Ultrastructural characterization of the border zone surrounding early experimental myocardial infarcts in dogs.

The existence of a border zone composed of reversibly injured myocardium surrounding an evolving infarct has been the subject of controversy. In experiments designed to search for such a border zone by electron microscopy, 12 mongrel dogs underwent permanent ligation of the left anterior descending coronary artery (LAD). Two to 6.5 (average = 4.2) hours later, the hearts were excised, the area at risk (myocardium perfused by the LAD) was outlined by injection of fluorescent microspheres, and the myocardial infarct was demonstrated by the nitro blue tetrazolium (NBT) gross histochemical method. Myocardial samples for electron-microscopic study were obtained from the periphery of the infarct (tissues unstained by NBT) and serially from the immediately adjacent myocardium, which was stained deep blue by NBT. Grossly, the infarcts always involved the subendocardial myocardium, extended for a variable distance in the epicardial direction, and closely approximated the lateral margins of the area at risk. When examined by electron microscopy, the infarct periphery showed evidence of irreversible damage, thus confirming the ability of NBT to detect early myocardial necrosis. Multiple samples of the NBT-stained myocardium immediately adjacent to the infarct showed varying degrees of reversible ischemia, thus demonstrating, at the ultrastructural level, the existence of a border zone of intermediate myocardial injury. This border zone was substantial (3--4 mm in width) along the subepicardial aspect of the infarct and very thin (1--2 mm) laterally. In conclusion, a significant border zone was demonstrable by electron microscopy in the subepicardial myocardium of 8 out or 12 canine hearts with recent coronary artery occlusion. In the remaining 4 hearts, the infarcts had already reached the epicardium at the time of study, and only a thin lateral border zone was present.     

Breast cancer detection: one versus two views

Mammographic examinations of 169 patients with 172 biopsy-proved carcinomas, and of 194 healthy subjects, were interpreted independently and retrospectively by three experienced mammographers, initially as single-view oblique examinations and 6 months later as two-view oblique-cephalocaudal examinations. For the single-view examinations of the cancer patients, 67% of the cancers were correctly recommended for biopsy, additional views were requested for 23%, and a "negative" interpretation was made for 10%. For the single-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were recommended for 32%. For the two-view examinations of women with cancer, 80% of the cancers were correctly recommended for biopsy, additional views were requested for 4%, and a "negative" interpretation was made for 16%. For two-view examinations of healthy subjects, biopsy was recommended for 7% and additional views were requested for only 5%. The authors conclude that single-view screening should not be performed, because it would lead to an excessive number of "call-back" examinations of healthy patients, producing additional cost and anxiety that would outweigh any theoretical benefit.     

Striated intramural gallbladder lucencies on US studies: predictors of acute cholecystitis

Ultrasound scans of 51 consecutive patients with gallbladder wall thickening were reviewed, and specific sonographic features were correlated with surgical and clinical follow-up. Two patterns of thickening were identified as specific indicators of the presence or absence of acute cholecystitis. "Striated" wall thickening, consisting of several alternating, irregular, discontinuous, lucent and echogenic bands, was seen in eight of 13 patients (62%) with acute cholecystitis. This pattern was not encountered in any of the patients who did not have acute cholecystitis. Conversely, "three-layer" thickening, consisting of a single circumferential lucent zone between two relatively uniform echogenic layers, was seen in only one of 13 patients (8%) with acute cholecystitis but in 11 of 38 patients (29%) with other diagnoses. Other abnormalities, including the presence of intramural echogenic foci and wall irregularities, were more frequently seen in patients with acute cholecystitis but were not as helpful. Use of these features may suggest or help exclude a diagnosis of acute cholecystitis in those patients in whom the cause of gallbladder wall thickening is otherwise not apparent.     

A randomized trial of high-dose methotrexate versus standard-dose methotrexate following cyclophosphamide, doxorubicin (adriamycin), vincristine, and prednisone with or without bleomycin in the therapy of diffuse large cell lymphoma: preliminary report of Cancer and Leukemia Group B Study 7851

Between 1979 and 1985, 166 patients with diffuse large cell (histiocytic) lymphoma were randomized to receive therapy with 3 courses of cyclophosphamide, doxorubicin (Adriamycin), vincristine, and prednisone (CAVP), with or without low-dose bleomycin, by continuous iv infusion. Responders were further randomized to 3 weeks of therapy with either high-dose methotrexate (3 g/m2 iv weekly with leukovorin rescue) or low-dose methotrexate (30 mg/m2 orally weekly without rescue). Therapy was concluded with 3 additional courses of CAVP. No significant differences among the 4 treatment programs were observed in complete response rates (ranging from 46% to 51%) or in failure-free survival. Of the 38 relapses that have occurred in patients treated with low-dose methotrexate, 5 included relapse in the central nervous system in conjunction with systemic relapse. However, none of 31 relapses observed in patients receiving high-dose methotrexate have occurred with involvement of the central nervous system. Patients entering this study with "B" symptoms had significantly poorer treatment results than those patients entering study without "B" symptoms.     

