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Biomedical subjects

E Salloum

Publications and source records attributed to E Salloum.

At least 19 recordsLinked to original sources

Neutropenic infections in 100 patients with non-Hodgkin's lymphoma or Hodgkin's disease treated with high-dose BEAM chemotherapy and peripheral blood progenitor cell transplant: out-patient treatment is a viable option.

A retrospective analysis was performed on 100 patients with non-Hodgkin's lymphoma (NHL, n = 75) or Hodgkin's disease (HD, n = 25) who underwent peripheral blood progenitor cell transplant (PBPCT) following high-dose chemotherapy (HDCT) with BCNU, etoposide, cytarabine and melphalan (BEAM) between March 1994 and June 1997. Following PBPCT and until engraftment all patients received oral ciprofloxacin and fluconazole, patients with positive Herpes simplex virus serology received acyclovir and 91 patients received filgrastim. The median days of neutropenia and days to an absolute neutrophil count (ANC) >500/mm3 were 6 and 9, respectively. Febrile neutropenia occurred in 68 patients. Gram-positive bacteremia occurred in 14 patients. No gram-negative infections, invasive fungal infections, intensive care visits or deaths occurred during the period of neutropenia or in the first 30 days following transplant. In multivariate logistic regression the risk of development of any infection was associated only with the duration of neutropenia (P = 0.02) and the risk of bacteremia was associated only with the number of CD34+ cells infused (P = 0.046). Among 49 patients treated in the outpatient setting, 14 (28%) were never admitted. High-dose chemotherapy with BEAM supported by PBPCT, prophylactic antibiotics and filgrastim resulted in a low incidence of infections and no acute mortality. WBC engraftment occurred rapidly allowing for a predictable course during which lengthy hospital stays and amphotericin therapy could be avoided.

Adult↗

Assessment of cardiac and pulmonary function in adult patients with Hodgkin's disease treated with ABVD or MOPP/ABVD plus adjuvant low-dose mediastinal irradiation.

We evaluated the long-term effects of combined modality therapy (CMT) with adriamycin, bleomycin, vinblastine, dacarbazine (ABVD) or mechlorethamine, vincristine, prednisone, procarbazine (MOPP)/ABVD plus adjuvant low-dose (< 30 Gy) involved-field radiation therapy (LDRT) on cardiac and pulmonary functions in adult patients with Hodgkin's disease (HD). Adjuvant LDRT (mean dose, 2340 cGy) to the mediastinum was administered to 24 patients after chemotherapy with MOPP/ABVD (n = 10) and ABVD (n = 14). The mean doses of doxorubicin and bleomycin were 233 mg/m2 and 92 IU/m2, respectively. Cardiac and pulmonary function tests were performed in all patients and, when available, were compared with pretreatment studies. After a median follow-up of 6.3 years, none of the patients had cardiac or pulmonary symptoms. A 4.7% overall decrease in left ventricular ejection fraction (LVEF) was observed (p = 0.03), but only one patient had a mildly decreased LVEF (47%). Diastolic function, LVEF, and left ventricular volume remained within the normal range in the other 23 patients. Mild pulmonary function study abnormalities occurred in 8 of 24 patients, 6 of whom were cigarette smokers. There were no significant changes in total lung capacity and forced vital capacity (FVC) values, but there was a 3% overall decrease in FEV1/FVC ratio (p = 0.05). In adult patients with HD, adjuvant LDRT after chemotherapy with ABVD or MOPP/ABVD did not result in a significant incidence of permanent pulmonary or cardiac toxicity after more than 6.3 years of median follow-up. Further studies are warranted to fully evaluate the impact of such therapy on cardiopulmonary function.

Adolescent↗

Estimation of oxygen delivery in newborns with a univentricular circulation.

