Effect of raw milk on lactose intolerance: a randomized controlled pilot study.

PURPOSE: This pilot study aimed to determine whether raw milk reduces lactose malabsorption and/or lactose intolerance symptoms relative to pasteurized milk. METHODS: We performed a crossover trial involving 16 adults with self-reported lactose intolerance and lactose malabsorption confirmed by hydrogen (H2) breath testing. Participants underwent 3, 8-day milk phases (raw vs 2 controls: pasteurized, soy) in randomized order separated by 1-week washout periods. On days 1 and 8 of each phase, milk consumption was 473 mL (16 oz); on days 2 to 7, milk dosage increased daily by 118 mL (4 oz), beginning with 118 mL (4 oz) on day 2 and reaching 710 mL (24 oz) on day 7. Outcomes were area under the breath H2 curve (AUC H2) and self-reported symptom severity (visual analog scales: flatulence/gas, audible bowel sounds, abdominal cramping, diarrhea). RESULTS: AUC H2 (mean ± standard error of the mean) was higher for raw vs pasteurized on day 1 (113 ± 21 vs 71 ± 12 ppm·min·10(-2), respectively, P = .01) but not day 8 (72 ± 14 vs 74 ± 15 ppm·min·10(-2), respectively, P = .9). Symptom severities were not different for raw vs pasteurized on day 7 with the highest dosage (P >.7). AUC H2 and symptom severities were higher for both dairy milks compared with soy milk. CONCLUSIONS: Raw milk failed to reduce lactose malabsorption or lactose intolerance symptoms compared with pasteurized milk among adults positive for lactose malabsorption. These results do not support widespread anecdotal claims that raw milk reduces the symptoms of lactose intolerance.

Micronutrient quality of weight-loss diets that focus on macronutrients: results from the A TO Z study.

BACKGROUND: Information on the micronutrient quality of alternative weight-loss diets is limited, despite the significant public health relevance. OBJECTIVE: Micronutrient intake was compared between overweight or obese women randomly assigned to 4 popular diets that varied primarily in macronutrient distribution. DESIGN: Dietary data were collected from women in the Atkins (n = 73), Zone (n = 73), LEARN (Lifestyle, Exercise, Attitudes, Relationships, Nutrition) (n = 73), and Ornish (n = 72) diet groups by using 3-d, unannounced 24-h recalls at baseline and after 8 wk of instruction. Nutrient intakes were compared between groups at 8 wk and within groups for 8-wk changes in risk of micronutrient inadequacy. RESULTS: At 8 wk, significant differences were observed between groups for all macronutrients and for many micronutrients (P < 0.0001). Energy intake decreased from baseline in all 4 groups but was similar between groups. At 8 wk, a significant proportion of individuals shifted to intakes associated with risk of inadequacy (P < 0.05) in the Atkins group for thiamine, folic acid, vitamin C, iron, and magnesium; in the LEARN group for vitamin E, thiamine, and magnesium; and in the Ornish group for vitamins E and B-12 and zinc. In contrast, for the Zone group, the risk of inadequacy significantly decreased for vitamins A, E, K, and C (P < 0.05), and no significant increases in risk of inadequacy were observed for other micronutrients. CONCLUSIONS: Weight-loss diets that focus on macronutrient composition should attend to the overall quality of the diet, including the adequacy of micronutrient intakes. Concerning calorie-restricted diets, there may be a micronutrient advantage to diets providing moderately low carbohydrate amounts and that contain nutrient-dense foods.

Claudin-2, a component of the tight junction, forms a paracellular water channel.

Whether or not significant amounts of water pass the tight junction (TJ) of leaky epithelia is still unresolved, because it is difficult to separate transcellular water flux from TJ-controlled paracellular water flux. Using an approach without differentiating technically between the transcellular and paracellular route, we measured transepithelial water flux with and without selective molecular perturbation of the TJ to unequivocally attribute changes to the paracellular pathway. To this end, MDCK C7 cells were stably transfected with either claudin-2 or claudin-10b, two paracellular cation-channel-forming TJ proteins that are not endogenously expressed in this cell line. Claudin-2 is typical of leaky, water-transporting epithelia, such as the kidney proximal tubule, whereas claudin-10b is present in numerous epithelia, including water-impermeable segments of the loop of Henle. Neither transfection altered the expression of endogenous claudins or aquaporins. Water flux was induced by an osmotic gradient, a Na(+) gradient or both. Under all conditions, water flux in claudin-2-transfected cells was elevated compared with vector controls, indicating claudin-2-mediated paracellular water permeability. Na(+)-driven water transport in the absence of an osmotic gradient indicates a single-file mechanism. By contrast, claudin-10b transfection did not alter water flux. We conclude that claudin-2, but not claudin-10b, forms a paracellular water channel and thus mediates paracellular water transport in leaky epithelia.

