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Biomedical subjects

A Roth

Publications and source records attributed to A Roth.

At least 55 records · Page 3Linked to original sources

Influence of ochratoxin B on the ochratoxin A inhibition of phenylalanyl-tRNA formation in vitro and protein synthesis in hepatoma tissue culture cells.

Ochratoxin B (OTB), the dechloro-analogue of ochratoxin A (OTA), was studied separately and in combination with OTA on the aminoacylation of phenylalanine tRNA (tRNAPhe) catalysed by mice liver phenylalanyl-tRNA synthetase. OTB was neither a significant inhibitor of the reaction nor an antagonist of OTA. OTB was also assayed for its possible antagonistic effect on the in vivo protein synthesis inhibition caused by OTA in hepatoma tissue culture cells. No prevention of OTA inhibition could be found for OTB. It rather showed a slight additional inhibitory activity when mixed (100-180 microM) with low concentrations of OTA (40-60 microM). In conclusion, these results are not in favor of an antagonistic effect of OTB with respect to OTA action, at least on the level of cellular protein synthesis.

Animals

(3-Amino-2-oxoalkyl)phosphonic acids and their analogues as novel inhibitors of D-alanine:D-alanine ligase.

The dipeptide D-alanyl-D-alanine is an essential precursor of bacterial peptidoglycan; thus, blocking its formation is a possible target for the design of novel antibacterial agents. The synthesis of this dipeptide by bacterial D-alanine:D-alanine ligase requires ATP. In analogy with glutamine synthetase, we hypothesized a mechanism for this enzyme involving the intermediacy of D-alanyl phosphate. Several (3-amino-2-oxoalkyl)phosphonic acids and their analogues have been synthesized as possible inhibitory mimics of this proposed intermediate. The most active of them, (3(R)-amino-2-oxobutyl)phosphonic acid (8a) and the corresponding aza analogue (22), were effective ligase inhibitors although they had no significant antibacterial activity. The ligase inhibition of these compounds is consistent with an acyl phosphate displacement step in the mechanism of DAla-DAla ligase.

Anti-Bacterial Agents

[Examination of central vision. Visual acuity, contrast sensitivity, color vision].

In the neurophysiological organization of the visual system, form, color, movement, and depth perception are processed separately. Therefore, sensorial examination methods should test each of these basic functions separately, since they may be affected individually or to different extents by pathologic processes. For diagnosis the limit of visual acuity, i.e., the capacity for discrimination must be searched for, using Paliaga's "limits method". Visual acuity can also be tested in infants by the preferential looking method. Contrast sensitivity is tested using sinusoidal grid patterns of varying contrast and spatial frequency. In routine practice, however, this is usually achieved more easily with acuity cards on which contrast is reduced in several stages. The "two-equation method" is a colorimetric test combining two metameric matches, red + green = yellow, and blue + green = cyan, for testing color vision. The test requires an anomaloscope or anomalometer with four light channels. With this method it is possible to test the "red", "green", and "blue" cones and the "red-green" and "blue-yellow" opponents. The test provides a qualitative and quantitative evaluation of color vision disorders. If no colorimeter is available, classic printed test can be used. However, they might never achieve the same qualitative and quantitative precision.

Color Perception Tests

[Blood vessel preservation in squint surgery].

The vascularization of the anterior section of the bulb depends partially on the anterior ciliary vessels. Circulatory disorders of the anterior uvea have been detected following conventional squint surgery in which several of these vessels were severed, even though there were no clinically detectable symptoms. It therefore makes good sense to spare the muscular and anterior ciliary vessels as far as possible, in order to preserve the muscles themselves and the anterior section of the bulb (a) by careful surgery and (b) by adopting surgical procedures in which the vessels are not sacrificed. In the final analysis, complete preservation of the vessels can only be achieved using the operating microscope.

Anterior Eye Segment

Leber's congenital amaurosis associated with high hyperopia in four sisters.

