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Biomedical subjects

M Sadek

Publications and source records attributed to M Sadek.

At least 19 recordsLinked to original sources
PubMed2003

Dynamic three-dimensional spiral computed tomographic cysto-urethrography: a novel technique for evaluating post-traumatic posterior urethral defects.

OBJECTIVE: To present a new method of identifying the anatomy of posterior urethral distraction defects (PUDDs) using three-dimensional spiral computed tomography/cysto-urethrography (CTCUG), as conventional two-dimensional CUG can give a false interpretation of the exact anatomy. PATIENTS AND METHODS: Twenty-one patients presenting with a PUDD were assessed between February 2001 and October 2002. All patients initially underwent combined ascending and micturating CUG (ACUG), followed by CTCUG analysed using special software. In this technique all soft-tissue densities were subtracted from the volume of interest leaving only high-density images, i.e. pelvic bony structure and the contrast medium-filled bladder and urethra. The images were taken over a sequence and 36 different images viewed by 'roll and spin' techniques, each of which had a different plane of vision. Images were supplied as static CT films and as a movie on a compact disk using a computer program. RESULTS: The technique allows one CT image to be viewed from 36 different angles both dynamically and statically, allowing the surgeon the unique opportunity to view the PUDD through several planes and precisely identify its anatomy. By comparing the data obtained with this technique to those obtained by conventional ACUG, and each in relation to the operative findings, the following aspects could be more thoroughly evaluated by CTCUG: the location of the distraction injury, the length of the distraction defect, the degree and direction of urethral end-alignment, the relation of the ectopic bony fragments and bone callus to the urethra, and the presence of various pathological defects, e.g. fistulae, false passages and diverticulae. CONCLUSION: With CTCUG, both static and dynamic images can be obtained, allowing the easier staging of a PUDD and thus better surgical planning and consequently better results from reconstruction.

Adult↗
PubMed2002

Comparative evaluation of the nuclear matrix protein, fibronectin, urinary bladder cancer antigen and voided urine cytology in the detection of bladder tumors.

PURPOSE: We evaluate the diagnostic efficacy of nuclear matrix protein-22 (NMP22, Matritech, Newton, Massachusetts), fibronectin and urinary bladder cancer antigen (UBC, IDL Biotech, Borlange, Sweden) compared with voided urine cytology in the detection of bladder cancer. MATERIALS AND METHODS: A total of 168 patients provided a single voided urine sample for NMP22, fibronectin an ideal monoclonal for urinary bladder cancer and cytology before cystoscopy. Cystoscopy was done for all patients as the reference standard for identification of bladder cancer. Biopsy of any suspicious lesion was performed for histopathological examination. Of the 168 cases 100 were histologically diagnosed as bladder cancer, whereas the remaining 68 had benign urological disorders. A group of 47 healthy volunteers were also enrolled in this study. Voided urine was evaluated by NMP22, fibronectin and UBC, and their values were expressed relative to mg. creatinine. RESULTS: The optimal threshold values for NMP22, fibronectin and UBC were calculated by receiver operator characteristics curves as 27 units per mg. creatinine, 198 mg./mg. creatinine and 13 ng./mg. creatinine, respectively. The levels and positive rates of the 3 parameters were significantly higher in the malignant group compared to either the benign group or normal controls. Of the entire group NMP22, fibronectin and UBC were positive in 93.2%, 91% and 68.2%, respectively in bladder cancer cases with positive cytology. Moreover, these positive rates were significantly higher in bilharzial bladder cancer cases (58.8%, 67.5%, 58.8%, respectively) compared to nonbilharzial cases (35.6%, 36.3%, 31.1%). Overall sensitivity and specificity were 85% and 91.3% for NMP22, 83% and 82.6% for fibronectin, 67% and 80.8% for UBC and 44% and 100% for voided urine cytology. Combined sensitivity of voided urine cytology with the 3 biomarkers together was higher than either combined sensitivity of voided urine cytology with 1 of the biomarkers or than that of the biomarker alone. CONCLUSIONS: Our data indicate that NMP22 and fibronectin had superior sensitivities compared to UBC and voided urine cytology, while NMP22 and voided urine cytology had the highest specificities. The combined use of markers increased the sensitivity of cytology from 44% to 95.3%. The higher sensitivities of markers in bilharzial than nonbilharzial bladder cancer highlight their clinical use in screening patients with urinary bilharziasis.

