Interrelationship of Cranial Suture Fusion, Basicranial Development, and Resynostosis Following Suturectomy in Twist1+/? Mice, a Murine Model of Saethre-Chotzen Syndrome

The interrelationships among suture fusion, basicranial development, and subsequent resynostosis in syndromic craniosynostosis have yet to be examined. The objectives of this study were to determine the potential relationship between suture fusion and cranial base development in a model of syndromic craniosynostosis and to assess the effects of the syndrome on resynostosis following suturectomy. To do this, posterior frontal and coronal suture fusion, postnatal development of sphenooccipital synchondrosis, and resynostosis in Twist1(+/+) (WT) and Twist1(+/-) litter-matched mice (a model for Saethre-Chotzen syndrome) were quantified by evaluating μCT images with advanced image-processing algorithms. The coronal suture in Twist(+/-) mice developed, fused, and mineralized at a faster rate than that in normal littermates at postnatal days 6-30. Moreover, premature fusion of the coronal suture in Twist1(+/-) mice preceded alterations in cranial base development. Analysis of synchondrosis showed faster mineralization in Twist(+/-) mice at postnatal days 25-30. In a rapid resynostosis model, there was an inability to fuse both the midline posterior frontal suture and craniotomy defects in 21-day-old Twist(+/-) mice, despite having accelerated mineralization in the posterior frontal suture and defects. This study showed that dissimilarities between Twist1(+/+) and Twist1(+/-) mice are not limited to a fused coronal suture but include differences in fusion of other sutures, the regenerative capacity of the cranial vault, and the development of the cranial base.     

The effects of FK778 in combination with tacrolimus and steroids: a phase II multicenter study in renal transplant patients

BACKGROUND: In animal and in vitro models, FK778 inhibits acute rejection, modifies vasculopathy, and shows anti-viral activity. We report first efficacy and safety data of FK778 in human kidney transplant recipients at two concentration-controlled ranges. METHODS: In a double-blind manner, 149 patients were randomized to a 12-week treatment with FK778 in combination with tacrolimus (Tac) and corticosteroids (S). Of the high-level group (H), 49 patients received 2 x 600 mg/day FK778 and continued on 150 mg/day, 54 patients of the low-level group (L) got 1 x 600 mg/day followed by 75 mg/day, and 46 patients received placebo (P). Subsequent FK778 doses were adjusted to trough levels of 100-200 microg/mL (H) and 10-100 microg/mL (L). The primary endpoint was the incidence of biopsy proven acute rejection (AR). RESULTS: In 93% of the patients in group L, targeted plasma trough levels were reached by Day 3; in half of the patients in group H, the targeted levels were reached by Day 9. Graft survival at week 16 was 89.7%, 88.8%, and 91.3%, and the incidences of AR were 26.5%, 25.9%, and 39.1% for groups H, L, and P. For the subgroup of patients in which target levels were reached by week 2, incidences were 7.7%, 27.1%, and 39.1%, respectively. Anemia, the most frequently reported adverse event especially in group H, was reversible. Mean total cholesterol and LDL-cholesterol levels were reduced during FK778 treatment compared with group P. CONCLUSION: FK778 is pharmacologically active, well-tolerated, and safe. To fully benefit from this promising new drug, FK778 dosing will be optimized in subsequent studies.     

Panning for gold: screening for potential live kidney donors.

BACKGROUND: Living donation is one method of addressing the gulf between supply and demand for kidney transplants. However, few manage to complete the extensive work up procedure. This study reviews the reasons for failure to complete the live donor renal assessment and suggests options, which may improve the situation. METHODS: Retrospective analysis of data collected over 5 years between 1997 and 2001 of all potential live donors entering the assessment programme. RESULTS: 189 (103 female, 86 male) potential donors entered the assessment process. Thirty-four (18%) actually donated comprising 17 (50%) siblings, nine (26%) parents and eight (24%) unrelated donors. Of the 155 who did not donate, 46 (30%) had blood group or immunological incompatibility and 42 (27%) withdrew. Twenty-three (15%) were medically unfit, mostly due to cardiovascular disease and 16 (10%) had insufficient renal function for safe donation. CONCLUSION: Live donor transplantation offers an attractive source of high quality organs, but considerable time and effort is required to realize this. Manipulation of immunological incompatibility, psychological assessment and counselling of those likely to withdraw may significantly enhance the yield. Support should also be provided for those unable to donate for whatever reason.     

Kyphoplasty for treatment of osteoporotic vertebral fractures

Cement reinforcement for the treatment of osteoporotic vertebral fractures is efficient mean with high success in pain release and prevention of further sintering of the reinforced vertebrae; however, the technique does not allow to address the kyphotic deformity. Kyphoplasty was designed to address the kyphotic deformity and help to realign the spine. It involves the percutaneous placement of an inflatable bone tamp into a vertebral body. Restoration of VB height and kyphosis correction is achieved by inflation of the bone tamp with liquid. After deflation, a cavity is created that eases the cement application. The potential of kyphosis reduction is given in fresh fractures with a range of 0–90% for height restoration and absolute correction of the kyphotic angle of 8.5°. The cavity formation, on one hand, and the different cementing technique leads to lower risk for cement extravasation. An alternative method for kyphosis correction represents the so-called lordoplasty where the adjacent vertebrae are reinforced first and with the cannulas in place acting as a lever the reduction of the collapsed vertebra can be performed. The results with respect to kyphosis correction are superior in comparison with a kyphoplasty procedure.     

