Pattern and process of growth of the abnormal human fetus

Identifying patterns of fetal growth alteration benefits both the clinician and the researcher. Twenty-four measurements in three variable sets (anthropometric measures, organ weights, and long-bone measures from radiographs) were taken on fetuses both with and without pathological conditions that are suspected to result in growth alteration. In addition, radiographs of each case were examined for the presence or absence of ossification centers. Based on least-squares regressions of the normal group, we calculated standardized residuals for the affected group to identify patterns of growth alteration. A large sample of fetuses between 15 and 42 weeks of gestational age with a variety of pathological conditions is described and evaluated for growth alterations. Symmetric and asymmetric growth alteration was detected in a small part of the sample and was predominantly isolated to fetuses in the late third trimester. Although patterns of growth alteration have been suggested as a means for noninvasive diagnoses of syndromes (such as trisomy 21), no consistent patterns are discernible in the current group. The sample provides a unique opportunity to evaluate fetal growth in terms of the interaction between genetic and environmental influences.     

Behavioral states in the human fetus

Simultaneous use of real-time ultrasonographic scanning and cardiotocography has demonstrated that the human fetus exhibits well-developed behavioral states from about 36 week's menstrual age onward. Four states have been identified that are very similar to states that have been described in neonates of equivalent age. Prior to 36 weeks, cycles are present in the state variables individually: however, these cycles are not synchronized. The implications of the alternation of behavioral states in the fetus for antepartum assessment of fetal condition are discussed.     

Synchrony in telomere length of the human fetus

We measured serum tumour necrosis factor-alpha (TNF-alpha) as well as interleukin-1betta (IL-1beta) and GH concentrations in 15 children with isolated growth hormone deficiency (GHD), age range 5.1-13.9 years, before and 4 and 24h after the first GH injection (0.1 IU/kg s.c.). No differences were found in basal concentrations of serum TNF-alpha and IL-1beta between GHD children (10.01 +/- 1.55 pg/ml and 2.14 +/- .16 ng/ml respectively) and sex- and age-matched controls (11.57 +/- 2.16 pg/ml and 3.78 +/- 1.46 ng/ml respectively). In GHD children, serum TNF-alpha and IL-1beta values had significantly increased (P < 0.002) 4h (26.75 +/- 5.57 pg/ml and 2.99 +/- 0.21 ng/ml respectively) and decreased again 24 h after GH administration. Likewise, serum GH levels had significantly increased 4 h (from 1.29 +/- 0.69 to 48.71 +/- 13.35 ng/ml, P < 0.001) and decreased to basal values 24h after GH administration. A significant correlation was found between basal serum concentrations of GH and those of both TNF-alpha (P < 0.01) and IL-1beta (P < 0.05). However, no correlation was found between serum GH concentration and either TNF-alpha or IL-1beta levels 4 and 24h after GH administration. Our data suggest that GH plays a role in modulating TNF-alpha and IL-1beta release in humans.     

The renal arterial pedicle in the human fetus

To analyze the incidence of renal arteries variations during the fetal period and compare these findings with previous findings in adults, we studied the renal arterial pedicle in 70 human fetuses ranging in age from 13 to 36 weeks postconception. The fetuses were injected through the right common carotid artery with a red polyester resin to fill in the arterial tree enabling the identification and dissection of the small fetal arteries. The renal arteries were analyzed considering their number, origin, direction and site of penetration. Among the 70 fetuses studied, 30 (42.8%) presented at least one kidney with renal artery variations. In 6 fetuses the variation was bilateral. Among the total of 140 renal pedicles studied, 36 presented arterial variations (25.7%). We did not find statistically significant difference between right and left kidneys and between male and female fetuses. In the present study we did find kidneys with more than 2 arteries, probably because we did not study kidneys with any kind of development anomaly. Even kidneys with malrotations of the vertical axis were removed from the study.     

Platelet mono-amine oxidase activity in the human fetus

Measurement of the platelet mono-amine oxidase (MAO) activity in the human fetus of 40 weeks gestation showed it to be equivalent to that found in the adult. The level represents a fully-developed mitochondrial MAO system in platelets and may reflect enzyme maturity in other tissues of the newborn.     

