Myocardial perfusion and function in dogs with moderate coronary stenosis

MRI studies of first-pass contrast enhancement with polylysine-Gd-DTPA and myocardial tagging using spatial modulation of magnetization (SPAMM) were performed to assess the feasibility of a combined regional myocardial blood flow and 2D deformation exam. Instrumented closed-chest dogs were imaged at a baseline control state (Cntl) followed by two interventions: moderate coronary stenosis (St) achieved by partial occlusion of the left anterior descending (LAD) and moderate coronary stenosis with dobutamine loading (StD). Hypoperfusion of the anterior region (ANT) of the myocardium (LAD distribution) relative to the posterior wall (POS) based on the upslope of the signal intensity time curve from the contrast-enhanced MR images was demonstrated only with dobutamine loading (ANT:POS Cntl=1.077 ± 0.15 versus ANT:POS StD=0.477 ± 0.11, P<0.03) and was confirmed with radio-labeled microspheres measurements (ANT:POS Cntl=1.18 ± 0.2 ml/min/g versus ANT:POS StD=0.44 ± 0.1 ml/min/g; P<0.002). Significant changes in regional myocardial shortening were only seen in the StD state (P<0.02); the anterior region showed impaired myocardial shortening with dobutamine loading (P=NS), whereas the nonaffected POS region showed a marked increase in shortening when compared with Cntl (Cntl=0.964 ± 0.02 versus StD=0.884 ± 0.03; P<0.001). These results demonstrate that an integrated quantitative assessment of regional myocardial function and semiquantitative assessment of myocardial blood flow can be performed noninvasively with ultrafast MRI.     

Evolution of resource competition between mutually dependent digital organisms

We study the emergence and dynamics of competing strains of digital organisms in a world with two depletable resources. Consumption of one resource produces the other resource as a by-product, and vice versa. As a consequence, two types of mutually dependent organisms emerge that each prey on the waste product of the other. In the absence of mutations, that is, in a purely ecological setting, the abundances of the two types of organisms display a wide range of different types of oscillations, from regular oscillations with large amplitude to irregular oscillations with amplitudes ranging from small to large. In this regime, time-averaged abundance levels seem to be controlled by the relative fitness of the organisms in the absence of resources. Under mutational pressure, on the other hand, populations evolve that seem to avoid the oscillations of intermediate to large amplitudes. In this case, the relative fitness of the organisms in the presence of resources plays an important role in the time-averaged abundance levels as well.     

Multiplex polymerase chain reaction.

The polymerase chain reaction (PCR) is a widely utilized assay for specifically amplifying small fragments of DNA. Multiplex PCR is the amplification of more than one DNA fragment per reaction and has many potential uses. When more than one primer set per reaction tube is utilized, the total number of tubes in any one experiment may be reduced, conserving expensive reagents and decreasing possible contamination. Multiplex PCR allows for an assay of the gene of interest and assures that the amplification process proceeds as expected with the use of a companion control genome primer set. Multiplex PCR is useful in assaying DNA extracted from samples of immunocompromised patients in which more than one infectious agent may be suspected such as simultaneous EBV and CMV detection. Multiplex PCR offers many advantages over single reaction PCR and has been found to be an useful adjunct in our laboratory.     

Rapid rise in plasma glucagon induced by acute cold exposure in man and rat

The effect of acute cold exposure on the concentration of glucagon in the blood was investigated in man and in intact and adrenalectomized rats.In man fasted overnight acute cold exposure, which caused a twofold increase in O₂-consumption resulted in a rapid rise in plasma glucagon. The levels of insulin and blood glucose remained unaltered, while the concentration of serum free fatty acids and -hydroxybutyrate increased.In fasted intact rats acute cold exposure lead to similar effects. A close parallelism between the rise in plasma glucagon and the concentration of hepatic cycloAMP was observed. Adrenalectomy did not impair the cold induced rise in plasma glucagon and hepatic cycloAMP.It is concluded that acute cold exposure caused a rapid rise in the concentration of plasma glucagon leading to an increase in the concentration of hepatic cycloAMP, thus enhancing the rate of hepatic gluconeogenesis and ketogenesis. As these alterations were similar in the absence of glucocorticoids and medulla-derived catecholamines, it is suggested that glucagon may play a role in the metabolic adaptation to acute cold exposure.     

