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Biomedical subjects

A Ezzat

Publications and source records attributed to A Ezzat.

At least 37 records · Page 2Linked to original sources
PubMed1999

Pharmacokinetics of S- and R-enantiomers of aminoglutethimide following oral administration of racemic drug in breast cancer patients.

This study was undertaken to examine the pharmacokinetics of both enantiomers of AG--that is, (R-AG) and (S-AG) and respective acetyl metabolites, R-AcAG and S-AcAG--in breast cancer patients. Six patients received a single dose (500 mg) of the racemic drug, and serial plasma samples and urine were collected over a 48-hour period. R-AG, S-AG, R-AcAG, and S-AcAg were measured simultaneously by high-performance liquid chromatography using two serial chiral separation columns with ultraviolet detection. The plasma concentrations of R-AG were about 1.5 times higher than those of S-AG, and the data for both enantiomers exhibited the characteristics of the one-compartment open model. There were no significant differences between R- and S-AG in ka, tmax, V/F, and t1/2. The formation of R- and S-AcAG was rapid, and no correlation was found between the t1/2 values of the AG enantiomers with that of their acetylated metabolites. Overall, 41% of the dose was excreted in urine as AG (15% R-AG and 26% S-AG) and 5.1% as AcAG (2.9% R-AcAG and 2.2% S-AcAG). Renal clearance of S-AG was significantly greater (i.e., 2.3-fold) than that of R-AG and appears to be most likely the cause for the other pharmacokinetic differences observed. Both enantiomers had low renal extraction ratios, suggesting extensive tubular reabsorption of the compounds. However, based on the data obtained, it was concluded that the main factor contributing to the therapeutic effectiveness of racemic AG is the large potency difference between the R- and S- forms (R > S). The pharmacokinetic differences between R-AG and S-AG appear to contribute only marginally to the activity of this drug as an aromatase inhibitor.

Adult↗
PubMed1999

Carcinoma of cervix, the King Faisal Specialist Hospital & Research Center experience--the need for screening for cervical cancer in developing countries.

The King Faisal Specialist Hospital and Research Center opened in 1975 to provide specialized medical treatment to the citizens of Saudi Arabia and to promote prevention of disease through research and education. It is a national and middle eastern tertiary care hospital for oncology and a principle center for radiation therapy in Saudi Arabia. In this retrospective study, 504 patients with carcinoma of the cervix were analysed. Of the 504 patients, 410 received treatment with curative intent, which comprised radical surgery alone, radical radiation alone or combination surgery and radiation. The overall 3, 5 and 10 years survival of all 504 patients was 64%, 55% and 40%, respectively and for 410 patients treated with curative intent it was 74%, 61% and 51%, respectively. Multivariate analysis, using the Cox regression method, showed that the stage of the disease is the only significant prognostic factor influencing relapse-free survival. Stage for stage, treatment outcomes at King Faisal Specialist Hospital and Research Center match those achieved in the First world, but two-thirds of patients (rather than one-third) present with advanced disease at diagnosis. Therefore, any improvement in overall outcomes will require earlier diagnosis, achievable only through an effective screening program in the Kingdom of Saudi Arabia and similarly in the other Third world countries where patients present with advanced stage disease.

Combined Modality Therapy↗
PubMed1998

The lack of age as a significant prognostic factor in non-metastatic breast cancer.

AIMS: To determine the prognostic significance of age at diagnosis in women with non-metastatic breast cancer. METHODS: A retrospective review of all newly diagnosed breast cancer in women between 1975 and 1991 was carried out at a tertiary Oncology Referral Centre. Patients were divided into three age groups: < 40 years, 40-50 years and > 50 years. Demographic and management/outcome details were collected from patients with UICC stages I-III. The effect of age on overall and relapse free survival was analysed by standard statistical methods. RESULTS: Of 1289 new cases registered during the study period, 710 (55%) were UICC stages I-III. Of the latter group 250 (35%) women were in the age group of less than 40 years, 237 (33%) were between 40 and 50 years and 223 (32%) were older than 50 years. Women from the younger age group had a higher proportion of breast-conserving surgery, and adjuvant chemo- and radiation therapy, while the proportion of hormone therapy usage was higher in older women. There was no difference in overall survival (P = 0.64) and relapse-free survival (P = 0.53) between the three age groups. CONCLUSION: In this study, age was not a prognostic factor in predicting overall or relapse-free survival in women with breast cancer.

