[The efficacy and safety of kinesytherapy in Becker muscular dystrophy]. / Effektivnost' i bezopasnost' kinezoterapii pri myshechnoi distrofii Bekkera.

Becker muscular dystrophy (BMD) is inherited X-linked neuromuscular disease characterized by progressive fatigue, atrophy, hypotonia and muscle weakness, that is predominantly located in muscles of pelvic girdle, femurs and lower leg. There are only singular studies at present showing the efficacy of different training programs for patients with muscular dystrophy, and there are no recommendations allowing to detect the optimal motor regimen, that is effective and safe for such patients. OBJECTIVE: To evaluate the efficacy of regular dynamic aerobic exercises in children with BMD, who are able to self-sustained movement. MATERIAL AND METHODS: The number of patients equal 13 with genetically confirmed BMD at the age from 8.9 to 15.9 years were examined. All patients took the course of exercise therapy for 4 months. The course was divided into 2 stages: the preparative (51-60% of the individual functional reserve of the heart (IFRH) with 6-8 repetitions of every exercise) and the training (61-70% of the IFRH with 10-12 repetitions of every exercise). The training duration was 60 min. The motor capabilities of patients were assessed by the 6-minute walk test, timed up & go test, MFM scale (sections D1, D2, D3) at the initial stage and during dynamic observation after 2 and 4 months. RESULTS: Statistically significant positive dynamics of indicators was revealed. The average distance in the 6-minute walk test at the initial stage was 526.9±12.7 m, after 4 months was 545.2±13.0 m (p<0.05). The average uplift time at the initial stage was 3.9±0.2 s, after 2 months was 3.5±0.2 s (p<0.05). The average running time for the distance of 10 m initially was 4.3±0.1 s, after 2 months was 3.8±0.1 s (p<0.05), after 4 months was 3.8±0.1 s (p<0.05). There was some positive dynamics in the evaluation of uplift and movement capabilities (D1) by the MFM scale: initially the indicator was 87.7±1.5%, after 2 months - 93.4±1.4% (p<0.001), after 4 months - 94.5±1.3% (p<0.001). Clinically significant adverse effects were not registered during the training courses. CONCLUSION: Aerobic trainings without weight combined with exercises on a cycle machine for 4 months allow to improve movement capabilities and are not characterized by clinically significant adverse effects in children with BMD.

Faculty calibration and students' self-assessments using an instructional rubric in preparation for a practical examination.

PURPOSE: The purpose of this study was to investigate the effect of faculty calibration and students' self-assessments on students' performances in a periodontal practical examination. METHODS: Before a new instructional rubric was implemented in the second-year periodontics course, faculty calibration was conducted with a pilot group of 32 third-year dental students. Afterwards, the new rubric was implemented in the second-year periodontics course. Second-year students used the rubric for their self-assessments before the practical examination. An intraclass correlation coefficient was used to test the reliability of the faculty members. A paired t test was used to compare scores between self-assessments of the pilot group (third-year students) and faculty evaluation. A two-way analysis of variance was performed to compare scores between self-assessments of second-year students and faculty evaluations. Chi-square tests were used to compare overall failure rates amongst four different classes. RESULTS: The reliability amongst the faculty members was strong (the ICC = 0.75 at the first and 0.97 at the second calibration). The mean self-assessment score from the pilot group was significantly higher than the faculty evaluation. However, the mean self-assessment score of second-year students was significantly lower than the faculty evaluation. The class that practiced self-assessments with the validated instructional rubric exhibited the lowest overall failure rate compared to three past classes. CONCLUSIONS: Using an instructional rubric and conducting faculty calibration improved the process of the periodontal practical examination. Improving the examination process and practicing self-assessments with feedback from faculty may have a positive impact on students' performances in the examination.

Use of high technology imaging for surveillance of early stage breast cancer.

