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Biomedical subjects

N Farah

Publications and source records attributed to N Farah.

At least 19 recordsLinked to original sources
PubMed2006

Outcome of clinical pregnancies after ovulation induction using metformin.

The objective of this study was to review the first 50 clinical pregnancies of women with polycystic ovarian syndrome (PCOS) who had ovulation induced either with metformin alone, or in combination with clomifene. The study was confined to women with PCOS attending our infertility service. A register of clinical pregnancies was maintained of women who conceived after metformin therapy. The metformin was continued throughout the first trimester. The outcome of pregnancy was determined by individual chart review. Of the 50 women, 21 conceived with a combination of clomifene and metformin, and 29 with metformin alone. Seven women had a first trimester loss and 43 had a live birth. There were no perinatal deaths, no neonatal seizures and no congenital malformations. There were also no multiple pregnancies. The overall caesarean rate was 37%, and none of the babies had an Apgar score less than 7, at 5 min. This study found no evidence of any adverse clinical effects when metformin is continued in the first trimester of women with PCOS following ovulation induction. There was also no evidence of an increase in the rate of miscarriage or multiple pregnancy.

Adult↗
PubMed2006

Allogeneic hematopoietic stem cell transplantation from an alternative stem cell source in Fanconi anemia patients: analysis of 47 patients from a single institution.

We transplanted 47 patients with Fanconi anemia using an alternative source of hematopoietic cells. The patients were assigned to the following groups: group 1, unrelated bone marrow (N = 15); group 2, unrelated cord blood (N = 17), and group 3, related non-sibling bone marrow (N = 15). Twenty-four patients (51%) had complete engraftment, which was not influenced by gender (P = 0.87), age (P = 0.45), dose of cyclophosphamide (P = 0.80), nucleated cell dose infused (P = 0.60), or use of anti-T serotherapy (P = 0.20). Favorable factors for superior engraftment were full HLA compatibility (independent of the source of cells; P = 0.007) and use of a fludarabine-based conditioning regimen (P = 0.046). Unfavorable factors were > or = 25 transfusions pre-transplant (P = 0.011) and degree of HLA disparity (P = 0.007). Intensity of mucositis (P = 0.50) and use of androgen prior to transplant had no influence on survival (P = 0.80). Acute graft-versus-host disease (GVHD) grade II-IV and chronic GVHD were diagnosed in 47 and 23% of available patients, respectively, and infections prevailed as the main cause of death, associated or not with GVHD. Eighteen patients are alive, the Kaplan-Meyer overall survival is 38% at approximately 8 years, and the best results were obtained with related non-sibling bone marrow patients. Three recommendations emerged from the present study: fludarabine as part of conditioning, transplant in patients with < 25 transfusions and avoidance of HLA disparity. In addition, an extended family search (even when consanguinity is not present) seeking for a related non-sibling donor is highly recommended.

Acute Disease↗
PubMed2004

[Melt granulation with glyceryl palmitostearate to obtain taste-masked acetaminophen].

A melt granulation process designed to obtain a taste-masked acetaminophen using glyceryl palmitostearte (Precirol Ato 5) is described. Melting this lipid material in a high-smear mixer gives granules which can be directly compressed after blending with the required excipients. The phase diagram shows the absence of interaction between the phases of the two components and no effect on acetaminophen polymorphism. A water dispersible tablet formulation is proposed for oral administration of cristallized acetominophen (500 mg) devoid of bitterness of which 90% dissolves within 15 minutes.

Acetaminophen↗
PubMed2004

Development of 400 microm pellets by extrusion-spheronization: application with Gelucire 50/02 to produce a "sprinkle" form.

The aim of this study was to develop monodimensional, spherical particles of 400 microm by extrusion-spheronization. An Alexanderwerk GA65 cylinder extruder with two counter-rotating rollers associated with a Caleva model 15 spheronizer were used. The study was made with an auxiliary substance of fatty consistency and with amphiphilic properties: Gelucire 50/02. The plasticity of the mass can be deduced using a piston extruder. Pellet quality can be determined by particle-size analysis and shape estimation by microscopy. Modifications to the cylinders and the extruder itself are required for feasibility studies of extruded materials of 400 microm. The horizontal plate of the spheronizer had to be adapted to take into account the small size of the extruded materials. For the chosen auxiliary substance, Gelucire 50/02, the formulation of the wet mass to be extruded and the conditions required to obtain this mass were defined. The results show the feasibility of 400 microm pellets with Gelucire 50/02. At least 90% of the pellets have a particle size of between 250 microm and 500 microm and particle shape is acceptable. In this form the dose can be adapted to individual patients. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, the association of a drug with it was considered.

