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The growth and development of the squirrel monkey (Saimiri Sciureus).

Squirrel monkeys of 2 subspecies, Bolivian and Colombian, were removed from their mothers on the day of birth and nursery reared for up to 2 years of age. Infants were tested weekly for 12 weeks, then monthly for 1 year, and at 2 years of age. Tests included morphology (body weight, crown-rump length, and head measurements), behavior (reflexes, activity, reaction to the surrogate), and physiology (heart rate, respiratory rate, temperature and optokinetic nystagmus). Data show some likenesses and some differences between the 2 subspecies.

Animals↗

Cardiovascular malformations in spontaneously aborted human fetuses.

Among 57 spontaneously aborted fetuses with a crown-rump length (CRL) ranging from 30 to 180 mm, 5 were found to have cardiovascular malformations. The number of cases with cardiovascular malformations (numerator) and the number of observed fetuses (denominator) classified according to their CRL were as follows: CRL 30-49 mm, 1/9 (persistent left superior vena cava); 50-69 mm, 4/11 (one case each of membranous VSD with aberrant right subclavian artery, high muscular VSD, pulmonary stenosis with muscular VSD and overriding aorta, right aortic arch with membranous VSD); 70-99 mm, 0/7; 100-139 mm, 0/16; 140-180 mm, 0/14. The above results clearly show a high prevalence of cardiovascular malformations in spontaneously aborted fetuses with a CRL of less than 70 mm. The practicability and potential value of microdissection of small fetuses are stressed.

Female↗

Histochemical investigations on the symphysis menti in the human fetus related to fetal skeletal maturation in the hand and foot.

Histochemical investigations on the symphysis menti region were performed on 72 human embryos and fetuses of crown-rump lengths (CRL) ranging from 16 to 162 mm, presenting skeletal maturity indices (CNO = composite number of ossified bones in the hand and foot) ranging from 0-0 to 19-11. The symphysis menti region is described in five developmental stages according to morphology and histochemical reactions at the interzone, enchondral bone formation, and Meckel's cartilage. The stages are described according to histochemical reactions for glycosaminoglucuronoglycans, collagen, glycogen, alkaline and acid phosphatase, and non-specific AS esterase. Silver impregnation followed by X-ray and histochemical control for Ca++ deposits supplemented the study. Special attention was paid to a fusion of the bilateral Meckel's cartilages in the midline characteristic of stage II. This is a finding not previously recorded in human fetuses. It is suggested to designate this fusion 'the rostral connection'. Histochemically, the fusion appeared as ordinary cartilage matrix (chondroitin-4- and/or-6-sulphate). The absence of a rostral connection characteristic of stage III is discussed. On the basis of reactions for glycosaminoglycans and activity of hydrolytic enzymes, the symphysis is characterized as a growth zone, active in mandibular growth in width as well as in length, during the first half of the prenatal period. The material available did not justify a description of skeletal development in the symphysis menti as a function of CRL, of skeletal maturation in the hand and foot, or as a function of a combination of these parameters.

Acid Phosphatase↗

The fine structure of haemopoiesis in the human fetal liver. II. Origin and differentiation of the megakaryocyte.

The differentiation of the megakaryocyte was studied at the ultrastructural level in the liver of human fetuses of between 49 and 134 mm crown-rump length. The development of the cells was traced from lymphoid elements with the features of haemopoietic stem cells and was divided on the basis of nuclear morphology into three stages. Granule formation commenced during the first stage and demarcation membrances could be demonstrated in the perinuclear cytoplasm early in the second stage. Late stage 2 cells often contained more than one nucleus, and the possibility that this was due to cellular fusion is discussed. The third stage was characterized by the appearance of cytoplasmic zoning and by the gradual extension of the demarcation system throughout the cytoplasm. There was evidence that the demarcation membrances were initially formed directly from the Golgi apparatus, but that their further development was due to the incorporation of elements of the agranular endoplasmic reticulum. The surface projections associated with platelet release were observed only in fully developed cells, and the formation of a zone of clear cytoplasm at the periphery was related to events occurring during the later stages of platelet release.

Blood Platelets↗

[Effects of 9-fluoro-11 beta, 21-dihydroxy-16 ampha-methylpregna-1, 4-diene-3, 20-dione (A41 304) and dexamethasone on the fetus of mice and rats].

