Possible effect of gestational age on the detection of fetal nucleated erythrocytes in maternal blood.

Maternal venous blood samples, obtained from six pregnant women, were used as a source of fetal nucleated erythrocytes (NRBC). Fetal cell enrichment was potentiated by flow sorting with the monoclonal antibodies TfR, Leu-4, and Leu-M3. Single copy Y chromosomal DNA sequences were detected in samples obtained from two women at 11 and 12 weeks' gestation. Y DNA sequences were absent in a subsequent sample from one of these women at 19 weeks and in two other women at 16 and 20 weeks. All four women delivered males. Y DNA sequences were not detected in two women who delivered females. By combining these results with prior data on the detection of Y chromosomal DNA sequences in maternal blood from male-bearing pregnancies, a relationship between gestational age and feto-maternal transfer of NRBC is suggested.     

Identification during the postpartum period of infants who are at high risk of child maltreatment

To determine whether clinicians correctly identify newborn infants who are at high risk of child maltreatment, we examined the outcomes of high-risk and non-high-risk children. Infants who were born at Yale-New Haven Hospital from 1979 to 1981 and who were referred by clinicians during the postpartum period to the hospital's child abuse registry because they were considered at high risk of child abuse or neglect became the high-risk group. For each high-risk infant, a comparison infant was selected and matched according to date of birth, gender, race, and method of payment for the hospitalization. For both groups, the occurrence of maltreatment was ascertained by reviewing the medical records until the child's fourth birthday. Each injury for which medical care was sought was classified into one of seven categories (from definite child abuse to accident) by a pediatrician who was unaware of the child's risk status. Information also was recorded about nonorganic failure to thrive and changes in the child's caretaker. Maltreatment (defined as abuse or neglect) occurred more frequently in the high-risk group than the comparison group (adjusted matched odds ratio = 4.3; 95% confidence interval = 1.41, 6.93; p less than 0.001), as did poor weight gain from a nonorganic cause (matched odds ratio = 7.0; 95% confidence interval = 1.59, 30.79; p less than 0.01) and changes in the child's caretaker (matched odds ratio = 9.0; 95% confidence interval = 3.80; 20.55; p less than 0.001). We conclude that as early as the postpartum period, clinicians can identify some families who are at high risk of maltreatment and other major adverse outcomes resulting from poor parenting.     

Magnetic resonance angiography findings in the early post-carotid endarterectomy period

This preliminary study was designed to investigate the ability of multiple axial volume three-dimensional fourier transform (3DFT) time-of-flight (TOF) magnetic resonance angiography (MRA) to depict the carotid bifurcation in the early post-carotid endarterectomy period. Five patients underwent intra-operative digital subtraction angiography (DSA) and carotid MRA within 5 days of carotid endarterectomy. An axial volume fast imaging in steady-state precession (FISP) gradient-echo 3DFT TOF carotid MRA technique in this limited series appeared to display accurately the surgically significant abnormalities at the carotid bifurcation after endarterectomy. However, in normal or near-normal intra-operative DSA studies, overestimation of internal carotid artery stenoses was encountered. Postoperative MRA demonstrates potential as a useful non-invasive investigation after carotid endarterectomy but should be interpreted with caution until larger studies become available.     

Mineral deficiency and the use of the FETAX bioassay to study environmental teratogens

The Frog Embryo Teratogenesis Assay: Xenopus (FETAX) bioassay has been employed extensively to screen compounds for teratogenic activity. Recent laboratory studies have indicated that low potassium concentrations retard Xenopus laevis development. The effects of varying concentrations of minerals on Xenopus laevis embryo length and development were examined to determine the utility of the FETAX bioassay in the study of environmental teratogens. Water samples collected from 18 wetlands in Minnesota and North Dakota correlated with low mineral levels, causing delayed embryonic development in the FETAX bioassay. When the concentration of sodium or potassium was <5 ppm, Xenopus laevis development was delayed. As a result, it was difficult to assess teratogenic activity after 96 h of incubation. Furthermore, the length of the embryos-an indication of development-paralleled changes in mineral composition. Comparisons between different wetlands based on changes in one specific mineral were not possible due to a synergism between various minerals. If the concentration of sodium and/or potassium was <5 ppm but > or =2 ppm, extension of the FETAX bioassay to 120 h allowed organogenesis to proceed through stage 46, as required for scoring in accordance with ASTM guidelines for the FETAX bioassay. In those cases in which the concentration of sodium and/or potassium were <2 ppm, the embryos could not develop to stage 46 within 120 h and the FETAX bioassay was not suitable for detecting teratogenic activity. Published in 2002 by John Wiley & Sons, Ltd.     

