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Biomedical subjects

T George

Publications and source records attributed to T George.

At least 55 records · Page 3Linked to original sources

Practical approach to diagnosis of strabismus.

Jampolsky's approach to the diagnosis of strabismus is simple. Certain tests are to be performed in sequence to determine 1) the presence of fusion in the habitual head position under normal viewing conditions and in the primary position at near and distance; 2) the presence and characteristics of fusion vergences and 3) the deviations that exist at distance and near. These are established by the cover tests and the prism cover test. 4) Incomitance of the strabismus, A-V phenomena and mechanical weaknesses and restrictions are assessed by observations of eye movements and the forceps tests. Finally, 5) inferences about the state of the sensory system are made based on the history, vision and clinical examination. Additional tests performed on indication are the 4 diopter prism test, the prism adaptation test and the forceps muscle tests. This approach allows an accurate and reproducible examination to be performed in an objective manner making it possible to compare clinical findings over time and allow a rational plan of management to be evolved. Errors in examination arise from poor control of three factors, accommodation, fixation and fusion vergence. These can be controlled by careful attention to the test conditions. This system of diagnosis is simple to follow and understand, economic on time and altogether less of a strain to examiner (and patient) than the traditional system.

Child↗

Basolateral membrane Na+/H+ exchange enhances HCO3- absorption in rat medullary thick ascending limb: evidence for functional coupling between basolateral and apical membrane Na+/H+ exchangers.

The role of basolateral membrane Na+/H+ exchange in transepithelial HCO3- absorption (JHCO3) was examined in the isolated, perfused medullary thick ascending limb (MTAL) of the rat. In Na(+)-free solutions, addition of Na+ to the bath resulted in a rapid, amiloride-sensitive increase in intracellular pH. In MTALs perfused and bathed with solutions containing 146 mM Na+ and 25 mM HCO3-, bath addition of amiloride (1 mM) or 5-(N-ethyl-N-isopropyl) amiloride (EIPA, 50 microM) reversibly inhibited JHCO3 by 50%. Evidence that the inhibition of JHCO3 by bath amiloride was the result of inhibition of Na+/H+ exchange included the following: (i) the IC50 for amiloride was 5-10 microM, (ii) EIPA was a 50-fold more potent inhibitor than amiloride, (iii) the inhibition by bath amiloride was Na+ dependent, and (iv) significant inhibition was observed with EIPA as low as 0.1 microM. Fifty micromolar amiloride or 1 microM EIPA inhibited JHCO3 by 35% when added to the bath but had no effect when added to the tubule lumen, indicating that addition of amiloride to the bath did not directly inhibit apical membrane Na+/H+ exchange. In experiments in which apical Na+/H+ exchange was assessed from the initial rate of cell acidification following luminal EIPA addition, bath EIPA secondarily inhibited apical Na+/H+ exchange activity by 46%. These results demonstrate basolateral membrane Na+/H+ exchange enhances transepithelial HCO3- absorption in the MTAL. This effect appears to be the result of cross-talk in which an increase in basolateral membrane Na+/H+ exchange activity secondarily increases apical membrane Na+/H+ exchange activity.

Absorption↗

Prostaglandin E2 regulation of ion transport is absent in medullary thick ascending limbs from SHR.

Regulation of HCO3- and Cl- absorption by arginine vasopressin (AVP) and prostaglandin E2 (PGE2) was examined in isolated, perfused medullary thick ascending limbs (MTAL) from 4- to 7-wk-old spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. AVP inhibited HCO3- absorption by 50% at 10(-10) M and by 25% at 2 x 10(-12) M in MTAL from both WKY and SHR. Cholera toxin (10(-9) M) or forskolin (10(-6) M) in the bath also inhibited HCO3- absorption by 50% in the SHR. In MTAL from WKY, PGE2 (10(-6) M in the bath) increased HCO3- absorption from 7.1 +/- 0.4 to 12.0 +/- 0.4 pmol.min-1.mm-1 (P < 0.005) and decreased Cl- absorption from 65 +/- 7 to 47 +/- 6 pmol.min-1.mm-1 (P < 0.001) in the presence of 10(-10) M AVP. Under the same conditions, PGE2 had no effect on HCO3- or Cl- absorption in MTAL from SHR. PGE2 also reversed submaximal inhibition of HCO3- absorption by 2 x 10(-12) M AVP in WKY but not in SHR. With 10(-10) M AVP in the bath, phorbol 12-myristate 13-acetate (10(-6) M in the bath) increased HCO3- absorption from 6.6 +/- 0.5 to 12.3 +/- 0.4 pmol.min-1.mm-1 in MTAL from WKY and from 7.6 +/- 0.7 to 12.6 +/- 1.2 pmol.min-1.mm-1 in MTAL from SHR (P < 0.005). These results demonstrate that 1) the effects of PGE2 to stimulate HCO3- absorption and inhibit Cl- absorption in the presence of AVP are absent in MTAL from SHR, 2) the defect may involve an inability of PGE2 to stimulate protein kinase C, and 3) regulation of HCO3- absorption by AVP via adenosine 3',5'-cyclic monophosphate is similar in MTAL from WKY and SHR. The lack of PGE2 inhibition of NaCl absorption in the MTAL may contribute to renal salt retention during the development of hypertension in the SHR.

Absorption↗

A preliminary comparison of reinforcer assessment methods for children with attention deficit hyperactivity disorder.

We evaluated the relative treatment utility of a verbal forced-choice questionnaire, child nomination, and direct observation for identifying the most potent reinforcers for children with attention deficit hyperactivity disorder. Results demonstrated that all three methods were more likely to disagree than to agree, that a forced-choice format may enhance verbal reinforcer assessment, and that further development and evaluation of verbal reinforcer-assessment methods are needed.

Attention Deficit Disorder with Hyperactivity↗

Intracellular dynamics of c-myc mRNA traffic in single cells in situ.

Processing and intracellular transport of RNA transcripts are essential for gene expression. Translational regulation of gene expression may occur by several mechanisms, including control of transcript movement from sites of synthesis to site(s) of translation. We describe temporal analysis of the intracellular translocation of c-myc transcripts from the site of synthesis in the nucleus to sites of translation in the cytoplasm. Fluorescence in situ hybridization (FISH) and quantitative fluorescence microscopy were used to measure intracellular traffic of c-myc transcripts in individual recombinant cells following activation of c-myc sequences linked to a heat shock promoter. C-myc nuclear transcripts are visible in the nucleus within minutes of heat exposure. Transcripts remain in the nucleus for at least 4 hr after gene activation. Transport of c-myc transcripts to the cytoplasm begins approximately 1 hr after cells are returned to 37 degrees C. These data demonstrate the feasibility of measuring intracellular transcript transport following gene activation and provide a description of the kinetics of intracellular traffic of inducible c-myc transcripts in heated cells in situ.

Animals↗

Methotrexate content in squamous cell carcinoma of the head and neck after low-dose methotrexate.

Eleven patients with squamous carcinoma of the head and neck who were scheduled for surgical resection or endoscopic biopsy of tumor received 15 mg/m2 of methotrexate (MTX). Samples of tumor, normal mucosa, and plasma were obtained at surgery or endoscopy, 18-24 hours after the last MTX dose. Tissue content and plasma concentration of MTX and folate were measured using sequential radioligand-binding assays. Median MTX content was 50.0 pmol/g wet weight in tumor, 19.0 in normal mucosa, and < 0.5 nM (pmol/ml) in plasma. Since dihydrofolate reductase (DHFR) content of human tumors has previously been shown to be less than 5 pmol enzyme/g wet weight, tumor MTX content exceeded expected DHFR content in all but one patient. These data support the concept that low doses of MTX saturate tumor DHFR and that, in this regard, dose escalation may have limited value.

Administration, Oral↗

Serotonin, violent behavior and alcohol.

