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Biomedical subjects

A Hussein

Publications and source records attributed to A Hussein.

At least 19 recordsLinked to original sources
PubMed1999

Impact of consolidation radiotherapy in patients with advanced breast cancer treated with high-dose chemotherapy and autologous bone marrow rescue.

PURPOSE: To examine the impact of consolidation radiotherapy (RT) after high-dose chemotherapy with autologous bone marrow rescue (HDC) in patients with advanced breast cancer. PATIENTS AND METHODS: Between 1988 and 1994,425 patients with metastatic or recurrent breast cancer received doxorubicin, fluorouracil, and methotrexate (AFM) induction chemotherapy in a single-institution prospective trial. One hundred patients who achieved a complete response were randomized to receive HDC (cyclophosphamide, cisplatin, carmustine), with autologous bone marrow rescue immediately after AFM, or to observation, with HDC to be administered at next relapse. Seventy-four of the 100 became eligible for RT; 53 received consolidation RT (HDC RT+ and 21 did not (HDC RT-). The assignment of RT was not randomized. The RT+ and RT- groups were similar with regard to number of involved sites, the fraction of patients with only local-regional disease, age, and interval since initial diagnosis. Local control at previously involved sites and distant sites was assessed with extensive radiologic and clinical evaluations at the time of first failure or most recent follow-up. The impact of RT on failure patterns, event-free survival, and overall survival was evaluated. RESULTS: Sites of first failure were located exclusively at previously involved sites in 28% of RT+ patients versus 62% of RT- patients (P < .01). Event-free survival at 4 years was 31% and 21% in the RT+ and RT-groups, respectively (P = .02). Overall survival at 4 years was 30% and 16% in the RT+ and RT- groups, respectively (P = .20). CONCLUSION: Patients with advanced breast cancer who were treated with HDC without RT failed predominantly at the initial sites of disease. The addition of RT appeared to reduce the failure rate at initial disease sites and may improve event-free and overall survival. Our observations await verification in a trial in which assignment to RT is randomized.

Adult↗
PubMed1998

Pharmacokinetic interaction between ondansetron and cyclophosphamide during high-dose chemotherapy for breast cancer.

PURPOSE: Both ondansetron and cyclophosphamide are thought to be metabolized by hepatic microsomal processes. The purpose of this study was to evaluate the potential pharmacokinetic interactions between ondansetron and high-dose alkylating agent chemotherapy. METHODS: A total of 54 breast cancer patients receiving high-dose cyclophosphamide, cisplatin and carmustine were treated prospectively in four sequential cohorts. Cohorts I and II received continuous infusions of both ondansetron and prochlorperazine, and cohorts III and IV received a continuous infusion of ondansetron alone at the same doses. All patients received lorazepam every 4 h. A group of 75 matched historical controls had received a continuous infusion of prochlorperazine with lorazepam. Pharmacokinetic monitoring of each drug used in the high-dose chemotherapy regimen was conducted. RESULTS: Median AUCs of cyclophosphamide in patients receiving ondansetron (73.6 mg/ml x min) were lower than those of the control patients (88.3 mg/ml x min, n = 75, P = 0.0004), but the median cisplatin AUC was approximately 10% higher and no difference in the disposition of carmustine was demonstrated. Patients treated with ondansetron displayed a higher frequency of headaches than the controls. The frequency of achieving complete emetic control was greater in the ondansetron + prochlorperazine groups compared to the ondansetron alone groups and was greater in both these groups than in the prochlorperazine alone group on the first day of therapy only. CONCLUSION: Ondansetron altered the systemic exposure to cyclophosphamide when these agents were administered concomitantly. Ondansetron did not substantially improve overall emetic control when used alone but may improve control in combination with prochlorperazine. Future randomized studies are needed to delineate the effect of ondansetron on the disposition of the active cyclophosphamide metabolites so that clinical implications can be addressed.

Antiemetics↗
PubMed1998

Reduced mortality following bone marrow transplantation for breast cancer with the addition of peripheral blood progenitor cells is due to a marked reduction in veno-occlusive disease of the liver.