The authors describe a family with five daughters, of whom four are affected with Leber's congenital amaurosis and high hyperopia ranging between +5.5 and +9 diopters. In addition, the second daughter is a little short for her age, and shows a slight dyscrania with prominent frontal and occipital bones, hypoplasia of the nasal bone, and deep and narrow orbits leading to marked enophthalmos. The symptoms are typical of Leber's amaurosis. All children have nystagmus, night blindness, weak or absent pupillary reflexes. Visual fields are constricted or not measurable. The electroretinogram is extinguished, and hyperopia of the axial type was confirmed by ultrasound. Fundus findings are variable with small, pale and somewhat protruding papillae (pseudo-papillitis), narrow retinal vessels, diffuse fundus pigmentation of pepper-and-salt type and unusual yellow coloration of the macular region (diffuse atrophy). The inheritance of Leber's congenital amaurosis is autosomal recessive. The combined occurrence of amaurosis and hyperopia in four children in one family, while the fifth is unaffected and has no refractive error, furnishes a further evidence for the existence of a particular amaurosis-hyperopia subtype of Leber's disease.

Blindness

[Pre-equatorial contusion syndrome. Analysis apropos of 59 cases].

The term "pre-equatorial syndrome" covers post-traumatic involvement of the anterior segment and of the pre-equatorial retina, due to a frontal distension mechanism. In a retrospective study, we studied 582 cases of ocular contusions from 1973 to 1986 in patients who required a brief hospitalisation in our clinic because of the severity of the initial injury. The aim of the study was to assess the occurrence of this syndrome, its clinical features and evolution. 59 complete pre-equatorial syndromes were found in this sample (10.2% of all the ocular contusions). The follow up ranged from one to 168 months. Games and sports injuries in children and work injuries in young men were most commonly found causes (2/3 of the cases). Hyphema and angle recession were the most frequently observed lesions (69%). All hyphemas disappeared spontaneously without surgical drainage. Subluxation of the lens was present in 10.6% and late post traumatic cataract occurred in four cases; all eyes were operated on by intracapsular extraction, three of them in the first year following the traumatism and the last twelve years latter. Intraocular pressure was high in 15.3% (but was easily controlled) and was very low in 5.1%. Retinal edema and haemorrhages were the most common involvement of the peripheral retina. Retinal dialysis was noticed in 13.6% especially in the upper nasal area: buckling surgery was performed in these cases with good results. Anterior and peripheral retinal damages was situated on the same meridian in 80% of the cases, five eyes showed a 180 degrees opposite setting while there was no obvious alignment in 15 of the cases. This syndrome did not impair final visual function alone, whereas severe associated ocular contusions of the posterior pole gave a very low visual outcome in 16 cases. This retrospective review emphasizes the main characteristics of this syndrome. Accurate examination of the irido-corneal angle and peripheral retina is of paramount importance in every ocular contusion.

Adolescent

Cytostatic treatment of metastatic cervical carcinoma.

The activity of cytostatics in cervical cancer has not as yet been sufficiently investigated. This is especially true for combined cytostatic treatments. The only two cytostatics that have been adequately examined in clinical trials in a larger number of patients are 5-fluorouracil and cis-dichlorodiamineplatinum. The paper presents the results of treatment with single cytostatic agents and the combinations of different cytostatics, emphasizing the role of combined treatment using irradiation and cytostatics. It also describes the preliminary results of a Phase II trial going on at the Central Institute for Tumors in Zagreb, using a combination of cis-DDP, 5-fluorouracil and vincristine. So far the results of 11 out of 14 patients included in the trial have been evaluated. Objective remission (CR + PR) was achieved in 4 patients (33%). Toxic side-effects were mild and tolerable for the patients. In conclusion, the reasons are given why chemotherapy has not as yet gained a more important place in the treatment of advanced forms of cervical cancer.

Antineoplastic Agents

[Recent trends and developments in the clinical study of color vision--the 2-comparison method].

Modern anomaloscopes with four independent light channels (i.e., the Besançon Anomalometer which was presented in 1980 at the DOG) allow accurate examinations of color vision. In our routine clinical examination, we use two metameric equations: the red-green Rayleigh equation and the blue-green Moreland equation. This two-equation method permits the diagnosis of congenital and acquired color vision defects in a precise quantitative way. In both equations the goal of the examination is to measure the absolute matching range. The diagnosis is abnormal color vision if the absolute matching range is shifted and/or enlarged in one or both of the two metameric equations. A computer-controlled clinical examination of color vision, which will make the procedure simpler and shorter for the patient, is presently being developed.

