Fate of TR-2, the hepatic metabolite of the tremorgenic mycotoxin verruculogen, in sheep

1. Verruculogen is eliminated in bile after transformation to TR-2, only a trace of which was excreted as such in faeces of sheep given verruculogen per os. Negligible TR-2 was present free in urine; no glucuronide was found. 2. An isomer of TR-2, a minor component of the bile of sheep given verruculogen, has been defined by 1H-n.m.r. spectroscopy and the isomerism involves the disposition of the two adjacent hydroxyl groups with a concomitant change in the conformation of the ring adjacent to the indole. 3. 14C-TR-2, added to the perfusate of isolated rat liver, was excreted unchanged in the bile, implying no significant loss of any biliary TR-2 subject to enterohepatic recycling in vivo. 4. 14C-TR-2 incubated anaerobically in sheep ileum contents was 95% transformed into more polar metabolites, the majority of the radiolabelled metabolites isolated being water soluble. 5. The principal fate of biliary TR-2 is as a metabolic substrate for the intestinal microflora.     

The importance of self-examination in the earliest diagnosis of multiple primary cutaneous melanomas: a report of 47 cases

BACKGROUND: Development of more than one primary melanoma in a patient is a relatively uncommon but well-recognized phenomenon. Its frequency has ranged from 1.2% to 8.2% in several series. This subgroup of patients with multiple primary lesions has not been characterized sufficiently. We report the experience of the Melanoma Unit of University Hospital Spedali Civili of Brescia, Italy. METHOD: Study subjects were drawn from 1240 patients with histologically confirmed melanoma, including melanoma in situ. From this group, multiple melanomas developed in 47 patients (3.79%). Every one of our patients has been taught to perform self-examination of the skin to detect suspicious pigmented lesions. RESULTS: Of the 47 patients described in this study, 38 had two primary melanomas, 7 had three melanomas and 2 had 5 and 10 melanomas, respectively. Mean age at first diagnosis was 46.2 years. The majority of subsequent melanomas (74.5%) were removed within 5 years of the initial operation. Synchronous lesions were found in 10 patients. In male patients, the lesion appeared most frequently on the trunk; in female patients, melanoma appeared mostly on the lower extremities. The second primary melanomas developed in the same anatomic region from the first in 53.2% of our patients. The proportion of in situ to invasive melanomas was greater for the second melanomas compared with the first melanomas. Regarding invasive melanomas, the mean thickness of the first melanomas was 1.31 mm compared with 0.66 mm for the second ones. Dividing patients into two groups, of more and less than 50, it is highlighted that in older patients synchronous lesions appear more frequently (36.4% vs. 8.0%); the median time interval between sequential melanomas is longer (84 vs. 63.7 months); and the ratio between the primary and secondary melanoma mean thickness is lower (1.21 : 1.08 vs. 1.43 : 0.63 mm). CONCLUSIONS: The study confirms that second primary melanoma is usually thinner than the first lesion, and it is more common in the same region of the body as the initial melanoma. The highest risk for a second melanoma is during the first 5 years, but a much longer time interval of 28 years is possible. Continued medical follow-up with complete skin examinations seems prudent, but it is very important to promote self-skin evaluation in patients to detect not only metastases but also subsequent primary melanomas in their earliest phases.     

Concordance between routine interictal magnetoencephalography and simultaneous scalp electroencephalography in a sample of patients with epilepsy.

Both electroencephalography (EEG) and magnetoencephalography (MEG) localize epileptiform activity but may yield different results. This discordance may arise from different detection capabilities or from different data collection and interpretation techniques. Comparisons of MEG and EEG have focused on detection of individual spikes. However, side-by-side comparisons of results as used in the clinical setting is lacking. In this report, we present our empirical comparison. We reviewed 58 simultaneous MEG-EEG recordings (35 paired-sensors, 23 whole-head) from a diverse epilepsy population, comparing previous clinical MEG interpretations with new blinded EEG interpretations, noting lobar concordance of readers' judgments of regional abnormalities. A second-pass unblinded analysis, using all available clinical data, assessed the relative contribution and plausibility of the results of each technique. Concordance was high (85%) overall. Discordance was sometimes caused by constraints imposed by MEG dipole fitting techniques. Even when results of the techniques did not match, MEG often disambiguated the clinical scenario, especially when combined with imaging information. Thoughtful analysis of combined MEG-EEG datasets, beyond algorithm-based interictal spike detection, can help guide clinical decision-making even when concordance between techniques is imperfect. In some cases, EEG and MEG are synergistic and provide complementary information.     

Critical ovarian hyperstimulation syndrome in a coasted in-vitro fertilization patient

We report an instance of critical ovarian hyperstimulation syndrome in a highly responsive in-vitro fertilization patient despite the preventive measure of a 4 day 'coast' interval during which no gonadotrophins were administered while gonadotrophin-releasing hormone agonist therapy continued until serum oestradiol concentrations fell below 3000 pg/ml.      

