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Biomedical subjects

H Ibrahim

Publications and source records attributed to H Ibrahim.

At least 19 recordsLinked to original sources

Candidate genes for the hypoxic tumor phenotype.

In this study, we have analyzed changes induced by hypoxia at the transcriptional level of genes that could be responsible for a more aggressive phenotype. Using a series of DNA array membranes, we identified a group of hypoxia-induced genes that included plasminogen activator inhibitor-1 (PAI-1), insulin-like growth factor-binding protein 3 (IGFBP-3), endothelin-2, low-density lipoprotein receptor-related protein (LRP), BCL2-interacting killer (BIK), migration-inhibitory factor (MIF), matrix metalloproteinase-13 (MMP-13), fibroblast growth factor-3 (FGF-3), GADD45, and vascular endothelial growth factor (VEGF). The induction of each gene was confirmed by Northern blot analysis in two different squamous cell carcinoma-derived cell lines. We also analyzed the kinetics of PAI-1 induction by hypoxia in more detail because it is a secreted protein that may serve as a useful molecular marker of hypoxia. On exposure to hypoxia, there was a gradual increase in PAI-1 mRNA between 2 and 24 h of hypoxia followed by a rapid decay after 2 h of reoxygenation. PAI-1 levels were also measured in the serum of a small group of head and neck cancer patients and were found to correlate with the degree of tumor hypoxia found in these patients.

Animals↗

Congenital chylothorax in neonatal thyrotoxicosis.

We report a patient with congenital chylothorax who also had neonatal thyrotoxicosis secondary to maternal Graves' disease. Fetal tachycardia with hydrops was detected at 28 weeks' gestational age. The fetus responded to antithyroid medication in utero but had persistent bilateral pleural effusion. At birth, he had respiratory distress due to massive pleural effusion. Cytologic studies of pleural fluid were consistent with chylothorax. To the best of our knowledge, the association of congenital chylothorax with fetal (neonatal) thyrotoxicosis, has not been reported previously.

Adult↗

[Should plasma prolactin assay be routinely performed in the assessment of erectile dysfunction? Report of a series of 445 patients. Review of the literature].

OBJECTIVE: To define the value of plasma prolactin assay in the assessment of erectile insufficiency. MATERIAL AND METHODS: Plasma prolactin assay (radioimmunoassay) was performed in 445 patients presenting with erectile insufficiency (mean age 52.5 years). RESULTS: 9 patients (2%) presented plasma prolactin levels greater than 25 ng/ml and 4 (0.9%) of them had levels higher than 35 ng/ml. Eight of these 9 patients were taking hyperprolactinaemic drugs. The aetiology remained unclear in 1 patient, but the pituitary gland was normal on CT scan. REVIEW OF THE LITERATURE: In the population of men with erectile insufficiency, 2.7% of subjects have plasma prolactin levels greater than 20 or 25 ng/ml. 1.3% have levels greater than 35 or 40 ng/ml and 0.6% present pituitary tumours. In the case of pituitary tumours responsible hyperprolactinaemia and erectile insufficiency: 1) plasma prolactin is greater than 30 ng/ml in 90% of cases and greater than 50 ng/ml in 83% of cases; 2) total plasma testosterone is less than 3 ng/ml in 88% of cases and less than 4 ng/ml in 96% of cases; 3) libido is decreased in 90% of cases. CONCLUSION: The prevalence of hyperprolactinemia and pituitary tumours in the population of men with erectile insufficiency is low. Moreover, certain criteria are suggestive of hyperprolactinemia, especially when it is secondary to a pituitary tumour. Consequently, routine plasma prolactin assay is not justified. This assay should only be performed when libido is impaired, total plasma testosterone is decreased or when the patient presents certain signs such as headache, gynaecomastia or visual disturbances.

Erectile Dysfunction↗

Not everything acid-fast is Mycobacterium tuberculosis--a case of Nocardia.

We report a case of a 47 year old woman who presented with a history of motor convulsions and a three month history of an increasingly painful and progressively enlarging mass on the right side of her back. Neurological examination revealed generalised wasting and a right sided hemiplegia. A biopsy of the mass was taken for microbiology which reported growing branching gram positive rods after three days of incubation. A mycological diagnosis of Nocardia asteroides was made. An MRI scan revealed extensive infiltration of the fungal mass into extending from the base of the skull to fifth cervical vertebra.

Biopsy↗

Production of genetically modified lysozymes having extreme heat stability and antimicrobial activity against gram negative bacteria in yeast and in plant.

