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INTRODUCTION: Cobalamin/Vitamin B12 (Cbl) is an essential vitamin, supplied mainly as hydroxocobalamin (OHCbl) by animal products, including cows' milk. Cyanocobalamin (CNCbl) is the usual form in vitamin pills. The aim was to explore absorption and tissue accumulation of two Cbl forms, administered alone or bound to milk protein. MATERIALS AND METHODS: We synthesized labeled OH[(57)Co]Cbl from commercially available CN[(57)Co]Cbl. Recombinant bovine transcobalamin (rbTC) was produced in yeast and skimmed milk obtained off the shelf. Male Wistar rats (250-300 g) received labeled Cbl by gastric gavage. First, we administered CN[(57)Co]Cbl, free or rbTC-bound (n = 15 in each group). Rats were sacrificed after two, 24, and 48 h. In the following studies, rats were sacrificed after 24 h. We compared absorption of free or rbTC-bound CN[(57)Co]Cbl added to cows' milk and analogous absorption of OH[(57)Co]Cbl, free or rbTC-bound, to absorption of free CN[(57)Co]Cbl, (n = 10 in each group). Blood, tissues, 24-h urine and feces were collected. Labeled Cbl was measured using a gamma counter. Results are expressed as percentage of administered dose. RESULTS: Absorptions of CNCbl and OHCbl were neither influenced by rbTC-binding nor administration in milk. Absorption increased in the first 24 h with no further tissue accumulation during the subsequent 24 h. Accumulation of free CNCbl and (OHCbl) was 1.4, (4.1) (liver); 20.2, (16.4) (kidney); and 0.05, (0.02) (plasma)% 24 h after administration. Total organ accumulations were 21.6, (20.5)%. While total accumulations of CNCbl and OHCbl were equal, distributions between liver, kidney, and plasma showed significant differences (p < 0.0001; p = 0.01; p < 0.0001). CONCLUSIONS: Cbl added to milk (spiked with rbTC) has high bioavailability matching that of free Cbl. OHCbl and CNCbl are absorbed equally well, but much more OHCbl accumulated in the liver. Benefits of oral supplementation with OHCbl compared to CNCbl should be investigated.

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Anoctamin 6 (ANO6), also known as TMEM16F, has been shown to be a calcium-activated anion channel with delayed calcium activation. The cellular function of ANO6 is under debate, and different groups have come to different conclusions about ANO6's physiological role. Although it is now quite well established that ANO6 is distinct from the volume-regulated anion channel, it is still unclear whether ANO6 or other anoctamins can be activated by cell swelling. In this study, we suggest that ANO1, ANO6, and ANO10 do not contribute to the volume-activated current in ANO-overexpressing HEK293 cells. Furthermore, knock-down of ANO6 in Ehrlich ascites tumor cells (EATC) and Ehrlich-Lettre ascites (ELA) did not decrease but instead significantly increased swelling-activated membrane currents. Knock-down of ANO6 in EATC did not reduce regulatory volume decrease (RVD) in the absence of extracellular calcium, whereas it significantly reduced RVD in the presence of calcium. Interestingly, we found that knock-down of ANO6 in ELA cells resulted in a decrease in cisplatin-induced caspase-3 activity, confirming earlier findings that ANO6 is involved in apoptosis. Finally, knock-down of ANO1 and ANO6 did not affect the volume-sensitive release of taurine in ELA cells. Thus, our data provide evidence that ANO6 cannot be activated directly by cell swelling unless Ca(2+) is present. We also conclude that ANO6 carries a current during RVD, provided extracellular calcium is present. Thus, swelling activation of ANO6 requires the presence of free calcium.

