A microcosting study of the surgical correction of upper extremity deformity in children with spastic cerebral palsy

Objective: Determine healthcare costs of upper-extremity surgical correction in children with spastic cerebral palsy (CP). Method: This cohort study included 39 children with spastic CP who had surgery for their upper extremity at a Dutch hospital. A retrospective cost analysis was performed including both hospital and rehabilitation costs. Hospital costs were determined using microcosting methodology. Rehabilitation costs were estimated using reference prices. Results: Hospital costs averaged €6813 per child. Labor (50%), overheads (29%), and medical aids (15%) were important cost drivers. Rehabilitation costs were estimated at €3599 per child. Conclusions: Surgery of the upper extremity is an important contributor to the healthcare costs of children with CP. Our study shows that labor is the most important cost driver for hospital costs, owing to the multidisciplinary approach and patient-specific treatment plan. A remarkable finding was the substantial amount of rehabilitation costs.     

Bimodality of plasma apolipoprotein B levels in familial combined hyperlipidemia.

To investigate possible genetic influences on plasma apolipoprotein (apo) B levels in familial combined hyperlipidemia (FCHL), commingling analysis was performed on data from seven large kindreds, including 183 individuals. The overall frequency distribution of apo B was skewed and was compatible with the presence of two normally distributed subdistributions (mean values, 117 and 172 mg/dl). The analysis was repeated after stratification of individuals by low density lipoprotein (LDL) subclass phenotype. Among subjects with phenotype A (predominance of large, buoyant LDL), a single apo B distribution was found (mean, 115 mg/dl). Among subjects with phenotype B (predominance of small, dense LDL), the distribution was bimodal, with mean values, 116 and 167 mg/dl, similar to the unstratified data set. Thus the skewing of the overall apo B distribution in FCHL family members may be due to a distinct subset of individuals with phenotype B who are genetically susceptible to even higher elevations of apo B. The higher apo B/phenotype B subjects also showed significantly higher levels of triglyceride and LDL-cholesterol than the lower apo B/phenotype B subjects. The lower apo B/phenotype B subjects had higher triglyceride and lower LDL-cholesterol than the phenotype A subjects. The enhanced information regarding apo B and lipid levels in the three subgroups of individuals identified here may facilitate a better understanding of genetic susceptibility to coronary heart disease.     

An additional breakpoint region in the BCL-1 locus associated with the t(11;14)(q13;q32) translocation of B-lymphocytic malignancy

The t(11;14)(q13;q32) translocation is associated with human B- lymphocytic malignancy. This translocation divides the IgH locus on chromosome 14q32 and may activate a postulated proto-oncogene, bcl-1, located on chromosome 11q13. Two samples of chronic lymphocytic leukemia with the t(11;14)(q32;q13) translocation were studied. The break in one sample was shown to join Jh sequences with the previously described bcl-1 major translocation cluster. DNA blots of the second sample suggested that Jh sequences were joined to a different breakpoint region on chromosome 11. This translocation was cloned and found to link the human Jh3 region and a new breakpoint region 63 kb telomeric of the major translocation cluster. This translocation occurred in part as the result of an aberrant D-J recombination. Recurrent translocations human B-lymphocytic malignancy. The definition of a new breakpoint region may aid the identification of the postulated bcl-1 gene.     

Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size.

Oxidative modification of low density lipoproteins (LDL) has been implicated in the sequence of events leading to fatty streak formation in the arterial intima. Increased oxidative modifications of dense versus buoyant LDL particles could contribute to increased atherosclerosis associated with lipoprotein profiles enriched in small, dense LDL. In the present studies, we compared rates of copper-induced oxidative changes for six LDL subfractions ranging in density from 1.023 to 1.053 g/ml and mean particle diameter from 282 +/- 10 to 245 +/- 3. Rates of formation of thiobarbituric acid-reactive substances (TBARS), as indicated by the time required for half-maximal TBARS formation (T1/2max), decreased with increasing density and decreasing particle diameter to a minimum in fraction 5 (d = 1.046 g/ml, diameter = 250 +/- 5) (P = 0.007). In parallel studies using unfractionated LDL (d = 1.019-1.063 g/ml), T1/2max values were inversely correlated with the predominant LDL species diameter as determined by 2-16% gradient gel electrophoresis (P less than 0.05), consistent with the involvement of subclass composition in determining oxidative behavior. In separate experiments, subfraction differences in oxidation rates as assessed by TBARS formation were verified by the finding of similarly dispartate changes in fluorescence intensity and anionic electrophoretic mobility. T1/2max values were not related to LDL contents of alpha-tocopherol, beta-carotene, protein, triglycerides or phospholipids, but were significantly correlated with unesterified cholesterol content (r = 0.46; P less than 0.001) and were inversely associated with cholesteryl ester content (r = 0.28; P less than 0.05). The positive association of T1/2max with unesterified cholesterol suggests that this constituent may impart resistance to oxidative modification, possibly by altering properties of the surface monolayer where it resides.     