Adult↗
PubMed1998

Associations between family history of asthma, bronchopulmonary dysplasia, and childhood asthma in very low birth weight children.

Very low birth weight (VLBW) infants are at risk for childhood wheezing and asthma, as are children with a family history of asthma. Family history of asthma may also be associated with premature labor and, among VLBW infants, with bronchopulmonary dysplasia (BPD) and chronic lung disease (CLD) of prematurity. This study targeted all neonates with birth weight <1,501 g who were admitted to seven perinatal centers in Wisconsin and Iowa between August 1, 1988 and June 30, 1991. Comprehensive information was collected for 723 of the 1,007 30-day survivors, and for 106 full-term controls. A representative subgroup of 257 VLBW children was contacted at age 5 years to ascertain bronchodilator and/or steroid use and diagnosis of asthma. Some evidence of an association between family history of asthma and premature birth was found, but it was not associated with neonatal BPD/CLD or BPD/CLD severity. Among BPD/CLD indicators, radiographic evidence of BPD at age 25-35 days was most strongly associated with bronchodilator use up to age 2 years (odds ratio (OR) = 10.1, 95% confidence interval (CI) 4.07-25.2) and with asthma between ages 2 years and 5 years (OR = 4.83, 95% CI 2.18-10.7). Among children without radiographic evidence of BPD, family history of asthma was associated with childhood asthma and bronchodilator use.

Asthma↗
PubMed1998

Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project.

Criteria in common use for the diagnosis of chronic lung disease of prematurity or bronchopulmonary dysplasia in the neonatal period have not been sufficiently compared and validated against indicators of later respiratory complications. In this study of all 680 infants < or = 1500 gm birth weight admitted to six perinatal centers August 1, 1988, to July 31, 1990, 524 were alive and had no major congenital anomalies at 5 years old. Of 419 who had given permission to release their names and addresses, 272 were located and participated in a follow-up study. The following diagnostic criteria for bronchopulmonary dysplasia and chronic lung disease of prematurity were used during the initial hospitalization: (1) use of supplemental oxygen on day 30 of life, (2) a comprehensive bronchopulmonary dysplasia severity score applied at 25 to 35 days of life developed by a clinician panel to adjust for practice variation in ventilatory support and blood gases, (3) use of supplemental oxygen on day 30 of life with radiographic evidence consistent with bronchopulmonary dysplasia between days 25 and 35 of life, (4) radiographic evidence consistent with bronchopulmonary dysplasia alone, and (5) use of supplemental oxygen at 36 weeks' postconceptional age. These criteria were assessed against use of bronchodilators or steroids during the first 2 years of life, diagnosis of asthma, and hospitalizations for respiratory causes up to age 5. Although all criteria were significantly associated with all the outcomes, radiographic evidence was most predictive. These results indicate that, during a period when 21% of neonates were exposed to antenatal steroids, 24% received surfactant and 9% received postnatal corticosteroids, radiographic evidence was more predictive of long-term respiratory outcome than other commonly used criteria.

Bronchopulmonary Dysplasia↗
PubMed1998

Association of tocolytic therapy with antenatal steroid administration and infant outcomes. Newborn Lung Project.

The use of tocolytic agents to halt premature labor is controversial. We examine a database on very low-birth-weight infants born following the onset of premature labor (n = 540) for association between tocolytic and antenatal steroid therapy, and to assess neonatal and childhood outcomes following combined therapy. Data are from a multicenter regionally based study of all infants below 1501 g at seven neonatal intensive care units (NICUs) in Wisconsin and Iowa, born August 1, 1988 through June 30, 1991. Infant outcomes analyzed are death in the first 30 days, respiratory distress syndrome (RDS), and intraventricular hemorrhage (IVH). Fewer deliveries occurred within 12 hours of labor onset with tocolytics (61 vs. 75% without). A strong association between tocolytic therapy and antenatal steroid administration was found [adjusted odds ratio OR = 5.7, 95% confidence interval CI: (3.3, 10.0)]. Tocolytics were associated with lower mortality in the first 30 days [OR = 0.29, CI: (0.15, 0.56)]. Joint administration of tocolytics and antenatal steroids versus neither was associated with lower incidence of the combined outcome of respiratory distress syndrome (RDS) or death [OR = .30, CI: (0.15, 0.60)] and grade III-IV IVH or death [OR = 0.35, CI: (0.14, 0.98)]. Tocolytic therapy alone was not associated with IVH grade III-IV [OR = 1.0, CI: (0.57, 1.9)] among survivors.