Adult↗
PubMed1998

Primary T-cell lymphoma of the urinary bladder.

Primary malignant lymphoma of the urinary bladder is very rare. Less than 100 cases have been reported; most are B-cell lymphomas. We report a case of primary T-cell lymphoma of the urinary bladder in a patient with a history of schistosomiasis. The patient is a 52-year-old man with suprapubic pain and hematuria. Examination revealed a large suprapubic mass. Computed tomography scan of the pelvis showed a large lobular mass occupying the urinary bladder. No pelvic or abdominal lymphadenopathy was noted, and results of metastatic workup were negative. The patient underwent a transurethral biopsy of the bladder mass that revealed a diffuse large cell lymphoma that was negative for the B-cell marker L-26 (CD 20) and positive for the T-cell marker CD-3. Polymerase chain reaction studies of the paraffin-embedded tissue revealed rearrangement of the T-cell receptor gamma gene. The patient was administered cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOPP) chemotherapy and currently is being treated. This case represents, to our knowledge, a very rare primary lymphoproliferative neoplasm of the urinary bladder that might represent an unusual immune response to schistosomiasis.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

F-18 FDG whole-body positron emission tomography scan in primary breast sarcoma.

Three patients with primary breast sarcoma showed intense F-18 FDG breast uptake on the whole-body scan. In two patients the uptake was irregular and associated with cold foci that corresponded to hypodense lesions noted on the chest CT; these represented areas of pathologically demonstrated tumor necrosis. There was also intense FDG uptake in pulmonary, axillary, and supraclavicular lymph node metastases. All lesions were confirmed by CT scan of the chest. Thus F-18 FDG positron emission tomographic scanning accurately staged the tumors in these two patients, and it documented local recurrence in the third patient. Histopathologic examination showed evidence of a high-grade sarcoma, a primary rhabdomyosarcoma, and a malignant cystosarcoma phyllodes of the breast. Similar to breast carcinoma, F-18 FDG whole-body positron emission tomographic imaging could be useful in diagnosing and staging primary breast sarcomas.

Adolescent↗
PubMed1998

F-18-FDG uptake in tuberculosis.

Two patients are described who showed abnormal fluorine-18 fluorodeoxyglucose (F-18 FDG) uptake that was due to benign disease, specifically tuberculous lymphadenitis and pneumonitis. The first patient had ulceration and oozing of the left nipple that was related to Paget's disease. An F-18 FDG PET, whole-body scan, which was performed for staging, showed no breast uptake. However, there was intense multifocal uptake in mediastinal, supraclavicular, and para-aortic areas that was confirmed radiologically to represent widespread lymphadenopathy. Pathologic examination of a mediastinal lymph node showed active tuberculosis. The second patient showed intense focal F-18 FDG uptake in mediastinal and supraclavicular areas and para-aortic lymphadenopathy due to non-Hodgkin's lymphoma. In addition, there was abnormal F-18 FDG lung uptake that revealed the presence of acid-fast bacilli on bronchial lavage. Intense focal F-18 FDG uptake in widespread lymphadenopathy or in the lung could be caused by infectious diseases such as tuberculosis. This possibility should be considered when whole-body scans of patients with cancer are interpreted, especially in those with a high incidence of infectious disease.

Adult↗
PubMed1997

Communicating with cancer patients in Saudi Arabia.

