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Biomedical subjects

N Haim

Publications and source records attributed to N Haim.

At least 37 records · Page 2Linked to original sources

Haptoglobin-related protein as a serum marker in malignant lymphoma.

A novel serum 21 kDa haptoglobin-related protein (Hpr) was investigated in patients with malignant lymphoma, to evaluate its correlation with clinical and histologic features at presentation and its possible role as a tumor marker for patient outcome. One hundred fifty eight serum samples were taken from 88 patients with non-Hodgkin's lymphoma (n=58) and Hodgkin's disease (n=30) at presentation and in the course of follow-up. Sera from 61 healthy volunteers served as normal controls. Serum Hpr levels in the lymphoma patients (median 430x10 u/ml, range 0-4000x10 ) were significantly higher than in the control group (median 68x10 u/ml, range 0-180x10 )(p=0.0001). Higher median Hpr values were detected in patients with advanced disease (p=0.013), "B" symptoms (p=0.029) and in males (p=0.053). There was also a significant correlation between Hpr and erythrocyte sedimentation rate (p=0.028). Serial determinations showed a significant decrease of the initial Hpr values obtained after treatment in 41 patients, 38 of whom achieved complete remission. In the follow-up period additional Hpr measurements were taken from 17 patients. Three of them eventually relapsed, and showed increased Hpr levels at the time of relapse. Hpr levels remained low in 11 of 14 patients who maintained complete remission, and increased in three. In conclusion, serum Hpr is a new serum tumor marker of potential use in the clinical setting of lymphoma.

Adolescent↗

Postsurgical etoposide-ifosfamide regimen in poor-risk nonmetastatic osteogenic sarcoma.

This prospective study was designed to test the activity of an ifosfamide-etoposide (VP-16) regimen on poor-risk, nonmetastatic, osteogenic sarcoma. A total of 13 patients with nonmetastatic osteogenic sarcoma with a poor histologic response to primary high-dose methotrexate-doxorubicin (Adriamycin)-cisplatinum chemotherapy received a total of six 5-day courses of ifosfamide (1,800 mg/m2) and etoposide (100 mg/m2) at three weekly intervals. The protocol was well tolerated, with only one case of transient renal failure. At present, eight patients (62%) have been in sustained complete remission with no evidence of recurrent disease for a mean follow-up of 3.4 years (range, 1.5-7.0 years). One patient is alive with lung metastases, and four have died of progressive disease. This prospective, albeit small, study confirms the efficacy of an ifosfamide-VP-16-based regimen in poor-risk, extremity, nonmetastatic osteogenic sarcoma. The demonstrated activity should spark large trials of ifosfamide-containing regimens in osteogenic sarcoma.

Adolescent↗

Inhibin A concentrations in the sera of young women during and after chemotherapy for lymphoma: correlation with ovarian toxicity.

PROBLEM: Inhibin A concentrations in serum may reflect the ovarian granulosa cell compartment. To characterize the correlation between ovarian function after gonadotoxic chemotherapy for Hodgkin's or non-Hodgkin's lymphoma in young women, the immunoreactive inhibin A concentrations in the sera of these patients was measured before, during, and after the gonadotoxic chemotherapy. METHOD OF STUDY: A prospective clinical protocol was undertaken in 20 cycling women with lymphoma, aged 15-40 years. A monthly injection of depot D-TRP6-GnRH-a (Decapeptyl CR, Ferring) was administered from before starting the chemotherapy until its conclusion, up to a maximum of six monthly injections. Most of the patients were treated with the mustargen-oncovin-procarbazine-prednisone (MOPP)/actinomycin D-bleomycin-vincristine (ABV) chemotherapy combination; 13 with and 7 without radiotherapy. A hormonal profile [follicle-stimulating hormone (FSH), luteinizing hormone (LH), 17-beta-estradiol (E2), testosterone (T), progesterone (P4), insulin-like growth factor (IGF)-1, IGF-BP3, and prolactin (PRL)] was taken before starting the gonadotropin-releasing hormone agonist (GnRH-a)/chemotherapy co-treatment and monthly thereafter until resuming spontaneous ovulation and menstrual cyclicity. This group of prospectively treated lymphoma patients was compared with a control group of 22 regularly cycling women who had been treated with chemotherapy (mostly MOPP/ABV) with or without radiotherapy for Hodgkin's or non-Hodgkin's lymphoma. Inhibin A immunoactivity developed by Nigel Groome was measured by an enzyme-linked immunoadsorbent assay (ELISA) commercial kit (Serotec). RESULTS: Whereas all but one (40 years of age) of the surviving patients in the GnRH-a/chemotherapy co-treatment group resumed spontaneous ovulation and menses within 6 months, only one half of the patients in the "control" group (chemotherapy without GnRH-a co-treatment) resumed ovarian function and regular cyclic activity (P < 0.05). The remaining 50% experienced premature ovarian failure (POF). Temporarily increased FSH concentrations were experienced by approximately one third of the patients resuming cyclic ovarian function, suggesting a reversible ovarian damage in a larger proportion of women than those experiencing POF. The inhibin A immunoactive concentrations decreased during the GnRH-a/chemotherapy co-treatment but increased to normal levels in patients who resumed regular ovarian cyclicity, and/or spontaneously conceived, as compared to low levels in menopausal women and those who had developed POF. CONCLUSIONS: If these preliminary data are consistent in a larger group of patients, inhibin A concentration may serve as a prognostic factor for predicting the resumption of ovarian function, in addition to the levels of FSH, LH, and E2.