BACKGROUND: The management of neonates with complex congenital anomalies depends on careful interpretation of arterial blood gas values. Improved interpretation of these oxygen parameters may allow clinicians to avoid unexpected cardiovascular events. This study examined whether systemic oxygen delivery (DO2) can be maximized by the use of indices derived from oxygen saturation measurements in neonates with hypoplastic left heart syndrome. METHODS AND RESULTS: For the single-ventricle heart with both circulations in parallel, we used a previously developed computer simulation to obtain DO2 as a function of systemic arterial (SaO2) and venous (SvO2) oxygen saturation, arteriovenous oxygen difference (Sa-vO2), or pulmonary-to-systemic flow ratio (Qp/Qs). We also examined the oxygen excess factor, SaO2/Sa-vO2 (Omega). We found that (1) slight increases in SaO2 may be associated with large decreases in DO2. (2) Low values for SvO2 indicate low values for DO2. (3) Curves for Sa-vO2 and Qp/Qs are redundant in the data provided. (Qp/Qs, however, provides these data in more physiologically relevant terms.) (4) High values for Qp/Qs (>4) are associated with low DO2. (5) Estimating Qp/Qs from oxygen saturation measurements may result in errors when pulmonary venous oxygen saturation is not available. (6) Maximizing DO2 is extremely difficult using SaO2, SvO2, and Qp/Qs. (7) A linear relationship exists between Omega and DO2, and this linear relationship is not altered by changes in cardiac output. CONCLUSIONS: Patients with low SvO2 values require attention. Ideally, after reducing Qp/Qs to <1.5, Omega might be a better index to guide further therapy and maximize DO2. Interventions that increased Omega would be considered beneficial, whereas interventions that decreased Omega would be considered detrimental.

Cardiac Output↗

Assessment of pulmonary and cardiac function after high dose chemotherapy with BEAM and peripheral blood progenitor cell transplantation.

BACKGROUND: Limited information is available regarding the cardiac and pulmonary effects of high dose chemotherapy (HDCT) and autologous peripheral blood progenitor cell (PBPC) transplantation. METHODS: The authors evaluated cardiac and pulmonary function after BEAM (BCNU 300 mg/m2, etoposide 400 mg/m2/day x 3 days, cytosine arabinoside 200 mg/m2/day x 4 days, and melphalan 140 mg/m2), HDCT, and PBPC transplantation in 26 patients with non-Hodgkin's lymphoma or Hodgkin's disease. Therapy prior to BEAM included doxorubicin (25 patients), bleomycin (6 patients), and mediastinal irradiation (4 patients). All patients had pulmonary function tests (PFTs) and equilibrium radionuclide angiography before and at a median of 57 weeks after transplantation. RESULTS: Prior to high dose therapy, 8 patients had abnormal PFTs, including 6 with a diffusing capacity of the lung for carbon monoxide (DLCO) <70% of predicted value. At the time of reevaluation after HDCT, all patients included in the study were in complete remission, and none had received additional therapy after transplantation. At a median of 77 weeks after transplantation, none of the patients had cardiac or pulmonary symptoms. Moreover, there were no significant changes in total lung capacity, forced vital capacity, forced expiratory volume in 1 second/forced vital capacity, DLCO, or left ventricular ejection fraction values when compared with baseline studies. CONCLUSIONS: The authors concluded that HDCT with BEAM and PBPC transplantation did not result in significant cardiac or pulmonary toxicity, even in patients with borderline pretransplantation PFT values. Further studies of patients undergoing HDCT and PBPC transplantation are needed.

Adult↗

Double grafting of the left anterior descending artery: is the distance between the internal mammary artery and supplemental vein graft anastomoses relevant in graft survival?

