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Biomedical subjects

L Schwartz

Publications and source records attributed to L Schwartz.

At least 19 recordsLinked to original sources
PubMed1992

Potency of depolarization-induced transmitter release is determined by divalent cation influx in PC 12 cells.

Evoked release of [3H]dopamine ([3H]DA) from pheochromocytoma cells (PC 12) is dependent on extracellular calcium ([Ca2+]ex), but it can take place if calcium ions (Ca2+) are substituted by other divalent ions such as strontium (Sr2+) and barium (Ba2+). The potency of the divalent cations at supporting release varies with the cell type; in PC 12 cells the order of potency is Ba2+ > Sr2+ > Ca2+. The close correlation between depolarization-evoked Ca2+ entry and depolarization-evoked transmitter release prompted us to examine whether the higher evoked transmitter release in the presence of Sr2+ correlates with an increased evoked Sr2+ influx. Influx studies were conducted on PC12 cells using a radioactive tracer (45Ca2+ or 85Sr2+, < 1 microM) in the presence of either Sr2+ (0.5 mM) or Ca2+ (0.5 mM). Depolarization with K Cl (60 mM) increased evoked 45Ca2+ influx 2-fold when Ca2+ was substituted with Sr2+. Similarly, evoked 85Sr2+ influx increased 1.87-fold by substituting Ca2+ for Sr2+. Thus the amount of evoked cation influx is determined by the type of divalent ion which is accessible in the extracellular medium, independently of the radioactive tracer used. Increased evoked transmitter release in the presence of Sr2+ was associated with increased evoked Sr2+ influx. This suggests that the potency of evoked transmitter release is determined predominantly by the influx of divalent cations. Furthermore, the steps subsequent to cation influx in the release process are equally efficient for both cations.

Animals↗
PubMed1992

Lymphohematopoietic cancer in styrene-butadiene polymerization workers.

1,3-Butadiene and styrene are suspected carcinogens and common chemicals used in the synthesis of rubber. To investigate any potential human hazards from exposure to these chemicals, a case-control study of 59 lymphohematopoietic cancers was conducted within a cohort of male workers employed between 1943 and 1982 in eight North American styrene-butadiene rubber polymer-producing plants. A total of 193 controls were matched to the cases by plant, age, year of hire, duration worked, and survival to time of death of the case. Each job was assigned an estimated exposure rank, and each worker's cumulated rank score was calculated on the basis of the time spent in each job throughout his employment. "Exposure" as a dichotomous variable was defined as a log rank score above the mean of the log scores for the total population of cases and controls within a subtype of cancer. Matched-pair analysis identified a strong association between leukemia and butadiene, with an odds ratio of 9.36 (95% confidence interval 2.05-22.9) and an association between styrene and leukemia (odds ratio = 3.13, 95% confidence interval 0.84-11.2) that did not achieve statistical significance. When exposure to both styrene and butadiene was included in a conditional logistic regression model, the odds ratio for butadiene remained high (odds ratio = 7.39), but the estimated association of leukemia with styrene was small. The results of this study support the hypothesis that exposure to butadiene is associated with the risk of leukemia. There also appears to be an additional risk from work in specific subdivisions of the industry.

Butadienes↗
PubMed1992

Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers.

BACKGROUND: Mutations of the tumor suppressor gene p53 have been identified in breast cancer cell lines, and some breast carcinomas are detectable by immunohistochemical assay because of p53 protein accumulation. PURPOSE: This study was designed to determine whether p53 protein accumulation in breast cancers correlates with p53 gene mutation, with survival, and with five pathobiologic factors associated with prognosis. METHODS: IgG1 monoclonal antibody to human p53 protein (PAb 1801) and immunohistochemical methods were used to detect p53 protein accumulation in archival formalin-fixed, paraffin-embedded, randomly selected carcinomas. We studied 295 invasive ductal carcinomas from the Massachusetts General Hospital; 151 were determined to be sporadic (not hereditary). We also studied 97 invasive ductal carcinomas--21 sporadic and 76 familial (hereditary)--from Creighton University. In addition, we examined 31 archival in situ carcinomas, 15 snap-frozen invasive ductal carcinomas, primary cell cultures from three benign breast tissue samples, and breast carcinoma cell lines MDA-MB-231 and MDA-MB-468. RESULTS: Nuclear p53 protein was observed in 16% of the 31 in situ carcinomas, 22% of the 172 sporadic carcinomas, 34% of the 50 tumors from patients with familial breast cancer, 52% of the 23 tumors from patients with the familial breast and ovarian cancer syndrome, and all three tumors from two patients with the Li-Fraumeni syndrome. There was complete concordance between p53 gene mutation and p53 protein accumulation in the 15 snap-frozen carcinomas and in both breast carcinoma cell lines. Statistically significant associations of p53 protein accumulation with estrogen receptor negativity and with high nuclear grade were found. There were statistically significant associations, independent of other prognostic factors, between p53 protein accumulation and metastasis-free and overall survival, for randomly accrued and for both sporadic and familial tumors. CONCLUSIONS: Immunohistochemically detected p53 protein accumulation was an independent marker of shortened survival and was seen more often in familial than in sporadic carcinomas. Our findings also suggest a correlation between p53 protein accumulation and p53 gene mutation.

