Digital arterial occlusive disease and parvovirus B19 infection

We report a case of a 37-year-old white woman, who presented with digital arterial occlusions associated with parvovirus B19 infection. Two other member of the family presented acute febrile illness, polyarthralgia (husband), and erythema infectiosum (son) during the same month. This new report gives weight to the concept that acute human parvovirus infection could become part of the differential diagnosis of acute digital occlusive arteriopathy.     

Effect of weight loss on muscle fiber type, fiber size, capillarity, and succinate dehydrogenase activity in humans

To examine the effects of weight loss on muscle oxidative properties, nine obese subjects (body mass index, 34 +/- 1.5) had muscle biopsies before and after weight loss and weight stabilization. Weight loss ranged from 13-32 kg and represented 20.8 +/- 2.1% of initial weight. After weight loss, there was no change in the proportions of oxidative (type I and type IIa) fibers and also no change in mean fiber cross-sectional area, whereas there was a small, but significant, decrease in the relative interstitial space (P < 0.05). However, weight loss resulted in a 32 +/- 6% (mean +/- SEM) increase in capillary/fiber ratio and a 54% increase in capillary density (P < 0.05). In addition, there was a 41 +/- 13% increase in succinate dehydrogenase (SDH) activity (P < 0.05). This increase in muscle capillarization and SDH activity was seen in all fiber types, even the relatively lower oxidative type IIx fibers. There was a strong correlation between the change in capillary/fiber ratio and the change in SDH activity (r = 0.82; P < 0.02). Thus, weight loss resulted in no change in muscle fiber type or cross-sectional area, but produced increases in capillary/fiber ratio, capillary density, and SDH activity, suggesting an increase in muscle oxidative capacity.     

Fibroblast structure and function during regeneration from hormone-induced acute pancreatitis in the rat

The regeneration of the rat exocrine pancreas from a hormone-induced pancreatitis was investigated. In a previous study it was shown that the [3H]thymidine labeling index of interstitial cells increases 20- to 30-fold on day 1.5 after the induction of pancreatitis. Here we show by electron microscopic autoradiography that 80% of the labeled interstitial cells are fibroblasts. Their replication, fine structure, and collagen biosynthesis was further investigated: By day 2.5 numerous mitotic figures were found, indicating an enhanced proliferative activity of fibroblasts at the early stage of pancreatic regeneration. The ultrastructural analysis revealed that many fibroblasts contain abundant cytoplasm with a well-developed rough endoplasmic reticulum, prominent Golgi complexes, and secretory granules filled with fibrillar material. In contrast, the pancreatic fibroblasts of saline-infused control animals were shown to be spindle-shaped and to contain only very little cytoplasmic organelles. The collagen biosynthesis was quantified by in vivo labeling with [3H]proline and quantification of [3H]hydroxyproline in pancreatic protein hydrolysates. The collagen biosynthesis of experimental pancreata was measured to be 15 times that of controls on days 1.5 and 2.5 after the induction of pancreatitis and to remain fourfold elevated on days 3.5 through 10.5. In pulse-chase experiments using [3H]proline as the labeled precursor for collagen, the newly synthesized collagen was shown to be degraded with a half-life of 35 h. We conclude that replication of pancreatic fibroblasts and collagen biosynthesis as well as collagen degradation play important roles in the early phase of pancreatic regeneration.     

Effects of pharmacologic coronary hyperemia on echocardiographic left ventricular function in patients with single vessel coronary artery disease

To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricular wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 +/- 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group. Although intracoronary mean flow velocity measured in the 14 group 1 patients and in 5 normal control subjects during papaverine treatment increased from 125% to 400% of basal flow velocity, papaverine induced new left ventricular wall motion abnormalities in only 5 of the 14 patients before coronary angioplasty. In three of five patients, left ventricular wall motion abnormalities persisted after successful coronary angioplasty. Four of the 14 patients demonstrated augmentation of left ventricular wall motion with papaverine. After intravenous dipyridamole, only 3 of the 13 group 2 patients developed new left ventricular regional asynergy. These data suggest that selective (papaverine) and, most likely, global (dipyridamole) augmentation of coronary flow alone does not reliably identify potential ischemic left ventricular regions affected by critical single vessel coronary artery disease.     