Multivariate predictors of blood product use in cardiac surgery

OBJECTIVE: To determine factors associated with an increased risk of post-cardiopulmonary bypass (CPB) blood product usage in adult cardiac surgical patients. DESIGN: Prospective observational study. SETTING: Academic hospital. PARTICIPANTS: Patients undergoing cardiac surgery with CPB were studied over a 7-month period. INTERVENTIONS: The outcomes studied were receipt of more than 2 U of packed red blood cells (PRBCs), receipt of any other blood component products (cryoprecipitate, fresh-frozen plasma [FFP], or platelets), or surgical re-exploration for bleeding. Preoperative and intraoperative risk factors for bleeding were analyzed. MEASUREMENTS AND MAIN RESULTS: Increased age and preoperative creatinine level, low body surface area, preoperative hematocrit, nonelective surgery, lower temperature on bypass, and duration of bypass were associated with an increased risk of transfusion of >2 U of PRBCs. Low body surface area, repeat surgery, nonelective surgery, and CPB time were associated with transfusion of platelets, fresh-frozen plasma, or cryoprecipitate and/or surgical re-exploration. The following factors were associated with neither transfusion of more than 2 U of PRBC nor transfusion of platelets, FFP or cryoprecipitate, or surgical re-exploration: gender, preoperative international normalized ratio, preoperative antiplatelet medications, and preoperative intravenous heparin. CONCLUSION: Therapies aimed at reducing transfusion of blood products should be aimed at those patients with low body surface areas, baseline anemia, and those undergoing long or repeat surgeries.     

Comparison of automated strategies for surveillance of nosocomial bacteremia.

OBJECTIVE: Surveillance of nosocomial bloodstream infection (BSI) is recommended, but time-consuming. We explored strategies for automated surveillance. METHODS: Cohort study. We prospectively processed microbiological and administrative patient data with computerized algorithms to identify contaminated blood cultures, community-acquired BSI, and hospital-acquired BSI and used algorithms to classify the latter on the basis of whether it was a catheter-associated infection. We compared the automatic classification with an assessment (71% prospective) of clinical data. SETTING: An 850-bed university hospital. PARTICIPANTS: All adult patients admitted to general surgery, internal medicine, a medical intensive care unit, or a surgical intensive care unit over 3 years. RESULTS: The results of the automated surveillance were 95% concordant with those of classical surveillance based on the assessment of clinical data in distinguishing contamination, community-acquired BSI, and hospital-acquired BSI in a random sample of 100 cases of bacteremia. The two methods were 74% concordant in classifying 351 consecutive episodes of nosocomial BSI with respect to whether the BSI was catheter-associated. Prolonged episodes of BSI, mostly fungemia, that were counted multiple times and incorrect classification of BSI clinically imputable to catheter infection accounted for 81% of the misclassifications in automated surveillance. By counting episodes of fungemia only once per hospital stay and by considering all cases of coagulase-negative staphylococcal BSI to be catheter-related, we improved concordance with clinical assessment to 82%. With these adjustments, automated surveillance for detection of catheter-related BSI had a sensitivity of 78% and a specificity of 93%; for detection of other types of nosocomial BSI, the sensitivity was 98% and the specificity was 69%. CONCLUSION: Automated strategies are convenient alternatives to manual surveillance of nosocomial BSI.     

Protective effect of Mangifera indica L. polyphenols on human T lymphocytes against activation-induced cell death.

Activation-induced cell death (AICD) plays an important role in maintenance of peripheral lymphocyte homeostasis. Reactive oxygen species (ROS) combined with simultaneous calcium (Ca(2+)) influx into the cytosol are required for induction of AICD. The extract obtained from the stem bark of Mangifera indica L. has shown to protect T cells from in vitro AICD. This extract is rich in polyphenolic compounds, the three main components of which are mangiferin (MA), catechin (C) and epicatechin (EC). The present study has focused on the possible contribution of the polyphenols MA, C and EC to the demonstrated protective effect of M. indica extract on in vitro human T cell AICD. Our results show that these polyphenols diminished the increase of intracellular ROS and free Ca(2+) induced by T cell receptor (TCR) triggering. In addition, these polyphenols attenuated AICD. Our findings suggest that the T cell survival effect of M. indica extract is mediated, at least in part, by its main polyphenols.     

Psychosocial counseling of cancer patients by telephone: A brief note on patient acceptance of an outcall strategy

Telephone counseling of cancer patients has existed on a limited basis for a number of years. One aspect of telephone counseling that has not been adequately explored involves using an outcall strategy, in which the counseling service would call the patient according to a prearranged schedule. Such a strategy could be used to overcome the potentially significant barrier of requiring the patient to proactively call the counseling service. As a preliminary phase in the development of a larger program of research on telephone counseling of cancer patients, two feasibility studies were conducted to assess patient willingness to receive outcall telephone counseling and their willingness to share sensitive psychosocial concerns over the telephone. The results obtained from both feasibility studies suggest that telephone outcalls are feasible for both breast and prostate cancer patients. Additional research is proposed to test the efficacy of psychosocial counseling by telephone using an outcall format.     

Mississippi Public Health Nurses and Midwives: A Partnership That Worked

Abstract At the turn of the century maternal and infant mortality rates were high in this southern state. Untrained midwives conducted many of the deliveries. Initial support for locating and training midwives by public health nurses was provided by the American Red Cross and the United States Public Health Services. Later, funding from a philanthropic organization (Rockefeller International Foundation) provided a mechanism that brought Mississippi public health nurses and midwives to a partnership that endured for over a half a century, and contributed to better maternal-infant health care outcomes for that state.