Clinical trials involving breast cancer in the Duke University Bone Marrow Transplant Program were evaluated to assess the association between type of hematopoietic support and treatment-related morbidity/mortality. Case histories of patients treated with high-dose chemotherapy and hematopoietic rescue on three separate protocols between 1986 and 1994 were reviewed. This included 307 patients with stage IV disease and 85 patients with high-risk (10 or more positive axillary lymph nodes) stage II or III disease. One hundred and twenty-eight of these patients were rescued with autologous bone marrow (BM) alone and 264 additionally received autologous peripheral blood progenitor cells (PBPC). The 100 day transplant-related mortality rate in those patients who received BM alone was 20.3%, with an overall mortality rate due to the high-dose chemotherapy procedure of 24.2%. The PBPC-treated group experienced a 100 day transplant-related mortality of only 6.1% and an overall trans-plant- related mortality of 10.2%. Sixteen of 31 deaths were attributed to veno-occlusive disease (VOD) in the group that received BM alone compared to only one VOD-related death in the PBPC group. These data demonstrate a marked improvement in transplant-related mortality which is related to the use of PBPC. This effect has been almost entirely due to a reduction in mortality from hepatic veno-occlusive disease.

Adult↗
PubMed1998

A randomized trial of recombinant human interleukin-11 following autologous bone marrow transplantation with peripheral blood progenitor cell support in patients with breast cancer.

This study assessed the safety and efficacy of recombinant human interleukin (rhIL)-11 in decreasing platelet transfusion requirements in patients with breast cancer who were undergoing autologous bone marrow transplantation (ABMT) with peripheral blood progenitor cell (PBPC) support. After high-dose therapy with cyclophosphamide, cisplatin, and carmustine, 80 patients were randomized to one of three treatment groups: placebo (26), 25 microg/kg of rhIL-11 (28), and 50 microg/kg of rhIL-11 (26). Of those randomized, 75 (94%) received at least one dose of the masked study drug and the remaining 5 (6%) withdrew consent before study drug administration. In the placebo group, each patient received an average 12.4 (+/-10.2) platelet transfusions vs. 9.2 (+/-5.0) in the 25-microg/kg rhIL-11 group (p = 0.17) and 9.9 (+/-3.5) in the 50-microg/kg rhIL-11 group (p = 0.34). There was no statistically significant difference between the rhIL-11 groups and the placebo group in the median number of days to platelet recovery. Neutrophil and red blood cell recovery were similar for all treatment groups. The imbalance in the number of patients already alloimmunized at study entry in the rhIL-11 groups (12) and in the placebo group (1) may have confounded the primary efficacy assessment. Most adverse events were related to the high-dose chemotherapy. Generally mild edema and minor conjunctival bleeding (grades 1 or 2) were statistically associated with rhIL-11 administration (p < 0.04). There was no association between rhIL-11 and the occurrence of atrial arrhythmias, although there was a suggestion of an association with rhIL-11, 5 of 50 cases vs. 1 of 25 in the placebo group. Two cardiovascular events, tachycardia and hypotension (grade 1 or 2), occurred in the 50-microg/kg rhIL-11 group. The number of patients who discontinued study drug dosing because of an adverse event was distributed across all treatment groups. In summary, rhIL-11 was safe and well tolerated in this study. The results did not demonstrate that rhIL-11 treatment significantly decreased platelet transfusion requirements after high-dose chemotherapy with ABMT and PBPC support.

Adult↗
PubMed1998

The addition of paclitaxel to continuous infusion 5-fluorouracil is an active regimen for metastatic breast cancer.

Metastatic breast cancer is commonly thought to be incurable. Treatment advances have resulted in increased response rates, although such responses are often more palliative than curative. A regimen of continuous infusion 5-fluorouracil (5FU) or continuous infusion 5-fluorouracil with paclitaxel was studied in patients with metastatic breast cancer and measurable disease. The induction therapy preceded high-dose ifosfamide, carboplatin, and melphalan in a phase I-II trial. Eighty-seven patients were enrolled in the trial. Forty-five received continuous infusion 5-fluorouracil as induction and 42 received 5-fluorouracil and paclitaxel. The single-agent, continuous infusion 5-fluorouracil cohort had one complete response (2%) and eight partial responses (18%). The combination continuous infusion 5-fluorouracil and 3-hour paclitaxel regimen produced four complete responses (10%) and 17 partial responses (40%). The combination regimen of continuous infusion 5-fluorouracil with bolus paclitaxel was well tolerated and with a 50% response rate, is an active regimen for women with metastatic breast cancer.

