyes in objects of everyday life. Preoperative antiallergic medication use does not prevent anaphylactic reactions but apparently reduces their severity. CONCLUSION: For better comparison and precision, the Chemical Abstracts Service number of the respective dye should always be given.     

Digital radiography of subtle pulmonary abnormalities: an ROC study of the effect of pixel size on observer performance

Forty conventional radiographs with examples of mild interstitial infiltrates and subtle pneumothoraces and 40 normal studies of the chest were selected and digitized, with pixel sizes of 1.0, 0.5, 0.2, and 0.1 mm. Observer performance tests were carried out using receiver operating characteristic analysis. Conventional radiographs and digitized images were compared. The results indicate that, in such cases, diagnostic accuracy increases significantly as the pixel size is reduced, at least to the 0.1-mm level. We conclude that, for digital systems using screen-film or similar image receptors, use of a pixel size substantially larger than 0.1 mm may result in some loss of diagnostic accuracy.