Effects of dietary fat and a vegetable-fruit mixture on the development of intestinal neoplasia in the ApcMin mouse

The variation in colorectal cancer (CRC) incidence worldwide strongly suggests a role for dietary influences. Based on epidemiological data, protective effects of vegetables and fruit intake on CRC are widely claimed, while other data indicate a possible increased CRC risk from (higher) dietary fat intake. Therefore, we have investigated single and interactive effects of dietary fat and a vegetable-fruit mixture (VFM) in the ApcMin mouse, a mouse model for multiple intestinal neoplasia. In this study, four different diets (A-D) were compared, which were either low in fat (20% energy diets A/B) or high in fat (40% energy diets C/D). In addition, 19.5% (wt/wt) of the carbohydrates in diets B and D were replaced by a freeze-dried VFM. The diets were balanced so that they only differed among each other in fat/carbohydrate content and the presence of specific plant-constituents. Because the initiation of intestinal tumors in ApcMin mice occurs relatively early in life, exposure to the diets was started in utero. Without the addition of VFM, mice maintained at a high-fat diet did not develop significantly higher numbers of small or large intestinal adenomas than mice maintained at a low-fat diet. VFM added to a low-fat diet significantly lowered multiplicity of small intestinal polyps (from 16.2 to 10.2/mouse, 15 animals/group), but not of colon tumors in male ApcMin mice only. Strikingly, addition of VFM to female mice maintained on a low-fat diet and to both sexes maintained on a high-fat diet significantly enhanced intestinal polyp multiplicity (from 16.5 to 26.7 polyps/mouse). In conclusion, our results indicate that neither a lower fat intake nor consumption of VFM included in a high-fat diet decreases the development of polyps in mice genetically predisposed to intestinal tumor development.      

Bronchoscopic cryotherapy: preliminary experience

Our preliminary experience with the bronchoscopic application of cryotherapy using rapid decompression of liquid nitrous oxide as cooling agent is reported. Seventeen applications through rigid bronchoscopy in twelve patients were performed. A single cryotherapy session was successful in the debulking of obstructive malignant lesions of the central airways in five patients (four non-small cell carcinoma, one renal cell cancer metastasis), and in the treatment of a capillary haemangioma (one patient). Two sessions were successful in the treatment of a metastatic melanoma (one patient) and benign granulation tissue (one patient). Cryotherapy was also successful in the treatment of early bronchial cancer (carcinoma in situ) in four patients, requiring repetitive sessions in two. There were no complications or side-effects. These preliminary findings confirm the safety and efficacy of bronchoscopic cryotherapy in a variety of airway lesions.     

Eradication of chronic methicillin-resistant Staphylococcus aureus infection in cystic fibrosis patients. An observational prospective cohort study of 11 patients

BackgroundChronic airway infection with methicillin-resistant Staphylococcus aureus (MRSA) in patients with cystic fibrosis (CF) is an increasing clinical problem, and therapeutic options are limited. Because chronic infection with MRSA can be associated with accelerated decline in lung function, eradication of MRSA is attempted in most CF centres today. The aim of this observational prospective cohort study was to determine whether it is possible to eradicate MRSA from airways of CF patients using prolonged oral antibiotic combination therapy together with topical decolonization measures.ResultsEleven CF patients, (median age: 9 years (range 1–43); median FEV₁: 91%pred (95%CI 74%–100%pred)) who were chronically infected with MRSA, were treated daily for six months with rifampicin and fusidic acid orally. This study did not include a patient control group. Two patients had to switch to an alternative schedule, using rifampicin and clindamycin, due to the resistance pattern of MRSA. Topical decolonization measures were applied to all patients and included mupirocin-containing nasal ointment in both nostrils three times daily for five days and chlorhexidine hair and body wash once daily for five days. Microbiological eradication was achieved in all patients at the end of the six-month eradication protocol, even when significant time (range 18 months to 9 years) had elapsed since initial isolation. In only one patient MRSA reappeared in the six-month follow-up period after the initial study period. Side-effects, like nausea, vomiting and diarrhoea were seen in five out of eleven patients, but did not lead to therapy cessation.ConclusionChronic MRSA infection can be eradicated from respiratory tract samples using a six month dual antibiotic regimen and topical MRSA decolonization measures.     

