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At least 19 recordsLinked to original sources

Therapeutic trial of aniline mustard in patients with advanced cancer. Comparison of therapeutic response with cytochemical assessment of tumor cell beta-glucuronidase activity.

Seventy-eight patients with advanced cancer received an adequate therapeutic trial with aniline mustard (NSC 18429). Significant anticancer activity with clinical benefit was demonstrated in five patients with cancer of the prostate and one patient with renal cancer. beta-glucuronidase levels in aspirate and imprint preparations of tumor cells were assessed by a timed cytochemical technique. A partial correlation appeared to exist between very intense glucuronidase staining and tumor regression in prostate and kidney lesions; however, these high levels were observed only rarely. Sequential observations in two patients demonstrated loss of enzymatic activity concomitant with development of clinical relapse.

Aniline Mustard

[Chronic arterial occlusive disease of the lower body. Diagnostic-therapeutic, especially surgical-therapeutic aspects and postoperative care].

The treatment of chronic arterial circulatory disorders of the lower extremities depends on the one hand on the presence of a type of occlusive process which can be confirmed angiologically and on the other hand by the degree of severity and thirdly on the availability of operative and conservative methods of treatment. According to the stage of ischemia (Stage III and IV) possibly only surgical measures offer the possibility of preventing amputation. The nearer the stenotic process to the aorta, the greater the possibility of success of a surgical intervention if the general condition does not represent a contraindication to surgery. The questions of indications for operation and the problems of the most suitable procedure (endarterectomy, bypass, prostheses, Dotter's transluminal dilatation) are discussed on the basis of many years' experience.

Aorta, Abdominal

[Prognosis with different therapeutic methods and therapeutic recommendations in operable breast cancers].

Breast carcinoma is the most frequent form of cancer in women. In Switzerland 1265 women died of it in 1975, the mortality rate is rising slowly, the cause of this fact being unclear. There is no uniformity about the best treatment of breast cancer. We analyzed 454 carcinomas, operated in the years 1961--1971 after Halsted, Patey and McWhirter. We found similar 5- and 10-year survival rates with the Halsted and the Patey method of operation, however, decidedly worse results with the simple mastectomy. Nowadays we recommend the modified radical excision of the breast after Patey at all stages; in addition we treat all patients with postoperative X-ray therapy or prescribe an adjuvant cytostatic therapy based on the experimental study of the SAKK (Swiss Therapy Group for Clinical Cancer Research).

Adolescent

[Urokinase. Biochemical therapeutical and therapeutical data (author's transl)].

Two thrombolytic agents are mainly used in patients: streptokinase (SK) and urokinase (UK). UK from human origin is an endopeptidase which is able to convert plasminogen into plasmin. UK is only secreted by the kidney and is only found in urine which is presently the only source of extraction. Studies in man have shown that UK produces a highly reproducible state of enhanced plasma thrombolytic activity with a high fibrinolysis/fibrnogenolysis ratio and a lack of toxicity and antigenicity. The half life in Animal is short as well as the duration of fibrinolytic activity in Man. In clinical experience, positive results have been reported in pulminary embolism while the issues in myocardial infarction are controversial. Suggestive results have been registered in deep vein thrombosis, in ophthalmologic field and in desobstruction of arterio-venious shunts. No evident benefit has been noted in cerebral vascular disease. Up to now, UK has been very well tolerated.

Animals

[Gilbert's jaundice. Current clinico-nosographic, physiopathological and therapeutic aspects. III. Therapeutic action of enzyme inductors with reference to unconjugated bilirubin icterus].

The value of phenobarbital in the treatment of free bilirubin icterus is demonstrated by a series of clinical experiments in which the drug was administered to patients with bilirubinaemia, even at high levels, the situation being brought back to normal within about two weeks. The percentage excreted with the urine in a conjugated form of various drugs proved higher in subjects treated with phenobarbital than in controls, thus proving that the drug acts as an enzymic inductor. Moreover it is ineffective in patients genetically lacking in the capacity to synthesize glycuronyltransferase. The induction of this latter enzyme, however, does not exhaust the effects of the barbiturate for it has been shown that phenobarbital is capable of speeding up the disappearance of exogenous bilirubin from the plasma in animals, of stimulating bile flow and increasing uptake of the pigment by the liver. The increase in bile flow is of the order of 30% and takes place by way of a modification in the flow fraction independent of bile salts. It would also appear that the drug is capable of increasing the activity of 7-alpha-hydroxylase, an enzyme that represents the rate limiting step in the synthesis of biliary salts. Other drugs commonly used in the treatment of free bilirubin icterus such as ethanol, rifampicin and uridindiphosphoglucose are considered. Finally the case of a female patient who from birth had presented persistent free bilirubin icterus of about 8 mg% is reported. After 14 days treatment with phenobarbital (100 mg X 2) blood levels of the pigment had returned to normal.

