Quantifying regeneration in patients following peripheral nerve injury.

Healthy nerve function provides humans with the control of movement; sensation (such as pain, touch and temperature) and the quality of skin, hair and nails. Injury to this complex system creates a deficit in function, which is slow to recover, and rarely, if ever, returns to what patients consider to be normal. Despite promising results in pre-clinical animal experimentation effective translation is challenged by a current inability to quantify nerve regeneration in human subjects and relate this to measurable and responsible clinical outcomes. In animal models, muscle and nerve tissue samples can be harvested following experimental intervention. This allows direct quantification of muscle mass and quality and quantity of regeneration of axons; such an approach is not applicable in human medicine as it would ensure a significant functional deficit. Nevertheless a greater understanding of this process would allow the relationship that exists between neural and neuromuscular regeneration and functional outcome to be more clearly understood. This article presents a combined commentary of current practice from a specialist clinical unit and research team with regard to laboratory and clinical quantification of nerve regeneration. We highlight how electrophysiological diagnostic methods (which are used with significant recognised limitations in the assessment of clinical medicine) can potentially be used with more validity to interpret and assess the processes of neural regeneration in the clinical context, thus throwing light on the factors at play in translating lab advances into the clinic.

Cervical dilation as a predictor of pregnancy outcome following emergency cerclage.

OBJECTIVE: To determine whether cervical dilation at the time of physical examination indicated cerclage placement can predicts latency and gestational age at delivery. METHODS: A retrospective cohort study of all women who underwent physical examination indicated cerclage placement from 1996 to 2011 at Duke University Hospital (DUH) was performed. Physical examination indicated cerclage was defined as cerclage placement after 16 weeks in women with a cervical length of less than 2.5 cm and/or cervical dilation greater than or equal to 1 cm at time of procedure. Subjects were divided into two groups depending on cervical dilation at time of procedure (2 cm, <2 cm) for comparison. A multivariate linear regression model for the outcome gestational age of delivery was constructed, controlling for confounding variables. RESULTS: A total of 110 women with complete data were available for analysis. Median gestational age at cerclage placement was similar between the two groups (20.3 vs. 20.3 weeks, p = 0.8). Women with cervical dilatation ≥ 2 cm dilation delivered at an earlier median gestational age than women with cervical dilation <2 cm (27.0 vs. 35.6 weeks, p < 0.001). Cervical dilation at the time of cerclage placement independently predicted gestational age at delivery while controlling for use of intracervical Foley balloon catheter for membrane reduction, cerclage suture type, history of prior preterm birth, race, insurance status, and tobacco use. CONCLUSIONS: Women who receive a rescue cerclage are more likely to deliver at an earlier gestational age when cervical dilation is ≥ 2 cm at the time of procedure.

CD4+CD45RBHi T cell transfer induced colitis in mice is accompanied by osteopenia which is treatable with recombinant human osteoprotegerin.

BACKGROUND AND AIMS: Transfer of CD4+CD45RBHi T cells into semi syngeneic immunodeficient mice represents a model of inflammatory bowel disease (IBD). As patients with IBD often suffer from osteopenia, we studied if this T cell transfer in mice results in osteopenia in addition to colitis, and if treatment with osteoprotegerin (OPG) has effects on the bone mineral density of T cell transferred mice. We also investigated whether osteopenia was due to malabsorption as a result of a dysregulated digestive tract or as a consequence of the inflammatory process. METHODS: CD4+CD45RBHi or CD4+CD45RBLo T cells (4 x 10(5)) were sorted from CB6F1 and transferred into C.B.17 scid/scid mice. Recipient mice were treated with human IgG1 Fc (control) or Fc-OPG three times per week in a prophylactic regimen as well as a therapeutic regimen (after 10% body weight loss) and were evaluated for osteopenia and colitis. RESULTS: Mice that received CD4+CD45RBHi T cells developed osteopenia (as indicated by decreased bone density accompanied by decreased osteoblasts and increased osteoclasts) and colitis (as indicated by histological changes in the large intestine). Mice that received CD4+CD45RBLo T cells developed neither osteopenia nor colitis. All animals consumed, on average, the same amount of food and water over the course of the study. Prophylactic treatment with Fc-OPG increased bone density in mice that received either CD4+CD45RBHi or CD4+CD45RBLo T cells but had no effects on the gastrointestinal tract. Fc-OPG treatment of osteopenic mice with established IBD caused the normalisation of bone density. Osteopenia in CD4+CD45RBHi T cell recipients was accompanied by hypoparathyroidism that was partially normalised by treatment with Fc-OPG. CD4+CD45RBHi T cell recipients also had a bone marrow inflammatory cell infiltrate expressing tumour necrosis factor alpha which was unaffected by treatment with Fc-OPG. CONCLUSIONS: CD4+CD45RBHi T cell transfer results in osteopenia in addition to colitis. Evidence suggests that this osteopenia was induced by inflammatory cell infiltration and not by malabsorption of calcium. Recombinant human osteoprotegerin effectively treated the osteopenia. OPG may be a useful therapeutic option for treating osteopenia in patients with IBD.