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OBJECTIVE: This study aimed to compare the prognostic value and the predictive accuracy of the PC-10 cell cycling marker with the largest tumor diameter, the mean of the largest nucleoli, and vascular patterns in posterior uveal melanoma. DESIGN: The study design was a case-control study. PARTICIPANTS: Eyes enucleated for posterior uveal melanoma from patients who either died of metastatic melanoma or survived without signs of metastatic disease 10 years or more after surgery were studied. INTERVENTION: Three observers assessed the above prognostic indicators and standard histopathologic characteristics from microslides without access to survival data. MAIN OUTCOME MEASURES: Univariate and multivariate Cox models for survival were constructed, and a multiparameter prognostic index was calculated for each patient, based on covariates obtained from the final Cox model. The prognostic accuracy was determined by receiver operating characteristic curve analysis. RESULTS: The log PC-10 count, vascular networks, mean of the largest nucleoli, largest tumor diameter, age of patient, and prognostic index were independently associated with outcome. However, each of these indicators had no more than a poor-to-moderate predictive accuracy, and only the prognostic index was significantly better than the largest tumor diameter. CONCLUSIONS: The PC-10 count retains a prognostic value in uveal melanoma when adjusting for the effect of the mean of the largest nucleoli and diverse vascular patterns. A prognostic index combining two or more indicators may improve the predictive precision.

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From 1977 to 1989 6488 patients under fifty years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of the total group with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on five- and ten year survival.

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From 1977 to 1989 6488 patients under 50 years with primary breast cancer were registered in the nationwide Danish Breast Cancer Cooperative Group (DBCG). Among these, information on last menstrual period prior to surgery was available in 1635 cases which constitute the study group of the present analysis. The group was representative of all women operated upon during the period with regard to prognostic factors and survival. In the study group time of surgery in relation to last menstrual period was found to have no influence on 5 and 10 years survival.

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A retrospective investigation revealed that in 11 out of 23 pregnant women submitted to operation on account of suspected appendicitis the diagnosis could be confirmed. The perinatal and the maternal mortalities were both 0. In the women submitted to operation, the frequency of obstetric complications was found to be 17%, 95% confidence limits 5-39%, and the frequency of surgical complications was 17%, 95% confidence limits 5-39%. The diagnostic specificity was found to be significantly higher in women who had previously born children. Brief duration of symptoms preoperatively and operation employing beta-sympathomimetics are recommended.

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Using a transurethral approach intravesical pressure and blood pressure were recorded in 10 males with acute urinary retention during either continuous or fractionated drainage. Upon evacuation of the initial 100 cm3 urine the intravesical pressure declined to approximately 50% of the initial value in both groups relieving pain in all patients. Blood pressure was significantly lowered following the procedure, but clinical manifestations were absent. One patient demonstrated hematuria, but treatment was not necessary. The study renders no support for previous recommendations of fractionated outlet of urine in this condition.

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59 patients with obstructive prostatic hypertrophy (BPH) were evaluated regarding the influence of prostatectomy on upper urinary tract function by means of [51Cr]EDTA clearance and gamma camera renography measurements. 25 patients were randomly allocated to transvesical and 34 patients to transurethral prostatectomy. At the 6-month follow-up a slight decrease in glomerular filtration rate (GFR) was seen in the total patient group. Residual renal activity 20 min following injection (A20) as well as half-peak time values showed upper urinary tract obstruction in 54% of the patients preoperatively, whereas dilatation of the upper urinary tract was demonstrated at i.v. pyelography in only 15%. Patients with renographic obstruction preoperatively had low GFR values compared with patients without obstruction. In patients with upper urinary tract obstruction, prostatectomy relieved the obstruction, even in the case of normal urography. In patients with normal upper urinary tract, a clinically insignificant decrease in GFR and increase in A20 and half-peak time was observed. No differences with regard to upper urinary tract function were seen on comparing transurethral with transvesical prostatectomy.

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The rewarming time of fingers after hand cooling to 10 degrees during ischaemia was significantly prolonged in all subjects with Raynaud's phenomenon of occupational origin compared with normal reaction and patients with primary Raynaud's phenomenon. The temperature is faster and easier to record than pressure or pulse volume. Population studies are in progress with the described technique.

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