Hen egg white lysozyme was genetically modified to have extreme heat stability and strong antimicrobial activity against Gram negative bacteria and the modified lysozymes were secreted in yeast and tobacco. Complementary DNA encoding lysozyme was subjected to site-directed mutagenesis to have the Asn-X-Thr(Ser) sequence that is the signal for asparagine-linked glycosylation at the positions 49. The glycosyl lysozyme enhanced heat stability was expressed in the yeast carrying the modified lysozyme cDNA. The expression amount of glycosyl lysozyme was about 10 mg/l of yeast culture medium. Using the same yeast expression system, the lysozyme enhanced antimicrobial action by inserting hydrophobic penta-peptide at the C-terminus were secreted in a small amount (less than 100 micrograms/l in the yeast culture medium). These cDNA constructs of modified lysozymes were engineered into tabacco through Agrobacterium-mediated transformation in order to construct antimicrobial plant. The expression of lysozymes was confirmed by the reverse transcriptional PCR, SDS-PAGE analysis and lytic activity of transformants of tobacco. The transformant having the highest lytic activity expressed about 40 micrograms of lysozyme per g of leaf tissue.

Anti-Bacterial Agents↗

Evaluation of fast disintegrants in terfenadine tablets containing a gas-evolving disintegrant.

Effects of four fast disintegrants on the dissolution of terfenadine tablets containing the gas-evolving disintegrant, CaCO3, were evaluated. In addition, effects of presence of starch along with the fast disintegrants on the dissolution of the tablets were examined. Dissolution data were treated to give dissolution parameters which reflected efficiency of the disintegrant combinations. The four fast disintegrants improved disintegration/dissolution of the original formulation. The relative efficiency of improvement was in the order crospovidone > Ac-Di-Sol > Primojel > low substituted hydroxypropylcellulose. The presence of starch advertently affected the role of the fast disintegrants. Scanning electron microscope studies revealed that starch covered the drug-containing granules and other particles of the tablet. pH changes during dissolution of representative tablets in 0.1 N HCl solutions were determined at specific time intervals. The progressive decrease in rates of acid consumption as a function of the amount of starch, along with the SEM studies, suggested that a barrier existed around the tablet particles. The barrier was generated by the swelled starch grains and was responsible for the loss of the dissolution-improving capacity of the fast disintegrants. Furthermore, the barrier interfered with the diffusion of the hydronium ions and therefore, impaired the function of the disintegrant combination.

Calcium Carbonate↗

Stabilization of Octastatin, a somatostatin analogue: comparative accelerated stability studies of two formulations for freeze-dried products.

Octastatin (vapreotide INN) is a somatostatin analogue being developed in gastro-enterologic, neuroendocrine and oncologic applications. The pharmaceutical form is a freeze-dried preparation for parental injection use. This study was intended to evaluate the stability of the freeze-dried products and to determine the optimally stable formulation. Two types of stabilizing agents (lactose and glutamic acid/sodium glutamate buffer) and three dosage forms (0.5, 1.5, 15 mg of vapreotide base) were investigated. The peptide content and chemical stability of cakes stored at 50 degrees C and 70% relative humidity were determined by HPLC and the regression analysis parameters calculated. Results indicate that the formulation with glutamate buffer is appropriate for long term storage.

Antineoplastic Agents↗

Development of a melanin-based high-performance liquid chromatography stationary phase and its use in the study of drug-melanin binding interactions.

Drug-melanin interactions were studied using a melanin-based HPLC column. Two approaches were chosen for the preparation of the stationary phases: covalent coupling of synthetic L-dopa melanin and in situ polymerization of L-dopa. Retention of a series of phenothiazines on melanin-based stationary phases was attributed to binding to melanin. Frontal affinity chromatography experiments on one melanin-based column allowed us to calculate the affinity and binding capacity of chlorpromazine and promethazine. A competition was observed between chlorpromazine and haloperidol which was qualitatively consistent with previously described results. Data indicated that the interaction was not a simple competition at one site.

Antipsychotic Agents↗

Stabilization of Octastatin, a somatostatin analogue. Preparation of freeze-dried products for parenteral injection.

Octastatin (RC-160, vapreotide INN) is a somatostatin analogue being developed for use in oncological, enterologic and neuroendocrine applications. The pharmaceutical form is a freeze-dried preparation for parenteral injection use. Three dosage forms containing 0.5, 1.5 and 15 mg of vapreotide base have been investigated. Various freeze-drying conditions, stabilizing agents, membranes for sterile filtration and heating procedures have been examined. The formulation with glutamic acid-sodium glutamate buffer as a stabilizing agent, the type of membrane for filtration and the freeze-drying procedure have been found appropriate for subsequent industrial production. No evident degradation was observed either after manufacturing, or after a three-week accelerated stability study at 50 degrees C and 70% relative humidity.

