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Biomedical subjects

R Malek

Publications and source records attributed to R Malek.

At least 19 recordsLinked to original sources
PubMed2005

Should the presence of congenital para-ureteral diverticulum affect the management of vesicoureteral reflux?

PURPOSE: The presence of congenital para-ureteral diverticulum (PUD) has been presumed to lower the resolution rate of vesicoureteral reflux (VUR). PUD is considered an important cause of distortion of the vesicoureteral junction and persistence of VUR. Early surgery has been recommended based on this assumption. However, the scientific evidence supporting this approach is weak. We have been managing this group of patients more conservatively in the last 7 to 8 years on the premise that the presence of PUD is not per se an indication for surgery. To test this hypothesis, we performed a retrospective cohort study to compare the outcome of VUR in children with and without PUD. MATERIALS AND METHODS: We identified 141 consecutive patients with VUR associated with PUD between 1990 and 2004. Of the patients 57 with duplication, ureterocele, neurogenic bladder or outlet obstruction were excluded from study. Median age of the remaining 84 patients at diagnosis was 2.9 years and 56 (69%) were males. Reflux was bilateral in 4 patients, and low (I to II), intermediate (III) and high (IV to V) grade in 39%, 35% and 26%, respectively. Followup was 3 to 168 months (median 47). The outcome was compared to a control group of 95 patients (150 units) with primary VUR and no PUD. The baseline parameters and followup were comparable in both groups. RESULTS: Overall, VUR resolved in 43%, persisted in 27% and was surgically corrected in 30% of the units with PUD. In the 25 patients (26 units) who underwent surgical intervention breakthrough urinary tract infection or new renal scars were the indication in only 5. The remainder were operated on because of persistent VUR and the presence of PUD, mainly before 1997. The incidence of breakthrough urinary tract infection or new renal scar was similar in the controls (6% in PUD group vs 10% in controls, p = 0.7). The resolution rate was 60% for low grade, 39% for intermediate grade and 22% for high grade VUR. These figures were not significantly different from those of the control group in which the resolution rates were 52%, 28% and 33% for comparable grades (p = 0.9). Kaplan-Meier analysis and log rank test did not show any difference in resolution of VUR in the 2 groups (p = 0.84). Multivariate analysis identified grade as the only variable affecting resolution (p = 0.028). The size of PUD did not affect the likelihood of resolution. CONCLUSIONS: The outcome of VUR is similar in children with or without PUD. Therefore, treatment of these patients should not differ. Surgery should be reserved for patients with breakthrough infection or renal scar progression.

Chi-Square Distribution↗
PubMed2003

Endovascular embolectomy of acute basilar artery occlusion.

Acute basilar artery occlusion has a mortality rate approaching 90%. The authors describe a case of acute basilar artery occlusion managed successfully with endovascular embolectomy. A 31-year-old man sought treatment for confusion, dysarthria, and right-sided weakness. He soon became unresponsive and was found to have a vertebral artery dissection and an associated basilar artery embolism. The dissection was managed with endovascular stenting, and the basilar artery embolus was removed with a clot retriever at 7 hours. The patient recovered without neurologic deficit.

Acute Disease↗
PubMed2002

[Care and management of cleft lip and palate by CLP Department hospital Robert Debre in Paris].

Cleft lip and palate repair must take a place at an early stage and respect physiology. Iatrogenic consequences harming maxillary growth must be avoided. Owing to early and reverse timing, short and long term results have been improved. Correction of the soft palate is performed at 3 months of age, lip and hard palate at 6 months without elevation of mucoperiosteum. A palatal plate is applied before and after each surgical stage. Patients receive phonetic, dental end ENT follow-up on a regular basis till end of growth. Correction of sequelae, especially of nasal tip, can be undertaken around grade school entrance at about 6 years of age. Nasal sequelae such as deviation of the septum must not be corrected before end of puberty. Surgery and follow-up must be conducted by an experienced multi-disciplinary team in which the surgeon plays the part of master of works.

Cleft Lip↗
PubMed2001

Sampling activated mechanisms in proteins with the activation-relaxation technique.