INTRODUCTION: Under certain conditions (small internal mammary artery (IMA) or large runoff), double grafting of the left anterior descending (LAD) artery system is necessary to avoid the ominous consequences of myocardial hypoperfusion. Previous studies have shown that a saphenous vein (SVG) adjacent to an IMA graft leads to failure of the IMA. This study compares IMA flow patterns when adjacent ( < 1 cm) and separated (3-4 cm) from a SVG placed on a proximally occluded LAD. METHODS: A SVG and right IMA (PIMA) to proximal LAD (2.5-3 mm) coronary bypass were performed in 12 mongrel dogs. The left IMA (DIMA) was anastomosed to the distal LAD (1.5 mm). All anastomoses were carried out without cardiopulmonary bypass. The native LAD was occluded proximally to the PIMA anastomosis, and all graft flows were measured in competitive and non-competitive flow conditions. RESULTS: Isolated graft to LAD flows were similar for the three conduits. There was a drop in flow in both the PIMA and DIMA when placed in competition with the SVG (10.1+/-3.0 vs. 19.1+/-4.6 ml/min; P < 0.05). The total drop in flow was significantly greater in the PIMA (67.6 vs. 39.9%; P < 0.05). Diastolic flow was better preserved in the distal IMA graft (19.6 + 5.6 vs. 10.2+/-3.0 ml/min; P < 0.05). The patterns of flow were much different during competition and there was significant retrograde systolic flow in all PIMA grafts while there was no (n = 5) or minimal retrograde flow (n = 7) in the DIMA grafts. CONCLUSION: An IMA graft, when adjacent to a SVG, sustains a significant decrease in both total and diastolic flows and develops an oscillating pattern of flow in early systole (retrograde then antegrade). Placing the IMA more distally on the LAD improves flow and decreases retrograde flow. In clinical situations requiring double grafting on the LAD, distance between grafts may be an important factor in maintaining IMA patency.

Analysis of Variance↗

Hyperleukocytosis and retinal hemorrhages after chemotherapy and Filgrastim administration for peripheral blood progenitor cell mobilization.

A 49-year-old man with mantle cell lymphoma received 2.5 g/m2 of cyclophosphamide and 900 mg/m2 of etoposide followed by 10 microg/kg/day of Filgrastim for PBPC mobilization. This was complicated by marked hyperleukocytosis and retinal hemorrhages. The patient's symptoms improved gradually following leukopheresis. To the best of our knowledge, this is the first report describing this complication in patients undergoing PBPC mobilization. Early recognition of symptoms is important in order to stop Filgrastim and initiate immediate leukapheresis.

Filgrastim↗

Lack of reactivity to CMV pp65 antigenemia testing in a patient with CMV disease following allogeneic bone marrow transplant.

Pre-emptive antiviral therapy based on the early detection of CMV infection is an important strategy for the prevention of CMV disease following allogeneic BMT. Accepted methods for early detection of CMV infection include viral culture of blood or bronchial lavage specimens or CMV pp65 antigenemia testing of peripheral blood specimens. We describe a patient with aplastic anemia with worsening liver transaminases after allogeneic bone marrow transplantation who had repeated negative tests for CMV pp65 antigenemia despite positive viral blood cultures. Re-examination of peripheral blood samples with a different pp65 antibody pool revealed the presence of high levels of CMV in peripheral blood leukocytes, confirming a lack of reactivity to the original antibody pool. Following institution of antiviral therapy, a prompt reduction in the number of pp65 antigen-positive peripheral blood leukocytes paralleled a reduction in abnormal transaminases. The practical implications of these findings are discussed.

Adult↗

Chlorambucil-induced seizures.