Adult

Unlocking the potential of bacteriophage-based therapeutic gene delivery in hepatocellular carcinoma.

Liver cancer, mainly hepatocellular carcinoma (HCC), remains a global health burden marked by poor prognosis with limited therapeutic efficacy, and high recurrence rates. HCC remains one of the most lethal malignancies worldwide, with limited therapeutic options and high resistance to conventional treatments. Despite low therapeutic efficacy, molecular heterogeneity, treatment resistance and high recurrence rate, hepatocellular carcinoma (HCC) is still a significant health problem worldwide. These restrictions have stimulated the research of focused methods for delivering therapeutic genetic payload into cancer cells. Bacteriophages have been gaining growing attention as an emerging delivery platform due to their genetic versatility, ease of engineering, ability to be surface modified and payload targeted. In this narrative review, the therapeutic potential of engineered bacteriophages in the context of HCC therapy is critically analyzed focusing on phage display-mediated tumor targeting, phage-mediated intracellular gene delivery, TRAIL gene delivery, and CRISPR/Cas-based therapeutic strategies. It has been previously noted in the literature that phage display can be used to attach tumor-targeting ligands to the surface of a phage, which may aid in the recognition of receptors at the tumor site and promote targeted delivery to the receptor. Therapeutic application is stunted by inefficient trafficking to the cytosol, endosomal degradation, immune recognition and clearance, vector stability, manufacturing scalability and regulatory issues. In conclusion, engineered bacteriophages are a promising and versatile tool for targeted gene delivery in HCC but more mechanistic, preclinical and translational research is needed to prove their therapeutic effectiveness and clinical usefulness for this purpose.

Humans

The Use of Deep Learning in RNA Therapeutic Development.

Ribonucleic acid (RNA)-based therapeutics have emerged as promising methods of disease treatment due to their ability to target the human genome and influence protein production, their versatility, and their relative lack of toxicity compared to other gene therapies. However, the RNA therapeutic design space is extremely large, encompassing multiple variables, including codon identities, secondary structure, and design of specific regions. RNA therapeutic optimization is difficult due to the impracticality of exploring such a vast design space experimentally. To address this limitation, deep learning methods have been employed to optimize RNA therapeutic development. In this review, we examine the application of deep learning models across three key aspects of RNA therapeutic development (RNA structure prediction, CRISPR activity, and RNA delivery), highlighting major contributions in these fields and analyzing how deep learning model architectures could affect model performance. We then discuss challenges associated with using deep learning for RNA therapeutics, such as computational and data limitations. Finally, we offer perspectives on areas for future exploration, such as emerging model architectures and methods of integration with more advanced high-throughput screening techniques. Ultimately, this review provides an overview of how deep learning is used in RNA therapeutic development and how it can evolve in the future.

Deep Learning

The therapeutic community as a research ward: myths and facts.

The clinical research ward run as a therapeutic community has been criticized as inefficient and scientifically unsound. This article discusses the therapeutic community as a research ward and identifies certain misconceptions which underlie many criticisms. The following myths are discussed and refuted: (1) There is an insurmountable community-research chasm. (2) The therapeutic community induces stress that interferes with research. (3) Patient passivity is engendered by research and this is destructive to the therapeutic community. (4) Symptoms are exacerbated by a research ward that is disruptive to the community. (5) Normal research subjects cannot live in a therapeutic community without pathologic psychic changes. These inaccurate myths are seen as a reflection of attempts to oversimplify very complex clinical and research issues. The use of mythology to simplify experiments, to artificially "clarify" complex issues, or to "protect" patients is seen as a disservice. The therapeutic community and research are syntonic when both receive appropriate support.

Adult

Beyond antibiotics: artificial intelligence-enabled anti-infective ecosystems for next-generation precision therapeutics against antimicrobial resistance.

The rapid global expansion of antimicrobial resistance (AMR) threatens to undermine decades of progress in infectious disease management and highlights the limitations of conventional antibiotic-centered therapeutic strategies. Although emerging technologies-including antimicrobial peptides, bacteriophage therapy, CRISPR-based antimicrobials, microbiome therapeutics, anti-virulence approaches, nanotechnology-enabled drug delivery, and artificial intelligence (AI)-have individually demonstrated considerable promise, they are predominantly being developed as independent interventions rather than as coordinated components of an integrated therapeutic strategy. This Perspective proposes the Intelligent Anti-Infective Ecosystem (IAIE) as a conceptual systems-level framework that computationally integrates multimodal diagnostics, pathogen genomics, microbiome profiling, AI-assisted decision support, programmable precision therapeutics, ecological monitoring, and longitudinal clinical feedback within a continuously learning dynamically optimized workflow. Unlike existing paradigms that primarily optimize individual technologies or therapeutic decisions, IAIE emphasizes closed-loop coordination among complementary antimicrobial approaches to support precision-guided infection management while preserving microbiome integrity and mitigating resistance selection pressure. We further outline the core components, operational principles, translational challenges, and technology readiness of the major therapeutic platforms that could contribute to such an ecosystem, while distinguishing clinically established interventions from emerging experimental strategies. Importantly, IAIE should be interpreted as a prospective conceptual architecture rather than an existing clinical platform. Its proposed clinical value remains to be established through sequential computational, preclinical, and prospective clinical investigations using standardized microbiological, ecological, and patient-centered outcome measures. By framing antimicrobial innovation within an responsive systems perspective, IAIE provides a roadmap for future multidisciplinary research aimed at integrating artificial intelligence and systems microbiology to enable sustainable management of antimicrobial resistance.

