Role of microRNAs in fluoropyrimidine-related toxicity: what we know.

Although more than half a century has passed since the discovery of fluoropyrimidines, they are still used in the treatment of many types of cancer, and it is estimated that annually two million patients undergo fluoropyrimidine-based chemotherapy. The toxicity resulting from the use of fluoropyrimidines affects about 30-40% of patients, which in some cases may prove to be lethal. The key player in fluoropyrimidine toxicity is DPD activity, and patients with deficits are more likely to develop significant adverse events. In addition to genotyping DPYD variants associated with DPD deficiency, overexpression of miR-27 has also been shown to be a predictive factor for fluoropyrimidine toxicity. This review aims to relate what we know so far about the involvement of miRNA in fluoropyrimidine toxicity and to open new perspectives in this field.

The Significance of Right Ventricle in Young Subjects with Diabetes Mellitus Type 1. An echocardiographyic study.

BACKGROUND: Diabetes mellitus type 1 (DM1) is associated with high risk for cardiovascular disease and early detection of myocardial dysfunction is very important for the prevention of cardiac complications. Although the functionality of right ventricule is important in a lot of disease affecting long time prognosis and progression, in diabetic type 1 patients has not been studied in depth yet. OBJECTIVES: To evaluate the right ventricular function by using both conventional echocardiography as well as speckle tracking echocardiography (STE) in young adults with diabetes mellitus type 1. METHODS: We included 60 young asymptomatic adults diagnosed with diabetes mellitus type 1 (mean interval from diagnosis 9±6 years) and 90 healthy controls. Conventional and STE Echocardiography was acquired using the GE Vivid S60 equipment. The longitudinal right ventricular strain 6 segments (RV GLS global) and 3 segments (RVFW GLS) of right ventricle (RV GLSbazal, RV GLSmid, RV GLSapex) as well were obtained using the EchoPAC BT13 workstation. RESULTS: No significant intergroup differences in EF were noted. Conventional echocardiographic parameters revealed lower tricuspid annular velocities Et, At and Et/At ratio compared to controls suggesting a diastolic disfunction in diabetes group. RV speckle tracking strain measurements showed no significant difference between the groups. CONCLUSIONS: Young adults with type 1 diabetes mellitus and without known heart disease have diastolic right ventricular dysfunction. The subclinical myocardial systolic function is preserved in early stages.

Histopathological and Morphometric Study of Fibrosis and Nuclear Pleomorphism in Dilated Cardiomyopathy.

Histopathological changes associated with dilated cardiomyopathy (CMD) are frequently nonspecific and often only present in the terminal stage of the disease. The study followed the histopathological and morphometric quantification of fibrosis and nuclear pleomorphism in CMD. We analyzed left ventricle myocardial fragments harvested during autopsy, from 35 cases with clinical diagnosis of CMD and 5 cases of normal myocardium. Fibrosis was present in all CMD cases, with higher values compared with control cases. Nuclear pleomorphism was identified in 18 cases (45%), two of the analyzed parameters, respectively the ratio of nuclear diameters and roundness of nucleus, revealing significant differences in CMD compared to the control cases. Myocardial fibrosis present in all cases of CMD represents a major feature of the disease. The nuclear pleomorphism due to the nuclei change in diameters and size was more pronounced in the vicinity of fibrosis areas, possibly related to this alteration.

Marfan Syndrome - Acute Aortic Dissection Due to Giant Aortic Aneurysm.

Marfan syndrome is a genetic disorder with an estimated prevalence of 1/5000 births. Clinical manifestation and disease progress can vary among individuals affected therefore serial follow-up examinations are mandatory in order to prevent serious complications.We report a case of giant proximal aorta aneurysm with associated aortic dissection in a young patient with Marfan syndrome who neglected medical advice to undergo periodic medical evaluation.Given the fact that clinical manifestations may differ among patients making prediction of disease progression very difficult, the patient with Marfan syndrome should be carefully monitored.

Echocardiographic Parameters in Acute Pulmonary Edema.

