Osteoprogenitor cells of mature human skeletal muscle tissue: an in vitro study.

The presence of osteogenic progenitors in human skeletal muscle is suggested by the formation of ectopic bone in clinical and experimental conditions, but their direct identification has not yet been demonstrated. The aims of this study were to identify osteogenic progenitor cells in human skeletal muscle tissue and to expand and characterize them in culture. Specimens of gracilis and semitendinosus muscle were obtained from young adults and digested to separate the connective tissue and satellite cell fractions. The cells were cultured and characterized morphologically and immunohistochemically using antibodies known to be reactive with primitive osteoprogenitor cells, pericytes, intermediate filaments, and endothelial cells. Alkaline phosphatase activity and osteocalcin gene expression were also determined. In the early stages of culture, the connective tissue cells obtained were highly positive for primitive osteoprogenitor cell and for pericyte markers. Alkaline phosphatase activity was detectable at early stages of culture and rose as a function of time, whereas primitive osteoprogenitor cell markers declined and osteocalcin mRNA expression became detectable by reverse transcriptase-polymerase chain reaction (RT-PCR). It is shown that human skeletal muscle connective tissue contains osteogenic progenitor cells. Their identification as pericytes, perivascular cells with established osteogenic potential, suggests a cellular link between angiogenesis and bone formation in muscle tissue. These cells are easily cultured and expanded in vitro by standard techniques, providing an alternative source of osteogenic progenitor cells for possible cell-based therapeutic use in certain conditions.

The effect of islet cell culture in vitro at 24 degrees C on graft survival and MHC antigen expression.

A period of in vitro culture prior to transplantation has been shown to prolong the survival of many types of MHC-incompatible endocrine grafts. The effectiveness of this strategy has been attributed to a selective depletion of intragraft antigen-presenting cells. We report that in vitro culture at 24 degrees C results in a significantly better survival of rat isolated islet allografts than does culture at 37 degrees C. Using in vitro assays of APC activity, we were unable to detect differences in the quantity of residual intraislet APCs between 24 degrees C and 37 degrees C culture preparations. In contrast, islet endocrine cells cultured at 24 degrees C evidenced a reduced level of cell surface class I MHC antigen expression and were significantly less vulnerable to lysis in vitro by CTL. These findings suggest that culture at 24 degrees C produces islet alterations other than APC depletion, and that its beneficial effect on graft survival correlates with a reduction in endocrine cell class I MHC antigen expression.

Work of breathing as a weaning parameter in mechanically ventilated patients.

STUDY OBJECTIVE: Predicting patient responses to changes in ventilatory support or weaning is primarily based on bedside measure of respiratory mechanics and clinical judgement. Work of breathing (WOB) has been considered to be the best predictive factor in weaning. This study evaluated patient WOB as a predictive measure of weaning and extubation. DESIGN: Blinded, descriptive evaluation of the accuracy of preextubation values of patient WOB in predicting successful extubation. SETTING: Critical care units of 500-bed major teaching hospital of the University of Hawaii. PATIENTS: Twenty-four patients from the medical and surgical ICU were enrolled in the study. Patient diagnoses included COPD, ARDS, pneumonia, and renal failure. MEASUREMENTS AND MAIN RESULTS: In all patients, weaning from mechanical ventilation was accomplished by the clinical ICU teams who were blinded to the patient WOB. After extubation, patient WOB was compared with extubation attempts. In 14 patients, WOB was elevated above normal levels prior to successful extubation, while only 1 patient whose WOB was abnormal prior to extubation required reintubation within 24 h. WOB and clinical parameters were normal in 10 successfully extubated patients. CONCLUSIONS: In this group of mechanically ventilated patients, measurement of patient WOB was less accurate than conventional weaning parameters and clinical judgement for predicting successful extubation. This clinical evaluation study suggests that WOB alone is inadequate as a weaning parameter.

Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock.

OBJECTIVE: To develop management guidelines for severe sepsis and septic shock that would be of practical use for the bedside clinician, under the auspices of the Surviving Sepsis Campaign, an international effort to increase awareness and improve outcome in severe sepsis. DESIGN: The process included a modified Delphi method, a consensus conference, several subsequent smaller meetings of subgroups and key individuals, teleconferences, and electronic-based discussion among subgroups and among the entire committee. The modified Delphi methodology used for grading recommendations built upon a 2001 publication sponsored by the International Sepsis Forum. We undertook a systematic review of the literature graded along 5 levels to create recommendation grades from A-E, with A being the highest grade. Pediatric considerations were provided to contrast adult and pediatric management. PARTICIPANTS: Participants included 44 critical care and infectious disease experts representing 11 international organizations. RESULTS: A total of 46 recommendations plus pediatric management considerations. CONCLUSIONS: Evidence-based recommendations can be made regarding many aspects of the acute management of sepsis and septic shock that will hopefully translate into improved outcomes for the critically ill patient. The impact of these guidelines will be formally tested and guidelines updated annually, and even more rapidly when some important new knowledge becomes available.

Extracranial repair of pediatric traumatic cerebrospinal fluid rhinorrhea.