Cerebral Hemorrhage↗
PubMed1996

Purification and characterization of an extracellular (1 --> 6)-beta-glucanase from the filamentous fungus Acremonium persicinum.

An endo-(1 --> 6)-beta-glucanase has been isolated from the culture filtrates of the filamentous fungus Acremonium persicinum and purified by (NH4)2SO4 precipitation followed by anion-exchange and gel-filtration chromatography. SDS/PAGE of the purified enzyme gave a single band with an apparent molecular mass of 42.7 kDa. The enzyme is a non-glycosylated, monomeric protein with a pI of 4.9 and pH optimum of 5.0. It hydrolysed (1 --> 6)-beta-glucans (pustulan and lutean), initially yielding a series of (1 --> 6)-beta-linked oligoglucosides, consistent with endo-hydrolytic action. Final hydrolysis products from these substrates were gentiobiose and gentiotriose, with all products released as beta-anomers, indicating that the enzyme acts with retention of configuration. The purified enzyme also hydrolysed Eisenia bicyclis laminarin, liberating glucose, gentiobiose, and a range of larger oligoglucosides, through the apparent bydrolysis of (1 --> 6)-beta- and some (1 --> 3)-beta-linkages in this substrate. K(m) values for pustulan, lutean and laminarin were 1.28, 1.38, and 1.67 mg/ml respectively. The enzyme was inhibited by N-acetylimidazole, N-bromosuccinimide, dicyclohexylcarbodi-imide, Woodward's Reagent K, 2-hydroxy-5-nitrobenzyl bromide, KMnO4 and some metal ions, whereas D-glucono-1,5-lactone and EDTA had no effect.

Acremonium↗
PubMed1996

The relation of maternal complications to outcomes in very low birthweight infants in an era of changing neonatal care.

We examine the relation of key neonatal outcomes to pregnancy complications and to the use of antenatal steroids and investigate whether there is evidence of recent change in this relation. Complete information on pregnancy and neonatal course was available for 749 out of 949 singleton births without major congenital anomalies below 1501 g admitted to seven regional neonatal intensive care units between August 1, 1988 and June 30, 1991. Mortality was highest in infants born after labor with spontaneous rupture of fetal membranes of less than 24 hours duration (odds ratio [OR] = 1.6, 95% confidence interval [1.0, 2.6]). Spontaneous rupture of membranes of over 24 hours duration was associated with decreased risk of respiratory distress syndrome (OR = 0.42, [0.28, 0.64]) and decreased risk of patent ductus arteriosus (OR = 43, [0.28, 0.66]). Pregnancy induced hypertension was associated with increased risk of respiratory distress syndrome in those born at less than 20 weeks' gestation (OR = 6.0, [2.0, 17]). Labor with or without rupture of membranes of short duration was associated with increased risk of intraventricular hemorrhage (OR = 1.9, [1.2, 2.5]). These associations were not different in early versus late time periods of the study. Antenatal steroids were associated with dramatically reduced risk of mortality (OR = 0.20, [0.09, 0.50] ), respiratory distress syndrome (OR = 0.52, [0.32, 0.85]), and intraventricular hemorrhage (OR = 0.37, [0.21-0.65]).

Adrenal Cortex Hormones↗
PubMed1995

Stereochemical course of glucan hydrolysis by barley (1-->3)- and (1-->3, 1-->4)-beta-glucanases.

The stereochemical course of hydrolysis of Laminaria digitata laminarin and barley (1-->3, 1-->4)-beta-glucan by barley (1-->3)-beta-glucanase (E.C. 3.2.1.39) isoenzyme GII and (1-->3, 1-->4)-beta-glucanase (EC 3.2.1.73) isoenzyme EII, respectively, has been determined by 1H-NMR. Both enzymes catalyse hydrolysis with retention of anomeric configuration (e-->e) and may therefore operate via a double displacement mechanism. We predict that all other members of Family 17 of beta-glycosyl hydrolases also follow this stereochemical course of hydrolysis.