PURPOSE: The present study proposes the comprehensive ultrasound evaluation of a consecutive batch of patients with acute cardiogenic pulmonary edema. METHOD: The registry included all patients with acute pulmonary edema from 2 emergency hospitals between February and May 2016. During the first 3 days of admission, a transthoracic ultrasound was performed which included the parameters of systolic and diastolic function of the left ventricle, right ventricular systolic function, heart cavity dimensions, estimated pulmonary pressure, and the presence and severity of valvular disease. RESULTS: A total of 70 patients were enrolled in the registry. The mean ejection fraction of the left ventricle was 39.5±11.4% and the average indexed end-diastolic volume was 77.7±29.5ml/m⊃2, above the upper limit of normal. All patients in whom diastolic function could be evaluated had a degree of diastolic dysfunction. Functional parameters of the right ventricle were normalized as average, and the mean pulmonary artery pressure was increased: 40.9±16.7mmHg. The most common valvular heart disease were mitral and tricuspid insufficiency, with moderate or severe impairment in 82.8%, respectively 65.7% of the patients.

Atrial fibrillation recurrence predictors after conversion to sinus rhythm.

PURPOSE: We aimed to identify predictors of atrial fibrillation recurrence after conversion to sinus rhythm. MATERIAL/METHODS: We included 100 patients with a history of documented atrial fibrillation in the last 12 months that were assessed by transthoracic echocardiography, 12-lead electrocardiogram and signal averaged electrocardiogram of the P wave. Follow-up was 7.3 ± 2.2 months. RESULTS: Atrial fibrillation recurrence was documented in 27 patients. It was more frequent in patients with longer duration of previous atrial fibrillation episode, with increased left atrium size and left ventricular mass, and it was correlated with the filtered P wave duration and Integral of the P wave. CONCLUSIONS: Signal averaged ECG of the P wave, left atrium size and left ventricular mass determined by echocardiography could be helpful in predicting the risk of atrial fibrillation recurrence after conversion.

Post-myocardial infarction arrhythmia risk stratification using microvolt T-wave alternans.

Since its initial description, a number of studies have described the use of microvolt T-wave alternans (MTWA) as a predictor of the primary or secondary occurrence of ventricular arrhythmic events. These studies, however, have been limited by small sample sizes and disparate patient populations. Studies of MTWA in post-myocardial infarction (MI) patients are few in number, but hold predictive value for risk of ventricular arrhythmias. We performed a study of MTWA in post-myocardial infarction patients to clarify the predictive accuracy and usefulness of MTWA compared to other invasive and non-invasive techniques. We enrolled 120 patients (74 men, 46 women, mean age 62.3 ± 15.2 years in men, and 64.2 ± 13.8 years in women) with a history of myocardial infarction but no prior sustained ventricular arrhythmias. Patients were assessed by echocardiography, Holter, signal averaged ECG, MTWA, and electrophysiology study. Mean follow-up was 14 months. The MTWA test had a good negative predictive value for arrhythmic events in post-MI patients and can be used for risk stratification. We consider that in patients with positive MTWA further invasive evaluation, respectively electrophysiology study, is necessary.

Aliskiren-based stepped-care treatment algorithm provides effective blood pressure control.

AIMS: Recent guidelines for the management of hypertension recommend an individualised stepped-care treatment approach in mild-to-moderate hypertensive patients, to achieve blood pressure (BP) goals. This study evaluated the probability of patients achieving BP targets with an aliskiren-based stepped-care treatment regimen. METHODS: This was a 24-week, open-label, non-comparator study design that included six sequential 4-week treatment periods in patients with mild-to-moderate hypertension. Over the potential 24 weeks of active treatment, incremental therapy included the following add-on therapies at 4-week intervals: aliskiren 150-300 mg once daily, hydrochlorothiazide (HCTZ) 12.5-25 mg once daily, and finally amlodipine 5-10 mg once daily, as needed to achieve target BP. Subjects achieving BP targets following any given 4 weeks of therapy were considered study completers, while subjects not achieving their clinical BP target entered into the next step of incremental therapy. The primary efficacy end-point was the estimated cumulative probability of patients achieving BP target. RESULTS: Of 256 patients treated, 232 (90.6%) completed the study. Baseline mean sitting BP was 155.7/91.7 mmHg. At study end-point, the estimated cumulative probability of reaching BP target was 86.12%. The stepped-care treatment regimen was well tolerated at the maximal recommended doses of all the individual complimentary therapies. CONCLUSION: An aliskiren-based stepped-care treatment regimen that subsequently included both HCTZ and amlodipine is effective in achieving BP goals in approximately 90% of patients with mild-to-moderate hypertension.

Holt-Oram syndrome.

