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PubMed1997

Continuous versus cyclical transdermal estrogen replacement therapy in postmenopausal women: influence on climacteric symptoms, body weight and bleeding pattern.

OBJECTIVES: To compare continuous and cyclical transdermal estrogen replacement therapy (ERT) with or without an oral progestogen regarding climacteric symptoms, body weight and bleeding pattern. METHODS: A total of 2459 postmenopausal women were treated for three cycles of 28 days in an open, randomized, parallel group multicenter study. Patients received an estrogen matrix patch (50 micrograms 17/beta-estradiol/day) twice weekly, either continuously (eight patches/cycle) or cyclically (six patches/cycle, i.e. 3 weeks on, 1 week off). A total of 1232 patients were treated continuously and 1227 cyclically. In the study group 1150 patients had an intact uterus (543 in the continuous and 607 in the cyclical treatment arm) and received, in addition to the estrogen patch, an oral progestogen in a transformation dose for 12 days of each cycle. Hysterectomized patients totaling 1309 (689 in the continuous versus 620 in the cyclical group) did not receive progestogen. Of the 2459 patients, 771 (31.4%) participated in a follow-up study with two further treatment cycles, which was offered to the patients at the end of the main study. The main outcome measures were climacteric symptoms, measured at the end of cycles 1-3 by a Visual Analogue Scale at baseline, and body weight measured at baseline at the end of cycles 3 and 5. In addition, the bleeding time per cycle (days) was evaluated in all patients with an intact uterus. RESULTS: Continuous and cyclical transdermal ERT reduced, over three treatment cycles, the average climacteric symptom score by 1.77 and 1.70, respectively. The percentage remission and improvement rates for the ten climacteric symptoms ranged between 69.3 and 88.0% and did not differ between the two groups. In patients with a higher symptom score at baseline, the continuous treatment was slightly more effective. However, this effect was statistically not significant. After three treatment cycles body weight increased in both treatment groups by between 500 and 700 g. Further treatment during the follow-up study induced an additional average weight gain of 200-400 g. These results were not influenced by the addition of an oral progestogen. In patients with an intact uterus, the average bleeding time at the end of the first cycle (5.4 days in the continuous versus 5.3 days in the cyclical group) increased slightly during cycle 2 and returned to baseline values at the end of cycle 3. CONCLUSIONS: Continuous and cyclical transdermal ERT were equally effective in reducing climacteric symptoms. The short term use of five cycles transdermal ERT induced a slight increase in body weight which was independent of the treatment regimen. These results were not influenced by the type and mode of administration of a progestogen. Both ERT regimens were very well tolerated and are suitable alternatives for estrogen replacement therapy of postmenopausal women.

Administration, Cutaneous↗
PubMedDate not supplied

Comparison of bipolar and tetrapolar impedance techniques for assessing fat mass.

Whole body fat mass (BF) can be predicted by different bioimpedance (BIA) techniques measuring the whole body (tetrapolar hand-to-foot technique, HF), lower body (bipolar foot-to-foot technique, FF), or upper body (bipolar hand-to-hand technique, HH). This study analyzed 146 healthy volunteers (age 18-84 years) for whether these three techniques differ in their estimates of BF, and whether sex and age of the subjects influence estimates of BF. Reproducibility of the techniques was tested by calculating the technical error (TE). Effects of BIA technique, sex, and age on predicted BF were analyzed with ANOVA for repeated measurements in a mixed effect design. Results showed high reproducibility for the three BIA techniques (TE = 0.01-0.03 kg). ANOVA indicated interactions between BIA technique and sex (P = 0.035), BIA technique and age (P < 0.001), as well as effects of sex (P = 0.004) and age (P = 0.001) on variation in BF. The HH technique gave the highest values for BF in males, but lowest values in females, whereas the reverse was found for the FF technique. The HH technique yielded the lowest values for BF in young adults, but highest values in older ones. The reverse was noted for the FF technique. The data suggest that the observed differences in the three BIA techniques in predicting BF reflect sex differences and age-associated changes in body fat patterning. Therefore, the whole body impedance method is preferred over the HH and FF techniques due to the interactions with sex and age.

Adolescent↗
PubMed2000

Pre-pleistocene refugia and differentiation between populations of the caucasian salamander (Mertensiella caucasica).

