Search PubMed⌕ Search

Biomedical subjects

M Sussman

Publications and source records attributed to M Sussman.

At least 19 recordsLinked to original sources
PubMed2005

Practice parameter: corticosteroid treatment of Duchenne dystrophy [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society.

BACKGROUND: The Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society develop practice parameters as strategies for patient management based on analysis of evidence. OBJECTIVE: To review available evidence on corticosteroid treatment of boys with Duchenne dystrophy. METHODS: Relevant literature was reviewed, abstracted, and classified. Recommendations were based on a four-tiered scheme of evidence classification, and areas for future research are defined. RESULTS: Seven class I studies and numerous less rigorous trials all demonstrated that corticosteroid treatment for 6 months with prednisone (0.75 or 1.5 mg/kg/day) increased muscle strength, performance, and pulmonary function and significantly slowed the progression of weakness. Two class I trials examined the effect of lower dosage of prednisone (0.30 and 0.35 mg/kg/day), demonstrated lesser but similar benefits, and showed a lower frequency of side effects (e.g., weight gain). The only significant side effects in all class I trials were weight gain and development of a cushingoid facial appearance. One longer-term trial of daily prednisone (0.3 to 0.7 mg/kg/day), a class III study, showed prolongation of functional ability and slower progression of weakness in patients during 3 years of treatment. One class IV, open trial of alternate-day prednisone (2 mg/kg for 2 months, then two-thirds dose every other day) extended ambulation by approximately 2 years in treated compared with untreated patients. Deflazacort, a corticosteroid similar in structure to prednisone, produced similar improvement in muscle strength and function with a similar side effect profile. CONCLUSIONS: Prednisone has been demonstrated to have a beneficial effect on muscle strength and function in boys with Duchenne dystrophy and should be offered (at a dose of 0.75 mg/kg/day) as treatment. If side effects require a decrease in prednisone, tapering to dosages as low as 0.3 mg/kg/day gives less robust but significant improvement. Deflazacort (0.9 mg/kg/day) can also be used for the treatment of Duchenne dystrophy in countries in which it is available. Benefits and side effects of corticosteroid therapy need to be monitored. The offer of treatment with corticosteroids should include a balanced discussion of potential risks.

Adolescent↗
PubMed2001

Sarcoplasmic reticulum Ca(2+) atpase (SERCA) 1a structurally substitutes for SERCA2a in the cardiac sarcoplasmic reticulum and increases cardiac Ca(2+) handling capacity.

Ectopic expression of the sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA) 1a pump in the mouse heart results in a 2.5-fold increase in total SERCA pump level. SERCA1a hearts show increased rates of contraction/relaxation and enhanced Ca(2+) transients; however, the cellular mechanisms underlying altered Ca(2+) handling in SERCA1a transgenic (TG) hearts are unknown. In this study, using confocal microscopy, we demonstrate that SERCA1a protein traffics to the cardiac SR and structurally substitutes for the endogenous SERCA2a isoform. SR Ca(2+) load measurements revealed that TG myocytes have significantly enhanced SR Ca(2+) load. Confocal line-scan images of field-stimulated SR Ca(2+) release showed an increased rate of Ca(2+) removal in TG myocytes. On the other hand, ryanodine receptor binding activity was decreased by approximately 30%. However, TG myocytes had a greater rate of spontaneous ryanodine receptor opening as measured by spark frequency. Whole-cell L-type Ca(2+) current density was reduced by approximately 50%, whereas the time course of inactivation was unchanged in TG myocytes. These studies provide important evidence that SERCA1a can substitute both structurally and functionally for SERCA2a in the heart and that SERCA1a overexpression can be used to enhance SR Ca(2+) transport and cardiac contractility.

Animals↗
PubMed2001

Alterations at the intercalated disk associated with the absence of muscle LIM protein.

In this study, we investigated cardiomyocyte cytoarchitecture in a mouse model for dilated cardiomyopathy (DCM), the muscle LIM protein (MLP) knockout mouse and substantiated several observations in a second DCM model, the tropomodulin-overexpressing transgenic (TOT) mouse. Freshly isolated cardiomyocytes from both strains are characterized by a more irregular shape compared with wild-type cells. Alterations are observed at the intercalated disks, the specialized areas of mechanical coupling between cardiomyocytes, whereas the subcellular organization of contractile proteins in the sarcomeres of MLP knockout mice appears unchanged. Distinct parts of the intercalated disks are affected differently. Components from the adherens junctions are upregulated, desmosomal proteins are unchanged, and gap junction proteins are downregulated. In addition, the expression of N-RAP, a LIM domain- containing protein located at the intercalated disks, is upregulated in MLP knockout as well as in TOT mice. Detailed analysis of intercalated disk composition during postnatal development reveals that an upregulation of N-RAP expression might serve as an early marker for the development of DCM. Altered expression levels of cytoskeletal proteins (either the lack of MLP or an increased expression of tropomodulin) apparently lead to impaired function of the myofibrillar apparatus and to physiological stress that ultimately results in DCM and is accompanied by an altered appearance and composition of the intercalated disks.

