Approximately a century ago, labral avulsion from the glenoid was described as a source of recurrent anterior shoulder dislocation. Since then, the significance of other origins of shoulder instability has been a controversial issue. Cadaveric dissection, biomechanical evaluation, and surgical observation have led to the discovery of additional pathologic conditions associated with glenohumeral instability that must be properly identified and addressed for operative success.
View Article and Find Full Text PDFHemophilia B is an X-linked coagulopathy caused by absence of functional coagulation factor IX (FIX). Using adeno-associated virus (AAV)-mediated, liver-directed gene therapy, we achieved long-term (> 17 months) substantial correction of canine hemophilia B in 3 of 4 animals, including 2 dogs with an FIX null mutation. This was accomplished with a comparatively low dose of 1 x 10(12) vector genomes/kg.
View Article and Find Full Text PDFA potential consequence of systemic administration of viral vectors is the inadvertent introduction of foreign DNA into recipient germ cells. To evaluate the safety of in vivo recombinant adeno-associated virus (rAAV) mediated gene transfer approaches for hemophilia B, we explored the risk of germline transmission of vector sequences following intramuscular (IM) injection of rAAV in four species of male animals (mouse, rat, rabbit and dog). In vector biodistribution studies in mice and rats, there is a dose-dependent increase in the likelihood that vector sequences can be detected in gonadal DNA using a sensitive PCR technique.
View Article and Find Full Text PDFThis study evaluated the effect of physiological, TSH-guided, L-thyroxine treatment on serum lipids and clinical symptoms in patients with subclinical hypothyroidism. Sixty-six women with proven subclinical hypothyroidism (TSH, 11.7 +/- 0.
View Article and Find Full Text PDFThe safety of several gene therapy approaches for treatment of the severe, X-linked bleeding disorder hemophilia is currently being evaluated in early phase clinical trials. One strategy seeks to correct deficiency of functional coagulation factor IX (hemophilia B) by intramuscular (IM) administration of an adeno-associated viral (AAV) vector. A potentially serious complication of any treatment for hemophilia is formation of inhibitory antibodies against the coagulation factor protein, a risk that increases in the setting of null mutations in the factor IX gene (F9).
View Article and Find Full Text PDFThe X-linked bleeding disorder hemophilia B is caused by absence of functional blood coagulation factor IX (F9) and can be treated by adeno-associated viral (AAV) mediated gene transfer to skeletal muscle. The safety of this approach is currently being evaluated in a phase I clinical trial. Efficacy of this and several other gene therapy strategies has been addressed in hemophilia B dogs, an important preclinical model of the disease.
View Article and Find Full Text PDFSmall dorsal root ganglion (DRG) neurons, which include nociceptors, express multiple voltage-gated sodium currents. In addition to a classical fast inactivating tetrodotoxin-sensitive (TTX-S) sodium current, many of these cells express a TTX-resistant (TTX-R) sodium current that activates near -70 mV and is persistent at negative potentials. To investigate the possible contributions of this TTX-R persistent (TTX-RP) current to neuronal excitability, we carried out computer simulations using the Neuron program with TTX-S and -RP currents, fit by the Hodgkin-Huxley model, that closely matched the currents recorded from small DRG neurons.
View Article and Find Full Text PDFThis study examined the demographic, medical, and psychiatric correlates of hallucinations and paranoid delusions reported by proxy informants for 822 elders aged 70 or older. This sample comprised people who were deemed unable to complete a direct interview in a large nationwide study of aging. Marital status, trouble with vision, and cognitive impairment were associated with report of both paranoid delusions and hallucinations.
View Article and Find Full Text PDFAlthough rat brain Nav1.3 voltage-gated sodium channels have been expressed and studied in Xenopus oocytes, these channels have not been studied after their expression in mammalian cells. We characterized the properties of the rat brain Nav1.
