ABSTRACT
BACKGROUND: Multiple relapsed/refractory germ cell tumor (GCT) patients have extremely poor prognosis. Cisplatin resistant testicular GCTs overexpress aldehyde-dehydrogenase (ALDH) isoforms and inhibition of ALDH activity by disulfiram is associated with reconstitution of cisplatin sensitivity in vitro as well as in animal model. This study aimed to determine the efficacy and toxicity of ALDH inhibitor disulfiram in combination with cisplatin in patients with multiple relapsed/refractory GCTs. METHODS: Disulfiram was administered at a dose of 400 mg daily until progression or unacceptable toxicity, cisplatin was administered at dose 50 mg/m2 day 1 and 2, every 3 weeks. Twelve evaluable patients had to be enrolled into the first cohort, and if 0 of 12 patients had treatment response, the study was to be terminated. The results of the first stage of the trial are presented in this report. RESULTS: Twelve patients with multiple relapsed/refractory GCTs were enrolled in the phase II study from May 2019 to September 2021. Median number of treatment cycles was 2 (range 1-6). None of patients achieved objective response to treatment, therefore the study was terminated in first stage. Median progression-free survival was 1.4 months, 95% CI (0.7-1.5 months), and median overall survival was 2.9 months 95% CI (1.5-4.7 months). Disease stabilization for at least 3 months was observed in 2 (16.7%) patients. Treatment was well tolerated, however, 5 (41.7%) of patients experienced grade 3/4 fatigue, 4 (33.3%) thrombocytopenia, 3 (25.0%) anemia, while 2 (16.7%) experienced neutropenia, nausea and infection. CONCLUSIONS: This study failed to achieve its primary endpoint and our data suggest limited efficacy of disulfiram in restoring sensitivity to cisplatin in multiple relapsed/refractory GCTs.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Antineoplastic Combined Chemotherapy Protocols/toxicity , Cisplatin/therapeutic use , Disulfiram/therapeutic use , Drug Resistance, Neoplasm , Humans , Male , Neoplasms, Germ Cell and Embryonal/drug therapy , Testicular Neoplasms/drug therapyABSTRACT
Arterial hypertension belongs to the most important factors of origin and lasting of tinnitus. We have studied 18 subjects suffering from tinnitus without the history of diagnosed or treated arterial hypertension. ABPM method was used for diagnosing arterial hypertension. 12 patients (66%) fulfilled the criteria for arterial hypertension. Our results illustrate that arterial hypertension diagnosis is devoted an insufficient attention in patients with tinnitus. ABPM should therefore be used in all patients with tinnitus, immediately after its manifestation and also repeatedly during its course. With early diagnosis and treatment of hypertension, some complications, such as myocardial infarction, stroke, heart and/or kidney failure can be thus prevented (Tab. 1, Fig. 5, Ref. 10). Full Text in free PDF www.bmj.sk.
Subject(s)
Blood Pressure Monitoring, Ambulatory , Hypertension/diagnosis , Tinnitus/etiology , Adult , Female , Humans , Hypertension/complications , Male , Middle AgedABSTRACT
Cryoglobulinemia is a rather rare condition accompanying quite a broad spectrum of different states and diseases. Mixed or polyclonal cryoglobulins can be seen in patients with autoimmune disorders, chronic infections and lymphoproliferative disorders. Monoclonal cryoglobulins are often revealed in patients with multiple myeloma or Waldenström's macroglobulinemia. Cryoglobulinemia is in most cases asymptomatic. Cryoglobulinemic vasculitis is an immune complex-mediated systemic disorder involving mostly small, but sometimes also larger vessels. In this report, we describe a case of a patient presented with gangrene of almost all fingers and toes, who was finally diagnosed and treated as cryoglobulinemic vasculitis due to multiple myeloma.
Subject(s)
Cryoglobulinemia/etiology , Fingers/blood supply , Multiple Myeloma/complications , Toes/blood supply , Vasculitis, Leukocytoclastic, Cutaneous/etiology , Aged , Amputation, Surgical , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Autopsy , Biopsy , Cryoglobulinemia/diagnosis , Cryoglobulinemia/pathology , Cryoglobulinemia/therapy , Fatal Outcome , Fingers/pathology , Fingers/surgery , Gangrene , Humans , Immunosuppressive Agents/therapeutic use , Male , Multiple Myeloma/diagnosis , Multiple Myeloma/pathology , Multiple Myeloma/therapy , Toes/pathology , Toes/surgery , Treatment Outcome , Vasculitis, Leukocytoclastic, Cutaneous/diagnosis , Vasculitis, Leukocytoclastic, Cutaneous/pathology , Vasculitis, Leukocytoclastic, Cutaneous/therapy , Vasodilator Agents/therapeutic useABSTRACT
Obesity is an independent risk factor for the development and progression of hypertension, cardiovascular disease and chronic kidney disease. There is growing evidence that obesity and associated metabolic abnormalities may induce and accelerate renal complications in essential hypertension. The clustering of obesity and other features of the metabolic syndrome might have important implications for prevention, particularly with regard to whether interventions targeted at visceral obesity would have beneficial effects on cardiovascular and renal morbidity.
Subject(s)
Hypertension/etiology , Obesity/complications , Obesity/physiopathology , Cardiovascular System/physiopathology , Humans , Metabolic Syndrome/physiopathology , Respiratory System/physiopathologyABSTRACT
OBJECTIVES: To compare the manual and digital cephalometric analyses and to research a new procedure of analog cephalogram digitalization. METHODS: 40 repeated measurements were used to evaluate the reproducibility and reliability of both methods. The analog x-ray was CHIRALUX2, the digital camera used was Canon PowerShot G5 and the digital tracing was done by Dolphin imaging version 10. The sample dispersion has been evaluated for each of the monitored cephalometric variables (SNA, SNB, ANB, PP/ML, inter-incisal angle and Wits). The difference of sample dispersion was tested (Morgan-Pitman). Four doctors processed 100 random analog cephalograms in total and evaluated them in a way established by Bland and Altman. RESULTS AND CONCLUSION: Validity and reproducibility of analyses carried out manually and digitally is in high mutual correlation and therefore the software analysis can fully substitute the manual method. The dispersion of values in repeated measurements was higher in manual method and therefore we consider the digital method more accurate (Fig. 4, Tab. 1, Ref. 15). Full Text (Free, PDF) www.bmj.sk.
Subject(s)
Cephalometry/methods , Image Processing, Computer-Assisted , Orthodontics , Humans , Photography , Radiography, Dental , Reproducibility of Results , SoftwareABSTRACT
OBJECTIVES: Authors evaluated the effect of the WEB 2.0 environment on dental education and estimated the difference in retention of knowledge by cephalometric analysis in orthodontics between conventional education and off-line e-learning. BACKGROUND: Five years of experience with complex web-based e-learning system allowed the evaluation by retrospective analysis and on-line questionnaire. RESULTS: The results revealed the current trends in on-line behavior of students based on the WEB 2.0 innovative technologies like Ajax. Results confirmed an increasing number of resources with a rising frequency of e-learning materials. CONCLUSION: The study confirmed that e-learning of the same subject is more efficient in immediate examination after the lecture with even better results after 12 and 24 months against the control group (Tab. 3, Fig. 1, Ref. 26).