Animals↗
PubMed2001

Selective intracellular retention of extracellular matrix proteins and chaperones associated with pseudoachondroplasia.

Mutations in the cartilage oligomeric matrix protein (COMP) gene result in pseudoachondroplasia (PSACH), which is a chondrodysplasia characterized by early-onset osteoarthritis and short stature. COMP is a secreted pentameric glycoprotein that belongs to the thrombospondin family of proteins. We have identified a novel missense mutation which substitutes a glycine for an aspartic acid residue in the thrombospondin (TSP) type 3 calcium-binding domain of COMP in a patient diagnosed with PSACH. Immunohistochemistry and immunoelectron microscopy both show abnormal retention of COMP within characteristically enlarged rER inclusions of PSACH chondrocytes, as well as retention of fibromodulin, decorin and types IX, XI and XII collagen. Aggrecan and types II and VI collagen were not retained intracellularly within the same cells. In addition to selective extracellular matrix components, the chaperones HSP47, protein disulfide isomerase (PDI) and calnexin were localized at elevated levels within the rER vesicles of PSACH chondrocytes, suggesting that they may play a role in the cellular retention of mutant COMP molecules. Whether the aberrant rER inclusions in PSACH chondrocytes are a direct consequence of chaperone-mediated retention of mutant COMP or are otherwise due to selective intracellular protein interactions, which may in turn lead to aggregation within the rER, is unclear. However, our data demonstrate that retention of mutant COMP molecules results in the selective retention of ECM molecules and molecular chaperones, indicating the existence of distinct secretory pathways or ER-sorting mechanisms for matrix molecules, a process mediated by their association with various molecular chaperones.

Aggrecans↗
PubMed2001

Comparison of three ankle-foot orthosis configurations for children with spastic hemiplegia.

The purpose of this study was to examine the effectiveness of the hinged ankle-foot orthosis (HAFO), posterior leaf spring (PLS), and solid ankle-foot orthosis (SAFO), in preventing contracture, improving efficiency of gait, and enhancing performance of functional motor skills in 30 children (21 male, 9 female; mean age 9 years 4 months; age range 4 to 18 years,) with spastic hemiplegia. Following a 3-month baseline period of no ankle-foot orthosis (AFO) use, each AFO was worn for 3 months after which ankle range of motion, gait analysis, energy consumption, and functional motor skills were assessed. The HAFO and PLS increased passive ankle dorsiflexion and normalization of ankle rocker function during gait. Normalization of knee motion in stance was dependent upon the knee abnormality present and AFO configuration. The HAFO was the most effective in controlling knee hyperextension in stance, while PLS was the most effective in promoting knee extension in children with >10 degree knee flexion in stance. Energy efficiency was improved in 21 of the children, with 13 of these children demonstrating the greatest improvement in HAFO and PLS. Improvements in functional mobility were greatest in the HAFO and PLS.

Adolescent↗
PubMed2001

Ischemic mitral valve reconstruction and replacement: comparison of long-term survival and complications.

