Cardiac magnetic resonance imaging in small animal models of human heart failure

The aim of this study was to test the feasibility of cine magnetic resonance imaging (MRI) for assessment of the infarcted rat and mouse heart and to compare the results with established methods. These models have been proven to predict genesis and prevention of heart failure in patients. The value of cine MRI was tested in studies investigating interventions to change the course of the remodeling process. MRI was performed for determination of left ventricular (LV) volumes and mass, myocardial infarct (MI) size and cardiac output. LV wet weight was determined after MRI. Rats underwent conventional hemodynamic measurements for determination of cardiac output and LV volumes by electromagnetic flowmeter and pressure-volume curves. Infarct size was determined by histology. MRI-acquired MI-size (18.5+/-2%) was smaller than that found by histology (22.8+/-2.5%, p<0.05) with close correlation (r=0.97). There was agreement in LV mass between MRI and wet weight (r=0.97, p<0.05) and in the MRI- and flowmeter measurements of cardiac output (r=0.80, p<0.05). Volume by MRI differed from pressure-volume curves with good correlation (r=0.96, p<0.05). In a serial study of mice after coronary ligation, LV hypertrophy at 8 weeks was detected (Sham 105.1+/-7.9 mg, MI 144.4+/-11.7 mg, p<0.05). Left ventricles were enlarged in infarcted mice (end-diastolic volume, week 8: Sham 63.5+/-4 microl, MI 94.2 microl, p<0.05). In conclusion, cine MRI is a valuable diagnostic tool applicable to the rat and mouse model of MI. Being non-invasive and exact it offers new insights into the remodeling process after MI because serial measurements are possible. The technique was applied to study several interventions and proved its usefulness.     

Do we need new indications for ECMO in neonates pretreated with high-frequency ventilation and/or inhaled nitric oxide?

OBJECTIVE: High-frequency ventilation (HFV) and/or inhaled nitric oxide (iNO) has reduced ECMO in neonates. But, frequently, improvement with HFV/iNO is temporary and only prolongs lung injury without preventing ECMO. We tried to identify a threshold oxygenation index (OI) that predicts temporary or persistent improvement with HFV/iNO in neonatal ECMO candidates as early as possible. DESIGN: Cohort study of all neonates with OI > 40 during intermittent positive pressure ventilation between 1992 and 1997. The first treatment was HFV; at an OI > 40 during HFV, iNO was added; at an OI > 40 during HFV+iNO, ECMO was initiated. Temporary improvement was defined as secondary need for ECMO or fatal chronic lung disease without ECMO. SETTING: University hospital level III neonatal intensive care unit. MAIN RESULTS: Ten of the 34 neonates studied rapidly required ECMO despite HFV/iNO. Eleven neonates temporarily improved for 1-10 days before the OI was again > 40. Nine received ECMO, two were denied ECMO after mechanical ventilation > 14 days and died of chronic lung disease. Thirteen neonates persistently improved with HFV/iNO without ECMO. The OI before, at 24 h or 48 h of HFV/iNO did not predict temporary or persistent improvement. However, after 72 h of HFV/iNO, neonates with persistent improvement had lower OIs than those with temporary improvement [median OI 16 (4-24) vs 31 (20-40); P = 0.0004]. In all neonates with an OI > or = 25 after 72 h, HFV/iNO eventually failed (positive predictive value 100%, sensitivity 91 %, specificity 100%, positive likelihood ratio 91). CONCLUSION: For neonates pretreated with HFV/iNO, an OI > 40 is an inadequate ECMO indication. Based on our data we hypothesize that an OI > or = 25 after 72 h of HFV/ iNO is a better ECMO indication that avoids prolonged barotrauma.     

Impact of family structure on long-term survivors of osteosarcoma

Goals of work Long-term outcomes of osteosarcoma have dramatically improved with the use of modern combination therapies. Such aggressive treatments, however, entail chronic complications. In the present study, we assessed the functional, psychological, and familial status of long-term survivors of osteosarcoma treated at our institution. Materials and methods Fifteen long-term survivors of osteosarcoma were evaluated for functional and psychological sequelae. Functional assessment was based on a method described by Enneking et al. Psychological assessment was based on General Health Questionnaire 28, Inventory Scale for Traumatic Neurosis, and Family System Test. Main results Ten patients showed mild functional impairments; only five patients were handicapped more seriously. Depressive symptoms were diagnosed in four patients. A total of six patients revealed unbalanced family structures, including three of the four patients with depressive symptoms, all four patients with symptoms of posttraumatic stress disorder, and five of seven patients who showed poor emotional acceptance. Conclusions Osteosarcoma survivors will generally recover good functional performance. Only a minority of them remain seriously impaired. One third of the patients present depressive symptoms and posttraumatic stress disorder. Poor coping is closely associated with unbalanced family structures. Therefore, the psychological and familial situation of patients with newly diagnosed osteosarcoma should be carefully assessed.     

Collection of a mobilized peripheral blood apheresis product from a patient with mucopolysaccharidosis type VII and subsequent CD34+ cell isolation

The effectiveness of bone marrow transplantation for lysosomal storage diseases like mucopolysaccharidosis type VII (MPSVII) suggests that a gene therapy strategy targeting autologous hematopoietic progenitor cells could be successful. Given the severe systemic manifestations of MPSVII including storage disease in the bone and bone marrow, it was unclear whether sufficient numbers of hematopoietic progenitor cells (CD34+) could be mobilized into the peripheral circulation and subsequently purified from these patients. As reported here, G-CSF mobilization and apheresis were successful, providing a product of 4 x 10(10) nucleated cells containing 0.3% CD34+ progenitors. CD34+ cells were magnetically separated from the product to a final purity of 85% with a 64% yield. These results indicate that hematopoietic progenitors can safely be gathered from an MPSVII patient in numbers sufficient for the trial of clinical gene therapy applications.     

Reported practice behaviors for medical care of patients with diabetes mellitus by primary-care physicians in Pennsylvania

OBJECTIVE: To compare the American Diabetes Association standards for the medical care of diabetic patients with reported care patterns. RESEARCH DESIGN AND METHODS: These standards were compared with reported care patterns obtained from a stratified random telephone survey of general practitioners, family physicians, and general internists in Pennsylvania. A total of 610 physicians completed the survey for a response rate of 73%. RESULTS: All primary-care physicians reported measurement of glycosylated hemoglobin, routine referrals to eye doctors, and patient self-monitoring of blood glucose less than recommended. Nearly all physicians performed foot exams, but the exams were infrequent for many of the physicians. Significant and independent differences (P less than 0.05) were noted between different groups of physicians. Older physicians and general practitioners reported patterns of care most different from the recommended standards for referral to eye doctors, measurement of glycosylated hemoglobin, and use of patient self-monitoring of blood glucose. General practitioners reported the lowest frequency of foot exams. CONCLUSIONS: Educational programs on diabetes for primary-care physicians should focus on reported behaviors most different from recommended standards and may need to target subgroups of physicians to achieve a more uniform level of care for all diabetic patients.