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At least 253 records · Page 14Linked to original sources
PubMed1985

[Pregnancy and fetal development after therapy of Hodgkin's disease].

The post-therapeutic pregnancy data of 122/244 women aged until 40 years who had been treated primarily in Freiburg i. Br. for Hodgkin's disease between 1949 and 1981 were obtained by an inquiry based on questionnaires. All of the 122 patients of the questionnaire group were in remission. 39 out of them (32%) became pregnant one or more times; 38/94 (40%) of these had been irradiated down to the promontory and 1/17 (6%) had been submitted to an irradiation including the pelvis with ovariopexy. The resulting 63 post-therapeutic pregnancies leaded to 41 normal births (65%), three premature infants (5%), two viable children suffering from malformations (3%) and five spontaneous abortions (8%). An interruption was performed in twelve cases (19%). There were no significant divergences from distributions of normal populations with regard to the percentages of normal births and negative variants, even under consideration of comparable literature reports. Neither in the questionnaire group nor in the group of 122 patients whose gynecologic data could only be evaluated by means of the medical records available, there was any indication suggesting an increased risk of morbidity or mortality.

Adult↗
PubMed1998

Angiotensin AT1 receptor inhibition, angiotensin-converting enzyme inhibition, and combination therapy with developing heart failure: cellular mechanisms of action.

BACKGROUND: Past studies have shown that angiotensin-converting enzyme inhibition (ACEI) alone, angiotensin AT1 receptor blockade (AT1 block) alone, and combined treatment have differential effects on left ventricular (LV) function and geometry with developing congestive heart failure (CHF). The purpose of this study was to more carefully examine the cellular basis for these differential effects by using a model of pacing CHF. METHODS AND RESULTS: Pigs were randomly assigned to five groups: (1) rapid pacing (240 bpm) for 3 weeks (n = 9), (2) concomitant ACEI (benazeprilat, 0.187 mg/kg/day) and pacing (n = 9), (3) concomitant AT1 block (valsartan, 3 mg/kg/day) and pacing (n = 9), (4) concomitant ACEI and AT1 receptor blockade (benazeprilat/valsartan, 0.05/3 mg/kg/day, respectively) and pacing (n = 9), and (5) sham controls (n = 10). The dosage protocol was based on obtaining a 50% reduction in angiotensin I and angiotensin II pressor response with no significant effects on mean basal arterial pressure. In the pacing group, LV fractional shortening (LVFS) fell compared with control group (13.4+/-1.4 v 39.1+/-1.0%, P < .05). With AT1 block, LVFS was unchanged from pacing only. ACEI and combined treatment increased LVFS from pacing values (25.2+/-0.9 v 20.9+/-1.9%, respectively, P < .05). LV myocyte shortening velocity was reduced with chronic pacing compared with control group (27.2+/-0.6 v 58.6+/-1.2 microm/s, P < .05) and remained reduced with AT1 block (28.0+/-0.5 microm/s, P < .05). Myocyte shortening velocity increased with ACEI or combination treatment (36.9+/-0.7 v 42.3+/-0.8 microm/s, respectively, P < .05). Concomitant treatment with either ACEI or AT1 blockade normalized myocyte action potential duration. In the combined ACEI and AT1 blockade group, all parameters of the myocyte action potential were unchanged from control values. CONCLUSIONS: This study showed that combined ACEI and AT1 receptor blockade produced beneficial effects on myocyte contractility and electrophysiology when compared with either monotherapy alone and therefore may provide unique benefits with CHF.

Action Potentials↗
PubMed2025

Genetic and Demographic Determinants of Fuchs Endothelial Corneal Dystrophy Risk and Severity.

IMPORTANCE: Understanding the pathogenic mechanisms of Fuchs endothelial corneal dystrophy (FECD) could contribute to developing gene-targeted therapies. OBJECTIVE: To investigate associations between demographic data and age at first keratoplasty in a genetically refined FECD cohort. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study recruited 894 individuals with FECD at Moorfields Eye Hospital (London) and General University Hospital (Prague) from September 2009 to July 2023. Ancestry was inferred from genome-wide single nucleotide polymorphism array data. CTG18.1 status was determined by short tandem repeat and/or triplet-primed polymerase chain reaction. One or more expanded alleles (&#x2265;50 repeats) were classified as expansion-positive (Exp+). Expansion-negative (Exp-) cases were exome sequenced. MAIN OUTCOMES AND MEASURES: Association between variants in FECD-associated genes, demographic data, and age at first keratoplasty. RESULTS: Within the total cohort (n&#x2009;=&#x2009;894), 77.3% of patients were Exp+. Most European (668 of 829 [80.6%]) and South Asian (14 of 22 [63.6%]) patients were Exp+. The percentage of female patients was higher (151 [74.4%]) in the Exp- cohort compared to the Exp+ cohort (395 [57.2%]; difference, 17.2%; 95% CI, 10.1%-24.3%; P&#x2009;<&#x2009;.001). The median (IQR) age at first keratoplasty of the Exp&#x2009;+&#x2009;patients (68.2 years [63.2-73.6]) was older than the Exp- patients (61.3 years [52.6-70.4]; difference, 6.5 years; 95% CI, 3.4-9.7; P&#x2009;<&#x2009;.001). The CTG18.1 repeat length of the largest expanded allele within the Exp+ group was inversely correlated with the age at first keratoplasty (&#x3b2;, -0.087; 95% CI, -0.162 to -0.012; P&#x2009;=&#x2009;.02). The ratio of biallelic to monoallelic expanded alleles was higher in the FECD cohort (1:14) compared to an unaffected control group (1:94; P&#x2009;<&#x2009;.001), indicating that 2 Exp+ alleles were associated with increased disease penetrance compared with 1 expansion. Potentially pathogenic variants (minor allele frequency, <0.01; combined annotation dependent depletion, >15) were only identified in FECD-associated genes in 13 Exp- individuals (10.1%). CONCLUSIONS AND RELEVANCE: In this multicenter cohort study among individuals with FECD, CTG18.1 expansions were present in most European and South Asian patients, while CTG18.1 repeat length and zygosity status were associated with modifications in disease severity and penetrance. Known disease-associated genes accounted for only a minority of Exp- cases, with unknown risk factors associated with disease in the rest of this subgroup. These data may have implications for future FECD gene-targeted therapy development.

