Corpus callosum shape and neuropsychological deficits in adult males with heavy fetal alcohol exposure.

Persons with brain damage consequent to prenatal alcohol exposure have typically been diagnosed with either fetal alcohol syndrome (FAS) or fetal alcohol effects (FAE), depending on facial features. There is great variability of behavioral deficits within these groups. We sought to combine neuroanatomical measures with neurocognitive and neuromotor measures in criteria of greater sensitivity over the variety of consequences of alcohol exposure. To this end, midline curves of the corpus callosum were carefully digitized in three dimensions from T1-weighted MR scans of 15 adult males diagnosed with FAS, 15 with FAE, and 15 who were unexposed and clinically normal. From 5 h of neuropsychological testing we extracted 260 scores and ratings pertaining to attention, memory, executive function, fine and gross motor performance, and intelligence. Callosal midline shape was analyzed by new morphometric methods, and the relation of shape to behavior by partial least squares. The FAS and FAE subgroups have strikingly more variability of callosal shape than our normal subjects. With the excess shape variation are associated two different profiles of behavioral deficit unrelated to full-scale IQ or to the FAS/FAE distinction within the exposed subgroup. A relatively thick callosum is associated with a pattern of deficit in executive function; one that is relatively thin, with a deficit in motor function. The two combine in a very promising bipolar discrimination of the exposed from the unexposed in this sample. Thus there is considerable information in callosal form for prognosis of neuropsychological deficits in this frequently encountered birth defect.     

Augmented experimental pulse-spray thrombolysis with tissue plasminogen activator, enabling dose reduction by one or more orders of magnitude

PURPOSE: To critically evaluate and optimize methodologic details of pulse-spray thrombolysis with tissue plasminogen activator (tPA) in a subacute rabbit inferior vena cava thrombosis model. MATERIALS AND METHODS: Occlusive inferior vena cava thrombi were produced in 104 rabbits and 2 days later were treated for 1 hour with pulse-spray thrombolysis using tPA. Methodologic variables included pulse frequency, concentration and amount of tPA, infusion versus pulse therapy, and admixture of heparin. After the rabbits were killed, residual thrombus was weighed. RESULTS: The authors' earlier standard regimen (3 mg of tPA in 6 mL of heparinized saline, 0.2-mL hand pulses, frequency 1 pulse per 2 minutes) produced 60% mean lysis. Optimization involved increasing the pulse frequency to two per minute and decreasing tPA concentration by 98% to 0.01 mg/mL, modifications that produced 22% more thrombolysis, despite 92% reduction in amount of tPA to 0.25 mg. CONCLUSION: Consistent with the in vitro work of other investigators, a roughly bell-shaped dose-response curve was elicited in vivo for pulse-spray with tPA. By diluting tPA to an optimal level, and increasing pulse frequency to two per minute, thrombolysis was markedly augmented. These results suggest that the conventional dose of tPA used for clinical pulse-spray thrombolysis can be reduced by one to two orders of magnitude, possibly markedly reducing procedural risk.     

Fetal and infant growth patterns of the mandibular symphysis in modern humans and chimpanzees (Pan troglodytes)

Comparison of the early development of the mandibular symphysis between primates and modern humans is of particular interest in human palaeontology. Using geometric morphometric methods, we explored and compared the ontogenetic shape changes of 14 chimpanzee mandibles (Pan troglodytes) against 66 human CT‐scanned mandibles over the age range from fetal life to the complete emergence of the deciduous dentition in a visualization incorporating the deciduous tooth arrangement. The results reveal that the symphysis is anteriorly inclined in the youngest chimpanzee fetuses but develops an increasingly vertical orientation up until birth. At the same time, the anterior teeth reorient before a vertical emergence, and a symphyseal tuber appears on the labial side. When the deciduous canine emerges, the symphysis inclines anteriorly again, exhibiting the adult characteristic slope. These two phases are characterized by a repositioning of the simian shelf. Unlike chimpanzees, the human symphysis remains vertical throughout fetal development. However, the combination of morphological changes observed in chimpanzee fetuses is similar to that of modern humans after birth, as the mental region projects forward. By elongating the alveolar process, the inclination of the chimpanzee symphysis could be a key event for emergence of the deciduous canine, as space is lacking at the alveolar ridge in a vertical symphysis once the deciduous incisors and molars have emerged. The repositioning of the simian shelf suggests that the suprahyoid muscles have a significant influence on the anterior growth of the symphysis. The anteroposterior positioning of the basal symphysis in both species may be related to hyoid bone position during ontogeny.     