Outcome of patients undergoing transabdominal cerclage: a descriptive study.

OBJECTIVE: Transabdominal cerclage is now evolving as an alternative to transvaginal cerclage in patients with cervical incompetence. The purpose of our study was to evaluate and describe our experience in patients selected to undergo transabdominal cerclage placement. METHODS: Outcome data for all patients who underwent transabdominal cerclage from January, 1990, through December, 1994, was collected. Indications for transabdominal cerclage included patients with prior failed vaginal cerclage, extremely shortened cervix, or anatomical defects judged unsuitable for transvaginal cerclage. RESULTS: Eleven patients underwent 12 transabdominal cerclage procedures. The mean gestational age at the time of cerclage placement was 12.5 weeks (range 10-14 weeks). The mean gestational age at delivery was 34 weeks. There were two neonatal deaths, which were related to extreme prematurity. The mean birthweight was 2,622 g. The fetal salvage rate was 83%. CONCLUSIONS: These findings suggest that in a highly select group of patients, the transabdominal cerclage can be a safe and effective procedure.

Umbilical cord thiocyanate and thyroid function in intrauterine growth-restricted infants of the smoking gravida.

OBJECTIVE: We evaluated maternal and umbilical cord thiocyanate and thyroid function in intrauterine growth-restricted infants of smoking mothers. STUDY DESIGN: One hundred six mother-infant pairs were studied and divided into four groups: smokers with appropriate for gestational age infants (n = 37), smokers with intrauterine growth-restricted infants (n = 19), nonsmokers with appropriate for gestational age infants (n = 33), and nonsmokers with intrauterine growth-restricted infants (n = 17). Sera from mothers were analyzed for thiocyanate levels. Serum from umbilical cord blood was analyzed for thiocyanate, thyroxine, resin triiodothyronine uptake, and thyroid-stimulating hormone. The free thyroxine index was then calculated. RESULTS: A significant correlation was found between maternal and umbilical cord thiocyanate levels (r = 0.90, p < 0.0001). Maternal and umbilical cord thiocyanate concentrations correlated with increased maternal cigarette use. For appropriate for gestational age and intrauterine growth-restricted infants, mean maternal and umbilical cord thiocyanate levels were not significantly different. The umbilical cord thiocyanate level did not correlate with thyroid function or birth weight. The umbilical cord thyroxine level was lower in nonsmokers than in smokers. CONCLUSION: Thiocyanate was not more concentrated in the intrauterine growth-restricted infant and did not correlate with thyroid function or birth weight. The thyroxine level was decreased significantly in intrauterine growth-restricted infants born to nonsmoking mothers. Further studies are necessary to evaluate the effects of smoking on thyroid function and on fetal growth and development.

The impact of the Women, Infants and Children Food Supplement Program on birth outcome.

OBJECTIVE: Our purpose was to compare the birth outcomes of pregnant women in the Women, Infants and Children Food Supplement Program with women not in the program. STUDY DESIGN: The vital records of 4713 women, 2895 enrolled in the Women, Infants and Children Food Supplement Program and 1812 not enrolled in the program, whose infants were delivered at Wishard Memorial Hospital over 18 months were reviewed with respect to age, education, race, substance habits, trimester of entry into prenatal care, maternal weight gain, and status in the program. The primary outcome variables evaluated were low birth weight, as defined by the delivery of an infant < 2500 gm, and infant mortality. The primary predictor was program participation versus nonparticipation. Analysis was by t test, chi2, and logistic regression models. RESULTS: Black women, women with no prenatal care, and women who smoke were more likely to deliver a low-birth-weight infant. The incidence of low birth weight was 13.1% for nonparticipants versus 10.2% for program participants (p < 0.05). Univariate analysis confirmed program participants to be at significantly less risk for a low-birth-weight delivery (odds ratio = 0.75, p < 0.05). This relation, however, was not significant in the multivariate model (odds ratio = 0.88), indicating that the effect of participating in the program is being confounded by race, entry into prenatal care, and smoking. The overall infant mortality rate was 12.4 per 1000 for participants and 16 per 1000 for nonparticipants (p = not significant). CONCLUSION: Nutritional and nonnutritional benefits to participation in the Women, Infants and Children Food Supplement Program were confirmed. Women enrolled in the program were less likely to deliver a low-birth-weight infant. Multiple variables likely contribute to the poorer outcome for nonparticipants.

