The relationship between the serum level of prostate specific antigen and bone and CT scans in the staging of the primary carcinoma of the prostate

OBJECTIVE: To determine the relationship between the serum level of prostate-specific antigen (PSA) and the presence of abnormalities in a skeletal or CT scan in patients with primary carcinoma of the prostate. DESIGN: Retrospective. SETTING: Academic Medical Centre, Amsterdam. PATIENTS AND METHODS: The serum PSA levels were compared with the findings in the skeletal and CT scans of 440 patients with carcinoma of the prostate without clinical signs of metastases, seen in the period from January 1990 to December 1994 in the outpatient clinics for Urology of the Academic Medical Centre (AMC) in Amsterdam, Hospital Gooi-Noord in Blaricum and Hospital De Heel in Zaandam. CT scan data were analysed only from the AMC and Hospital Gooi-Noord. RESULTS: There were 76 patients with a positive bone scan (17.3%) and 31 (out of 337; 9.2%) with a positive CT scan. Higher PSA serum levels went together with increasing risk of abnormalities in bone or CT scan. Of 85 patients with PSA values < 10 micrograms/l, none had a positive bone scan and one (out of 73; 1%) a positive CT scan; of the 180 patients with PSA levels < 20 micrograms/l, 4 (2.2%) had a positive bone scan and 2 (out of 154; 1.3%) a positive CT scan. The T stage, the histological grading and the serum alkaline phosphatase activity appeared not to have any supplementary value. CONCLUSION: In view of the low frequency of abnormalities in a bone or CT scan in patients with low PSA levels, it appears justified no longer to recommend bone or CT scanning for staging of patients for a clinically non-metastasized carcinoma of the prostate and serum PSA levels < 20 micrograms/l.     

High-resolution electrocardiography in monitoring myocardial damage after therapy with anthracyclines in children

BACKGROUND: Anthracycline cytostatics, widely used in oncologic practice, may induce discrete myocardial damage occasionally culminating in life-threatening cardiologic complications. The most serious clinical manifestations of anthracycline cardiotoxicity are dilated cardiomyopathy, heart failure and fatal arrhythmias. OBJECTIVES, STARTING POINT AND MAIN PURPOSE: High-resolution electrocardiography (HRECG) is one of the latest cardiologic methods, which can be promising for early identification of patients at risk of anthracycline cardiotoxicity. The aim of this study is the evaluation of the incidence of HRECG abnormalities in a group of paediatric patients treated with anthracyclines and the usefulness of HRECG for stratification of patients at risk of the clinical cardiotoxicity. PATIENTS AND METHODS: A set of 60 oncologic paediatric patients treated with anthracyclines was divided into two groups. The first group was formed by 15 patients undergoing evaluation during their anthracycline therapy (median after the last administration of antracyclines was 3.2 days). Their average age at the time of examination was 14.7 +/- 4.1 years. The total cumulative dose of antracyclines was 40-300 mg/m2 (median 150 mg/m2). The second group was formed by 45 patients who were evaluated after completing anthracycline therapy. The interval of time from the last administration of antracycline in this subgroup of patients was 3 months-12 years (median 5.5 years). Their average age at the time of HRECG examination was 14 +/- 4.1 years. The total cumulative dose of anthracyclines was 90-440 mg/m2 (median 230 mg/m2). Six patients of this group (13.3%) were treated also with mediastinal radiotherapy (18-40 Gy). 43 patients (95.5%) of second group were in complete remission, two other patients yielded a progression of their malignancy. 10 patients (22%) were examined by HRECG 2-5 times in app. two-month intervals. The control group was formed by 30 randomly selected healthy children and adolescents with normal ECG. Average age was 15.1 +/- 5.8 years. Using HRECG the time- and frequency-domain characteristics of the ECG signal were analyzed. The time-domain analysis was performed at 40-250 Hz filter. The frequency-domain analysis was performed by fast Fourier transformation (FFT), a 120 ms segment starting 20 ms before the end of the QRS complex was analyzed. The altered frequency content was expressed as the ratio of frequency areas (area ratio, AR) 20-50 Hz/0-20Hz. The average level of noise was 0.56 microV in the first group, 0.62 microV in the second group of patients and 0.68 microV in the control group. RESULTS: Abnormalities in the time-domain analysis (ventricular late potentials, VLP) were present in 2 (13.3%) of 15 patients during the anthracycline therapy in the first group and in 4 (8.8%) of 45 patients after completing therapy in the second group. No abnormalities in the time-domain analysis were detected in the control group. Using frequency-domain analysis, abnormalities in AR20-50 Hz/0-20 Hz were found in 8 (53.3%) of 15 patients of the first group, and in 11 (24.4%) of 45 patients of the second group. Significant differences were observed in the frequency parameters of the ECG signal in patients of the first group in comparison to the control group (p = 0.0018) and also when comparing the patients of the second group and the control group (p = 0.045). CONCLUSION: The HRECG results in time- and frequency-domain analyses indicate to high incidence of HRECG abnormalities in patients examined both during and after the antracycline therapy in comparison to the control group. The prognostic use of the HRECG abnormalities must be established in a larger and longer study. (Fig. 4, Tab. 2, Ref. 43.)     

