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Biomedical subjects

N Ibrahim

Publications and source records attributed to N Ibrahim.

At least 37 records · Page 2Linked to original sources
PubMed1998

Docetaxel (Taxotere) plus cisplatin: an active and well-tolerated combination in patients with advanced non-small cell lung cancer.

The activity of the combination of intravenous docetaxel 75 mg/m2 plus cisplatin 100 mg/m2 administered every 3 weeks for 3 cycles then every 6 weeks was investigated in 51 chemotherapy naive patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The population was 92% male, with a median age of 54 years and median performance status of 1; 80% of patients had metastatic disease, including 37% with bone involvement. All patients received prophylactic premedication (ondansetron, dexamethasone plus cetirizine) and standard hyperhydration. With a median of 4 treatment cycles (range 1-9), 14 of 42 evaluable patients responded (overall response rate 33.3%, 95% CI 19.6-49.6%); the median response duration was 7.3 months, median survival 8.4 months, and 1-year survival rate 35%. The most common adverse event was neutropenia, occurring in two-thirds of patients. Neurosensory effects were cumulative but generally mild. No treatment-related deaths occurred. This combination of docetaxel/cisplatin showed activity in advanced NSCLC. While it was not clearly superior to single-agent docetaxel, due to differences in prognostic factors among the patients in open trials, a randomised study would be needed to demonstrate definitively whether cisplatin adds to the activity of docetaxel or not.

Adolescent↗
PubMed1998

Actions of prostaglandin E2 on rat supraoptic neurones.

Prostaglandins (PGs) have been implicated in the regulation of vasopressin (VP) and oxytocin (OT) release in response to various stimuli. To examine the site and mechanism of actions of PGs, we studied effects of PGE2 and PG-receptor agonists on supraoptic nucleus (SON) neurones of rat hypothalamic slice preparations using extracellular recording and whole-cell patch-clamp techniques. PGE2 modulated the electrical activity of more than 80% of the neurones studied. The effects of PGE2 on both phasic and non-phasic neurones were mostly excitatory, and dose-dependent. The effects of PGE2 were mimicked by PGF2alpha or the FP agonist, fluprostenol, whereas PGD2 or the selective EP, IP or TP agonist was less effective or had no effect. The effects of PGE2 were unaffected by the EP1 antagonist, SC-51322, but reduced to 80% of control by the EP1/FP/TP antagonist, ONO-NT-012, which reduced the effects of fluprostenol to 32% of control. Moreover, some neurones responsive to PGE2 did not respond to fluprostenol. Patch-clamp analysis in SON slice preparations revealed that PGE2 at 10(-6) M depolarized the membrane potential by 3.9+/-0.3 mV from the resting membrane potential of -58.4+/-2.2 mV in the current-clamp mode. In the voltage-clamp mode, PGE2 induced inward currents at a holding potential of -70 or -80 mV, while it did not affect spontaneous excitatory postsynaptic currents. PGE2 induced currents also in dissociated SON neurones and the reversal potential of the currents was -35.5+/-0.9 mV, which was similar to that of currents induced by fluprostenol. These results suggest that SON neurones possess at least two types of PG receptors, FP receptors and EP receptors of a subclass different from EP1, EP2, or EP3, and that activation of these receptors leads to the opening of nonselective cation channels, membrane depolarization and increase of the action potential discharge.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1997

Mechanisms of resistance in a human cell line exposed to sequential topoisomerase poisoning.

Camptothecins are a new class of anticancer drugs that target DNA topoisomerase I; current efforts are directed toward elucidating optimal combinations of these drugs with other antineoplastic agents. A rationale for the use of sequential therapy involving the combination of camptothecins with topoisomerase II-targeting drugs, such as etoposide, has arisen from observations of increased topoisomerase II protein levels in cell lines resistant to camptothecin. In an effort to understand potential mechanisms of resistance to this strategy, we developed a U-937 cell subline, denoted RERC, that is capable of surviving exposure to sequential topoisomerase poisoning. The RERC cells are 200-fold resistant to camptothecin, 8-fold resistant to etoposide, and 10-fold hypersensitive to cisplatin compared to the parental U-937 cells. Biochemical analyses indicate that the resistant phenotype involves alterations in both topoisomerase I and topoisomerase IIalpha. Topoisomerase I catalytic activity in the resistant cells is similar to that of the parental line but is resistant to camptothecin. Moreover, the resistant cells express a single mRNA species of topoisomerase I that codes for a mutation in codon 533. In addition, topoisomerase IIalpha protein levels are decreased 10-fold in the resistant line, coincident with a two-fold decrease in the expression of topoisomerase IIalpha mRNA. Collectively, these results indicate that resistance to sequential topoisomerase poisoning may involve a reduction in total cellular topoisomerase activity.