GOLPH2 expression may serve as diagnostic marker in seminomas.

BACKGROUND: GOLPH2 (Golgi phosphoprotein 2) is a novel Golgi membrane protein. Despite its unknown physiologic function, however, it has been proposed as a biomarker for hepatocellular and prostate carcinoma due to its upregulation in those cancer entities. Whether the overexpression of GOLPH2 is tumour specific or a generic parameter of malignancy and whether this finding is true for additional carcinomas has not been determined. In this study, we aimed to evaluate the expression pattern of GOLPH2 in testicular seminomas, the most common histologic subtype of testicular neoplasm. METHODS: GOLPH2 protein expression was assessed by immunohistochemistry in 69 testicular seminomas and compared to the expression rates in matching normal testicular tissue and intratubular germ cell neoplasia of unclassified type (IGCNU). In addition, a subset of Leydig cell tumours was analyzed accordingly. RESULTS: GOLPH2 was consistently overexpressed (89.9%) in seminomas. Matching non-neoplastic tissue showed weak or negative staining. The observed differences between non-neoplastic and neoplastic tissue were statistically highly significant (p < 0.001). There were no significant associations with tumour status. Interestingly, GOLPH2 was also highly expressed in the intertubular Leydig cells as well as in Leydig cell tumours. CONCLUSIONS: GOLPH2 protein is highly expressed in seminomas and in Leydig cell tumours. This study fosters the association of GOLPH2 with malignant neoplastic processes. The staining pattern is easily assessable and consistent which is a favourable property especially in clinical settings. GOLPH2 could be a novel immunohistochemical marker for the assessment of testicular neoplasms, especially against the background that in analogy to hepatocellular carcinomas complementary GOLPH2 serum levels might be helpful in detecting metastases or recurrent tumour. Therefore serum studies and analyses of GOLPH2 expression in non-seminomatous germ cell tumours are strongly warranted.

Prostatic soy isoflavone concentrations exceed serum levels after dietary supplementation.

BACKGROUND: The effects of soy isoflavones on prostate cancer may be concentration-dependent. The impact of soy supplementation on isoflavone concentrations in prostate tissues and serum remain unclear. OBJECTIVE: To assess and compare concentrations of soy isoflavones in prostate tissue and serum among 19 men with prostate cancer who had elected to undergo radical prostatectomy. METHODS: Participants were randomized to receive either daily soy supplements (82 mg/day aglycone equivalents) or placebos for 2 weeks (14 days) prior to surgery. Serum samples were obtained at the time of the surgery. Isoflavone concentrations were measured by HPLC/ESI-MS-MS. RESULTS: The median (25th, 75th percentile) total isoflavone concentration in the isoflavone-supplemented group was 2.3 micromol/L (1.2, 6.9) in the prostate tissue and 0.7 micromol/L (0.2, 1.2) in the serum. Total isoflavone concentrations in this group were an average of approximately 6-fold higher in prostate tissue compared to serum; the tissue versus serum ratio was significantly lower for genistein than daidzein, 4-fold versus 10-fold, P = 0.003. Tissue and serum levels of isoflavones among the placebo group were negligible with a few exceptions. CONCLUSIONS: The findings from the present study suggest that prostate tissue may have the ability to concentrate dietary soy isoflavones to potentially anti-carcinogenic levels.

The FUSE binding proteins FBP1 and FBP3 are potential c-myc regulators in renal, but not in prostate and bladder cancer.