BACKGROUND: Anecdotal reports of chlorambucil-induced seizures have sporadically appeared, mainly in the nononcologic literature. The majority of cases have occurred in patients treated with high dose therapy and in children with nephrotic syndrome. Because of its rarity, oncologists and hematologists may not be aware of this potential complication. METHODS: Two elderly patients with a remote history of seizures had generalized tonic-clonic seizures 3 days after chlorambucil therapy was initiated. A MEDLINE search was performed of previously reported cases and additional cases were found in the bibliographies of retrieved articles. RESULTS: In addition to the 2 new cases presented here, there have been 28 reported cases of chlorambucil-induced seizures. Underlying diseases included nephrotic syndrome (n = 12 cases), solid tumors (n - 10 cases), non-Hodgkin's lymphoma (n = 3 cases), and chronic lymphocytic leukemia (n = 1 case). Five cases were secondary to accidental overdose. Sixteen of 30 patients were younger than 18 years; 11 had nephrotic syndrome, 1 had choriocarcinoma, and 4 accidentally ingested the medication. Nine of 14 adults received high dose chlorambucil in Phase I-II studies or as part of a conditioning regimen prior to bone marrow transplantation for solid tumors, 3 were on intermittent pulse therapy, 1 was on daily low dose administration of chlorambucil, and 1 patient had an accidental poisoning. Two patients had recurrent seizures when they were rechallenged with chlorambucil. CONCLUSIONS: A relatively high incidence of chlorambucil-induced seizures in children with nephrotic syndrome may be due to an increased sensitivity in childhood or altered pharmacokinetics. In adults without a seizure history, seizures were observed only in patients treated with high dose chlorambucil; however, in adults with a seizure history, lower doses as used in pulse therapy also caused seizures. In the latter group of patients, daily low dose chlorambucil or, more likely, an alternative drug may be the safest approach to therapy.

Aged↗

Gallium scans in the management of patients with Hodgkin's disease: a study of 101 patients.

PURPOSE: To evaluate the utility of periodic gallium (67Ga) scans in the management of patients with Hodgkin's disease. PATIENTS AND METHODS: From 1990 to 1994, 101 patients treated for Hodgkin's disease (stage I to II, n = 67; stage III to IV, n = 34) had a positive 67Ga scan at the time of diagnosis. Treatment included chemotherapy in 27 patients, radiation therapy in 28, and combined modality therapy in 46. All patients underwent 67Ga scans at the time of diagnosis, near the end or just after treatment, and at periodic follow-up evaluation. RESULTS: After treatment, the 67Ga scan remained positive in four patients and was interpreted as negative in 97. Among the four patients with positive scans, two died of progressive disease and two relapsed. Among the remaining 97 patients with negative 67Ga scans, 16 patients relapsed, including five with stage I to II (7.5%) and 11 with stage III to IV (34.4%) disease. The negative predictive value of posttherapy 67Ga scan was 83.5% for all patients; however, when calculated according to stage, it was 92.4% for patients with stage I to II disease and 64.5% for patients with stage III to IV disease (P < .01). CONCLUSION: A positive 67Ga scan at the end of therapy is rarely seen in patients with Hodgkin's disease and should be considered a manifestation of gross residual disease. However, a negative 67Ga scan after therapy had a significantly lower predictive value in patients with stage III to IV disease compared with stage I to II disease. The predictive value of 67Ga scans, as well as newer imaging studies, should be analyzed according to pretreatment stage.

Adolescent↗

[Isolated invasive sphenoid aspergillosis].

Isolated aspergillosis of the sphenoid sinus is a difficult diagnosis because the often misleading clinical manifestations of this rare disease develop late. We report a case of invasive aspergillosis uniquely involving the sphenoid sinus revealed by clinical features suggesting pseudotumor of the pituitary in an immunocompetent man. A 71-year-old man presented sudden onset palsy of the abductor nerve of the left eye. Neuroimaging suggested a pseudotumor of the pituitary. Sphenoid sinusitis was discovered at surgery. The diagnosis of aspergillosis was provided by the histology examination of the sphenoid mucosa. Despite medical treatment with itraconazol alone then in combination with amphotericine B, the infectious process progressed to the pituitary, the cavernous sinus, the upper orbital fissue and the optic canal. Cure was finally achieved after a second surgical procedure to drain and aerate the sphenoid sinus. Aspergillosis of the sphenoid sinus is usually discovered due to neurological signs such as a cavernous sinus syndrome, pseudotumor of the pituitary or the orbit. Diagnosis is often made intraoperatively or at histology examination. Invasive forms almost always are seen in immunosuppressed subjects. In our case, the patient was immunocompetent and had no past history of sinusitis. The invasive sphenoid aspergillosis invaded bone tissue, the cavernous sinus and the meninges.

