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Biomedical subjects

L Schwartz

Publications and source records attributed to L Schwartz.

At least 145 records · Page 8Linked to original sources

Dystrophin and disease.

Recent advances concerning the genetic and biochemical basis of Duchenne and Becker muscular dystrophies have resulted in a good understanding of the etiology of these common dystrophies. An important secondary consequence of the genetic and biochemical research has been the generation of gene-based and protein-based diagnostic tools which enable a 'molecular diagnosis' for patients and their families. This review summarizes our current understanding of the genetics, biochemistry, and pathophysiology of Duchenne dystrophy, and gives an overview of the molecular diagnostic tools and their applications. Recent correlations of clinical, genetic and biochemical data have indicated that dystrophinopathies can present with a wide range of neuromuscular symptoms, and that neither male sex nor proximal weakness are diagnostic prerequisites for consideration of an underlying dystrophin abnormality.

Amino Acid Sequence↗

Clinical, physiologic, anatomic and procedural factors predictive of restenosis after percutaneous transluminal coronary angioplasty.

In a recent prospective double-blind placebo-controlled trial, a combination of aspirin and dipyridamole was not associated with a reduction in the rate of restenosis within the 1st 6 months after coronary angioplasty. The purpose of this study was to determine whether clinical, anatomic or procedural factors were predictive of the observed restenosis rates in that prospective trial. A total of 247 patients and 280 segments underwent follow-up angiography and quantitative coronary angiographic analysis between 4 and 7 months after coronary angioplasty. Two baseline clinical characteristics--angina class and duration of angina in months--were related to the rate of restenosis by univariate analysis. Patient-related stepwise logistic regression analysis identified severity of angina as the only clinical predictor of restenosis. Three univariate baseline anatomic characteristics--percent diameter stenosis before angioplasty, stenosis greater than 10 mm in length and calcific stenosis--and two early postangioplasty characteristics--residual percent diameter stenosis and residual mean pressure gradient--were predictive of restenosis. Of these, only two--length of stenosis and residual percent diameter stenosis--were independently related to restenosis by multivariate analysis and only the former is identifiable before the procedure. It is concluded that in prospective studies in contrast to retrospective studies, few clinical and anatomic factors appear to be predictive of restenosis after coronary angioplasty.

Angioplasty, Balloon, Coronary↗

Physiological effects of exercising with handweights.

Research demonstrates a positive and graded relationship between handweighted exercise energy costs, the distance through which handweights are swung and the weight used. The energy costs of handweighted exercise when swinging 0.45 to 1.36kg handweights have been shown to be 3 to 155% greater than costs of unweighted exercise at any pace. The upper limit of such increases is unknown. Moreover, the use of handweighted arm swings can convert walking, benchstepping or running from leg dominated endurance training modalities to exercises that simultaneously challenge muscles of both the upper and lower body. The use of handweights may induce a pressor response characterised by elevated heart rate and blood pressure responses at a given exercise intensity. However, such elevations have not been consistently reproduced and when they occurred, were on average small and of little physiological concern. Individual blood pressure responses may vary more widely between handweighted and unweighted walking, with some exhibiting higher and others lower blood pressures when using handweights. Taken together, research suggests that the prescription of handweighted exercise is safe for most individuals. However, it should be prescribed using precautions similar to those used when implementing new exercise regimens, particularly among those with cardiovascular complications. Potential strength and endurance training adaptations to handweighted exercise that incorporates large arm and leg range of motion movement patterns have yet to be determined.

Blood Pressure↗

USSR nationality redistribution by republic, 1979-1989: from published results of the 1989 all-Union census.

"An additional report on the results of the 1989 population census...describes changes in the ethnic composition of Soviet republics and other major regions (e.g., Siberia), as well as changes in the spatial distribution of the country's major ethnic groups. Data from the major 1989 Goskomstat source publication are refined and supplemented by information from more recent sources. Coverage is in a format similar to the reported ethnic results of the 1979 population census...to facilitate comparability."

Censuses↗

[The concept of cure in children with cancer].