The Holt-Oram syndrome or atriodigital dysplasia is an autosomal dominant disorder with near complete penetrance and variable expression, caused by mutations of the TBX5 gene (12q24.1), affecting one in 100 000 live births. 60% of cases are familial and 40% sporadic. We present the case of a 24 years old male patient with a personal history of bilateral coxa vara surgically corrected on the right at the age of 8 years, complicated by osteochondritis, short stature (160 cm), underweight (37 kg, BMI 14.45 kg/cm(2)), triangular face, micrognathia, down slanting palpebral fissures, hypertelorism, low set ears, scoliosis, narrow shoulders, shortened left arm, left thumb agenesia, limited supination, abnormal toes, hypoplastic muscles, atrial septal defect ostium secundum type, incomplete right bundle branch block, hypoacusia and normal intelligence.

Diabetes mellitus and Turner syndrome.

Noninsulindependent diabetes mellitus is 2-4 times more prevalent in Turner subjects as compared to normal females, and tends to develop at a younger age, but it is usually mild and responsive to weight loss or monotherapy. The primary pathogenic event is beta cell dysfunction, but insulin resistance also plays a central role and is worsened by the presence of hypertension, obesity and dyslipidemia which are common in Turner syndrome. We present the case of a 30 year-old female patient with short stature, 141cm (<-- 2.5 SD), overweight 51kg, waist circumference 79cm, triangular facies, downslanting palpebral fissures, low set ears, short neck, secondary amenorrhea, palpitations, a history of polyuria, polydypsia of three months duration and a fasting morning glucose of 260 mg/dL. Cardiac and renal defects were excluded, hormonologic evaluation was consistent with hypergonadotropic hypogonadism (FSH 65 mUI/mL) and primary hypothyroidism (TSH 5.68 microUI/mL) and karyotype was 45,XO. She also had hypercholesterolemia (247 mg/dL), hypocalcemia (8 mg/dL), mild elevation of hepatic enzymes (ALAT 51 U/L) and osteopenia (Tscore--2.22). Glycaemic control was achieved with diet only; therapy consisted of hormone replacement theraphy, thyroxine and beta blockers.

Ellis-van Creveld syndrome.

Ellis-van Creveld syndrome is a rare autosomal recessive disorder caused by mutations in the EVC and EVC2 gene (4p16), characterized by chondrodystrophy, postaxial polydactyly, ectodermal dysplasia and cardiac anomalies. We present the case of a 24 years old female patient with unaffected parents and an affected sister, with a personal history of surgically corrected postaxial polydactyly of both hands and atriventricular canal. Clinical features were: a marked acromesomelic short stature (135 cm height), narrow thorax, genu valgum, club feet, brachydactyly, malposed toes, hypoplastic nails and teeth, diffuse alopecia, atrioventricular canal, hypoplastic mammary glands and a small goiter. Radiologic evaluation revealed short metacarpals and phalanges, capitat and hamat fusion on the left, left ulnar epiphysis with areas of osteolysis and osteocondensation, genu valgum, short fibulae, narrow thorax, cardiac enlargement with hilar congestion. Echocardiogram showed absence of the atrial sept and the basal portion of the ventricular sept and electrochardiogram--right bundle branch block, left anterior fascicular block and left ventricular hypertrophy. Free thyroxine, TSH and usual laboratory parameters were in the normal range with exception of ionic calcium which was low (3.8 mg/dL).

[The exacerbating role of the vascular factor in the evolution of open-angle glaucoma]. / Rolul agravant al factorului vascular în evolutia glaucomului cu unghi deschis.

UNLABELLED: The paper proposes to study the ophthalmic and carotid circulation of patients with primary open-angle glaucoma in varied stages of evolution. MATERIAL AND METHOD: The lot is formed by 8 patients with primary open-angle glaucoma, selected such that one eye to be absolute or quasiabsolute and the congener eye in incipient stage. The average (medium) age is 64 years, the patients having blood pressure within normal limits. The study of ophthalmic and carotid circulation was made by echo-Doppler and the calcul of velocimetric indices. RESULTS: The resistance index is increased in concordance with the stage of glaucoma. The diastolic flux is the most serious affected. There is no parallelism between the blood pressure value and the grade affectation of velocimetric indices. CONCLUSIONS: The local vascular diseases, ophthalmic and carotid, influence unsatisfactory the evolution of primary open-angle glaucoma.