OBJECTIVE: This study reviews the 223 consecutive mitral valve operations for ischemic mitral insufficiency performed at New York University Medical Center between January 1976 and January 1996. The results for mitral valve reconstruction are compared with those for prosthetic mitral valve replacement. METHODS: From January 1976 to January 1996, 223 patients with ischemic mitral insufficiency underwent mitral valve reconstruction (n = 152) or prosthetic mitral valve replacement (n = 71). Coronary artery bypass grafting was performed in 89% of cases of mitral reconstruction and 80% of cases of prosthetic replacement. In the group undergoing reconstruction, 77% had valvuloplasty with a ring annuloplasty and 23% had valvuloplasty with suture annuloplasty. In the group undergoing prosthetic replacement, 82% of patients received bioprostheses and 18% received mechanical prostheses. RESULTS: Follow-up was 93% complete (median 14.6 mo, range 0-219 mo). Thirty-day mortality was 10% for mitral reconstruction and 20% for prosthetic replacement. The short-term mortality was higher among patients in New York Heart Association functional class IV than among those in classes I to III (odds ratio 5.75, confidence interval 1.25-26.5) and was reduced among patients with angina relative to those without angina (odds ratio 0.26, confidence interval 0.05-1.2). The 30-day death or complication rate was similarly elevated among patients in functional class IV (odds ratio 5.53; confidence interval 1.23-25.04). Patients with mitral valve reconstruction had lower short-term complication or death rates than did patients with prosthetic valve replacement (odds ratio 0.43, confidence interval 0.20-0.90). Eighty-two percent of patients with mitral valve reconstruction had no insufficiency or only trace insufficiency during the long-term follow-up period. Five-year complication-free survivals were 64% (confidence interval 54%-74%) for patients undergoing mitral valve reconstruction and 47% (confidence interval 33%-60%) for patients undergoing prosthetic valve replacement. Results of a series of statistical analyses suggest that outcome was linked primarily to preoperative New York Heart Association functional class. CONCLUSIONS: Initial mortalities were similar among patients undergoing prosthetic replacement and valve reconstruction. Poor outcome was primarily related to preexisting comorbidities. Patients undergoing valve reconstruction had fewer valve-related complications. Valve reconstruction resulted in excellent durability and freedom from complications. These findings suggest that mitral valve reconstruction should be considered for appropriate patients with ischemic mitral insufficiency.

Aged↗
PubMed2000

Overexpression of SERCA2b in the heart leads to an increase in sarcoplasmic reticulum calcium transport function and increased cardiac contractility.

The sarcoplasmic reticulum calcium ATPase SERCA2b is an alternate isoform encoded by the SERCA2 gene. SERCA2b is expressed ubiquitously and has a higher Ca(2+) affinity compared with SERCA2a. We made transgenic mice that overexpress the rat SERCA2b cDNA in the heart. SERCA2b mRNA level was approximately approximately 20-fold higher than endogenous SERCA2b mRNA in transgenic hearts. SERCA2b protein was increased 8-10-fold in the heart, whereas SERCA2a mRNA/protein level remained unchanged. Confocal microscopy showed that SERCA2b is localized preferentially around the T-tubules of the SR, whereas SERCA2a isoform is distributed both transversely and longitudinally in the SR membrane. Calcium-dependent calcium uptake measurements showed that the maximal velocity of Ca(2+) uptake was not changed, but the apparent pump affinity for Ca(2+) (K(0.5)) was increased in SERCA2b transgenic mice (0.199 +/- 0.011 micrometer) compared with wild-type control mice (0.269 +/- 0.012 micrometer, p < 0.01). Work-performing heart preparations showed that SERCA2b transgenic hearts had a higher rates of contraction and relaxation, shorter time to peak pressure and half-time for relaxation than wild-type hearts. These data show that SERCA2b is associated in a subcompartment within the sarcoplasmic reticulum of cardiac myocytes. Overexpression of SERCA2b leads to an increase in SR calcium transport function and increased cardiac contractility, suggesting that SERCA2b plays a highly specialized role in regulating the beat-to-beat contraction of the heart.

Animals↗
PubMed2000

Late results of mitral valve reconstruction in the elderly.

BACKGROUND: This study attempts to confirm favorable results with mitral valve reconstruction (MVP) in patients greater than or equal to 70 years of age and to examine complication rates by actual analysis. METHODS: Between June of 1980 and December of 1997, 278 patients 70 years of age or older (mean, 75.2 years; range, 70 to 87 years) underwent MVP for mitral regurgitation. Most involved insertion of an annuloplasty ring. Concomitant procedures were performed in 72.3%, and 55.0% required coronary revascularization. RESULTS: For isolated MVP, the in-hospital mortality rate was 6.5% and 17.0% when combined with coronary revascularization. The mortality rate when combined with another valve procedure was 13.2%. The 5-year freedom from late cardiac death was 100% in the isolated MVP group and 79.7% for MVP with a concomitant procedure (p = 0.006). Complications were analyzed using actual (cumulative incidence) analysis to eliminate the competing risk of noncardiac death. Mean NYHA class improved from 3.32 to 1.71 postoperatively. Repair failure was rare, with a 5-year freedom from reoperation of 91.2%. CONCLUSIONS: These findings confirm the favorable outcome of MVP in elderly patients. Late repair failures are rare; comorbid disease is an important predictor of outcome.

Aged↗
PubMed2000

The Quattro valve and active infective endocarditis of the mitral valve.