Right ventricular arrhythmia in the absence of arrhythmogenic dysplasia: MR imaging of myocardial abnormalities

PURPOSE: To evaluate right ventricular abnormalities with magnetic resonance (MR) imaging in patients with arrhythmia but without arrhythmogenic dysplasia. MATERIALS AND METHODS: In 53 patients being evaluated for right ventricular arrhythmia and 15 control subjects, MR imaging was performed to evaluate fixed thinning, fatty replacement, or reduced systolic wall thickening or motion. A diagnosis of idiopathic right ventricular outflow tract tachycardia or indeterminate was assigned for each patient, and the severity of arrhythmia was categorized. RESULTS: Right ventricular abnormalities were revealed in 32 (60%) of the 53 patients: fixed thinning in 27 (84%), fatty replacement in eight (25%), and reduced wall thickening or motion in 31 (97%). Right ventricular abnormalities were found in 35 (76%) of 46 patients with idiopathic right ventricular outflow tract tachycardia and in seven (39%) of 18 patients with indeterminate diagnoses (P = .022). CONCLUSION: Mild right ventricular abnormalities are likely sources for arrhythmias, even in the absence of arrhythmogenic right ventricular dysplasia.     

Arthroscopic removal of an osteoid osteoma at the talar neck

PURPOSE: This study used simultaneous videomanometry to measure pressure characteristics in a group of patients with evidence of laryngeal and/or tracheal barium penetration, and to compare the results to those of one group of healthy volunteers and one group of patients with dysphagia but a normal barium swallow. MATERIAL AND METHODS: Videomanometry during barium swallowing was performed in 25 patients who showed penetration of barium into the laryngeal vestibule. Manometric abnormalities were determined by comparing these mean values with those of 25 healthy volunteers, and the frequency of manometric abnormalities was compared to that of 19 patients presenting with oropharyngeal dysphagia with a normal barium swallow. RESULTS: The frequency of abnormalities for four parameters (pharyngo-esophageal segment (PES) resting pressure, PES relaxation duration, pharyngeal peak pressure, pharyngeal contraction duration) differed significantly between the patients with penetration and those with normal barium studies. There was, however, no association between manometric abnormalities and the degree of barium penetration. CONCLUSION: The differences in manometric abnormalities between patients with laryngeal penetration and patients with normal barium swallows may be useful in identifying the mechanisms of laryngeal penetration.     

Discrimination between myocardial and skeletal muscle injury by assessment of the plasma ratio of myoglobin over fatty acid-binding protein

BACKGROUND: Myoglobin and fatty acid-binding protein (FABP) each are useful as early biochemical markers of muscle injury. We studied whether the ratio of myoglobin over FABP in plasma can be used to distinguish myocardial from skeletal muscle injury. METHODS AND RESULTS: Myoglobin and FABP were assayed immunochemically in tissue samples of human heart and skeletal muscle and in serial plasma samples from 22 patients with acute myocardial infarction (AMI), from 9 patients undergoing aortic surgery (causing injury of skeletal muscles), and from 10 patients undergoing cardiac surgery. In human heart tissue, the myoglobin/FABP ratio was 4.5 and in skeletal muscles varied from 21 to 73. After AMI, the plasma concentrations of both proteins were elevated between approximately 1 and 15 to 20 hours after the onset of symptoms. In this period, the myoglobin/FABP ratio was constant both in subgroups of patients receiving and those not receiving thrombolytics and amounted to 5.3 +/- 1.2 (SD). In serum from aortic surgery patients, both proteins were elevated between 6 and 24 hours after surgery; the myoglobin/FABP ratio was 45 +/- 22 (SD), which is significantly different from plasma values in AMI patients (P < .001). In patients with cardiac surgery, the ratio increased from 11.3 +/- 4.7 to 32.1 +/- 13.6 (SD) during 24 hours after surgery, indicating more rapid release of protein from injured myocardium than from skeletal muscles. CONCLUSIONS: The ratio of the concentrations of myoglobin over FABP in plasma from patients with muscle injury reflects the ratio found in the affected tissue. Since this ratio is different between heart (4.5) and skeletal muscle (20 to 70), its assessment in plasma allows the discrimination between myocardial and skeletal muscle injury in humans.     

The significance of fetal myocardial and skeletal muscle function as a factor affecting its viability

Histologic study of the heart and functionally active zones of skeletal muscles of the lower limbs of fetuses and newborns (71 cases) is undertakes to distinguish the factors affecting the viability of the fetus (new-born) and detect the total-system muscle tissue involvement after the general morphogenetic mechanism. The basic criteria of a pathological process caused by capillarotrophic myocardial insufficiency are dystrophy, necrosis, and sclerosis. Various forms of nonspecific prenatal myopathy were detected in the skeletal muscles; they were combined with symptoms of chronic myocardial hypoxia. A relationship between cardiovascular abnormalities and intrauterine and neonatal death is revealed.     

Relationships between myocardial bioenergetic and left ventricular function in hearts with volume-overload hypertrophy

BACKGROUND: Left ventricular (LV) hypertrophy secondary to volume overload can result in alterations in myocardial bioenergetics and LV dysfunction. This study examined whether bioenergetic abnormalities contribute to the pump dysfunction. METHODS AND RESULTS: Severe mitral regurgitation (MR) was produced in 10 dogs by disruption of the chordal apparatus. Hemodynamics and ventricular function were examined 11.7 months later under baseline conditions and during treadmill exercise. Myocardial high-energy phosphates were measured by using magnetic resonance spectroscopy at rest, during coronary vasodilation with adenosine, and during oxidative stress induced by rapid pacing and dobutamine. Chronic MR caused a 30% increase in LV mass and a 65% increase in LV volume. In MR animals, the hemodynamic and LV function were normal at rest, but abnormalities developed during beta-blockade and exercise. Myocardial creatine phosphate-to-ATP ratios were significantly lower in each layer across the LV wall in MR hearts than normal hearts. Myocardial blood flow and coronary reserve were normal in MR hearts. Moreover, hyperperfusion did not correct the abnormal bioenergetics. Despite altered bioenergetics at rest, the MR hearts tolerated rapid pacing and dobutamine infusion well. CONCLUSIONS: In volume-overloaded LV hypertrophied hearts, alterations in myocardial high-energy phosphate levels do not induce abnormal mechanical performance at rest but may be related to a decreased contractile reserve during exercise.     

Hereditary elliptocytosis

Recently a number of different red cell membrane skeletal abnormalities have been identified in patients with hereditary elliptocytosis (HE). In Japanese patients with HE, most of skeletal abnormality was protein 4.1 abnormalities. alpha-spectrin abnormality was found only one lineage in Japan, in spite of these abnormalities were most common abnormalities in western countries. On the contrary beta-spectrin abnormalities were found in two lineages, in spite of these abnormalities were rare abnormalities in western countries. The other abnormalities, such as band 3 abnormalities and glycophrin abnormalities, were found in HE. We described here about clinical features and above mentioned abnormalities of red cell membrane skeleton in HE.     

Short communication: skeletal maturation of children with sex chromosome abnormalities

Skeletal maturity, or "bone age," is one of the several criteria used to determine developmental or physiologic age as opposed to chronologic age. The purpose of this study of skeletal maturation of children with sex chromosome abnormalities (45,X, 47,XXX, 47,XXY, X-chromosomal mosaics) and controls is 2c-fold: (1) to investigate if children with sex chromosome aneuploidy ascertained in an unbiased fashion differ in skeletal maturation from their siblings and other normal healthy children born in Denver, Colorado, and (2) to assess if the skeletal age standards currently in use (Greulich-Pyle; Tanner- Whitehouse) are applicable to Denver children when evaluating radiographs for skeletal maturation. Mean chronologic and skeletal age were measured. Mean differences between skeletal and chronologic age for all groups across all measures were calculated. The 45,X females constitute the only group studied with bone ages lower than expected (0.05 greater than P greater than 0.01; two-tailed test). We found no other significant differences in skeletal maturation between Denver children with sex chromosome abnormalities and their siblings or the control sample of Denver children. Although we found the Tanner-Whitehouse standards to be more applicable for use with this population, all the Denver groups investigated yielded consistently lower bone ages than expected published norms. This is the first documentation in a group of children with sex chromosome abnormalities, ascertained in an unbiased fashion, that, with the exception of those with a 45,X karyotype, bone age is not significantly different from that of the normal population.     

Disturbed intracoronary hemodynamics in myocardial bridging: early normalization by intracoronary stent placement

BACKGROUND: The purpose of this study was to evaluate the hemodynamic mechanisms leading to myocardial ischemia in patients with myocardial bridging. Myocardial bridging is known to induce angina and even severe myocardial ischemia. METHODS AND RESULTS: In 12 symptomatic patients with myocardial bridges, quantitative coronary angiography was performed to obtain systolic/diastolic vessel diameters within the bridged segments. Coronary flow velocities, flow reserve, and pressures were determined with a 0.014-in Doppler and a 0.014-in pressure microtransducer. In 3 symptomatic patients, coronary stents were implanted and hemodynamic measurements were repeated immediately and after 7 weeks. An in vitro validation of the pressure measurements was performed. Angiography revealed a systolic diameter reduction of 80.6+/-9.2% and a persistent diastolic reduction of 35.3+/-11% within the bridged segment. Diastolic flow velocities (cm/s) were increased (31.5+/-14.3 within versus 17.3+/-5.7 proximal and 15.2+/-6.3 distal, P<.001). Coronary flow reserve distal to the bridge was 2.5+/-0.5. There was an increased peak systolic pressure within the bridged segment (171+/-48 versus 113+/-10 mm Hg proximal, P<.001). Stent placement abolished the phasic lumen compression, the diastolic flow abnormalities, the intracoronary peak systolic pressure, and clinical symptoms. Coronary flow reserve improved to 3.8+/-0.3. CONCLUSIONS: Coronary hemodynamics in myocardial bridges are characterized by a phasic systolic vessel compression with a localized peak pressure, persistent diastolic diameter reduction, increased blood flow velocities, retrograde flow, and a reduced flow reserve. These alterations may explain the occurrence of symptoms and ischemia in these patients. Intracoronary stent placement abolished all hemodynamic abnormalities and may improve clinical symptoms in otherwise unsuccessfully treated patients with myocardial bridges.     

Postoperative arrhythmias and myocardial electrolytes in patients undergoing coronary artery bypass grafting

Electrolyte changes in right atrial and skeletal muscle pre- intra- and postoperatively, and their relationship to the development of postoperative atrial fibrillation or flutter were evaluated in 31 patients with coronary artery bypass grafting (CABG). Such postoperative arrhythmias occurred in 14 patients (45%). Before CABG the skeletal muscle potassium concentration was lower in these patients than in the others: median 261.4 (range 148.2-329.5) vs 298.6 (167.1-416.4) mumol/g dry weight, p = 0.017. The right atrial potassium concentration was normal, but sodium levels were higher in the patients with, than in those without postoperative arrhythmias: median 340.3 (263.7-454.9) vs 296.3 (203.9-355.0) mumol/g dry weight, p = 0.008, indicating disturbed transmembrane electrolyte transfer. During CABG the potassium levels fell and sodium increased in both right atrium and skeletal muscle, and on postoperative day 2 the potassium content in skeletal muscle was not yet restored. Magnesium levels showed no changes in right atrium or skeletal muscle, but serum magnesium declined postoperatively. As the observed electrolyte derangements may be important in the development of postoperative arrhythmias, concomitant potassium and magnesium supplement postoperatively may be beneficial in restoring cellular potassium concentration.     

