Relationship between cranial mechanics and dysmorphic dentofacial characteristics: a cross-sectional study.

AIMS: The aim of the present study was to evaluate if cranial dysfunctions felt by osteopaths could correlate with sagittal dysmorphologies diagnosed by orthodontists, using cephalometric traces in the sagittal plane. Metholology: One hundred and six children between 6 and 12 years old (42 boys and 64 girls) were tested by an osteopath to determine if the cranial movement felt was considered to be eased in flexion or extension. To test reproducibility intra-operator, 27 randomly selected subjects were tested twice, at a one-month interval by the same osteopath before the start of their orthodontic treatment. These tests were then correlated with a cephalometric analysis of the sagittal plane to determine what type of dysmorphology existed, if any, as well as the angle of the spheno-occipital synchondrosis (SOS). RESULTS: Practitioners systematically found more cranial movement in extension for all the bones in patients in skeletal class II than in the others. Similarly, they systematically found more cranial movement in flexion in patients in skeletal class III than in the other skeletal classes. However, there was no significant difference found in SOS angulation between skeletal classes I, II, and III. DISCUSSION: This study tends to confirm the correlation, described previously by orthodontists, between the mobility of the bones of the cranial vault and dysmorphic dentofacial characteristics in the sagittal plane. Anomalies during development could lead to the typical cranial characteristics of flexion or extension. As such, these situations could be related to skeletal classes III and II respectively.

Histomorphometric and microtomographic evaluation of the effects of hyperbaric oxygen and systemic ozone, used alone and in combination, on calvarial defect healing in rats.

PURPOSE: The aim of this study was to compare the efficacy of hyperbaric oxygen and systemic ozone, used separately and in combination, on the healing of bone defects. MATERIAL AND METHODS: Sixty male Wistar rats were divided into 4 groups (n = 15) according to treatment (control, hyperbaric oxygen [HBO], ozone [O], and HBO plus O [HBO-O]) and divided further into 3 subgroups according to day of sacrifice (postsurgical days 5, 15, and 30). Surgery was performed under general anesthesia to create a critical-size bone defect (5 mm in diameter) in the cranium. After sacrifice, microtomographic images of all samples were recorded, and histomorphometric analysis was performed. RESULTS: Histologic and radiologic measurements showed that the values of all experimental groups were higher than those of the control group. Histologic scores for all experimental groups were statistically higher than those for the control group day 30 (O, P = .045; HBO, P = .049; HBO-O, P = .042). Histologic scores also were statistically higher for the HBO group on day 5 (P = .045) and day 15 (P = .009) compared with the control group. Microtomographic scores were higher for the experimental groups than for the control group, with statistically significant differences for group O on day 5 (P = .033) and day 30 (P = .0045) and for group HBO on day 15 (P = .005). Histologic and radiologic analyses showed positive correlations. CONCLUSION: Within the limitations of this study, the use of hyperbaric oxygen and ozone, separately and in combination, were shown to be effective in increasing bone healing. Combined usage was no more effective in stimulating bone healing than separate usage.

The effects of tissue-non-specific alkaline phosphatase gene therapy on craniosynostosis and craniofacial morphology in the FGFR2C342Y/+ mouse model of Crouzon craniosynostosis.

OBJECTIVES: Craniosynostosis, the premature fusion of cranial bones, has traditionally been described as a disease of increased bone mineralization. However, multiple mouse models of craniosynostosis display craniosynostosis simultaneously with diminished cranial bone volume and/or density. We propose an alternative hypothesis that craniosynostosis results from abnormal tissue mineralization through the downregulation of tissue-non-specific alkaline phosphatase (TNAP) enzyme downstream of activating mutations in FGFRs. MATERIAL AND METHODS: Neonatal Crouzon (FGFRC342Y/+) and wild-type (FGFR+/+) mice were injected with lentivirus to deliver a recombinant form of TNAP. Mice were sacrificed at 4 weeks postnatal. Serum was collected to test for alkaline phosphatase (AP), phosphorus, and calcium levels. Craniofacial bone fusion and morphology were assessed by micro-computed tomography. RESULTS: Injection with the TNAP lentivirus significantly increased serum AP levels (increased serum AP levels are indicative of efficient transduction and production of the recombinant protein), but results were variable and dependent upon viral lot and the litter of mice injected. Morphological analysis revealed craniofacial form differences for inferior surface (p=0.023) and cranial height (p=0.014) regions between TNAP lentivirus-injected and vehicle-injected Crouzon mice. With each unit increase in AP level, the odds of lambdoid suture fusion decreased by 84.2% and these results came close to statistical significance (p=0.068). CONCLUSION: These results suggest that TNAP deficiency may mediate FGFR2-associated craniosynostosis. Future studies should incorporate injection of recombinant TNAP protein, to avoid potential side effects and variable efficacy of lentiviral gene delivery.

Effect of St John's wort on bone formation in the orthopaedically expanded premaxillary suture in rats: a histological study.

