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Biomedical subjects

H M Lazarus

Publications and source records attributed to H M Lazarus.

At least 145 records · Page 8Linked to original sources
PubMed1992

Endovascular grafting for the treatment of abdominal aortic aneurysms.

Endovascular repair of an aortic aneurysm will allow aneurysm exclusion using a graft passed inside the aorta either percutaneously or from a small groin incision. Morbidity and mortality associated with this procedure should be decreased considerably. The first grafting systems currently being developed will be appropriate for repair of aneurysms of the abdominal and descending thoracic aorta that can be repaired using tube grafts. Several research groups have shown that endovascular grafting of the aorta can be accomplished successfully.

Animals↗
PubMed1992

Kinetics of erythrogenesis after bone marrow transplantation.

To determine the kinetics of bone marrow erythrogenesis after bone marrow transplantation, the authors counted reticulocytes (by blood smear and flow cytometry) and compared those data with neutrophil and platelet recovery in 23 consecutive bone marrow transplant patients. The earliest indication of marrow recovery after allogeneic and autologous bone marrow transplantation was defined as the second increasing cell count after the lowest recorded count, provided that the trend continued upward. Recovery of marrow function was detected earlier in 10 of 23 patients using reticulocyte counts than by either neutrophil or platelet count alone. Specifically, in 8 of these 10 patients, recovery of erythropoiesis was determined earlier by flow cytometric examination than by the blood smear method. On the other hand, combining the data using the earliest value of platelet, neutrophil, and reticulocyte counts indicated that the mean day of recovery in our patient population was determined to be 12.1 +/- 4 days after marrow infusion. In patients undergoing autologous and allogeneic bone marrow transplantation, serial neutrophil and reticulocyte count determinations are complementary in early clinical detection of successful engraftment.

Adolescent↗
PubMed1992

Bone marrow and blood findings after marrow transplantation and rhGM-CSF therapy.

Sequential bone marrow biopsy specimens and peripheral blood findings were evaluated from patients treated with recombinant human granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for recurrent non-Hodgkin's lymphoma. Parallel increases were found in white blood cell count and marrow cellularity and in absolute neutrophil count, monocyte count, and marrow myeloid:erythroid ratio. Platelet count recovery and the reappearance of megakaryocytes occurred later than granulocyte/monocyte recovery. Elevated peripheral eosinophil counts and eosinophilic hyperplasia in the marrow were noted during recombinant human granulocyte-macrophage colony-stimulating factor administration, as was the appearance of distinctive, prominently granulated and/or vacuolated neutrophils and neutrophilic precursors in the blood and bone marrow. No detrimental effects of recombinant human granulocyte-macrophage colony-stimulating factor administration in the marrow or peripheral blood were observed.

Adult↗
PubMed1992

High-dose carmustine, etoposide, and cisplatin and autologous bone marrow transplantation for relapsed and refractory lymphoma.

PURPOSE: We determined the toxicity and efficacy of a new preparative autologous bone marrow transplantation (ABMT) regimen in patients with relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. PATIENTS AND METHODS: Forty-four non-Hodgkin's lymphoma and 35 Hodgkin's disease patients 16 to 63 years of age were given intravenous carmustine (BCNU) 600 to 1,050 mg/m2, etoposide 2,400 to 3,000 mg/m2, and cisplatin 200 mg/m2 (BEP) and ABMT. Fifty-nine patients also received 15 to 20 Gy local radiation (involved-field radiotherapy [RI]) to active or previously bulky (> 5 cm) disease sites. RESULTS: Nonhematologic toxicities included nausea, vomiting, high-tone hearing loss, stomatitis, esophagitis, diarrhea, and hepatic and pulmonary toxicity. Two patients died within 40 days of marrow infusion as a result of sepsis and one patient died 7 months after transplant as a result of pulmonary fibrosis. Complete remissions (CRs) were noted in 72% (n = 57) of patients (n = 33 non-Hodgkin's lymphoma; n = 24 Hodgkin's disease). Forty patients (51%) remained alive and disease-free (n = 24 non-Hodgkin's lymphoma; n = 16 Hodgkin's disease) at a median of 17 (range, 8 to 57) months after marrow reinfusion. CONCLUSIONS: This regimen seems to be effective for relapsed lymphoma patients whose disease continues to exhibit chemotherapy sensitivity (16 of 24 [67%] disease-free). Furthermore, this regimen seems to be effective in patients who have never attained a CR (seven of 19 [37%] disease-free).

