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Biomedical subjects

L Schwartz

Publications and source records attributed to L Schwartz.

At least 73 records · Page 4Linked to original sources
PubMed1998

The transcription factor HNF3beta is required in visceral endoderm for normal primitive streak morphogenesis.

During early embryogenesis, the transcription factor HNF3beta is expressed in visceral and definitive endoderm, node, notochord and floorplate. A targeted mutation in the HNF3&bgr ; gene results in the lack of a definitive node and notochord. Furthermore, lack of HNF3beta results in failure of proper primitive streak elongation. To address whether HNF3beta is required in visceral endoderm, we have used tetraploid embryo-ES cell aggregations to generate chimeric mouse embryos with wild-type visceral endoderm and homozygous mutant HNF3beta embryonic ectoderm or vice versa. Replacing the visceral endoderm of mutant HNF3beta embryos rescued proper primitive streak elongation and, conversely, mutant visceral endoderm imposed a severe embryonic-extraembryonic constriction on wild-type embryonic ectoderm. Restoration of normal streak morphogenesis was not sufficient to allow formation of the node and notochord in HNF3beta mutant embryos. Thus, our results demonstrate that HNF3beta has two separate roles in primitive streak formation. One is to act within the visceral endoderm to promote proper streak morphogenesis. The second is autonomous to the node and its precursors and involves specification of node and notochord cell fates. HNF3beta mutant embryos rescued for the embryonic-extraembryonic constriction developed further than mutant embryos, allowing examination of later roles for HNF3beta. We show that such mutant embryos lack foregut and midgut endoderm. In addition, left-right asymmetry is affected in the mutant embryos.

Animals↗
PubMed1997

A requirement for Flk1 in primitive and definitive hematopoiesis and vasculogenesis.

Mouse embryos lacking the receptor tyrosine kinase, Flk1, die without mature endothelial and hematopoietic cells. To investigate the role of Flk1 during vasculogenesis and hematopoiesis, we examined the developmental potential of Flk1-/- embryonic stem cells in chimeras. We show that Flk1 is required cell autonomously for endothelial development. Furthermore, Flk1-/- cells do not contribute to primitive hematopoiesis in chimeric yolk sacs or definitive hematopoiesis in adult chimeras and chimeric fetal livers. We also demonstrate that cells lacking Flk1 are unable to reach the correct location to form blood islands, suggesting that Flk1 is involved in the movement of cells from the posterior primitive streak to the yolk sac and, possibly, to the intraembryonic sites of early hematopoiesis.

Amnion↗
PubMed1997

The effect of treatment positioning on normal tissue dose in patients with prostate cancer treated with three-dimensional conformal radiotherapy.

PURPOSE: To prospectively assess the effect of supine vs. prone treatment position on the dose to normal tissues in prostate cancer patients treated with the three-dimensional conformal technique. METHODS AND MATERIALS: Twenty-six patients underwent three-dimensional treatment planning in both the supine and prone treatment positions. The planning target volume and normal tissue structures were outlined on each CAT scan slice, and treatment plans were compared to assess the effect of treatment position on the volume of rectum, bladder, and bowel exposed to the high dose of irradiation. RESULTS: The average dose to the rectal wall and the V95 (volume of rectal wall receiving at least 95% of the prescription dose) for the prone position were 64 and 24% of the prescription dose, respectively, compared to 72 and 29%, respectively, for the supine position (p < 0.05). When the average rectal wall dose was used as an endpoint, 14 of the 26 patients (54%) had an advantage for the prone position compared to 1 (4%) who demonstrated an advantage for the supine position (p < 0.0002). Similarly, when V95 of the rectal wall was used as a measure of comparison, 15 patients (58%) had an advantage for the prone position compared to 1 (4%) who demonstrated an advantage for the supine position (p < 0.0002). In 13 patients (50%), a change from supine to the prone position was associated with reduction of the V95 to levels < 30% of the prescription dose compared to 3 patients (11%) in whom such an advantage resulted from change of the prone to the supine position (p < 0.005). The effect of treatment position on the rectal wall dose was most pronounced in the region of the seminal vesicles. An increased volume of bowel was also noted in the supine position. The treatment position, however, had no significant impact on the dose to the bladder wall. CONCLUSIONS: Three-dimensional conformal radiotherapy for prostate cancer in the prone position is associated with significant reduction of the dose to the rectum and bowel resulting in an improvement in the therapeutic ratio.

Humans↗
PubMed1997

Coronary angioplasty of a posterolateral branch with severe proximal vessel tortuosity.