Drug Compounding↗
PubMed2003

The caesarean section rate in the Republic of Ireland in 1998.

The Caesarean section (CS) rate has risen dramatically in the United Kingdom and North America over the past 20 years. There are no recent data in the Republic of Ireland on CS rates. Our aim was to ascertain the national CS rate for the year 1998. In addition, we sought to determine instrumental delivery rates and epidural rates. Twenty-two of 24 units replied to a questionnaire giving a response rate of 92%. The CS rate was 17.8% (12.8-26.7%), 7.5% were elective and 10.3% were emergency. The size or type of the maternity unit did not influence the CS rate. The cause for the rise in the CS rate is multifactorial. Review of the current literature would suggest that a further rise in the CS rate in Ireland is likely.

Analgesia, Epidural↗
PubMed2002

Developing a study method for producing 400 microm spheroids.

The aim of this work was to obtain 400 microm spheroids that can be sprinkled on food to improve patient compliance particularly in the case of children and old people. A methodology to select wet masses for extrusion-spheronization through a 400 microm orifice was developed. The first step was to define the parameters that make it possible to assess the qualities required by the wet mass and the extrudates and evaluation norms: plasticity, cohesiveness, brittleness of the mass and the extrudates, and appearance of extrudates. A feasibility assay was then performed on the cylinder extruder, showing that extrusion of the lactose/Avicel PH 101/water (50/50/60) mass is not feasible through the 400 microm orifice. Precirol ato 5 and Gelucire 50/02 wetted with a sodium lauryl sulfate solution at 0.5% show plastic flow through the 400 microm diameter orifice. The presence of Avicel PH 101 does not improve plasticity for this orifice. Micropellets of 400 microm have been proved feasible as long as excipients with suitable pharmaceutical technological properties are used. After proving the feasibility of 400 microm spheroids of Gelucire 50/02, we considered the association of a drug with it.

Cellulose↗
PubMed2000

Hot-melt coating technology. I. Influence of Compritol 888 Ato and granule size on theophylline release.

The aim of this work was to study the influence of theophylline granule size and the percentage of Compritol 888 Ato on in vitro drug release from granules and tablets. The granules were coated in a fluidized bed apparatus. The dissolution profiles of these granules differed from those of granules coated with classical agents, and there were also differences between the various sieve fractions studied. Drug release was characterized by a rapid-release phase, followed by a slow-release phase. Results indicate that theophylline release can be controlled by controlling granule size. Inspection of the appearance of the tablets at the end of the dissolution test revealed that all tablets containing Compritol 888 Ato remained intact. This indicated that the Compritol 888 Ato used in the tablet formulation created an inert matrix through which the drug diffused. It was found that the Higuchi relationship of linear square root of time was the best model to describe the release kinetics of the drug from tablets. This also confirmed that a matrix diffusion-controlled mechanism was operative. Given the difference between the dissolution profiles of the granules and the tablets, it was concluded that this matrix is formed during compression.

Bronchodilator Agents↗
PubMed2000

Cisplatin DNA adduct detection and depurination measured by 32P DNA radiolabeling and two-dimensional thin-layer chromatography: a time and concentration study.

Platinum-based chemotherapies cause the formation of DNA adducts and have profound effects on DNA. This study measured cis-diamminedichloroplatinum II (cisplatin) DNA adducts by 32P-radiolabeling DNA, enzymatically digesting radiolabeled DNA, separating the formed adducts on two-dimensional thin-layer chromatography, and quantitating the adducts with autoradiography and densitometry. HeLa DNA was incubated with cisplatin at varying concentrations (6.25-325 nM) and times (0 min to 72 hr). Cisplatin rapidly depurinated dGMP and dAMP (90%, 15-min incubation with 325 nM cisplatin). Partial depurination of dGMP (15%) and dAMP (25%) occurred with lower cisplatin concentrations at equal incubation times. A minimum of four new adducts, with relatively rapid migratory patterns, were detected at high cisplatin concentrations with short incubation times. These results indicate that the depurination of DNA correlates with DNA adduct formation and that the quantification of these adducts may be applicable to monitoring tumor and host cell response to cisplatin chemotherapy.

Adenosine Monophosphate↗
PubMed2000

Hot melt coating technology: influence of Compritol 888 Ato and granule size on chloroquine release.