Adolescent↗
PubMed1992

High-dose carboplatin and etoposide with autologous bone marrow transplantation in refractory germ cell cancer: an Eastern Cooperative Oncology Group protocol.

PURPOSE: A phase II trial was undertaken to assess the feasibility, toxicity, and efficacy of high-dose carboplatin and etoposide with autologous bone marrow transplantation in patients with relapsed or refractory germ cell tumors. PATIENTS AND METHODS: Forty patients with recurrent germ cell cancer received carboplatin 500 mg/m2 and etoposide 400 mg/m2 given at 7, 5, and 3 days before marrow infusion. Autologous marrow infusion (day 0) was accomplished using one half of the bone marrow harvested before chemotherapy. Patients who achieved a complete or partial response with the first cycle of treatment received a second identical cycle of chemotherapy followed by infusion of the remaining cryopreserved bone marrow. RESULTS: Objective responses were obtained in 17 of the 38 patients (45%) assessable for response, including eight partial and nine complete remissions. Five of these patients remain in continuous complete remission with minimal follow-up of 1 year. Toxicity encountered was primarily hematologic, and five patients (13%) died of treatment-related complications. Significant toxicities often seen with high-dose cisplatin (ototoxicity, neurotoxicity, and renal toxicity) were manageable in this regimen of high-dose carboplatin. CONCLUSIONS: This trial confirms the curative potential of high-dose carboplatin and etoposide in highly refractory germ cell cancer.

Adolescent↗
PubMed1992

Phase II clinical trial of carboplatin in relapsed and refractory leukemia.

Carboplatin is a second-generation platinum complex drug which has demonstrated activity against a variety of neoplasms including acute leukemia, particularly when given by continuous intravenous (i.v.) infusion. Adults with acute myelogenous leukemia (AML) or acute lymphoblastic leukemia (ALL), either refractory or in first or second relapse, were given a continuous i.v. infusion of carboplatin at a dose of 315 mg/m2 daily for 5 days. A second course was given if the bone marrow at day 14 showed persistent leukemia. If the marrow was hypoplastic, treatment was delayed until marrow recovery was documented. Those with residual leukemia were given a second course. Those achieving complete remission (CR) were given an additional course as consolidation. Of the 46 eligible patients entered (36 AML and 10 ALL) eight achieved CR (17%) of which 6 were AML and 2 ALL. Of nine primary refractory patients, two achieved CR, one AML and one ALL. Excluding the inevaluable patients (protocol violations, patient refused further therapy, early deaths prior to day 14, the CR rate was eight of 28 (29%). All except two CRs required two courses of induction. The non-hematologic toxicity was minimal except for renal and auditory toxicity. Renal toxicity greater than grade 2 was seen in 17 patients and was associated with concomitant use of nephrotoxic antibiotics. In two patients, renal failure was a major factor in the cause of death. Ototoxicity was observed in 11 patients, but was grade 3 in only three. There were 18 deaths during the study. Fourteen died of infection, two died of infection and hemorrhage, one died of hemorrhage while aplastic, and one died of other causes. This trial indicates that carboplatin is an active agent in acute leukemia and warrants further investigation.

Bone Marrow↗
PubMed1992

Abdominal aortic aneurysm. Incidence in a hospital population at risk.

