Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease

To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus- host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.     

Laws pertaining to healthcare-associated infections: a review of 3 legal requirements

We reviewed US state and territorial healthcare-associated infection (HAI) laws, specifically addressing 3 legal requirements: data submission, reporting of data to the public, and inclusion of facility identifiers in public reports. The majority of US states and territories have HAI laws. The 3 studied legal provisions are all commonly included in state HAI laws in varying forms; however, only a minority of states and territories specifically mandate all 3 legal requirements. The laws of the remaining states vary considerably.     

Low risk of viral infection after administration of vapor-heated factor VIII concentrate. International Investigator Group

A multicenter prospective study was carried out to evaluate whether a vapor-heated factor VIII concentrate transmitted blood-borne viral infections over a surveillance period of 15 months. Thirty-five patients with hemophilia and von Willebrand disease who had never received any blood components were treated. Twenty-eight were analyzed and found not to have non-A, non-B hepatitis. Sera from 20 of these 28 patients were also tested for the antibody to the hepatitis C virus. None had sero-converted during the follow-up period. None of the patients analyzed developed markers of the hepatitis B virus (n = 17) or the human immunodeficiency virus (n = 31). This vapor-heated factor VIII concentrate carries a low risk of transmitting hepatitis and human immunodeficiency virus infection.     

Stem Cell Implants for Cancer Therapy: TRAIL-Expressing Mesenchymal Stem Cells Target Cancer Cells In Situ

Purpose

Tumor-specific delivery of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), an apoptosis-inducing peptide, at effective doses remains challenging. Herein we demonstrate the utility of a scaffold-based delivery system for sustained therapeutic cell release that capitalizes on the tumor-homing properties of mesenchymal stem cells (MSCs) and their ability to express genetically-introduced therapeutic genes.

Methods

Implants were formed from porous, biocompatible silk scaffolds seeded with full length TRAIL-expressing MSCs (FLT-MSCs). under a doxycycline inducible promoter. In vitro studies with FLT-MSCs demonstrated TRAIL expression and antitumor effects on breast cancer cells. Next, FLT-MSCs were administered to mice using three administration routes (mammary fat pad co-injections, tail vein injections, and subcutaneous implantation on scaffolds).

Results

In vitro cell-specific bioluminescent imaging measured tumor cell specific growth in the presence of stromal cells and demonstrated FLT-MSC inhibition of breast cancer growth. FLT-MSC implants successfully decreased bone and lung metastasis, whereas liver metastasis decreased only with tail vein and co-injection administration routes. Average tumor burden was decreased when doxycycline was used to induce TRAIL expression for co-injection and scaffold groups, as compared to controls with no induced TRAIL expression.

Conclusion

This implant-based therapeutic delivery system is an effective and completely novel method of anticancer therapy and holds great potential for clinical applications.     

Alarm settings for the Marquette 8000 pulse oximeter to prevent hyperoxic and hypoxic episodes

OBJECTIVE: To determine safe and appropriate alarm limits for the Marquette 8000 pulse oximeter to prevent hyperoxic and hypoxic episodes in neonates. It is necessary to define these limits for each brand of oximeter because of the variance in nonuser adjustable calibration algorithms used in pulse oximeters. METHODOLOGY: Oxygen saturation values obtained from a Marquette 8000 pulse oximeter (SpO2) were compared with simultaneous arterial blood gas PaO2 values obtained from blood gas analysis, for 322 samples in 24 consecutive neonates (median 30 weeks' gestation). RESULTS: In order to prevent 95% of hyperoxic episodes (PaO2 > 90 mmHg), the upper alarm limit was 95% SpO2. Similarly, to prevent 95% of hypoxic episodes (PaO2 < 40 mmHg), the lower alarm limit was 95% SpO2. A sensitivity lower than 95% had to be accepted to develop an alarm range which prevented both hyperoxic and hypoxic episodes. To maintain PaO2 values between 40 and 90 mmHg, an appropriate alarm range of 94-97% SpO2 (90% sensitivity, 28% specificity) was established. CONCLUSIONS: The relative merits of high sensitivity versus high specificity should be considered when determining appropriate alarm limits. Alarm limits which represent a balance between sensitivity and specificity will minimise false alarms and provide a clinically practical range. It would be useful for this type of information to be available for each brand of oximeter, to assist the user in determining appropriate alarm settings.     

Recurrent abdominal pain and Helicobacter pylori in a community-based sample of London children

Helicobacter pylori is accepted as an important factor in the pathogenesis of peptic ulcer disease. Infection is probably most commonly acquired in early life but there is still limited information on the prevalence or symptomatology of H. pylori infection in childhood. The aim of the present study was to establish the prevalence of H. pylori infection in a large sample of urban school children and to determine its relationship, if any, to a history of recurrent abdominal pain. Using a commercial ELISA significant levels of anti- H , pylori IgG antibody were detected in 107/640 (16.7%) of school children (M, 383; F, 257; mean age 9.15 years, range 4-13). No relationship was demonstrated between H. pylori seropositivity and a personal or family history of recurrent abdominal pain or the nature of the pain.     

Diabetic mothers and their newborn infants – rooming‐in and neonatal morbidity

Aim: As a result of increased neonatal morbidity, the infants of diabetic mothers have routinely been admitted to a neonatal special care unit (NSCU). We therefore investigated whether the offer of rooming‐in diabetic mothers and their newborn infants has an effect on neonatal morbidity. Methods: The records of an old cohort of 103 infants routinely admitted to the NSCU, and a new cohort (N = 102), offered rooming‐in were assessed for neonatal morbidity. Results: Eighty‐four (82%) of the new cohort infants followed their mothers to the maternity ward; whereas 19 (18%) were transferred to the NSCU chiefly because of prematurity. Ten infants were later transferred to the NSCU for minor problems. Neonatal morbidity and neonatal hypoglycaemia were significantly less common in the new cohort than in the old cohort [27 (26%) vs. 55 (54%), p < 0.001 and 42 (41%) vs. 64 (63%), p = 0.0027 respectively]. Maternal HbA1c in late pregnancy was significantly lower in the new cohort, but the only independent predictors of neonatal morbidity were belonging to the old cohort and preterm delivery. Conclusion: Neonatal care with rooming‐in mothers with type 1 diabetes and their newborn infants seems safe and is associated with reduced neonatal morbidity, when compared with routine separation of infants from their mothers.     

Spontaneous Resolution of Aberrant Cerebellar Tonsil Movement in a Patient with Improving Chiari I Malformation

Chiari malformation Type 1 (CMI) is traditionally characterized as a descent of the cerebellar tonsils more than 5mm below the foramen magnum. In some patients with CMI, there is aberrant pulsatile movement of the tonsils downward during cardiac systole which can affect cerebrospinal fluid (CSF) flow at the foramen magnum. Here, we present an 18-year-old female patient with CMI who presented with worsening symptoms of her CMI. Magnetic resonance imaging (MRI) at this time indicated an increase in cerebellar tonsil movement and decreased CSF flow at the foramen magnum. At her follow-up appointment, she had complete resolution of the aberrant motion of her tonsils and CSF flow returned to baseline without surgical intervention. Her symptoms also improved during this time, and she is now able to be followed by her primary care physician. The increased pulsatile movement of cerebellar tonsils in patients with CMI has been linked to diminished CSF flow at the foramen magnum and symptom severity. Spontaneous resolution of CMI is rare and has only ever been documented as ascension of the cerebellar tonsils. This case describes restoration of normal tonsil movement and baseline CSF flow corresponding with a resolution of symptoms where a complete resolution in tonsillar ectopia was not present.