A41 304 at 400 mug/kg produced depression of body weight gains in the rat dams but did not increase the number of the fetuses with gross malformations. At 400 mug/kg of dexamethasone, body weight gains of the rat dams were markedly depressed and fetuses presented cleft palate and depression of the placental weight, body weight and crown-rump length. As for the influence of both drugs upon the fetal skeleton, ossification of the odontoid process and metatarsus was delayed and lumbar ribs increased. Dexamethasone at 400 mug/kg, in addition to these findings, caused prominently delayed ossification to the caudal vertebrae. When A41 304 at 1600 mug/kg and dexamethasone at 400 mug/kg were given to pregnant mice, cleft palate occurred with high incidences, but neither visceral abnormalities nor skeletal malformations attributable to the drug administration were observed. The critical period of cleft palate which was noted in the mice given A41 304 was day 11 through day 15 of pregnancy, mainly 11 approximately 13 of pregnancy. Cleft palate was seen in a dose-related manner in either A41 304-treated groups or dexamethasone-treated groups, but the incidence at the same dosage level was higher in dexamethasome-treated groups than in A41 304-treated groups.

Abnormalities, Drug-Induced↗

Histological development of stapes footplate in human embryos.

Normal development of the human stapes footplate was investigated in serial sections by light microscopy. Materials were obtained from 35 Japanese embryos from the 6th to 32nd week of embryonal age. Eighteen embryos up to 16 weeks of age (3.5mm to 105mm in crown-rump length) were examined, focusing particularly on the lamina stapedialis of the otic capsule. The present study showed that primordial formation of the lamina stapedialis appeared in 16mm embryo and that the lamina was completely formed and fused to the base of the annular stapes in a 35mm embryo. In a 50mm embryo, the adult form of stapes was found with a rim and annular ligament. The results, therefore, seemed to essentially agree with the theory of dual origin and development of the footplate proposed by Cauldwell and Anson, and teratogenic agents might affect any stage of the process producing anomalies, including congenital footplate fixation, congenital absence of the oval window and calcification of the annular ligament.

Ear Ossicles↗

Peptidergic (VIP) innervation of the esophagus.

Nerves displaying vasoactive intestinal polypeptide (VIP) immunoreactivity were demonstrated in the esophagus of rats, cats, and pigs. Furthermore, electron microscopy revealed the presence of nerve terminals displaying the features of peptidergic nerves. VIP nerves were abundant within the smooth muscle layer of the lower esophagus of cat and pig. Immunoreactive nerve fibers and nerve cell bodies were found in the plexuses of the esophageal wall. In pig fetuses VIP immunoreactive nerve cell bodies were observed already at crown-rump length of 4 cm. VIP nerves were also observed in human fetal esophagus. For recording of the motor effects of VIP, segments were taken from cat esophagus close to the esophagogastric junction. VIP induced a dose-dependent relaxation upon contraction by carbamylcholine.

Animals↗

Changes in axonal numbers in developing human trochlear nerve.

Complete axonal counts have been made in the intracranial parts of trochlear nerves from human fetuses of 9.2, 10 and 24 cm crown-rump length. A count was also made in the intraorbital part of the nerve from the 10 cm specimen. Schwann cell nuclei were also counted in typical cross sections, but do not necessarily reflect very accurately the schwann cell contents of the nerves. Axonal numbers conform to the propositions (1) that they do not all grow out at once, (2) do not all survive and (3) that degeneration may occur before or after myelination has begun. It seems inevitable that some loss of Schwann cells occurs in relation to the degeneration of myelinated axons, but there is no evidence for or against such a loss in relation to the degeneration of unmyelinated axons. Overall, however, Schwann cell numbers tend to increase as the number of myelinated axons increases.

Axons↗

Muscular development of the bladder neck in the human fetus.

We conducted a histologic study of the muscular development of the bladder neck in human fetuses of 5 to 23 cm crown-rump length (CRL) and in neonates in special reference to the middle circular layer of the posterior wall of the bladder neck (posterior circular muscle of the bladder neck) and the deep trigonal muscle. Our attempt was to determine the anatomic relationship between and the origins of the two musculatures. The posterior circular muscle had begun to differentiate in the fetus of 8.3 cm CRL in which the trigonal musculature was indistinguishable. Differentiation of the deep trigonal musculature was evident in the fetus of 17 cm CRL; a complete growth in which the muscle was connected to the posterior circular muscle of the bladder neck was evident only in the largest fetus (23 cm CRL). We conclude that the deep trigonal muscle and the posterior circular muscle of the bladder neck are of different origins.

Gestational Age↗

Palatal shelf elevation in the Wistar rat fetus.