Adolescent

Comparison of nalbuphine hydrochloride versus morphine sulfate for acute myocardial infarction with elevated pulmonary artery wedge pressure.

The hemodynamic and respiratory effects of intravenous nalbuphine hydrochloride and morphine sulfate were compared in a randomized fashion in 20 patients (age 65 +/- 11 years) with acute myocardial infarction and elevated pulmonary artery wedge pressure. Titration of the nalbuphine dose to lower pulmonary artery wedge pressure by greater than or equal to 25% resulted in a decrease of this parameter from 22 +/- 3 to 15 +/- 4 mm Hg, and was associated with a reduction in heart rate from 106 +/- 20 to 96 +/- 19 beats/min (p less than 0.05) and decreases in mean blood pressure (78 +/- 8 to 70 +/- 12 mm Hg, p less than 0.05) and mean pulmonary artery pressure (31 +/- 4 to 22 +/- 5 mm Hg, p less than 0.05), without any remarkable change seen in cardiac index (2.21 +/- 0.43 to 2.22 +/- 0.50 liter/min/m2, difference not significant), stroke volume index (22 +/- 7 to 23 +/- 4 ml/m2, difference not significant), stroke work index (17 +/- 7 to 18 +/- 7 g.m/m2), or systemic and pulmonary vascular resistances (1,675 +/- 333 to 1,513 +/- 508 and 191 +/- 78 to 170 +/- 109 dynes.s.cm-5 respectively, all differences not significant). Nalbuphine also significantly reduced respiratory rate (32 +/- 8 to 26 +/- 8 resp/min, p less than 0.05) and pH (7.45 +/- 0.04 to 7.41 +/- 0.03, p less than 0.05) and increased arterial PCO2 (32 +/- 6 to 35 +/- 6 mm Hg, p less than 0.05) without any major change in arterial PO2 (63 +/- 13 to 66 +/- 17 mm Hg, difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

POEMS syndrome presenting as systemic sclerosis. Clinical and pathologic study of a case with microangiopathic glomerular lesions.

A rare form of plasma cell dyscrasia characterized by the various association of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes has been termed POEMS syndrome. The pathogenesis of the multisystemic features of this syndrome remains unclear. Herein is reported a case of POEMS syndrome with striking clinical similarities with scleroderma, and microangiopathic glomerular lesions, as well as diffuse perivascular non-amyloid deposits, which could explain certain features of the syndrome, including peripheral nerve demyelination. It is proposed that a pathogenic role might be played by a non-immunoglobulin vasculotoxic component.

Adult

Evidence for an enterohepatic circulation of ochratoxin A in mice.

The distribution and elimination of [3H]ochratoxin A (OTA) from stomach content and tissue, intestine content and tissue, liver, bile, serum and urine of Swiss male mice which had received a single low dose of OTA by intubation was followed as a function of time. The profiles of radioactivity do not show a smooth decline after the absorption period, but an oscillating pattern with rapid declines followed by increases which favour the assumption of an enterohepatic circulation. Between 28% and 68% of conjugated OTA together with OTA cleavage products were found in bile giving evidence for biliary excretion of OTA and its metabolites in mice. When given i.m. to mice [3H]OTA is already found after 30 min in bile and intestine contents and its elimination patterns show several peaks confirming the biliary excretion and the enterohepatic circulation. Cholestyramine, which is known to prevent the enterohepatic circulation of drugs and toxins, changes the profile of elimination of OTA which no longer presents the cyclic pattern. This result is also in favour of an enterohepatic circulation of OTA. When phenylalanine is given together with OTA by oral gavage the toxicokinetics of the mycotoxin change completely in the different body fluids, in stomach and intestine content and tissues. Phenylalanine seems to facilitate the gastric absorption of OTA and the gastro-intestinal transit. It increases also its early excretion into urine and bile. However, its elimination pattern no longer shows the oscillating pattern. Thus phenylalanine seems to inhibit the intestinal reabsorption of OTA conjugates.

Animals

Resistance to isosorbide dinitrate in patients with severe chronic heart failure: incidence and attempt at hemodynamic prediction.

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult