PubMed Health⌕ Search

Biomedical subjects

A Taher

Publications and source records attributed to A Taher.

At least 55 records · Page 3Linked to original sources

Efficacy and side effects of deferiprone (L1) in thalassemia patients not compliant with desferrioxamine.

We report our experience with deferiprone (L1) (DFP) in 17 thalassemic patients, followed up in one center in Lebanon, who were initially on desferrioxamine and then shifted to DFP at a dose of 50-75 mg/kg/day as the sole chelator during 1-year follow-up. All 17 patients were compliant with therapy and there was no change in physical examination over the study period. Eight patients (47.1%) were positive for hepatitis C virus (HCV) antibodies. Urinary iron excretion was 21.8 +/- 14 mg/24 h (mean +/- SD) 1 week after starting DFP and dropped 12 months later to 13 +/- 7.4 mg/24 h (p = 0.009, paired t test). The initial serum ferritin level was 3,863 +/- 2,344 microg/l which dropped to 3,179 +/- 2,075 at 12 months after starting therapy (p = 0.07). HCV-negative patients as a group exhibited a significant decrease in serum ferritin after 6 and 12 months of DFP therapy (3,942 +/- 2,739 vs. 2,341 +/- 1,179 and 2,681 +/- 1,519 microg/l; p < 0.03 and p < 0.05, respectively). The most frequent side effects were joint pain, stiffness or swelling in 6 patients (35.3%), and nausea in 7 patients (41.2%), but these were well tolerated and did not require stopping treatment.

Adolescent↗

Acquired protein C deficiency following cisplatinum-navelbine administration for locally advanced breast cancer. Case report.

Thromboembolic events have recently been reported following diverse regimens of chemotherapy for breast cancer. This is a report of a 39-year-old woman, a diagnosed case of locally advanced breast cancer, who received many regimens of chemotherapy. She presented with deep venous thrombosis 2 months after starting the cisplatinum-navelbine regimen. Protein C deficiency was the only abnormal coagulation test that normalized after cessation of chemotherapy.

Adult↗

Diving accident management, with special emphasis on the situation in the Red Sea.

Accident management is a concept commonly misunderstood, frequently confused with accident treatment. The situation in the Sinai and the Red Sea makes a broad definition of the term "management" necessary. Management encompasses the whole spectrum: from recognition of the need for a hyperbaric facility, establishing one, education of dive center management, instructors, boat skippers and deck hands, to actual contingency plans set according to the different geographical sites. The essential elements of communication, oxygen first aid, transportation, and actual recompression therapy or other treatments and follow-up must be included. Furthermore, a link to the international organisations involved with diving accident management is an essential and desired backup.

Accident Prevention↗

Thiamine-responsive myelodysplasia.

The triad of thiamine-responsive anaemia, diabetes mellitus and deafness has been reported in 15 patients with macrocytic anaemia, sometimes associated with moderate thrombocytopenia. The bone marrow aspirate usually shows megaloblastic changes and ringed sideroblasts. However, tri-lineage myelodysplasia has never been reported. We describe two patients who presented with diabetes, deafness and thiamine-responsive pancytopenia. Bone marrow aspirate and biopsy were typical of tri-lineage myelodysplasia. These findings suggest that thiamine may have a role in the regulation of haemopoiesis at the stem cell level. We propose the term 'thiamine-responsive myelodysplasia' rather than that of thiamine-responsive anaemia.

Child↗

The relation between erythropoietin, hematocrit and hemoglobin in breast cancer patients on non-nephrotoxic chemotherapy.

Serum erythropoietin (EPO), hematocrit and hemoglobin levels were determined in 17 female patients with stage II breast cancer before, during and at the conclusion of non-nephrotoxic chemotherapy. Serum EPO levels were determined using the ELISA technique. No irradiation was given to any patient. The hemoglobin and hematocrit levels remained stable. However, a statistically significant increase in EPO was noted (p<0.05). The possible factors involved in this increase are reviewed, however the exact mechanism remains to be elucidated.

Adenocarcinoma↗

Cyclic nucleotide phosphodiesterase in human cavernous smooth muscle.

Cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) are important second messengers in mediating relaxation of various smooth-muscle cells. This second-messenger pathway also appears to be essential for cavernous smooth-muscle relaxation on the basis of the assumption it would be of theoretical and clinical interest to determine the functional relevance of various phosphodiesterase (PDE) isoenzymes in human cavernous smooth-muscle This study was concentrated on characterizing PDE isoenzymes that exist in cavernous smooth muscle and evaluating the effect of selective PDE inhibitors on relaxation that is needed for the initiation of erection. Separation of PDE isoenzymes was performed using anion-exchange chromatography [diethylaminoethanol (DEAE)-Sepharose column], and a modification of the PDE-assay method proposed by Thompson and Lakey was used. The relaxation effect of PDE inhibitors was evaluated in an organ-bath study. Three different PDE isoenzymes have been shown in human cavernous smooth-muscle homogenate: cGMP-inhibited PDE (PDE III), cAMP-specific PDE (PDE IV), and cGMP-specific PDE (PDE V). All PDE inhibitors tested showed a relaxation effect on isolated human cavernous smooth-muscle, albeit with differing potency. Quazinone (a selective PDE III inhibitor) had potency at least equal to that of papaverine (a non-selective PDE inhibitor) and had a superior effect as compared with Rolipram (a selective PDE IV inhibitor) and zaprinast (a selective PDE V inhibitor). The present study provides the rationale and opens the possibility of using selective PDE inhibitors in the treatment of patients with erectile dysfunction.

Animals↗

Interplay of structure and disorder in cochaperonin mobile loops.

Protein-protein interactions typically are characterized by highly specific interfaces that mediate binding with precisely tuned affinities. Binding of the Escherichia coli cochaperonin GroES to chaperonin GroEL is mediated, at least in part, by a mobile polypeptide loop in GroES that becomes immobilized in the GroEL/GroES/nucleotide complex. The bacteriophage T4 cochaperonin Gp31 possesses a similar highly flexible polypeptide loop in a region of the protein that shows low, but significant, amino acid similarity with GroES and other cochaperonins. When bound to GroEL, a synthetic peptide representing the mobile loop of either GroES or Gp31 adopts a characteristic bulged hairpin conformation as determined by transferred nuclear Overhauser effects in NMR spectra. Thermodynamic considerations suggest that flexible disorder in the cochaperonin mobile loops moderates their affinity for GroEL to facilitate cycles of chaperonin-mediated protein folding.

Amino Acid Sequence↗

The renal paracrine peptide system--possible urologic implications of urodilatin.

Cardiodilatin/atrial natriuretic peptide (CDD/ ANP) is a hormone system of great clinical importance. The prohormone CDD/ANP-1-126 is a peptide synthesized in the heart and cleaved during exocytosis into the circulating form CDD/ANP-99-126. Urodilatin (CDD/ ANP-95-126) is a homologue natriuretic peptide that differs from CDD/ANP-99-126 by four amino acids. Whereas CDD/ANP-99-126 circulates in blood plasma and is not excreted into the urine, urodilatin is detected only in urine. Urodilatin exerts its renal effects in a paracrine fashion. After its secretion from cells in the distal tubule, it interacts with luminally located receptors in the collecting duct, resulting in increased diuresis and natriuresis. Results suggest that urodilatin plays an important role in the physiologic regulation of fluid-balance and sodium homeostasis. Pharmacology studies reveal significant differences when urodilatin and CDD/ANP-99-126 are given intravenously, showing that stronger diuresis and natriuresis are induced by urodilatin as compared with those induced by CDD/ANP-99-126. Clinical studies indicate the prophylactic and therapeutic effect of urodilatin in patients suffering from acute renal failure following heart and liver transplantation. A significant reduction in requirements for hemodialysis/hemofiltration can be achieved using urodilatin. Postobstructive diuresis and natriuresis is probably due to a defective urinary concentrating mechanism and is usually resistant to treatment with antidiuretic hormone. The distal tubule and collecting duct have often been considered to be the site of altered sodium and water excretion following relief of obstruction. Since circulating CDD/ANP-99-126 levels are markedly elevated during obstruction and decrease upon relief of the obstruction, natriuretic peptides may play an important role in this clinical feature. On the basis of recent findings attributing an important role in sodium homeostasis to urodilatin in contrast to CDD/ANP-99-126, future studies have to clarify whether urodilatin, not CDD/ANP-99-126, might be responsible for the altered renal sodium excretion observed in postobstructive diuresis. In the past decade a considerable amount of research has led to the identification and characterization of hormones of the natriuretic peptide family [13]. These peptides are involved in the regulation of salt and water homeostasis. The prototype of the natriuretic hormones is cardiodilatin/atrial natriuretic peptide (CDD/ANP), or A-type natriuretic peptide. CDD/ANP is primarily produced in the heart [6]. It is synthesized as a precursor molecule, CDD/ ANP-1-126, in specific granules in atrial myoendocrine cells [15]. The prohormone, upon appropriate stimuli for release, is cleaved into the C-terminus CDD/ANP-99-126 and excreted into the circulation via exocytosis [16]. Further members of the natriuretic peptide family are brain natriuretic peptide (BNP, or B-type natriuretic peptide) [45] and C-type natriuretic peptide (CNP) [46]. All the members of this family share many common features, including tissue distribution of gene expression, biosynthetic pathways, and pharmacologic effects in target organs [13,26]. The main biologic effects of these hormones are natriuresis, diuresis, and vasodilation [5, 6, 14, 22], but these vary among the individual peptides. Natriuretic effects such as increased glomerular filtration, inhibition of aldosterone production, and secretion result from direct inhibition of sodium absorption in the collecting duct. Urodilatin (INN: Ularitide) is a member of the natriuretic peptide family, discovered in 1988 by Schulz-Knappe et al. [43]. This hormone is presumably synthesized in the kidney and exerts potential paracrine renal effects [17]. Results of clinical phase I-II trials suggest a potent therapeutic effect of urodilatin in the treatment of acute renal failure in patients following organ transplantation [4, 27, 33].

