Effects of hormone replacement therapy on plasma viscosity and Doppler variations in postmenopausal non-smokers and heavy smokers.

OBJECTIVES: To evaluate the effects of transdermal hormone replacement therapy (HRT) on some biological cardiovascular risk factors, specifically thromboxane B2 level and plasma viscosity. Furthermore, we investigated Doppler flow modifications at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries, and evaluated whether there were significant differences, in the examined parameters, between postmenopausal women who were non-smokers and heavy smokers. METHODS: Forty-three postmenopausal women (age 53.6 +/- 3.3 years, mean +/- standard deviation) participated in the study and were divided into two groups (Group I: n = 21, normal controls; and Group II: n = 22, heavy smokers). Patients were treated with continuous estradiol transdermal supplementation and 12-day courses of medroxyprogesterone acetate every 2 months. They were studied at baseline and after 6 months (in the estrogen-only phase of the cycle). RESULTS: Results showed a beneficial effect of hormone substitution after 6 months of therapy. Plasma viscosity decreased significantly after 6 months of therapy both in non-smokers and heavy smokers (-18% and -14%, respectively). Plasma levels of thromboxane B2, which were similar at baseline, underwent a dramatic reduction in both Group I and Group II (-93% and -88%, respectively). Doppler assessment of pulsatility index at the level of the uterine, internal carotid, ophthalmic and bladder wall arteries showed a significant reduction in vascular impedance at the end of treatment in both groups. However, the treatment was significantly less beneficial, in terms of the analyzed factors, in heavy smokers. CONCLUSIONS: Cigarette smoking represents a cardiovascular risk factor that can only partially be modified by the administration of transdermal HRT.     

The ''dark nucleus'' and disruptions of follicular architecture: possible new histological aids for the diagnosis of the follicular variant of papillary carcinoma of the thyroid

AIMS: In order to facilitate the diagnosis of malignancy in solitary thyroid nodules which are non-invasive low-grade tumours, i.e. follicular variant of papillary carcinoma (FVPC) for which few histological discriminators exist, a search was made for additional diagnostically useful histological features. Methods and results: Haematoxylin and eosin (H & E)-stained sections of 70 resection specimens of solitary thyroid nodules were re-evaluated by a panel of three pathologists, and their consensus and original diagnoses compared. In addition, H & E- and periodic acid-Schiff-stained sections were evaluated for various histological features and sections were stained by various immunohistochemical markers to evaluate their discriminative powers. The above features were also assessed in a group of 24 papillary carcinomas of the thyroid (PTCs) associated with regional metastases. The finding of 'Orphan Annie eye' nuclei was the best indicator of malignancy, and was closely related to the presence of nuclear grooves and cells with dense, dark nuclei. In addition, distorted follicular architectural features, i.e. 'interconnecting cell masses' and 'fenestration', were also significant indicators of malignancy. Tumours diagnosed as FVPCs had a significantly lower incidence of associated lymph node metastases than the classical PTCs. CONCLUSIONS: The use of optically clear nuclei as a diagnostic criterion when found only focally may not be sufficiently stringent in distinguishing FVPCs from follicular adenomas. When classical histological indicators of malignancy are equivocal, the diagnosis of FVPC may be facilitated by the above-mentioned features.     

Rhythmic variation in the rate of ectopic pregnancy throughout the year.

OBJECTIVE: This study was conducted to determine whether the incidence of ectopic pregnancy follows a seasonal rhythm of occurrence. STUDY DESIGN: A retrospective analysis was performed on 15,639 pregnancies reported in a single department in 5.5 years (January 1992-June 1997). For each pregnancy the time of conception was estimated from medical records. Frequencies of conceptions that terminated in birth, spontaneous abortion, legally induced abortion, and ectopic pregnancy were distributed across the 12-month period. RESULTS: Total pregnancy showed a seasonal rhythm of occurrence, with peak values in March. The rate of ectopic pregnancy showed a rhythm with 2 peaks, in June and December. Nadirs were coincident with the peak and nadir of total conceptions and also with the equinoxes. Spontaneous abortions tended to show a rhythm the inverse of that of ectopic pregnancy. CONCLUSIONS: These data show an influence of the seasons on the rate of ectopic pregnancy, which may have implications for both the understanding of ectopic pregnancy's causative mechanisms and its prevention.     

Dementia, ataxia, extrapyramidal features, and epilepsy: phenotype spectrum in two Italian families with spinocerebellar ataxia type 17

Abstract. We observed two families with a dominantly inherited complex neurological syndrome with onset in adulthood. Family F included 9 affected in four generations. One patient showed prominent anticipation of onset age. Onset was with cerebellar signs followed by dementia, psychiatric symptoms, seizures, and extrapyramidal features. Family M included 14 affected individuals in five generations. Presenting symptoms were either psychiatric and cognitive impairment or a cerebellar syndrome. Extrapyramidal features, dysphagia, incontinence, seizures, and myoclonus may occur. In both families magnetic resonance imaging showed marked atrophy of the brain and cerebellum. Molecular analyses demonstrated an expanded CAG/CAA repeat in the in the TATA box-binding protein (TBP) gene (SCA17).     

Transdermal hormone replacement therapy and Doppler findings in normal and overweight postmenopausal patients.