OBJECTIVE: To examine the methods of extracranial repair of traumatic defects in the cribriform plate and ethmoid roof resulting in persistent cerebrospinal fluid (CSF) rhinorrhea in pediatric patients. DESIGN: Retrospective case series. SETTING: A single-institution, tertiary care, pediatric hospital. PATIENTS: Four children, ranging in age from 3 1/2 to 9 years, who sustained fractures in the cribriform plate or ethmoid roof. INTERVENTION: Transnasal endoscopic repair in 4 patients, with 2 patients also undergoing external ethmoidectomy because of the large bony defect and the need for further exposure for repair. MAIN OUTCOME MEASURES: Time free from CSF leaks or recurrence, meningitis, and other postoperative complications. RESULTS: All patients except 1 have been free of recurrent CSF leaks, meningitis, and other postoperative complications. The 3 patients who solely underwent the extracranial approach did not experience the complications of the traditional intracranial approach. CONCLUSIONS: In a select group of pediatric patients, the extracranial approach for the repair of CSF leaks is appropriate. Successful use of an extracranial approach in 3 of 4 patients supports this method.

An evidence-based evaluation of the use of sodium bicarbonate during cardiopulmonary resuscitation.

The use of bicarbonate is rooted in three decades of clinical experience and observational studies. For many years, bicarbonate passed the tried and true test for clinical therapies; however, administration of sodium bicarbonate during cardiac arrest and hypoxic acidosis has become increasingly controversial. The controversy provides an excellent opportunity to evaluate the impact an evidence-based approach might have on a common clinical practice. Is bicarbonate efficacious in the treatment of the severe acidosis that accompanies cardiac arrest during cardiopulmonary resuscitation (CPR)? Are the deleterious effects of bicarbonate clinically relevant? What is the evidence upon which a rational decision may be based? This review evaluates and ranks the evidence supporting the use of sodium bicarbonate in the therapy of acidosis associated with cardiac arrest during CPR.

Pulmonary capillary pressure. Clinical implications.

Pulmonary capillary pressure (Pcap) is the true edema-forming pressure within the pulmonary vascular bed. Pulmonary artery occlusion pressure has long been used to approximate Pcap. These two pressures may not always be well correlated, which has significant implications for fluid resuscitation and the evolution of pulmonary edema. This article reviews the technique for bedside measurement of Pcap.

Evidence-based medicine. A tool for enhancing critical care practice.

Evidence-based medicine (EBM) involves caring for patients by explicitly integrating clinical research evidence with pathophysiologic reasoning, caregiver experience, and patient preferences. EBM is a style of practice and teaching which may also help plan future research. This article discusses the application of EBM to critical care.

Clinical and financial outcomes of lateral rotation low air-loss therapy in patients in the intensive care unit.

OBJECTIVE: To determine the clinical impact and cost-effectiveness of two lateral rotation low air-loss therapy beds and their supporting protocols in the treatment of critically ill patients. DESIGN: Retrospective-cohort (2:1 design) study consisting of chart reviews of patients on two types of lateral rotation low air-loss therapy and their protocols from January 1992 through July 1993. SETTING: Three intensive care units (ICUs) (30 medical and surgical beds) in a 506-bed community hospital. PATIENTS: Fifty-six critically ill patients admitted to the ICU and prescribed lateral rotation therapy. Patients treated on both beds were excluded from the study. MEASUREMENTS: Data were collected on age, sex, Acute Physiology and Chronic Health Evaluation II score, Therapeutic Intervention Scoring System on admission to the ICU, and the time interval (number of days) from ICU admission until placement on a specialty bed (Lag Time). Outcome measurements included presence of pneumonia, adult respiratory distress syndrome, and multiorgan system dysfunction during the ICU stay, and the number of intubation days, ICU hours, hospital length of stay, and mortality during hospitalization. RESULTS: Statistically significant differences in group outcomes were found as follows: (1) pneumonia (p = 0.001), (2) adult respiratory distress syndrome (p = 0.002), (3) hospital length of stay (p = 0.04), and (4) hospital costs (p = 0.0001). CONCLUSIONS: In this study, patients treated by a prevention protocol with the Restcue beds (Support Systems International, Inc., Charleston, S.C.) had better clinical and financial outcomes than patients treated on Biodyne beds (Kinetic Concepts, Inc., San Antonio, Texas) with a more restricted, cost-conscious protocol aimed primarily at patients who have or who are at a higher risk for severe pneumonia, presence of septic shock, or adult respiratory distress syndrome.

Beta Cell Replacement Therapy in the 1990's An Overview of Pancreatic and Islet Cell Transplantation.

The goal of pancreatic beta cell replacement therapy is to restore normoglycemia in insulinopenic Type I diabetics patients. Pancreas transplantation is now considered a therapeutic option for Type I diabetic patients. It can no longer be considered an experimental procedure. Although a number of techniques have been applied in an attempt to restore normal glucose metabolism in Type I diabetic patients, pancreatic transplantation is the only therapy that consistently achieves normal glycosylated hemoglobin levels, an accomplishment rarely if ever achieved with frequent insulin injections or insulin pump therapy. Restoration of normoglycemia can be accomplished by either selectively transplanting isolated pancreatic islet cells or by transplanting the pancreas, usually as a composite graft of duodenum and whole pancreas. At this time, the likelihood of achieving independence from insulin is greater with a whole pancreas transplant than with an islet transplant. However, considerable progress in the field of islet transplantation has been made. This chapter will review the state of pancreas and islet transplantation.