The activated dynamics of proteins occur on time scales of milliseconds and longer. Standard all-atom molecular dynamics simulations are limited to much shorter times, of the order of tens of nanoseconds. Therefore, many activated mechanisms that are crucial for long-time dynamics will not be observed in such molecular dynamics simulation; different methods are required. Here, we describe in detail the activation-relaxation technique (ART) that generates directly activated mechanisms. The method is defined in the configurational energy landscape and defines moves in a two step fashion: (a) a configuration is first brought from a local minimum to a nearby first-order saddle point (the activation); and (b) the configuration is relaxed to a new metastable state (the relaxation). The method has already been applied to a wide range of problems in condensed matter, including metallic glasses, amorphous semiconductors and silica glass. We review the algorithm in detail, discuss some previously published results and present simulations of activated mechanisms for a two-helix bundle protein using an all-atom energy function.

Algorithms↗
PubMed2001

[Prevalence of type 2 diabetes mellitus and glucose intolerance in the Setif area (Algeria)].

OBJECTIVE: Diabetes mellitus stands as a major public health issue in Algeria and has an important socioeconomical impact. Our study involved a representative sample of 1457 subjects and aimed at assessing the prevalence of type 2 diabetes and glucose intolerance in the population of Setif Wilaya, aged between 30 and 64 years old. MATERIAL AND METHODS: Diagnosis was based on oral glucose tolerance test, according to World Health Organisation criteria. RESULTS: Diabetes prevalence was 8.2% (CI: 95%: 6.8% to 9.6%). It increased with age, while 50% of cases were undiagnosed, without any difference according to sex nor urban (7.3%)/rural (9.7%) distribution. Glucose intolerance prevalence was 7.1 (CI 95%: 5,8% to 8,4%). Age-standardized prevalence, according to world population data provided by WHO, was 9.08% for diabetes and 7.5% for glucose intolerance. When the new American Diabetes Association Criteria were used, prevalence of type 2 diabetes was 8.8 (CI: 95%: 7.3% to 10.2%) and that of fasting hyperglycemia was 6.9% (CI: 95%: 5.6 to 8.2). According to these new criteria, among the 66 cases with undiagnosed diabetes, 79% presented with a fasting blood glucose > or =126 mg/dl. CONCLUSION: This relatively high diabetes prevalence calls for an appropriate management and health education, particularly focused on high risk subjects. These results bring the the first detailed prevalence data in an Algerian population.

Adult↗
PubMed2000

Dynamics of lennard-jones clusters: A characterization of the activation-relaxation technique

The potential energy surface of Lennard-Jones clusters is investigated using the activation-relaxation technique (ART). This method defines events in the configurational energy landscape as a two-step process: (a) a configuration is first activated from a local minimum to a nearby saddle-point and (b) is then relaxed to a new minimum. Although ART has been applied with success to a wide range of materials such as a-Si, a-SiO2 and binary Lennard-Jones glasses, questions remain regarding the biases of the technique. We address some of these questions in a detailed study of ART-generated events in Lennard-Jones clusters, a system for which much is already known. In particular, we study the distribution of saddle-points, the pathways between configurations, and the reversibility of paths. We find that ART can identify all trajectories with a first-order saddle point leaving a given minimum, is fully reversible, and samples events following the Boltzmann weight at the saddle point.

Journal Article↗
PubMed1996

Ciliary neurotrophic factor regulates nicotinic acetylcholine receptors on human neuroblastoma cells.

We have investigated the effects of several neurokine/cytokine family members on the level of alpha-bungarotoxin-binding to neuronal nicotinic acetylcholine receptors. Exposure of human neuroblastoma cells (SH-SY5Y and IMR-32) to ciliary neurotrophic factor (CNTF), leukemia inhibitory factor or oncostatin-M resulted in a 30-40% decline in alpha-bungarotoxin receptors on the cells with no decrease seen in either muscarinic acetylcholine receptors or in L-type Ca2+ channels. The level of nicotinic receptor was not affected by the related cytokine, interleukin-6. Treatment of IMR-32 cells with 40 pM CNTF produced a half-maximal decrease of alpha-bungarotoxin binding which compared well with the affinity estimated from binding of 125I-CNTF (Ki approximately 40 pM) and the concentration causing c-fos activation in SH-SY5Y cells, as detected by nuclear run-on assays (60-120 pM). Previous results have indicated that the differentiating agents, phorbol esters and retinoic acid, also decrease nicotinic receptor numbers. Here the effects of CNTF, which did not induce neural differentiation, were enhanced by differentiation with 12-O-tetradecanoylphorbol 13-acetate (10 nM) and prevented by retinoic acid (10 microM). Therefore, the response of neuroblastoma cells to cytokines may be under developmental control. These cells offer a system to examine cytokine responses and signal transduction mechanisms during neural development.

