Postnatal cytokines and boosts improve chimerism and hematological parameters in beta-thalassemic mice transplanted in utero

We have developed a murine model of in utero transplantation in nonanemic, beta-thalassemic mice to study chimerism, tolerance, and changes in hematological parameters in response to cytokines and postnatal boosts with donor cells. We have documented improved survival of homozygous fetuses by 40% as compared with controls. Low-level, mixed chimerism was improved by postnatal cytokine therapy and boosts and was associated with improvement in hemoglobin levels, reticulocyte counts, and iron stores. Cytotoxicity assays demonstrated higher responses to donor cells in control mice as compared with in utero transplanted animals (at 50:1 effector to target ratios, transplanted mice showed 8.66% target lysis and control mice showed 51.85% target lysis, P=0.0003), indicating tolerance. The combination of prenatal tolerance to allogeneic cells with postnatal boosts in primed hosts may become an effective, nontoxic strategy for the improvement of hemolytic anemia in beta-thalassemic patients.     

Discrimination between neoplastic and nonneoplastic brain lesions by use of proton MR spectroscopy: the limits of accuracy with a logistic regression model

BACKGROUND AND PURPOSE: The most accurate method of clinical MR spectroscopy (MRS) interpretation remains an open question. We sought to construct a logistic regression (LR) pattern recognition model for the discrimination of neoplastic from nonneoplastic brain lesions with MR imaging-guided single-voxel proton MRS data. We compared the LR sensitivity, specificity, and receiver operator characteristic (ROC) curve area (Az) with the sensitivity and specificity of blinded and unblinded qualitative MRS interpretations and a choline (Cho)/N-acetylaspartate (NAA) amplitude ratio criterion. METHODS: Consecutive patients with suspected brain neoplasms or recurrent neoplasia referred for MRS were enrolled once final diagnoses were established by histopathologic examination or serial neurologic examinations, laboratory data, and imaging studies. Control spectra from healthy adult volunteers were included. An LR model was constructed with 10 input variables, including seven metabolite resonance amplitudes, unsuppressed brain water content, water line width, and the final diagnosis (neoplasm versus nonneoplasm). The LR model output was the probability of tumor, for which a cutoff value was chosen to obtain comparable sensitivity and specificity. The LR sensitivity and specificity were compared with those of qualitative blinded interpretations from two readers (designated A and B), qualitative unblinded interpretations (in aggregate) from a group of five staff neuroradiologists and a spectroscopist, and a quantitative Cho/NAA amplitude ratio > 1 threshold for tumor. Sensitivities and specificities for each method were compared with McNemar's chi square analysis for binary tests and matched data with a significance level of 5%. ROC analyses were performed where possible, and Az values were compared with Metz's method (CORROC2) with a 5% significance level. RESULTS: Of the 99 cases enrolled, 86 had neoplasms and 13 had nonneoplastic diagnoses. The discrimination of neoplastic from control spectra was trivial with the LR, reflecting high homogeneity among the control spectra. An LR cutoff probability for tumor of 0.8 yielded a specificity of 87%, a comparable sensitivity of 85%, and an area under the ROC curve of 0.96. Sensitivities, specificities, and ROC areas (where available) for the other methods were, on average, 82%, 74%, and 0.82, respectively, for readers A and B, 89% (sensitivity) and 92% (specificity) for the group of unblinded readers, and 79% (sensitivity), 77% (specificity), and 0.84 (Az) for the Cho/NAA > 1 criterion. McNemar's analysis yielded significant differences in sensitivity (n approximately 86 neoplasms) between the LR and reader A, and between the LR and the Cho/NAA > 1 criterion. The differences in specificity between the LR and all other methods were not significant (n approximately 13 nonneoplasms). Metz's analysis revealed a significant difference in Az between the LR and the Cho/NAA ratio criterion.     

Predictive value of photoscreening and traditional screening of preschool children.