BACKGROUND AND AIM OF THE STUDY: Even today, infective endocarditis remains a therapeutic challenge. Active endocarditis at the time of valve implantation is an important risk factor for the development of prosthetic valve infection. This study reports results following implantation of the Quattro valve, a stentless chordally supported quadrileaflet mitral valve made from bovine pericardium. METHODS: The Quattro valve was implanted in seven patients (four females, three males; mean age 34 years) requiring isolated mitral valve replacement for active bacterial endocarditis. All had congestive heart failure; two were in cardiogenic shock. The diagnosis of active endocarditis was based on clinical and echocardiographic findings, together with macroscopic evidence of acute infection at surgery, blood culture or histopathological evidence of valve infection. Postoperatively, all patients received at least four weeks of parenteral antibiotic therapy. RESULTS: Congestive heart failure (and large pedunculated vegetations and mobile septic left atrial thrombi in two patients) prompted early surgical intervention. Patients underwent surgery at a mean of 7 days (range: 1-16 days) after admission. Endocarditis was caused by Gram-positive cocci in all patients except one. At a mean follow up of 15 months (range: 6-24 months) all patients were alive and symptomatically improved. To date, all remain free of prosthetic valve endocarditis, reoperation and thromboembolism. CONCLUSION: The Quattro valve can be implanted safely in patients with acute bacterial endocarditis. The results also reflect the benefit of early surgical intervention in patients with infective endocarditis complicated by congestive heart failure, with or without large vegetations.

Adult↗
PubMed1999

Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta.

In principle, transplantation of mesenchymal progenitor cells would attenuate or possibly correct genetic disorders of bone, cartilage and muscle, but clinical support for this concept is lacking. Here we describe the initial results of allogeneic bone marrow transplantation in three children with osteogenesis imperfecta, a genetic disorder in which osteoblasts produce defective type I collagen, leading to osteopenia, multiple fractures, severe bony deformities and considerably shortened stature. Three months after osteoblast engraftment (1.5-2.0% donor cells), representative specimens of trabecular bone showed histologic changes indicative of new dense bone formation. All patients had increases in total body bone mineral content ranging from 21 to 29 grams (median, 28), compared with predicted values of 0 to 4 grams (median, 0) for healthy children with similar changes in weight. These improvements were associated with increases in growth velocity and reduced frequencies of bone fracture. Thus, allogeneic bone marrow transplantation can lead to engraftment of functional mesenchymal progenitor cells, indicating the feasibility of this strategy in the treatment of osteogenesis imperfecta and perhaps other mesenchymal stem cell disorders as well.

Bone Density↗
PubMed1999

The biology of cystitis: host and bacterial factors.

Cystitis is caused by a relatively small number of bacterial species. To colonize and grow in the urinary tract, these organisms have developed and acquired special properties (virulence factors) that allow them to overcome the defences of the urinary tract, particularly clearance by urine flow. These virulence factors are unlikely to be required during transmission from host to host, and sometimes their constitutive expression may actually be disadvantageous. Such factors are therefore regulated by the environment and in a coordinate manner to ensure their most appropriate expression for the conditions encountered. This review focuses on the biology of the urinary tract and the bacterial properties necessary to cause cystitis. The regulation of virulence factors at the different stages of the infection is considered, and a general model for the pathogenesis of urinary tract infection is proposed.

Bacteria↗
PubMed1999

Isaac Israeli and his Book of Urine.

Isaac Israeli (c850-950), philosopher and physician was born in Egypt where he practised as an oculist before moving to Kairouan, in Tunisia, where he served as physician to the Caliph Ziyadat Allah and later to 'Ubayd Allah al-Mahdi. His best known medical work Book of Fevers (Kitab al-Hummayat) was widely used as a medical text until the seventeenth century. This paper reviews Israeli's medical career through his Book of Urine (Kitab al-bawl), based on a fifteenth century Hebrew manuscript Sefer Hasheten (MS Hunter 477) in the Hunterian Collection of the University of Glasgow. This manuscript, most likely a translation from the original Arabic, describes the formation of urine and the value of visual examination of urine for the diagnosis and prognosis of disease. Israeli emerges as an outstanding physician and scholar who made a lasting contribution to Arab-Jewish medicine in its most productive period.

Egypt↗
PubMed1999

The stentless quadrileaflet bovine pericardial mitral valve: early clinical results.