Aged↗

Spontaneous regression of lymphoproliferative disorders in patients treated with methotrexate for rheumatoid arthritis and other rheumatic diseases.

PURPOSE: To determine the clinicopathologic features of lymphoproliferative disorders (LPD) that occur in the setting of methotrexate (MTX) therapy for rheumatic diseases (RD) and to define the relationship between the presence of Epstein-Barr virus (EBV) in tumor cells and the response of LPD to MTX withdrawal. PATIENTS AND METHODS: In addition to nine new cases, we analyzed 28 cases previously reported in the literature of LPD in patients receiving MTX for RD. In addition to MTX, immunosuppressive therapy included corticosteroids in 19 patients, azathioprine in three, and cyclosporine in one. Extranodal disease was identified in 16 patients, but none had CNS involvement. Pathologic findings included five cases of Hodgkin's disease and seven low-grade lymphomas. The remaining patients had intermediate or aggressive lymphomas. In situ hybridization studies (ISHS) for EBV-RNA transcripts were positive in 12 of 27 patients (44%). RESULTS: Among 37 patients, 16 were initially observed after MTX withdrawal without additional antitumor therapy. Six achieved a spontaneous complete remission (CR), three had a partial response (PR), one had a minimal response, and six had no response to MTX withdrawal. Of 10 responding patients, EBV was detected by ISHS (n = 6) or polymerase chain reaction (PCR) (n = 2); one patient had a CR despite the absence of EBV by PCR and one had a CR but did not have viral assays performed. Only one of six patients with negative EBV by ISHS or PCR responded to MTX withdrawal. CONCLUSION: MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Responses were consistently observed, but not limited to patients in whom EBV was detected by ISHS or PCR. Further studies are required to confirm these findings and to evaluate the role for EBV in LPD that occur in patients receiving MTX.

Adult↗

Second solid tumors in patients with Hodgkin's disease cured after radiation or chemotherapy plus adjuvant low-dose radiation.

PURPOSE: Late solid tumors (STs) are a significant cause of morbidity and mortality in long-term survivors of Hodgkin's disease. To investigate the carcinogenic potential of two different therapeutic approaches, we measured the relative risk (RR) of STs in patients with early-stage disease cured after primary full-dose (approximately 40 Gy) radiation therapy (RT) and in patients with advanced disease who were treated with chemotherapy followed by low-dose (15 to 30 Gy) involved-field radiation (CMT). PATIENTS AND METHODS: Because therapy-induced STs generally begin after a latency period of 5 to 10 years, we restricted our analysis to patients treated before 1986 who achieved durable remissions. Patients who required salvage chemotherapy or who died of Hodgkin's disease were excluded from analysis. The RR of STs was calculated by dividing the observed number of cases by the expected number in a matched population from the Connecticut Tumor Registry. The actuarial incidence of STs was also measured. RESULTS: A total of 197 patients formed the RT group and 116 the CMT group. The median follow-up period in the RT group was 12.8 years, versus 13.5 years in the CMT group. The overall RR of STs in the CMT group was 1.5 (95% confidence interval [CI], 0.6 to 3.5; P = .122). There were no cases of lung or breast cancer. In the RT group, the overall RR of STs was 3.3 (95% CI, 2.0 to 5.3; P < .001). There were seven cases of lung cancer (RR = 10.8; 95% CI, 5.3 to 22.2; P < .001) and two cases of breast cancer (RR = 2; 95% CI, 0.6 to 7.4; P = .07). All six benign tumors occurred in the RT group. CONCLUSION: In patients cured by initial treatment for Hodgkin's disease, RT was associated with a statistically significant increase in STs, particularly lung cancer. CMT was not associated with a significant increase in STs. These data may have important implications for the design of newer therapies for early-stage Hodgkin's disease.