Acute Kidney Injury↗

Properties of incompletely immortalized cell lines generated from a line established from temperature-sensitive SV40 T-antigen gene transgenic mice.

Kidney tubule cell line (TKC2) established from temperature-sensitive (ts) SV40 T-antigen gene transgenic mice exhibited cell death by apoptosis at nonpermissive temperature (39 degrees C). To learn how immortalization occurs, we generated T-antigen-independent immortalized cells (resistant clones) by culturing TKC2 cells at 39 degrees C. These independently isolated resistant clones exhibited ts properties in T-antigen and contained only wild-type p53. They grew similarly at 39 degrees and at 33 degrees C, but cell death was induced soon after they reached confluency at 39 degrees C. However, cell death was equally prevented by transfecting the bcl-2 gene. While TGF-beta showed no growth-suppressive effect in the sensitive and resistant clones at 33 degrees C, it induced significantly earlier cell death in the resistant clones at 39 degrees C. Thus, the resistant clones may be incompletely immortalized cell lines which induce cell death in response to the growth-suppressive effects of contact inhibition.

Animals↗

Phosphodiesterase isoenzymes in human ureteral smooth muscle: identification, characterization, and functional effects of various phosphodiesterase inhibitors in vitro.

Phosphodiesterases (PDE) are key enzymes regulating intracellular cyclic nucleotide metabolism and, thus, contraction and relaxation of the muscle. At present, five different families of isoenzymes of PDE exist that show a distinct species-specific and organ-specific distribution. The aim of the present study was to analyze the PDE isoenzymes present in the human ureter and to evaluate the functional effects of isoenzyme-specific inhibitors in this tissue. Normal ureteral tissue was obtained during radical nephrectomies, homogenized, centrifuged, and the supernatant fraction was separated using DEAE-Sephacel anion-exchange chromatography. PDE assay was then performed and the isoenzymes characterized on the basis of their kinetic characteristics and their sensitivity to allosteric modulators and inhibitors. In vitro, longitudinal ureteral strips as well as ureteral rings were precontracted, and different selective and nonselective PDE inhibitors were added incrementally. Three different PDE isoenzymes were identified: PDE I (Ca/calmodulin-stimulated), PDE II (cyclic guanosine monophosphate-stimulated), and PDE IV (cyclic adenosine monophosphate-specific). All PDE inhibitors relaxed the strips dose-dependently with an EC50 of 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The existence of three different PDE isoenzymes was shown in this study. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low effect on the systemic circulatory parameters, may open a possibility of using selective PDE IV inhibitors in the treatment of ureteral colics or ureteral stones.

Chromatography, Ion Exchange↗

Characterization of cyclic nucleotide phosphodiesterase isoenzymes in the human ureter and their functional role in vitro.

