Combination chemotherapy with mitomycin C,vindesine and melphalan for refractory metastatic breast cancer

Summary A combination of mitomycin C, vindesine and melphalan was administered to 33 patients with heavily pretreated refractory breast cancer. The overall response rate was 27% with a mean duration of more than 10.2 months. A stabilization with a mean duration of 5.1 months was seen in 56% of cases, while 20% of patients progressed. Gastrointestinal toxicity, mostly grade 1 or 2 nausea/vomiting was seen in 85% of cases, grade 1 or 2 leukopenia in 60% of patients, and grade 1 or 2 thrombocytopenia in 42%. Considering the good compliance of this regimen and the poor prognosis of patients with refractory advanced breast cancer, this combination can be useful as a palliative treatment of breast carcinoma.Abbreviations MMC mitomycin C - VDS vindesine - L-PAM melphalan     

Hb Southern Italy: coexistence of two missence mutations (the Hb Sun Prairie alpha2 130 Ala --> Pro and Hb Caserta alpha2 26 Ala --> Thr) in a single HBA2 gene

This study describes a new molecular condition in the alpha(2)-globin gene (HBA2) found in six unrelated families from Southern Italy (Campania and Sicily). This new double mutant form of haemoglobin is called Hb Southern Italy and originated from the coexistence of two known mutations occurring in the same globin gene, HBA2 26 G-->A (Hb Caserta) and HBA2 130 G-->C (Hb Sun Prairie). Hb Sun Prairie was originally observed in Indian patients in either the homozygous state, with severe hemolytic anemia, and in the heterozygous state with microcytosis, or in asymptomatic cases as an alpha-thalassemia carrier phenotype. Hb Caserta was observed for the first time in a Casertian family (South Italy) that displayed a slowmigrating haemoglobin upon investigation. We report the clinical phenotype and molecular study of this new double mutant form of haemoglobin in heterozygous and homozygous subjects, as well as in association with alpha degrees delectional thalassemia.     

Manometric patterns of rat colonic motor activity and defecation

We investigated in conscious and unrestrained rats, the major patterns of colonic pressure waves, as related to defecation. A manometric low compliance perfusion system, which was set at a very low flow rate (0.03 ml/min), permitted simultaneous recordings of intraluminal pressure in the proximal, transverse, and distal colon. Pressure waves in control rats reflected two types of motor activity: short-duration waves (<15 sec), that were frequent throughout the colon (about 40–90/hr with aborally decreasing frequency), and propulsive, long-duration, high-amplitude waves (>15 sec, >15 mm Hg) that occurred only occasionally (1/hr or less) in the transverse and distal, but not in the proximal colon; these waves appeared to migrate aborally and were associated with defection. The serotonin 5HT_1A agonist 8-OH-DPAT dramatically and dose-dependently increased the frequency of long-duration, high-amplitude waves in the transverse and distal colon, and concurrently promoted defecation; these effects were prevented by the putative 5HT_1A antagonist pindolol. We conclude that 5HT_1A agonists such as 8-OH-DPAT may promote defecation and occurrence of propulsive waves through the same serotoninergic mechanism.A preliminary account of this work was presented at the 13th International Symposium on Gastrointestinal Motility, Kobe, Japan, Abstract 172. J Gastrointest Motil 3, 1991.     

Galectina-3 Associada a Formas Graves e Mortalidade em Longo Prazo em Pacientes com Doença de Chagas

Background The histopathological characteristics of Chagas disease (ChD) are: presence of myocarditis, destruction of heart fibers, and myocardial fibrosis. Galectin-3 (Gal-3) is a biomarker involved in the mechanism of fibrosis and inflammation that may be useful for risk stratification of individuals with ChD.Objectives We sought to evaluate whether high Gal-3 levels are associated with severe forms of Chagas cardiomyopathy (CC) and whether they are predictive of mortality.Methods We studied anti-T. cruzi positive blood donors (BD): Non-CC-BD (187 BD without CC with normal electrocardiogram [ECG] and left ventricular ejection fraction [LVEF]); CC-Non-Dys-BD (46 BD with CC with abnormal ECG but normal LVEF); and 153 matched serum-negative controls. This cohort was composed of 97 patients with severe CC (CC-Dys). We used Kruskall-Wallis and Spearman’s correlation to test hypothesis of associations, assuming a two-tailed p<0.05 as significant.Results The Gal-3 level was 12.3 ng/mL for Non-CC-BD, 12.0 ng/mL for CC-Non-Dys-BD, 13.8 ng/mL for controls, and 15.4 ng/mL for CC-Dys. LVEF<50 was associated with higher Gal-3 levels (p=0.0001). In our linear regression adjusted model, we found association between Gal-3 levels and echocardiogram parameters in T. cruzi-seropositive subjects. In CC-Dys patients, we found a significant association of higher Gal-3 levels (≥15.3 ng/mL) and subsequent death or heart transplantation in a 5-year follow-up (Hazard ratio – HR 3.11; 95%CI 1.21–8.04; p=0.019).Conclusions In ChD patients, higher Gal-3 levels were significantly associated with severe forms of the disease and more long-term mortality, which means it may be a useful means to identify high-risk patients. (Arq Bras Cardiol. 2021; 116(2):248-256)     