"True" high-tension electrical injuries

A series of 48 patients with high-voltage electrical injuries managed over a six-month period was reviewed. The line voltage at the time of injury was recorded for 40 of the patients, with an average of 14,200 volts. The mean duration from injury to admission was 11 hours. The study group of 48 patients was readily divided into two subgroups: a majority (31) sustained a "true" high-voltage, prolonged contact electrical injury, and a smaller subgroup (17) sustained flash and clothing burns. There was no difference between the two subgroups in the magnitude of voltage exposure. However, patients in the "true" high-voltage subgroup sustained a wide variety of injuries to almost every organ system. Transient EKG abnormalities were noted in 16 patients. The occurrence of myoglobinuria and/or hemoglobinuria was nearly universal and was treated by volume expansion alone without bicarbonate or mannitol. Resuscitation of the "true" group required an average of 7 cc/kg/% BSA of Ringer's lactate. No incidence of acute tubular necrosis was observed. Initial debridement was almost always performed on patients in the "true" subgroup on the day of admission. Flap coverage and/or amputation was required in 70% of these 31 patients. Wound management required an average of 2.4 debridements and 2.2 wound closure procedures. There was no evidence of delayed or progressive tissue necrosis. The principles of resuscitation and aggressive operative management are discussed.     

Low-Dose ATG/GCSF in Established Type 1 Diabetes: A Five-Year Follow-up Report

Previously, we demonstrated low-dose antithymocyte globulin (ATG) and granulocyte colony-stimulating factor (GCSF) immunotherapy preserved C-peptide for 2 years in a pilot study of patients with established type 1 diabetes (n = 25). Here, we evaluated the long-term outcomes of ATG/GCSF in study participants with 5 years of available follow-up data (n = 15). The primary end point was area under the curve (AUC) C-peptide during a 2-h mixed-meal tolerance test. After 5 years, there were no statistically significant differences in AUC C-peptide when comparing those who received ATG/GCSF versus placebo (P = 0.41). A modeling framework based on mean trajectories in C-peptide AUC over 5 years, accounting for differing trends between groups, was applied to recategorize responders (n = 9) and nonresponders (n = 7). ATG/GCSF reponders demonstrated nearly unchanged HbA_1c over 5 years (mean [95% CI] adjusted change 0.29% [–0.69%, 1.27%]), but the study was not powered for comparisons against nonresponders 1.75% (–0.57%, 4.06%) or placebo recipients 1.44% (0.21%, 2.66%). These data underscore the importance of long-term follow-up in previous and ongoing phase 2 trials of low-dose ATG in recent-onset type 1 diabetes.     

Hospital‐based health systems 20 years later: A taxonomy for policy research and analysis

ObjectiveBuilding on the original taxonomy of hospital‐based health systems from 20 years ago, we develop a new taxonomy to inform emerging public policy and practice developments.Data SourcesThe 2016 American Hospital Association''s (AHA) Annual Survey; the 2016 IQVIA Healthcare Organizations and Systems (HCOS) database; and the 2017‐2018 National Survey of Healthcare Organizations and Systems (NSHOS).Study DesignCluster analysis of the 2016 AHA Annual Survey data to derive measures of differentiation, centralization, and integration to create categories or types of hospital‐based health systems.Data CollectionPrincipal components factor analysis with varimax rotation generating the factors used in the cluster algorithms.Principal FindingsAmong the four cluster types, 54% (N = 202) of systems are decentralized (−0.35) and relatively less differentiated (−0.37); 23% of systems (N = 85) are highly differentiated (1.28) but relatively decentralized (−0.29); 15% (N = 57) are highly centralized (2.04) and highly differentiated (0.65); and approximately 9 percent (N = 33) are least differentiated (−1.35) and most decentralized (−0.64). Despite differences in calculation, the Highly Centralized, Highly Differentiated System Cluster and the Undifferentiated, Decentralized System Cluster were similar to those identified 20 years ago. The other two system clusters contained similarities as well as differences from those 20 years ago. Overall, 82 percent of the systems remain relatively decentralized suggesting they operate largely as holding companies allowing autonomy to individual hospitals operating within the system.ConclusionsThe new taxonomy of hospital‐based health systems bears similarities as well as differences from 20 years ago. Important applications of the taxonomy for addressing current challenges facing the healthcare system, such as the transition to value‐based payment models, continued consolidation, and the growing importance of the social determinants of health, are highlighted.     

Practice improves even the simplest movements

Summary Three subjects practiced accurate, fast elbow flexions of 54° to a 3° wide target. Movements of 36°, 54° and 72° were then tested. Comparison over the three distances showed that the normally monotonic relationship between movement distance and movement time is alterable by specific training. Subjects learn to go faster over the practiced distance by refining their neural commands to the muscles. The benefits of practice only partially transfer to other distances. We conclude that many of the relationships seen among movement variables in simple tasks are plastic in nature and affected by prior experience.     

In vitro assembly of infectious nucleocapsids of bacteriophage phi 6: formation of a recombinant double-stranded RNA virus.

A system is described for assembling infectious bacteriophage phi 6 nucleocapsids in vitro. Procapsids encoded by cDNA copies of genomic segment L in Escherichia coli were used to package and replicate viral RNA segments. The resulting filled particles were shown to be capable of infecting host cell spheroplasts after incubation with purified nucleocapsid shell protein P8. The infected spheroplasts yielded infectious virions. A modified cDNA-derived RNA segment was inserted into virions by this method. The resulting infectious virions contained the same 4-base-pair deletion as the modified cDNA. These findings support the contention that the preformed procapsids are the "machine" that replicates the phi 6 genome, by showing that the cDNA-derived procapsids are competent to package and replicate RNA properly.