Platelets interact with fibrin only after activation

Interactions between platelets and fibrin have been visualized by phase contrast, epifluorescence, and scanning electron microscope examination of clots formed with dansylcadaverine-labeled fibrin and gel-filtered platelets. After thrombin activation, the platelets appeared as fluorescent aggregates with bridging strands of fibrin; formaldehyde- fixed platelets were not fluorescent under the same experimental conditions. Scanning electron micrographs demonstrated that thrombin- activated cells had numerous pseudopods to which the fibrin strands adhered; fixed platelets exhibited a smooth discoid appearance and did not interact with the clot. Platelets trapped in clots formed with Batroxobin (Pentapharm) (platelets are not activated by Batroxobin as confirmed by light-scattering aggregometry measurements) remained as nonfluorescent, discoid cells, whereas platelets first activated by adenosine diphosphate formed brightly fluorescent aggregates. Light- scattering data of thrombin activation (0.2 U/mL) indicated that preincubation of platelets with 0.1 mmol/L prostaglandin E1 (PGE1) prior to addition of thrombin decreased the extent and rate of platelet shape change and resulted in 100-fold slower aggregation. Clots formed in the presence of PGE1 revealed decreased fluorescence intensity and fewer platelet-fibrin contacts. Gly-Pro-Arg-Pro, which blocks fibrinogen binding and fibrin assembly, was also effective in blocking platelet-fibrin interactions. These results indicate that platelet activation is a prerequisite for attachment of platelets to fibrin.     

Acute hemodynamic and antiischemic effects of intravenous amiodarone

The acute hemodynamic and antiischemic properties of amiodarone were investigated in 16 patients with more than 70% diameter reduction of a left coronary artery. Two successive atrial pacing stress tests (APST I and II) were performed, with an interval of 40 minutes in between, and amiodarone, 5 mg/kg/5 min, was infused 30 minutes after APST I. Hemodynamic changes during amiodarone administration consisted of a 20% decrease in left ventricular (LV) systolic pressure, a 13% decrease in systemic vascular resistance and an 18% decrease in stroke work. Coronary vascular resistance was reduced 19% and coronary sinus flow increased 23%. Despite a secondary 14% increase in heart rate, contractility decreased 21%, accompanied by a 45% increase in LV end-diastolic pressure, which persisted until APST II. Although most hemodynamic changes were observed only during the infusion, contractility and LV systolic pressure were still diminished at the beginning of APST II and remained so during pacing, resulting in a reduction in myocardial oxygen demand compared to APST I. Although overall myocardial oxygen consumption and coronary flow were equal during both pacing tests, amiodarone significantly reduced pacing-induced myocardial ischemia. Lactate metabolism remained normal during APST II (lactate extraction 12 +/- 3% vs -28 +/- 8% (APST I) at maximal pacing rates [p less than 0.05]), while ST-segment depression, LV end-diastolic pressure postpacing and angina were also significantly reduced during APST II. Thus, in humans, intravenous amiodarone reduces vascular resistance and contractility and inhibits pacing-induced myocardial ischemia, presumably by reducing myocardial oxygen demand.     

Degranulation and abnormal bactericidal function of granulocytes procured by reversible adhesion to nylon wool

Granylocyte bactericidal capacity, chemotaxis, hexose monophosphate shung activity (before and after phagocytic stimulus), and quantitative nitroblue tetrazolium reduction and enzyme content were examined in cells obtained by filtration leukaphresis (FL) and continuous-flow centrifugation (CFC). A decrease in the bactericidal efficiency of FL- produced cells compared to that of both normal and CFC-procured granulocytes was found; the decrease was 17% with a cell-to-bacteria ratio of 5:1, and 55% with a 1:1 ratio. Moreover, FL-acquired cells were often vacuolated and consistently contained less acid phosphatase and beta-glucuronidase than did normal granulocytes. When normal cells were incubated for 1-2 hr with nylon wool, 30% of the total acid phosphatase and beta-glucuronidase was released, with no evidence of cell death, thus suggesting degranulation. Similar results were obtained with glass, cotton, or polysulfone plastic fibers. Electron microscopic and peroxidase cytochemical studies of the adherence of normal granulocytes to nylon fibers were also carried out. After 30 min of incubation, cell-to-fiber attachment and cellular aggregation had occurred, although the cells per se appeared normal. After 60 and 120 min, other changes became apparent: (1) a decrease in the amount of cytoplasmic granules; (2) large, intracytoplasmic vaculoles; and (3) extracellular peroxidase on fiber surfaces. We conclude that granulocytes obtained by adherence to nylon fibers show both morphological and biochemical evidence of degranulation and diminished bactericidal capacity, and that these abnormalities may be causally related to decreased granulocyte survival in transfusion recipients.     

Differential transesophageal echocardiographic diagnosis between linear artifacts and intraluminal flap of aortic dissection or disruption

BACKGROUND: The relatively low specificity of transesophageal echocardiography (TEE) for the diagnosis of aortic dissection (AD) or traumatic disruption of the aorta (TDA) has been attributed to linear artifacts. We sought to determine the incidence of intra-aortic linear artifacts in a cohort of patients with suspected AD or TDA, to establish the differential TEE diagnostic criteria between these artifacts and true aortic flaps, and to evaluate their impact on TEE diagnostic accuracy. METHODS AND RESULTS: During an 8-year period, patients at high risk of AD (n = 261) or TDA (n = 90) who underwent a TEE study and had confirmed final diagnoses were studied. In an initial retrospective series, linear artifacts were observed within the ascending and descending aorta in 59 of 230 patients (26%) and 17 of 230 patients (7%), respectively. TEE findings associated with linear artifacts in the ascending aorta were as follows: displacement parallel to aortic walls; similar blood flow velocities on both sides; angle with the aortic wall > 85 degrees; and thickness > 2.5 mm. Diagnostic criteria of reverberant images in the descending aorta were as follows: displacement parallel to aortic walls, overimposition of blood flow, and similar blood flow velocities on both sides of the image. In a subsequent prospective series (n = 121), systematic use of these diagnostic criteria resulted in improved TEE specificity for the identification of true intra-aortic flaps. CONCLUSIONS: Misleading intra-aortic linear artifacts are frequently observed in patients undergoing a TEE study for suspected AD or TDA. Routine use of the herein-proposed diagnostic criteria promises to further improve TEE diagnostic accuracy in the setting of severely ill patients with potential need for prompt surgery.