Adult↗
PubMed1997

A phase I trial of recombinant human interleukin-1 beta (OCT-43) following high-dose chemotherapy and autologous bone marrow transplantation.

We studied the effects of escalating doses of recombinant human IL-1 beta in patients receiving high-dose chemotherapy and ABMT for metastatic breast cancer or malignant melanoma. Sixteen patients received IL-1 beta, 4 to 32 ng/kg/day administered subcutaneously for 7 days beginning 3 h after bone marrow infusion. Three patients at the highest dose level also received G-CSF following completion of IL-1 beta. All patients completed the 7 days of therapy. The majority of patients experienced chills and fever following one or more injections, and seven had severe pain at the injection site. There was one episode of hypotension and one episode of transient confusion at the highest dose level; other significant toxicity was not identified. Recovery of neutrophils to > 0.5 x 10(9)l and platelet transfusion independence occurred at a median of 23 and 22 days, respectively, which was comparable to historical controls. The mean number of bone marrow colony-forming unit granulocyte-macrophage (CFU-GM) per 10(5) mononuclear cells on day +21 post-ABMT was more than twice that of control patients or patients receiving G-CSF or GM-CSF. A linear correlation was found between the dose of IL-1 beta and endogenous concentrations of several cytokines. These patients also displayed significantly higher concentrations of endogenous G-CSF compared to historical controls receiving GM-CSF. While IL-1 beta was moderately toxic and had no effect on recovery of peripheral blood counts after ABMT, the increased number of bone marrow CFU-GM suggests that the addition of G- or GM-CSF to a short course of IL-1 beta may accelerate hematologic recovery.

Adult↗
PubMed1997

Maintenance electroconvulsive therapy and cognitive function.

BACKGROUND: ECT is rarely used as a prophylactic treatment. A 74-year-old woman with unstable bipolar affective disorder receiving maintenance ECT presented a unique opportunity to measure the cognitive effects of continuing ECT. METHOD: A single case report with serial psychometric testing during over 400 ECT treatments as a single maintenance treatment. RESULTS: Serial testing did not demonstrate progressive cognitive deterioration, but consistent cognitive deficits typical of acute treatment were evident. The degree of cognitive difficulty may be related to the frequency of treatment. CONCLUSIONS: Maintenance ECT can be an effective prophylactic treatment for selected patients. Cognitive effects would appear to be no greater than with acute treatment and seem to be non-progressive.

Aged↗
PubMed1996

A double-blind clinical trial comparing World Health Organization oral rehydration solution with a reduced osmolarity solution containing equal amounts of sodium and glucose.

OBJECTIVE: To compare the safety and efficacy of an oral rehydration solution (ORS) containing 75 mmol/L of sodium and glucose each with the standard World Health Organization (WHO) ORS among Egyptian children with acute diarrhea. METHODS: One hundred ninety boys, aged 1 to 24 months, who were admitted to the hospital with acute diarrhea and signs of dehydration were randomly assigned to receive either standard ORS (311 mmol/L) or a reduced osmolarity ORS (245 mmol/L). Intake and output were measured every 3 hours. RESULTS: In the group treated with reduced osmolarity ORS, the mean stool output during the rehydration phase was 36% lower (95% confidence interval, 1%, 100%) than in those treated with WHO ORS. The relative risk of vomiting during the rehydration phase was significantly lower in children treated with reduced osmolarity ORS (relative risk, 2.4; 95% confidence interval, 1.2, 4.8). During the maintenance phase, stool output, mean intake of food and ORS, duration of diarrhea, and weight gain were similar in the treatment groups. The relative risk of treatment failure (need for unscheduled administration of intravenous fluids) was significantly increased in children receiving standard WHO ORS (relative risk, 7.9; 95% confidence interval, 1.1, 60.9). The mean serum sodium concentration at 24 hours was significantly lower in children receiving the reduced osmolarity ORS solution (134 +/- 6 mEq/L) than in children receiving the standard WHO ORS (138 +/- 7 mEq/L) (p < 0.001). The relative risk of the development or worsening of hyponatremia was not increased in children given the reduced osmolarity ORS, and urine output was similar in the treatment groups. CONCLUSION: The reduced osmolarity ORS has beneficial effects on the clinical course of acute diarrhea in children by reducing stool output, and the proportion of children with vomiting during the rehydration phase, and by reducing the need for supplemental intravenous therapy. These results provide support for the use of a reduced osmolarity ORS in children with acute noncholera diarrhea.