Osteomuscular symptoms on motorcycles in the city of Rio Branco,Acre, Brazil,West Amazon

Musculoskeletal disorders gradually affect workers in different parts of the world, compromising their occupational health and quality of life. Professionals exposed to these symptoms include the motorcycle taxi driver, whose pain is due to the overuse of the musculoskeletal system and little time to recover it.To identify the prevalence of musculoskeletal symptoms in motorcycle taxi drivers in the city of Rio Branco, Acre, Brazil, West Amazon.Cross-sectional study, involving 296 motorcycle taxi drivers in the city of Rio Branco-Acre, Brazil, male, from December 2016 to February 2017. The Nordic Musculoskeletal Questionnaire was used to collect information related to symptoms (pain, discomfort, or numbness) in the last 7 days of work. For the exclusion criteria were, being female; not reside outside the city of Rio Branco, Acre; having less than 3 months of work activity; not be carrying out their work activities at the time of application of the protocol; be limited by clinical or physical issues at the time of application of the protocol. The data obtained in the questionnaire were entered into the Epidata program (Epidata Association, Odense, Denmark) and then transferred to the STATA 10 statistical program (Stata Corp., College Station), for categorization and statistical analysis.The study population is over 36 years old; most reported having a partner and a higher education level. The average daily working hours of the participants were 12 hours, with the majority working over 12 hours daily. Most of the epidemiological variables factors were associated with musculoskeletal pain when the prevalence and prevalence ratio analyzes were performed. Higher prevalence of musculoskeletal symptoms in the lumbar region is with 17.9%. In the lower limbs, the most affected joint was the ankle (5.7%), followed by the hip (5.07%) and knee (5.07%), respectively. Insomnia was present in 55.35% and self-reported headache in 49.4% of participants.The musculoskeletal disorders generated by the daily service of motorcycle taxi drivers are directly affecting the quality of life of these professionals.     

A Higher Angiogenin Expression is Associated With a Nonnuclear Maspin Location in Laryngeal Carcinoma

Objectives

In numerous malignancies, angiogenin (ANG) and Maspin are important proangiogenic and antiangiogenic regulators, respectively. The aim of this study was to identify potential relationships between the biological roles of these two proteins in laryngeal squamous cell carcinoma (LSCC).

Methods

Immunohistochemical staining for ANG and Maspin was performed on specimens from 76 consecutive LSCC patients treated with surgery alone, considering the subcellular pattern of Maspin expression. Univariate and multivariate statistical models were used for prognostic purposes.

Results

On univariate analysis, a different level of ANG expression was seen for patients stratified by subcellular Maspin expression pattern: the mean ANG expression was higher in cases with a nonnuclear MASPIN expression than in those with a nuclear pattern (P=0.002). Disease-free survival (DFS; in months) differed significantly when patients were stratified by N stage (P=0.01). Patients whose Maspin expression was nonnuclear (i.e., it was cytoplasmic or there was none) had a significantly higher recurrence rate (P<0.001), and shorter DFS (P=0.01) than those with a nuclear Maspin pattern. The mean ANG expression was significantly higher in cases with loco-regional recurrent disease (P=0.007); and patients with an ANG expression ≥5.0% had a significantly shorter DFS than those with an ANG expression <5.0% (P=0.007). On multivariate analysis, ANG expression ≥5.0% was a significant, independent, negative prognostic factor in terms of DFS (P=0.041).

