Biomedical subjects

A Roth

Publications and source records attributed to A Roth.

At least 163 records · Page 9Linked to original sources

PubMed1992

The complex for replication initiation of Escherichia coli.

We probed the complex between oriC and DnaA protein using two types of mutants in oriC. Base changes in the DnaA binding sites, DnaA boxes, had little effect on origin function. Mutations which change the distance between DnaA boxes R3 and R4, on the other hand, inactivated oriC unless the mutation deleted or inserted one complete helical turn. Origins with other 10 base pair insertions in the interval between DnaA boxes R2 and R3 were functional, but not insertions in the R1-R2 interval. FIS protein binds to a bipartite site in oriC between DnaA boxes R2 and R3. A model for the oriC/DnaA complex based on these results suggests an array of DnaA monomers with a 34 A spacing upon which oriC is arranged.

Bacterial Proteins↗

PubMed1992

Assessment of flap perfusion in a porcine model with a heated laser Doppler probe.

Skin and musculocutaneous flaps in a pig model were studied for their response to heating of the laser Doppler probe, both in the perfused state and in conditions of vascular occlusion. Even though heating the probe resulted in an elevation of perfusion of the flaps with no occlusions, it also increased the apparent perfusion of flaps that were occluded. The ability of flows to a augment with heating, therefore, could not be perfectly correlated with impeded vascular flow. The addition of a heated perfusion reading for assessment of vascular occlusion did not improve the accuracy of the laser Doppler for monitoring of capillary-bed perfusion to detect vascular occlusion.

Animals↗

PubMed1992

[Strabismus induced by peripheral vestibular lesions].

Little attention has been paid in the ophthalmological literature to strabismus resulting from lesions located in the peripheral vestibular system. However, this phenomenon is commonly encountered in clinical practice. As a rule, this kind of strabismus shows a prominent vertical component. It is generally combined with a change in perception of verticality, conjugate cyclotorsion of the eyes, and head tilt. This association is known as "ocular tilt reaction". It occurs in a number of clinical settings which are believed to be related with alteration in the otolithical and/or vertical semicircular canal pathways. Strabismus occurring as a feature of ocular tilt reaction might result from different mechanisms according to the location of the lesion, e.g. in the utricles, in the midbrain tegmentum, and in the dorso-lateral medulla oblongata. This phenomenon is illustrated here with the report of a patient suffering from Ménière disease, who underwent selective vestibular neurectomy. Methods of ophthalmological evaluation in such cases is described.

Aged↗

PubMed1992

SOS induction in Escherichia coli by infection with mutant filamentous phage that are defective in initiation of complementary-strand DNA synthesis.

We report that the SOS response is induced in Escherichia coli by infection with mutant filamentous phage that are defective in initiation of the complementary (minus)-strand synthesis. One such mutant, R377, which lacks the entire region of the minus-strand origin, failed to synthesize any detectable amount of primer RNA for minus-strand synthesis. In addition, the rate of conversion of parental single-stranded DNA of the mutant to the double-stranded replicative form in infected cells was extremely slow. Upon infection, R377 induced the SOS response in the cell, whereas the wild-type phage did not. The SOS induction was monitored by (i) induction of beta-galactosidase in a strain carrying a dinD::lacZ fusion and (ii) increased levels of RecA protein. In addition, cells infected with R377 formed filaments. Another deletion mutant of the minus-strand origin, M13 delta E101 (M. H. Kim, J. C. Hines, and D. S. Ray, Proc. Natl. Acad. Sci. USA 78:6784-6788, 1981), also induced the SOS response in E. coli. M13Gori101 (D. S. Ray, J. C. Hines, M. H. Kim, R. Imber, and N. Nomura, Gene 18:231-238, 1982), which is a derivative of M13 delta E101 carrying the primase-dependent minus-strand origin of phage G4, did not induce the SOS response. These observations indicate that single-stranded DNA by itself induces the SOS response in vivo.

Coliphages↗

PubMed1991

The FIS protein binds and bends the origin of chromosomal DNA replication, oriC, of Escherichia coli.