We present a case of a patient who experienced recurrent angina 15 months after coronary bypass surgery. A single lesion distal to a graft anastomosis was identified in the posterolateral coronary artery. There were two severe angulations, each greater than 90 degrees proximal to the lesion, with access possible only through the saphenous vein graft to the posterior descending artery. For ultimate success, such challenging anatomy required a combination of an array of guidewires, secondary support catheters, and a deflecting balloon.

Angina Pectoris↗
PubMed1997

Evolution of cardiovascular risk after liver transplantation: a comparison of cyclosporine A and tacrolimus (FK506).

The development of atherosclerotic cardiovascular complications is a common and serious problem for the long-term survivors of organ transplantation. Cyclosporine A plus steroid-based immuno-suppression regimens in these patients are associated with the development of hypertension, hyperlipidemia, obesity, and diabetes mellitus. Whether the new immunosuppressive agent tacrolimus (FK506) confers any advantage in terms of these cardiovascular risk factors has been less well studied. We compared serial changes in blood pressure, lipids, body weight, and glucose levels during the first 12 months after liver transplantation in patients using either cyclosporine A (n = 39) or tacrolimus (n = 24)-based immunosuppression. By 12 months, the prevalence of hypertension, hypercholesterolemia, and obesity was increased in the cyclosporine A group compared to tacrolimus: 82% versus 33%, 33% versus 0%, and 46% versus 29%, respectively (all p < .05). Triglyceride and total cholesterol levels were 196 +/- 23 versus 125 +/- 13 mg/dL and 225 +/- 9 versus 159 +/- 7 mg/dL for the cyclosporine A versus tacrolimus groups, respectively (p < .05). Cumulative posttransplant steroid dose was not related to the observed lipid changes in either group, although the increase in triglycerides was positively correlated to weight gain and diuretic use in the cyclosporine A group. The incidence of diabetes mellitus was not increased from baseline in either group. These results indicate that tacrolimus, compared to cyclosporine A, is associated with a less adverse cardiovascular risk profile in the first year after liver transplantation. Whether these differences persist and become clinically relevant to a liver transplant recipient population that is increasingly older and has more preexisting cardiovascular disease remains to be determined.

Adult↗
PubMed1997

Hymenoptera sting anaphylaxis and urticaria pigmentosa: clinical findings and results of venom immunotherapy in ten patients.

BACKGROUND: Occasional patients with urticaria pigmentosa and anaphylaxis after Hymenoptera stings have been described. In this situation the question arises: Is anaphylaxis IgE-mediated or induced by pharmacologic mediator release from mast cells? METHODS: We investigated 10 patients with histologically confirmed urticaria pigmentosa and a history of anaphylaxis after honeybee or Vespula stings before and during immunotherapy with the respective venom. RESULTS: In eight of 10 patients, an elevated serum tryptase level was found. In two of 10 patients, no venom-specific IgE could be detected by either skin tests or RAST. Five patients had no detectable venom-specific serum IgE, and in the remaining patients the level was low (<1 Phadebas RAST unit). Venom immunotherapy was well tolerated and caused only one mild systemic reaction in a patient during the dose increase phase. Six patients were re-stung while receiving venom immunotherapy: only one had a mild systemic reaction (angioedema) after a Vespula sting. CONCLUSION: Anaphylactic symptoms after Hymenoptera stings in patients with urticaria pigmentosa are most often IgE-mediated but can occasionally be observed in the absence of IgE sensitization to venom allergens. Venom immunotherapy can be safely and successfully used in patients with urticaria pigmentosa and sting anaphylaxis.

Adult↗
PubMed1997

A double-blind, randomized study of three antimicrobial regimens in the prevention of infections after elective colorectal surgery.

