No evidence of microsatellite instability in bone tumours.

Microsatellite instability has recently been reported in sporadic and familial colorectal tumours and can be due to defects in DNA mismatch repair genes. Such instability has subsequently been detected in several other types of sporadic tumours. We studied 29 specimens of bone tumours with different histopathological diagnoses and found no evidence of microsatellite instability. Our results suggest that mismatch repair defects are unlikely to play a significant part in the tumorigenesis of bone neoplasms. Loss of heterozygosity with at least one marker was detected in 11, i.e. in 38% of the tumour samples, most frequently with markers D2S136 at 2p (eight of 28 informative specimens, 29%) and D11S904 at 11p (four of 21 informative specimens, 19%).     

Five-year clinical experiences with NOVA T 380 copper IUD

In an open, single-group, phase III clinical trial of 5 years, the clinical performance of NOVA T 380 was investigated in three centers. The device having a higher copper surface of 380 mm(2) is a modification of NOVA T. A total of 400 voluntary women were enrolled in the study. The mean age was 31.4 years (SD 5.5) with the minimum of 18 and the maximum of 44 years. At the end of the study, 211 women had passed the 60-month visit. Cumulative discontinuation rates at the end of the first and the fifth year calculated by Kaplan-Meier estimates, were respectively as follows: pregnancy 0.5 and 1.9, expulsion 1.3 and 4.1, bleeding 4.4 and 14.0, pain 1.3 and 4.2, removal for other medical reason 1.4 and 6.4, planning pregnancy 0.8 and 13.5, and removal for other personal reason 2.4 and 11.9 per 100 users. Neither ectopic pregnancies nor episodes of pelvic inflammatory diseases (PIDs) occurred. One perforation was recorded; the calculated rate is 0.3 per 100 women (first year). The continuation rate was 88.3 and 52.5 at 1 and 5 years, respectively. In conclusion, the 5-year performance of NOVA T 380 was good compared to other "high-loaded" copper devices. Safety was acceptable over the entire study period.     

Recurrent gains of 1q, 8 and 12 in the Ewing family of tumours by comparative genomic hybridization.

Comparative genomic hybridization (CGH) was used to detect copy number changes of DNA sequences in the Ewing family of tumours (ET). We analysed 20 samples from 17 patients. Fifteen tumours (75%) showed copy number changes. Gains of DNA sequences were much more frequent than losses, the majority of the gains affecting whole chromosomes or whole chromosome arms. Recurrent findings included copy number increases for chromosomes 8 (seven out of 20 samples; 35%), 1q (five samples; 25%) and 12 (five samples; 25%). The minimal common regions of these gains were the whole chromosomes 8 and 12, and 1q21-22. High-level amplifications affected 8q13-24, 1q and 1q21-22, each once. Southern blot analysis of the specimen with high-level amplification at 1q21-22 showed an amplification of FLG and SPRR3, both mapped to this region. All cases with a gain of chromosome 12 simultaneously showed a gain of chromosome 8. Comparison of CGH findings with cytogenetic analysis of the same tumours and previous cytogenetic reports of ET showed, in general, concordant results. In conclusion, our findings confirm that secondary changes, which may have prognostic significance in ET, are trisomy 8, trisomy 12 and a gain of DNA sequences in 1q.     

Rapid eye movement stage of sleep participates in the generation of the nocturnal meal pattern in the rat

Twenty-four hour cycles of food intake were continuously recorded in eight male rats on a $\text{12}\text{12}$ hr light/dark schedule during baseline conditions and rapid eye movement sleep deprivation. The results suggest that food intake in the rat is controlled by two different mechanisms, one serving control of immediate caloric demands during the dark part of the LD cycle and the other, activated prior to the beginning of the inactive light hours, being responsible for the intake of a few large meals covering the total energy requirement for this time period. The correct timing of the consumption of these large meals with respect to the LD cycle seems to be dependent on undisturbed rapid eye movement sleep.     

Comparison of genetic changes in primary sarcomas and their pulmonary metastases.