The incidence of abdominal aortic aneurysms has been studied in various selected patient groups. In this study, 100 male patients on a cardiology service who were older than 60 years and over 170 cm (5 ft 7 in) tall were examined by abdominal ultrasonograms. A total of 11 aneurysms were found, 2 of which were more than 4.5 cm in diameter. Other abnormalities that were found included renal disease in 20 patients (1 carcinoma treated with a curative nephrectomy), gallbladder disease in 22 patients, and miscellaneous intra-abdominal disease in 6 patients; 47 patients had no abnormalities found. The aneurysms of these patients were classified by a patient's height in 5-cm (2-in) increments. No significant difference in the incidence of aneurysms was found within the groups, but these groups are small and a significant difference would not be expected. It is of interest that the two large aneurysms were in persons taller than 180 cm (5 ft 11 in). Previous ultrasonographic studies of aneurysmal incidence have not reported other intra-abdominal disease.

Aged↗
PubMed1992

Serum erythropoietin levels and blood component therapy after autologous bone marrow transplantation: implications for erythropoietin therapy in this setting.

To determine the potential impact of recombinant human erythropoietin (EPO) therapy in patients undergoing autologous bone marrow transplantation (BMT) and colony-stimulating factor therapy, we assayed endogenous serum EPO levels and noted blood transfusion requirements in relapsed non-Hodgkin's lymphoma patients treated with high-dose chemo-radiation therapy and autologous BMT. Hematocrit and reticulocyte counts were determined daily, and hematocrit was maintained in the 25-30% range by transfusion according to criteria established by our hospital transfusion committee. EPO levels were measured by radioimmunoassay and were determined at baseline, throughout therapy, and 2 and 3 months after BMT. Serum EPO levels increased more than 25-fold above baseline in most subjects after initiating chemoradiation therapy. No correlation was noted between serum EPO and hematocrit, reticulocyte count or serum creatinine. Total red blood cell units transfused ranged from 4 to 15 (mean 7.7). Mean total donor exposures (red blood cell plus platelet units transfused) were 83.6 units (range 16-175). Serum EPO levels increased early in the course of preparation for autologous BMT and remained elevated for at least 2-3 weeks thereafter although at a lower level. Red blood cell transfusions were required despite very high EPO levels after BMT. Red cell transfusions, moreover, accounted for only 9.2% (69 of 746) of total donor exposures and only 5.8% (42 of 746) of donor exposures during the interval when pharmacologic doses of erythropoietin might be of benefit. In contrast to the potential benefit of colony-stimulating factors such as G-CSF and GM-CSF in BMT, our study suggests limited value for erythropoietin therapy in this setting.

Adult↗
PubMed1992

Escalating the intensity of post-remission therapy improves the outcome in acute myeloid leukemia: the ECOG experience. The Eastern Cooperative Oncology Group.

These ECOG trials have demonstrated that progressive increments in the intensity of post-remission therapy result in improving long-term, disease-free survival in adults with AML. The median duration of disease-free survival and long-term outcome from different post-remission therapies are summarized in Table 4. [table: see text] Despite the suggestive evidence of the ordered increment in value of intensive consolidation therapy, allogeneic and autologous bone marrow transplantation, it remains to be proved that the differences observed in our preceding studies are statistically significant and clinically meaningful. These remaining questions led to the current ECOG study, EST 3489, a randomized intergroup study conducted with members of the Southwest Oncology Group. The study includes all patients with de novo AML up to age 55; the schema is shown in Figure 3. Induction therapy consists of idarubicin plus cytarabine instead of DAT. A modified short course of this induction therapy is repeated after CR. Patients who have a histocompatible sibling are offered allogeneic bone marrow transplantation. The remaining patients are randomized to receive either autologous bone marrow transplantation or a single course of high-dose cytarabine. Autologous bone marrow transplantation utilizes the previously described high-dose busulfan and cyclophosphamide regimen plus 4-HC purging of the bone marrow. The dosage of cytarabine in the intensive consolidation arm is 3 gm/M2/day IV on days 1-6. The results of this study should determine the relative merits of these different approaches to post-remission therapy. [table: see text] As mentioned earlier, demonstration of improved CR rates is limited by the morbidity and mortality from the myelosuppression that results from induction therapy. This is especially marked for older patients with AML. In patients, ages 55-70 years old, the ECOG is conducting a randomized trial (EST 1490) of conventional induction therapy +/- GM-CSF to determine if accelerated neutrophil recovery can reduce the mortality of induction therapy and thereby increase the remission rate. It may be that the application of GM-CSF and other colony-stimulating factors can increase the CR rate for all patients, increasing the number of patients potentially eligible for cure by post-remission therapy.