Intrauterine growth retardation of the fetus and the pregnancy

IUGR (intrauterine growth retardation) is a serious complication of pregnancy. The author compared in the submitted paper different diagnostic and therapeutic possibilities in a six-year retrospective group of 181 hypotrophic foetuses. Based on the results he emphasizes the necessity of magnesiotherapy and prevention of IUGR by acylpyrin. It is impossible to monitor and treat adequately a pregnant woman with a hypotrophic foetus without Doppler sonography. Combination of indexes from various areas (brain, umbilicus) is useful. Even the somewhat obsolete method of assessment of estriol in the urine of pregnant women should not be refuted. Even during the present period of transformation of health services IUGR therapy under ambulatory conditions is not recommended. The author emphasizes the comprehensive character of evaluation of all diagnostic methods for the detection of IUGR.     

Secretion and Sex differences in cord serum growth hormone levels of the human fetus (author's transl)

Cord venous growth hormone (GH) and somatostatin levels were measured by radioimmunoassay in 86 infants and 11 anencephalic infants. 1) Cord GH levels were 69.2 +/- 20.2 ng/ml (N = 6, gestational weeks (GW) : 21-30W, mean +/- S.D.), 31.5 +/- 24.3 ng/ml (N = 11, GW : 31-36W), and 17.6 +/- 8.9 ng/ml (N = 71, GW: 37-41). In anencephalic infants, cord GH levels were significantly lower (2.3 +/- 1.4 ng/ml) than those in preterm and fullterm infants. 2) In fullterm infants, cord GH levels of small infants (19.2 +/- 9.2 ng/ml, N = 33, birth weight less than 3,250g) were significantly higher than that of large infants (15.1 +/- 8.1 ng/ml, N = 38, birth weight greater than of equal too 3,250g). On the other hands, cord somatostatin levels were relatively lower in small infants than in large infants. 3) There was a significant difference between male cord GH levels (20.6 +/- 8.9 ng/ml, N = 35) and female cord GH levels (14.6 +/- 8.0 ng/ml, N = 36). These results suggest that fetal GH secretion is suppressed by GH inhibiting factor (somatotropin release inhibiting factor) from mid gestation toward term and there is a sex difference of fetal GH secretion in fullterm fetus.     

The role of melatonin in the human fetus (review)

Melatonin, an indole amine, primarily derived from the pineal gland is secreted during the hours of darkness. Melatonin acts as a hormonal transduction of photoperiod influencing the timing of seasonal and daily (circadian) physiological rhythms. Maternal melatonin crosses the placenta and enters the fetal circulation providing photoperiodic information to the fetus influencing the subsequent circadian and seasonal rhythms of the offspring. The function of melatonin in humans is more obscure. However, melatonin has attained prominence as a treatment for disturbed circadian rhythms and sleep patterns which occur as a result of transmeridian travel, shift work or blindness. The biological clock, the hypothalamic suprachiasmatic nuclei (SCN), possesses melatonin receptors, in both the adult and fetal human. This concurs with the reported influence of melatonin on human circadian rhythmicity and indicates that this influence may begin in utero. Melatonin receptors are widespread in the human fetus and occur in both central and peripheral tissue from early in fetal development. Thus, the influence of melatonin on the developing human fetus may not be limited to entraining circadian rhythmicity. Considering the transplacental availability of melatonin to the fetus the ingestion of melatonin by pregnant women may be inadvisable.     

Aesthetic facial reconstruction: blending human perception and the facial subunit theory

Facial reconstructive surgical results play a key role in how an individual accepts themselves and how society accepts the individual. Surgeons must strive to create the most aesthetic results, which includes reestablishing the expected contours, highlights, and landmarks. By understanding the subunits theory, plastic surgical nurses can provide patients with knowledgeable preoperative teaching, and can better anticipate the scope and necessary equipment for each reconstruction.     

Dental and craniofacial development in the normal and growth-retarded human fetus

Craniofacial and dental development were examined in 32 human fetuses, 22--42 weeks of gestational age, nine of which were classified as light-for-dates (LFD). Statistically significant differences were detected between the LFD and the normal group with respect to upper and lower jaw size and cranial base length but not in the case of neurocranial length, orbital height or deciduous molar crown size. The structures which are least affected by intrauterine growth retardation are those whose growth rate is normally either low throughout the second half of gestation or falls substantially during the 10 weeks prior to term.     