At the NIAAA intramural research program, in collaboration with investigators at the Department of Psychiatry, University of Helsinki, we have mounted an extensive research program on early onset male alcoholism. A central serotonergic deficit is common among these patients. This finding has led to behavioral, biochemical, physiological and molecular genetic studies on the serotonin system in early onset, antisocial and violent male alcoholics and in appropriate control populations. The results of the studies completed by the fall of 1993 are summarized in this communication.

Age Factors↗

The Australian multicentre double-blind comparative study of remoxipride and thioridazine in schizophrenia.

A double-blind, randomized study of parallel group design comparing remoxipride and thioridazine (dose range 150-600 mg/day of either drug) was undertaken at 11 Australian centres. A total of 144 patients (remoxipride = 73, thioridazine = 71) with DSM-III-R schizophrenia or schizophreniform disorder commenced the study, and 89 patients (remoxipride = 45, thioridazine = 44) completed the 6 weeks of the trial. The mean daily doses at last rating were 404 mg (remoxipride) and 378 mg (thioridazine). Initial Brief Psychiatric Rating Scale scores decreased by a mean 8.7 points in both remoxipride and thioridazine groups. Equivalent treatment responses were also confirmed by Clinical Global Impression. During the study, sedatives or hypnotics were needed by 68% of the remoxipride patients and 51% of the thioridazine patients. Thioridazine was associated with more postural hypotension, drowsiness, increased sleep, headache, dizziness on rising, dry mouth, sexual dysfunction and weight gain, while remoxipride patients reported more insomnia. There were no differences between remoxipride and thioridazine on dystonia, hypokinesia, dyskinesia, rigidity and akathisia. The results indicate that remoxipride has similar antipsychotic efficacy to thioridazine but causes fewer side effects.

Adolescent↗

Physical deletion of the p53 gene in bladder cancer. Detection by fluorescence in situ hybridization.

To understand better the role of physical p53 deletion in bladder cancer, 106 formalin-fixed and 45 unfixed bladder tumors were examined using fluorescence in situ hybridization. Probes for centromere 17 and the p53 locus were hybridized simultaneously to interphase tumor cells to analyze p53 and chromosome 17 copy number on a cell by cell basis. 17p deletion was found in four of 43 pTa tumors, 18 of 43 pT1 tumors and 29 of 58 pT2-4 tumors (P = 0.0001). 17p deletion was also highly correlated with grade (P = 0.0001) and with p53 immunostaining (P = 0.0005). Chromosome 17 polysomy was associated with stage, grade, 17p deletions, and p53 immunostaining (P = 0.0001). The strong difference in centromere 17 copy number and 17p deletions between pTa and pT1 tumors supports a relevant biological distinction between pTa and pT1 tumors.

Alleles↗

Clinical and angiographic features of patients with an occluded versus a patent infarct vessel after intravenous streptokinase for acute myocardial infarction.

Despite early treatment with thrombolytic agents for acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. To study the various factors related to achieving patency in the infarct vessel, 201 patients who received streptokinase within six hours of symptoms were studied. All patients underwent cardiac catheterization during the same hospitalization at 5.40 +/- 3.26 days after admission. Forty-five (22.4%) patients were found to have an occluded infarct artery (group 1) and 156 (77.6%) had a patent infarct vessel (group 2). There was no difference in the time from onset of symptoms to receiving streptokinase between the two groups. The two groups were similar to each other with regard to age, gender, history of myocardial infarction or angina, and major risk factors for coronary disease. Coagulation parameters before and after streptokinase therapy, reflecting the lytic state, were similar in both groups. The left ventricular end diastolic pressure was significantly higher and the left ventricular ejection fraction was significantly lower in group 1 than in group 2. These observations suggest that despite early initiation of thrombolytic therapy in patients with acute myocardial infarction, a significant portion of patients fail to achieve a patent infarct artery. This failure cannot be explained by the observed clinical parameters or the lytic state after streptokinase.

Adult↗

Rate of recovery of D1 and D2 dopaminergic receptors in young vs. adult rat striatal tissue following alkylation with ethoxycarbonyl-ethoxy-dihydroquinoline (EEDQ).