Antineoplastic Agents↗
PubMed1997

Inhibition of spontaneous EPSCs and IPSCs by presynaptic GABAB receptors on rat supraoptic magnocellular neurons.

1. The function of presynaptic GABA receptors in the regulation of transmitter release in supraoptic nucleus (SON) magnocellular neurons was investigated by recording spontaneous postsynaptic currents from rat magnocellular SON neurons in a slice preparation (150 microns thick, 1.8 mm in diameter) using the whole-cell patch-clamp technique. 2. Both the spontaneous EPSCs and IPSCs were TTX resistant. The EPSCs were abolished by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), whereas the IPSCs were abolished by picrotoxin, suggesting that the EPSCs and IPSCs are synaptic inputs from glutamatergic and GABAergic neurons, respectively. 3. The selective GABAB agonist, baclofen, reduced the frequency of both the EPSCs and IPSCs without affecting the amplitude. The time constant of the decay phase of both the EPSCs and IPSCs remained unchanged after baclofen application. 4. The reduction of the frequency of the synaptic currents by baclofen was dose dependent (10 nM to 100 microM) and the EC50 values were 5.8 and 8.5 microM for the EPSCs and IPSCs, respectively. 5. The effect of baclofen (10 microM) was antagonized by the selective GABAB antagonist, 2-hydroxy-saclofen (2OH-saclofen), at 300 microM. 6. When given alone, 2OH-saclofen (100 microM) increased the frequency of both the EPSCs and IPSCs without affecting their amplitude, suggesting that endogenously released GABA in the slice acts on presynaptic GABAB receptors. 7. The GABAA agonist, muscimol, reduced the frequency of EPSCs, and picrotoxin increased the frequency of the EPSCs, suggesting that GABAA receptors also participate in the presynaptic inhibition of glutamate release. 8. Taken together, these data suggest that GABAB receptors are present on the presynaptic terminals of both GABA and glutamate neurons in the SON, and that these presynaptic GABAB receptors play an important role in the regulation of the neuronal activity in SON magnocellular neurons.

Animals↗
PubMed1997

Chemical and biological evaluation of proteins and mucilages from roots and seeds of Glossostemon bruguieri Desf. (Moghat).

The powdered roots of moghat (Glossostemon bruguieri) have been traditionally used in Eastern countries for their nutritive and therapeutic value. However, the biological effects of the plant constituents have not been proved on the basis of scientific research. The present study aimed to evaluate the content and composition of proteins and mucilages of the roots and seeds of moghat, as well as the hypoglycemic effect of the mucilages. The crude protein constituted 19.5% of the seeds, while it made up 4.5% of the peeled dried roots of Glossostemon bruguieri (Moghat). Glutamic acid, proline, leucine, phenylalanine, histidine and arginine were abundant in the protein of both plant parts; 72 and 83%, respectively. Valine, cysteine, methionine and lysine were detected only in seed protein. Molecular weights of the seed proteins were 50,000, 45,000 and 22,000. Moghat seeds contained 5.0% mucilage, while 15.75% and 29.60% were recorded in roots of one- and two-year-old plants, respectively. GLC investigation showed that both these plant parts contained rhamnose, xylose, mannose and galacturonic acid. Arabinose (1.8%) and glucuronic acid (14.6%) were present only in the seeds, while galactose constituted 33.7 to 34.5% of the root mucilage. Age of the roots was reflected in quantitative differences rather than qualitative ones. The root mucilages had remarkable hypoglycemic activity, decreasing the blood glucose level in diabetic rats by 54.5% within 15 days. Accordingly, moghat roots should be investigated as potential medical and nutritive food.

Adhesives↗
PubMed1997

Automated detection of clustered microcalcifications on mammograms: CAD system application to MIAS database.

To investigate the detection performance of our automated detection scheme for clustered microcalcifications on mammograms, we applied our computer-aided diagnosis (CAD) system to the database of the Mammographic Image Analysis Society (MIAS) in the UK. Forty-three mammograms from this database were used in this study. In our scheme, the breast regions were firstly extracted by determining the skinline. Histograms of the original images were used to extract the high-density area within the breast region as the segmentation from the fatty area around the skinline. Then the contrast correction technique was employed. Gradient vectors of the image density were calculated on the contrast corrected images. To extract the specific features of the pattern of the microcalcifications, triple-ring filter analysis was employed. A variable-ring filter was used for more accurate detection after the triple-ring filter. The features of the detected candidate areas were then characterized by feature analysis. The areas which satisfied the characteristics and specific terms were classified and displayed as clusters. As a result, the sensitivity was 95.8% with the false-positive rate at 1.8 clusters per image. This demonstrates that the automated detection of clustered microcalcifications in our CAD system is reliable as an aid to radiologists.