A 350-bp fragment of the mitochondrial cytochrome-b gene was sequenced in the Caucasian salamander, Mertensiella caucasica, representing 10 populations from across its range along the Black Sea coast. Five haplotypes were discovered among 65 fragments analyzed, differing at 2-50 positions. The highest differentiation between haplotypes was observed in animals from the eastern part of the species' range (Borjomi) compared to those from the remainder of the species' range. Randomly amplified nuclear DNA revealed a pattern of spatial genetic variation similar to that of the mitochondrial genome. M. caucasica, as currently known, represents two evolutionary lineages that evolved independently, perhaps since the lower Pliocene. These lineages represent taxa, possibly to be described as species, distributed in the Borjomi area in central Georgia and in southwestern Georgia and northeastern Turkey. The multivariate analysis of morphological data did not reveal significant differences between the taxa. However, substantial morphological differentiation was observed within both lineages, showing parallel patterns in body proportions and coloration patterns. This variation is possibly associated with extant ecological conditions. Salamanders with reduced pigmentation from southwestern Georgia were not genetically distinguishable from neighboring populations.

Animals↗
PubMed2003

Heart development: molecular insights into cardiac specification and early morphogenesis.

The heart develops from two bilateral heart fields that are formed during early gastrulation. In recent years, signaling pathways that specify cardiac mesoderm have been extensively analyzed. In addition, a battery of transcription factors that regulate different aspects of cardiac morphogenesis and cytodifferentiation have been identified and characterized in model organisms. At the anterior pole, a secondary heart field is formed, which in its molecular make-up, appears to be similar to the primary heart field. The cardiac outflow tract and the right ventricle to a large extent are derivatives of this anterior heart field. Cardiac mesoderm receives positional information by which it is patterned along the three body axes. The molecular control of left-right axis development has received particular attention, and the underlying regulatory network begins to emerge. Cardiac chamber development involves the activation of a transcription program that is different from the one present in the primary heart field and regulates cardiac morphogenesis in a region-specific manner. This review also attempts to identify areas in which additional research is needed to fully understand early cardiac development.

Animals↗
PubMed1997

Determinants of sex hormone-binding globulin blood concentrations in premenopausal and postmenopausal women with different estrogen status. Virgilio-Menopause-Health Group.

In women, sex hormone-binding globulin (SHBG) concentrations are the result of a balanced effect of stimulatory and inhibitory factors. Estrogens represent the principal stimulatory hormones, whereas androgens, insulin, excess body fat, and the pattern of body fat distribution have inhibitory effects. Menopause is characterized by major changes in blood sex steroid concentrations, notably a marked reduction of estradiol levels. In this study, we therefore investigated the relationship between hormonal and nonhormonal regulatory factors of SHBG and its blood levels in two groups of premenopausal and postmenopausal women characterized by normal-high or reduced estrogen concentrations. The data were obtained from an analysis of the cross-sectional database obtained during the first survey of the Virgilio-Menopause-Health Project, an epidemiologic longitudinal study aimed at investigating the impact of menopause on body weight, fat distribution, and related major metabolic, hormonal, and cardiovascular risk factors. A total of 329 women, 133 in premenopause and 196 in postmenopause without diabetes, thyroid diseases, or relevant cardiovascular, renal, and hepatic dysfunction, were included in the study. A clinical history (including dietary and physical-activity habits), anthropometry (body mass index [BMI], waist to hip ratio [WHR], and bioelectrical impedance analysis [BIA]), and morning blood samples in the fasting state for sex hormones, insulin, and biochemistry were available for all the women. Premenopausal and postmenopausal women showed no significant difference in SHBG concentrations (38.7 +/- 17.9 v 36.6 +/- 17.5 nmol/L, respectively). On the contrary, postmenopausal women were characterized by a marked reduction of estradiol levels and significantly lower levels of testosterone. After adjusting for age, insulin was lower and the glucose to insulin ratio was higher in postmenopause than in premenopause. Age-adjusted values for all anthropometric parameters were not significantly different in the two groups. In simple correlation models, SHBG was significantly and negatively correlated with BMI, WHR, and insulin and testosterone levels in both premenopausal and postmenopausal women, whereas estradiol levels correlated positively and significantly with SHBG only in the premenopausal group. A significant positive correlation between the glucose to insulin ratio and SHBG was present in both groups. Using multiple regression models, in the premenopausal group, SHBG levels were correlated positively with estradiol and negatively with testosterone and insulin, but not with the WHR. On the contrary, in the postmenopausal group, SHBG values had a significant negative correlation with the WHR, whereas the relationship with estradiol was not significant; moreover, the relationship with testosterone and insulin, although significant, became less marked. In conclusion, this study indicates that (1) there is no significant difference in SHBG blood concentrations between premenopause and postmenopause; (2) SHBG values are correlated positively with estradiol and negatively with insulin and testosterone concentrations, but the predictive value of these variabiles on SHBG appears to be different in premenopause and postmenopause; and (3) SHBG levels decrease with increasing WHRs, particularly in the postmenopausal group. Therefore, determinants of SHBG blood concentrations are likely to change on passing from premenopausal to postmenopausal status. In particular, there seems to be a threshold level for which estradiol is an important determinant of SHBG blood concentrations.