A comparative cephalometric study of the cranial base in craniofacial anomalies: Part I: Tensor analysis

The method of mean tensor analysis was used to study the cranial base in six craniofacial anomalies: Crouzon's disease, Apert's syndrome, Pfeiffer's syndrome, craniofacial microsomia (CFM), Treacher Collins (TC) syndrome, and frontonasal dysplasia (FND). The form was represented by five landmarks: the nasion (N), basion (Ba), sella (S), frontomaxillonasal suture (FMN), and sphenoethmoidal registration point (SE), and the deformities were computed as mean deformations from age- and sex-matched normal mean forms. The cranial base in CFM is normal in shape. The other five syndromes manifest four distinct patterns of shape variation. Only in TC and Pfeiffer's syndrome is the cranial-base angle distinctive. In Apert's and Crouzon's syndromes, point SE is displaced anteriorly upon a cranial base, small in size but otherwise normal in shape. In TC syndrome and FND, point SE is displaced posteriorly toward the sella.     

Efficacy of adjunctive intrathrombic heparin with pulse spray thrombolysis in rabbit inferior vena cava thrombosis.

RATIONALE AND OBJECTIVES. The efficacy and speed of pharmacomechanical thrombolysis may be limited by thrombotic effects of activated platelets and thrombin within the lysing clot. The authors designed an animal model of subacute venous thrombosis which was used to evaluate the effect of intrathrombic versus intravenous heparin during thrombolysis. METHODS. Inferior vena cava (IVC) thrombosis was induced in rabbits by balloon catheter injury and placement of steel coils. Venacavagrams were obtained 48 hours later to document clot formation and for angiographic estimation of clot volume. Pulse-spray thrombolysis was performed by forceful injections of various agents through a catheter with multiple side holes spanning the clot. Most animals were given aspirin (30 mg orally) before treatment. After 1 hour of therapy, repeat venacavography was performed. Animals were killed, and residual clot weight was determined. RESULTS. Occlusive IVC thrombi were present in 94% of rabbits at 2 days. Mean residual clot weight per milliliter of estimated initial clot volume (mg/mL) for the various treatment groups was as follows: saline (n = 5) 632 +/- 54; tissue-type plasminogen activator (t-PA) 3 mg, (n = 6) 443 +/- 162; t-PA 3 mg + heparin 750 U intravenously, (n = 7) 408 +/- 128; t-PA 3 mg + heparin 500 U intrathrombic + heparin 250 U intravenously, (n = 8) 213 +/- 166. Differences among these groups (except t-PA alone versus t-PA + intravenous heparin) were significant. The extent of lysis with intrathrombic + intravenous heparin was not significantly retarded by withholding aspirin (n = 6, 194 +/- 72), or improved by giving half the intrathrombic heparin before t-PA injections (n = 6, 280 +/- 158). CONCLUSIONS. The results demonstrate the advantage of adjunctive intrathrombic + intravenous heparin over intravenous heparin alone in increasing the extent of pulse-spray thrombolysis in this IVC thrombosis model.     

A new statistical method for testing hypotheses of neuropsychological/MRI relationships in schizophrenia: partial least squares analysis.

We applied partial least squares (PLS) as a novel multivariate statistical technique to examine neuropsychological correlates of magnetic resonance imaging (MRI) measures of brain volumes in a well studied sample of 15 male patients with chronic schizophrenia. In the current study, because the total number of measures far surpassed the total number of subjects, extant multivariate techniques such as canonical correlation could not be used to examine relationships among simultaneous measures of MRI and neuropsychology. Moreover, because MRI measures were expected to be highly inter-correlated, as would be neuropsychological test scores, extant multivariate statistical techniques would be substantially limited because they typically assume statistical independence among sets of measures. PLS, on the other hand, proved to be especially well suited to examining the relationships among function and anatomy measures in this sample, where statistically significant relationships were demonstrated that were entirely consistent with prior studies using univariate correlation techniques. In particular, statistically significant relationships emerged among sets of MRI temporal lobe measures and neuropsychological tests of verbal memory and categorization as well as among MRI frontal measures and neuropsychological tests of working memory.     

Landmarks in three dimensions: reconstruction from cephalograms versus direct observation

A method for generating three-dimensional landmark locations from routine biplane pairs of cephalograms was previously introduced. In this article we compare the locations thus reconstructed to the same configurations as directly recorded through a redundant network of interpoint distances measured with calipers. Six mandibular landmarks were located by both methods on each of 10 dry skulls. With the caliper distances is associated a standard error that can be estimated without explicit remeasurement by the method of "adjustment of networks" familiar from surveying. These standard errors are consistent with the remeasurement error both of the caliper measurements and of the stereolocation from cephalograms; the methods appear to have the same precision, about 0.4 mm per distance. The bias (systematic shift) of the biplane reconstructions with respect to the points used for laying down the calipers may be estimated by regressions of distance discrepancies on the direction cosines of the separations between pairs of landmarks. The caliper tips placed condylion approximately 10 mm medially and a bit forward of where we chose to reconstruct it from biplane cephalograms. The caliper locations of gonion average about 1.6 mm back of their cephalometric position, while those at menton and lower incisal edge are forward by some 1.4 mm. We conclude that the biplane reconstruction (the "three-dimensional cephalogram") is sufficiently accurate for routine clinical and surgical application.