Native associations of early hematopoietic stem cells and stromal cells isolated in bone marrow cell aggregates

In suspensions of murine bone marrow, many stromal cells are tightly entwined with hematopoietic cells. These cellular aggregations appear to exist normally within the marrow. Previous studies showed that lymphocytes and stem cells adhered to stromal cells via vascular cell adhesion molecule 1 (VCAM1). Injection of anti-VCAM1 antibody into mice disrupts the aggregates, showing the importance of VCAM1 in the adhesion between stromal cells and hematopoietic cells in vivo. Early hematopoietic stem cells were shown to be enriched in aggregates by using a limiting-dilution culture assay. Myeloid progenitors responsive to WEHI-3CM in combination with stem cell factor (c-kit ligand) and B220- B-cell progenitors responsive to insulin-like growth factor-1 in combination with interleukin-7 are not enriched. We propose a scheme of stromal cell-hematopoietic cell interactions based on the cell types selectively retained within the aggregates. The existence of these aggregates as native elements of bone marrow organization presents a novel means to study in vivo stem cell-stromal cell interaction.     

Determinants of respiratory muscle weakness in stable chronic neuromuscular disorders

In neuromuscular disease, the precise relationship between general and respiratory muscle weakness is at present unclear. That relationship and the influence on respiratory muscle strength of such factors as type and duration of neuromuscular disease, distribution of general muscle weakness, and nutritional status were studied in 30 patients with stable chronic neuromuscular disease not presenting with respiratory symptoms. The degree of general muscle weakness was assessed by clinical examination of the strength of 17 muscle groups, yielding a general muscle strength index. The degree of respiratory muscle weakness was assessed by measuring maximal static inspiratory and expiratory mouth pressures. Maximal inspiratory (mean +/- SD: 68 +/- 28 percent predicted) and expiratory (66 +/- 29 percent predicted) mouth pressures were frequently reduced, but did not correlate with general muscle strength. The ability to estimate the degree of respiratory muscle weakness improved to some extent when the type of neuromuscular disease and the distribution of general muscle weakness were taken into account: thus, maximal expiratory mouth pressure was significantly lower (p less than 0.05) in myopathy than in polyneuropathy, and in proximal than in distal muscle weakness. Duration of neuromuscular disease and nutritional status did not influence respiratory muscle strength. It is concluded that in stable chronic neuromuscular disease, respiratory muscle involvement depends on a complexity of factors, in particular the type of neuromuscular disease and the distribution, rather than the degree, of general muscle weakness. In the individual patient, however, only direct measurement of maximal inspiratory and expiratory mouth pressures allows accurate assessment of respiratory muscle strength. These tests ought to complement neurologic examination.     

Quantitative diffusion weighted imaging for differentiation of benign and malignant breast lesions: The influence of the choice of b‐values

Purpose:

To evaluate the influence of the choice of different combinations of b‐values on the ADC and on the diagnostic performance of quantitative diffusion weighted imaging (DWI) in breast lesions.

Materials and Methods:

Seventy‐three patients (90 lesions) underwent 3 Tesla (T) breast MRI including a DWI‐scan using b‐values 0, 150, 499, and 1500 s/mm² and histological analysis. Five combinations of b‐values were used to calculate the ADC, each with different sensitivities to perfusion and diffusion effects. The median ADC of benign lesions, noninvasive carcinomas and invasive carcinomas and the diagnostic performance of the five methods were compared.

Results:

Eighty‐eight lesions were analyzed (37 benign, 13 noninvasive carcinomas, 38 invasive carcinomas). The median ADC was highest in benign lesions, intermediate in noninvasive carcinomas and lowest in invasive carcinomas for all methods. Calculating the ADC with the lowest 2 b‐values yielded the highest ADC for all lesions types; the highest 2 b‐values yielded the lowest ADC. The area under the receiver operating characteristic curve was approximately equal for all methods.

Conclusion:

The ADC of breast lesions varied substantially with the choice of different b‐values, indicating that absolute ADC threshold values to differentiate benign and malignant lesions should be interpreted with caution. However, the diagnostic performance of quantitative DWI was not affected by the choice of different b‐values. J. Magn. Reson. Imaging 2010;31:1100–1105. © 2010 Wiley‐Liss, Inc.