The objective of this study was to assess the prophylactic efficacy of cefoxitin, ceftizoxime, and metronidazole-gentamicin in colorectal surgery. A double-blind, randomized prospective clinical trial design was used in a Canadian tertiary care teaching hospital. Patients were randomized to one of three treatment groups and received three doses of a study drug (30 min preoperative and 2 postoperative doses at 12 and 24 h). Cefoxitin and ceftizoxime were given as 1000-mg doses. Metronidazole-gentamicin was given as 500 mg of metronidazole plus 120 mg of gentamicin in a minibag. High-risk patients (bowel ischemia, diabetic, current steroid use, etc.) received 10 postoperative doses. Patients with infections, prior antibiotics, or study drug allergies were excluded. Over 30 months, 153 patients were enrolled. Thirty-one patients were excluded for protocol violations. Of the 122 evaluable patients (38 ceftizoxime, 45 metronidazole-gentamicin, 39 cefoxitin), there was no difference across groups regarding sex, age, weight, preoperative Apache II score, and prior history of bowel surgery. Groups were equivalent regarding surgeon, nursing unit, high-risk status (six ceftizoxime, seven metronidazole-gentamicin, seven cefoxitin), bowel preparation, and procedure (including blood loss, drains, organ injury, intraoperative complications). Clinically significant infection requiring systemic antibiotics (7-day hospital and 30-day follow-up) was identified in 0% of ceftizoxime, 15% of metronidazole-gentamicin, and 26% of cefoxitin receiving patients (p = 0.005). Mean ASEPSIS scores for each group were 2.3 (range 0-15) for ceftizoxime, 9.2 (range 0-45) for metronidazole-gentamicin, and 10.4 (range 0-75) for cefoxitin (p = 0.01). Ceftizoxime patients tended to have a shorter total hospital stay (12.2 days versus 19.7 days for cefoxitin versus 13.9 days for metronidazole-gentamicin; p = 0.04), although the procedure to discharge interval was not significantly different (p = 0.09). There was no difference in clinical outcome according to risk status. Anaerobic bacteria were observed more commonly in the ceftizoxime and cefoxitin groups, whereas enteric Gram-negative aerobes were observed most often in the metronidazole-gentamicin group. The study regimens were generally well tolerated. Drug costs were equivalent between ceftizoxime and cefoxitin and lowest with the metronidazole-gentamicin regimen. Ceftizoxime appears to be more effective for the prevention of infection in colorectal surgery than either cefoxitin or metronidazole-gentamicin in the dosage regimens studied.

Adult↗
PubMed1997

[Initial results of proton therapy in choroidal melanoma at the d'Orsey Center for Proton Therapy; the first 464 cases].

PURPOSE: Retrospective analysis of the treatment of choroidal melanoma with protontherapy at the Centre de protonthérapie d'Orsay, France. PATIENTS AND METHODS: Between September 1991 and September 1995, 612 patients presenting with choroidal melanoma were treated by protontherapy in Orsay. Following initial management of the first 464 patients, results were analyzed, as were results after a 1-year follow-up for 305 patients, a 2-year follow-up for 169 patients, and a 3-year follow-up for 59 patients. RESULTS: Univariate analysis showed that the actuarial local recurrence rate was 5%, the 3-year survival rate 88%, and the overall metastasic rate 5%. The initial tumor volume was the most significant predictive factor for visual results and metastases. Multivariate analysis revealed that visual results were significantly related to the initial tumor volume, initial retinal detachment, and total dose delivered to the optic nerve and macula. CONCLUSION: Protontherapy of choroidal melanoma allows in most cases conservation of the eye without modification of survival. Visual results mainly depend on the site and size of the tumor.

Choroid Neoplasms↗
PubMed1997

Mortality related to diagnostic cardiac catheterization. The importance of left main coronary disease and catheter induced trauma.

BACKGROUND: The mortality of diagnostic catheterization is very low but still exists. Large series have documented left main disease as the most important anatomical risk factor but have not clarified the mechanism. OBJECTIVES: To determine the mortality of diagnostic catheterization in a single high volume centre over a 9 year period and assess any change during this period; to compare this experience with that of larger multicentre surveys; to identify the clinical and anatomical risk factors; to investigate the mechanism of the event; to develop guidelines for prevention METHODS: Cardiac catheterization records were reviewed over a 9 year period and patients dying during or within 24 hours were identified. The clinical and anatomical profile of the patients who died were compared with the overall group to search for independent risk factors. The angiograms of the deaths were reviewed for a mechanism. RESULTS: There were 30 deaths in 42,345 procedures (0.071%). There was no change in the incidence over the 9 years. Left main coronary disease was an overwhelming risk factor (incidence 0.7%, p < .002 compared to all other subgroups) and no other anatomical subgroup including triple vessel disease was at greater risk than the overall group. Dissection of the left main coronary artery by the diagnostic catheter was the mechanism of death in 20 cases (67%) CONCLUSIONS: Left main disease and catheter induced trauma are the most important risk factor for and mechanism of death during diagnostic catheterization and may account for the unchanging incidence. Technical guidelines are described which may reduce this risk.

Adult↗
PubMed1997

Time-limited psychotherapy with Operation Desert Storm veterans.

Time-limited psychotherapy conducted 2 to 9 months after demobilization was evaluated with Persian Gulf Theater veterans of Operation Desert Storm (ODS). Thirty five treatment-seeking veterans were contrasted with 20 non-treatment-seeking ODS Persian Gulf veterans in a repeated measures design at pretest, posttest, and 6-week followup assessments. In addition, psychotherapy participants at followup were contrasted with 80 non-treatment-seeking ODS Persian Gulf veterans from the same military units who were assessed one time at a comparable time point. Time-limited psychotherapy was associated with sustained improved psychosocial functioning and reduced levels of psychiatric and stress-related symptomatology.