Adolescent↗

Dexamethasone, etoposide, ifosfamide, and cisplatin as second-line therapy in patients with aggressive non-Hodgkin's lymphoma.

BACKGROUND: This study analyzed the long term results of a combination of dexamethasone, etoposide, ifosfamide, and cisplatin (DVIP) used at the study center as standard second-line combination therapy in patients with aggressive non-Hodgkin's lymphoma (NHL) after prior exposure to doxorubicin. METHODS: All drugs were given intravenously for 4 consecutive days. The maximum daily doses of etoposide, ifosfamide, and cisplatin were 75 mg/m2, 1200 mg/m2, and 20 mg/m2, respectively. The dexamethasone dose was 20 mg twice daily. Cycles were repeated every 3 weeks. RESULTS: Fifty-six patients were included in the study. Partial response was noted in 18 patients (32%) and complete response (CR) in 18 patients (32%). Pretreatment factors that predicted CR were CR with prior therapy (CR in 17 of 34 in patients with a recurrence vs. 1 of 21 in patients with primary refractory NHL) and age (CR in 12 of 25 patients age < or = 65 years vs. 6 of 31 patients age > 65 years). Median time to treatment failure (TTF) and median survival were 11.5 months and 30 months, respectively, for patients with a CR and 3.5 months and 8 months, respectively, for all patients. Five patients (9%) remained disease free for > 24 months. By multivariate analysis, age was the only independent prognostic factor for TTF, whereas age, serum lactate dehydrogenase, and number of extranodal sites were independent predictors for survival. Myelosuppression (median granulocyte nadir and median platelet nadir of 350/mm3 and 77,000/mm3, respectively) was the major toxicity. There was one possible drug-related death associated with myelosuppression. CONCLUSIONS: DVIP is a relatively safe salvage combination therapy in patients with aggressive NHL. Response to first-line therapy and age are the most important predictors for prognosis after the administration of DVIP. This regimen is highly active in patients with recurrent NHL, but relatively ineffective in patients with primary refractory NHL.

Adult↗

Cisplatin-based chemotherapy in advanced seminoma: experience of the Northern Israel Oncology Center: 1981-1994.

BACKGROUND: The efficacy of cisplatinum combined chemotherapy modalities was investigated in a variety of trials for patients with advanced seminoma. Results regarding remission rates and survival are encouraging. METHODS: Between December 1981 and January 1994, 13 patients with either relapsed (following radiotherapy failure) or primarily advanced seminoma were treated with cisplatin-based chemotherapy at the Northern Israel Oncology Center. RESULTS: Eleven (84%) patients achieved complete clearance of all sites of disease. One patient demonstrated clinically and radiographically remarkable shrinkage of an abdominal mass, and laparotomy revealed fibrotic/necrotic tissue without viable tumor cells. After a mean follow-up of 58 months (range 4-168), 12 patients (92%) are alive and well without evidence of malignancy. One patient, in whom a 2-cm abdominal mass is stable radiographically, is under observation with no sign of tumor activity. Side effects were tolerable; no patient developed chemotherapy-induced sepsis. One patient developed spontaneous pneumothorax a few days after completion of his first chemotherapy cycle, which resolved with treatment. CONCLUSIONS: Our results confirm the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma, even in pre-irradiated patients.

Adult↗

Benign proliferative lesions mimicking recurrence of Hodgkin's disease.