The aim of this study was to evaluate the effects of transdermal hormone replacement therapy on some biological cardiovascular risk factors, specifically the thromboxane B2 levels, plasma viscosity and the lipid profile. Furthermore, we investigated the Doppler flow modifications at the level of the uterine artery, the internal carotid, the ophthalmic and the bladder wall arteries, and we finally evaluated whether there were significant differences in the examined parameters between normal and overweight postmenopausal women. Forty-five postmenopausal women (mean age+/-standard deviation, 53.5+/-3.8 years) participated in the study and were divided into two groups (27 with a body mass index of < 25 kg/m2 and 18 with a body mass index of > 25 kg/m2). Patients were treated with a continous estradiol transdermal supplement and a 12-day course of medroxyprogesterone acetate every 2 months, and were studied at baseline and after 6 months (in the estrogen-only phase of the second cycle). Our results showed a beneficial effect of hormone substitution on plasma viscosity, thromboxane B2 levels and lipid profile after 6 months of therapy and significant improvements of Doppler flow parameters in the examined vessels. Furthermore, we observed a lower impact of the treatment in overweight women. In conclusion, obesity represents an additional cardiovascular risk condition and it can only partially be modified by the administration of hormone replacement therapy.     

Dietary administration of an extract from rosemary leaves enhances the liver microsomal metabolism of endogenous estrogens and decreases their uterotropic action in CD-1 mice

We evaluated the effects of a methanol extract from the leaves of the plant Rosmarinus officinalis L. (rosemary) on the metabolism and action of estradiol and estrone. Treatment of female CD-1 mice with 2% rosemary in AIN-76A diet for 3 weeks increased the liver microsomal 2- hydroxylation of estradiol and estrone by approximately 150%, increased their 6-hydroxylation by approximately 30% and inhibited the 16alpha- hydroxylation of estradiol by approximately 50%. Treatment of female CD- 1 mice with 2% rosemary diet for 3 weeks also stimulated the liver microsomal glucuronidation of estradiol and estrone by 54-67% and 37- 56%, respectively. In additional studies, feeding 2% rosemary diet to ovariectomized CD-1 mice for 3 weeks inhibited the uterotropic action of estradiol and estrone by 35-50% compared with animals fed a control diet. The results of this study showed that feeding female mice a 2% rosemary diet increased the liver microsomal oxidation and glucuronidation of estradiol and estrone and inhibited their uterotropic action.      

Diurnal variation of semen quality in human males.

The possibility of a diurnal variation in semen quality was tested in 54 human males attending our infertility clinic. Of the enrolled subjects, 24 were normozoospermic and 30 were suffering from oligo- and/or asthenozoospermia. Seminal fluid was collected by masturbation twice by each subject, once in the morning (7:00-7:30 a.m.) and once in the afternoon (5:00-5:30 p.m.). Abstinence from sexual intercourse for 3-4 days before each of the two collections was requested. Semen parameters were evaluated independently by two biologists before and after pellet swim-up. Beside similar macroscopic parameters, specimens collected in the afternoon showed a higher number (P < 0.01) and concentration (P < 0.01) of spermatozoa. Also, immediately (P < 0.05), and at 1 h (P < 0.02) and 2 h (P < 0.01) after pellet swim-up, the number of spermatozoa with progressive linear motility was higher in the afternoon than in the morning. These data are the first documenting a diurnal rhythm in sperm quality which may contribute to the reported variability in semen parameters, and may prove useful for spontaneous and assisted conceptions.     

HLA-DRB1*08, DRB1*03/DRB3*0101, and DRB3*0202 are susceptibility genes for Graves' disease in North American Caucasians, whereas DRB1*07 is protective.

Graves' disease is known to be HLA-D associated; however, the primary loci involved remain unclear. We examined HLA genotypes of DRB1 and DQB1 plus DRB3 subtypes using PCR-based sequence-specific priming in two groups of North American (Gainesville, FL; and Toronto, Canada) Caucasian patients with Graves' disease. We stratified patients into those with either early age at onset (<20 yr; 13.1 +/- 4.8 yr; n = 30) and later age at onset of disease (38.8 +/- 9.7 yr; n = 62) and compared the results to 192 normal controls. As expected, we found that DRB1*03 was associated with Graves' disease, but at a higher odds ratios for early-onset than later-onset patients (3.7 vs. 2.2). The frequency of DRB1*08 was also increased in both groups of patients, but significantly so only in patients with early-onset Graves' (P = 0.001; chi2 = 10.8). DRB3 was highly associated with Graves' in both groups of patients (P = 0.009; chi2 = 6.83 and P = 0.0015; chi2 = 10.1, respectively); however, the subtypes of DRB3 revealed differential susceptibilities. Whereas the frequencies of both DRB3*0101 and DRB3*0202 were increased over the entire cohort, that of DRB3*0301 was not. Significant P values were found for DRB3*0101 in patients with early-onset and for DRB3*0202 in patients with later onset of Graves' disease. When the haplotypes of DRB1*03-DRB3 of all subtypes were removed for analysis (all DRB1*03 positive also had DRB3*0101), the frequency of DRB3*0202 remained significantly higher in the patients with later onset of Graves' disease than in controls (P = 0.0043; chi2 = 8.13), but DRB3 was no longer positively associated with the early-onset group. In addition, we found that DRB1*07 was negatively associated with both groups of patients (P = 0.024; chi2 = 5.10 and P = 0.0085; chi2 = 6.93). These data suggest that DRB3*0202 is more likely to be the primary susceptible locus than DRB1*03 for patients with later onset of Graves' disease.