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Biomedical subjects

H Darwish

Publications and source records attributed to H Darwish.

At least 19 recordsLinked to original sources

Correlation between penile duplex findings and stress electrocardiography in men with erectile dysfunction.

The aim of this work is to assess the association between vasculogenic erectile dysfunction (ED) and coronary artery disease in men above the age of 40 y. The study included 40 patients above 40 y of age with vasculogenic ED of more than 3 months duration. A dynamic duplex study after intracavernosal injection of a bimix solution (60 mg papaverine + 2 mg phentolamine mesylate) was carried out using a color ultrasound machine. The patients underwent a stress ECG test, carried out on a motor-driven treadmill according to the 'Bruce Protocol'. A total of 12 patients were diagnosed with positive ischemic heart disease (IHD). Their mean peak systolic velocity (PSV) was PSV = 19.58 cm/s. In all, patients were diagnosed with negative IHD; their mean PSV was 36.21 cm/s. A statistically significant difference was observed between patients with positive IHD and patients with negative IHD regarding PSV (P = 0.003). The sensitivity of a PSV of less than 35 cm/s in predicting IHD was 50% with a specificity of 100%. Positive predictive value for abnormal stress ECG to predict a PSV of less than 35 cm/s was 100%. In conclusion, the PSV of cavernosal arteries is a reliable measure for predicting IHD in patients with vasculogenic ED. Patients with a PSV of less than 35 cm/s should be referred for cardiologic assessment as they carry a real risk of having silent IHD.

Adrenergic alpha-Antagonists↗

Fighting colorectal cancer: molecular epidemiology differences among Ashkenazi and Sephardic Jews and Palestinians.

BACKGROUND: To evaluate and compare differences in the molecular genetics among high-risk (Ashkenazi Jews), intermediate-risk (Sephardic Jews) and low-risk (Palestinians) groups for colorectal cancer who live in the same geographical region. PATIENTS AND METHODS: The 1995-1996 records from the Tel Aviv Medical Center and Muqased hospital (East Jerusalem) randomly identified patients with colorectal cancer. There were 25 patients from each ethnic group. Epidemiological data were obtained from interviews with the patients and from their hospital charts. The levels of cyclin D1, beta-catenine, p27, p53, Ki-67 and Her-2/neu proteins were determined by immunohistochemistry. The main outcome measures were the association between gene expression and colorectal incidence in the different ethnic groups. RESULTS: Ashkenazi Jews have the highest rate of colorectal cancer, and are diagnosed at an early stage compared with Palestinians (72% and 33% of the cases are in Dukes' A and B, respectively), and, hence, this may explain the better 5-year survival rate among this group. Sephardic Jews are diagnosed at a more advanced stage, the tumors are poorly differentiated and they lack p27. Palestinians have significantly higher cyclin D1 levels. There was a statistically significant inverse correlation between the expression of beta-catenine and cyclin D1, as well as p53 and p27 (P <0.05). CONCLUSIONS: Increased expression of cyclin D1, p53, Ki-67, beta-catenine and Her-2/neu, and decreased expression of p27 may be important events in the three ethnic groups with colorectal cancer. The lower mortality rate among Ashkenazi Jews may be partially explained by their better molecular biology profile.

Aged↗

The cognitive and behavioural effects of clobazam and standard monotherapy are comparable. Canadian Study Group for Childhood Epilepsy.

PURPOSE: To compare the cognitive and behavioural effects of clobazam versus standard monotherapy in the treatment of childhood epilepsy. METHODS: A randomized, double-blind, prospective design was carried out at three Canadian pediatric epilepsy centres. This study was part of a larger multi-centre study on the efficacy of clobazam. Children with newly diagnosed epilepsy were assigned randomly to receive clobazam or carbamazepine. Children who had failed previous treatment with carbamazepine were assigned randomly to clobazam or phenytoin. Children who had failed on any other antiepileptic drug were assigned randomly to receive clobazam or carbamazepine. In a subset of patients neuropsychological assessments were carried out at 6 weeks and 12 months after initiation of medication. Intelligence, memory, attention, psychomotor speed, and impulsivity were assessed. RESULTS: There were no differences between the clobazam and standard monotherapy groups on any of the neuropsychological measures obtained at 6 weeks or 12 months. There was no evidence for a deterioration in performance for those children who remained on clobazam for the entire 12-month study period. CONCLUSION: The cognitive and behavioural effects of clobazam appear to be similar to those of standard monotherapy.

Adolescent↗

Vitamin D-regulated gene expression.

The major emphasis of this review is on the molecular events that occur in target tissues when stimulated by 1,25-dihydroxyvitamin D3. The vitamin D receptor is a 55,000-kDa protein whose domains have been described roughly for human and rat. A single receptor appears to carry out all of the known functions of vitamin D and is likely a nucleoprotein. The receptor binds to vitamin D response elements found in the promoter region of responsive genes. An accessory protein is required for the binding of the receptor to these response elements. The accessory protein has a molecular weight of approximately 62,000 kDa but has not been cloned. The response elements are two repeat sequences separated by three bases. A negative response element is known for the parathyroid gene and is a single arm homologous to one arm of the osteopontin response element. Phosphorylation in the ligand binding domain of the receptor follows binding of 1,25-(OH)2D3. The receptor then becomes transcriptively active and interacts with other transcription factors to bring about gene expression. It is unknown, if following phosphorylation, the ligand is released, and final proof that the phosphorylated receptor is the transcriptively active form of the protein is not yet available.

Animals↗

1,25-Dihydroxyvitamin D and not calcium is the major regulator of calbindin-D 9-kDa mRNA levels in vivo.