BACKGROUND/OBJECTIVE: The aim of this study was to investigate the effect of systemic St John's wort (Hypericum perforatum) on bone formation in the expanded premaxillary suture in rats. MATERIALS/METHODS: A total of 28 rats were randomly divided into four groups of equal numbers: control (C); only expansion (OE); St John's wort extract given only during the expansion and retention period (a total of 17 days; SJW group); and St John's wort extract given during the nursery phase before expansion (a period of 40 days), and during the expansion and retention periods (a total of 57 days; N + SJW group). After the 5 day expansion period was completed, the rats in the OE, SJW, and N + SJW groups underwent 12 days of mechanical retention, following which they were killed, and their premaxilla dissected and fixed. Histological examination was performed to determine the number of osteoclasts and capillaries, as well as the number of osteoblasts, inflammatory cell infiltration, and the amount of new bone formation. RESULTS: Statistical analysis showed that the number of osteoclasts and capillaries, and the inflammatory cell infiltration, as well as new bone formation, were higher in the SJW and N + SJW groups than in the other groups. However, statistical analysis demonstrated that among these two groups, all parameters, with the exception of the number of capillaries, were higher in the N + SJW group than the SJW group. CONCLUSIONS/IMPLICATIONS: Although more effective in long-term usage, systemic use of St John's wort hastens new bone regeneration at the premaxillary suture and may help prevent relapse after expansion.

Multiple Wormian bones and their relation with definite pathological conditions in a case of an adult cranium.

Wormian bones, also known as intrasutural bones, are present as an anatomical variation in healthy individuals. However, a higher than the usual incidence can be an important feature of some congenital pathological conditions. In this study we describe a case of an adult cranium with multiple Wormian bones. The cranium was a single sample obtained from an archaeological excavation in Vinitsa, Northeastern Bulgaria, and probably dated in the Chalcolithic. The Chalcolithic is a period of human history connected with discovering and using of copper. Actually, it is a transitional phase between the Neolithic and the Bronze Age. In this case the Wormian bones are mostly large in size and arranged in a mosaic pattern in several cranial regions. The cranium also shows features such as dolichocrany, a moderate platybasia, a notch in the posterior margin of the foramen magnum, hypoplastic and asymmetrical frontal sinuses, underdeveloped mastoid air cells, hyperostosis cranii interna, moderate frontal bossing, a complete metopic suture, a delayed sutural closure, relatively small facial bones, an early loss of teeth, dental caries and hypoplastic enamel defects on two preserved molars. Differential diagnosis indicates that the combination of all these features shows a link with pathological conditions involving dysplasias with prominent membranous bone involvement and an increased bone density such as cleidocranial dysplasia and pyknodysostosis.

Effect of excessive methionine on the development of the cranial growth plate in newborn rats.

OBJECTIVE: Methionine is an essential amino acid and pivotal for normal growth and development. However, previous animal studies have shown that excessive maternal intake of methionine causes growth restrictions, organ damages, and abnormal growth of the mandible in newborn animals. However, the effect of excessive methionine on the development of the cranial growth plate is unknown. This study investigated histological alterations of the cranial growth plate induced by high methionine administration in newborn rats. DESIGN: Twenty pregnant dams were divided into a control and an experimental group. The controls received a diet for rats and the experimental group was fed from the 18th gestational day with a special manufactured high methionine diet for rats. The high methionine diet was maintained until the end of the lactation phase (day 20). The offspring of both groups were killed at day 10 or 20 postnatally and their spheno-occipital synchondroses were collected for histological analysis. RESULTS: The weight of the high-dose methionine treated experimental group was considerably reduced in comparison to the control group at day 10 and 20 postnatally. The cartilaginous area of the growth plate and the height of the proliferative zone were markedly reduced at postnatal day 10 in the experimental group. CONCLUSIONS: In summary, the diet-induced hypermethioninemia in rat dams resulted in growth retardations and histomorphological changes of the spheno-occipital synchondrosis, an important craniofacial growth centre in newborns. This finding may elucidate facial dysmorphoses reported in patients suffering from hypermethioninemia.

[Neurological paleopathology in the pre-Columbian cultures of the coast and the Andean plateau (I). Artificial cranial deformation]. / Paleopatologia neurologica en las culturas precolombinas de la costa y altiplano andino (I). Deformaciones craneales intencionales.