An increase in cyclic nucleotide monophosphate levels is suggested to play a prominent role in mediating smooth-muscle relaxation. Cyclic nucleotide phosphodiesterase (PDE) influences smooth-muscle tone by decreasing the level of cyclic nucleotides. At present, five different families of isoenzymes of PDE exist that show a distinct species- and organ-specific distribution. Our study was done to evaluate the existence of specific PDE isoenzymes and its functional role in human ureteral tissue. Normal ureteral tissue was homogenized and centrifuged and the supernatant fraction was separated using anioin-exchange diethylaminoethyl (DEAE)-Sephacel chromatography. A PDE assay was then performed and the peak fractions were added to different specific PDE activators and inhibitors. In vitro, longitudinal ureteral strips were precontracted and different selective and non-selective PDE inhibitors were added incremently. Three different PDE isoenzymes were characterized: PDE I (calmodulin-sensitive), PDE II (cGMP-stimulated), and PDE IV (cAMP-specific). All PDE inhibitors relaxed the strips dose-dependently, with the 50% effective concentrations (EC50) being 30 microM for papaverine, 40 microM for zaprinast, 25 microM for quazinone, and 0.1 microM for rolipram. The ureter-relaxing effect of the PDE IV inhibitor at low concentrations, combined with its low-level effect on the systemic circulatory parameters, may open the possibility of using selective PDE IV-inhibitors in the treatment of ureteral colics or for ureteral stone passage.

3',5'-Cyclic-AMP Phosphodiesterases↗

Posttransfusion graft-versus-host disease in two immunocompetent patients.

Graft-versus-host disease may occur in certain immunocompromised patients after a blood transfusion. The disease is characterized by fever, a skin eruption, gastrointestinal disturbances, liver dysfunction, and bone marrow aplasia. Two cases of fatal graft-versus-host disease are reported. Both patients were immunocompetent and had received transfusions of nonirradiated blood from their children during surgery. The importance of preventing this complication by irradiating blood products given to patients by their first-degree relatives is underscored.

Aged↗

Intracavernous application of SIN-I in rabbit and man: functional and toxicological results.

The mode of action of the active metabolite SIN-I of the vasodilator prodrug molsidomine was studied in vitro and in vivo in corpus cavernosum of rabbit and man. SIN-I produces a dose-dependent relaxation of isolated human cavernous smooth muscle strips. In the rabbit, the intracavernous application of SIN-I increased the intracavernous pressure to a full erection (approximately 100 cm H2O). This response was highly reproductible. SIN-I was also injected intracavernously 6 times in five rabbits over 2 weeks; no inflammatory or fibrotic reactions were found on histology. SIN-I may be a reliable drug for the treatment of impotence without side-effects.

Animals↗

[A phlebocavographic evaluation of the size of the inferior vena cava for the placement of a DIL percutaneous caval filter. A preliminary study apropos of 10 cases].

With the DIL filter it is possible to make the partial interruption of the inferior vena cava percutaneously. It exists in three sizes corresponding to the variations of the size of the vena cava. The aim of this study is to estimate the real size of the vena cava by means of the radiological measures of the phlebocavography permitting--the correct choice of the size of the filter necessary for the optimisation of its efficiency--to avoid the difficulties of the placing.

Humans↗

Erythroblastic islands in erythroleukemia.

Erythroblastic islands are distinct anatomical units allowing direct transfer of ferritin molecule into developing erythroblasts. A patient with Fanconi's anemia who developed acute erythroleukemia and hypotransferrinemia exhibited numerous erythroblastic islands in the bone marrow. This unusual finding in our patient is thought to be in response to an increased demand for iron caused by neoplastic erythropoietic proliferation in the absence of an adequate amount of transferrin.

Adolescent↗

Cure of metastatic uterine carcinosarcoma to lungs: a case report.

Most patients with advanced or recurrent uterine sarcoma experience disease progression and ultimately die. We present a case of uterine sarcoma with lung metastasis treated with systemic chemotherapy and with no evidence of disease for more than 5 years. A 77-year-old woman underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy for carcinosarcoma of the uterus followed by external pelvic radiotherapy. Ten months later, the tumor recurred in the apex of the vagina and was treated with brachytherapy. After 6 months of remission, she presented with pulmonary metastasis. After four cycles of systemic chemotherapy with cisplatin and ifosfamide, the pulmonary nodules completely disappeared. Currently she is still in complete remission after more than 5 years, but unfortunately she has developed myelodysplastic syndrome. This is the first reported case in the literature of cured metastatic uterine carcinosarcoma to lungs, with long-term survival of 5 years.

Aged↗