The tangential spray technique was used to coat chloroquine granules with Compritol 888 Ato in a fluidized bed (Glatt GPCG-1,1). After validation of the assay method for chloroquine, dissolution tests were carried out on four size fractions obtained from the same batch of granules. The dissolution profiles obtained showed differences in the rate of release between one fraction and another, despite the fact that each of these fractions had been coated with the same quantity of wax. This suggests that the rate of release of the chloroquine may be adjusted by controlling the size of the granules. Furthermore these dissolution profiles were characterized by a rapid release phase followed by a slow release phase. Examination of the surfaces of the granules from the various size fractions under a scanning electron microscope revealed that Compritol did not form a continuous film but existed rather as a lipid environment around the granule. This lipid environment was made up of solidified droplets of the wax which had become piled up on the surface of the granule. Compression of the granules produced tablets which remained intact until chloroquine dissolution was complete. This undicated that the active substance diffused across the Compritol matrix generated during compression. Determination of the dissolution kinetics using the Higuchi model demonstrated the diffusion release mechanism.

Amebicides↗
PubMed1999

Compritol 888 ATO: an innovative hot-melt coating agent for prolonged-release drug formulations.

The aim of the present study was to assess the coating of drug-loaded sugar beads and lactose granules with Compritol 888 (National Formulary (NF)--Glyceryl Behenate). Theophylline was used as tracer and layered onto the beads, or granulated with lactose and sugar. Coating conditions (temperature, spray-rate, air pressure, etc.) were investigated for the production of prolonged release beads or granules, and dissolution kinetic curves were discussed. The study confirms the satisfactory coating potential of the hot-melt fluid-bed coating process on large spherules or granules. The optimized conditions confirm previous work, underscoring the considerable importance of the temperature of molten coating materials and the atomization air pressures. More sophisticated equipment would undoubtedly produce more efficient coating but the technique nevertheless seems promising. Practical data is now available for standard top spray equipment for fine and coarse granules. (1) Granule and spherule surface adhesion is controlled and consistent; (2) the coating is homogeneous, with continuous atomization and spraying onto the support; and (3) the release profile is directly related to the quantity of wax applied. Several competing mechanisms are also involved, including a diffusion-controlled process and a dissolution mechanism. Dissolution profiles appear to be consistent from one batch to another.

Air Pressure↗
PubMed1997

In vivo determination of 5-bromo-2'-deoxyuridine incorporation into DNA tumor tissue by a new 32P-postlabelling thin-layer chromatographic method.

The halopyrimidine 5-bromo-2'-deoxyuridine (BUDR) can serve as one of many indicators of tumor malignity, complementary to histologic grade. We have developed a thin-layer chromatographic (TLC) technique that can assess tumor DNA base composition and analogue (BUDR) incorporation which vies with immunochemistry for BUDR. This requires post-labeling DNA by nick-translation and radioactive 5'-phosphorylation of representative 32P-alpha-dNMPs (deoxynucleotide monophosphates). Subsequent 3'-monophosphate digest exchanges a radioactive 32PO4 for the neighboring cold nucleotide. Separation in two dimensional PEI-cellulose TLC is carried out in acetic acid, (NH4)2SO4, and (NH4)HSO4. TLC of dNMPs was applied to control HeLa DNA, and HeLa cells receiving BUDR. BUDR is detected in 10(6) HeLa cells after 12-72 h incubations. Findings in HeLa DNA demonstrate normal TLC retention factors for all 32P-dNMPs. Two dimensional R(F) (x,y axes in cm) demonstrate: dAMP=1.4, 9.4; dCMP=10.0, 13.5; dGMP=4.6, 4.4; dTMP=9.0, 7.4; and BUDRMP 6.4, 6.6. This technique quantifies BUDR--which parallels tumor S phase, and serves as an indicator of labelling index (LI).

Bromodeoxyuridine↗
PubMed1997

Retrograde treatment of ureteropelvic junction obstruction using the ureteral cutting balloon catheter.

PURPOSE: We assessed the efficacy and safety of a new cutting balloon catheter to treat symptomatic ureteropelvic junction obstruction in adults. MATERIALS AND METHODS: A total of 32 adults (mean age 40 years, range 18 to 79) underwent retrograde balloon incision for symptomatic ureteropelvic junction obstruction (27 primary and 5 secondary cases). Treatment outcome was based on improvement of symptoms and resolution of obstruction by excretory urography or diuretic renal scintigraphy. RESULTS: A total of 36 retrograde endopyelotomies was performed on 32 patients. Of 4 patients who underwent repeat endopyelotomy 2 had resolution of persistent obstruction. At a mean followup of 14 months (range 3 to 28) 28 of 32 patients (87.5%) were rendered symptom-free and had no obstruction on excretory urography or diuretic renography. Average hospital stay was 1.8 days (range 0 to 6) and the complication rate was 15.6% (postoperative bleeding, fever and ileus). Treatment failed in 4 patients and subsequent open pyeloplasty was successful. CONCLUSIONS: Retrograde balloon incision endopyelotomy appears to be a safe and effective treatment for ureteropelvic junction obstruction.