The FIS protein (factor for inversion stimulation) is known to stimulate site-specific recombination processes, such as the inversion of the G segment of bacteriophage Mu, by binding to specific enhancer sequences. It has also been shown to activate transcription from rRNA promoters both in vitro and in vivo. We have identified a specific binding site for FIS in the center of the origin of chromosomal DNA replication, oriC. The DNA bends upon FIS binding. Occupation of the FIS site and binding of DnaA, the initiator protein, to its adjacent binding site (R3) are mutually exclusive. A fis mutant strain can not be efficiently transformed with plasmids which carry and replicate from oriC, suggesting that FIS is required for minichromosome replication.

Bacterial Proteins↗

PubMed1991

Prognostic importance of delayed Q-wave evolution 3 to 24 hours after initiation of thrombolytic therapy for acute myocardial infarction.

The timing of Q-wave evolution and its prognostic significance was studied in 201 patients who received thrombolytic therapy for a first acute myocardial infarction (AMI). One hundred forty-one patients (70%) had evidence of a Q-wave AMI within 3 hours of the initiation of thrombolytic therapy, 31 (16%) developed Q waves after 3 hours but before hospital discharge, and 29 (14%) were discharged with a non-Q-wave AMI. Laboratory indicators of myocardial damage and in-hospital morbidity and mortality were greater among patients with Q-wave AMIs than with non-Q-wave AMIs. When these indexes were examined with respect to the timing of Q-wave evolution, the prognosis of patients with delayed Q-wave development was similar to that of patients with non-Q-wave AMIs. Thus, compared to patients with early (less than or equal to 3 hours) Q-wave evolution, patients with delayed Q-wave evolution or with a non-Q-wave AMI had a smaller creatine kinase peak (mean 661 to 1,081 vs 1,251 to 1,541 IU; p = 0.005), better preservation of left ventricular function as measured by radionuclide ventriculography before discharge (mean +/- standard deviation 54 +/- 11% vs 47 +/- 13%; p less than 0.01), and a lower incidence of congestive heart failure at discharge (3 vs 15%; p = 0.02). In-hospital mortality was lower among patients with delayed Q-wave evolution or with a non-Q-wave AMI (5 of 141 vs 0 of 60; difference not significant).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1991

Incidence of left ventricular thrombi formation after thrombolytic therapy with recombinant tissue plasminogen activator, heparin, and aspirin in patients with acute myocardial infarction.

To evaluate the prevalence of left ventricular thrombi after thrombolytic therapy, 144 consecutive patients with acute myocardial infarction (AMI) were prospectively studied with two-dimensional echocardiography 1 and 8 days after admission. Patients were treated 2.1 +/- 0.8 hours after the onset of symptoms. Thrombolytic protocol included 120 mg of recombinant tissue plasminogen activator (rt-PA), 5000 IU of heparin, followed by a continuous infusion of 25,000 IU/24 hours for at least 5 days, and 250 mg of aspirin a day. Seventy-six patients had AMI of the anterior wall; of these, seven (9.2%) developed left ventricular thrombi. The remaining 68 patients had infarctions of the inferior wall; of these, two (2.9%) developed left ventricular thrombi. Since anterior wall infarction not treated with thrombolytic therapy is associated with a 25% to 40% rate of left ventricular thrombi, we conclude that early thrombolytic therapy with rt-PA, heparin, and aspirin reduces the formation of left ventricular thrombus in AMI of the anterior wall. Apical left ventricular thrombi developed more frequently in patients with previous infarctions compared with those without (4 of 17 versus 4 of 127, p = 0.01). During the 12-month follow-up period, no patient in the study had manifestations of peripheral emboli.

Aged↗

PubMed1991

Iris modifications following extracapsular cataract extraction with posterior chamber lens implantation.

We prospectively examined 94 eyes of 93 consecutive patients who had planned extracapsular cataract extraction or phacoemulsification with posterior chamber intraocular lens (IOL) implantation. The observed postoperative iris biomicroscopic modifications are described and classified. Iris synechial formation was more frequently observed in eyes with pseudoexfoliation syndrome, when an irregular anterior capsulotomy was performed, when the IOL was other than in the bag, and in cases of postoperative fibrinous exudation. Synechias occurred more frequently in intraoperatively injured iris areas. Pupil capture was the only postoperative iris modification that was observed to affect visual acuity. The maximal postoperative dilation was greater and the pupillary photic reaction was significantly less modified postoperatively (P = .0058) when the IOL was fixated within the capsular bag.

Adult↗

PubMed1991

Detection of antibody formation in mice, rats and rabbits immunized with different Pneumocystis carinii antigens.