Age Factors↗
PubMed1992

Impaired vascular reactivity following angioplasty is mainly due to endothelial injury.

Vasoconstriction occurs frequently following coronary angioplasty and is implicated in the pathogenesis of abrupt closure and restenosis. Control of vasomotor tone is regulated in part directly by smooth muscle cells and indirectly through the endothelium. To study the mechanisms underlying vasoconstriction, the effect of angioplasty and endothelial denudation on endothelium-dependent and -independent relaxation was examined in 15 mongrel dogs. Percutaneous transluminal angioplasty and endothelial denudation of the right femoral artery were performed. Endothelial injury was assessed by adhesion of indium-111-labeled platelets. Endothelium-dependent and -independent relaxation were assessed using acetylcholine and nitroglycerin, respectively. Vessels precontracted with potassium chloride and exposed to acetylcholine showed impaired relaxation in both the angioplasty and denuded groups (angioplasty = 14 +/- 5%, denuded = 0 +/- 0%, normal = 73 +/- 12%; P less than 0.05 for both angioplasty and denuded compared to normal). Precontraction with phenylephrine yielded similar results (angioplasty = 16 +/- 8%, denuded = 4 +/- 2%, normal = 39 +/- 10%; P less than 0.05 only for denuded segment compared to normal). Segments precontracted with phenylephrine and exposed to nitroglycerin did not demonstrate impaired relaxation (angioplasty = 73 +/- 9%, denuded = 68 +/- 9%, normal = 71 +/- 7%, P = ns). Mean indium-111 counts were similar in both the angioplasty and denuded segments (2820 +/- 1481 and 2963 +/- 1228 counts/min/g, respectively) compared to a lower count in the normal segment (1514 +/- 956 counts/min/g). Thus, angioplasty produces significant vascular injury and impairment of vasodilator function, comparable to that caused by endothelial denudation alone. This implies that vasoconstriction seen following coronary angioplasty may be due to endothelial injury and the resultant loss of control of vasomotor tone.

Acetylcholine↗
PubMed1992

Randomized trial of chemotherapy versus chemotherapy plus radiotherapy for stage III-IV A & B Hodgkin's disease.

A total of 151 patients with previously untreated Hodgkin's disease, clinical stages III-IV A & B, were randomized to receive CVPP for 6 cycles, or CVPP plus RT 3000 cGy to previously involved areas between the 3rd and 4th cycles. CVPP consists of cyclophosphamide 600 mg/m2/i.v., vinblastine 6 mg/m2/i.v. on day 1, procarbazine 100 mg/m2/p.o. and prednisone 40 mg/m2/p.o. on days 1 to 14. Both groups displayed similar clinical characteristics at diagnosis. Sixty-six were treated with CVPP + RT (52 St III and 14 St IV) and 85 with CVPP alone (68 St III and 17 St IV). Complete remission was obtained in 57 (86%) of 66 patients who received CVPP plus RT, and in 62 (73%) of 85 patients treated with CVPP. Five and sixteen patients, respectively, achieved partial responses, while 2 in each group died during treatment. At 7 years, duration of complete remission and failure-free survival were: 51% and 45% for those treated with CVPP plus RT, and 23% and 21% with CVPP alone (p = 0.0150 and P = 0.0016, respectively). Overall survival at 7 years was 71% and 58%, respectively (p = 0.1488). A dose analysis performed in 84 pts showed that 91% and 88% received full protocol doses of CPM and PCZ, respectively, in the CVPP + RT group, and 95% and 94% for CVPP. The WBC nadir was 3.5 and 3.7 x mm3, respectively. Of 25 pts on CVPP + RT who relapsed, 9 are now disease-free, 5 are alive with disease and 11 have died, and with CVPP, of 37 relapsing pts, 18 are disease-free, 5 are alive with disease and 14 are dead.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Emergency percutaneous nephrostomy in the septic kidney.

From 250 upper tract obstructive uropathy cases we have studied 64 patients hospitalized with toxico-septic shock. The constant symptom was arterial hypotension. Other 3 patients with long-standing urinary infection due to lithiasis developed this dreaded complication after PNL (staghorn stones-2, pyelic stone-1). In complicated obstructive uropathy cases associated with toxico-septic shock, percutaneous nephrostomy for high urinary derivation in emergency is usually made under local anaesthesia. Its aim is rapid and efficient clearance of kidney obstruction, with minimal damage for the patient; then it is followed by strong antibiotherapy associated with other reanimation and intensive care measures. There were 11 deaths. The stone generating obstructive uropathy was removed subsequently, after the improvement of biological constants and general state of the patient, under the protection of percutaneous nephrostomy.