Conclusion

Our results support the hypothesis that a higher ANG expression is associated with a nonnuclear Maspin expression pattern in patients with LSCC. Further studies are needed to clarify the relationship between the ANG and Maspin pathways, and their potential diagnostic and therapeutic role in LSCC.     

Selective targeted delivery of TNFalpha to tumor blood vessels

We sought to enhance the selective toxicity of tumor necrosis factor alpha (TNFalpha) to permit its systemic use in cancer therapy. Because ligand-targeted therapeutics have proven successful in improving the selective toxicity of drugs, we prepared a fusion protein (L19mTNFalpha) composed of mouse TNFalpha and a high-affinity antibody fragment (L19 scFv) to the extradomain B (ED-B) domain of fibronectin, a marker of angiogenesis. L19mTNFalpha was expressed in mammalian cells, purified, and characterized. L19mTNFalpha was an immunoreactive and biologically active homotrimer. Radiolabeled L19mTNFalpha selectively targeted tumor neovasculature in tumor-bearing mice, where it accumulated selectively and persistently (tumor-to-blood ratio of the percentage of injected dose per gram [%ID/g] of 700, 48 hours from injection). L19mTNFalpha showed a greater anticancer therapeutic activity than both mTNFalpha and TN11mTNFalpha, a control fusion protein in which an antibody fragment, irrelevant in the tumor model used, substituted for L19. This activity was further dramatically enhanced by its combination with melphalan or the recently reported fusion protein L19-IL2. In conclusion, L19mTNFalpha allows concentrating therapeutically active doses of TNFalpha at the tumor level, thus opening new possibilities for the systemic use of TNFalpha in cancer therapy.     

New technique for assessing fetal heart growth using three-dimensional ultrasonography: description of the technique and reference curves

Objective: To describe a new technique for assessing fetal growth using three-dimensional ultrasonography (3DUS) using the extended imaging virtual organ computer-aided analysis (XI VOCAL) software and its respective reference curves.

Methods: We conducted a cross-sectional study on 303 normal singleton pregnancies between their 20th and 34th weeks. To assess fetal heart growth, we used the XI VOCAL software with 10 planes in which the reference lines (beginning and end) were placed at the cardiac apex, the output level of the vessels and the base above the diaphragm, respectively. To assess the correlation between distance and interval, polynomial regressions were performed with adjustments using the coefficient of determination (R²). To assess the inter-observer reproducibility, we used the intraclass correlation coefficient (ICC).

Results: The mean distance between the apex and the base of the fetal heart ranged from 14.41?±?1.24?mm to 26.24?±?2.62?mm between the 20th and 34th weeks, respectively. The mean interval between the apex and the base of the fetal heart ranged from 1.56?±?0.13?mm and 2.94?±?0.30?mm between the 20th and 34th weeks, respectively. We observed good correlation of distance and interval with the gestational age, with R²?=?0.73 and 0.74, respectively. We observed a good inter-observer to the interval and distance with ICC?=?0.983 and 0.996, respectively.

Conclusion: We described a new technique for assessing fetal heart growth using 3DUS and determined reference curves for the distance and interval between the 20th and 34th weeks of pregnancy.     

Myocardial Salvage Imaging: Where Are We and Where Are We Heading? A Cardiac Magnetic Resonance Perspective

Purpose of Review

Cardiac magnetic resonance (CMR) has emerged in recent years as a reliable tool to assess, in a single examination after a reperfused myocardial infarction, the initially area at risk (AAR), the final infarct size (IS), and from their difference the salvaged myocardium (SM). The aim of the present review is to summarize recent advances in the CMR imaging of SM.

Recent Findings

While there is consensus on the use of late gadolinium enhancement (LGE) to calculate IS, how to assess the AAR is a debated topic. The use of T2-weighted short-TI inversion recovery (T2W-STIR) is to date supported by a large amount of data, but it is affected by several limitations. Newer techniques have been developed to overcome T2W-STIR limitations, some of them have been already used in randomized clinical trials (RCTs) while others are showing promising results. The use of CMR to generate surrogate endpoints in RCTs is gaining attention; in this context, analysis of data from recent RCTs suggests that the assessment of SM as outcome measure could be useful to reduce sample sizes and costs of trials.

Summary

CMR is a reliable technique for the assessment of SM. LGE is the gold standard for IS measurement, while which is the best technique for the evaluation of AAR is still debated. When using CMR-derived endpoints in RCTs, the assessment of SM is advisable.