The following factors are relevant to the communication problems that exist in this country: 1. CULTURAL ASPECTS: The impression is that patients here cope better with terminal illness at home than do patients elsewhere. The extended family, with its strong ties, and the strong Islamic faith that encourages its members to provide for parents and children in case of need mean that any input by health professionals is magnified by the family in the care of the patient. At first, it was uncertain if foreign health professionals would be accepted into Saudi homes (which are intensely private and protected for the family) for the purpose of caring for patients. This has proved unfounded. Hospitality is a very important part of Saudi society; nurses and doctors are welcomed and respected. Much of this success is due to the use of Saudi men as drivers and translators. These people provide 24-hour service, act as social workers assessing the needs of the family, and are the link between the patient and family, the nurse, and the doctor. 2. "CURE" OR "PALLIATION": The emphasis for cancer patients in Saudi Arabia is still on "curative treatment," even after any realistic hope of a cure is gone. The problem this causes is compounded by many patients being excluded from the decision-making process. Decisions made by the family may not always reflect the patient's wishes. Greater communication is needed to guide treatment decisions. 3. TRUTH-TELLING: Denying information of the patient's illness is probably more a historical than a cultural phenomenon. Similar attitudes prevailed until very recently in practically all other countries. In this very conservative country, people are committed to preserving Islamic culture in the face of Western technology. As medicine continues to demonstrate its effectiveness as well as its limitations, people will come to realize that the right of patients to know and understand their illness allows them to cope much better, and is compatible with the responsibility of the family to care for them. 4. WORK FORCE: The government employs 14,500 doctors, but only 12% are Saudi nationals. Nearly all the 33,000 nursing work force are expatriates. There is a constant turnover of expatriate staff. The commitment to continuing care with proper communication that is required for the whole of medicine is likely to be fully realized only when the majority of the workforce are Saudi nationals. 5. PRIMARY, SECONDARY, AND TERTIARY CARE SERVICES: The Kingdom is well served by a system of 174 public hospitals and numerous private clinics. However, for a patient with a chronic or terminal illness, continuing care, even in the community, tends to be provided by the hospital service; whereas the polyclinics and health centers seem to provide mainly crisis management. The aim should be to develop community care for chronic illness as part of the primary health care system. The impact of Western medicine on Saudi society has been dramatic and sudden, as evidenced by the high growth rate of the population. There is now widespread interest in matching the culture to the technology. Much of the drive to change the attitudes of both patients and health professionals comes from young Western-trained Saudi doctors, who are in the best position to merge the strengths of both cultures in this sensitive area.

Adaptation, Psychological↗
PubMed1997

A phase II trial of circadian-timed paclitaxel and cisplatin therapy in metastatic breast cancer.

PURPOSE: In a phase II study with combination paclitaxel and cisplatin in metastatic breast cancer using circadian timing, we attempted to maximise response and minimise toxicity. MATERIALS AND METHODS: Forty-one patients with histologically-proven metastatic breast cancer with or without previous chemotherapy were treated with Paclitaxel 135 mg/m2 administered as a three-hour infusion at 06.00 hours followed by cisplatin 75 mg/m2 as a one-hour infusion at 18.00 hours utilising circadian timing. Six cycles were planned once every 21 days. Response assessment was performed every two cycles, and toxicity was measured using WHO criteria. RESULTS: All patients were evaluable for response and toxicity. There were nine (22%) complete responses (CR), and 24 (59%) partial responses (PR), for an overall response rate of 80% (95% confidence interval (CI) 69-92). Responses were seen in patients previously treated with anthracyclines (75%) (95% CI 57-92), and in patients who had had no prior chemotherapy (90%) (95% CI 71-100). Responses were seen in all metastatic sites: liver 80%, lung 76%, bone 69%, and soft tissues 71%. The overall median response duration was seven months (range 3-26, 95% CI 5.0-9.8), and 14 of the responses (42%), (95% CI 28-62) were durable. A total of 212 cycles of chemotherapy were given. There were 15 episodes (7%) of grade 3-4 neutropenia, seven (3.2%) of grade 3-4 neurologic toxicity, and three (1.4%) of grade 3-4 nephrotoxicity. There were no toxic deaths. CONCLUSION: The combination of paclitaxel and cisplatin is very effective in metastatic breast cancer, and with application of circadian timing, toxicity has been acceptable. This combination is being tested as primary therapy in locally-advanced breast cancer at our institution.