Bungarotoxins↗
PubMed1996

The catabolism of intact, reactive centre-cleaved and proteinase-complexed C1 inhibitor in the guinea pig.

Clearance rates in the guinea pig were determined for intact guinea pig and human C1 inhibitor, the complexes of both inhibitors with human Cls, beta factor XIIa and kallikrein, and for each inhibitor cleaved at its reactive centre with trypsin. Intact human and guinea pig C1 inhibitor were cleared from the circulation more slowly (t1/2s of 9-7 h and 12.1 h and fractional catabolic rates (FCRs) of 0.09 and 0.117) than any of their cleaved or complexed forms. The reactive centre-cleaved inhibitors were cleared with half-lives of 6.75 h for humans and 10.1 h for the guinea pig. The complexes with target proteases were catabolized much more rapidly, with half-lives ranging from 3-08 h to 4.3 h. The complexes with kallikrein were cleared more slowly than those with Cls and beta factor XIIa. Complexes prepared with the guinea pig and human inhibitors were cleared at equivalent rates. The free inactivated proteases were cleared at rates similar to the equivalent complexes, except for kallikrein, which was cleared more rapidly than its complex. The fact that the complexes with different target proteases differed in their catabolism and that protease and complex catabolism were similar suggests that protease may play a direct role in clearance.

Amino Acid Sequence↗
PubMed1995

Regulation of nicotinic acetylcholine receptors on human neuroblastoma cells during differentiation.

Neuronal nicotinic acetylcholine receptors are expressed on a variety of cells in the nervous system where they play key roles in synaptic transmission and information transfer. Little is known, however, about the molecular mechanisms that control their expression, distribution, and function during nervous system development. We have investigated the control of expression during differentiation of one class of acetylcholine receptors that bind alpha-bungarotoxin of human neuroblastoma cells. We report that induction of differentiation of SH-SY5Y, SK-n-SH or IMR-32 cells by the phorbol ester 12-O-tetradecanoyl phorbol 13-myristate (10 nM, TPA) or by retinoic acid resulted in as much as a 70% decline in alpha-bungarotoxin receptors on the cells. The response to the phorbol ester was blocked by the protein kinase C inhibitors staurosporine and bisindolylmaleimide. The decrease in receptors induced by 10 microM retinoic acid was not affected by either agent. However, responses to lower (10 nM) concentrations of retinoic acid were blocked by staurosporine but not bisindolylmaleimide, suggesting a dual mechanism of action for retinoic acid in regulating acetylcholine receptors. It appears that acetylcholine receptors on neuroblastoma cells are regulated during differentiation by both protein kinase C-dependent and -independent mechanisms.

Binding Sites↗
PubMed1995

Intravenous manganese-mesoporphyrin as a magnetic resonance imaging contrast agent: an experimental model using VX-2 carcinoma in rabbits.

RATIONALE AND OBJECTIVES: We investigated the potential of manganese (III) mesoporphyrin (Mn-mesoporphyrin) as a hepatobiliary contrast agent for magnetic resonance (MR) imaging in rabbits given VX-2 carcinoma liver implants. METHODS: Rabbits given VX-2 carcinoma liver implants (n = 8) were imaged before and after the intravenous (i.v.) administration of 0.04 mmol/kg Mn-mesoporphyrin. MR images were correlated with gross-specimen cross-sections. The distribution of Mn in various tissues following i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin was determined using atomic absorption analysis. A standard panel of serum chemistries was followed over 7 days in six rabbits following this same dose of Mn-mesoporphyrin and compared with chemistries from two control rabbits. RESULTS: I.v. administration of 0.04 mmol/kg (25 mg/kg) Mn-mesoporphyrin resulted in improvement of tumor-to-liver contrast, with enhancement of normal liver (99.7 +/- 14.7%) and the gallbladder (442 +/- 116%), but not VX-2 tumor tissue (14.8 +/- 13.9%), (n = 8, p = .05). Analysis of tissue Mn levels 100 min after i.v. Mn-mesoporphyrin injection demonstrated preferential distribution of Mn to normal liver tissue (57.8 +/- 15.3 micrograms Mn/g) compared with VX-2 tumor (4.28 +/- 1.48 micrograms Mn/g). No significant change was found in the serum chemistries of six normal rabbits over a 7-day period after the i.v. administration of 0.04 mmol/kg Mn-mesoporphyrin. CONCLUSION: I.v. Mn-mesoporphyrin improved lesion-to-liver contrast because of preferential distribution of Mn-mesoporphyrin to normal liver parenchyma and bile.