A possible role of calcium in vivo on intestinal calbindin-D 9-kDa mRNA levels has been studied in rats. In vitamin D-deficient rats, a marked increase in dietary calcium has a small but significant effect on calbindin-D 9-kDa mRNA levels, despite a dramatic increase in serum calcium concentration that clearly resulted from increased intestinal absorption of calcium. On the other hand, vitamin D under all circumstances increased calbindin-D 9-kDa mRNA levels, with the greatest levels found in animals on a low calcium diet where little or no calcium is available for absorption. These results strongly support the idea that 1,25-dihydroxyvitamin D is directly responsible for the induction of calbindin-D 9-kDa.

Animals↗

An estrogen-responsive element mediates the transcriptional regulation of calbindin D-9K gene in rat uterus.

The rat calbindin (molecular mass 9 kDa) gene sequence revealed the presence of an imperfect palindromic estrogen-responsive-like element (ERE) located at position +51 from the transcriptional initiation site. This element has the sequence AGGTCAGGGTGATCT which differs by one nucleotide from the vitellogenin ERE palindromic sequence AGGTCACTGTGACCT. The activity of this element to induce transcription in response to estrogen and the ability to bind estrogen receptor was investigated. This sequence confers estrogen-dependent transcriptional activity when cloned upstream from the tkp-CAT construct in pBLCAT2 plasmid and transfected into T47D cells, similar to the vitellogenin gene ERE activity but to a lesser extent. This element binds to the estrogen receptor in vitro as assessed by gel retardation assay similar to the vitellogenin gene ERE. No such binding was detected when a mutant sequence AGATCACTGTGATCT was used. The specificity of the complex was confirmed using polyclonal antibodies, ER712 raised against the estrogen receptor. Furthermore, competition assays showed that both sequences were able to compete for binding to the estrogen receptor. The in vivo transcriptional regulation of the calbindin D-9K gene by estrogen was also investigated in the rat. Female animals maintained on a vitamin D-sufficient or a vitamin D-deficient diet were ovariectomized, housed for 3 weeks, and then injected with 17 beta-estradiol (0.5 micrograms/kg body weight/day). Slot blot analysis of total RNA showed a marked increased in calbindin D-9K mRNA levels in the uterus but not in the intestine by 26 and 50 h post-injection. These results demonstrate that the calbindin D-9K gene is transcriptionally regulated by estrogen in the uterus mediated by an estrogen-responsive element identified in the gene.

Animals↗

The vitamin D system: 1990.

Many new aspects of vitamin D have made their appearance. New roles for vitamin D in reproduction, parathyroid function, skin proliferation, and differentiation, in myeloid cell differentiation, and as anti-cancer agents will be new areas of investigation. At the basic science level, much effort will be expended to understand how the vitamin D hormone and its receptor bring about gene expression and how these expressed genes bring about cellular functions of the vitamin D system. Similarly, future work will center on the molecular mechanism of regulation of the hydroxylases of the vitamin D endocrine system. All of this is based on the original discovery that vitamin D must be first metabolically altered before function, producing the vitamin D hormone 1 alpha,25-(OH)2D3 in the proximal convoluted tubule cells of the kidney. There is no doubt that the vitamin D area will continue to expand in the next decade as new functions of the vitamin D system are uncovered.

Amino Acid Sequence↗

Structure and nucleotide sequence of the rat intestinal vitamin D-dependent calcium binding protein gene.

The vitamin D-dependent intestinal calcium binding protein (ICaBP, 9 kDa) is under transcriptional regulation by 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3], the hormonal active form of the vitamin. To study the mechanism of gene regulation by 1,25-(OH)2D3, we isolated the rat ICaBP gene by using a cDNA probe. Its nucleotide sequence revealed 3 exons separated by 2 introns within approximately 3 kilobases. The first exon represents only noncoding sequences, while the second and third encode the two calcium binding domains of the protein. The gene contains a 15-base-pair imperfect palindrome in the first intron that shows high homology to the estrogen-responsive element. This sequence may represent the vitamin D-responsive element involved in the regulation of the ICaBP gene. The second intron shows an 84-base-pair-long simple nucleotide repeat that implicates Z-DNA formation. Genomic Southern analysis shows that the rat gene is represented as a single copy.

Amino Acid Sequence↗

Correlation between EEG and auditory perceptual measures in auditory agnosia.

We describe a child who acquired a gradual sustained speech deficit for which no specific etiology was found, and who had an associated epileptogenic abnormality on EEG. Assessment of auditory perceptual skills and receptive language confirmed that gradual parallel improvement occurred with the EEG after therapeutic anticonvulsant blood levels were obtained. Prospective trials of anticonvulsant drugs in conjunction with serial measures of central auditory abilities are necessary to establish their value in the management of the linguistic deficit in children with auditory agnosia.

Agnosia↗

The anterior spinal artery collateral in coarctation of the aorta. A clinical angiographic correlation.

A 10-year-old boy had acute flaccid paraparesis with sensory deficits. Attention was drawn to his hitherto asymptomatic coarctation of the aorta. Aniography defined the extent of the dilated anterior spinal artery, and reversal of the flow pattern. The residual deficits consisted of minimal impairment of long motor and lateral sensory tract functions in a unilateral fashion, suggesting a steal syndrome with transient ischemia to the spinal cord. Recovery preceded surgical correction of the coarctation.

Angiography↗

Enlarged cisternae magnae and posterior fossa cysts simulating Dandy-Walker syndrome on computed tomography.

Computed tomography was performed on 5 children with posterior fossa cystic abnormalities. On an axial tomogram, an enlarged cisterna magna could not be distinguished from a Dandy-Walker variant, nor could an encysted fourth ventricle be distinguished from a subarachnoid cyst. Supplementary air encephalography or sagittal reconstruction of tomograms is necessary to define posterior fossa cysts accurately.

Adolescent↗