Central (interior) osteophytes of the distal femur. Imaging and pathologic findings

RATIONALE AND OBJECTIVES: To characterize central osteophytes (COs) of the distal femur, imaging features that enable their differentiation from intra-articular bodies were identified, and the frequency of overlying articular cartilage abnormalities was determined. METHODS: The authors inspected 133 distal femoral specimens and retrospectively reviewed knee radiographs of 48 symptomatic patients and magnetic resonance images of 60 symptomatic patients for presence of COs. The location and imaging features of COs, and their association with marginal osteophytes (MOs), were recorded. Articular cartilage abnormalities, if any, were documented in patients who underwent magnetic resonance imaging. RESULTS: Specimen analysis showed a 41% prevalence of COs, 95% association of COs with MOs, and predominance of large COs in the medial femoral condyle (81%). Radiographic analysis revealed a 9.8% prevalence of COs in the distal femur. Magnetic resonance images demonstrated a 14.3% prevalence of COs, with the majority (73%) accompanied by an overlying cartilage that had abnormal signal intensity or morphology, or both. CONCLUSIONS: Central osteophytes are a common finding in the distal femur. Based on their location and cortical continuity with the underlying bone, most COs can be differentiated from intra-articular bodies.     

Surgical treatment of extratemporal epilepsy: clinical, radiologic, and histopathologic findings in 60 patients

PURPOSE AND METHODS: The aim of this study was to analyze clinical, radiologic, and histopathologic findings in 60 consecutive patients with medically intractable extratemporal epilepsy who were operated on between November 1987 and May 1993. RESULTS: Histologically, there were distinct structural abnormalities in 50 (83%) of the surgical specimens. Signal abnormalities on magnetic resonance imaging (MRI) were present in all patients with neoplastic lesions (n = 17) and in 94% of patients with nonneoplastic focal lesions (n = 32). Overall, structural abnormalities were detected by MRI in 47 (96%) of 49 patients with focal lesions. During a mean follow-up of 4 years, 30 (54%) patients remained completely seizure free, 11 (20%) had < or = 2 seizures per year, seven (12%) showed a seizure reduction of > or = 75%, and eight (14%) had < 75% reduction in seizure frequency. The fraction of seizure-free patients was 12 (80%) of 15 in patients with neoplastic lesions, 16 (52%) of 31 in patients with nonneoplastic focal lesions, and two (20%) of 10 for those without histopathologic abnormalities. The differences in seizure outcome between patients with and without focal lesions were statistically significant (p < 0.05), if seizure-free outcome was compared with persistent seizures. CONCLUSIONS: Focal lesions and particularly neoplasms are associated with improved postoperative seizure control compared with patients without histopathologic abnormalities. We advise caution in considering surgery to treat extratemporal epilepsy in patients who have normal MRI scans, because the outcome with the approach described in this study is poor in such cases.     

Mechanistic action of pediocin and nisin: recent progress and unresolved questions

BACKGROUND: Present knowledge of mechanisms involved in human fertilization has uncovered a new group of pathologic conditions that have been generically named fertilization abnormalities. AIM: To determine the contribution of chromosomal alterations to in vitro fertilization failures. MATERIALS AND METHODS: A cytogenetic analysis of oocytes that were not fertilized after insemination with normal spermatozoa. Oocytes were obtained from patients subjected to in vitro fertilization in a public hospital of Metropolitan Santiago. Ovulation was induced in these patients administering GnRh-a, FSH, HMG and HCG. The double fixation technique described by Wramsby was used to obtain chromosomes. RESULTS: One hundred and seven oocytes coming from 45 women aged 25 to 42 years old were studied. The frequency of aneuploidy in these oocytes was 37.3%, with a 11.8% of hypohaploidy, a 21.6% of hyperhaploidy and a 3.9% of diploid oocytes. In hyperhaploid as well as in hypohaploid oocytes, the chromosomes involved in aneuploidy pertained to groups D. and G. CONCLUSIONS: Although the total frequency of aneuploidy is within normal ranges, the frequency of hyperhaploidy is superior to previous reports. An explanation for this finding could be that the occurrence of a lack of disjunction with chromosomal retention in the parental cell occurs with a higher frequency than that in which the chromosomes are retained in the polocyte. We also suggest that oocyte chromosomal aneuploidy could contribute to the failure of in vitro fertilization procedures.     