Effect of dynamization on gap healing of diaphyseal fractures under external fixation

We asked whether dynamization of externally fixed diaphyseal fractures could improve bone healing in comparison to rigid fixation of fractures having similar remaining gap sizes. To answer this question we evaluated metatarsal osteotomies in 12 sheep. The osteotomy with a 0.6-mm gap was stabilized with a specially designed high bending and torsional stiffness external ring fixator. Osteotomies in six sheep were stabilized rigidly (axial movement < 0.06 mm) or dynamically (axial movement 0.15-0.34 mm). The cyclical axial interfragmentary movement was caused by the load-bearing of the operated limb. With increasing healing time, the initially allowed movement was decreased by callus formation around the osteotomy. The reduction in interfragmentary movement was measured and monitored by a linear variable displacement transducer at the external fixator and a telemetry system. After 9 weeks the sheep were sacrificed and the healed bones were investigated biomechanically and histomorphologically. Compared to the rigidly fixed osteotomies, the dynamized osteotomies showed significantly (P < 0.05) greater (+41%) callus formation and 45% greater tensile strength of the newly formed bone in the cortical osteotomy gap. Histological analysis indicated that the effect of dynamization occurred mainly after the 5th week. RELEVANCE: From these results we conclude that dynamic fixation of diaphyseal gaps is advantageous in comparison to stable external fixation.     

Prevalence of hypovitaminosis a in children of peripheral districts of Campinas São Paulo, Brazil

The prevalence of hypovitaminosis A among children of the peripheral districts of the city of Campinas, S o Paulo, Brazil, was estimated by determining serum retinol levels by High Performance Liquid Chromatography (HPLC) in a sample of 131 children aged between three and ten years, between April 1991 and February 1992. A prevalence of 17.6% and retinol concentrations in the range of 0.35 to 0.70 micromol/L were found (CI=11.1-24.1; 95%), indicating the existence of public health risk Ophthalmological examinations, however, failed to detect any cases of xerophthalmy. Additional characterization of the sample was obtained from 341 children. The per capita income of the average household was surprisingly high for low-income areas. According to FAO-WHO standards, food consumption was adequate only for protein (133.96%). Adequacy levels were low for energy (87.76%) and particularly for vitamin A (66.13%) and iron (42.14%). Height for-age and weight-for-height anthropometric indices revealed that many children were located below -1 standard deviation.     

Effects of specimen length on the monosegmental motion behavior of the lumbar spine

STUDY DESIGN: An in vitro biomechanical analysis of the segmental motion behavior of the same segments in polysegmental (five segments), bisegmental, and monosegmental specimens using sheep lumbosacral spines. OBJECTIVES: To investigate the effect of specimen length on monosegmental motion behavior. These data may be helpful in planning in vitro tests and in comparing results of studies using specimens of different lengths. SUMMARY OF BACKGROUND DATA: The length of spinal specimens used for in vitro stability tests varies greatly, depending on the purpose of the study. Some investigators prefer testing specimens with one adjacent segment on either end of the region of interest. Others favor specimens as short as possible. METHODS: In a first step, seven sheep spine specimens, L3-S1 (note that sheep spines normally have seven lumbar vertebrae), each were tested without preload in a spine-loading apparatus. Alternating sequences of pure lateral bending, flexion/extension, and axial rotation moments (+/-3.75 Nm) were applied continuously. The motion in each single segment was measured simultaneously. Then, these polysegmental specimens were cut into two bisegmental specimens, L3-L5 and L6-S1, and tested in the same way. Finally, another vertebra was removed to obtain two monosegmental specimens, L3-L4 and L7-S1, and to test them as described. RESULTS: In general, the range of motion at L3-L4 and L7-S1 was smaller when tested in polysegmental than in monosegmental specimens. In polysegmental specimens (five segments), the range of motion at L3-L4 and L7-S1 was approximately 80% (range, 70.6-92.5%) and in bisegmental specimens approximately 95% (range, 66.7-100%) of their range of motion measured in monosegmental specimens. Neutral zone and coupled motions showed the inverse behavior. Significant differences were found. However, they were not consistent with either the loading direction or with the specimen length. CONCLUSIONS: For comparison of results, the specimen length should be kept constant within one experiment. Segmental motion behavior of specimens with different lengths should be compared only qualitatively.     