Actuarial Analysis↗

Burkitt's lymphoma-leukemia in patients treated for Hodgkin's disease.

We reviewed all reported cases of Burkitt's lymphoma and/or Burkitt's leukemia (BLL) occurring following therapy for Hodgkin's disease. In addition to the case described in this report, a total of 19 patients have been previously reported. The male/female ratio was 3.75. Treatment for Hodgkin's disease included chemotherapy combined with radiation therapy in 15 patients, chemotherapy in 3 patients, and radiation therapy alone in 1 patient. Median interval between Hodgkin's disease and the diagnosis of BLL was 97 months. Patient characteristics are similar to those with de novo BLL. Bone marrow, abdomen, central nervous system, as well as extranodal organs were commonly involved. Typical cytogenetic translocations seen in patients with primary BLL were found in 6 patients, but 5 of these patients had additional cytogenetic abnormalities. Only 2 patients achieved complete remission after chemotherapy. The mechanism for the development of BLL after treatment for Hodgkin's disease is unknown. Although the majority of cases have been seen in patients treated with combined-modality therapy, the role of previous therapy in causing this complication cannot be assessed in this study.

Adult↗

Primary gastrointestinal lymphomas.

Recent evidence suggests that a significant proportion of primary gastrointestinal lymphomas are driven by exogenous agents/antigens. In the stomach, Helicobacter pylori appears to be responsible for most cases of low-grade lymphomas (MALToma), whereas an infectious etiology is suspected in immunoproliferative small intestine disease (IPSID). Similarly, enteropathy-associated T-cell lymphomas appear to result from a disordered response to gluten, although this profile remains controversial. Accordingly, although traditional antineoplastic treatments, such as surgery and radiation, are still important for the treatment of primary GI lymphomas, antibiotics may be the first line of therapy for low-grade gastric MALToma, and they are often used alone or in combination with chemotherapy for IPSID. In patients with celiac sprue, a gluten-free diet appears to markedly reduce the risk for lymphoma. An important caveat for the treatment of gastric lymphomas is that only low-grade gastric MALTomas have consistently responded to antibiotics. Treatment of high-grade gastric lymphoma is evolving. Although surgery was once considered central to diagnosis, staging, and treatment of gastric lymphoma, most patients can now have a diagnosis established by endoscopic biopsy and are candidates for chemotherapy and adjuvant radiation. The risks of fatal hemorrhage and perforation have probably been vastly overestimated and appear to be equal or less than the mortality associated with surgery. In addition, the long-term effects of gastric resection on quality of life have been almost completely ignored. Systemic lymphomas involve the GI tract far more often than is clinically apparent. In most cases, treatment should not be affected.

Celiac Disease↗

Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome.

A 28-year-old man with Wiskott-Aldrich syndrome presented with ulcerative-proliferative lesions on his face from which herpes simplex type 1 (HSV-1) was isolated. He was initially treated with 10 mg/kg of acyclovir (Zovirax) intravenously every 8 h, but his skin lesions worsened. Clinical resistance to acyclovir was suspected, and therapy with this drug was intensified. The dosage of acyclovir was increased to 45 mg/kg, administered by continuous infusion, and the lesions subsequently resolved. The strain of HSV recovered from the patient showed acyclovir-resistance in vitro, using the colorimetric method with neutral red. Herpes simplex virus resistance to acyclovir is rare. It is more common in immunocompromised patients if subtherapeutic doses are administered in the treatment of chronic persistent forms of infection. Whenever clinical resistance to acyclovir is suspected, the dosage should be increased to 2 mg/kg per h administered via an infusion pump. If no improvement is observed in the patient's condition with this regimen, a phosphorylated medication whose mechanism of action is not dependent on viral thymidine kinase, such as foscarnet (phosphonoformic acid), should be substituted.

Acyclovir↗