Adaptation, Psychological↗
PubMed1997

Do patient and physician expectations predict response to pain-relieving procedures?

OBJECTIVE: To evaluate the relationships between patient and physician pretreatment expectations of pain relief and subsequent pain relief reported by chronic pain patients immediately after treatment. DESIGN: Prospective study of consecutive patients undergoing a procedure in a pain clinic for treatment of chronic pain. Patients rated their current pain level and their expectation of pain relief immediately prior to undergoing a procedure (e.g., intravenous drug infusion, nerve block) for the treatment of chronic pain. Simultaneously and independently, the treating physician completed a similar questionnaire. At completion of the procedure, patients rated their current pain level and degree of pain relief. SETTING: University of Washington Multidisciplinary Pain Center procedure suite. PATIENTS: Forty-six consecutive chronic pain patients. INTERVENTION: Intravenous drug infusions and nerve blocks. OUTCOME MEASURES: Current pain and pain relief ratings. RESULTS: Patients' pain relief expectation ratings were not correlated significantly with their postprocedure pain relief ratings or pre-post procedure changes in pain ratings. However, a statistically significant correlation was found between physician expectations of pain relief and patient pain relief ratings and patient pre-post procedure changes in pain. CONCLUSIONS: The results of this study suggest that physicians are better predictors than are patients of patients responses to these procedures and/or that physicians may somehow subtly communicate their expectations to patients during the procedure, and these expectations then influence patient response. Patient pretreatment expectations may not always play a significant role in nonspecific treatment effects.

Adult↗
PubMed1997

Bicalutamide for advanced prostate cancer: the natural versus treated history of disease.

PURPOSE: To determine the therapeutic effects of bicalutamide 200 mg in patients with prostate cancers of different hormone sensitivities. METHODS: Patients with progressive prostate cancer were treated with bicalutamide 200 mg daily. Before treatment, patients' tumors were classified on the basis of prior hormone exposure and by serum testosterone levels into androgen-dependent and androgen-independent groups. Prior exposure to flutamide and response to flutamide withdrawal was also considered. Outcomes were reported independently on the basis of posttherapy changes in prostate-specific antigen (PSA), measurable disease, and radionuclide bone scans. RESULTS: Outcomes varied by prior hormone exposure as a higher proportion of patients with progression of androgen-dependent tumors showed posttherapy PSA decreases of more than 50% or more than 80%, measurable disease regression, and improvement on radionuclide bone scans than did patients with androgen-independent progression. Within the category of androgen-independent progression, clinical benefit was observed in patients who had previously progressed on flutamide, independent of the response to flutamide withdrawal. Patients who had progressed on a gonadotropin-releasing hormone (GnRH) analog alone had a low response proportion, whereas those who progressed after two or more hormone therapies did not respond. Overall, the drug was well tolerated. After progression on bicalutamide monotherapy, one third of patients with androgen-dependent progression responded to medical castration with a GnRH analog. CONCLUSION: Classifying patient tumors on the basis of prior hormone exposure permits a more precise estimate of the potential benefit of a specific hormone therapy for the individual patient. The precision is further increased by reporting the effects of a drug on each parameter of disease independently. The difference in outcomes for patients with androgen-independent progression suggests that the specific hormone therapy administered and the response to that therapy can influence the biology of the relapsing tumor and the sensitivity to subsequent therapies. The sensitivity to bicalutamide after progression on flutamide deserves further study.

Aged↗
PubMed1997

Chimeric analysis of fibroblast growth factor receptor-1 (Fgfr1) function: a role for FGFR1 in morphogenetic movement through the primitive streak.