BACKGROUND: The three far-upstream element (FUSE) binding proteins (FBP1, FBP2, and FBP3) belong to an ancient family of single-stranded DNA binding proteins which are required for proper regulation of the c-myc proto-oncogene. Whereas it is known that c-myc alterations play a completely different role in various carcinomas of the urogenital tract, the relevance of FBPs is unclear. METHODS: FBP1, FBP3 and c-myc expression was studied in 105 renal cell, 95 prostate and 112 urinary bladder carcinomas by immunohistochemistry using tissue microarrays. RESULTS: High rates of FBP1 and FBP3 expression were observed in all cancer types. There was a concomitant up-regulation of FBP1 and FBP3 in renal cell and prostate carcinomas (p < 0.001 both). C-myc expression was detectable in 21% of prostate, 30% of renal and 34% of urothelial carcinomas. Interestingly, strong FBP1 and FBP3 expression was associated with c-myc up-regulation in clear cell renal cell carcinomas (p < 0.001 and 0.09 resp.), but not in bladder or prostate cancer. CONCLUSION: The correlation between FBP1/FBP3, c-myc and high proliferation rate in renal cell carcinoma provides strong in vivo support for the suggested role of FBP1 and FBP3 as activators of c-myc. The frequent up-regulation of FBP1 and FBP3 in urothelial and prostate carcinoma suggests that FBPs also have an important function in gene regulation of these tumors.

Claudin-1 protein expression is a prognostic marker of patient survival in renal cell carcinomas.

PURPOSE: Claudin-1 is a tight junction protein described in normal tissues as well as in malignancies. We aimed to assess the diagnostic or prognostic significance of claudin-1 expression in renal cell carcinoma and to correlate the expression of claudin-1 with clinical, histopathologic, and prognostic parameters in renal cell carcinoma. EXPERIMENTAL DESIGN: A tissue microarray was constructed using formalin-fixed, paraffin-embedded tissue from renal cell carcinomas and corresponding normal renal tissue from 318 patients. The protein expression of claudin-1 was assessed and correlated to clinicopathologic tumor parameters including patient survival. A separate cohort of 44 papillary renal cell carcinoma was used for validation of results. RESULTS: Claudin-1 was expressed in 29.9% of renal cell cancer cases. Whereas the vast majority of clear cell carcinomas were negative for claudin-1, most papillary tumors (76-86%) were positive. Claudin-1 expression was associated with markers of unfavorable tumor biology in clear cell renal cell carcinoma, whereas the opposite was valid for papillary renal cell carcinoma. In clear cell renal cell carcinoma claudin-1 positivity was a prognosticator of shortened disease-specific patient survival in univariate analysis (P=0.008), which also remained significant in multivariate analyses in the clinically important subgroups of nonmetastasized or asymptomatic patients. CONCLUSIONS: Claudin-1 is expressed in the majority of papillary renal cell carcinomas, suggesting a diagnostic value of this marker. Its expression is an independent prognosticator of shortened disease-specific patient survival in clinically relevant subgroups of clear cell renal cell carcinoma. Further functional studies are needed to clarify the different biological roles of claudin-1 expression in these histologic subtypes of renal cell carcinoma.

Acute partial segmental thrombosis of the corpus cavernosum: imaging findings on ultrasound, computed tomography, and magnetic resonance imaging.

Partial segmental thrombosis of the corpus cavernosum is a rare disease of unknown etiology; the thrombosis is always located in the proximal part of the corpus cavernosum, usually unilaterally. Typical clinical presentation with perineal pain and swelling in combination with cross-sectional imaging allows one to confidentially establish this diagnosis.

A bibliometric evaluation of publications in urological journals among European Union countries between 2000-2005.

OBJECTIVES: To perform a bibliometric evaluation of publications from European Union (EU) countries in the international urological journals between 2000-2005 according to their national origin and in relation to international context. METHODS: Articles except reviews, editorials, letters, and reports published during 2000-2005 in 19 international urological journals were screened using Web of Science database. The total number of publications and the cumulative impact factor were determined for the first 15 EU member states (EU15), the USA, and the world. These data were related for every country to the population size and the socio-economic indicators gross domestic product, gross domestic expenditure on research and experimental development, and expenditure on health care. RESULTS: A total of 19.709 articles were published of which 6.878 (34.9%) came from the EU15 countries and 7.927 (40.2%) from the USA. About 15% of all papers from the EU15 countries were in collaboration with USA researchers. In the EU, the number of publications and the cumulative impact factor were dominated by United Kingdom, Germany, and Italy with about 52% of all papers and 50% of the cumulative impact factor. If adjusted for demographic and socio-economic factors the smaller countries Austria, Denmark, Finland, the Netherlands, and Sweden (alphabetical order) revealed a distinctly higher publication rate. CONCLUSIONS: This study based on bibliometric analyses in urological journals demonstrated a feasible solution to validate and compare the contribution of the various EU countries towards the urological research.