Automation↗
PubMed1997

The University of Texas M.D. Anderson Cancer Center experience with paclitaxel in breast cancer.

The first phase II study of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in breast cancer was completed at M.D. Anderson Cancer Center, and included 25 patients with metastatic breast cancer who had been previously treated with one chemotherapy regimen. Fourteen of these patients achieved a major objective response; the median response duration was 9 months, and the median survival time, 20 months. Additional trials showed that paclitaxel maintained its antitumor efficacy in patients with two and three prior chemotherapy regimens, including patients with anthracycline-resistant breast cancer. Combination therapy with doxorubicin showed that this combination was effective, although with the long infusion duration used for both agents, sequence-dependent toxic interactions were encountered. In combination with vinorelbine, dose-limiting toxicity included neutropenic fever and neuropathy. High-dose single-agent paclitaxel is currently being explored in the management of inflammatory breast cancer and as part of neoadjuvant chemotherapy for stages II and III operable disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

Paclitaxel-containing combination chemotherapy for metastatic breast cancer.

After demonstration of the marked antitumor activity against metastatic breast cancer of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ), other clinical trials explored the possibility of combining this new active agent with other cytotoxic drugs with proven efficacy against breast carcinoma. Paclitaxel plus doxorubicin, thought to be the most effective single agents against breast cancer, yielded remission rates ranging from 60% to 80%, including some complete remissions. Schedule-dependent toxic interactions were observed when paclitaxel preceded the administration of doxorubicin. Paclitaxel by 3-hour infusion plus doxorubicin by bolus proved to be a highly tolerable regimen, with overall remission rates in excess of 90% and complete remission rates approaching 50%. A paclitaxel plus cisplatin combination has been studied at numerous schedules and doses with variable activity and tolerability, although one group in Vancouver, Canada, reported an 85% overall response rate with the combination administered on a 14-day schedule in previously treated patients, most of whom had received doxorubicin. Paclitaxel also has been combined with cyclophosphamide, mitoxantrone, edatrexate, 5-fluorouracil, and other agents for the treatment of breast cancer. Of interest are recent reports on paclitaxel and vinorelbine, showing this combination to be clearly active, with good tolerability and rapid recovery after myelosuppression. Trials of this combination are ongoing with granulocyte colony-stimulating factor support, on an every-14-day schedule. The doxorubicin/paclitaxel doublet remains the most promising in terms of activity, although other combinations with a high degree of activity and good tolerance are being sought.

Aminopterin↗
PubMed1995

Infant feeding practices and attitudes of mothers in Kelantan towards breastfeeding.

The incidence of breastfeeding among 96 mothers (88/96 were Malays) who were attending various clinics at Universiti Sains Malaysia Hospital and Kota Bharu General Hospital was about 95%. The feeding patterns show that about 72% of mothers gave mixed feedings (breastmilk plus infant formula) while only 30% gave exclusive breastmilk to their infants in the first six months. Two main reasons for giving mixed feedings were that mothers had to start working soon after giving birth and reported "insufficient milk". Mixed feedings were seen to be more prevalent in the higher income group mothers (> RM1000 per month). About 64% of them who breastfed their child continued to do so beyond 6 months. Regarding their knowledge on breastfeeding, most mothers (98%) knew that breastmilk is good for baby's health, economical, strengthens bonding between mother and child, and was sufficient for the sustenance of the baby. However, when asked about colostrum, 66% of mothers who breastfed their child threw away the colostrum before feeding; some of the reasons given were that colostrum is dirty, and not suitable for the baby's health and it might cause some diseases.

Adult↗
PubMed1994

Determination of trace elements in cockle Anadara Granosa L. Using INAA.

This study determines the trace metal content in Anadara Granosa L., a popular seafood amongst South-East-Asians. Using the technique of instrumental neutron activation analysis (INAA) identification has been made of the presence of 17 trace metals including elements which are classified as toxic (As, Br, Cs) and those which are rare-earths (Eu, Ce, Lu, Tb, Yb).

Animals↗
PubMed1992

Intussusception in the adult: clinical, radiological and histological features.

Intussusception in the adult is an unusual cause of bowel obstruction. Unlike in childhood the clinical presentation is not clear cut and there are no distinct pathognomonic features. The radiological features are variable. Five patients presented to Frenchay Hospital over a five month period. The patients' clinical courses demonstrate the differing presenting features. Ultrasound investigation and CT scanning may show characteristic signs. Surgical treatment is mandatory as there is nearly always an underlying pathological abnormality which may be malignant.