Antibody formation to P. carinii of human origin was determined by an indirect immunofluorescence antibody assay (IFA) after immunization of mice, rats and rabbits with pronase-treated whole cysts and soluble antigen in order to obtain more detailed data about the production of polyclonal antibodies. Antibody titre profiles over defined periods have shown that noticeable differences between the immunoreactions to whole cysts and soluble antigen occur. The soluble antigen produced an earlier and stronger titre rise (peak titres of up to 1:2560 2 to 4 weeks after immunization). In contrast to this, whole cysts produced equally high, although retarded, antibody titre peaks only in normal mice and rats and when the dose had been doubled. Nu/nu mice failed to demonstrate any reaction to these P. carinii immunogens. Cross-reactivity of the antibodies with P. carinii antigen from rat lungs was demonstrated. Possible reasons for different immunoreactions to these antigens, the importance of proteolytic digestion for the results obtained and the potential applicability of these polyclonal antibodies to a histochemical demonstration of the parasite are discussed.

Animals↗

PubMed1991

In vitro toxicity testing for antibacterials against human keratinocytes.

The use of cultured human keratinocytes in an in vitro comparison of topical antibacterial toxicity for epithelial cells was examined. The complement of three assessments allows testing of epithelial migration, growth, and survival. The three assessments included (1) flow cytometry for determination of cell survival, (2) a comparison of confluent cell culture growth after antibacterial exposures, and (3) an evaluation of cell migration using a technique of dermal explants to study radial migration. A comparative ranking of the toxicities of the various topical antibacterials was determined with the three assessments. This has confirmed anecdotal reports that many of the topical antibacterials are cell-toxic and may inhibit wound healing. This information can be directly extrapolated to the clinical setting, unlike many of the animal data for wound healing that currently exist.

Anti-Bacterial Agents↗

PubMed1991

Antiemetic efficacy of droperidol or metoclopramide combined with dexamethasone and diphenhydramine. Randomized open parallel study.

We have performed an open parallel randomized study of the efficacy of two antiemetic drug combinations. Dexamethasone (10 mg i.v.), diphenhydramine (25 mg i.v.), and metoclopramide (3 mg/kg, 15 min i.v.) or droperidol (1.25 mg slow push) were given 30 min before and 90 min after start of chemotherapy. Thirty-six patients treated with cisplatin-based regimens (30 mg/m2 x 3 days or 60 mg/m2 day 1 only), have been observed for 48 h after their last chemotherapy. Twelve (67%, confidence interval 95%: 41-87%) experienced no vomiting while on metoclopramide and 11 (61%, confidence interval 36-83%) were protected by droperidol. Further patient accrual was stopped because of side effects in one study arm. Moderate sedation (difficulty to keep up a conversation) was observed in 48% of those on metoclopramide versus 14% of those on droperidol (p less than 0.05). We conclude that low-dose droperidol combinations can offer antiemetic protection for patients treated with moderate-dose cisplatin-based chemotherapies. In view of the potential for severe long-term neurologic problems due to metoclopramide or droperidol, these and similar drugs should be used at the lowest possible dose.

Adolescent↗

PubMed1991

Randomized study to evaluate the relation between oral isosorbide dinitrate dosing interval and the development of early tolerance to its effect on left ventricular filling pressure in patients with chronic heart failure.