The aims of the present study were to compare genetic aberrations in primary sarcomas and their pulmonary metastases and to explore the pathways associated with disease spreading. The primary tumor and its subsequent pulmonary metastasis of 22 patients were analyzed by comparative genomic hybridization. All samples were obtained before the initiation of chemo- or radiotherapy. The mean total number of aberrations per tumor was 7.6 (range, 0-17) in primary tumors and 7. 5 (range, 0-19) in metastases. The mean numbers of high-level amplifications per tumor were similar (0.32 in primary tumors and 0. 36 in metastases). The frequencies of the most common aberrations were relatively similar in primary tumors and metastases: the most frequent gain affected 1q (minimal common regions 1q21-q23 in 36% of primary tumors and 1q21 in 45% of metastases). The most frequent losses were detected at 9p (9p22-pter in 32% of primary tumors and 9p21-pter in 32% of metastases), 10p (10p11.2-p12 in 41% of primary tumors and 10p11.2-pter in 32% of metastases), 11q (11q23-qter in 36% of primary tumors and 32% of metastases), and 13q (13q14-q21 in 45% of primary tumors and 50% of metastases). No aberrations specific to metastases were detected. An increase in the total number of changes during progression was a predominant feature in a majority of these paired samples. Also, the number of differences in the genetic profile outnumbered common changes in a majority of the samples. However, despite the heterogeneous and numerous changes, all pairs with aberrations in both specimens had some shared alterations in both samples. Genes Chromosomes Cancer 25:323-331, 1999.     

Ovarian function during use of vaginal rings delivering three different doses of Nestorone.

Contraceptive vaginal rings delivering various progestins alone or in combination with estrogen have been previously studied, showing adequate steroid vaginal absorption and acceptability by the users. Nestorone progestin (NES) is a potent 19-nor-progesterone derivative, inactive by the oral route, but an excellent option for vaginal delivery. The purpose of this study was to evaluate ovarian function during 6 months of continuous use of progestin-only vaginal rings delivering 3 different doses of NES: 50, 75, and 100 microg per day. Blood samples were taken twice a week for 5 consecutive weeks during a control cycle and on months 1, 3 and 6 of use, for the measurement of estradiol (E2), progesterone (P), and NES. A total of 87 volunteers randomly received each of the 3 doses. After an initial peak, NES serum levels remained fairly constant throughout the duration of the study at about 125, 200 and 250 pmol/L, respectively, decreasing slightly with time. Luteal activity occurred very rarely (1.2-2.6% of sampling periods) with no apparent difference between doses. Low E2 levels (< or =100 pmol/L) in all samples of a run were rare (5%) and only with the high dose ring (100 microg/day). E2 remained within normal levels (101-1500 pmol/L) in most of the segments studied. We conclude that the 50 and 75 microg/day NES rings provide adequate ovulation inhibition without hypoestrogenism, while the 100 microg/day ring may deliver an unnecessarily high dose.     

Morphotypes of the Subgingival Microflora in Diabetic Adolescents in Finland

The morphotypes of the subgingival microflora from 85 12 to 18–year–old Finnish adolescents with insulin–dependent diabetes mellitus (IDDM) were studied in Gram– and Rhodes–stained smears. A comparison was made with subgingival plaque samples from paired age– and sex–matched healthy controls. Significant differences were found in the distribution of the morphotypes. The microflora in the IDDM patient group contained significantly lower proportions of Gram–positive and Gram–negative cocci and total Gram– positive bacteria and higher proportions of Gram–negative rods, fusiforms, and total Gram– negative bacteria. In the Rhodes–stained samples, the patients had more straight and curved rods and less fusiforms than the controls. The proportions of spirochetes and flagellated bacteria were almost identical in both groups. The clinical periodontal status of the subjects had been reported in a separate study. In spite of similar Plaque Index scores, the patients had more gingivitis than the controls. This finding may be explained by the distribution of morphotypes: more Gram–negative rods and total Gram–negative bacteria (periodontally more pathogenic forms) in the diabetic patients. {J Periodontol 1989;60:526–528).     

Blood cadmium and plasma zinc measurements in acute myocardial infarction.

Blood cadmium and plasma zinc were measured in a series of 47 patients admitted for myocardial infarction (MI) and in 37 control subjects divided into 3 groups. Certainly increased blood cadmium values, for the MI patients, were found in 33%. The mean blood cadmium value of the MI series was significantly (P less than 0.001), but not invariably, higher against the control subjects. The difference between the zinc values of the series was studied in 35 MI patients with raised serum enzyme activity. In MI patients, the mean plasma zinc content was significantly (0.001 less than P less than 0.01) lower than in healthy controls. Of the enzymes, the highest positive correlation was found between the ratio of blood cadmium to plasma zinc and the GOT activity. Of the ratio, the MI patients had values in excess of the controls range in 43%, and values within the limits of the healthy controls in 40%. Therefore, the rise in the ratio is of limited value for the diagnosis of myocardial infarction in an individual patient.