Resection of the right middle lobe and lingula for mycobacterial infection

BACKGROUND: In a series of 229 patients infected with mycobacterial organisms, we noted a specific female phenotype that involves isolated infections of the middle lobe and lingula. METHODS: Thirteen patients were found to have infections of the middle lobe, lingula, or both. All of them were infected with Mycobacterium other then Mycobacterium tuberculosis, all were women, 12 of the 13 were slender, and most had variable combinations of skeletal abnormalities. All underwent resection of the middle lobe, lingula, or both. RESULTS: There were no operative deaths. Only 2 patients have had reactivation requiring additional antibiotic therapy. All patients have had a decreased number of pulmonary infections in the postoperative period. Anatomic findings at operation included a complete major fissure and at least a partially complete minor fissure with middle lobe resections or an elongated lingula. CONCLUSIONS: Mycobacterial infection of the middle lobe and lingula is primarily a disease of asthenic women and is often associated with skeletal abnormalities and complete fissures or an elongated lingula. We recommend that surgical intervention be performed early once the condition is identified.     

Endothelial cell compatibility of glycopeptide antibiotics for intravenous use

OBJECTIVE: The aim of this study was to evaluate the pulmonary CT findings in patients with Churg-Strauss syndrome to determine the frequency and nature of parenchymal abnormalities. MATERIALS AND METHODS: CT examinations performed at the time of diagnosis in 17 patients with Churg-Strauss syndrome were retrospectively evaluated by two observers who reached a decision by consensus about the presence and nature of parenchymal abnormalities. High-resolution CT (1- to 3-mm collimation) was performed in 14 patients and conventional CT (6- to 10-mm collimation) was performed in three cases. RESULTS: Predominant CT findings consisted of parenchymal opacification (consolidation or ground-glass attenuation) (n = 10), pulmonary nodules (n = 2), bronchial wall thickening or dilatation (n = 2), interlobular septal thickening (n = 1), and normal anatomy (n = 2). Parenchymal opacification was predominantly peripheral (n = 6) or random in distribution (n = 4). CONCLUSION: The most common CT finding in patients with Churg-Strauss syndrome consists of areas of parenchymal opacification that may be random or peripheral in distribution. These findings are nonspecific.     

Haematological, ocular and skeletal abnormalities in a samoyed family

Haematological, ocular and skeletal abnormalities were documented in a samoyed male and its five offspring. Haematological abnormalities, found in repeated tests in all the dogs, included marked eosinophilia, eosinophilic bands and absence of Barr bodies. Two of the dogs had bilateral buphthalmia, retinal detachments and other ocular abnormalities. Three of the dogs had skeletal abnormalities including chondrodysplasia (dwarfism) and brachygnathia (undershot jaw). A similar combination of inherited skeletal and ocular disorders, without the haematological abnormalities, has been described in samoyeds. Acquired causes for the haematological findings, which are similar to the inherited Pelger-Hu?t anomaly described in several species, have been eliminated. Eosinophilic bands and scarcity of Barr bodies could be a marker, or a previously unreported manifestation, of an inherited disorder in samoyeds.     