Between 1987 and 1991, 248 long-term survivors of childhood cancer have been studied at the Oncology Unit of the Children's Hospital of Buenos Aires. The tumors were diagnosed between 1965 and 1986 as, retinoblastoma: 65, lymphoma: 57, nephroblastoma: 36, neuroblastoma: 25, germ-cell tumors: 18, sarcoma: 19, bone tumors: 7, lymphoepithelioma of cavum: 4, histiocytosis X: 9, others: 8. The treatment consisted of, surgery: 25, surgery+chemotherapy: 40, surgery+radiotherapy: 8, chemotherapy: 23, chemotherapy+radiotherapy: 42, and surgery+chemotherapy+radiotherapy: 110. There are alive without evidence of cancer disease 234 survivors between 5 and 25 years after diagnosis. Severe organic disabilities were observed in 181 survivors and moderate in 142. Thirteen patients died because of second malignant neoplasia and 1 patient with lung metastasis 9 years after diagnosis of nephroblastoma. In 180 survivors the data of instruction was available. Seventy participate in sports and 13 in artistic activities. Eight survivors are university graduates and 24 are employees. Five young women were mothers and one young man was a father. The meaning of concept of "cure" is discussed from the point of view of the physicians and the survivors. In order to detect deleterious late effects of cancer and their treatment the follow-up must be continuous.

Adolescent↗

Potentiation of neurotransmitter release coincides with potentiation of phosphatidyl inositol turnover. A possible in vitro model for long term potentiation.

Carbachol (CCh) a cholinergic agonist which hydrolyses phosphatidyl-inositol bisphosphate (PIP2) to produce the breakdown products inositol trisphosphate (IP3) and diacylglycerol (DAG) was tested for its ability to induce [3H]norepinephrine ([3H]NE) release and to accumulate [3H]inositol phosphate ([3H]IP) under normal and membrane depolarizing conditions. Our results suggest two major points: first, muscarinic acetylcholine receptor (mAChR) agonists and depolarizing agents (of which KCl is the most effective) act in concert to induce potentiation of PI turnover and potentiation of neurotransmitter release. The simultaneous presence of both a depolarizing agent and a receptor agonist is obligatory for eliciting potentiatory effect. Facilitation of release by muscarinic agonist and K+, added together, was 2 to 5-fold above additivity and the levels of [3H]IP accumulated were 3-5-fold above additivity by K+ and CCh. Enhancement of release and of [3H]IP formation is reversed by pirenzepine, a muscarinic (MI) specific antagonist, Kdiss = 0.4 and 0.8 microM, respectively. Second, synergy of IP accumulation in correlation with synergy of neurotransmitter release elicited by mAChR activation and membrane depolarization, suggests a possible role for phospholipase C (PLC) in the bifurcating control of neurotransmitter release and for the involvement of PLC and voltage sensitive channels in mediation of long-term potentiation (LTP).

Animals↗

Twelve-lead electrocardiogram recording during percutaneous transluminal coronary angioplasty. Analysis of reciprocal changes.

Coronary angioplasty was used as a human model of transient myocardial ischemia to evaluate the electrocardiographic characteristics and significance of "reciprocal" ST-segment depression and T wave changes. Continuous 12-lead ECGs were recorded before and during coronary angioplasty in 20 patients, 19 of whom had single vessel disease. In 12 of 14 patients, LAD occlusion produced ischemic changes (peaked T and/or ST elevation) in L1, AVL and at least two precordial leads. "Reciprocal" changes (ST depression and/or T inversion) were observed in at least two inferior wall leads. One patient had ST depression in V4-V6 with no change in the inferior leads and in the other the only ECG change was inferior ST depression with partial inversion of the T wave. In four of six patients, RCA occlusion produced ischemic changes in at least two inferior wall leads and "reciprocal" changes in L1, AVL and at least two anterior wall leads. In LAD as well as RCA occlusions "reciprocal" changes were characterized by inversion of the T wave or inversion of its ascending limb with or without ST depression. The magnitude of the ischemic changes tended to be proportional to the magnitude of the "reciprocal" changes. Our data suggest that: (1) "Reciprocal" changes are not a specific indicator of distant myocardial ischemia due to multivessel disease; (2) the magnitude of ischemic changes correlates with the magnitude of "reciprocal" changes; (3) "Reciprocal" changes may be the only manifestation of acute myocardial ischemia; and (4) "Reciprocal" changes may be represented by inversion of the T wave without displacement of the ST-segment.

Angioplasty, Balloon, Coronary↗

Prevention of acute complications after percutaneous transluminal coronary angioplasty.

