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R J Lederman

Publications and source records attributed to R J Lederman.

At least 19 recordsLinked to original sources
PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30&#xb1;10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗
PubMed1999

Robert Schumann.

Robert Schumann, one of the giants of early romantic music, was born in Saxony in 1810 and died in an asylum shortly after his 46th birthday. Early in life, he demonstrated extraordinary skills in both music and journalism; he remained active in both areas until his final illness. His marriage to the remarkable pianist, Clara Wieck, provided him with both much-needed emotional support and a highly effective champion of his music throughout her lengthy career. Schumann's plans to be a concert pianist were thwarted at least partially by an injury to his right hand, the nature of which has been the subject of much speculation. After considering what few facts are available, the author concludes that this may have represented focal dystonia. His compositional output waxed and waned dramatically over his professional life, reflecting to some degree his emotional state. It is considered most likely that he suffered from a major affective disorder, bipolar type. This ultimately led to a suicide attempt in February 1854, and to his eventual death in July 1856. Despite wide-spread and reasonable suspicion that he may have died from neurosyphilis, severe malnutrition from self-starvation seems more likely.

Bipolar Disorder↗
PubMed1998

Acute hemodynamic changes during carotid artery stenting.

To determine the clinical significance of acute hemodynamic disturbances during stenting in the carotid sinus region, we assessed the relation between intraprocedural changes in heart rate (HR) and blood pressure (BP) and adverse neurologic and cardiac outcomes. Eighteen patients underwent carotid stenting with the Wallstent (Schneider Inc). Suitable candidates had at least 60% diameter stenosis of the carotid artery by angiography. Initial and nadir HR and BP were recorded during the predilatation, stent delivery, and postdilatation periods. Bradycardia was defined as HR < or =60 beats/min and hypotension as systolic BP < or =100 mm Hg. Nineteen Wallstents were successfully deployed in all 19 carotid arteries. Some degree of bradycardia or hypotension occurred in 68% of carotid stent procedures, but administration of vasoactive medications was necessary in only 7 patients (37%) with more persistent hemodynamic disturbances. Hypotension or the need for continuous vasopressor therapy was significantly more common during postdilatation (32%) than in the predilatation period (5%) (p = 0.02). Bradycardia was not reduced by prophylactic atropine. In 1 patient the hemodynamic response to stenting may have contributed to an adverse neurologic and cardiac outcome. Thus, despite frequent fluctuations in HR and BP, most carotid stenting procedures were performed with excellent overall results, even in patients at high risk.

Aged↗
PubMed1998

Superimposed stents in the management of acute recoil after Palmaz-Schatz stenting.

We report a patient in whom aorto-ostial stenting with a Palmaz-Schatz coronary stent was complicated by significant acute elastic recoil, despite appropriate positioning of the stent and full expansion of a high-pressure, postdilatation balloon. Superimposing a Palmaz biliary stent overcame the inward radial force of this lesion and achieved an adequate lumen.

Aged↗
PubMed1998

Kissing stents in the aortic bifurcation.

BACKGROUND: We report the first series of simultaneously delivered stents used to treat stenosis of the aortic bifurcation. Surgical treatment of aortoiliac occlusive disease carries up to a 3% mortality rate. Percutaneous balloon techniques to treat aortic bifurcation stenosis, although safer, are still associated with up to a 9% incidence of dissection, thrombosis, or significant residual stenosis. Kissing stent insertion should decrease the incidence of these complications. METHODS: Twenty patients underwent kissing stent insertion. Suitable candidates included patients with symptoms of lower limb ischemia and significant atherosclerotic lesions in both ostial common iliac arteries (n = 15) or with extremely complex single ostial iliac stenoses (n = 5). Palmaz stents were delivered simultaneously to both limbs of the aortic bifurcation. RESULTS: Kissing stent insertion was successfully performed in all 20 patients without acute complications. Mean percent stenosis decreased from 46.2%+/-24.8% to -6.8%+/-13.3% (P = .0001) in the right iliac artery, 42.3%+/-22.8% to -1.6% +/-18.1% (P = .0001) in the left iliac artery, and 19.1%+/-16.6% to 2.3%+/-16.4% (P= .0008) in the distal aorta. Intermittent claudication symptoms were improved in 18 (95%) of 19 patients with 12 (63%) of 19 patients becoming totally asymptomatic. The strongest predictor of clinical outcome after kissing stent insertion was the preprocedural extent of femoropopliteal disease: 8 (89%) of 9 patients with femoropopliteal narrowing <75% bilaterally became completely asymptomatic at follow-up compared with only 3 (30%) of 10 patients with more severe stenoses (P = .02). CONCLUSIONS: We have demonstrated in 20 patients that stenoses of the aortic bifurcation can be treated effectively with kissing stents with few serious adverse events.

Aged↗
PubMed1996

Postpartum neuralgic amyotrophy.