Towards a pathogenesis-oriented therapy of acute myeloid leukemia

Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics by which three main subgroups can be discriminated: AML with balanced translocations, AML with unbalanced aberrations and AML without cytogenetically detectable aberrations. Within the latter group molecular alterations are identified in more than half of cases such as NPM mutations, FLT3 mutations, MLL duplications and mutations of CEBP-alpha. The clinical meaning of these findings is illustrated by substantial differences in response to therapy and long-term outcome. As demonstrated by the recent multicenter trial of the German AML Cooperative Group (AMLCG) and other studies intensification of induction therapy may improve the results in distinct subtypes but fails to do so in others. Therefore, new strategies need to be explored which incorporate the knowledge about the biology of AML to develop biology adapted treatment strategies. This process has just begun and is predominantly determined by the availability of new agents and their evaluation in clinical phase I and II studies. A variety of targets are currently explored and some trials have yielded promising results already. The step towards a biology adapted treatment of AML is long and requires the combined efforts of researchers, clinicians and the pharmaceutical industry. The first steps towards this goal have been taken and give rise to the hope for more effective and more specific therapies of AML.     

Intravenous adenosine: continuous infusion and low dose bolus administration for determination of coronary vasodilator reserve in patients with and without coronary artery disease

To assess the use of adenosine as an alternative agent for determination of coronary vasodilator reserve, hemodynamics and coronary blood flow velocity were measured at rest and during peak hyperemic responses to continuous intravenous adenosine infusion (50, 100 and 150 micrograms/kg per min for 3 min) and intracoronary papaverine (10 mg) in 34 patients (17 without [group 1] and 17 with [group 2] significant left coronary artery disease), and in 17 patients (11 without and 6 with left coronary artery disease) after low dose (2.5 mg) intravenous bolus injection of adenosine. The maximal adenosine dose did not change mean arterial pressure (-10 +/- 14% and -6 +/- 12% for groups 1 and 2, respectively) but increased the heart rate (15 +/- 18% and 13 +/- 16, respectively). For continuous adenosine infusions, mean coronary flow velocity increased 64 +/- 104%, 122 +/- 94% and 198 +/- 59% and 15 +/- 51%, 110 +/- 95% and 109 +/- 86% in groups 1 and 2, respectively for each of the three doses. Mean coronary flow velocity increased significantly after 100 and 150 micrograms/kg of adenosine and 10 mg of intracoronary papaverine (48 +/- 25, 52 +/- 19 and 54 +/- 21 cm/s, respectively; all p less than 0.05 vs. baseline) and was significantly higher than in group 2 (37 +/- 24, 32 +/- 16, 41 +/- 23 cm/s; all p less than 0.05 vs. group 1). The coronary vasodilator reserve ratio (calculated as the ratio of hyperemic to basal mean flow velocity) for adenosine and papaverine was 2.94 +/- 1.50 and 2.94 +/- 1.00, respectively, in group 1 and was significantly and similarly reduced in group 2 (2.16 +/- 0.81 and 2.38 +/- 0.78, respectively; both p less than 0.05 vs. group 1). Low dose bolus injection of adenosine increased mean velocity equivalently to that after continuous infusion of 100 micrograms/kg, but less than after papaverine. There was a strong correlation between adenosine infusion and papaverine for both mean coronary flow velocity and coronary vasodilator reserve ratio (r2 = 0.871 and 0.325; SEE = 0.068 and 0.189, respectively; both p less than 0.0005). No patient had significant arrhythmias or prolongation of the corrected QT (QTc) interval with adenosine, but papaverine increased the QT (QTc) interval from 445 +/- 44 to 501 +/- 43 ms (p less than 0.001 vs. both maximal adenosine and baseline) and produced nonsustained ventricular tachycardia in one patient.(ABSTRACT TRUNCATED AT 400 WORDS)