The prevention of major complications occurring during or early after percutaneous transluminal coronary angioplasty was evaluated in 376 patients in a randomized, double-blind, placebo-controlled multicenter trial. Starting 24 hours before angioplasty, 187 patients received an aspirin-dipyridamole combination and 189 were given placebo. There were no periprocedural deaths. Periprocedural non-fatal myocardial infarction was diagnosed in 34 patients (9.0%). Q wave myocardial infarction occurred in 16 patients: 3 (1.6%) in the aspirin-dipyridamole group and 13 (6.9%) in the placebo group (p = 0.0113). Non-Q wave myocardial infarction occurred in 18 patients: 6 (3.2%) in the active drug group and 12 (6.3%) in the placebo group (p = 0.1538). Emergency myocardial revascularization was performed in 9 patients in each treatment arm. Q wave myocardial infarction occurred following revascularization in 5 patients (55.5%) in the placebo group and in only 2 (22.2%, p = 0.1670) in the aspirin-dipyridamole group. Thus the incidence of periprocedural Q and non-Q wave myocardial infarction is high in patients not on antiplatelet therapy (13.2%) and is markedly lower in those on the aspirin-dipyridamole combination (4.8%, p = 0.0044). Short-term antiplatelet therapy before and after angioplasty can be recommended for patients who do not have contraindications to this medication.

Acute Disease↗

Percutaneous coronary laser balloon angioplasty: initial results of a multicenter experience.

A multicenter clinical trial was initiated to test the potential safety and short-term efficacy of a percutaneous coronary application of laser balloon angioplasty, which has been shown experimentally to alleviate the common causes (dissection, recoil, thrombus) of suboptimal luminal results of conventional balloon angioplasty. Fifty-five patients, the majority (62%) of whom had relatively high risk lesions, were treated in 10 centers with a laser balloon that was identical in size (3 x 20 mm) to a balloon used for conventional balloon angioplasty performed on the same lesion immediately before laser balloon angioplasty. One or more neodymium:yttrium aluminum garnet (Nd:YAG) (1,060 nm) laser doses of 250 to 450 J were each delivered over a 20 s duration per exposure. Immediately and 1 day after laser balloon angioplasty no significant adverse effects on the arterial lumen were noted in any patient. By computerized image analysis of cineangiograms initial conventional balloon angioplasty failed to achieve a minimal luminal diameter greater than 1.5 mm in 14 patients (25%), including 3 patients with acute closure. However, after subsequent laser balloon angioplasty, minimal luminal diameter exceeded this value in all patients including this subgroup. Overall, minimal luminal diameter increased from 1.74 +/- 0.46 mm after conventional balloon angioplasty to 2.32 +/- 0.31 mm after laser balloon angioplasty (p less than 0.001) with no change found on 1 day and 1 month follow-up angiograms. Thus, laser balloon angioplasty is a safe, effective procedure for improving luminal dimensions after conventional balloon angioplasty.

Adult↗

The role of antiplatelet agents in modifying the extent of restenosis following percutaneous transluminal coronary angioplasty.

We previously reported that a combination of aspirin and dipyridamole given before, during, and for 6 months following percutaneous transluminal coronary angioplasty (PTCA) did not reduce the incidence of restenosis. In that trial, a total of 272 successfully dilated segments in 243 patients reached final quantitative angiography and of these, 86 segments (31.6%) had restenosed (46 of 130 segments in the group of patients given placebo and 40 of 142 segments in the aspirin-dipyridamole group). A secondary analysis of these 86 segments revealed that at follow-up angiography the severity of restenosis was greater in the 46 segments in the placebo group than in the 40 segments in the active treatment group (mean minimal luminal diameter at the stenosis = 0.76 +/- 0.52 and 1.03 +/- 0.45 mm, respectively, p = 0.01). The frequency of total or subtotal occlusions was higher in the placebo group (17.4%) than in the active treatment group (5.0%), but this observation did not reach statistical significance (p = 0.07). Although long-term treatment with aspirin and dipyridamole after successful PTCA does not reduce the incidence of recurrence, this secondary analysis suggests that it is associated with a decreased likelihood of severe restenosis.

Adult↗

Mortality of a cohort of workers in the styrene-butadiene polymer manufacturing industry (1943-1982).