BACKGROUND AND AIMS OF THE STUDY: Although bioprosthetic valves currently in use have low thrombogenicity, durability remains very unsatisfactory. Valve failure occurs early from calcification, and later from tissue wear. Stentless design lessens the latter, and anticalcification treatments the former. Recently, a stentless chordally supported quadrileaflet mitral valve (QMV) bioprosthesis made of selected tanned bovine pericardium, treated to minimize calcification, has become available for clinical study. The aim of this study was to report the early results relating to valve performance, and patient outcome. METHODS: Since December 1996, the QMV has been implanted in 23 patients (mean age 38 +/- 12 years) requiring isolated mitral valve replacement for valve lesions not suited for repair. All patients were symptomatic (three in NYHA functional class II, 16 in class III, four in class IV). Preoperatively, all underwent full clinical and echocardiographic assessment, and intraoperative transesophageal evaluation immediately after valve implantation. Blood tests for hemolysis were performed preoperatively and at 3 months after surgery. RESULTS: After a mean follow up of 8.3 months (range: 1 to 18 months), 22 patients were alive and symptomatically improved (NYHA class I or II). One patient died of sternal sepsis soon after surgery. There have been no reoperations, nor cases of infective endocarditis or thromboembolism. Subclinical hemolysis was shown pre- and postoperatively in 35% and 32% of cases, respectively. Intraoperative transesophageal echocardiography post valve implantation demonstrated mitral regurgitation which was trivial in 15 patients (78%) and mild in five (22%). CONCLUSIONS: The QMV can be implanted safely, and the early clinical results relating to patient outcome and valve performance are encouraging.

Adult↗
PubMed1997

High dose neostigmine treatment of malignant sinus tachycardia.

Sinus tachycardia caused by circulating catecholamines in the setting of congestive heart failure may impair systemic perfusion because of decreased diastolic filling time. We report the case of a patient with Wolff-Parkinson-White syndrome with angina and cardiogenic shock who improved dramatically following administration of neostigmine. Cardiac output, blood pressure, and stroke volume increased as heart rate was reduced. A previous attempt at heart rate control, in the same patient, using a low dose beta-antagonist, precipitated hemodynamic collapse. The remarkable recovery of our patient suggests that acetylcholinesterase inhibitors may warrant further investigation in patients with severe sinus tachycardia.

Adult↗
PubMed1994

An African swine fever virus gene with similarity to the T-lymphocyte surface antigen CD2 mediates hemadsorption.

An open reading frame, LMW8-DR, in the African swine fever virus (ASFV) genome possesses striking similarity to the lymphocyte membrane antigen CD2. All characterized CD2 domains, including the amino-terminal signal sequence, IgV, hinge, IgC2, stalk, transmembrane, and proline-rich carboxy cytoplasmic domains, are highly conserved in the ASFV gene. Critical residues for the binding of the lymphocyte function-associated antigen (LFA-3) and CD59 and for T-cell activation are also partially conserved. LMW8-DR is actively transcribed in ASFV-infected swine macrophages and Vero cells at late times in the infection cycle and Vero and COS cells transiently expressing the LMW8-DR open reading frame hemadsorbed swine red blood cells. The structural and functional similarities of LMW8-DR to CD2, a protein that is involved in cell-cell adhesion and immune response modulation, suggest a possible role in the pathogenesis of ASFV infection.

African Swine Fever Virus↗
PubMed1992

The influence of human immunodeficiency virus infection and intravenous drug abuse on complications of hemodialysis access surgery.

To examine the influence of human immunodeficiency virus (HIV) infection on complications in dialysis access surgery, a review was performed on patients undergoing hemodialysis at two major metropolitan medical centers over a 30-month period. One hundred eight patients underwent a total of 169 graft procedures; mean follow-up was 14 1/2 months. There were 18 (17%) patients who were HIV-positive who had no symptoms, 11 (10%) patients with acquired immunodeficiency syndrome (AIDS), and 79 (73%) patients who were HIV-negative. Twenty-three percent (25/108) of patients had a history of intravenous drug abuse (IVDA), most of whom also had either AIDS or asymptomatic HIV infection. Dialysis procedures included 44 autogenous reconstructions (26%), 117 polytetrafluoroethylene (PTFE) grafts (69%), and 8 (5%) procedures of unknown type. Arteriovenous fistula or graft thrombosis was a frequent complication. The overall 12-month graft patency rate was 41%, and patients with HIV infection or a history of IVDA did not have a significantly increased risk of thrombosis. Multivariate analysis showed that the use of PTFE as opposed to autogenous reconstruction was the only significant risk factor found for occlusion within the first 12 months after operation (p < 0.01). Twenty-five graft infections occurred, all in PTFE grafts. The PTFE graft infection rate was 43% in patients with AIDS, 36% in patients who were HIV-positive and who had no symptoms, and 15% in patients who were HIV-negative (p < 0.05). Patients with a history of IVDA had a 41% PTFE graft infection rate versus a 13% infection rate in patients who did not have a history of IVDA (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