Acute Disease↗
PubMed1991

Recombinant granulocyte-macrophage colony-stimulating factor after autologous bone marrow transplantation for relapsed non-Hodgkin's lymphoma: blood and bone marrow progenitor growth studies. A phase II Eastern Cooperative Oncology Group Trial.

Sixteen patients with relapsed non-Hodgkin's lymphoma underwent autologous bone marrow transplantation and infusion of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF). Treatment consisted of involved-field radiotherapy, cyclophosphamide 60 mg/kg/d intravenously (IV) for 2 days, and fractionated total body irradiation (1,200 cGy). Autologous bone marrow was thawed and infused IV, followed 3 hours later by the first infusion of IV rhGM-CSF 11 micrograms/kg/d over 4 hours. Infusions of rhGM-CSF were continued daily until either both neutrophil count exceeded 1,500/microL and platelet count exceeded 50,000/microL, or until 30 days after marrow re-infusion. Toxicities encountered were mild and included fever, chills, hypertension, alopecia, rash, diarrhea, stomatitis, myalgias, and synovial (knee) effusions. Neutrophil recovery greater than 500/microL occurred a median of 14 days (range, 9 to 30 days) after marrow infusion, significantly earlier than in a comparable group of historic controls who recovered counts at a median time of 20 days (range, 12 to 51 days) (P = .00002). Median time to self-sustaining platelet counts greater than 20,000/microL was 23.5 days (range, 12 to 100 days), comparable with the historic group (P = .38). One bacteremia (central venous catheter exit site infection with Staphylococcus epidermidis) and one local infection (Giardia lamblia in stool) occurred. Patients received a median of 11.4 (range, 4.4 to 20.2) x 10(4) colony-forming unit granulocyte-macrophage (CFU-GM) progenitors per kg. Stem cell progenitors CFU-GM, CFU-granulocyte, erythroid, monocyte, megakaryocyte (CFU-GEMM), and burst-forming unit-erythroid (BFU-E) were detected in the bone marrow as early as 7 days after marrow re-infusion, and increased in proportion to peripheral blood counts, but by 30 to 60 days still remained much lower than before transplant. Neutrophils transiently decreased in 13 of 16 patients (median decrease, 42%) within 24 to 72 hours of discontinuing rhGM-CSF infusions. These data suggest that rhGM-CSF therapy enhances neutrophil recovery by forcing stem cells to produce mature elements at an enhanced rate but may not affect marrow stem cell and early progenitor population sizes.

Adult↗
PubMed1991

Selective in vivo removal of rheumatoid factor by an extracorporeal treatment device in rheumatoid arthritis patients.

A prospective phase II trial was conducted to assess the feasibility, tolerance, and efficacy of a device designed for selective removal of rheumatoid factor from the plasma of rheumatoid arthritis patients. The device contained terpolymer hydrogel-coated plates with chemically attached, aggregated human immunoglobulin G, and it operated as an immunoaffinity column. Sixty-one patients aged 25 to 73 underwent weekly plasmapheresis treatments (the primary therapy phase). During the trial, patients continued current rheumatoid arthritis medications without dose adjustments. All patients received two to six treatments (primary therapy). Responding patients were eligible to continue apheresis treatment every 2 to 6 weeks (maintenance therapy). No serious, untoward side effects were noted in the course of this study; of 640 treatments, only 2 (in different patients) were aborted, one because of complaints of dizziness and angioedema and the other because of chest tightness and shortness of breath. Except for a significant (p less than 0.05) decrease in serum iron, no significant changes in complete blood count, serum electrolytes, renal and hepatic function tests, or serum C3 and C4 were noted. Although the trial was not designed to determine clinical efficacy, patients noted less morning stiffness, longer time to onset of fatigue, and improved global pain assessment (p less than 0.004); significant objective improvements were noted in joint pain, tenderness, swelling, and the number of affected joints (p less than 0.001). One-half of the treated patients had at least a 50 percent improvement in objective measures of antirheumatic activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Topical fluoroquinolones: antimicrobial activity and in vitro corneal epithelial toxicity.