A cohort of 12,110 male workers employed 1 or more years in eight styrene-butadiene polymer (SBR) manufacturing plants in the United States and Canada has been followed for mortality over a 40-year period, 1943 to 1982. The all-cause mortality of these workers was low [standardized mortality ratio (SMR) = 0.81] compared to that of the general population. However, some specific sites of cancers had SMRs that exceeded 1.00. These sites were then examined by major work divisions. The sites of interest included leukemia and non-Hodgkin's lymphoma in whites. The SMRs for cancers of the digestive tract were higher than expected, especially esophageal cancer in whites and stomach cancer in blacks. The SMR for arteriosclerotic heart disease in black workers was significantly higher than would be expected based on general population rates. Employees were assigned to a work area based on job longest held. The SMRs for specific diseases differed by work area. Production workers showed increased SMRs for hematologic neoplasms and maintenance workers, for digestive cancers. A significant excess SMR for arteriosclerotic heart disease occurred only in black maintenance workers, although excess mortality from this disease occurred in blacks regardless of where they worked the longest. A significant excess SMR for rheumatic heart disease was associated with work in the combined, all-other work areas. For many causes of death, there were significant deficits in the SMRs.

Butadienes↗

[Second malignant tumor in children. Report of 22 cases].

Between 1965 and 1988, at the Children's Hospital of Buenos Aires, 22 children developed two successive malignant tumors of different histology. The first tumor was diagnosed between 3 months and 12 years of age: 13 retinoblastoma, 2 rhabdomyosarcoma, 2 non-Hodgkin lymphoma, 2 Hodgkin disease, 1 brain stem glioma, 1 endodermal sinus tumor and 1 Ewing sarcoma. Familial cancer was registered in 6 patients. Children were treated with surgery, intensive chemo and radiotherapy. The second malignancy developed after 2 to 13 years: 10 osteosarcoma, 2 Ewing sarcoma, 2 rhabdomyosarcoma, 2 glioblastoma, 1 medulloblastoma, 1 synoviosarcoma, 1 fibrosarcoma, 1 thyroid carcinoma, 1 acute lymphoblastic leukemia and 1 acute myeloblastic leukemia. In 17 patients, the tumor developed in irradiated field. There was no evidence of the first tumor and only 1 patient was still under chemotherapy. Oncologic treatment was frustrating for these second tumors and 18 children died. Three are alive with no evidence of disease at 2 years, 2 years and 4 months and 3 years after diagnosis. One patient was lost to follow-up. It if postulated that second malignant tumors are consecutive to genetic predisposition and/or to the oncogenic effect of chemo and radiotherapy. The intensity of each treatment modality must be reduced as much as possible to obtain survival while limiting the secondary effects.

Argentina↗

Pharmacological profile of SK&F 105809, a dual inhibitor of arachidonic acid metabolism.

The effects of SK&F 105809, 6,7,-dihydro-2-[4(methylsulfinyl) phenyl]-3-(4-pyridyl) -5[H]-pyrrolo[1,2-a] imidazole, on eicosanoid metabolism, inflammatory responses, algesia and ulcer formation are described. SK&F 105809 was determined to be a prodrug for the sulfide metabolite SK&F 105561 which is an inhibitor of 5-lipoxygenase (5-LO) and prostaglandin H (PGH) synthase activities seen with both the isolated enzyme (IC50S 3 microM) and human monocyte production of the eicosanoids leukotriene B4 (LTB4, IC50 1.0 microM) and prostaglandin E2 (PGE2, IC50 0.1 microM). In-vivo conversion of SK&F 105809 to the active principle SK&F 105561 was observed in both mice and rats. SK&F 105809 inhibited LTB4 and PGE2 production in vivo in inflammatory exudates as well as the production of LTB4 and thromboxane B2 (TxB2) ex vivo in rat blood. SK&F 105809 inhibited oedema and inflammatory-cell infiltration in arachidonic acid-induced inflammation in the mouse ear and rat paw as well as in carrageenan- and monosodium urate crystal-induced peritonitis. SK&F 105809 was also effective in inhibiting mouse collagen-induced arthritis and associated acute-phase reactant protein. At the same time, these acute and chronic models of inflammation were found to be resistant to the action of selective cyclooxygenase inhibitors such as naproxen. In addition, SK&F 105809 possessed analgesic activity in phenylquinone-induced abdominal constriction assay and inhibited indomethacin-induced ulcers.

Administration, Oral↗

Fatal left ventricular perforation following balloon mitral valvuloplasty.

Left ventricular perforation following a balloon mitral valvuloplasty is a rare complication. This paper reports morphological findings in such a case that was fatal. Cardiac tamponade was suspected clinically, but could not be confirmed or treated because of extensive anterior pericardial adhesions related to a previous closed mitral commissurotomy.

Balloon Occlusion↗