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Biomedical subjects

L Schwartz

Publications and source records attributed to L Schwartz.

At least 127 records · Page 7Linked to original sources

Definition and measurement of restenosis after successful coronary angioplasty: implications for clinical trials.

Angiographic restenosis represents the most established measure of long-term outcome in most prospective clinical trials of coronary angioplasty (PTCA). The accuracy of assessing this endpoint is of utmost importance. The purpose of this article is to propose guidelines for the use of coronary angiography in this setting. First, the cineangiograms must be of high technical quality and performed in a high proportion of consecutive patients in follow-up under controlled study conditions that are reproducible. Second, computer-assisted quantitative coronary angiographic analysis is essential to minimize interobserver and intraobserver variability in stenosis measurement between successive studies. The following recommendations are presented for quantitative coronary angiographic analysis. Because biplane orthogonal views cannot always be performed both at baseline and at follow-up, stenosis measurement in the single-plane, most severe view often constitutes the most consistent and practical approach. The edge-detection method is still much more reproducible and accurate than densitometry and should be the preferred method of analysis. Measurement of reference diameter by the interpolated method is more objective than measurement by the user-defined approach and should be used whenever possible. Finally, measurements of absolute minimum diameter and percent diameter stenosis are both important in the assessment of outcome in clinical trials. Absolute minimum diameters are independent of variations in reference diameter, and the extent of reduction in minimum diameter between the immediate postangioplasty and follow-up angiograms, when expressed in dichotomous or continuous fashion, accurately defines the extent of vessel wall hyperplasia as an endpoint. On the other hand, vessel size corresponds in general to the size of myocardium subserved, and absolute changes do not take into account this physiologic fact. Therefore defining restenosis in terms of significant reduction in percent diameter stenosis is also a useful approach because of its clinical relevance. Thus clinical restenosis requires that a successfully dilated segment (< 50% diameter stenosis) show a > or = 50% diameter stenosis at follow-up angiography with, in addition, a meaningful degree of change, that is, exceeding 2 SDs of observer variability in quantitative measurements which, in our experience, translates into > or = 15% difference between early postangioplasty and follow-up angiography measurements.

Angioplasty, Balloon, Coronary↗

Acute hemodynamic and respiratory effects of amniotic fluid embolism in the pregnant goat model.

OBJECTIVE: Our purpose was to determine the acute-phase central hemodynamic and respiratory effects of raw, filtered, filtered and boiled, and meconium-containing amniotic fluid. STUDY DESIGN: Pregnant goats (Capra hircus) in the last one third of pregnancy were given freshly collected autologous amniotic fluid in a volume of 2.5 ml/kg of body weight. Observations were then made at 10, 30, 60, 120, and 180 minutes after amniotic fluid embolism. Pulmonary artery catheters and femoral artery lung water catheters were placed for specimen and data collection. RESULTS: Marked pressor responses were observed in both the pulmonary and systemic circulations with all amniotic fluid infusions. The pressor response was similar with raw, filtered, and filtered and boiled amniotic fluid. The pressor response seen with amniotic fluid containing meconium was significantly greater than that seen with the other forms. No significant effects were observed on cardiac or respiratory function except in the meconium group, where transient left ventricular dysfunction was accompanied by an acute increase in extravascular lung water and dysoxia. CONCLUSIONS: The Capra hircus model is appropriate for the further study of amniotic fluid embolism. The acute pressor effects are transient and involve both the systemic and pulmonary circulations. Left ventricular dysfunction and dysoxia were observed only with embolism of amniotic fluid containing meconium.

Amniotic Fluid↗

Lack of clinical evidence of sodium retention in children with idiopathic short stature treated with recombinant growth hormone.

In adults patients, administration of human growth hormone and growth hormone synthesized by recombinant DNA technology (rGH) results in sodium and fluid retention and weight gain. This study was performed to determine whether rGH administration in children with idiopathic short stature (ISS) caused any clinical evidence of sodium retention. The parameters assessed included blood pressure, height, weight, plasma renin activity (PRA), aldosterone, and atrial natriuretic peptide (ANP). These were measured in nine treated children after 0, 3, 6, 9, and 12 months of growth hormone therapy; seven untreated children served as controls. After 12 months, the treated children had no significant increases in measurements of blood pressure, PRA, aldosterone, and ANP. Although treated children gained more weight than control patients, they also grew faster. Therefore, there was no significant difference in weight for height percentile for treated children when compared with normal controls. After 1 year of therapy, the administration of rGH to children with ISS does not result in any clinically significant evidence of sodium retention.