Comparison of hematopoietic progenitor cells in human umbilical cord blood collected from neonatal infants who are small and appropriate for gestational age.

BACKGROUND: Cord blood has been used for transplantation. The purpose of this study was to compare numbers of hematopoietic progenitors in cord blood collected from neonatal infants who are small for their gestational age and those who are normal. STUDY DESIGN AND METHODS: Sixteen pregnant women diagnosed with intrauterine growth restriction were prospectively identified. Cord blood was collected at delivery. Fourteen cord blood samples were obtained from gestational age-matched, appropriately grown newborns. In vitro assays for hematopoietic progenitors were performed and results of the two compared. Comparisons were also made with numbers of hematopoietic progenitor cells previously found by this laboratory in samples collected with the possibility of use for transplantation. RESULTS: Gestational age, the women's pregnancy and delivery histories, maternal risk factors for intrauterine growth restriction, maternal age, delivery method, umbilical cord blood gases, and 5-minute Apgar scores were similar in the two groups. Newborns who were small for their gestational age had significantly lower birth weights and longer stays in the neonatal intensive care unit with no evidence for viral infections in the immediate neonatal period. The mean number of progenitors per collection of cord blood in the small newborns was about half that per collection from appropriately grown newborns, but in most cases, these differences were not significant in the two groups, and many numbers in the small newborns fell within the range associated with successfully engrafting cord blood collections. CONCLUSION: Hematopoietic progenitor cells in the small newborns may be adequate for transplantation purposes in many cases. Their possible use in this context should, however, involve careful consideration of the numbers of progenitors collected as well as of possible viral or other contamination.

Umbilical cord blood gas assessment of twins.

Umbilical cord arterial and venous blood gas values were compared in 63 twin pairs, of which 57 pairs had birth weights of 1500 g or more each. Small differences between the first and second twins existed for PO2, PCO2, and pH. However, bicarbonate values did not differ significantly. These cord gas differences represent minor respiratory aberrations, as reflected by a tendency toward carbon dioxide retention by the second twin. Route of delivery, time interval between deliveries, and nonvertex presentations were not associated with significant deviations from these observed acid-base patterns.

Premature placental calcification in maternal cigarette smokers.

Ultrasonographic examinations, including placental grading, were done in 145 smoking and 100 nonsmoking low-risk obstetric patients at 37 weeks' gestation. Extensive calcification--grade III changes--occurred significantly more often in smokers than in nonsmokers (36 versus 14%; P less than .0001). Two groups of smokers, consuming five to 15 cigarettes per day or one or more packs per day, also had significant differences in grade III placenta when compared with nonsmokers. Smokers under age 20 years were more likely to have premature grade III changes; however, parity did not influence premature placental calcification in smokers and nonsmokers. The incidence of small for gestational age infants delivered was not significantly higher in smokers, and grade III placental changes appeared to occur no more often in SGA infants of smokers than of nonsmokers. Our findings suggest that the smoking gravida is at increased risk for premature placental calcification.

Leprosy in a mangabey monkey--naturally acquired infection.

Naturally acquired leprosy was detected in an otherwise normal "sooty" mangabey monkey (Cercocebus atys). This animal was imported from West Africa in 1975 and developed clinical symptoms of leprosy in 1979. Histopathologic findings were those of subpolar-lepromatous to borderline-lepromatous leprosy in the Ridley-Jopling classification. The disease was progressive, with crippling neuropathic deformities of the hands and feet. The disease regressed under specific therapy. The etiologic agent was identified as Mycobacterium leprae by the following criteria: invasion of nerves of host, staining properties, electron microscopic findings, noncultivable on mycobacteriologic media, DOPA-oxidase positive, lepromin reactivity, infection patterns in mice and armadillos, sensitivity to sulfone, and DNA homology. We believe the animal acquired the disease from a patient with active leprosy. The mangabey monkey offers promise as a primate model for leprosy, and adds a third reported species to animals with naturally acquired leprosy.