Magnetic resonance imaging in the staging of solitary plasmacytoma of bone

PURPOSE: To assess prospectively the role of magnetic resonance (MR) imaging in the staging of patients with a solitary bone plasmacytoma (SBP). PATIENTS AND METHODS: Twelve consecutive patients with an apparent SBP underwent MR imaging of both the primary tumor and the thoracic and lumbosacral spine to seek additional foci of marrow involvement that might have been undetected by standard skeletal survey. All patients received megavoltage irradiation (total dose, 40 Gy) to the primary lesion. RESULTS: MR imaging of the thoracic and lumbosacral spine showed additional foci of marrow replacement in four of 12 patients, with signal characteristics identical to those of the primary tumor. In all four patients, the abnormal protein persisted at greater than 50% of the pretreatment value following radiation treatment. In contrast, the myeloma protein disappeared or was reduced by greater than 50% in five of the six patients with secretory disease and without additional marrow abnormalities. One of four patients progressed to multiple myeloma 10 months after diagnosis with new lesions on conventional radiographs in the same areas as detected previously by MR imaging. CONCLUSION: Four of 12 patients considered to have a SBP by standard criteria may have been understaged, because MR imaging showed additional marrow abnormalities consistent with myeloma. MR imaging of the spine may contribute to the initial staging of SBP, especially since some patients may be cured with radiotherapy.     

Skeletal muscle mitochondrial DNA injury in patients with unilateral peripheral arterial disease

BACKGROUND: Patients with peripheral arterial disease (PAD) have exercise limitation due to claudication-limited pain and metabolic alterations in skeletal muscle. PAD is also associated with oxidative stress, which is a known cause of mitochondrial DNA (mtDNA) injury. The present study was designed to test the hypothesis that PAD is associated with mtDNA injury, as reflected by an increased frequency of a specific 4977-base pair (bp) mtDNA deletion mutation. METHODS AND RESULTS: The deletion frequency was quantified in gastrocnemius muscle of 8 patients with unilateral PAD and 10 age-matched control subjects with the use of polymerase chain reaction methodologies. Muscle from the hemodynamically unaffected (less affected) PAD limb showed an 8-fold increased deletion frequency and the hemodynamically affected (worse affected) PAD limb had a 17-fold increased deletion frequency compared with muscle from control subjects. The frequency of the 4977-bp deletion in the worse-affected limb was positively correlated with the age of the patients but not the claudication-limited exercise performance of the patients. Total mtDNA content, citrate synthase activity, and cytochrome c oxidase activity were not different in the muscle from the 3 limb populations. However, the ratio of citrate synthase to cytochrome c oxidase was higher in the worse- versus less-affected limbs of PAD patients. CONCLUSIONS: The present study demonstrates a large increase in the frequency of the mtDNA 4977-bp deletion in patients with PAD but in a distribution not limited to the hemodynamically affected limb.     

Decreased proportion of type I myofibers in skeletal muscle of dogs with chronic heart failure

BACKGROUND: Whether biochemical and histological abnormalities of skeletal muscle (SM) develop in patients with chronic heart failure (HF) remains controversial. In the present study, dogs with chronic HF were used to examine potential alterations of SM fiber type, fiber size, number of capillaries per fiber (C/F), beta-adrenergic receptor density (Bmax), and fiber ultrastructural integrity. METHODS AND RESULTS: HF was produced in 17 dogs by sequential intracoronary microembolizations. Biopsies of the lateral head of the triceps muscle were used in all studies. Type I and type II fibers were differentiated by myofibrillar ATPase (pH 9.4 or 4.2). Bmax was assessed by radioligand binding and SM ultrastructure by transmission electron microscopy. Comparisons were made with biopsies obtained from nine control dogs. The percentage of SM type I fibers was reduced in HF dogs compared with control dogs (19 +/- 2% versus 32 +/- 5%) (p < 0.001), whereas the percentage of SM type II fibers was increased (81 +/- 2% versus 68 +/- 5%) (p < 0.001). The change in fiber type composition was not associated with a preferential atrophy or hypertrophy of either fiber type. There was no difference in SM Bmax (198.9 +/- 14.3 versus 186.8 +/- 17.3 fmol/mg protein) or in C/F (5.37 +/- 0.26 versus 5.84 +/- 0.21) between HF dogs and control dogs. No ultrastructural abnormalities were present in SM fibers of HF dogs. CONCLUSIONS: In dogs with HF, there is a decrease in the relative composition of the slow-twitch type I SM fibers and an increase in fast-twitch type II fibers. The shift in fiber type composition is not associated with preferential atrophy of either fiber type or with a reduction in C/F, beta-adrenergic receptor density, or structural abnormalities of the myofibers.