Long-acting forms of Sonic hedgehog with improved pharmacokinetic and pharmacodynamic properties are efficacious in a nerve injury model

The therapeutic effects of the Sonic hedgehog (Shh) have been difficult to evaluate because of its relatively short serum half-life. To address this issue polyethylene glycol modification (PEGylation) was investigated as an approach to improve systemic exposure. Shh was PEGylated by a targeted approach using cysteines that were engineered into the protein by site-directed mutagenesis as the sites of attachment. Sixteen different versions of the protein containing one, two, three, or four sites of attachment were characterized. Two forms were selected for extensive testing in animals, Shh A192C, which provided a single site for PEGylation, and Shh A192C/N91C, which provided two sites. The PEGylated proteins were evaluated for reaction specificity by SDS-PAGE and peptide mapping, in vitro potency, pharmacokinetic and pharmacodynamic properties, and efficacy in a sciatic nerve injury model. Targeted PEGylation was highly selective for the engineered cysteines and had no deleterious effect on Shh function in vitro. Systemic clearance values in rats decreased from 117.4 mL/h/kg for unmodified Shh to 29.4 mL/h/kg for mono-PEGylated Shh A192C that was modified with 20 kDa PEG-maleimide and to 2.5 mL/h/kg for di-PEGylated Shh A192C/N91C modified with 2, 20 kDa PEG vinylsulfone adducts. Serum half-life increased from 1 h for unmodified Shh to 7.0 and 12.6 h for the mono- and di-PEGylated products. These changes in clearance and half-life resulted in higher serum levels of Shh in the PEG-Shh-treated animals. In Ptc-LacZ knock-in mice expressing lacZ under regulation of the Shh receptor Patched, about a 10-fold lower dose of PEG-Shh was needed to induce beta-galactosidase than for the unmodified protein. Therapeutic treatment of mice with PEG-Shh enhanced the regeneration of injured sciatic nerves. These studies demonstrate that targeted PEGylation greatly alters the pharmacokinetic and pharmacodynamic properties of Shh, resulting in a form with improved pharmaceutical properties.     

Vertical distance from the crest of bone to the height of the interproximal papilla between adjacent implants

BACKGROUND: As patient demand increases for more natural restorations in the esthetic zone, clinicians must have the highest level of skill and knowledge to maintain or reform the interdental papilla between teeth, between implants and teeth, and between adjacent implants. To date, there are no reports that have measured the distance from the contact point to the bony crest between implants. One reason for this may be the fact that, with two adjacent implants, the contact point of the crown can be established at any distance from the gingival margin according to the restorative dentist's specifications. Therefore, in this study, the height of the soft tissue to the crest of bone was measured between two adjacent implants independent of the location of the contact point. The purpose of this study was to determine the range and average height of tissue between two adjacent implants. METHODS: A total of 136 interimplant papillary heights were examined in 33 patients by eight different examiners in five private dental offices. After administration of appropriate local anesthesia, a standardized periodontal probe was placed vertically from the height of the papilla to the crest of bone. The measurements were rounded off to the nearest millimeter. RESULTS: The mean height of papillary tissue between two adjacent implants was 3.4 mm, with a range of 1 mm to 7 mm. CONCLUSIONS: Clinicians should proceed with great caution when placing two implants adjacent to each other in the esthetic zone. In most cases, only 2, 3, or 4 mm of soft tissue height (average 3.4 mm) can be expected to form over the interimplant crest of bone. These results showed that modification of treatment plans may be necessary when esthetics are critical for success.