Guidelines do not support utilization of high technology radiologic imaging (HTRI) for surveillance after curative treatment for early stage breast cancer. Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data were used to identify 25,555 women diagnosed with stage I-II breast cancer between 1998 and 2003 who survived ≥ 48 months from diagnosis without evidence of second primary or recurrent cancer in this interval. HTRI utilization (computerized tomography scanning (CT), bone scan (BS), breast magnetic resonance imaging, and positron emission tomography scans) was measured in months 13-48 post-diagnosis. Cases were individually matched to 75,669 female Medicare enrollees without cancer. Factors associated with HTRI utilization were evaluated. Forty percent of women with stage I-II breast cancer and 25% of controls had ≥ 1 HTRI during the surveillance interval (P < 0.001). High utilization rates were observed for CT (30%) and BSs (19%). The proportion of women who had a CT during the surveillance period increased in both cancer survivors and controls. Among breast cancer cases age <80, higher comorbidity index, stage II disease, and more recent diagnosis were independently associated with receipt of HTRI. Paralleling patterns observed in controls, HTRI utilization for surveillance following diagnosis of early stage breast cancer has steadily increased among Medicare beneficiaries. Strategies to foster judicious utilization of HTRI should be a priority.

Primary Neural Degeneration in the Human Cochlea: Evidence for Hidden Hearing Loss in the Aging Ear.

The noise-induced and age-related loss of synaptic connections between auditory-nerve fibers and cochlear hair cells is well-established from histopathology in several mammalian species; however, its prevalence in humans, as inferred from electrophysiological measures, remains controversial. Here we look for cochlear neuropathy in a temporal-bone study of "normal-aging" humans, using autopsy material from 20 subjects aged 0-89 yrs, with no history of otologic disease. Cochleas were immunostained to allow accurate quantification of surviving hair cells in the organ Corti and peripheral axons of auditory-nerve fibers. Mean loss of outer hair cells was 30-40% throughout the audiometric frequency range (0.25-8.0 kHz) in subjects over 60 yrs, with even greater losses at both apical (low-frequency) and basal (high-frequency) ends. In contrast, mean inner hair cell loss across audiometric frequencies was rarely >15%, at any age. Neural loss greatly exceeded inner hair cell loss, with 7/11 subjects over 60 yrs showing >60% loss of peripheral axons re the youngest subjects, and with the age-related slope of axonal loss outstripping the age-related loss of inner hair cells by almost 3:1. The results suggest that a large number of auditory neurons in the aging ear are disconnected from their hair cell targets. This primary neural degeneration would not affect the audiogram, but likely contributes to age-related hearing impairment, especially in noisy environments. Thus, therapies designed to regrow peripheral axons could provide clinically meaningful improvement in the aged ear.

Chemotherapy of an experimental glioma with nitrosoureas.

Chemotherapy experiments were performed with 2 nitro-sourea drugs in an experimental mouse brain tumor model. Cell suspensions of a transplantable mouse ependymoblastoma were injected i.c. by means of a stereotactic frame. The drugs used were 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea and 1-(2-chloroethyl)-3-(trans-4-methylcyclohexyl)-1-nitrosourea and were given by either i.p. or by direct intraneoplastic (i.n.) injection on the fifth day after tumor cell implantation. Injections i.n. of drugs were made with the stereotactic frame. Both drugs were highly effective in increasing the median day of death and in yielding large numbers of long-term survivors. Effectiveness was evident after i.p. or i.n. injection. However, with certain dosage schedules such as every 2 hr for 5 injections daily on 2 consecutive days, i.n. injection was more effective and less toxic than i.p. injection. The reason why repeated i.n. injections produced less toxicity than repeated i.p. injections is not definitely known but may be due to local metabolism of the drugs in the tumors and surrounding brain to a less toxic form. This is the first laboratory report of direct i.n. injection of the nitrosoureas, and the authors consider these results encouraging.

Continuous intravenous diltiazem infusion for short-term ventricular rate control in children.

Intravenous diltiazem was administered to 10 pediatric patients with primary atrial tachyarrhythmias with rapid ventricular response. Rapid, consistent, and safe temporary ventricular rate control was obtained in all patients given this medication.

Displacement of carcinomatous epithelium in surgical breast specimens following stereotaxic core biopsy.

A variety of needling procedures in the breast may lead to dislodgment and displacement of fragments of breast carcinoma into tissue outside the target lesion of the needling procedure. To assess how frequently displaced fragments of carcinoma are seen in surgical breast specimens following stereotaxic core needle biopsies, slides were reviewed from 43 consecutive cases of breast carcinoma in which surgical excision and/or mastectomy had been performed following an initial diagnostic stereotaxic 14-gauge core biopsy procedure. In 12 of 43 (28%) cases, displaced carcinomatous fragments were identified outside of the main tumor mass. These patients were subjected to other needling procedures that included local anesthetic injection at the time of core biopsy (43 cases), needle localization (22 of 43 cases), suture placement (18 of 43 cases), and fine-needle aspiration (1 of 43 cases). Attributing carcinomatous displacement solely to the core needle biopsy is complicated by these additional needling procedures. In 18 instances, local anesthetic injection by 25-gauge needle was the only needling procedure other than the core biopsy. In 7 of these 18 (39%) cases, fragments of displaced carcinoma were observed outside the main tumor mass. The authors have previously observed only one case in which a 25-gauge needle was associated with epithelial displacement, suggesting that the core biopsy was more likely to have been the cause of displaced epithelium in these cases. Long-term clinical follow-up will be necessary to determine the biologic and clinical significance of these findings.

Bulboventricular foramen resection: hemodynamic and electrophysiologic results.

BACKGROUND: The two major surgical approaches to the relief of bulboventricular foramen (BVF) obstruction in patients with single left ventricle (LV) are the Damus-Kaye-Stansel (DKS) procedure or direct BVF resection. Theoretical advantages of the DKS include better out-flow gradient relief, lower potential incidences of postoperative heart block and lower incidences of reoperation. Potential disadvantages of this approach include increased semilunar valvar insufficiency, lack of feasibility when attempting septation-type operations for univentricular hearts, and a technically more difficult operation. We report the results of direct surgical BVF resection. METHODS: From June 1990 to June 1999, 9 patients had direct BVF resection performed at our institution. The median age at surgery was 16.5 years (range 1 month to 27 years). Diagnoses in these patients were [S,L,L] single LV (n = 8) and [S,D,D] single LV tricuspid atresia (n = 1). Eight of 9 patients had pulmonary artery bands placed either before BVF resection or at the same time as this procedure. Three patients required reoperation for reobstruction at the BVF (12 total operations in 9 patients). RESULTS: Median preoperative peak systolic gradient across the BVF measured at cardiac catheterization was 47 mm Hg (range 10 to 63 mm Hg). The median peak gradient measured by Doppler echocardiography was 44 mm Hg (range 5 to 125 mm Hg). Eight of 9 patients survived the operation to discharge from the hospital and 7 of 9 are alive at follow-up. At a median follow-up of 22 months (range 5 to 76 months), 8 of 8 surviving patients had an unobstructed BVF as determined by qualitative two-dimensional echocardiography and Doppler color flow imaging. There was one perioperative and one late death 5 months postoperatively (secondary to fungal sepsis). No patient developed new or worsened aortic insufficiency after BVF resection. Eight of 9 patients had no change in AV nodal conduction after surgery. One patient developed Mobitz II heart block requiring postoperative implantation of a pacemaker. CONCLUSIONS: Direct resection of an obstructive BVF can be performed with total relief of obstruction although reoperation may be required. Atrioventricular nodal function can be preserved in most patients with this operative approach, including those with [S,L,L] segmental anatomy.

Clinical management issues in percutaneous core breast biopsy.