Aged↗
PubMed1989

Arachnidism: a serious new Australian disease.

Necrotizing dermatitis, or arachnidism, is a new life-threatening syndrome of which many clinicians are unaware. The condition commences as a rapidly spreading, painful skin inflammation which progresses to fulminating necrotizing dermatitis, involving considerable skin loss. Two cases of arachnidism are presented.

Aged↗
PubMed1987

Primary small intestinal lymphoma in adults. A comparative study of IPSID versus non-IPSID in the Middle East.

Seventy-five cases of primary small intestinal lymphoma (PSIL) were diagnosed in adults at the American University of Beirut Medical Center (AUBMC) during the period from 1961 to 1980. Two additional cases of immunoproliferative small intestinal disease (IPSID) in the premalignant phase also were studied. Thirty-two patients had IPSID; 27 non-IPSID; and in 18 patients it was difficult to distinguish IPSID from non-IPSID. While the former was shown to be a distinct disease entity with characteristic clinical, pathologic, and immunologic features, the latter was found to have no particular features in this part of the world. In addition to alpha heavy chain protein (AHCP) which is the biological marker of IPSID, the most important finding that distinguished the two diseases was that IPSID was always associated with a dense, compact mucosal cellular infiltrate (MCI) that was continuous and uninterrupted all along the length of the small intestine. In non-IPSID, MCI was lacking and the pathology was confined to sites of gross abnormalities. Sites distant to the primary lesion were free of disease. It was reported previously that the MCI in IPSID is characteristically diffuse plasmacytic or lymphoplasmacytic (DLP). Our study indicates that in addition to this infiltrate, the disease may be associated with another type of infiltrate which is follicular lymphoid (FL). Sixteen patients had DLP; ten, FL; and three, mixed infiltrate. The relationship of AHC disease and IPSID is discussed. AHCP may be found in intestinal fluid, serum, within the abnormal cell, or at its surface. Immunofluorescence and immunoperoxidase studies must be done on all intestinal and nodal tissue specimens in all patients with PSIL for the detection of AHCP, particularly in those where serum and intestinal fluid are negative for this protein. The hypothesis that the DLP infiltrate represents the secretory form of IPSID, while the FL the nonsecretory form, is introduced. IPSID is an ideal model for the study of the etiology and pathogenesis of lymphoma in man.

Adolescent↗
PubMed1987

Efficacy of continuous high-dose metoclopramide in patients receiving daily cisplatin infusions.

Continuous high-dose metoclopramide (MCP), 2 mg/kg/24 hours, was administered for a period of 84-90 hours to 30 consecutive patients with various advanced solid malignancies receiving concomitantly a 3-day infusion of cisplatin. The latter was given at a dose of 40 mg/m2/day over 6 hours every day, in combination with doxorubicin and cyclophosphamide. Diphenhydramine and dexamethasone were also administered. This prolonged antiemetic therapy proved to be safe with only a 16% incidence (five of 30 patients) of extrapyramidal side effects not necessitating discontinuation of MCP. Also, antiemetic efficacy was demonstrated with 63% of the patients not experiencing any emesis.

Adult↗
PubMed1986

Non-Hodgkin's lymphomas in the Middle East. A study of 417 patients with emphasis on special features.

A total of 417 evaluable patients with non-Hodgkin's lymphomas were diagnosed between January 1974 and December 1983 at the American University of Beirut Medical Center in Beirut, Lebanon. Of these, 179 (43%) patients had nodal lymphomas, and 183 (44%) had extranodal lymphomas. The commonest lymphoma was diffuse large cell (27%), followed by large cell immunoblastic (21%). The histopathologic pattern was follicular in 18% of the nodal lymphomas and in 5.3% of the extranodal forms. The most common site of extranodal lymphoma was the gastrointestinal tract (46.5%), followed by Waldeyer's ring (19%). Small intestinal lymphomas were three times more common than gastric lymphomas. Immunoproliferative small intestinal disease (IPSID) was diagnosed in 20 of 59 patients who had primary small intestinal lymphoma. Of the 34 patients who had Waldeyer's ring lymphoma, 7 had gastrointestinal involvement at some time during the course of the disease. Nodal lymphomas were associated with poor prognostic factors: 82% were diffuse; 77% had advanced disease at presentation; 77% had intermediate- or high-grade malignancy lymphoma; 40% had marrow involvement; and 46% had B symptoms. In children, the most common lymphoma was Burkitt's, and 80% of pediatric lymphomas were high-grade malignancy. In conclusion, this study delineates the special features of non-Hodgkin's lymphomas in the Middle East: The presence of IPSID; the high incidence of extranodal forms, in particular the intestinal ones; and the rarity of follicular lymphomas.

Adolescent↗