Adult↗
PubMed2000

Weight gain and hormone replacement therapy: are women's fears justified?

Fear of weight gain is one of the main factors contributing to the poor compliance seen with hormone replacement therapy (HRT). Although an increase in weight can be a result of rehydration, (which in turn may alleviate some of the effects of skin ageing), many women consider weight gain to be cosmetically unacceptable. Moreover, excess body weight or certain patterns of body fat distribution can lead to health problems such as cardiovascular disease and breast cancer. The menopause is associated with a decrease in the resting metabolic rate that reduces the utilisation of calories and hence increases body weight. A number of studies have shown that weight gain is greatest in the peri-menopausal years. There also appears to be a redistribution of fat mass at the time of the menopause, with an increase in the waist-to-hip ratio. Although it is a common belief that HRT inevitably causes weight gain, available evidence suggests that this is not true. Indeed, some HRT regimens, such as continuous 17beta-oestradiol 2 mg/day combined with sequential dydrogesterone 10 mg/day for 14 days/cycle (Femoston), may actually help to prevent an increase in body fat mass and fat redistribution. Informing women about the effects of the menopause on body weight/fat distribution and the potential beneficial effects of some HRT regimens should help to improve HRT compliance.

Adult↗
PubMed2006

The Wnt code: cnidarians signal the way.

Cnidarians are the simplest metazoans with a nervous system. They are well known for their regeneration capacity, which is based on the restoration of a signalling centre (organizer). Recent work has identified the canonical Wnt pathway in the freshwater polyp Hydra, where it acts in organizer formation and regeneration. Wnt signalling is also essential for cnidarian embryogenesis. In the sea anemone Nematostella vectensis 11 of the 12 known wnt gene subfamilies were identified. Different wnt genes exhibit serial and overlapping expression domains along the oral-aboral axis of the embryo (the 'wnt code'). This is reminiscent of the hox code (cluster) in bilaterian embryogenesis that is, however, absent in cnidarians. It is proposed that the common ancestor of cnidarians and bilaterians invented a set of wnt genes that patterned the ancient main body axis. Major antagonists of Wnt ligands (e.g. Dkk 1/2/4) that were previously known only from chordates, are also present in cnidarians and exhibit a similar conserved function. The unexpectedly high level of genetic complexity of wnt genes evolved in early multi-cellular animals about 650 Myr ago and suggests a radical expansion of the genetic repertoire, concurrent with the evolution of multi-cellularity and the diversification of eumetazoan body plans.

Animals↗
PubMedDate not supplied

Characterization of amphioxus AmphiWnt8: insights into the evolution of patterning of the embryonic dorsoventral axis.

The full-length sequence and developmental expression of an amphioxus Wnt gene (AmphiWnt8) are described. In amphioxus embryos, the expression patterns of AmphiWnt8 suggest patterning roles in the forebrain, in the hindgut, and in the paraxial mesoderm that gives rise to the muscular somites. Phylogenetic analysis indicates that a single Wnt8 subfamily gene in an ancestral chordate duplicated early in vertebrate evolution into a Wnt8 clade and a Wnt8b clade. Coincident with this gene duplication, the functions of the ancestral AmphiWnt8-like gene appear to have been divided between vertebrate Wnt8b (exclusively neurogenic, especially in the forebrain) and vertebrate Wnt8 (miscellaneous, especially in early somitogenesis). Amphioxus AmphiWnt8 and its vertebrate Wnt8 homologs probably play comparable roles in the early dorsoventral patterning of the embryonic body axis.

Amino Acid Sequence↗
PubMed1997

Role of inositol 1,4,5-trisphosphate receptor in ventral signaling in Xenopus embryos.

The inositol 1,4,5-trisphosphate (IP3) receptor is a calcium ion channel involved in the release of free Ca2+ from intracellular stores. For analysis of the role of IP3-induced Ca2+ release (IICR) on patterning of the embryonic body, monoclonal antibodies that inhibit IICR were produced. Injection of these blocking antibodies into the ventral part of early Xenopus embryos induced modest dorsal differentiation. A close correlation between IICR blocking potencies and ectopic dorsal axis induction frequency suggests that an active IP3-Ca2+ signal may participate in the modulation of ventral differentiation.