Fibroblast growth factor (FGF) signaling has been implicated in the patterning of mesoderm and neural lineages during early vertebrate development. In the mouse, FGF receptor-1 (FGFR1) is expressed in an appropriate spatial and temporal manner to be orchestrating these functions. Mouse embryos homozygous for a mutated Fgfr1 allele (fgfr1(delta tmk)) die early in development, show abnormal growth and aberrant mesodermal patterning. We have performed a chimeric analysis to further study FGFR1 function in the morphogenesis and patterning of the mesodermal germ layer at gastrulation. At E9.5, fgfr1(delta tmk)/fgfr1(delta tmk) cells showed a marked deficiency in their ability to contribute to the extra-embryonic, cephalic, heart, axial and paraxial mesoderm, and to the endoderm of chimeric embryos. Analysis at earlier stages of development revealed that fgfr1(delta tmk)/fgfr1(delta tmk) cells accumulated within the primitive streak of chimeric embryos, and consequently failed to populate the anterior mesoderm and endodermal lineages at their inception. We suggest that the primary defect associated with the fgfr1(delta tmk) mutation is a deficiency in the ability of epiblast cells to traverse the primitive streak. fgfr1(delta tmk)/fgfr1(delta tmk) cells that accumulated within the primitive streak of chimeric embryos tended to form secondary neural tubes. These secondary neural tubes were entirely fgfr1(delta tmk)/fgfr1(delta tmk) cell derived. The adoption of ectopic neural fate suggests that normal morphogenetic movement through the streak is essential not only for proper mesodermal patterning but also for correct determination of mesodermal/neurectodermal cell fates.

Animals↗
PubMed1997

Implementation and evaluation of patient-specific three-dimensional internal dosimetry.

UNLABELLED: Current methods for calculating the absorbed dose in a target region from a source region rely on a standard "reference man" geometry and assume an uniform distribution of radiolabel. While this approach is acceptable at the low levels of radioisotope administered for most diagnostic purposes, the generality of the calculations is not adequate for doses at the higher levels required for therapy and is not easily extendible to tumor dosimetry. METHODS: We have developed an integrated system which utilizes patient anatomy and radionuclide distribution in the calculation of absorbed dose rate or total dose to any user-defined target region. Images of radionuclide distribution (PET/SPECT) are registered to anatomic images (CT/ MRI) and then entered into a three-dimensional internal dosimetry software system (3D-ID) where regions of interest are defined. Dose calculations are performed by the mathematical convolution between a user-specified, dose-point kernel with the activity in the source volume over the target volume. The resulting dose rate distribution may be scaled by cumulated activity to yield absorbed dose. In addition to calculating the mean dose, dose-volume histograms may be generated which plot absorbed dose with respect to percent of volume. The method was evaluated using selected standard man phantom organs. RESULTS: Dose estimates for two patient studies are included to illustrate differences between patient-specific and MIRD-based calculations. The package provides an alternative approach to image display and three-dimensional internal dose calculations. CONCLUSION: The dose-volume histogram representation of absorbed dose to a target volume provides valuable information in assessing tumor control probability and normal tissue toxicity.

Dose-Response Relationship, Radiation↗
PubMed1997

Clinical outcomes of patients more than one year following randomization in the Canadian Coronary Atherectomy Trial (CCAT).

BACKGROUND: The Canadian Coronary Atherectomy Trial (CCAT) assessed, in a randomized comparison, the clinical and angiographic outcomes following atherectomy with those following balloon angioplasty for the treatment of de novo lesions in the proximal one-third of the left anterior descending artery (LAD). Although the procedural success rate was somewhat higher and the postprocedure lumen larger in patients treated with atherectomy, lumen dimensions, restenosis rates and clinical outcomes were similar in the two groups at six months. To determine whether late differences emerged between the groups, clinical follow-up was obtained at a median of 18 (range 10 to 31) months after randomization. METHODS AND RESULTS: Patients were contacted monthly by telephone for the first six months. Subsequent follow-up information was obtained in 272 (99%) of the 274 randomized patients via a clinic visit or telephone interview with the patient and/or a relative. Additional information was obtained from the referring physician as required. There were no differences in adverse events between the two groups during follow-up. In patients randomized to atherectomy compared with balloon angioplasty, death occurred in 1.5% versus 2.2% (cardiac death 0.7% versus 0.7%); myocardial infarction in 5.1% versus 5.9% (Q wave 1.5% versus 1.5%); coronary bypass surgery in 13.1% versus 12.6%; and repeat target lesion intervention in 22.6% versus 21.5%. Persistent or recurrent Canadian Cardiovascular Society class III/IV angina not treated by a further intervention was present in 1.5% versus 2.2%. The combined end-point of death or nonfatal myocardial infarction occurred in nine (6.6%) versus 11 (8.1%) patients and any adverse cardiac event in 50 (36.5%) versus 53 (39.3%). Multivariate logistic regression indicated that unstable angina, reference vessel size and preprocedure minimum lumen diameter were the only variables independently associated with adverse events. CONCLUSIONS: The initial choice of directional atherectomy or balloon angioplasty had no impact on clinical outcome over a period of 18 months in this patient population. With either technique, just over 60% of patients with proximal LAD disease experienced sustained symptomatic improvement without an adverse event following a single procedure, and 80% achieved this status following a repeat percutaneous intervention.

Angioplasty, Balloon, Coronary↗