Apoptosis and proliferation under conditions of deoxynucleotide pool imbalance in liver of folate/methyl deficient rats

Weanling male F344 rats were fed either a semi-purified diet low in methionine and lacking in choline and folic acid (folate/methyl deficient) or a supplemented control diet for periods of 2, 5, 7 days, 3 weeks, and 9 weeks. Two days after initiating the folate/methyl deficient diet in weanling F344 rats, the incidence of apoptotic bodies, identified by in situ end-labeling of 3'-OH DNA strand breaks, was significantly increased in liver sections from the deficient rats. Apoptotic cell death was confirmed biochemically by an increase in nuclear Ca2+/Mg2+-dependent endonuclease activity that paralleled the increase in apoptotic bodies over the 9-week feeding period. There was no morphologic evidence of necrotic foci or necrosis-associated inflammatory response over the 9-week period. Confirming that cell turnover is chronically elevated in this model, the increase in apoptotic rate was accompanied by a sustained increase in the mitotic index (MI). The DNA repair-associated enzyme, poly(ADPribose) polymerase (PARP), was similarly elevated and was associated with significant decreases in the substrate for ADPribose polymer synthesis, nicotinamide adenine dinucleotide (NAD). Because folate metabolites are essential for de novo purine and thymidine biosynthesis, prolonged deficiency in folic acid can induce an imbalance in the deoxynucleotide precursors for DNA replication/repair and negatively affect the fidelity of DNA synthesis. Using an HPLC method, hepatic deoxyuridine triphosphate (dUTP) levels were increased at 3 and 9 weeks after initiation of the deficient diet and levels of thymidine triphosphate (dTTP) were reduced. An increase in dUTP/ dTTP ratio is consistent with a block in folate-dependent de novo thymidylate biosynthesis and may predispose to uracil misincorporation and DNA repair-related DNA strand breaks.      

Meniscal tear characteristics in young athletes with a stable knee: arthroscopic evaluation

BACKGROUND: There has been great interest in the literature regarding meniscal tears in unstable knees, but there is not as much information available on stable knees. PURPOSE: To report the characteristics of isolated meniscal tears (type and location) in athletes with intact cruciate ligaments. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Arthroscopic surgery was performed on 314 (83.1%) knees in the acute phase ( < 6 weeks) of injury and on 64 (16.9%) knees more than 6 weeks after injury for a total of 364 athletes (378 knees). Cooper's classification was used to classify the meniscal tears according to the type and location. RESULTS: Overall, 262 of 378 tears (69.3%) were located in the medial meniscus and 116 (30.7%) in the lateral meniscus. Vertical tears (77.5%) were significantly more frequent than were horizontal tears (22.5%; chi(2) test, P < .001). A total of 23.2% of tears involved the peripheral zones (zone 0 or 1), and tears that extended into the posterior horn accounted for 75.7%. Regarding the tear shape between male and female athletes, on both sides there were no statistically significant differences in the percentage of horizontal, bucket-handle, longitudinal, or radial tears. CONCLUSION: The characteristics of isolated meniscal tears differ with regard to the sport, sex, and tear location and type from those seen in unstable knees. This knowledge is useful in knee injury management.     

The appearance of kissing contusion in the acutely injured knee in the athletes

Background: Bone contusions are often identified at magnetic resonance imaging (MRI) in the acutely injured knee. Contusions of both surfaces of the joint are known as kissing contusions.

Objective: To determine the frequency, type, and distribution of kissing contusions occurring in association with injuries of the knee joint.

Methods: 255 MRI examinations in athletes with acutely injured knees (197 men; 58 women; mean age 24.2 years) were reviewed by two independent examiners; 219 MRIs were done within the first month after the injury and 36 within two to four months. None of the knees had been injured before. No fractures were present on x ray.

Results: Bone contusions were diagnosed in 71 cases (27.8%); 55 (22.5%) were identified as single contusions and 16 (6.3%) as kissing contusions. Eight of the kissing contusions were associated with anterior cruciate ligament tears, three with menisceal tears, four were isolated lesions, and one was delayed, following a menisceal tear. The 32 bone contusions (16 kissing contusions) were located as follows: lateral femoral condyle (n = 14; 8 type I, 6 type II); lateral tibial condyle (n = 9; 3 type I, 1 type II, 5 type III); medial tibial condyle (n = 7; 2 type I, 5 type III); medial femoral condyle (n = 2; both type I). The associated injuries were confirmed by arthroscopy in 12/16 patients.

Conclusions: Kissing contusion is a significant injury often associated with ligamentous or menisceal injuries. Type I lesions are most common on the lateral femoral condyle and type III on the lateral tibial condyle.

     

Determination of the DDE and PCB contents of peregrine Falcon eggs: A comparison of whole egg measurements and estimates derived from eggshell membranes

A method using eggshell membranes to determine egg content levels of DDE and polychlorobiphenyls (PCBs), two of the most ubiquitous environmental contaminants, has been validated. A comparison was made between the residue levels determined from the egg contents of 40 Peregrine Falcon (Falco peregrinus) eggs and from hexanesoluble extracts of the dried eggshell membranes. The results confirm the use of museum eggshells for estimations of DDE and PCB levels of the original egg contents. This method should be valid for other lipophilic compounds. The data generated are of use not only to determine the records of past contamination, but may be expected to provide useful information on patterns of contamination encountered in different geographical areas. The membrane extraction technique allows pollutant levels to be measured without removing viable material from endangered species.     

Water safety: age-specific changes in knowledge and attitudes following a school-based intervention.

OBJECTIVES: To explore whether an intervention during mandatory schooling can lead to age-specific changes in water safety knowledge and attitudes. METHODS: Age-specific questionnaires were distributed to 202 kindergarten and grade one pupils, 220 elementary school pupils and 337 pupils attending the first three high school grades in Greater Athens. The information was used to design an educational package that was subsequently presented to pupils of the same grades and similar socio-demographic profiles attending different schools in the same area. One month later, a post-exposure evaluation was conducted using the initial questionnaires, in which 115, 205 and 321 pupils from the respective grade categories provided their responses. In order to compare the performance of pupils exposed to the educational intervention with that of pupils who participated only in the initial assessment, mean differences in scores measuring overall knowledge and attitudes were estimated within each of the three grade groups adjusting for age, gender, sibship size, maternal education and swimming knowledge. RESULTS: Among kindergarten and grade one pupils, those who received the intervention scored significantly higher for knowledge (17.40%, 95% CI 6.41% to 28.39%) and attitudes (23.64%, 95% CI 4.48% to 42.79%). Among elementary school pupils the gains in knowledge were less evident (14.58%, 95% CI -3.05% to 32.21%)) and almost null in attitudes (5.64%, 95% CI -11.47% to 22.77%). Further advancement of age showed no improvement in knowledge (-0.15%, 95% CI -5.30% to 4.99%) and a minimal, insignificant increase in attitudes (6.32%, 95% CI -1.87% to 14.52%) among exposed high school pupils. CONCLUSION: The school-based intervention resulted in considerable positive changes in knowledge and attitudes among very young pupils. Elementary schooling seems to provide meagre opportunities to simply improve knowledge. Alternative/complementary approaches should be sought in any attempt to modify behavior.     

Balo’s concentric sclerosis: Value of magnetic resonance imaging in diagnosis

We report two cases of Balo’s concentric sclerosis that demonstrate the typical magnetic resonance imaging (MRI) findings of concentric rings of demyelination involving the superficial and deep white matter and sparing the cortex. In both cases biopsy was not performed as MRI findings and multi-mode evoked potential studies were consistent with demyelinating illness. The theories regarding the pathogenesis of this peculiar appearance are briefly reviewed.     

Programming Antitachycardia Pacing for Primary Prevention in Patients With Implantable Cardioverter Defibrillators: Results From the PROVE Trial

Programming ATP for ICD Patients. Objectives: The PROVE trial was designed to determine if antitachycardia pacing (ATP) is clinically beneficial for primary prevention in patients who have implantable cardioverter defibrillators (ICDs) or cardiac resynchronization therapy defibrillators (CRT‐Ds). Background: Use of ICDs and CRT‐Ds reduces mortality in patients with ventricular dysfunction and mild to moderate heart failure. However, in studies of the primary prevention population, shock‐only ICDs are predominantly used, without ATP programming for less painful termination of ventricular tachycardia (VT). Methods: We conducted a prospective, nonrandomized, multicenter study using market‐released ICDs and CRT‐Ds. Patients received devices programmed to deliver ATP for VT cycle lengths of 270–330 ms. Follow‐up evaluation was performed at 3, 6, and 12 months. The incidence of VT and the rate of successful termination by ATP were analyzed. Results: Of 830 patients in the study population (men, 73%; mean age, 67.3 ± 12 years), 32% received single‐chamber ICDs, 44% dual‐chamber ICDs, and 24% CRT‐Ds. ATP was attempted for 112 VT episodes in 71 patients, and 103 (92%) of the VT episodes were successfully terminated. Three VT episodes were accelerated by ATP and required termination by ICD shock; 6 episodes terminated spontaneously or by ICD shock. Conclusions: VT is common in patients without a history of this arrhythmia who have received ICDs or CRT‐Ds for primary prevention indications. Programming ICDs for ATP therapy at the time of implantation could potentially terminate most VT episodes and reduce the number of painful shocks for these patients. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1349‐1354, December 2010)     

Total Pectoral Implantation: A New Technique for Implantation of Transvenous Defibrillator Lead Systems and Implantable Cardioverter Defibrillator

We describe a new approach to tolal pectoral implantation of cardioverter defibrillators with an endocardial defibrillation lead system. Endocardial lead configuration used was an FDA approved right atrial-superior vena cavo defibriliation spring electrode, right ventricular bipolar sensing electrode, and a pectoral patch. Endocardial leads were implanted via a cephalic or an axillary venesection. Pectoral patch was placed in a sabmuscular position. In case of failure to obtain satisfactory thresholds, a small intercostal thoracofomy was performed via fhe same skin incision and patch placed over the epicardium instead of submuscular position and used with Ihe right atrial spring electrode. The device was implanted in the pectoral region, submuscularly, over the patch. Sixteen consecutive patients underwent this approach. With a submascular patch, adequate defibrillation thresholds (< 15 joules [J]) were obtained in 14 (87.5%) patients. In the other two, defibrillation thresholds of ≤ 15) were obtained with a epicardial patch. Pectoral implantation of the device was feasible in all 16 patients and none needed repositioning. Average postimplant hospital stay was 5 days. During follow-up period (average 5 months), none of the patients reported any major local symptoms and no problems have been encountered in device interrogation. Thus, total pectoral implantation of the cardioverter defibrillator including the patch, leads, and the device is feasible. Furthermore, in case of foilure to obtain adequate defibrillotjon thresholds with submuscular patch, an epicardial patch can easily be implanted and allows 100% successful defibrillation at energy levels of ≤ 15 J with right atrial patch configuration.