Acute Disease↗
PubMed1996

Modification of the standard pterional approach for aneurysms of the anterior circle of Willis.

A modification of the standard pterional approach for aneurysms of the anterior circulation is described. Our technique utilizes a smaller curvilinear skin incision, splitting the temporalis and a limited craniectomy. Reduced tissue dissection results in a smoother postoperative course and improves cosmesis without compromising neurological recovery. Minimal brain retraction is required as the technique allows the surgeon to make full use of the basal opening without temporalis muscle obscuring the view.

Aneurysm, Ruptured↗
PubMed1996

Xanthogranulomatous pyelonephritis--an unusual renal disease in childhood.

We report on a 6-year-old boy with Xanthogranulomatous pyelonephritis. This unusual type of renal inflammation has a typical clinical picture that is important to bear in mind. The affected child is often seriously ill with a palpable flank mass leading to initial suspicion of malignancy. Modern imaging procedures help in obtaining a pre-operative diagnosis.

Child↗
PubMed1996

Thrombotic microangiopathy as a complication of high-dose chemotherapy for breast cancer.

Five hundred and eighty-one patients with stage II-IV breast cancer were treated at Duke University Medical Center with high-dose chemotherapy, followed by hematopoietic support. All patients received a conditioning regimen of cyclophosphamide, cisplatin and carmustine. Of these patients, 15 (2.6%) developed symptoms similar to the hemolytic-uremic syndrome with evidence of thrombotic microangiopathy (TMA). The time of onset ranged from 75 days to 281 days post-transplant, with a median of 143 days. Hemolytic anemia and thrombocytopenia, without alternative cause, were required for diagnosis. All patients were treated with steroid therapy. In addition, 12 patients were treated primarily with plasmapheresis, and received a median of 46 treatments. Additional therapy included staphylococcal protein A column apheresis (eight patients), vincristine (three patients) and danazol (one patient). The mortality rate was 11 of 15 patients (73%). These patients had a median survival of 41 days from diagnosis of TMA (range 2-76 days). The four survivors are alive at 76, 186, 1837 and 2387 days from diagnosis of TMA. Three of these patients received twice daily plasmapheresis and protein A column apheresis therapy. One patient recovered without specific therapy. TMA is an infrequent complication of high-dose chemotherapy, but is associated with a high mortality. It frequently follows significant pulmonary drug toxicity. Survival may be improved with early diagnosis and aggressive plasmapheresis therapy.

Anemia, Hemolytic↗
PubMed1996

Ocular toxicity following high dose chemotherapy and autologous transplant.

A 49-year-old woman received an autologous transplant for breast cancer. Six weeks later she noticed visual disturbance of the left eye which correlated with a visual field abnormality. There was a milder degree of visual disturbance in the right eye. Treatment with high-dose steroids partially stabilized the problem, which was felt to be an ischemic optic neuropathy. She ultimately died of respiratory failure. Pathology of the optic nerves revealed demyelination. Visual disturbances following high-dose chemotherapy are uncommon; the pathology to date has not been elucidated. Steroid therapy may be useful.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Use of densitometric measurements for evaluation of bone regeneration in lengthening of the long bone shaft].

A series of 18 long bone lengthenings in 16 children has been analyzed. To assess new bone formation sonography, DEXA and computerized tomography have been employed. Sonography proved to be most useful for elongation monitoring, but densitometry delivered most data concerning quantity and distribution of the new bone formation especially during stabilization stage. DEXA combined with CT allowed for making decision of the removal of ilizarov apparatus.

Bone Density↗
PubMed1995

Guillain-Barre syndrome following autologous bone marrow transplantation.

The pathogenesis of the Guillain-Barre syndrome (GBS) is felt to involve alterations in cellular and humoral immune responses. We report the case of a 44-year-old female with stage IV breast cancer who developed GBS 2 days after receiving high dose chemotherapy with bone marrow and peripheral progenitor cell support, and granulocyte-macrophage colony stimulating factor (GM-CSF). Her clinical status stabilized with plasmapheresis. This report lends further support to hypotheses regarding cellular immune alterations in the pathogenesis of GBS.

Adult↗