[Genetic predisposition in glaucoma]. / Predispozitia genetica în glaucom.

The comparative study of the genetic factors implication in low-tension and high-tension glaucoma showed the presence of glaucoma familial cases in both form. In 3 cases of low-tension glaucoma the presence of other familial cases of high-tension glaucoma was revealed. The existence of hereditary cases of high-tension glaucoma in families with low-tension glaucoma suggests the existence of some common factors, responsible for producing both affections. On the other hand, the systematic research of the existent glaucomatous deficits at the patients with glaucoma familial cases deserves greater attention.

[Chronic tuberculous iridocyclitis]. / Iridociclita tuberculoasa cronica.

One patient is seventy-one years old, diagnosed four years ago with latero-cervical ganglionic tuberculosis, presents approximately one year and half, progressive loss of the vision in both eyes, predominant in the left-eye; for several months periocular pains referred to the left hemicranial field are presented. Ocular exam: visual acuity was 1/100 in the right eye and perception movements of the hand in the left eye: intraocular pressure was 28 mmHg in the right eye and 8 mmHg in the left eye: perikeratic congestion, chemosis, pigmented precipitates on the posterior face of the corneo, iris in "umbrella", seclusion and occlusion of the pupillary at the left eye, posterior synechiae at the right eye were noted. The eye ground exam is not possible due the pupillary partial seclusion at the right eye and the pupillary seclusion-occlusion at the left eye. The general exam releaves several latero-cervical keloid scars and pronounced dysphonia. Laboratory exam: IDR of the tuberculin was high positive, chest radiography shows hilar bilateral calcifications, ORL exam shows a tumor at the foot of the epiglottis and anatomopathological exam shows low differentiated epidermoid carcinoma. Using the anamnestic dates, clinical and paraclinical exams, we established the diagnosis: chronic tuberculosis iridocyclitis with pupillary seclusion and occlusion at the both eyes; secondary glaucoma at the right eye: latero-cervical ganglionic tuberculosis: epidermoid laryngeal carcinoma.

[Adenocarcinoma of the meibomian gland with invasion of the orbit]. / Adénocarcinome de la glande de Meibomius avec invasion de l'orbite.

Adenocarcinoma of the meibomian glands is a tumor with atypical glandular features, that appear initially as a chalazion formation and then invades the neighbouring tissues. The patient, a 63 years old woman, presents a chalazion at the level of the left lower eyelid, which, after developing for a year, stars bleeding and infiltrates the ground of the inferior sac and the orbit. The tumoral formation makes a common body with the eyeball and the cornea, which, lacking protection, becomes opaque. Removal of the ulcerous eyelids is performed, with partial exenteration of the orbit. Anatomopathological investigation show the diagnosis: adenocarcinoma of the meibomian glands. Adenocarcinoma of the meibomian glands is the most malignant palpebral tumor. The signs of malignity are: infiltrated and relapsing aspect of the chalazion in on aged person, with low sebaceous secretion in the presence of pigmentations and bleedings in the tumor.

[Malignant palpebral tumors. Comments on 111 cases]. / Tumori maligne palpebrale. Consideratii privind 111 cazuri.

During 1991-1995, 111 patients with palpebral malignant tumours were hospitalized. They represented 15% of the face malignant tumours. The maximal incidence was mentioned after the age of 60 years, only 21 patients were under 60 years of age. The most cases (88) were located at the level of inferior eyelid and internal canthus. From an anatomo-pathological point of view, 88 cases were baso-cellular epitheliomas, 10 were spino-cellular epitheliomas. 1 case was malignant melanoma and 1 case was adenocarcinomas of Meibomius gland. In 30% of the cases the patients come lately. The surgery of palpebral neoplasm requires both an oncological-oriented operation and a plastic-reparatory operation; the reparatory operations using free or pedicled grafts [correction of pediculate graphs] are presented.

[Post-varicella keratoendothelitis]. / Cheratoendotelita postvaricela.

The female patient, convalescent after varicella, presented in the tenth day after disappearance of the cutaneous eruption the first ocular symptoms with perikeratic congestion, endothelial precipitations, folds of the Descemet membrane, thick stroma, endothelial edema with appearance like keratoendothelitis. Ocular manifestations in varicella are produced through sanguine circulation of the virus like a varicella uveitis. The paper insists on various ocular manifestations in varicella.