BACKGROUND: Early development of nitrate tolerance has been shown in patients with chronic congestive heart failure (CHF) receiving continuous nitroglycerin therapy. The influence of dosing interval of oral isosorbide dinitrate (ISDN), the nitrate preparation most widely used for the treatment of CHF, has not been investigated. METHODS AND RESULTS: We performed a prospective, randomized study to evaluate the effect of various regimens of oral ISDN on the development of early tolerance to its effect on left ventricular filling pressure in patients with moderate to severe CHF. Forty-four responders (20% or greater reduction in mean pulmonary artery wedge pressure lasting 1 hour or longer) were divided into four groups of 11 patients each, and randomized to receive their effective ISDN dose (40-120 mg) Q 4 hours, Q 6 hours, Q 8 hours, or t.i.d. (drug given at 0, 6, 12, and 24 hours allowing 12 hours of ISDN washout interval between the third and fourth doses). All groups demonstrated a significant and comparable reduction in LV filling pressure following administration of the first ISDN dose. Early attenuation of hemodynamic response was demonstrated with frequent dosing (Q 4 hours and Q 6 hours) ISDN. Tolerance was with a Q 8-hour regimen as demonstrated by preserved hemodynamic response to each dose. The effect of each dose, however, was short-term, with return of pulmonary artery wedge pressure to baseline level at 2 to 4 hours, resulting in an intermittent effect totaling no longer than 12 hours of the 30-hour study period. The use of a t.i.d. regimen resulted in marked attenuation of response after the third dose with complete restoration of nitrate effect following a 12-hour washout period between the third and fourth doses. ISDN plasma concentration was measured in five patients in each of the Q 4- and Q 8-hour groups. In the Q 4-hour group, plasma levels were significantly higher after administration of the last dose than after the first dose (area under the curve, 242 +/- 216 versus 123 +/- 130 ng/ml, p less than 0.05), and trough levels before administration of the second and the fifth dose (15 +/- 17 and 27 +/- 27 ng/ml, respectively) were both markedly higher than the baseline value of 2 +/- 4 ng/ml. CONCLUSIONS: Our data demonstrate the development of tolerance and early attenuation of effect on left ventricular filling pressure with frequent oral dosing (Q 4 and Q 6 hours) with ISDN in patients with chronic CHF, which may be related to persistently elevated trough blood levels of ISDN. The development of tolerance can be reversed after a washout period of 12 hours and can be prevented with a Q 8-hour administration. These regimens, however, are limited by an inconsistent effect. Although long-term implications of these findings need further evaluation, the present study demonstrates the difficulty of maintaining a persistent ISDN-mediated reduction in left ventricular filling pressure in patients with chronic, moderate to severe CHF. These results suggest the need to use intermittent ISDN therapy allowing a daily nitrate washout interval and the rationale for combined vasodilator therapy in patients with CHF.

Drug Administration Schedule↗

PubMed1991

[Psychological impact of cataract surgery in the elderly patients].

A standardized interview was undertaken in twenty patients, mean age of 70, suffering from cataract fifteen days following extra-capsular extraction of the cataract, and implantation of a lens in the posterior chamber. The patients were selected on the basis that they had no risk factors of socio-psychological complications either during the illness or post-operatively. The study investigated retrospectively the impact of cataract on different aspects of personality and life-style in these patients. We also studied the degree of reactive depression in the postoperative period, as measured by the Hamilton depression scale. Although the precise psychological correlation between the two time periods was not possible, half of the patients suffered from a major affective disorder, as classified by DSM-III, 15 days before the operation and a quarter of these were depressed after the operation. Our results show this condition to be associated with considerable but non specific socio-affective upheaval in these patients.

Aged↗

PubMed1990

Randomized controlled trial of late in-hospital angiography and angioplasty versus conservative management after treatment with recombinant tissue-type plasminogen activator in acute myocardial infarction.

Although both the European Cooperative Study Group and the Thrombolysis in Myocardial Infarction IIB trial indicated that angiography and angioplasty as routine measures after thrombolytic treatment do not improve clinical outcome in patients with acute myocardial infarction, the potential benefit of angioplasty may have been negated by the fact that the procedure was performed too soon (less than 32 hours) after admission. A similar study was designed in which delayed invasive treatment was compared with conservative treatment in 201 patients with acute myocardial infarction given recombinant tissue-type plasminogen activator. The 97 patients randomized to the invasive group underwent routine coronary angiography and angioplasty 5 +/- 2 days after thrombolytic therapy, whereas the 104 patients randomized to the conservative group underwent angiography only for recurrent postinfarction angina or exercise-induced ischemia. Baseline characteristics of both groups were similar. In the invasive group, 92 patients underwent angiography, 49 angioplasty and 11 coronary artery bypass surgery. In the conservative group, 40 patients experienced early ischemia, 39 underwent angiography, 20 angioplasty and 4 coronary artery bypass surgery. Reinfarction rate and preservation of left ventricular function at discharge or 8 weeks after discharge did not differ in the 2 groups. Total mortality after a mean follow-up of 10 months was 8 of 97 in the invasive and 4 of 104 in the conservative groups (p = 0.15). However, if only patients who died after the timing of the scheduled protocol catheterization in the invasive arm were included, mortality was 5 of 94 and 0 of 100 in the invasive and conservative treatment groups, respectively (p = 0.02). (ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

Improved survival but not left ventricular function with early and prehospital treatment with tissue plasminogen activator in acute myocardial infarction.