Animals↗
PubMed1995

Magnetic resonance imaging of the hepatobiliary system: intestinal absorption studies of manganese mesoporphyrin.

RATIONALE AND OBJECTIVES: We studied the intestinal absorption of manganese mesoporphyrin (Mn-mesoporphyrin), a potential oral hepatobiliary contrast agent. METHODS: Mn-mesoporphyrin was complexed with monoolein and taurocholate (mixed micelles). Portal venous delivery and biliary excretion were measured after intestinal administration in rats and rabbits, and the mechanism of intestinal transport was studied in a combined lymph-bile fistula model in rats. T1-weighted magnetic resonance (MR) images of the liver were obtained in rats and domestic pigs before and after gastric administration of Mn-mesoporphyrin in mixed micelles. RESULTS: A 2.2-fold increase of portal venous Mn concentration was found 90 min after intestinal administration of the complex. None was found in the lymph collected from the thoracic duct, indicating a transcellular transport mechanism through the intestinal mucosa with portal venous delivery. Mn-mesoporphyrin levels in bile peaked between 240 and 270 min after administration (200-fold increase). The greatest liver enhancement (20-90%) was measured 360 min after administration. CONCLUSION: The feasibility of intestinal delivery of Mn-mesoporphyrin, a lipophilic hepatobiliary contrast agent was demonstrated.

Animals↗
PubMed1994

[Deformities of the fingers secondary to fingersucking].

After prolonged finger-sucking in early infancy, skeletal digital deformities, especially of the index finger, may occur. Thumb-sucking causes primarily dental disturbances whereas prolonged index--sucking may deform this finger, with functional as well as aesthetic consequences on the grip. Acquired rotation of the index finger is the most frequent deformity and does not always resolve spontaneously so that a rotation osteotomy had to be performed in 3 cases.

Finger Joint↗
PubMed1994

Inactivation of the Porphyromonas gingivalis fimA gene blocks periodontal damage in gnotobiotic rats.

Fimbrial production by Porphyromonas gingivalis was inactivated by insertion-duplication mutagenesis, using the cloned gene for the P. gingivalis major fimbrial subunit protein, fimA. by several criteria, this insertion mutation rendered P. gingivalis unable to produce fimbrilin or an intact fimbrial structure. A nonfimbriated mutant, DPG3, hemagglutinated sheep erythrocytes normally and was unimpaired in the ability to coaggregate with Streptococcus gordonii G9B. The cell surface hydrophobicity of DPG3 was also unaffected by the loss of fimbriae. However, DPG3 was significantly less able to bind to saliva-coated hydroxyapatite than wild-type P. gingivalis 381. This suggested that P. gingivalis fimbriae are important for adherence of the organism to saliva-coated oral surfaces. Further, DPG3 was significantly less able to cause periodontal bone loss in a gnotobiotic rat model of periodontal disease. These observations are consistent with other data suggesting that P. gingivalis fimbriae play an important role in the pathogenesis of human periodontal disease.

Alveolar Bone Loss↗
PubMed1992

Conjugal transfer of plasmid and transposon DNA from Escherichia coli into Porphyromonas gingivalis.

Using the broad host-range vector R751 to provide transfer functions, plasmid pVAL-1 and transposon Tn4351 were conjugally mobilized from Escherichia coli into Porphyromonas gingivalis. Transfer frequencies for both elements varied between 10(-6) and 10(-11), depending upon the recipient. The behavior of pVAL-1 and Tn4351 in P. gingivalis was essentially as described previously in Bacteroides spp. These data indicate that plasmid and transposon DNA can be conjugally transferred into P. gingivalis and that these elements can be used to genetically manipulate the organism in examining putative virulence determinants that may participate in the induction or exacerbation of periodontal disease.

Autoradiography↗