Percutaneous imaging-guided core biopsy is a less invasive and less expensive alternative to surgical biopsy for the evaluation of breast lesions. Percutaneous core biopsy is most often used for evaluation of BI-RADS category 4 lesions, but may also be helpful in the evaluation of some BI-RADS category 5 lesions. Stereotactic guidance is particularly useful for calcifications; for masses that can be seen with ultrasound, ultrasound guidance may be preferable because of the absence of radiation and lower cost. The automated core biopsy needle is excellent for mass lesions, but directional vacuum-assisted biopsy is superior for calcifications. Directional vacuum-assisted biopsy may also be preferable for small lesions that may require placement of a localizing clip and lesions that are superficial or in thin breasts. The more expensive ABBI device has substantial limitations, and its role in percutaneous breast biopsy has not been demonstrated. Complete removal of the mammographic target can occur at percutaneous biopsy, and is a more frequent event when the larger tissue acquisition devices are used. Complete removal of the mammographic target does not ensure complete excision of the histologic process. Further investigation is necessary to determine in which lesions, if any, complete removal of the target is advantageous. Epithelial displacement can occur during all breast needling procedures, but may be less frequent at directional vacuum-assisted biopsy than at fine-needle aspiration or automated core biopsy. There is no evidence that displaced cells are of biologic significance, but displaced DCIS can mimic infiltrating carcinoma. The pathologist should be aware of the findings of epithelial displacement, to avoid misdiagnosing DCIS as infiltrating ductal carcinoma. Some lesions warrant repeat biopsy or surgical excision after percutaneous core biopsy. Repeat biopsy is warranted if histologic findings and imaging findings are discordant. Surgical excision is warranted for lesions yielding a percutaneous diagnosis of ADH or possible phyllodes tumor. Controversy exists regarding the need for surgical excision after percutaneous diagnosis of radial scar, papillary lesion, ALH, or LCIS. Follow-up is necessary if percutaneous biopsy yields benign findings concordant with imaging characteristics. Follow-up protocols vary, but all require substantial commitment of time and resources. We have an embarassment of riches for performing percutaneous core biopsy of the breast. It can be estimated that approximately 1 million breast biopsies will be performed this year to diagnose approximately 200,000 breast cancers. Percutaneous core biopsy may spare many of these women the need for a more deforming, invasive, and expensive surgical biopsy. Further work is necessary to optimize criteria for patient selection, develop and define the role of new technologies for tissue acquisition, refine protocols for management after percutaneous breast biopsy, and assess long-term outcome, so that more women can benefit from this minimally invasive approach to breast diagnosis.

Stereotactic breast biopsy: indications and results.

Imaging-guided breast biopsy performed with large-core needles can accurately diagnose most breast pathologies, often allowing a diagnosis to be made more quickly and less expensively than with surgical biopsy. Major complications, such as hemorrhage and infection, are extremely rare, although post-biopsy ecchymosis and tenderness are not unusual. Because less tissue is removed, post-biopsy cosmetic deformity does not occur. Stereotactic biopsy is performed by triangulating the position of a breast lesion and by obtaining views angled equally off a central axis. This can be done using dedicated tables or add-on equipment. Stereotactic core biopsy has a reported accuracy of at least 90%. All lesions for which biopsy would ordinarily be recommended are amenable to stereotactic techniques, but those near the chest wall or in the axilla may be more difficult to biopsy with some equipment. Lesions characterized by calcifications are sometimes more difficult to sample. A biopsy diagnosis of ductal atypia, because of its histologic heterogeneity, requires surgical excision to exclude coexistent carcinoma, which has been found in half of women at subsequent surgical excision. A core biopsy diagnosis of ductal carcinoma in situ does not preclude the discovery of invasive carcinoma at surgery. In rare instances, the small tissue volume removed at stereotactic biopsy does not permit a final diagnosis to be made; this occurs most commonly when differentiating phyllodes tumor from fibroadenoma.

Percutaneous core biopsy of nonpalpable breast lesions: utility and impact on cost of diagnosis.