Adolescent↗
PubMed1993

Comparison of nephrostomy drainage systems.

Forty patients undergoing nephrostomy insertion were randomised into 2 groups: those maintained on intermittently closed and those on permanently closed drainage systems. The average cost of managing a patient in the former group was one-eighth that of the latter and was not associated with any increase in morbidity.

Costs and Cost Analysis↗
PubMed1992

Synthesis of cell-impermeable Cl-sensitive fluorescent indicators with improved sensitivity and optical properties.

Quinolinium compounds have been used as Cl-sensitive fluorescent indicators in cells and cell-free membrane fractions. To improve Cl sensitivity and for conjugation via nucleophilic reaction, the compounds 6-methoxy-N-(n-aminoalkyl)quinolinium bromide hydrochloride (AAQ) with alkyl chain lengths (n) of 2 (AEQ), 3 (APQ), and 4 (ABQ) were synthesized. AAQ was water soluble, fluorescent, and quenched by Cl. The Stern-Volmer constants (KCl) for quenching of protonated AEQ, APQ and ABQ by Cl were 354, 322, and 272 M-1, respectively, higher than KCl for 6-methoxy-N-(3-sulfopropyl)quinolinium (SPQ; 118 M-1). To eliminate pH-dependent fluorescence, 6-methoxy-N-(3-trimethylammoniumpropyl)quinolinium dibromide (TMAPQ) was synthesized (KCl, 310 M-1). To red shift fluorescence excitation and emission spectra, 6-phenyl-N-(3-trimethylammoniumpropyl)quinolinium dibromide (phenyl-TMAPQ) (emission 475 nm) and N-(3-trimethylammoniumpropyl)phenanthridinium dibromide (TMAPP) (excitation 380 nm) were synthesized. AEQ and ABQ were conjugated with neutral dextran activated by cyanogen bromide to give indicator-to-dextran mole ratios of 5 to 20. KCl values at pH 7.4 were 132 (AEQ-dextran) and 237 M-1 (ABQ-dextran). To construct a single molecule with Cl-sensitive and insensitive moieties, the bichromophores 6-methoxy-N-(n- dansylsulfonamidoalkyl)quinolinium with alkyl chains of two and four were synthesized. The new Cl-sensitive indicators were used for measurement of intracellular Cl activity and for the labeling of endocytic vesicles in 3T3 fibroblasts and T84 cells. Our results indicate that N-substitution of quinoline with positively charged moieties gives increased Cl sensitivity, and extension of ring conjugation gives indicators with red-shifted fluorescence spectra.

Cell Membrane Permeability↗
PubMed1989

New combination chemotherapy programme for bladder cancer.

Forty patients with either metastatic, post-radiotherapy recurrent, or poor prognosis locally advanced transitional cell carcinoma of the bladder were treated in a new combination chemotherapy programme with methotrexate, vinblastine, mitozantrone and JM8 (carboplatin); 33 patients were assessable for response. There were 9 complete responses (27%), 12 partial responses (36%) and 7 disease stabilizations (21%); 5 patients (15%) had progressive disease. The median duration of complete response has not been reached and is in excess of 9 months (range 4- greater than 18 months). This regimen was without significant toxicity and this is in contrast with M-VAC, which is thought to be currently the most effective treatment for urothelial cancer.

Adult↗
PubMed1989

Two-monthly depot gonadotropin releasing hormone agonist (buserelin) for treatment of prostatic cancer.

The agonist analogues of gonadotropin-releasing hormone provide an alternate medical therapy for prostatic cancer. Current methods of administration of these analogues by daily injection or nasal spray is sub-optimal in an elderly population. We have performed a pharmacological and endocrine evaluation of a new depot preparation of one such analogue, buserelin, active for 2 months. Thirty patients with advanced symptomatic prostatic cancer were treated. Serum testosterone was suppressed for the duration of treatment which ranged up to 14 months. The release characteristics of the depot were consistent and showed minimal variation between patients. This 2-month preparation of buserelin offers and advantage to the patient with prostatic cancer, over current treatment regimens.

Adult↗