To assess the potential of fluoroquinolones as topical antimicrobial agents, we evaluated in vitro the antimicrobial activity of five fluoroquinolones (ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, and temafloxacin), as well as gentamicin, tobramycin, and cefazolin against 96 isolates of common bacterial corneal pathogens. Ciprofloxacin and temafloxacin were the most active quinolones [minimal inhibitory concentration inhibiting 90% of stains (MIC90) of 1 microgram/ml], followed by ofloxacin (MIC90 2 micrograms/ml), and norfloxacin and pefloxacin (MIC90s 4 micrograms/ml). In contrast, gentamicin and tobramycin MIC90s were 32 and 64 micrograms/ml, respectively; cefazolin MIC90 was greater than 2048 micrograms/ml. The corneal epithelial cytotoxicity of the fluoroquinolones also was evaluated utilizing an in vitro assay of 3H-thymidine uptake of rabbit corneal epithelial cell cultures. The least to greatest toxicity of the fluoroquinolones were as follows: ciprofloxacin and temafloxacin less than norfloxacin less than ofloxacin less than pefloxacin. Our study suggests that the fluoroquinolones, especially ciprofloxacin and temafloxacin, possess excellent in vitro activity against common bacterial corneal pathogens and are less toxic to the corneal epithelium than the aminoglycosides.

4-Quinolones↗
PubMed1991

Contamination during in vitro processing of bone marrow for transplantation: clinical significance.

We determined the prevalence and clinical significance of positive microbiologic cultures obtained from 194 consecutive bone marrow harvests intended for infusion in 188 consecutive adult bone marrow transplant patients. Microbiologic cultures were obtained at harvest, after manipulation in vitro (for ABO imcompatibility or purging procedures), and at the time of thawing and infusion (after earlier cryopreservation). Only one of 194 marrow harvests was culture-positive intra-operatively (from an ABO-compatible allogeneic marrow that was infused without manipulation). None of 39 other allogeneic marrows (including 21 ABO-incompatible marrows which were manipulated in vitro) and none of 154 autologous marrows (including 40 which were purged in vitro) grew bacteria or fungi. On the other hand, 12 of 153 (8%) bone marrow samples were positive for micro-organisms after thawing at the time of infusion. The predominant organisms cultured were gram negative bacilli (including five Pseudomonas sp.), probably introduced during the thawing process in a water bath. In only one of 13 contaminated marrows was the same organism(s) (Pseudomonas picketti and Pseudomonas paucimobilis) recovered in vivo during the transplant course. This patient experienced a bacteremia which was eradicated without sequelae. Contamination of marrow can occur during the procurement and in vitro handling processes. With proper sterile technique bone marrow infusion does not pose a significant infectious risk for the immunocompromised transplant patient.

Adolescent↗
PubMed1990

The treatment of progressive non-Hodgkin's lymphoma with intensive chemoradiotherapy and autologous marrow transplantation.

Intensive chemoradiotherapy, with or without additional local radiotherapy, and unpurged autologous marrow transplantation was given to 68 patients with progressive non-Hodgkin's lymphoma. Responses were attained in 44 patients (65%, 95% confidence intervals [CI], 52% to 76%), including 37 who achieved complete responses. Fifteen patients (22%, 95% C.I. 13% to 34%) remain free of disease (including 11 continuously) at a median of 5.3 (range 3.1 to 9.1) years later. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and the absence of a history of prior radiotherapy (P = .02, chi 2 test) were associated with achievement of complete plus partial responses. Higher Karnofsky scores (P less than .01, Mann-Whitney U test) and less resistant disease status at transplantation (P = .04, chi 2 test) were significant when calculations were limited to complete responses. Karnofsky scores were also associated with the probability of freedom from progression (P = .02, log-rank) for responding patients. Also, Karnofsky scores and the absence of prior radiotherapy (P less than .01 and P = .01, respectively, log-rank) were associated with improved survival. Progressive lymphoma was the chief cause of failure; progression usually occurred less than 6 months after transplantation, most often at the sites of active disease before the transplant. However, five patients (including four with high-grade non-Hodgkin's lymphoma) suffered hematogenous patterns of relapse; four of these five patients had no prior history of marrow involvement. Other causes of mortality included interstitial pneumonitis, sepsis, hemorrhage and renal failure. Intensive chemoradiotherapy and autologous marrow transplantation produces durable remissions in some patients with progressive non-Hodgkin's lymphoma. Since such therapy is more effective when given to patients with signs of less advanced disease, earlier treatment would be the simplest way to produce improved results. However, improved conditioning regimens will also be needed, and measures to reduce occult lymphoma stem cell contamination with the autograft may also be required to increase the likelihood of cure in some patients.