Palatogenesis in the Wistar rat fetus was studied macroscopically, microscopically, ultrastructurally and experimentally between days 13 and 19. The developmental ages of the fetuses were calculated from the smear age of the litter adjusted for individual variations in crown-rump lengths. Palatal shelf elevation occurs at day 16.4 +/- 0.1. Experimentally induced shelf elevation in freshly delivered fetuses was sluggish at day 14, but by day 16.3 it occurred in less than 1 second. Both shelf elevation and shelf fusion begin anteriorly where the shelves show a marked convexity of their margins, and proceed posteriorly. The extreme posterior part of each shelf (future soft palate) is horizontal from the beginning. The matrix of the shelf mesenchyme (especially in the region of the anterior convexities) shows an increasing accumulation of mucopolysaccharides from day 14 to day 16.3 and becomes increasingly oedematous. The shelf attachment to the main maxillary process is progressively undercut by epithelial invagination, producing a fulcrum for shelf elevation. The maxillary and palatine osteogenic blastemata are present at the base of the shelf prior to elevation and rapidly invade the shelves after the event. The elevated palatal shelves fuse with the nasal septum anteriorly, but posteriorly the palate is not attached to the septum. The posterior septum at first has a free lower edge, but then it develops lateral flanges which fuse with corresponding bulges on the lateral nasal walls. In this way two sphenoethmoidal recesses are formed above the fused flanges, while a common nasal passage is formed above the palate, roofed anteriorly by the septal flanges and posteriorly by the cranial base. The space needed to create (simultaneous with shelf elevation) the common nasal passage is made available by flattening of the tongue and protrusion of its tip out of the oral cavity--this protrusion being facilitated by the sloping bulge of the primary palate and nasal septum. Many existing theories of shelf elevation are inconsistent with these observations. It was concluded that shelf elevation occurs very rapidly at a rather precise developmental stage and that turgor (due to binding of water to mucopolysaccharides) is the intrinsic force which elevates the shelves, a force which at 16.4 days reaches a threshold level enabling the shelves to force their way up and over the intervening tongue.

Animals↗

Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.

The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).

Ammonia↗

[The effect of glucocorticosteroids on sex differentiation in rats].

The influence of two glucocorticoids (hydrocortisone and dexamethasone) on the somatic sex differentiation of female rats was investigated. During the time of sexual differentiation of their foetuses, pregnant rats were given dexamethasone (0.1-0.3 mg/day) or hydrocortisone (20-200 mg). Both compounds interfere with foetal development by virtue of their strong growth-inhibitory activity which manifests itself in reduction of the body weight, the crown-rump length, the length of the genital folds and the genital cord. The inhibition of growth seems to be reversible. Only hydrocortisone acts teratogenically as it causes a shift of the differentiation of the female genital tract into male direction. This virilisation consists of partial stabilisation of the Wolffian ducts, the suppression of mammary nipple development and a male-type differentiation of the urogenital sinus. The relevance of these findings for human beings is briefly discussed.

Animals↗

Experimental amniocentesis and teratogenesis. 1. Evaluation of the intra-amniotic route of treatment in teratological studies.

Experiments were designed to evaluate the usefulness of the intra-amniotic route of administration of test-substances in teratological studies. Particular attention was given to the differences in fetal parameters of growth and development and the incidence of fetal mortality between treated and untreated offspring which might be induced as a result of the treatment. Amniocentesis on gestational days 14, 15 or 16 produced a high incidence of fetal mortality and a significant reduction in the weights and crown-rump lengths of treated offspring. With increasing gestational age at the time of treatment and by reducing the volume of solvent injected, fetal mortality was decreased.

Amnion↗

Electron microscopy of the early embryonic development of the human corneal epithelium.

The eyes of a human embryo in the 6th week, 11 mm crown-rump (C.R.) length, and of a human embryo in the 7th week, 19 mm C.R. length, were examined. In the embryo of 11 mm C.R. length, the lens vesicle had just detached from the surface ectoderm, the presumptive corneal epithelium. The acellular primary corneal stroma appeared between the lens vesicle and the overlying ectoderm. The fine structure of the ectodermal cells, of their basal lamina, and of the primary stroma is described. In the embryo of 19 mm C.R. length, mesenchymal cells had moved from the periphery into the space between the ectoderm and the lens. There were remarkable changes in the structure of the corneal epithelial cells, in their basal lamina, and in the underlying substances of the primary stroma.

Cornea↗

Estimating the age of the human foetus from crown-rump measurements.

When data from various sources were compared, it was found that estimates of foetal age based upon crown-rump measurements varied considerably. These variations are probably related to the positions in which the foetuses were measured. Tables relating foetal age to foetal length should therefore specify the precise posture in which the foetus was placed for measurement. A standard readily reproducible position is proposed for the foetus when recording its length and it is suggested that crown-rump length should be related to "conceptual" age instead of the more conventional "menstrual" age.

Anthropometry↗

Early intrauterine development: I. The rate of growth of Caucasian embryos and fetuses between the 6th and 20th weeks of gestation.