Aldosterone↗

Role of transforming growth factor-beta in chronic lymphocytic leukemia.

TGF-beta is an important immunoregulator as it suppresses proliferation and function of B- and T-lymphocytes. In the present study we have examined the cellular localization and secretion of TGF-beta in B-cells from normal donors and patients with CLL and have assessed the influence of TGF-beta 1 on DNA synthesis in these cells. Using anti-LC(1-30)--a polyclonal anti-TGF-beta 1 antibody--TGF-beta was localized to discrete sites within the cytoplasm of both normal and malignant lymphocytes. These areas co-localized with areas detected by an antigranule antibody (D545), suggesting that TGF-beta may be stored within cytoplasmic secretory vesicles. Both normal B- and CLL cells contained low or undetectable levels of TGF-beta mRNA and secreted low and equivalent amounts of TGF-beta. Compared to untreated cells, DNA synthesis was reduced by TGF-beta 1 to a mean +/- S. E. of 0.84 +/- 0.07 in CLL cells and this was significantly less (p < 0.001) than that observed in normal B-cells (mean +/- S. E. of control, 0.12 +/- 0.02). In 3 of the 18 patients, TGF-beta 1 stimulated DNA synthesis. The reduced inhibition of leukemic cell DNA synthesis by TGF-beta 1 in CLL may provide these cells with a growth or survival advantage over normal lymphocytes and contribute to their selective accumulation.

DNA, Neoplasm↗

A birdcage resonator for intracavitary MR imaging.

An intracavitary probe for magnetic resonance imaging of the pelvis has been developed that takes advantage of the "inside-out" spatial characteristics of a birdcage resonator. The probe consists of an eight-leg, birdcage resonator in a low-pass configuration operating in receive-only mode. The resonator circuit is mounted on a solid rod, is encased in Teflon, and has been used to obtain detailed images of pelvic anatomy in a male canine. The approximate cylindrical symmetry of the external sensitivity profile of this type of circuit, employed in an intracavitary application, demonstrates the potential superiority of this type of probe design over single-loop intracavitary coils. Axial, coronal, and sagittal MR images, obtained with 8 and 16 cm fields of view, are presented to illustrate the advantages of this type of intracavitary probe compared with conventional body-coil images. The prototype described in this report has been designed for clinical use in human subjects and is currently undergoing testing to determine its efficacy in the evaluation of rectal, prostate, and gynecologic pathology.

Animals↗

Cancer epidemiology among styrene-butadiene rubber workers.

The standardized mortality ratios for some cancers of the lymphohaematopoietic system were high in an early cohort analysis. Since the presence of large numbers of unexposed workers could conceal risks within a cohort, a case-control study was designed to examine the relationship between estimated exposures and the occurrence of these cancers. The results suggested that the risk for leukaemia was associated with exposure to butadiene and with work in specific areas. Modelling, using rank scores, indicated an increase in the risk for leukaemia with increasing exposure score. Use of cases validated by review of hospital records and selection of a new set of controls did not change the findings. The data indicated that comparison of scores within the same time frame improved the model and increased the estimated odds ratio, suggesting that exposure time or dose rate may prove to be the important variable for risk. Exact measurements from the companies involved showed significant correlations between assigned ranks and level of exposure derived from personal monitoring for butadiene but not for styrene. Thus, use of the measured values might be expected to show an association between leukaemia and exposure to butadiene. The standardized mortality ratio for leukaemia among long-term workers hired before 1960 who had worked in the three plants where the geometric mean butadiene level was three to five times higher than those in the other plants is 1.8 times higher than that of the US population. An appropriate algorithm for comparing cases and controls on the bases of the measured samples is being developed.

Butadienes↗

[Invasive carcinoma of the conjunctivo-corneal limbus. Apropos of a case].

The limbus is an elective site of epithelial malignancies, mostly represented by precarcinomatous lesions. An 83-year-old female patient was operated for an exophytic tumor of the limbus. Histological examination showed an invasive squamous carcinoma. As the excision was not complete, complementary radiation therapy (45 Gy) was applied with a good short-term result. This case report emphasizes the value of early diagnosis and treatment of limbal tumors at the stage of precancerous lesions.

Aged↗

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↗

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↗

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↗

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↗

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↗

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↗

[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↗

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↗

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↗

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↗