Adolescent↗
PubMed1990

Phase I trial of high-dose etoposide, high-dose cisplatin, and reinfusion of autologous bone marrow for lung cancer.

We undertook a phase I trial using fixed-dose cisplatin, escalating doses of etoposide, and reinfusion of previously obtained autologous bone marrow in 29 relapsed or refractory small cell and non-small-cell lung cancer patients. Median age was 59 years (range of 38-68 years). Three patients had small-cell and 26 patients had non-small-cell lung cancer. Patients received i.v. cisplatin 200 mg/m2 over 5 days and i.v. etoposide 600 mg/m2/day for 3 days (total of 1,800 mg/m2) that was escalated to 800, 1,000, 1,200, 1,400, and 1,600 mg/m2/day for 3 days (total of 2,400-4,800 mg/m2). Cryopreserved autologous bone marrow was thawed and reinfused through a central venous catheter the second day after the completion of chemotherapy. Toxicities included nausea, vomiting, alopecia, high-tone hearing loss, mucositis, diarrhea, renal insufficiency, metabolic acidosis, and severe myelosuppression. The duration of neutropenia (less than 500 neutrophils/microliter) ranged from 5 to 22 days (median of 11 days) and the duration of severe thrombocytopenia (platelets of less than 20,000/microliters untransfused) ranged from 2 to 19 days (median of 9 days). Reversible renal insufficiency (peak serum creatinines of 6.7, 6.6, 4.3, and 3.5 mg/dl) occurred in four patients who completed the therapy. In three patients, death occurred within 4 weeks of chemotherapy and marrow reinfusion. Three complete and 12 partial remissions (range of 1+(-)22+ months, median of 3 months) were observed. No response was noted in eight patients and tumor progression within 1 month of transplant occurred in two patients. The maximally tolerated dose of etoposide was 1,400 mg/m2/day (total of 4,200 mg/m2), since two of three patients developed life-threatening diarrhea at the 1,600 mg/m2/day (total of 4,800 mg/m2) dose. The encouraging antitumor effects of this regimen suggest that this approach may be useful therapy for lung cancer and other tumors sensitive to VP-16 and cisplatin.

Adult↗
PubMed1990

Infusion of high doses of undiluted etoposide through central venous catheters during preparation for bone marrow transplantation.

We employed a new method to administer etoposide in high doses to 51 patients undergoing autologous bone marrow transplantation. Undiluted etoposide (20 mg/ml) was sterilely drawn into Luer-Lok plastic syringes, connected to IV extension tubing, and infused intravenously by a syringe pump over 3-4 hours. Patients received etoposide at doses ranging from 400 to 1600 mg/m2 per day (median dose: 800 mg). Total actual etoposide doses infused during the transplant period ranged from 2200 to 9000 mg. The infusion rate range was 4.1-13.4 mg/min. No episodes of hypotension, bronchospasm, or hemorrhagic cystitis were noted during or within 3 days of the etoposide infusion. In addition, no cracking of the infusion apparatus was observed in any of the 148 separate infusions. Serum bicarbonate concentrations fell significantly in 6 patients who received the higher etoposide doses. This procedure is superior to the standard method of etoposide drug delivery, since large doses of etoposide may be given without the concomitant administration of large volumes of fluid over short periods of time.

Adenocarcinoma↗