Carbohydrate Conformation↗
PubMed1994

Comparison of native and mutant proteins provides a sequence-specific assignment of the cysteinyl ligand proton NMR resonances in the 2[Fe4S4] ferredoxin from Clostridium pasteurianum.

A sequence-specific assignment is presented for the eight low-field paramagnetically shifted cysteinyl ligand proton NMR resonances in the 2[Fe4S4] ferredoxin from Clostridium pasteurianum. The assignment is based upon comparison of chemical shifts in 1D and 2D NMR spectra of native oxidized protein and those of three mutants. The mutant proteins G12A and G41A were designed to produce minor local structural changes (hence small chemical shift perturbations) in either cluster I (glycine 12 to alanine) or in cluster II (glycine 41 to alanine). Observed chemical shift changes in spectra of the double mutant G12,41A support the interpretation. The comparison is aided by structural models derived from the crystal structure of the related ferredoxin from Peptococcus aerogenes. Each of the eight low-field resonances is assigned to a beta-proton from a different cysteinyl ligand, and so connectivities established from previous TOCSY and HMQC data allow assignment of all 24 cysteinyl ligand protons.

Amino Acid Sequence↗
PubMed1994

A new radiographic scoring system for bronchopulmonary dysplasia. Newborn Lung Project.

OBJECTIVES: To develop a simple, clinically meaningful radiographic score for bronchopulmonary dysplasia (BPD). To investigate its reliability, validity, and usefulness and to compare it to the Edwards score. WORKING HYPOTHESIS: Our radiographic scoring of BPD is reliable, correlates with respiratory support, and provides a necessary standardization in comparing severity of respiratory disease between hospitals. STUDY DESIGN: Prospective cohort study. PATIENT SELECTION: The study included all neonates (n = 366) with birth weight below 1501 g admitted to 7 neonatal intensive care units, who had chest radiographs taken at age 25-35 days. METHODOLOGY: A simple radiographic scoring system was developed. Scores ranging from 0 to 6 were assigned based on standard radiographs and descriptors of degree of abnormality. All radiographs taken between days 25 and 35 of age (n = 1087) were graded by a radiologist and a neonatologist. Radiographs from a stratified random sample of 37 neonates (10%) were also scored by the method of Edwards (n = 128 radiographs). A respiratory support index was constructed for days 25-35 and correlated with the radiographic score. RESULTS: Between-reader correlation was r = 0.87 for our score and r = 0.88 for the Edwards score. The two scores correlated with each other at r = 0.94. The respiratory support index correlated with our radiographic score at r = 0.75 overall, and r = 0.56 to 0.88 within hospitals. Higher postnatal corticosteroid use was found at the hospitals with the lower correlations. CONCLUSIONS: Our radiographic scoring is reliable, valid, and gives results similar to the Edwards score. Radiographs play a standardizing role in assessing severity of BPD between hospitals.

Age Factors↗
PubMed1993

Determination of the solution structure of neuropeptide K by high-resolution nuclear magnetic resonance spectroscopy.

1H NMR chemical shift assignments for neuropeptide K (NPK) and neurokinin A (NKA) have been determined at 600 MHz in 28% trifluoroethanol/water solution. Two-dimensional NMR techniques were used to assign proton resonances, and interproton distances were estimated from the observed nuclear Overhauser effects (NOEs). These distances were used as constraints in a simulated annealing protocol within the program XPLOR to generate structures consistent with experimental data. NPK forms a regular amphipathic alpha-helical structure from Asp 3, terminating at Gly 18. Slowly exchanging amide protons identified in this region are likely to be involved in hydrogen bonds to stabilize the helix. The remainder of the molecule displays many sequential NOEs, with some i-(i + 2) contacts, but little further evidence of defined secondary conformation. NKA displays strong sequential connectivities between amide protons from Thr 3 to Met 10, and some i-(i + 2) connectivities suggestive of a series of dynamic turns in equilibrium. A comparison of the tail region of NPK with the related peptide homologue, neurokinin A, in the same solvent system, indicates that both show increasing order when trifluoroethanol is titrated into water solution, with the appearance of sequential NOEs between backbone amide protons. Differences between the corresponding spans of primary sequence appear to be minimal. The clear finding that NPK adopts a well-defined helix in its N-terminal half and is relatively disordered in the C-terminal half, which includes the entire NKA sequence, may have important implications for understanding the increased selectivity of NPK over NKA for one class of neurokinin receptor.