Amino Acid Sequence↗

Effectiveness of a specialized asthma clinic in reducing asthma morbidity in an inner-city minority population.

Asthma is the most common chronic disease of childhood and a leading cause of morbidity in adults. Despite significant advances in medical therapy, asthma morbidity and mortality rates have risen dramatically over the past two decades, especially in minority and socioeconomically disadvantaged populations. Numerous intervention programs have been designed in an attempt to reduce asthma morbidity but few have targeted poor or minority populations. The purpose of this study was to assess whether an outpatient intervention program specifically targeted at a high-minority population in East Harlem, in New York City, was successful in reducing asthma morbidity. A retrospective chart review of 84 patient records was conducted. The patients were divided into two groups, an intervention group (n = 45), who were followed by an asthma specialist (allergist/immunologist), and a nonintervention group, followed by a general internist or pediatrician. Outcome variables including clinic walk-in visits, emergency room visits, and hospitalizations were determined and compared in the pre- and postintervention period in both groups. Patients in the intervention group had reduced total walk-in visits (73 vs. 27, p < 0.001), emergency room visits (30 vs. 5, p < 0.001), and hospitalizations (16 vs. 2, p < 0.001). In contrast, patients in the nonintervention group had no change in total walk-in visits (88 vs. 72), increased emergency visits (7 vs. 22, p < 0.05), and no change in hospitalizations (5 vs. 2), respectively. The outpatient intervention program has been successful in reducing asthma morbidity in the high-risk minority community of East Harlem. Future larger studies are warranted to extend this pilot program to other high-risk minority populations.

Adolescent↗

Erythropoietin (EPO) levels in fetal rats after ritodrine and terbutaline administration.

Beta-2 sympathomimetics, such as terbutaline, have been shown to alter erythropoietin (EPO) secretion in animal studies. More recently introduced sympathomimetics, such as ritodrine, have been extensively used to inhibit uterine contractions in preterm labor. It has not been determined what effect ritodrine may have on EPO production. We investigated the effect of RD administered to rats in the last day of gestation on the dam and the fetuses' levels of EPO. Rats at the 20th day of gestation were given, under anesthesia, either 3000 micrograms/kg ritodrine over a 10-min period or a similar volume of saline as control (CTL). Fetuses were removed at 0 and 4 h after injection. Ritodrine administration produced a decrease of dam EPO (23.4 +/- 4.2 to 12.0 +/- 2.9 pmol/ml), while the CTL showed no changes. The fetuses from the ritodrine-injected dams exhibited a marked decline over the 4-h period, while the CTL fetuses did not change. In other experiments 500 micrograms terbutaline was administered daily during the last 5 days of rat gestation. The drug produced a significant decline in EPO at delivery time, but plasma EPO in the pups was unchanged. Blood hematocrits were comparable to those of controls. The data show that acute administration of ritodrine reduces fetal and dam plasma EPO, while long-term terbutaline treatment late in gestation alters maternal, but not fetal plasma EPO, indicating that neither drug has any direct regulatory effect on the erythropoietic ability of the fetuses.

Animals↗

[Hemodynamic diagnosis of aortocaval fistula complicating abdominal aortic aneurysm].

A 78-year-old man with a history of hypertension was admitted for a fall with back pain. The blood pressure was at 110/50 mmHg and the pulse at 115 b.min-1. A pulsatile abdominal mass was palpated. No signs of respiratory insufficiency or congestive heart failure were found. The diagnosis of abdominal aortic aneurysm was promptly confirmed by echography. Before laparotomy, a pulmonary artery catheter was inserted for haemodynamic monitoring which showed a high cardiac output, low systemic vascular resistances, increased pulmonary artery wedge pressure and a high SvO2 (93%). This was not consistent with a hypovolaemic shock but rather an aortocaval fistula. After incision and aortic clamping, surgical procedure consisted of transaortic closure of the fistula and restoration of arterial continuity with a prosthetic graft. Initial control of venous bleeding was obtained by passing a Foley's catheter distally and by clamping the vena cava. The postoperative course was initially satisfactory. The patient was extubated, but remained with a major renal insufficiency. After a stay of 15 days in the intensive care unit, he died from nosocomial pneumonia. Aortocaval fistulas are either traumatic or spontaneous. Spontaneous fistulas are more common, and in about 90% of the cases result from a rupture of an atherosclerotic aortic aneurysm. Clinical findings include signs of high cardiac output symptoms of venous hypertension and regional arterial insufficiency. Haemodynamic changes can be of value for the recognition of an aortocaval fistula. Most authors emphasize the importance of preoperative diagnosis, allowing the use of appropriate operative techniques and a prompt control of the fistula. This could decrease haemodynamic instability and transfusion requirements.