AIMS: The aim of this work was to study the cranial trepanations and deformations carried out by the ancient Paraca, Huari, Tiahuanaco and Inca cultures. To do so, we conducted a field study involving visits to archaeological remains and anthropological museums on the Andean plateau and the Peruvian coast. DEVELOPMENT: Cranial deformation was more common in the Andean regions and was performed by putting little pieces of wood or compressive bandages on newborn infants' heads in order to modify the growth axis of the cranial cavity. Cranial deformations were performed for aesthetic and magic religious reasons, but were also used as a means of ethnic or social identification, as a symbol of nobility or to distinguish the ruling classes. The immediate consequence of such deformation was the modification of the normal process by which the cranial sutures close. There is a significant correlation between the presence of posterior and lateral wormian bones, according to the degree of artificial deformation. The persistence of metopic suture and exostosis of the outer ear canal have been found in 5% of the skulls belonging to pre Columbine mummies. Other paleopathological findings include cranial fractures (7%), porotic hyperostosis (25% of children's skulls), spina bifida occulta, signs of spinal disk arthrosis and Pott's disease. CONCLUSIONS: Artificial cranial deformation was a very widespread practice in the Andean regions in pre Columbine times.

Identification of IGF-I in the calvarial suture of young rats: histochemical analysis of the cranial sagittal sutures in a hyperthyroid rat model.

Premature closure of cranial sutures has been known as one of the complications of juvenile or congenital hyperthyroidism. Thyroid hormone is an anabolic agent for bone formation in the early stages of childhood development. In children, excess thyroid hormone acts as an acceleration factor for the skeletal bone, whereas in adult hyperthyroidism, it causes bone mineral loss due to the high turnover rate of bone formation and consequently bone resorption. In addition, there are numerous literature descriptions concerning the interactions among bone metabolism, hormones, and growth factors, among which insulin-like growth factor I (IGF-I) is the most abundantly found growth factor in osteoblasts and in bone models in vivo. We therefore investigated whether or not the cranial sutures show accelerated closure and how the local growth factors or cytokines participate and function in local bone metabolism after administration of exogenous excess thyroid hormone in a rat model. A total of 60 female Wistar rats, aged 10 days, were divided into two groups, the triiodothyronine (T3)-treated group (n = 30, T3 0.1 microgram/gm of body weight per day) and the control group (n = 30, saline vehicle only), and were maintained and subsequently sacrificed at 15, 30, and 60 days. The parameters of cranial width derived from the morphologic measurements of the skull indicated that the lambda-asterion distance at 30 days and the pterion-bregma distance at 60 days in the T3-treated group were significantly decreased compared with those of the control group. Furthermore, the fluorescent histologic findings showed fluorescent labeling with no interruption along the suture edges, suggesting continuous bone formation, and displayed narrowing of the suture gap of the sagittal suture in the T3-treated group. Tartrate resistant acid phosphatase staining showed very little osteoclastic activity in the sagittal suture, especially in the T3-treated group. The intensity of immunohistochemical staining of IGF-I was markedly increased in the suture margins of the T3-treated group. There were no significant differences observed either in the skull base measurements or in the histologic and histochemical findings of the skull base or the coronal suture between the groups. More significantly, excess administration of thyroid hormone enhanced the cranial sagittal suture closure; therefore, it was proposed that local IGF-I plays an important role in sagittal sutural bone formation.

Acute toxicity of vitamin A given with vaccines in infancy.

A double-blind, randomised, placebo-controlled trial was conducted to evaluate the safety and toxicity of vitamin A supplementation within the Expanded Programme on Immunisation (EPI) in rural Bangladesh. 191 infants received 3 doses of either 50,000 IU of vitamin A or placebo at about 1.5, 2.5, and 3.5 months and were examined on days 1, 2, 3, and 8 after supplementation. 11 infants (11.5%) supplemented with vitamin A had episodes of bulging of the fontanelle as opposed to 1 (1%) in the placebo group. 16 of the 17 events occurred in the vitamin A supplemented group. No other side effects were noted. There was a tendency towards a cumulative effect of toxicity with increasing doses.

PIP: The International Center for Diarrhoeal Disease Research, Bangladesh, conducted a double-blind, randomized, placebo-controlled trial in the Matlab to examine the possibility of side effects in 191 infants who received 3 doses of either 50,000 IU vitamin A or a placebo at 1.5, 2.5, and 3.5 months within the Expanded Program of Immunization. Physicians examined the infants on the day of supplementation on days 1,3 and 8 after supplementation. The fontanelles bulged in 12 infants. The incidence of fontanelle bulging was more common in the vitamin A group than in the placebo group (11.5 vs. and 1%). There were 17 fontanelle bulging episodes, 16 taking place after vitamin A supplementation (5.5 vs. 0.3% after placebo supplementation). 8 (50%) of the vitamin A induced bulged fontanelle episodes occurred after the 3rd dose. 3 infants had fontanelle bulging episodes after the 2nd and 3rd doses. 2 other infants had these episodes after the 1st and 3rd doses. The bulging episodes persisted for 24-48 hours in all but 2 cases (48-72 hours) and returned to normal without treatment. No infant with a bulging fontanelle died. No other side effects occurred. The increased incidence of bulging fontanelles among infants receiving vitamin A supplementation and the fact that almost all episodes occurred after vitamin A supplementation suggested that vitamin A supplementation caused the bulging fontanelles. Increased intracranial pressure caused by vitamin A toxicity was responsible for the bulging fontanelles.