PURPOSE: To compare the usefulness of traditional vision screening and photoscreening of 3- and 4-year-old children in the pediatrician's office. METHODS: Following training of pediatricians and office staff, six pediatric clinics used both the MTI PhotoScreener (Medical Technology Industries, LLC, Riviera Beach, FL) and traditional acuity and stereopsis screening materials (HOTV charts/Random Dot E tests as recommended by established AAP-MCHB-PUPVS guidelines) during well-child exams. Clinics used one testing method for a 6-month period and switched to the other for the following 6 months, in a randomized manner. Referred children received a complete eye examination with cycloplegic refraction by local ophthalmologists or optometrists who forwarded the results to Vanderbilt Ophthalmology Outreach Center. Amblyogenic factors were defined using standardized published criteria. RESULTS: Six hundred five children were screened with the photoscreener and 447 were screened with traditional techniques. Mean time for screening was less with the photoscreener: 2.5 versus 5.9 minutes ( P < 0.01). Untestable rates were similar (18% vs 10%, respectively P = NS), but higher with the photoscreener due to one clinic's 70% unreadable rate. Referral rates were also similar: 3.8% versus 4.5%. The positive predictive value (PPV) rate differed greatly. With follow-up results obtained from 56% of referred children, 73% of photoscreening referred children (8/11 examined) had amblyogenic factors confirmed on formal eye exams, whereas all children referred using traditional screening methods (10/10 examined) were normal. CONCLUSION: Photoscreening is more time efficient than traditional screening and has a significantly higher PPV in 3- and 4-year-old children. This study was unable to validate traditional screening techniques in this preschool age group. If these results can be replicated, support for traditional vision screening must undergo intense scrutiny, and attention should be turned toward making photoscreening feasible for widespread implementation.     

Increase in plasma volume after the transfusion of washed erythrocytes

During a four day period, each of 14 healthy mongrel dogs that had splenectomy was twice bled 450 milliliters of blood and twice reinfused with 500 milliliters of isotonic sodium chloride solution. On the sixth day, the dogs were hypovolemic and anemic; they had 10 per cent reductions in total blood volume and 50 per cent reductions in erythrocyte volume, but no change in plasma volume. Seven of the dogs were transfused with autologous washed erythrocyte concentrates and seven others with an equal volume of autologous plasma. Two units of autologous washed erythrocyte concentrations with hematocrit values of 80 volumes per cent increased plasma volumes to levels similar to those achieved with 2 units of autologous plasma. The serum oncotic pressure, total protein and albumin concentrations were similar in the two groups, except that, two hours after transfusion, the serum albumin level was significantly higher in the dogs transfused with plasma. These data demonstrate that erythrocyte transfusions increase both the erythrocyte and plasma volumes.     

Omentum is highly effective in the management of complex cardiothoracic surgical problems

OBJECTIVES: Vascularized, pedicled tissue flaps are often used for cardiothoracic surgical problems complicated by factors that adversely affect healing, such as previous irradiation, established infection, or steroid use. We reviewed our experience with use of the omentum in these situations to provide a yardstick against which results with other vascularized flaps (specifically muscle flaps) could be compared. METHODS: A retrospective review was undertaken of 85 consecutive patients in whom omentum was used in the chest. In 47 patients (group I), use of omentum was prophylactic to aid in the healing of closures or anastomoses considered to be at high risk for failure. In 32 patients (group II), omentum was used in the treatment of problems complicated by established infection. In 6 patients (group III), omentum was used for coverage of prosthetic chest wall replacements after extensive chest wall resection. RESULTS: Overall, omental transposition was successful in its prophylactic or therapeutic purpose in 88% of these difficult cases (75/85). Success with omentum was achieved for 89% of patients (42/47) in group I, 91% of patients (29/32) in group II, and 67% of patients (4/6) in group III. Three patients (3.5%) had complications of omental mobilization. Four patients (4.7%) died after the operation as a result of failure of the omentum to manage the problem for which it was used. CONCLUSIONS: Results with omental transposition compare favorably with published series of similarly challenging cases managed with muscle transposition. Complications of omental mobilization are rare. We believe that its unique properties render the omentum an excellent choice of vascularized pedicle in the management of the most complex cardiothoracic surgical problems.