Aged↗

Albendazole therapy of hydatid disease: 2-year follow-up of 40 cases.

Forty patients with 63 Echinococcus granulosus cysts affecting different sites were treated with albendazole and have been followed up for at least 24 months from completion of therapy. Twenty-one patients (53%) with 37 cysts (59%) showed evidence of healing. The criteria and pattern of healing are outlined. The most serious complication of albendazole therapy was hepatoxic jaundice, which occurred in 5% of patients. Recurrence during the observation period was encountered in 9.5% of patients with a positive response. It is suggested that patients suffering from uncomplicated hydatid disease should be given the benefit of a trial course of albendazole therapy, before surgery is undertaken.

Adolescent↗

Coronary collateral circulation in the transplanted heart.

BACKGROUND: The concept that coronary collateral (CC) circulation can develop in cardiac transplant recipients (CTR) is controversial. Indeed, a decreased occurrence of CC in CTR has been previously reported. METHODS AND RESULTS: We reviewed 102 coronary angiograms in 73 CTR to evaluate the presence and significance of CC in denervated human hearts. These angiograms were compared with angiograms of 70 nontransplanted patients. Twenty-six CTR who had undergone at least two coronary angiograms, thus allowing comparative evaluations, form the basis for this study. Angiograms were analyzed using a modification of CC classification (Rentrop et al) from grade 0 for complete absence to grade 4 representing mature collateral with clear filling of epicardial vessels. Coronary artery disease was classified according to the scheme reported by Gao et al. For the purpose of this study, all type A lesions were grouped as large vessel disease (LVD), and types B1, B2, and C were collectively grouped as small vessel (epicardial) disease (SVD). The presence of CC circulation in all 73 CTR was grade 0, 7 (10%); grade 1, 41 (56%); grade 2, 33 (45%); grade 3, 30 (41%); and grade 4, 5 (7%). However, in control nontransplanted subjects grades 0, 1, 2, 3, and 4 were found in 47 (67%), 22 (31%), 4 (6%), 11 (15%), and 16 (20%) patients, respectively. The presence of mature collaterals (grade 4) in both groups were associated with type A lesions and was frequent in nontransplanted hearts. In contrast, grade 2 and grade 3 vascular channels probably representing CC with "myocardial blush" was more frequent in CTR and was mostly associated with small vessel coronary arteriopathy. CONCLUSIONS: These results suggest the presence of atypical CC in patients with cardiac allograft arteriopathy. It is speculated that this atypical form of CC with "blush pattern" may represent an angiogenic response to microvascular ischemia due to allograft coronary arteriopathy.

Adult↗

Desmopressin has no beneficial effect on excessive postoperative bleeding or blood product requirements associated with cardiopulmonary bypass.

Cardiopulmonary bypass during open-heart surgery is sometimes associated with excessive perioperative bleeding. Following a non-randomized study suggesting that desmopressin acetate (desmopressin) reduced blood product requirements in these patients, we conducted a double-blind, placebo-controlled randomized trial of desmopressin (0.3 micrograms/kg, i. v.) in 92 patients with overt bleeding and a prolonged bleeding time. Mean blood loss during the first 24 h post-treatment was similar in the desmopressin and placebo groups (582 vs 465 ml, respectively; p = 0.15). Red-cell (p = 0.76), fresh frozen plasma (r = 0.66) and platelet unit (p = 0.74) requirements were also similar. The haemostatic effect of desmopressin has been attributed to the release of von Willebrand factor (vWF) and a reduced bleeding time. In our study, vWF and factor VIII:C levels increased while the bleeding time decreased significantly at 90 min and 24 h in both groups and, although vWF and factor VIII:C levels were slightly higher in desmopressin-treated patients at 90 min, the difference was not significant. Thrombin-antithrombin III complex, fibrinogen degradation product and tissue plasminogen activator levels, reflecting activation of the coagulation and fibrinolytic systems, respectively, decreased uniformly in both groups. We conclude that desmopressin is not useful in reducing blood loss or blood product requirements in patients with excessive immediate postoperative bleeding.

Adolescent↗