One hundred ninety patients with acute myocardial infarction (AMI) were treated with recombinant tissue-type plasminogen activator (rt-PA) 2.0 +/- 0.8 hours after the onset of symptoms. Eighty-seven patients were enrolled via mobile intensive care units and 103 through the emergency ward. Patients who were enrolled via the mobile intensive care units were randomized to immediate, prehospital treatment initiation, or to delayed, in-hospital treatment initiation. All 190 patients except 2 underwent delayed coronary angiography and, when indicated, angioplasty at 72 hours after enrollment. Patients treated within 2 hours and those treated 2 to 4 hours after symptom onset had similar preservation of left ventricular function, and similar prevalence of congestive heart failure at discharge. Patients treated within 2 hours of symptom onset had significantly lower short- (0.0 vs 6.3%, p = 0.01) and long-term (1.0 vs 9.5%, p = 0.03) mortality. Prehospital initiation of rt-PA appeared to be safe and feasible and resulted in a 40-minute decrease in the time from symptom onset to treatment initiation.

Aged↗

PubMed1990

Open phase II with 5-fluorouracil, 4-epi-doxorubicin and mitomycin C (FEM) in advanced gastric cancer.

Forty-four patients with advanced gastric cancer were treated with a combination including 5-fluorouracil, 4-epi-doxorubicin and mitomycin C. 4-Epi-doxorubicin was substituted for adriamycin in MacDonald's original schedule. The combined treatment involved 600 mg/m2 i.v. of 5-fluorouracil on days 1, 8, 29 and 36; 80 mg/m2 i.v. of 4-epi-doxorubicin on days 1 and 29; and 10 g/m2 i.v. of mitomycin C on day 1. The cycle was repeated on day 57 after the start of treatment. Out of 44 patients, 39 were evaluable. Thirteen partial remissions (33%) were achieved. The average duration of remission was 7 months (range, 3-12 months). The average survival of the responders was 9 months, and that of nonresponders 3.5 months. Toxicity was moderate, well-tolerated and, as compared with the FAM schedule, less pronounced, particularly as regards myelotoxicity. Thus, the substitution of 4-epi-doxorubicin for adriamycin in the original schedule of MacDonald et al. (1980) did not improve treatment results, but the observed toxicity was less pronounced.

Adenocarcinoma↗

PubMed1990

Diffusion of O2 in normal and ischemic retinas of anesthetized miniature pigs in normoxia and hyperoxia.

Transretinal PO2 profiles were recorded with O2-sensitive microelectrodes in the normal retina and in ischemic retinal foci induced by the occlusion of a retinal branch vein with argon laser photocoagulation in anesthetized miniature pigs. In the normal retina there are two PO2 gradients: one from the inner retina and the other from the choroid, both directed toward the middle of the retina. Both PO2 gradients persisted during hyperoxia. Thus, even in hyperoxia, the choroid does not supply the whole thickness of the normal retina with O2. Preretinal and transretinal PO2 measurements in ischemic inner retinal foci showed the existence of two PO2 gradients in steady-state systemic normoxia, as did those in the normal retina. This finding indicates that even in ischemia the choroid does not supply O2 to the inner retina; as a result, tissue hypoxia is maintained. During systemic hyperoxia, the intraretinal PO2 measurements in the ischemic foci showed only one gradient going from the choroid toward the inner retina. This gradient indicates that under these conditions, the choroid can supply O2 to the entire thickness of the ischemic retina. Extending a previously formulated hypothesis, we propose that in the ischemic retina as opposed to the normal retina, hyperoxia does not induce an increase in the O2 consumption of the outer retina. This suggestion could explain the rise in PO2 in the inner ischemic retina during hyperoxia.

Animals↗

PubMed1990

A patient with features of both Bardet-Biedl and Alström syndromes.

We describe a 30-year-old patient with acanthosis nigricans, diabetes mellitus with insulin resistance, hypogonadotropic hypogonadism, pigmentary degeneration of the retina and cerebellar, pyramidal and posterior columnar involvement. He had normal mental function, normal hearing and no hexadactyly. The patient had symptoms of both Bardet-Biedl and Alström syndromes, but did not manifest all the main features of either syndrome. This suggests either that the Bardet-Biedl, Alström, Laurence-Moon syndromes (including the variant described by Edwards) have a highly variable expression or that our case is a new variant within this group of syndromes.

Acanthosis Nigricans↗