Liberalization of abortion laws in various countries and states of Europe and America has offered an opportunity for the study of the correlations between menstrual age and the rate of bodily development of human embryos and fetuses. In several institutions where local bylaws mandated the consent of the patients requesting therapeutic abortion to pathological investigation of the products of conception, various parameters of growth were measured systematically. These included crown-rump and foot lengths and body weight. The analysis of the data indicated that in the embryosic stages of development the rate of growth is substantially slower than it had been assumed previously. In the more advanced fetal stages of development the findings supported the validity of the long-established standard of Streeter. Since the current study has been based on apparently normal gestations of healthy women, whereas earlier data had rested, to a great extent, on spontaneously aborted and extopic embryon and fetuses, it seems evident that pathological specimens are not suitable for the purpose of establishing reliable standards of normal intrauterine growth rate. The present data support the suggestion, based on various experimental and clinical observations, that pathological gestations often result from abnormal ovulations that occur at times other than the mid-cycle and that such conceptions are frequently followed by a bleeding episode that simulates menstruation. It is likely that the inclusion of a high number of such cases biased the results of earlier investigations concerning embryonic growth rate on account of the frequent incidence of erroneous menstrual histories. The material available did not permit the extension of the investigation beyond the 20th week of gestation. It appears, however, that the average growth rate in the mid-trimester may be slower than the data adopted by the American Academy of Pediatrics would indicate. The possible causes of some phenomena observed in the course of the investigation, such as unexplained scatter of growth-rate patterns at all developmental stages and discrepancies among various literary data, have been discussed in some detail. While a tentative attempt has been made to correlate the investigated parameters of fetal growth with biparietal diameters of the head, a measurement accessible to direct assessment by sonography during pregnancy, the necessity of improving these standards through a prospective study has been emphasized.

Abortion, Therapeutic↗

Development of the omasum in sheep.

Data are presented on the histogenesis of the omasal mucosa in sheep from the 2.5 cm crown-rump (c-r) length fetus to the adult. 11 stages of fetal development, and 4 post-natal stages, were studies. The distribution of glycogen in the omasal epithelium was also studied. During fetal life the omasal epithelium was initially stratified cuboidal in type, but the superficial layers of cells became flattened in later stages of gestation. This epithelium became extremely thick by the late stages of fetal life, reaching a maximum of 358 micron, and consisting of greater than 20 layers of cells, in the 45 cm c-r fetus (approximatelay 140 days). After birth the epithelium became markedly reduced in thickness, being approximately 77 micron in the adult, and had differentiated into a cornified stratified squamous epithelium of the adult type by 12 weeks after birth. Glycogen was extremely abundant in the omasal epithelium of the 2.5 cm fetus, and declined gradually thereafter to be almost completely absent in post-natal specimens. 4 orders of laminae were present in the adult omasum, distributed in the seqeunce 1-4-3-4-2-4-3-4-1. The 1st order was already present in fetuses of 2.5 cm c-r length, with the 2nd, 3rd and 4th appearing by the 3.5, 5.5 and 11.0 cm stages, respectively. Initial stages in the development of conical papillae were first seen in 15.0 cm fetuses, but the development of these papillae was not completed until after birth.

Age Factors↗

Foot length--a new and potentially useful measurement in the neonate.

The foot length, occipito-frontal head circumference (OFC), crown-rump, and crown-heel length (CHL) of 123 neonates of gestational ages 26-42 weeks, were measured between 12 hours and 5 days. A gauge, designed and constructed at St Mary's Hospital, Manchester, was used to measure foot length. In term babies (37-42 weeks) who were of weights appropriate for gestational age (AGA) the scatter about the mean of foot length measurements was small (coefficient of variation = 4.5%) compared with birthweight (coefficient of variation = 12.0%). The wide range of foot length measurements in babies of different gestational ages prevented maturity being accurately estimated. The mean birthweight of term light-for-dates (LFD) babies was 30.9% lower than term AGA babies, whereas the mean foot length, OFC, and body length of LFD babies was reduced by only 4.2-8.8%. There was a positive linear correlation between foot length and other indices of body size in LFD and AGA babies of all gestational ages. However, in premature babies (less than 37 weeks) the correlation between foot length and birthweight (r = 0.95) and foot length and CHL (r = 0.96) was pronounced. The 95% confidence limits of the regression lines were +/- 327 g and +/- 2.3 cm respectively. Birthweight and CHL of premature babies can therefore be estimated from a measurement of foot length that is performed simply and rapidly. Measurements of foot length are valuable in premature babies who are too ill at birth for conventional anthropometric measurements to be made, and in whom such measurements cannot be carried out subsequently because of the encumbrance of the incubator and intensive care apparatus. Drug dosages and intravenous fluid requirements based on body weight or surface area can be indirectly calculated from a measurement of foot length.

Anthropometry↗