Adult↗
PubMed1997

Pharmacokinetic monitoring of anticancer drugs at King Faisal Specialist Hospital, Riyadh, Saudi Arabia.

Pharmacokinetic monitoring of anticancer agents has the potential to become of considerable clinical value. Recognizing this and the leading role of the King Faisal Specialist Hospital and Research Centre (KFSH & RC) in healthcare delivery in the Kingdom of Saudi Arabia, particularly in oncology, the authors have established a pharmacokinetics service and research laboratory equipped with the state-of-the-art analytical instrumentation. After the acquisition of these instruments, we initiated research work that lead to the development of improved analytical methods for methotrexate and 7-OH methotrexate (high-performance liquid chromatography [HPLC]), doxorubicin (HPLC), etoposide (HPLC), 5-fluorouracil (HPLC), mitoxantrone (HPLC), mesna and dimesna (HPLC), taxol (HPLC), aminoglutethimide (HPLC), tamoxifen (HPLC), and acrolein (HPLC), cisplatin or carboplatin (electrothermal atomic absorption spectrophotometry, ETAAS), cyclophosphamide (gas chromatography) and CCNU and BCNU (gas chromatography). Currently, most of these drugs are monitored selectively as requested by oncologists at the KFSH & RC. The authors are aware that controlled, randomized studies of the concentration-effect relationships for many of these drugs are still missing. However, the authors hope that once these studies become available, this service will be used more fully.

Antineoplastic Agents↗
PubMed1997

Effect of tamoxifen on the pharmacokinetics of doxorubicin in patients with non-Hodgkin's lymphoma.

The authors examined the effect of tamoxifen (TAM), a multiple-drug resistance modulator, on the pharmacokinetics of doxorubicin (DOX) in patients with non-Hodgkin's lymphoma treated according to the CHOP-protocol which included DOX, cyclophosphamide, vincristine, and prednisone. The dose of DOX was 50 mg/m2, but was reduced 25% if the patient was older than 60 years. Of these, 10 randomly-selected patients received a daily dose of 480 mg of TAM (Group-1) and 10 others did not (Group-2). Blood samples were collected at different time intervals, and DOX was measured in plasma by liquid chromatography. The concentration-time data of DOX exhibited the characteristics of the two-compartment open model well. The mean (SEM) values of alpha, beta, k12, k21, k10, Vc, Vss, AUC, total clearance, and mean residence time observed in Group-1 were 4.06 (0.96) hr(-1), 0.0395 (0.0068) hr(-1), 3.13 (0.79) hr(-1), 0.264 (0.052) hr(-1), 0.708 (0.19) hr(-1), 525 (156) l/m2, 1060 (163) l/m2, 1145 (234) microg x hr/l, 49.3 (8.5) l/hr x m2, and 26.8 (6.6) hours, respectively. Those in Group-2 were 4.99 (1.13) hr(-1), 0.0432 (0.0073) hr(-1), 2.46 (0.63) hr(-1), 0.111 (0.026) hr(-1), 2.46 (0.86) hr(-1), 231 (53) l/m2, 812 (149) l/m2, 1690 (276) microg x hr/l, 30.3 (4.1) l/hr x m2, and 29.7 (5.1) hours, respectively. Of these parameters, the difference between the two groups was significant (p < or = 0.0169) only in k21. Thus, the coadministration of TAM at the earlier-mentioned dose appears generally to have no significant influence on the pharmacokinetics of doxorubicin when used in the CHOP-protocol.

Adult↗
PubMed1997

Primary pancreatic non-Hodgkin's lymphoma in a renal transplant recipient.

Primary pancreatic non-Hodgkin's lymphoma (NHL) is rare and accounts for less than 1% of all lymphomas. The development of NHL following transplant is well recognized. However, there are no previous reports on localized lymphomatous pancreatic involvement in a transplant patient. We report on the first case of primary pancreatic NHL developing in a renal transplant recipient. The patient was treated without reducing immunosuppression and received combination chemotherapy and radiation. The patient is in complete remission at 10-month follow-up.

Biopsy, Needle↗
PubMed1996

Impact of pregnancy on non-metastatic breast cancer: a case control study.