We report 11 women with at least one episode of neuralgic amyotrophy occurring postpartum. One woman had three episodes-two postpartum and a third occurring after minor foot surgery. Two others had a second episode, one following a first trimester spontaneous abortion and one after a viral syndrome. Pain followed delivery from as little as 1 to 2 hours to up to 2 weeks and usually lasted from a few weeks to several months. Weakness, if delayed, followed onset of pain by 2 or 3 days up to 5 weeks. Four of the episodes were bilateral. Clinical weakness and electrodiagnostic findings varied widely, from involvement of a single peripheral nerve (e.g., long thoracic, anterior interosseous) to multiple bilateral proximal and distal nerves. Functional recovery was excellent (90 to 100%) in 8 of the 10 with adequate follow-up, requiring as little as 2 weeks or up to 3 years. Two women have moderate persisting weakness (both bilateral) at 3 years and 2 years. Five patients went on to subsequent deliveries without recurrence of neuralgic amyotrophy. Only one of the 11 women had a history suggesting familial neuralgic amyotrophy, a disorder generally thought to be associated particularly with postpartum episodes. Although the etiology of postpartum neuralgic amyotrophy remains unknown, an immunologic mechanism is suspected. Focal demyelination may play a role in some, but clearly axonal degeneration is predominant in the majority.

Adult↗
PubMed1994

AAEM minimonograph #43: neuromuscular problems in the performing arts.

Over the past 10-15 years, there has been increasing interest in the health problems of performing artists. In this review, I will discuss the major playing-related disorders seen in instrumental musicians. Among the 672 instrumentalists evaluated, the major diagnoses identified included musculoskeletal disorders in 64%, peripheral nerve problems in 22.5%, and focal dystonia in 7%. Sixty percent of instrumentalists were female although males predominate in the group with focal dystonia. The average age of those evaluated was 32 years. Among musculoskeletal disorders overuse syndrome is the most common. Frequent peripheral nerve disorders include thoracic outlet syndrome, carpal tunnel syndrome, and ulnar neuropathy. A characteristic distribution of symptoms and signs is identified for each instrument group. Electrodiagnostic studies are an important part of the evaluation of these disorders. With carefully designed treatment, the majority of instrumental musicians can be returned to full and pain-free playing activities. The success rate is highest in some entrapment neuropathies but remains low in focal dystonia.

Dystonia↗
PubMed1992

Neurological complications following liver transplantation.

Neurological complications occurred in 4 (19%) of 21 consecutive patients (Group II) undergoing orthotopic liver transplantation, compared with a 47% (9/19) incidence in our initial series (Group I). In Group II, the neurological problems included new recurrent headaches and delayed intracerebral hemorrhage (1 patient), partial third nerve palsy and brachial plexopathy (1 patient), and ataxic dysarthria with encephalopathy (2 patients). Seizures, noted in 8 of 9 neurologically affected Group I patients, were not encountered in Group II. Of the 4 patients in the entire series with the cerebrocerebellar syndrome, 2 had partial recovery after stopping treatment with cyclosporine, 1 stabilized when cyclosporine was discontinued but later worsened when rechallenged, and 1 had full recovery but died following a second transplantation. Brain magnetic resonance images appeared normal in 3 of the 4 patients. Complications affecting vision included cortical blindness in 2 patients and occipital lobe hemorrhage in 1. All completely recovered. Survival was comparable for patients with and those without neurological complications (69% and 63%, respectively). Immediate withdrawal of cyclosporine at the onset of a change in mental status or dysarthria and improvement in intra- and postoperative management may have contributed to the decreased incidence of neurological complications.

Adult↗
PubMed1991

Alternating sequential intracarotid BCNU and cisplatin in recurrent malignant glioma.

The authors entered 43 patients with recurrent malignant glioma in a trial of alternating sequential intracarotid BCNU and cisplatin. Protocol design was alternating courses of BCNU (2 doses, 300 to 400 mg each) and cisplatin (2 doses, 150 to 200 mg each) each at 4-week to 6-week intervals. Eight of 40 patients (20%) evaluable after the first course of BCNU showed partial or minor response. Only 18 patients were evaluable after the first course of cisplatin, and 5 were evaluable after the second course of BCNU. Median survival was 9 months (range, 2 weeks to 6 years). Cerebral or ocular toxicity unique to this method of chemotherapy administration and failure to show clinical improvement were the most common reasons for removal from study. Because of the high attrition rate, the authors were unable to determine a meaningful response to alternating sequential BCNU and cisplatin or to test the clinical degree of cross-resistance to these agents in human malignant glioma.

Adult↗
PubMed1989

Peripheral nerve disorders in instrumentalists.

I evaluated 226 instrumentalists for playing-related symptoms. There were 103 players (46%) of string instruments, 7 keyboard instrumentalists (32%), 44 players (19%) of wind instruments, and 6 percussionists (3%). The mean age was 32 years; 58% were women. Sixty-five patients (29%) had a peripheral nerve disorder; 27 had symptoms of thoracic outlet syndrome; 12 had median neuropathies (carpal tunnel syndrome in 9); 9 had ulnar neuropathies; 6 had cervical radiculopathy; 5 had digital neuropathies; 3 had cranial neuropathies; and 3 had other peripheral nerve disorders. Treatment consisted of modification of playing schedules and technique, plus physical and occupational therapy in 51 and surgical procedures in 9 patients; 5 were not treated. Follow-up at 1 to 8 years showed 74% had a satisfactory result, 14% had slight or minimal improvement, and 12% had no improvement. At the time of writing, all but 4 patients remained in the music profession. It is concluded that playing-related symptoms among instrumentalists are frequently neurological in origin and that the large majority can be helped by conservative or, on occasion, surgical means.

Adolescent↗
PubMed1989

Primary biliary cirrhosis in a patient with multiple sclerosis.

A 47-yr-old patient with primary biliary cirrhosis and multiple sclerosis is reported. Although primary biliary cirrhosis has been associated with numerous other autoimmune disorders, it has not, to the authors' knowledge, previously been reported in association with multiple sclerosis.

Autoimmune Diseases↗