Percutaneous image-guided core breast biopsy is faster, less invasive, less deforming, and less expensive than surgical biopsy for diagnosing nonpalpable breast lesions. Percutaneous biopsy may be performed using different imaging guidance modalities (e.g., stereotaxis or ultrasound) and different tissue acquisition devices (e.g., automated needles or vacuum-assisted biopsy probes). Stereotactic biopsy may be used for all lesion types (masses and calcifications). Stereotactic 14-gauge automated core biopsy spared a surgical procedure in 76-85% of cases, decreasing the cost of diagnosis by 40-56%. Annual national savings from use of stereotactic 14-gauge automated core biopsy rather than surgical biopsy for nonpalpable lesions would exceed 100 million dollars. Stereotactic 11-gauge vacuum-assisted biopsy yields significant improvement in diagnosis of calcifications and may be used in lesions that are not amenable to stereotactic 14-gauge automated core biopsy. Stereotactic 11-gauge vacuum-assisted biopsy spared a surgical procedure in 76% cases, decreasing cost of diagnosis by 20%. Use of stereotactic 11-gauge vacuum-assisted biopsy for calcifications and for nonpalpable masses not amenable to stereotactic 14-gauge automated core biopsy would yield annual national savings exceeding 50 million dollars. Ultrasound-guided biopsy, used primarily for masses, has several advantages including speed, comfort, lack of radiation exposure, and real-time needle visualization. Ultrasound-guided core biopsy spared a surgical procedure in 85% cases, decreasing the cost of diagnosis by 56%. Although both ultrasound-guided core biopsy and stereotactic biopsy are less expensive than surgery, cost savings are greater for ultrasound-guided core biopsy. An annual national savings over $50 million could be realized with the use of ultrasound-guided core biopsy for nonpalpable masses. Future work should include evaluating the emerging new technologies for percutaneous breast biopsy and optimizating the choice of biopsy method for different clinical scenarios. Society may benefit from cost reduction as women benefit from a faster, less invasive, and less deforming approach to diagnosis.

Ultrasound-assisted cannulation of the right internal jugular vein during electrophysiologic studies in children.

Percutaneous access of the right internal jugular vein for coronary sinus cannulation in pediatric patients undergoing electrophysiologic studies may be technically difficult. We report the use of an ultrasound-guided technique for obtaining jugular venous access. Forty-five pediatric patients who underwent electrophysiologic study were analyzed. Access was obtained in 100 % of the patients using this technique with no major complications. Ultrasound guidance for access of the internal jugular vein for coronary sinus cannulation during electrophysiologic studies in pediatric patients, may increase the success rate and prevent the development of complications.

Mammary cystosarcoma with mature adipose stromal differentiation (lipophyllodes tumor) arising in a lipomatous hamartoma.

This report documents an uncommon variant of benign cystosarcoma phyllodes with mature adipose stromal differentiation, for which the term lipophyllodes tumor is proposed. Origin of this unusual tumor within a lipomatous hamartoma was confirmed by histologic and mammographic observations. The lesion developed in a 40-year-old woman 2 months post partum, and she remained well after treatment by biopsy. Lipophyllodes tumor, which features mature adipose tissue in much of the stromal component of a cystosarcoma, should not be mistaken for a malignant neoplasm. Complete excision is adequate therapy.

EZH2 promotes a bi-lineage identity in basal-like breast cancer cells.

The mechanisms regulating breast cancer differentiation state are poorly understood. Of particular interest are molecular regulators controlling the highly aggressive and poorly differentiated traits of basal-like breast carcinomas. Here we show that the Polycomb factor EZH2 maintains the differentiation state of basal-like breast cancer cells, and promotes the expression of progenitor associated and basal-lineage genes. Specifically, EZH2 regulates the composition of basal-like breast cancer cell populations by promoting a 'bi-lineage' differentiation state, in which cells co-express basal- and luminal-lineage markers. We show that human basal-like breast cancers contain a subpopulation of bi-lineage cells, and that EZH2-deficient cells give rise to tumors with a decreased proportion of such cells. Bi-lineage cells express genes that are active in normal luminal progenitors, and possess increased colony-formation capacity, consistent with a primitive differentiation state. We found that GATA3, a driver of luminal differentiation, performs a function opposite to EZH2, acting to suppress bi-lineage identity and luminal-progenitor gene expression. GATA3 levels increase upon EZH2 silencing, mediating a decrease in bi-lineage cell numbers. Our findings reveal a novel role for EZH2 in controlling basal-like breast cancer differentiation state and intra-tumoral cell composition.