The rate of recovery of D1 and D2 receptor binding sites in rat striatal tissue labeled with [3H]SCH-23390 or [3H]YM-09151-2 was followed daily after irreversible blockade of these receptors with the alkylating agent ethoxycarbonyl-ethoxy-dihydroquinoline (EEDQ). These rates were significantly higher in young post-weaning rats than in young adults (14% vs. 7% per day). The findings suggest that rates of synthesis of new D1 and D2 receptor proteins may be increased during a phase of neurodevelopment in the first postnatal month when the accumulation of both receptor types, especially of D1 receptors, is about maximal.

Alkylating Agents↗

Clinical and angiographic features of patients from the Indian subcontinent treated with intravenous streptokinase for acute myocardial infarction: experience in Qatar.

The authors reviewed their experience with 245 patients who were treated with intravenous streptokinase for acute myocardial infarction at an average time of less than three hours from the onset of chest pain. Of these, 148 patients were from the Indian subcontinent (Group 1) and the remaining (Group 2) were predominantly from an Arabic background. Group 1 patients were younger and had lower serum cholesterol and fibrinogen levels than the Group 2 patients. Group 1 patients had a lower incidence of previous myocardial infarction (p = 0.0006) and antecedent angina pectoris (p = 0.017). A patency rate of 77.5% was seen in all patients studied at 5.37 +/- 2.96 days after admission and was similar in both the groups. Group 1 patients had a lesser extent of coronary artery disease (p = 0.01) manifested as a higher incidence of single-vessel disease (p = 0.06) and a lower incidence (p = 0.06) of three-vessel obstruction. The overall mortality for the initial hospitalization was 2.18% and showed no difference between the two groups. Patients from the Indian subcontinent presenting with acute myocardial infarction appear to be a unique population in that they are younger, have a somewhat lower cardiac risk profile, and have less extensive coronary artery disease than their Arabic counterparts.

Adult↗

An Australian multicentre study of moclobemide versus amitriptyline in the treatment of depression.

This paper reports the results of a multicentre study of the new monoamine oxidase inhibitor, moclobemide, in the treatment of major depression. Moclobemide is a specific monoamine oxidase-A inhibitor which does not bind irreversibly to the enzyme, unlike the currently available MAOIs. Recent studies would suggest that in subjects taking moclobemide blood pressure elevation caused by tyramine is significantly less than that induced by the irreversible MAOIs, particularly when tyramine is administered in an oral form. Forty-eight patients with major depression were randomly allocated to treatment with either moclobemide or amitriptyline for 4 weeks in a double-blind comparison. There were no statistically significant differences between the two groups on measures of efficacy. Patients taking amitriptyline reported a greater number of side-effects and more patients in the amitriptyline group dropped out because of these. There were no reports of interactions with tyramine-containing foods.

Adult↗

Nitroimidazoles, Part XXIII--activity of satranidazole series against anaerobic infections.

A large number of nitroimidazoles have been examined for in vitro activity against three anaerobes - Bacteroides fragilis (Bf), a strain of Bf resistant to metronidazole (16a) and Clostridium perfringens and many found to be active. Among these may be mentioned 1-methyl-5-nitroimidazoles carrying N - bound hetetocycles at position 2, such as satranidazole 1a, 1b, 1c, 1k, 1n and 1v which are at least twice as active as metronidazole (16a), ornidazole (16b) and tinidazole (16c). Even more active are 5-nitroimidazolyl benzimidazole 5d, -thiazolidinone 6b and thiadiazolidine dioxide 8a. Many other types of compounds derived from 1-methyl-2-amino-5-nitroimidazole are feebly active. Among 5-nitroimidazoles with a carbon substituent at position 2, 16a, 16b and 16c are equiactive while dimetridazole 14f is more active than 16a against Bf. Some 2-vinyl derivatives are very potent, with 18f and 18i being outstanding. Activity better than that of metronidazole is seen for nitroimidazooxazepines, e.g. 29d. 5-Nitroimidazoles are more active against anaerobes than 4-nitro isomers. Antianaerobic and antiamoebic activities generally run parallel in these classes of compounds. The study has led to the elaboration of the antianaerobic profile of satranidazole 1a.

Amebicides↗