Humans

An implementation of therapeutic community in a private mental health center.

The concepts of milieu therapy have, in the past 20 years, been widely applied to various facilities for treatment of people with emotional and mental illness. One type of milieu therapy, the Therapeutic Community, has gained increasing acceptance, as a means of implementing milieu therapy. This paper describes the application of therapeutic community concepts to the in-hospital population of a private, open-staffed, open-door psychiatric facility, and some of the effects that this has had on both the staff, and the patient population. Since the development of the therapeutic community concept almost 25 years ago, programs have been developed in various centers which implement the concepts of social psychiatry in different ways. This paper describes the development of a particular therapeutic community on the in-patient adult and adolescent psychiatric services of a private psychiatric hospital. Parkwood was developed as a small (40 bed) psychiatric hospital in Atlanta, Georgia in 1966 by a group of physicians wanting to implement the ideas of milieu therapy in an area where no such program was available. In its initial stages, the hospital -- of attractive, middle-class decor -- was built in a wooded setting on the edge of a large metropolis. It was open-staffed, with psychiatrists having an eclectic, though psychoanalytically based, orientation toward treatment. The concepts of milieu therapy were interpreted to mean the following: a warm, pleasant atmosphere, in pleasant surroundings, conducive to the usual brief psychotherapy, chemotherapy, or somatic therapy, which had previously been used in non-milieu psychiatric hospitals. The total hospital patient population was divided in half and met in group sessions with a psychiatrist once each week. The Medical Director, a psychiatrist, had weekly staff meetings, in which he discussed various administrative problems. In 1969, a Medical Director with a therapeutic community orientation was employed. Over a five-year period, the total complexion of the hospital changed to its present state, an open-staffed, open door, comprehensive, community mental health center financed on a private basis. The facility now provides out-patient, partial or total hospitalization, emergency services, and community education for children, adolescents, adults and alcohol addicted patients. This paper deals with the therapeutic community on the adult and adolescent units.

Adolescent

Precision diagnostic and therapeutic interventions in rare genetic neurodevelopmental disorders.

Neurodevelopmental disorders (NDDs) include a broad spectrum of phenotypes spanning from intellectual disability (ID) to developmental delay (DD) and autism spectrum disorder (ASD). As neurodevelopmental phenotypes are a common presenting feature of an underlying genetic condition, professional medical organizations recommend genetic testing for all individuals with a NDD. When testing is pursued, identified genetic differences can lead to personalized clinical management with early diagnosis supporting the development of surveillance and intervention for co-occurring adverse health outcomes. Despite this, barriers to testing have prevented individuals from receiving a genetics referral and testing. Current therapeutic modalities including small molecule drugs, gene therapies, and antisense oligonucleotide therapies have emerged and shown promise in preclinical trials with therapeutic drugs gaining FDA approval. However, translational challenges are extensive, especially for identifying biomarkers of drug effects in the CNS. In this review, we discuss diagnostic approaches and clinical utility of genetic testing for rare genetic neurodevelopmental disorders, emerging development of individualized therapies, and progress for current therapeutics in addition to challenges with clinical translation and delivery. We will highlight opportunities for early diagnosis and treatment that are steadily gaining ground in favor of optimizing long-term health outcomes and improving quality of life for neurodiverse individuals. IMPACT: The path from genomics to therapeutics for neurodevelopmental disorders continues to present multiple opportunities and challenges. While emerging genome-wide sequencing and gene editing technologies deliver increased diagnostic yields and alternatives to life-long small molecule therapies, clinical translation has been challenging due to inherent cost and genetic heterogeneity. Limited access to genetic testing despite practice guidelines remains a barrier towards precision therapeutics for rare neurodevelopmental disorders, while pre-clinical investigations face obstacles when translating to human subjects. This review will summarize the impact of existing successes in diagnosis and therapeutics for neurodevelopmental disorders while highlighting ongoing challenges and areas of future opportunities.

Humans