View Article and Find Full Text PDFWe performed HLA-mismatched stem cell transplantation with megadoses of purified positively selected mobilized peripheral blood CD34(+) progenitor cells (PBPC) from related adult donors in 39 children lacking an otherwise suitable donor. The patients received a mean number of 20.7 +/- 9.
View Article and Find Full Text PDFThis study examines the psychometric properties of two new abbreviated versions of standard measures of depression, a revised eight-item Center for Epidemiological Studies-Depression Scale (CES-D) and a short-form Composite International Diagnostic Interview (short-form CIDI). A sample of 6,133 elders, age 70 years or older, completed both measures as part of the Asset and Health Dynamics Study of the Oldest Old. The revised CES-D had an internal consistency and factor structure comparable to that of prior versions of the CES-D.
View Article and Find Full Text PDFSpine (Phila Pa 1976)
April 2001
Study Design: A retrospective chart review.
Objectives: To report the correlation between the side of a concordantly painful, post-discography computer tomography (CT) visualized, annular tear, and the side of a patients' low back pain.
Summary Of Background Data: An annular fissure extending from the nucleus to the outer one-third of the annulus is thought to be the nociceptive source stimulated during provocative lumbar discography.
Inbred immunocompetent C57BL/6 mice have been a favored strain to study transgene expression of human blood coagulation factor IX (hF.IX) from viral vectors because systemic expression of the secreted protein is not limited by antibody responses following intravenous (i.v.
View Article and Find Full Text PDFHemophilia B is caused by the absence of functional coagulation factor IX (F.IX) and represents an important model for treatment of genetic diseases by gene therapy. Recent studies have shown that intramuscular injection of an adeno-associated viral (AAV) vector into mice and hemophilia B dogs results in vector dose-dependent, long-term expression of biologically active F.
View Article and Find Full Text PDFRecent data demonstrate that the introduction into skeletal muscle of an adeno-associated viral (AAV) vector expressing blood coagulation factor IX (F.IX) can result in long-term expression of the transgene product and amelioration of the bleeding diathesis in animals with hemophilia B. These data suggest that biologically active F.
View Article and Find Full Text PDFBackground: Loss of bone mass is a continuing problem in long-term space flight. Although counter-measure programmes have been developed, effective assessment of these programmes is hampered by a lack of monitoring techniques that can be used in-flight.
Materials And Methods: Three techniques were used to evaluate changes in bone during two missions of 180 and 20 days to the MIR space station, involving three subjects.
Objectives: The ability of older people to estimate their own memory, often referred to as "metamemory," has been evaluated in previous studies with conflicting reports regarding accuracy. Some studies have suggested that an older person's metamemory is mostly accurate, whereas others have demonstrated little relationship between memory complaint and actual impairment. This study examines memory complaint in a large national sample of older people aged > or = 70.
View Article and Find Full Text PDFWe report the first case of zygoapophyseal joint cyst-induced radicular pain successfully treated with therapeutic selective nerve root block. A 56-year-old dentist presented with pain involving the lateral thigh, lateral calf, and foot dorsum that worsened with standing and walking. Magnetic resonance imaging of the lumbar spine showed a cyst emanating from the right L4-L5 zygoapophyseal joint, resulting in central canal and lateral recess stenosis.
View Article and Find Full Text PDFDefining immune responses against the secreted transgene product in a gene therapy setting is critical for treatment of genetic diseases such as hemophilia B (coagulation factor IX deficiency). We have previously shown that intramuscular administration of an adeno-associated viral (AAV) vector results in stable expression of therapeutic levels of factor IX (F.IX) and may be associated with humoral immune responses against F.
View Article and Find Full Text PDFObjective: MR imaging is the optimal imaging technique to study the normal and abnormal conditions of the pectoralis major muscle and tendon unit. The purpose of this study was to use MR imaging to provide an anatomic survey of the normal pectoralis major tendon and its insertion and to compare these findings with surgically proven cases of rupture.
Conclusion: MR imaging shows the normal pectoralis major myotendinous unit has low signal intensity on both T1- and T2-weighted images.