Salvage treatment in patients with recurrent Hodgkin's disease is more effective when tumor burden is minimal. That is why more intensive follow-up strategies, including frequent imaging tests, have been recently developed for the detection of early relapse. However, as screening procedures become more sensitive, there is an increasing risk of false-positive results, demonstrating nonmalignant proliferative disorders. We describe three young patients who had lymphocyte-predominant or mixed-cellularity Hodgkin's disease and were in clinical complete remission for 2.5-3 years after a combined treatment with chemotherapy and radiation. Imaging tests revealed new gallium-avid lymphadenopathy in the chest in two cases. Pathologically enlarged pelvic lymph nodes were identified in another case, after a diagnosis of recurrent disease in axilla. Those findings were interpreted as relapse, and the patients underwent thoracotomy and laparotomy, respectively, for histologic confirmation. The results showed progressively transformed germinal centers and sarcoid-like lesions, two benign proliferative disorders. When patients with Hodgkin's disease in remission show new lymphadenopathy, even with positive gallium scan, it seems mandatory to obtain tissue for histologic examination, even through invasive procedures such as laparotomy and thoracotomy, to avoid wrong diagnosis and unnecessary treatment.

Adult↗

Cardiac valvular vegetations in cancer patients: a prospective echocardiographic study of 200 patients.

PURPOSE: Nonbacterial thrombotic endocarditis can complicate various malignancies and may cause morbidity and mortality mainly as a result of systemic embolism. The antemortem diagnosis of nonbacterial thrombotic endocarditis is rare. The purpose of our study was to assess the frequency, echocardiographic characteristics, and clinical correlation of nonbacterial thrombotic endocarditis in cancer patients. PATIENTS AND METHODS: A prospective echocardiographic screening of 200 nonselected ambulatory patients with solid tumors was performed. Patients were evaluated for evidence of thromboembolic events and for plasma D-dimer levels. A cohort of 100 consecutive patients without overt heart disease referred to echocardiography for the detection of an occult arterial embolic source served as a control group. It consisted of 52 males and 48 females, median age 60 years. RESULTS: The study group included 87 women and 113 men, median age 64 years (range 21 to 91). The frequent malignancies were lymphoma (26%), carcinoma of the gastrointestinal tract (20%), and carcinoma of the lung (16%). Cardiac valvular vegetations were found in 38 patients (19%) compared with only in 2 patients in the control group (2%, P < 0.001). Vegetations were found on the mitral or on the aortic valve in 19 and 18 patients, respectively. Isolated tricuspid valve vegetation was found in 1 patient. Valvular lesions were mostly common in patients with carcinoma of the pancreas (3 of 6, 50%), carcinoma of the lung (9 of 32, 28%), and lymphoma (10 of 52, 19%). Thromboembolism was diagnosed in 22 (11%) patients (12 deep vein thrombosis, 4 emboli to extremities, 2 cerebrovascular accidents, and 4 "silent" segmental left ventricular wall motion abnormalities on echocardiography). Thromboembolism was noticed in 9 of 38 patients (24%) with vegetations compared with 13 of 162 patients without vegetations (8%; P = 0.013). Plasma D-dimer level was examined in a subgroup of 170 patients. D-dimer level was increased in 19 of 21 patients (90%) with thromboembolism compared with 76 of 149 patients without thromboembolism (51%; P = 0.001). CONCLUSIONS: This study demonstrated a high prevalence of cardiac valvular lesions in patients with solid tumors. Vegetations were associated with thromboembolism. Plasma D-dimer level was significantly increased in patients with thromboembolism.

Adult↗

Prevention of gonadal damage during cytotoxic therapy.

Infertility represents one of the main remote sequelae of cytotoxic chemotherapy given for various malignant diseases. The impairment of gonadal function after cytotoxic chemotherapy is more frequent in the male than in the female. Because dividing cells are more sensitive to the cytotoxic effects of alkylating agents than are cells at rest, it has been hypothesized that inhibition of the pituitary-gonadal axis by gonadotropin-releasing hormone (GnRH) agonists would render the germinal epithelium less susceptible to the cytotoxic effects of chemotherapy. This hypothesis has not been thoroughly clinically tested until recently, although several investigators have demonstrated that GnRH-agonistic analogues (GnRH-a) inhibit chemotherapy-induced ovarian follicular depletion in the rat and Rhesus monkeys. Based on this rationale, we have undertaken a prospective evaluation to determine whether GnRH-a administration during combination chemotherapy for Hodgkin's and non-Hodgkin's lymphoma could prevent posttreatment ovarian damage in women by inducing a temporary prepubertal hormonal milieu. While over 93% of the surviving patients in the GnRH-a and chemotherapy group resumed spontaneous ovulation and menses, less than 40% of the women in the control group of chemotherapy without the GnRH-a cotreatment resumed normal ovarian cyclic activity. More than 60% of the women experienced premature ovarian failure (POF) in the chemotherapy alone group. Our preliminary results suggest that GnRH-a cotreatment protects against POF during cytotoxic chemotherapy. The GnRH-a and chemotherapy cotreatment may be also suggested for young women treated by cyclophosphamide pulse therapy or other gonadotoxic treatments for systemic lupus erythematosus, organ transplantation and other autoimmune diseases. The technology of cryopreservation of human ova for future fertility in these patients awaits clinical validation and substantiation. This review discusses possibilities to prevent gonadal damage induced by cytotoxic therapy and presents the clinical data currently available.