Modulation of 5-fluorouracil with methotrexate and low-dose N-(phosphon-acetyl)-L-aspartate (PALA) is inactive in advanced pancreatic carcinoma

Purpose: To evaluate the effect of biochemical modulation by PALA and methotrexate on the therapeutic activity of 5-fluorouracil (5-FU) in patients with advanced pancreatic adenocarcinoma.Patients and methods: The treatment protocol consisted of phosphonacetyl-L-aspartate (PALA) 250 mg/m² i.v. 15-minute infusion followed by methotrexate 200 mg/m² i.v. 30-minute infusion on day 1 and 5-FU 600 mg/m² i.v. push on day 2. Folinic acid was given at 15 mg/m² p.o. every six hours for eight doses, starting 24 hours after methotrexate infusion. Cycles were repeated every two weeks.Results: Thirty patients with advanced chemotherapy-naive pancreatic cancer were included; 26 had measurable disease. Median age 56 years (27–72); median PS 1 (0–2). One PR (3.9%) was achieved; nine patients had stable disease. Median time to progression was 91 days. Median survival was 177 days and one year survival was 13.3% (4 of 30 patients). Treatment was well tolerated; diarrhea WHO grade 2 or 3 occurred in six patients; stomatitis WHO grade 2 and 3 in nine patients.Conclusions: Modulation of 5-FU by PALA and MTX given in this dose and schedule appears to be ineffective in patients with advanced pancreatic adenocarcinoma.     

Paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil plus leucovorin in the second-line treatment of metastatic breast cancer: Results of a phase II study

Purpose: To evaluate the antitumor activity in terms of response rate (RR), time to progression (TTP) and survival of paclitaxel in combination with weekly 24-hour infusional 5-fluorouracil (5-FU)/leucovorin in pretreated metastatic breast cancer (MBC).Patients and methods: Fifty-four patients with bidimensionally measureable disease were included during phase II. Thirty-two had anthracycline resistant disease. Treatment consisted of 5-FU (24-hour i.v. infusion) 2.0 g/m², leucovorin (two-hour i.v. infusion prior to 5-FU) 500 mg/m², weekly for six weeks (day 1, 8, 15, 22, 29, 36) and paclitaxel (three-hour i.v. infusion) 175 mg/m² was administered additionally on days 1 and 22, q 50 days.Results: We observed complete remissions in 4% of patients (2 of 54), partial remissions in 55% (30 of 54), stable disease in 37% (20 of 54) and progressive disease in 4% (2 of 54). The overall RR was 59% (95% CI 48%–72%). The RR in 32 patients with anthracycline resistant disease was 59% (19 of 32). The median duration of response was 12 months (3–22), median TTP eight months (2–22) and median survival time 15 months (2–28). Neutropenia was common, but of CTC grade 2 or 3 in most patients. Nonhematologic toxicities mostly consisted of CTC grade 1 and 2 myalgia, diarrhea, mucosits, nausea and vomiting.Conclusions: Paclitaxel combined with weekly 24-hour infusional 5-FU/leucovorin is well tolerated in the second line treatment of MBC. High efficacy was documented even in the treatment of anthracycline resistant disease, which warrants further evaluation.