Growth in and breakdown of purified rabbit small intestinal mucin by Yersinia enterocolitica.

The mucus lining of the gastrointestinal tract serves as a protective barrier over the epithelial surface that must be crossed by invading bacteria seeking entry into the mucosa. The gel-forming component of mucus is mucin, a large polymeric glycoprotein. The present study examined the growth of Yersinia enterocolitica (with and without its virulence plasmid) in purified rabbit small intestinal mucin and the ability of bacteria to degrade mucin. Both virulent and nonvirulent organisms showed enhanced growth in mucin-supplemented media compared with unsupplemented media, but only at 37 degrees C and not at 25 degrees C. The effects of mucin were not specific because medium supplemented with bovine serum albumin also enhanced bacterial growth at 37 degrees C. Purified mucin was broken down into lower-molecular-weight components (assessed by monitoring its elution profile on a Sepharose CL-2B column) by plasmid-bearing Y. enterocolitica but not by plasmid-cured organisms. Culturing virulent Y. enterocolitica at 25 degrees C completely suppressed its capacity to degrade mucin, suggesting that this activity depends on plasmid expression. These results were confirmed in similar studies with purified rabbit colonic mucin. Mucin-degrading activity could be demonstrated in spent culture media from virulent Y. enterocolitica incubated at 37 degrees C but not in bacterial membrane preparations. Changes in the elution profiles of small intestinal and colonic mucins exposed to plasmid-bearing Y. enterocolitica at 37 degrees C were consistent with proteolytic depolymerization. The ability to grow well in mucin may help Y. enterocolitica to colonize the intestine, while the production of a mucin-degrading enzyme(s) by plasmid-bearing organisms may assist pathogenic strains to solubilize and penetrate the mucus gel layer.     

Colour Doppler changes and thromboxane production after ovarian stimulation with gonadotrophin-releasing hormone agonist

The objective of this study was to evaluate the Doppler flow variations which occur following the use of different protocols of ovarian stimulation in an IVF programme, and to investigate the thromboxane production by cultured endometrial cells and its influence on embryo implantation. A total of 60 patients underwent three different ovarian stimulation protocols: long gonadotrophin-releasing hormone agonist (GnRH-a), short GnRH-a and no GnRH-a. Transvaginal ultrasonography and colour Doppler analysis were performed before and during the treatment. On the day that the Doppler examination took place, luteinizing hormone, follicle stimulating hormone, plasma oestradiol and thromboxane concentrations were assayed. On the day of oocyte retrieval, endometrial cells were collected and cultured, and their thromboxane production evaluated. No significant differences in hormonal, ultrasonographic or Doppler parameters were observed between the three groups. Ten out of 56 patients who had a successful embryo transfer became pregnant. In the group of pregnant women the pulsatility index values of both uterine and spiral arteries was lower than in non-pregnant patients, and was associated with significantly lower thromboxane concentrations from cultured endometrial cells. It is concluded that thromboxane plays a role in embryo implantation, and that Doppler flow analysis of uterine and spiral arteries in infertile patients may be important in the management of ovarian stimulation.      

A longitudinal study of maternal serum inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC and follistatin during pregnancy

Maternal serum concentrations of inhibin-A, inhibin-B, activin-A, activin-AB, pro-alphaC-related inhibin forms, total follistatin, steroids and gonadotrophins were measured longitudinally in six normal singleton pregnancies. Maternal venous blood was collected randomly during a spontaneous follicular phase prior to donor insemination, at 5, 7, 9, 11, 16, 20, 24, 28, 32 and 36 weeks after the first missed menses and in the early puerperium. Steroid and gonadotrophin profiles conformed to previous reports. While at week 5 of gestation inhibin-A, activin-A and follistatin concentrations were similar to those at the follicular phase, all three increased progressively (P < 0.001) to maximal concentrations in week 36: approximately 48-fold (3740 +/- 1349 ng inhibin-A/ml), approximately 22-fold (6109 +/- 1443 ng activin-A/ml) and approximately 10-fold (3563 +/- 418 ng follistatin/ml) higher. Pro- alphaC concentrations reached a maximum in weeks 5 (approximately 5- fold, P < 0.001) and 36 (1027 +/- 174 pg/ml, P < 0.01). Inhibin-B (71 +/- 23 pg/ml prior to pregnancy) was undetectable (<12 pg/ml) between week 5-16 of gestation but increased slightly in the third trimester (26 +/- 7 pg/ml in week 36). Activin-AB was undetectable throughout pregnancy. Post-partum concentrations of inhibin-A (41 +/- 12 ng/ml), inhibin-B (<12 pg/ml), activin-A (950 +/- 149 pg/ml), pro-alphaC (128 +/- 22 pg/ml) and follistatin (990 +/- 79 ng/ml) were substantially lower than at week 36 of gestation. The activin-A:follistatin ratio increased from 0.5 in week 5 to 1.8 in week 36, suggesting that more free activin-A is available in the maternal circulation during late pregnancy.