Acute Disease↗
PubMed1992

[Review of results and clinical analysis of conservative partial surgery associated with postoperative radiotherapy in operable breast cancers stages I amd II].

Over the last 25 years, conservative forms of treatment have been used for the locoregional treatment of early breast cancer, stages I and II (< 3 cm in diameter). At present, the same carcinological results are obtained with conservative surgery and radiation therapy as with radical surgery, and the aesthetic and functional results have improved. Several parameters should be taken into account, ie tumour volume, breast volume, multifocal nature and histologic type. A number of questions still remain unanswered namely: what is the most appropriate conservative surgery (quadrantectomy, tumourectomy or local excision)? What is the most appropriate total irradiation dose (50 Gy over 5 weeks: or 45 Gy over 4.5 weeks)? What is the value of radiation boost in patients with negative resection margins? What is the value of radiation boost in patients with a high local risk of recurrence? What is the most appropriate radiation technique for boost in the primary tumour bed (electrons or iridium implants)? Does the external irradiation of regional lymph nodes improve survival rate? Is it possible to extend conservative treatment to a 4-cm diameter tumour? What is the impact of adjuvant systemic chemotherapy and/or hormonotherapy on the risk of isolated breast cancer recurrence?

Adult↗
PubMed1991

A prospective study on the treatment of retinoblastoma in 72 patients.

Seventy-two patients with retinoblastoma (RTB) (unilateral [47 patients] and bilateral [25 patients]) were studied for a period of 6 years. Treatment consisted of enucleation of those eyes that had severe involvement and was followed by radiation therapy and/or chemotherapy (systemic or intrathecal) according to clinical pathologic staging. All patients who underwent nonsurgical treatment received systemic chemotherapy. Intrathecal chemotherapy was administered when there was involvement of the central nervous system. Nonsurgical treatment consisted of radiation therapy and/or light coagulation, followed by enucleation if there was no response. The overall survival rates were 79% for unilateral disease (median follow-up time, 63 months) and 72% for bilateral disease (median follow-up time, 81 months). Vision was regained in 14 of 21 conserved eyes.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Stress response protein (srp-27) determination in primary human breast carcinomas: clinical, histologic, and prognostic correlations.

Expression of an estrogen-regulated protein known as the 27,000-d heat-shock or stress-response protein (srp-27) was evaluated in human breast carcinomas and established breast cancer cell lines. Results obtained by Northern and Western blot analyses and immunohistochemical methods were concordant. Immunohistochemical assessment of srp-27 expression in 300 breast carcinomas (with median patient follow-up of 8 years) was performed. Twenty-six percent of lymph node-negative and 45% of lymph node-positive tumors were overexpressors. Univariate analysis demonstrated significant correlations between srp-27 overexpression and estrogen receptor (ER) content, pS2 protein expression, nodal metastases, advanced T stage, lymphatic/vascular invasion, and a shorter disease-free survival period (but not a shorter overall survival) for the study population as a whole. Regression tree analysis showed that srp-27 expression was an independent prognostic indicator for disease-free survival only in patients with one to three positive lymph nodes. The Cox proportional hazards model confirmed the independent prognostic significance of nodal involvement, T stage, and ER content but failed to recognize srp-27 overexpression as a significant independent parameter predictive of patient outcome in the patient population as a whole. The observed associations between srp-27 overexpression and more aggressive tumors suggest a biologic role for srp-27 in human breast carcinomas.

Blotting, Western↗
PubMed1991

Evaluation of mast cell activation (tryptase) in two patients suffering from drug-induced hypotensoid reactions.

Tryptase is predominantly found in mast cells, where it resides in secretory granules, and is released with other mediators during mast cell degranulation. By using a newly developed commercial assay for measurements of tryptase levels we have investigated two cases of suspected drug-induced anaphylaxis. Each patient had a similar clinical presentation, consisting of hypotension and cyanosis after administration of thiopentone and suxamethonium. One of the patients showed a highly elevated serum level of tryptase reaching 26 micrograms/l 30 min after the initial reaction. In addition, slightly elevated levels of specific IgE antibodies to thiopentone were detected. The other patient with similar symptoms showed no increase in the level of tryptase, nor any specific IgE to thiopentone or suxamethonium. These data indicate the patient I suffered from true anaphylaxis, whereas the reaction of patient II occurred by a different mechanism.

Anaphylaxis↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

[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↗
PubMed1990

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↗
PubMed1990

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↗