Amino Acid Sequence↗
PubMed1990

Conformational analysis of cyproheptadine hydrochloride.

A nuclear magnetic resonance and theoretical study on the conformations and molecular flexibility of cyproheptadine hydrochloride (1) is reported. In the 1H NMR spectrum of 1 in CDCl3, two conformational forms are observed to occur in an approximate ratio of 1:4. In both forms, NOE and coupling constant measurements suggested that the terminal N-methyl group is equatorial. NOE experiments identified the more populated conformer (labeled D) as similar to the form seen in the X-ray crystal structure of cyproheptadine. The other form observed (A) may in principle be converted to D via either inversion of the central ring (T(inv)) or concerted nitrogen (N(inv)) and piperidine ring inversion (P(inv)). Chemical-exchange peaks in the 400-MHz 2D NOESY/chemical-exchange spectrum suggested that the latter mechanism is responsible for interconversion between the two forms. A theoretical study of the various interconversion processes using both molecular mechanics (MM2) and molecular orbital (AM1) approaches is also reported.

Chemical Phenomena↗
PubMed1990

Preparation of lipid emulsions by pressure extrusion.

Lipid emulsions consisting of a surface monolayer of phospholipid enclosing a core of neutral lipids have been prepared by repeated extrusion through polycarbonate filters of defined pore size. Particle size, as measured by photon correlation spectroscopy, decreases on successive passes through a 100 nm filter, reaching a near constant value (130-150 nm) after 4 passes. A corresponding decrease in the standard deviation of the particle size distribution occurs during this process. The recovery of lipids, especially of cholesterol and cholesterol ester, is improved if the emulsion is sonicated before extrusion through filters. [31P]-NMR and fluorescence techniques are used to confirm that the resulting structures are emulsions rather than lipid bilayers.

Cholesterol↗
PubMed1989

Morpheus: a conformation-activity relationships and receptor modeling package.

Our molecular modeling software package, MORPHEUS, allows the study of the interactions between biologically active molecules and their receptors. The package is capable of exploring the multidimensional conformational space accessible to each molecule of the data set under study. By specifying distance constraints or hypothetical receptor binding points, the package is able to filter the biologically accessible conformations of each active compound and deduce a three-dimensional model of the binding sites consistent with the properties of the agonists (or antagonists) under scrutiny. The electrostatic potentials in the environment of a putative binding site can also be investigated using the MORPHEUS package. The molecular modeling module CRYS-X, which is written in FORTRAN 77 for IBM PC machines, is capable of building, displaying and manipulating molecules.

Computer Graphics↗
PubMed1986

Conformational energy calculations and electrostatic potentials of dihydrofolate reductase ligands: relevance to mode of binding and species specificity.

Classical potential energy calculations are reported for a series of 11 structurally diverse substrates, products, and inhibitors of dihydrofolate reductase. In almost every case, the calculations reveal a range of potential biologically active conformations accessible to the molecule, and geometry optimization with molecular mechanics and molecular orbital calculations further expands the range of accessible conformations. The energy calculations are supplemented with electrostatic potential energy surfaces for the heterocyclic components of each molecule. These data are used in conjunction with the energy calculations and the crystallographically determined enzyme structures to compare two alternative proposed binding modes of folates known to bind with their pteridine rings inverted relative to that of methotrexate. It is shown that the conformational flexibility of the connecting chain between the benzoyl glutamate and pteridine moieties in the folates actually allows the pteridine ring to shift between these alternative binding modes, a combination of which may offer the best explanation for the observed activity. The electrostatic potentials and conformational energy data are also used in an attempt to account for the species specificity of inhibitors of mammalian, bacterial, and protozoal dihydrofolate reductases. The results show that while these techniques can be used to explain many of the observed results, others require recourse to the observed crystal structures to provide a satisfactory explanation.

Aminopterin↗