Human intrathymic lineage commitment is marked by differential CD7 expression: identification of CD7- lympho-myeloid thymic progenitors

The identity and lineage potential of the cells that initiate thymopoiesis remain controversial. The goal of these studies was to determine, at a clonal level, the immunophenotype and differentiation pathways of the earliest progenitors in human thymus. Although the majority of human CD34(+)lin(-) thymocytes express high levels of CD7, closer analysis reveals that a continuum of CD7 expression exists, and 1% to 2% of progenitors are CD7(-). CD34(+)lin(-) thymocytes were fractionated by CD7 expression and tested for lineage potential in B-lymphoid, T-lymphoid, and myeloid-erythroid conditions. Progressive restriction in lineage potential correlated with CD7 expression, that is, the CD7(hi) fraction produced T and NK cells but lacked B and myelo-erythroid potential, the CD7(int) (CD10(+)) fraction produced B, T, and NK cells, but lacked myelo-erythroid potential. The CD7(-) fraction produced all lymphoid and myelo-erythroid lineages and expressed HSC-associated genes. However, CD34(+)lin(-)CD7(-) thymocytes also expressed early T lymphoid genes Tdt, pTalpha, and IL-7Ralpha and lacked engraftment capacity, suggesting the signals that direct lymphoid commitment and corresponding loss of HSC function are rapidly initiated on arrival of HSC in the human thymus. Thus, differential levels of CD7 identify the progressive stages of lineage commitment in human thymus, initiated from a primitive CD7(-) lympho-myeloid thymic progenitor.     

Cognitive workload reduction in hospital information systems

Order sets are a critical component in hospital information systems that are expected to substantially reduce physicians’ physical and cognitive workload and improve patient safety. Order sets represent time interval-clustered order items, such as medications prescribed at hospital admission, that are administered to patients during their hospital stay. In this paper, we develop a mathematical programming model and an exact and a heuristic solution procedure with the objective of minimizing physicians’ cognitive workload associated with prescribing order sets. Furthermore, we provide structural insights into the problem which lead us to a valid lower bound on the order set size. In a case study using order data on Asthma patients with moderate complexity from a major pediatric hospital, we compare the hospital’s current solution with the exact and heuristic solutions on a variety of performance metrics. Our computational results confirm our lower bound and reveal that using a time interval decomposition approach substantially reduces computation times for the mathematical program, as does a K ?means clustering based decomposition approach which, however, does not guarantee optimality because it violates the lower bound. The results of comparing the mathematical program with the current order set configuration in the hospital indicates that cognitive workload can be reduced by about 20.2% by allowing 1 to 5 order sets, respectively. The comparison of the K ?means based decomposition with the hospital’s current configuration reveals a cognitive workload reduction of about 19.5%, also by allowing 1 to 5 order sets, respectively. We finally provide a decision support system to help practitioners analyze the current order set configuration, the results of the mathematical program and the heuristic approach.     

The diffusion of information technology among health maintenance organizations

This article examines the information technology functions, staffing and cost, services provided, and advanced technologies among health maintenance organizations (HMOs) using a national sample of HMOs from mid-1995. HMOs have a well-developed capability to use data from administrative functions, such as claims processing. Nationally affiliated HMOs and HMOs in markets with greater HMO penetration support more IT functions. Relatively little work has been completed integrating clinical with administrative systems.     

The pediatric use of bilevel positive airway pressure therapy for obstructive sleep apnea syndrome: a retrospective review with analysis of respiratory parameters

The purpose of this study was objective documentation of clinical benefits of bilevel positive airway pressure in pediatric patients with obstructive sleep apnea. We performed a retrospective chart review and data collection/analysis in a suburban tertiary care children's hospital. The study consisted of 10 pediatric patients (age range: 3 to 18 years); 3 patients had craniofacial abnormalities, 1 patient had neuromuscular disease, and 6 patients were obese. Eleven-channel polysomnography and support with bilevel positive airway pressure were used. We measured obstructive sleep apnea indices, lowest oxygen saturation rate, and average breath lengths before and after bilevel positive airway pressure use. We found that the apnea index decreased from 19.7 +/- 26.46 to 0.82 +/- 1.01, the lowest oxygen saturation increased from 75.60% +/- 14.93% to 89.50% +/- 5.50%, and breath length increased from 3.22 +/- 0.95 to 3.68 +/- 0.82. Bilevel positive airway pressure may be considered as a treatment modality for pediatric patients with obstructive sleep apnea.     

The child with persistent cough

Coughing is a healthy reflex. Causes of a cough can vary from minor upper respiratory illnesses to malignancy. When a child's cough continues for weeks, parents worry. Primary care providers must decide when reassessment is needed and if a vigorous workup and referral to a pulmonologist are required. The above discussion should assist these physicians.     

(i) Irritable hip and septic arthritis of the hip

Transient synovitis needs to be differentiated from septic arthritis of the hip when a child presents with features of an irritable hip. Although there is considerable overlap in the clinical presentation of the two conditions, the natural history, treatment strategy and potential range of outcomes are quite distinct. While transient synovitis is a self limiting condition, emergent surgical intervention in the form of arthrotomy and wash out of joint is the mainstay of treatment of septic arthritis. Clinical decision algorithms have been developed using a combination of clinical and laboratory parameters to help differentiate the two conditions.     

Adjuvant Therapy with Hyaluronidase Prior to Excision of Dermatofibrosarcoma Protuberans

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) are uncommon, low grade cutaneous malignancies, which rarely metastasize. Although surgery is the main therapy for these tumors, they commonly recur in spite of wide excisions. Hyaluronidase (HD) has been used both intralesionally as well as intravenously as an adjuvant in therapy of both epithelial and mesenchymal malignancies to decrease local spread, to potentiate differentiation induced apoptosis, and to potentiate the tissue penetration of chemotherapeutic agents. In addition, there is a long history of intralesional HD use without significant complications. The biologic characteristics of DFSP including the observation that hyaluronic acid is commonly present and sometimes is increased in these tumors and the known effects of HD therapy in other malignancies suggested to us that HD pretreatment may be a helpful adjuvant in the surgical management of DFSPs. Following diagnostic biopsy of a recurrent DFSP, the patient was treated for 4 weeks with intralesional HD injections. RESULTS: Based on margins necessary for complete excision from past studies, this patient had decreased margin width and thus had a postoperative wound size less than was expected. The patient has had no evidence of recurrence at 24 months follow-up.     

Do we need to replace the patella in knee arthroplasty for rheumatoid disease?

We have examined the anterior knee function in two patient groups who had undergone primary knee arthroplasty without patellar resurfacing to identify differences for osteoarthrosis compared with rheumatoid disease. We identified two consecutive series of patients who had undergone knee replacement surgery for either osteoarthritis or rheumatoid disease between 1992 and 1994 under the care of a single surgeon using the same implant and surgical technique. There were 90 patients in each group. All were examined and asked to complete a questionnaire so as to determine Hospital for Special Surgery (HSS) score, Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) score, Bartlett patellar score and a Visual Analogue score (VAS) for any persistent anterior knee pain at rest. We failed to identify any significant differences in terms of anterior knee function between these two groups of patients. The re-operation rate was similar for both groups. It would appear that primary knee replacement for rheumatoid disease is met with a similarly good outcome for anterior knee function despite absence of patellar resurfacing. We would question the contention that patellar resurfacing is necessary for patients undergoing knee replacement for rheumatoid disease.