The diagnosis of breast cancer during pregnancy remains uncommon and therefore leads to non-standardized management. We reviewed retrospectively 28 such women treated at this centre and compared them with age and stage matched controls. Differences in management and outcome were analysed for statistical significance. There was no significant difference in overall survival (P = 0.86) and relapse-free survival (P = 0.48) between the two groups. Chemotherapy after the first trimester of pregnancy carried no significant morbidity. Pregnancy does not appear to be an adverse prognostic factor for breast cancer.

Adult↗
PubMed1996

Primary pancreatic non-Hodgkin's lymphomas.

Primary pancreatic lymphomas are rare. We reviewed our experience at King Faisal Specialist Hospital and Research Center; the hospital tumor registry identified five patients with primary pancreatic lymphoma among the 1,212 adult non-Hodgkin's (NHL) cases referred to this institute during 1987-1994. The histology was diffuse large cell in all cases. According to the Ann Arbor classification, four patients had stage IE and one patient stage IIE disease. The diagnosis was established by laparotomy in three and ultrasound or CT-guided biopsy in two patients. All patients received chemotherapy. Radiotherapy was used in two cases; in one patient the pancreatic bed was irradiated, whereas in the other radiation was given for obstructive jaundice. Four patients are alive with no evidence of disease at 84, 26, 24, and 21 months follow-up. One patient relapsed at 12 months following chemotherapy and is alive with disease at 23 months follow-up. The clinical and radiological findings in primary pancreatic NHL are not pathognomonic, and the diagnosis is only established on histopathological examination. The management should be nonsurgical as the response to chemotherapy and radiation appears to be no different from NHL at other sites.

Adult↗
PubMed1996

Neutrophil-rich Ki-1-positive anaplastic large cell lymphoma presenting as a testicular mass.

Ki-1-positive large cell lymphoma is an uncommon subtype of lymphoma that may involve lymph nodes as well as a variety of extranodal locations. To the best of our knowledge, the occurrence of such a tumor in the testis has not been previously documented. We report a case of Ki-1-positive large cell anaplastic lymphoma presenting as a testicular mass in a 56-year old Saudi. Immunohistochemical staining revealed positive staining for Ki-1 and UCHL-1, which indicated a T-cell phenotype. This was further confirmed by polymerase chain reaction analysis, which demonstrated a monoclonal cell population with rearrangement of gamma T-cell receptor. Another interesting morphologic feature was the presence of large numbers of neutrophils throughout the tumor. Similar neutrophil-rich lymphomas have been described recently as a special subtype of Ki-1-positive anaplastic large cell lymphoma.

Anaplasia↗
PubMed1995

Liquid chromatographic separation and measurement of optical isomers of aminoglutethimide and its acetyl metabolite in plasma, saliva, and urine.

An accurate and specific liquid chromatographic method for the separation and analysis of the R(+) and S(-) enantiomers of both aminoglutethimide (AG) and its acetylated metabolite (AcAG) in plasma, saliva, and urine is described. The separation was achieved by use of two serial Chiralcel OD columns [cellulose tris(3,5-dimethylphenyl carbamate)] with a mixture of hexane/isopropanol/methanol (65:17.5:17.5, per volume) as a mobile phase. The flow rate was 0.7 ml/min, and the compounds were detected in the effluent spectrophotometrically at 245 nm. The plasma, saliva, or urine sample (300 microliters) was extracted with dichloromethane after the addition of an equal volume of acetate buffer (pH 5.6) to the sample. The extraction recovery of the R(+) and S(-) enantiomers of AG and AcAG from plasma, saliva, and urine at different concentrations under these conditions was > 80.9%. No interference from any endogenous substance or concomitantly used drug was observed. The ratio of the peak area of R(+) and S(-) enantiomers of both AG and AcAG/internal standard was linearly (r > or = 0.995) related to concentration in the range 0.83-40.0 micrograms/ml, and the coefficient of variation (CV) at different concentrations was consistently < or = 13%. We are presently employing this method to study the pharmacokinetics of each of these enantiomers in breast cancer patients.

1-Propanol↗