Animals↗

Prevention of irreversible chemotherapy-induced ovarian damage in young women with lymphoma by a gonadotrophin-releasing hormone agonist in parallel to chemotherapy.

To examine whether the concomitant administration of a gonadotrophin-releasing hormone agonist (GnRHa) during combination chemotherapy to young women with lymphoma may facilitate preservation of gonadal function, a prospective clinical protocol was undertaken in 18 cycling women with lymphoma, aged 15-40 years. Thirteen patients suffered from Hodgkin disease (HD) and 5 from non-Hodgkin lymphoma. After informed consent a monthly injection of depot D-TRP6-GnRHa was administered for a maximum of 6 months starting prior to chemotherapy. Most of these patients (15/18) were treated with the MOPP/ABV(D) combination chemotherapy followed by mantle field irradiation in 10 patients. Hormonal profile [luteinizing hormone (LH), follicle stimulating hormone (FSH), oestradiol, testosterone, progesterone, insulin-like growth factor (IGF)-1, prolactin] was taken before the GnRHa/chemotherapy co-treatment, and monthly thereafter until resuming spontaneous ovulation and menses. This group of prospectively treated lymphoma patients was compared to a matched control group of 18 women (aged 17-40 years) who have been treated with chemotherapy, mostly MOPP/ABV (14/18), with (11) or without (7) mantle field radiotherapy. Fourteen had Hodgkin's and four non-Hodgkin's lymphoma. Gonadal function was determined clinically, hormonally (LH, FSH, oestradiol, progesterone), and sonographically. Two of the patients in each group died from refractory disease. Of the remaining 16 patients, 15 (93.7%) resumed spontaneous ovulation and menses within 3-8 months of termination of the combined chemotherapy/GnRHa co-treatment. In contrast, only seven (39%) of the 18 similarly treated patients in the control group (chemotherapy without GnRHa) resumed ovarian cyclic activity (regular menses). The other 11 experienced premature ovarian failure (POF) (61%). Out preliminary data suggest a possible significant protective effect of GnRHa co-treatment with chemotherapy from irreversible ovarian damage (POF).

Adolescent↗

Diffuse lung uptake of Ga-67 after treatment of lymphoma: is it of clinical importance?

PURPOSE: To determine if diffuse lung uptake (DLU) of gallium-67 at scintigraphy in patients with lymphoma is indicative of lymphomatous involvement of the lungs. MATERIALS AND METHODS: Thirty-eight patients (24 male, 14 female; aged 15-76 years) with DLU were examined. The relation between DLU and lymphoma was investigated. Radiographic and computed tomographic findings and the persistence of Ga-67 uptake were investigated to detect lymphomatous involvement of the lungs. The relations between chemotherapy and radiation therapy, previous lung or heart disease, and DLU were also examined. RESULTS: DLU appeared only during or after chemotherapy. No clinical, radiologic, or follow-up evidence indicated that patients with DLU had active lymphomatous involvement of the lungs. The difference in survival between patients with persistent and patients with transient DLU was not statistically significant. No statistically significant correlation between DLU and any possible inductive factor was indicated at multivariate analysis. CONCLUSION: DLU after treatment does not indicate lymphomatous involvement of the lungs.

Adolescent↗

Utility of gallium-67 scintigraphy in low-grade non-Hodgkin's lymphoma.