Adult↗
PubMed1994

Quinolone resistance in Pseudomonas aeruginosa and Staphylococcus aureus. Development during therapy and clinical significance.

This review focuses on published information on the experimental as well as clinical data on the emergence of quinolone resistant isolates. In the course of clinical use of fluoroquinolones, only a sporadic emergence of quinolone resistance has been noted. The resistant organisms emerged particularly in certain clinical settings where large numbers of organisms frequently causing chronic infections are present and/or in loci where quinolone concentrations may not be optimal. In terms of occurrence in individuals, quinolone resistance has emerged most frequently in hospitalized and nursing-home patients with identifiable risk factors. Epidemiological studies revealed that in nearly all the cases studied one or one predominating quinolone resistant clone was selected that was horizontally transmitted. Thus, the emergence of quinolone resistance is not due to an independent selection of resistant strains in a number of patients, but to the clonal spread of one strain once it has acquired quinolone resistance. Therefore, the rate of quinolone resistance is very likely to be lower than reported.

Animals↗
PubMed2000

[Recent developments in therapy of condylar fractures of the mandible].

Due to advances in surgical methods, such as miniplate and lag screw osteosynthesis, there is current discussion about the adequate therapy of condylar fractures. Regarding the insufficient outcome of conservative treatment confirmed by refined methods of functional diagnosis, there is a trend towards surgical therapy, at least in cases of condylar displacement out of the fossa. This trend was also prompted when surgeons learned that the condyle determines local growth but does not serve as a growth center of the mandible. Along with increased interest in temporomandibular function and surgical therapy of internal disorders, surgical therapy of traumatic soft tissue lesions was emphasized. This consequently led to surgical restoration of intraarticular fractures. Conservative treatment will nonetheless be sufficient in cases of minor displacement due to a higher ability of remodeling, even more so in children.

Bone Plates↗
PubMed2003

New developments in therapy for colorectal cancer.

Colorectal cancer remains a significant cause of cancer death, and its treatment is the subject of active, ongoing investigation within all treatment modalities, including surgery, chemotherapy, and radiotherapy. In this review we discuss selected interesting and important research findings since the year 2000 and comment on their potential impact on the adjuvant and advanced disease management of patients with colon and rectal cancer.

Clinical Trials as Topic↗
PubMed1982

The hyperventilation test as a method for developing successful therapy in Prinzmetal's angina.

In 10 cases of Prinzmetal's angina in which episodes of myocardial ischemia were easily and reproducibly induced by hyperventilation, this test was performed 111 times, 41 times under control conditions and 70 times during treatment with one or more of the following drugs: phentolamine, isosorbide dinitrate, propranolol, verapamil, nifedipine and amiodarone. Seventeen of 18 negative tests performed under the influence of a long-acting drug coincided with total remission of the patient's anginal episodes when this drug was administered on a short- or long-term basis. No patient died or sustained infarction during a follow-up period of 10.9 months. A negative test was thus a good indication that the clinical response to the corresponding drug would be favorable. The electrocardiographic changes and chest pain provoked by hyperventilation occurred not when alkalosis was greatest (hydrogen ion [pH] change from 7.42 to 7.58, p less than 0.001), but when pH was approaching normal or control values. The onset of electrocardiographic changes occurred an average of 175 seconds after the end of hyperventilation and, in two cases, the time lag was as much as 480 and 705 seconds, respectively. This raises several questions regarding the true mechanism triggering coronary spasm under such conditions. The hyperventilation test appears to be a useful and safe procedure for selecting the best possible drug for long-term treatment of Prinzmetal's angina as well as for comparing the relative efficacy of different drugs.

Adult↗
PubMed2005

Anti-macular degeneration agents.

Anti-VEGF therapy is a promising new avenue for the treatment of ocular neovascular diseases. Early preclinical data and recent clinical data support the efficacy and safety of several novel anti-VEGF for NVAMD. Whether these novel biologics are used on their own, in combination with previously available therapies, or with newly developing therapies, they represent a new avenue in treatment. These agents are highly selective in their targeted approaches, and when administered appropriately , offer treatment with minimal damage to retinal tissue. In the future, biotherapeutic agents will certainly play a powerful role in the treatment of human choroidal neovascular membrane formation.

Angiogenesis Inhibitors↗
PubMed2005

[Involvement of PI3K/Akt pathway in prostate cancer. Potential strategies for developing targeted therapies].

Because of the unavailability of effective therapies to block or reverse the progression of androgen-independent prostate cancer, it seems obvious to target growth signaling pathways for which frequently recurring mutations have been identified. Acquired mutations of the PTEN gene have been reported in several tumor types, including up to 30% - 60% of prostate cancer tumors. This results in constitutive activation of the PI3K/Akt pathway which then represents a major target to prevent dysfunctions in cell growth, survival and motility. Our experience and, therefore, our own tools allow us to design new inhibitors of growth factor receptor tyrosine kinase, PDK-1 and farnesyltransferase activities. These original compounds could selectively switch off one or several steps of the multifunctional pathway and constitute lead compounds in the design of new classes of potent drugs.

Alkyl and Aryl Transferases↗