Tissue distribution of erythropoietin and erythropoietin receptor in the developing human fetus

The purpose of this exploratory study was to describe a group of African American women who smoke crack. Using aggregate data from 208 interviews with women crack smokers, we randomly selected 25 women's interview data to create the 25 life-lines. These life-lines were developed in a similar manner to the time-line analysis described by Fullilove and her colleagues (1992); we focused on events that are either extraordinarily disturbing (e.g., rape, incest, death of a child, etc.), events that are usual but often stressful (e.g., birth of a child, death of a parent, etc.), and on periods of drug use. We chose this method of analysis so as to highlight the context in which many women come to use crack cocaine. The life-lines provided a retrospective (but time-ordered) perspective and in several ways provided preliminary support for a stress-diathesis perspective.     

Cellular localization of insulin-like growth factor II mRNA in the human fetus and the placenta: detection with a digoxigenin-labeled cRNA probe and immunocytochemistry

IGF-II plays a major role in the regulation of human fetal growth and development. However, more extensive information on the cellular sites of IGF-II synthesis in the fetus would provide more insight into its role in fetal organogenesis. Thus we have determined the sites of IGF-II synthesis in 18-26-wk gestation human fetal tissues using in situ hybridization with a digoxigenin-labeled cRNA probe to localize IGF-II mRNA in fetal liver, kidney, adrenal gland, cerebral cortex, costal cartilage, skeletal muscle, and lung, and in placental tissue. In human fetal tissues it has to date been impossible to clearly assign IGF-II mRNA to epithelial cells of entodermal origin. Besides their already known localization in cell matrix and a variety of mesodermal cell types, strong IGF-II mRNA-positive signals were detected in epithelial cells in the liver (hepatocytes), bronchial and bronchiolar epithelium, undifferentiated renal tubular epithelium, mature glomerular epithelium, pelvic urothelium, and adrenal epithelial cells of the zona persistens. To identify the cellular location of immunoreactive IGF-II, we also performed immunocytochemical studies in tissues of the same fetuses. Every tissue studied except the cerebral cortex contained immunoreactive cells; however, immunostaining was generally weaker than in situ hybridization signals. Our data show that the distribution of IGF-II in human fetal tissue is much more widespread than hitherto thought. A digoxigenin-labeled detection system for IGF-II is more capable of detecting the cellular expression pattern of IGF-II than radioactive probes and is suitable for analysis of routinely prepared paraffin-embedded material.     

A quantitative study of nerve fibers in the human facial nerve

The facial and intermediate nerves were quantitatively evaluated in seven patients who died from systemic malignancies not involving the facial nerve. In addition, five of the specimens were also qualitatively evaluated by measuring the total and axon diameters of the facial and intermediate nerve fibers. In two cases the facial nerve fibers were counted at five different levels. The total number of myelinated nerve fibers in the facial nerve varied from 7500 to 9370. The total number of myelinated nerve fibers in the intermediate nerve varied between 3120 and 5360. The peak diameter of the facial nerve axon was between 4 and 6 microns, and was between 2 and 3 microns in the intermediate nerve. When comparing nerve segments at different anatomical levels, the largest amount of nerve fibers was found at the level of the middle mastoid portion. However, this number did not reach the amount of nerve fibers counted in the internal acoustic meatus.     

Development of quinolone-resistant Campylobacter fetus bacteremia in human immunodeficiency virus-infected patients

Campylobacter fetus subspecies fetus has been recognized as a cause of systemic illness in immunocompromised hosts, including relapsing bacteremia in human immunodeficiency virus (HIV)-infected patients. Acquired resistance to quinolone therapy, while reported for a variety of bacteria, including Campylobacter jejuni, has not been previously documented for C. fetus. Two cases of quinolone-resistant C. fetus bacteremia were detected in HIV-infected patients. Cloning and nucleotide sequencing of the C. fetus gyrA gene in the 2 resistant isolates demonstrated a G-to-T change that led to an Asp-to-Tyr amino acid substitution at a critical residue frequently associated with quinolone resistance. In addition, comparison of the pre- and posttreatment isolates from 1 patient documented outer membrane protein changes temporally linked with the development of resistance. Relapsing C. fetus infections in quinolone-treated HIV-infected patients may be associated with the acquisition of resistance to these agents, and this resistance may be multifactorial.     

Morphological study of endothelial cells in the human fetus during early period of gestation

During the formation of blood vessels, proliferation and migration of endothelial cells (ECs) are one of the most important mechanisms. The development of the vessels involves two different mechanisms: vasculogenesis i.e. differentiation of ECs in situ from mesenchymal precursors, and angiogenesis i.e. sprouting of ECs from pre-existing vessels. The frontal lobes from 20 brains of human fetuses ranging from 8 to 17 weeks of gestation (GW) were subjected to correlative light and electron microscopic studies. Our observations demonstrate the sprouting of ECs from pre-existing vessels in leptomeninges (angiogenesis) during the formation of a capillary network of the fetal human brain. In addition, the study did not reveal after the 8th GW the mitotic proliferation of ECs in examined specimens which allows to underline the importance of sprouting and elongation of ECs channels for this phase of vascularization of cerebral hemispheres.     

The vascular relationship between the temporomandibular joint and the middle ear in the human fetus

Mutations in the X-linked gene doublecortin, which encodes a protein with no dear structural homologues, are found in pedigrees in which affected females show "double cortex" syndrome (DC; also known as subcortical band heterotopia or laminar heterotopia) and affected males show X-linked lissencephaly. Mutations in doublecortin also cause sporadic DC in females. To determine the incidence of doublecortin mutations in DC, we investigated a cohort of eight pedigrees and 47 sporadic patients with DC for mutations in the doublecortin open reading frame as assessed by single-stranded conformational polymorphism analysis. Mutations were identified in each of the eight DC pedigrees (100%), and in 18 of the 47 sporadic DC patients (38%). Identified mutations were of two types, protein truncation mutations and single amino acid substitution mutations. However, pedigrees with DC displayed almost exclusively single amino acid substitution mutations, suggesting that patients with these mutations may have less of a reproductive disadvantage versus those patients with protein truncation mutations. Single amino acid substitution mutations were tightly clustered in two regions of the open reading frame, suggesting that these two regions are critical for the function of the Doublecortin protein.     

Distribution of fibroblast growth factor (FGF)-2 and FGF receptor-1 messenger RNA expression and protein presence in the mid-trimester human fetus

Fibroblast growth factors (FGF) are known to have key roles in embryonic growth and morphogenesis, but their presence and contributions to fetal development are unclear. In particular, little information exists as to the relevance of FGF and their specific receptors to human fetal development. We studied the anatomical distribution of messenger RNA encoding FGF-2 and one of its high affinity receptors, FGFR1, using in situ hybridization in a variety of human fetal tissues in early second trimester. Corresponding protein distributions were determined by immunohistochemistry. Both FGF-2 and FGFR1 mRNA and proteins were found to be present in every organ and tissue examined, but with defined cellular localizations. In skeletal muscle, both FGF-2 and FGFR1 mRNA and peptides were present in differentiated fibers, and both co-localized to proliferating chondrocytes of the epiphyseal growth plate. FGF-2 and FGFR1 mRNA and peptides were also present within cardiac or gastrointestinal smooth muscle. Within the gastrointestinal tract FGF-2 mRNA and peptide were located in the submucosal tissue, whereas FGFR1 was expressed within the overlying mucosa. Similarly, in skin, FGF-2 was expressed within the dermis whereas FGFR1 mRNA and peptide were most apparent in the stratum germinativum of the epidermis. In kidney and lung, FGFR1 mRNA was located in the tubular and alveolar epithelia respectively, whereas FGF-2 was expressed in both epithelial and mesenchymal cell populations. Both growth factor and receptor were widespread in both neuroblasts and glioblasts in the cerebral cortex of the brain. Immunoreactivity for FGF-2 and FGFR1 was seen in all vascular endothelial cells of major vessels and capillaries. Within the skin, kidney, lung, and intestine FGF-2 immunoreactivity was found in basement membranes underlying epithelia, and was associated with the extracellular matrix and plasma membranes of many cell types. The results show that FGF-2 and one of its receptors are widely expressed anatomically in the mid-trimester human fetus.