Activins↗
PubMed2004

Loss of function but no gain of function caused by amino acid substitutions in the hexapeptide of Hoxa1 in vivo.

Homeodomain containing transcription factors of the Hox family play critical roles in patterning the anteroposterior embryonic body axis, as well as in controlling several steps of organogenesis. Several Hox proteins have been shown to cooperate with members of the Pbx family for the recognition and activation of identified target enhancers. Hox proteins contact Pbx via a conserved hexapeptide motif. Previous biochemical studies provided evidence that critical amino acid substitutions in the hexapeptide sequence of Hoxa1 abolish its interaction with Pbx. As a result, these substitutions also abolish Hoxa1 activity on known target enhancers in cellular models, suggesting that Hoxa1 activity relies on its capacity to interact with Pbx. Here, we show that mice with mutations in the Hoxa1 hexapeptide display hindbrain, cranial nerve, and skeletal defects highly reminiscent of those reported for the Hoxa1 loss of function. Since similar hexapeptide mutations in the mouse Hoxb8 and the Drosophila AbdA proteins result in activity modulation and gain of function, our data demonstrate that the functional importance of the hexapeptide in vivo differs according to the Hox proteins.

Amino Acid Substitution↗
PubMed2003

Genetic evaluations of dairy bulls for daughter energy balance profiles using linear type scores and body condition score analyzed using random regression.

The difference in body lipid between the start and end of lactation represents the body energy lost (or gained) in support of maintaining lactation including the nonproduction components of lactation. This source of energy is ignored in current genetic evaluations for production for dairy sires. The depletion and accretion of body tissue creates a pattern of body energy content over time that is, in part, under genetic control. Using random regression and field data, we modeled changes in body condition score (BCS) and liveweight, predicted from linear type traits, on first parity cows to produce daily breeding values of their sires for energy balance. These curves show that sires differ in the way their daughters lose and regain body energy throughout lactation. For all sires, the overall mean maximum daughter body energy loss was 1499 MJ (SD = 144 MJ) and occurred at d 99 (SD = 12.8 d) of lactation and the mean total daughter body energy loss at d 305 of lactation was 779 MJ (SD = 224 MJ). In this study, the profiles of body energy loss indicate that daughters of most sires lost body energy before d 150 and then recovered body energy, whereas the daughters of a few sires continued to lose body energy through to the end of lactation. Some sires with high merit for production may have daughters with body tissue mobilization profiles associated with poorer health and fertility leading to higher costs. A method of accounting for this cost could be to correct yield for body tissue mobilization. Deducting kilograms of milk from the breeding value for milk for each sire, equivalent in energy content to the body energy lost, resulted in a correlation of 0.98 between the ranking of sires for milk kilograms before and after adjustment. However, some sires changed rank bylarge amounts, the largest being +355 positions. Breeding values for energy balance can be calculated from single observations of BCS and linear type traits on daughters of a sire; data that can routinely be collected in national conformation assessment schemes.

Animals↗
PubMed2004

[Gail's coefficient in breast cancer patients with respect to menstrual status, body mass and estrogen receptor pattern of tumor].

Groups at high risk for breast cancer are generally identified using Gail's coefficient (GC) which is calculated on the basis of up-to-date age, recorded menarche, at primapara age, having kinswomen with breast cancer, number of biopsy examinations and morphological evidence of atypical hyperplasia of the breast in case history. We established GC versus estrogen receptor pattern of tumor and body weight in 108 cancer patients. Estimated mean GC values for the next 5 years and survival time did not differ significantly from those in healthy subjects (n=60). They were lower than in the US population which is likely to be due to a number of ethnic, hormonal and screening-related factors. GC tended to grow in RE+ tumor bearers, particularly at reproductive age, and in obese postmenopausal patients. Further study is expected to throw light on the relationships of GC, on the one hand, and certain hormono-metabolic characteristics and clinical course of breast cancer, on the other. This in turn may prove useful in designing therapeutic strategies and, in particular, administration of antisteroid and antimetabolic drugs for prophylaxis in groups at high risk.

Adult↗
PubMedDate not supplied

[Determination of areas of alternating magnetic field action on a patient's body].