PURPOSE: Low-grade non-Hodgkin's lymphoma (LGNHL) has traditionally been considered non-gallium-avid. The sensitivity of gallium 67 (67Ga) scintigraphy when using modern equipment and techniques in patients with LGNHL was investigated. MATERIALS AND METHODS: Fifty-seven consecutive patients with LGNHL underwent 67Ga scintigraphy at initial presentation (n = 40), when tumor progression occurred during treatment (n = 3), and at suspected disease recurrence after continuous clinical remission (CCR) (n = 14). Planar and tomographic images were obtained with either a very large field-of-view or a dual-head digital camera. Of 45 patients with Ga-avid LGNHL, 30 underwent 93 follow-up scans (one to six studies per patient). Scan findings were correlated with clinical and computed tomographic (CT) findings and with patient outcomes. RESULTS: 67Ga scintigraphy was positive in 45 of 57 patients (sensitivity, 79%) and in 113 of 164 disease sites (sensitivity, 69%). The sensitivity was higher in the more common types of LGNHL: follicular, predominantly small cleaved cell (FSC), and follicular, mixed small cleaved and large cell (FM) (84% and 91% in patients and 72% and 71% in disease sites, respectively). Sensitivity was lower in patients with mucosa-associated lymphoid tissue lymphoma (MALT) and small lymphocytic lymphoma (SL). Among 28 patients with disease recurrence after CCR (14 with and 14 without baseline studies), 67Ga scan was positive in 25, for a sensitivity of 89% for detection of disease recurrence. CONCLUSION: When modern technology is used, 67Ga scintigraphy has good sensitivity in patients with LGNHL. It therefore can be used to monitor response to therapy and to provide early detection of disease recurrence in these patients.

Adult↗

Spontaneous pneumothorax complicating chemotherapy for metastatic seminoma. A case report and a review of the literature.

BACKGROUND: Spontaneous pneumothorax complicating chemotherapy has been reported mainly in metastatic sarcoma, particularly of the osteogenic type. The main factor in the etiology of spontaneous pneumothorax could be related to tumor lysis and/or rapid rupture of chemosensitive peripheral or subpleural metastasis into the pleural cavity, thus leading to a bronchopleural fistula. METHODS AND RESULTS: A 49-year-old patient in whom spontaneous pneumothorax developed after successful chemotherapy for metastatic seminoma is described. On chest tube drainage, the lung reexpanded rapidly and the patient became clinically and radiographically symptom free. CONCLUSION: To the authors' knowledge, this is only the second case of spontaneous pneumothorax complicating chemotherapy-induced rapid regression of lung and mediastinal metastases in patients with seminoma. Spontaneous pneumothorax should be included in the spectrum of chemotherapy-related side effects in chemosensitive solid tumors with lung metastases.

Antineoplastic Combined Chemotherapy Protocols↗

[Treatment of urinary bladder cancer--a retrospective analysis].

Data on 482 stage A-0--D2 bladder cancer patients referred between 1975-86 were analyzed. Prognosticators of survival were stage, histologic subtype and differentiation. 143 patients with disease localized to the pelvis (stage A-0--D1) received definitive radiotherapy with 60 Gy or more, and 25 underwent preoperative irradiation and cystectomy. Later, a group of 56 selected patients with stage B--D1, referred between 1988-1991, received neo-adjuvant MCV chemotherapy (methotrexate, cisplatin and vinblastine) preceding either definitive radiotherapy or surgery. The 2-year overall actuarial survival rates were similar: 63% for radiotherapy only, 72% for cystectomy and 68% for neo-adjuvant chemotherapy; they were also similar when broken down by stage and grade.

Antineoplastic Combined Chemotherapy Protocols↗

Primary Hodgkin's disease of the bone.

A primary extranodal presentation occurs in less than 0.25% of patients with Hodgkin's disease (HD) and we describe the primary clinicopathologic findings in a rare case of a 21-year-old female with primary bony involvement of Hodgkin's disease. The patient presented with microcytic, hypochromic anemia and shoulder pain. The diagnosis of HD (lymphocyte depleted type) was made by biopsy taken from a lytic lesion in the lateral third of the clavicle. Staging work-up revealed an additional lesion in the ilium, but there was no evidence of lymph node involvement. MOPP/ABV (nitrogen mustard, Oncovin, procarbazine, prednisone/adriamycin, bleomycin, and vinblastine) chemotherapy resulted in complete response lasting, to date, 36 months. To the best of our knowledge, this is only the second reported case of disseminated primary Hodgkin's disease of the bone and all have had a favourable response to combination chemotherapy. A review of the literature is also presented.

Adult↗

Cardiac tamponade as the initial manifestation of primary pericardial mesothelioma.

Although cardiac tamponade is a known complication of malignancy, it is rarely the initial manifestation. We report a 46-year-old male who presented with malignant cardiac tamponade 6 months prior to the definitive diagnosis of primary pericardial mesothelioma. A thorough literature search has not revealed a similar care.

Cardiac Tamponade↗