The pattern of an induction field (B) is of great importance for physiotherapeutical treatment using an alternating magnetic field (AMF). The outline of the B field is determined by the shape of a device generator. Programmes for calculating the B induction field at any space point for the generator as a current ring and a square current loop are given. To know the spatial pattern of the B magnetic field is inadequate to determine the areas of biophysical AMF action. AMF induces a stress field (ES). The latter with regard to the human body and organs gives rise to a drop field of acting potentials (Ua). The latter is a measure of biophysical action at each local point of a patient's body. The Es field depends solely on the shape of the device generator. The Ua field does on this and the form of the human body and organs. Whether the Ua field can be found is discussed. The author proposes to develop programmes for calculating the Ua fields when the generator and human body are usually aligned. It is concluded that the shapes of the generators to act on each specific organ should be standardized.

Action Potentials↗
PubMed1987

Changes in ventilation and breathing pattern produced by changing body temperature and inspired CO2 concentration in turtles.

Respiratory minute ventilation (VE), breathing pattern, oxygen consumption (VO2) and arterial blood gases and pH were measured in freshwater turtles (Chrysemys picta) at 10, 20 and 30 degrees C while the animals breathed gases of varying CO2 concentration (FICO2 = 0, 2, 4, 6 and 8%). Increasing body temperature produced unequal increases in VE and VO2 such that VE/VO2 decreased. This relative hypoventilation led to a rise in PaCO2 and fall in pHa. Increasing FICO2 at all temperatures greatly elevated VE. The magnitude of this response increased with increasing temperature. Thus, paradoxically, there was an increase in both PaCO2 and CO2 sensitivity with increasing temperature. Increases in VE due to increases in temperature were primarily due to a shortening of the periods of breath holding. Although changes in VT contributed to changes in VE with increasing FICO2, the changes in f, due to shortening the periods of breath holding, contributed twice as much. In relative terms, increasing temperature had no effect on the CO2 response of any respiratory variable. Analysis of the data indicates that all changes which occurred in VE, PaCO2 and pHa with changes in body temperature can be explained by equal Q10 effects of roughly two on both metabolic rate and ventilatory sensitivity to changes in PaCO2.

Animals↗
PubMed2006

Percutaneous vertebroplasty: relationship between vertebral body bone marrow edema pattern on MR images and initial clinical response.

PURPOSE: To prospectively investigate the relationship between initial clinical response and bone marrow edema pattern on preprocedural magnetic resonance (MR) images in vertebral bodies selected for percutaneous vertebroplasty (PVP). MATERIALS AND METHODS: Institutional review board approval and written informed consent were obtained. PVP was performed for osteoporotic compression fractures in 80 consecutive patients (mean age, 72.4 years; range, 44-85 years; 67 women and 14 men; 157 vertebrae). Patients were divided into three groups according to the proportion of the vertebra in which the bone marrow edema pattern was observed on sagittal MR images: group 1, 50% or more of the vertebra; group 2, less than 50%; group 3, no edema pattern observed. By using Wilcoxon rank sum test, Fisher exact test, and Wilcoxon signed rank test, groups were examined for differences in treatment efficacy, which was defined as the difference between preprocedural and postprocedural pain as assessed by means of visual analog scale (VAS) score at 1-3 days after PVP. RESULTS: Forty-four patients were assigned to group 1, 14 to group 2, and 22 to group 3. No significant difference was seen between the groups with respect to age, sex, number of treated vertebrae, or preprocedural VAS score. In group 1, VAS score decreased from 7.5 before the procedure to 2.9 after (improvement of 4.6). In group 2, the score decreased from 6.8 to 3.1 (improvement of 3.7). In group 3, the score decreased from 7.0 to 4.3 (improvement of 2.7). Improvement was significantly greater in group 1 than in group 3 (P < .005). CONCLUSION: PVP resulted in significantly greater clinical improvement in patients with an extensive bone marrow edema pattern than in those without this pattern. (c) RSNA, 2006.

Adult↗
PubMed2002

Another road to making embryonic pattern.

The body plan of a n animal is formed during embryonic development. One mechanism employs gradients of morphogens to direct cells in different parts of the embryo to become different adult structures. But is this the only way of producing tissue patterns? An alternative patterning is suggested by work on social amoebae.

Animals↗
PubMed1999

Patterning mechanisms in the body trunk and the appendages of Drosophila.

During evolution, many animal groups have developed specialised outgrowths of the body wall, limbs or appendages. The type of appendage depends on the identity of the segment where they appear, indicating that the Hox genes contribute to appendage specification. Moreover, work carried out principally in Drosophila has identified the gene products and the mechanisms involved in pattern formation in the appendages. In this essay, we compare the morphogenetic processes in the appendages and the body wall; the function of the Hox genes and the response to the signalling molecules involved in local patterning. We speculate that, although the basic mechanisms are similar, there are significant differences in the manner the body trunk and appendages respond to them.

Animals↗