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Adverse drug reactions represent a major public health problem, both from an economic point of view and, mainly, from the point of view of the induced pathology (iatrogenic diseases), being difficult to differentiate from other pathological conditions or even from the treated disease. Thus, these aspects prevent the use of the first-choice drugs needed for a particular treatment, in different therapeutic classes: beta-lactam antibiotics; sulfonamides; macrolide antibiotics; quinolones; non-steroidal anti-inflammatories; corticosteroids; Angiotensin converting enzyme (ACE) inhibitors; general anesthetics; biological drugs; antiepileptic drugs etc. On the other hand, adverse drug reactions represent a major problem for both clinical practice and preclinical research, in order to develop new drugs. Hypersensitivity reactions mainly refer to the adverse effects that can be harmful, disturbing, and sometimes fatal, that appear under the conditions of a normal immune system, including allergies and autoimmune reactions, both triggered by an immunological-allergic mechanism. The main purpose of this paper is to review the main classes of drugs involved in inducing hypersensitivity reactions.

Background/Aim: Vesico-uterine fistulas represent a rare type of genito-urinary fistulas; however, due to the increasing incidence of Caesarean section (C-section) in the last decade, this abnormal communication between the urinary and genital tracts has been reported more often after such surgical procedures. The aim of the current article was to report the case of a 28-year-old patient who was submitted to surgery for a vesico-uterine fistula seven years after a C-section. Case Report: The 28-year-old patient with a previous history of four vaginal deliveries and one C-section was self-presented to the Gynecology Department for cyclic hematuria and diagnosed with a vesico-uterine fistula after injecting methylene blue in the uterine cavity during hysteroscopy. The patient was further submitted to surgery, and a parcelar myometrectomy en bloc with parcelar cystectomy, cystography, and prophylactic salpingectomy was performed. The postoperative outcome was uneventful. Conclusion: Although vesico-uterine fistulas represent rare events, they should be considered, especially in young patients with a previous history of C-section.

Sarcoidosis is a multisystemic inflammatory disease of unknown etiology, characterized by noncaseous epithelioid cell granulomas. The evolution of the disease may be complicated by opportunistic infections such as aspergillosis, that usually appears in type IV sarcoidosis. We present the case of a 74 year-old women with a history of sarcoidosis for over 7 years, who presented for hemoptysis. She was diagnosed with pulmonary cavitary aspergillosis and treatment with ltraconazole was initiated. The patient was monitored every two months. At the one year follow up, the patient was asymptomatic, with a good treatment tolerance and no decline in lung function, despite the pulmonary fibrosis. The sputum exams continued to be positive for Aspergillus, the HRCT-scan described a chronic pulmonary aspergillosis. The antifungical treatment was continued, under careful monitoring. The patient remained asymptomatic with no further decline in lung volumes. The particularity of the case consists in the lack of symptoms, despite pulmonary fibrosis, and the therapeutic challenges of chronic pulmonary aspergillosis.

Positive pressure therapy (CPAP) in patients with cardiac arrhythmias and obstructive sleep apnea (OSAS) may have favorable effects by correcting intermittent hypoxemia and sympathetic activation.To assess the effect of CPAP added to pharmacological treatment in the rate control and prevention of arrhythmias recurrence in patients with OSA.Prospective, interventional study study which included patients diagnosed with OSAS (cardiorespiratorypolygraphy, AHI5/hour), and arrhythmias (ECG, Holter ECG), divided in two groups: group A (pharmacological therapy only) and group B (pharmacological therapy and CPAP). The patients were evaluated at enrollment (T0), at 3 and 6 months (T3 and T6) regarding the type, severity and recurrence of cardiac arrhythmias.36 patients (31 men), mean age: 63.2 ± 12 years were enroled. In group A: 7 patients with ventricular extrasystoles, 8 with permanent atrial fibrillation, 1 patient with atrial flutter and 2 patients with paroxystic supraventricular tachycardia. In group B: 8 patients with ventricular extrasystoles, 5 with permanent atrial fibrillation, 2 patients with recurrent episodes of atrial fibrillation and 3 with paroxystic supraventricular tachycardia. A positive correlation (r: 0.74, p0.001) between Oxygen Desaturation Index and AHI was found. At T6, 12 patients from group B, and 18 from group A were evaluated. In group B, the mean heart rate in patients with atrial fibrillation was 69/min., lower than in group A (82/min.), no cases with recurrent atrial fibrillation were found, and more patients with class II Lown ventricular extrasystoles passed in class I Lown, compared to group A. In group B, heart rate statistically correlated with AHI (r: 0.53, p0.005).In patients with OSAS, adding CPAP to pharmacological therapy has favorable effects on preventing recurrences, heart rate control in patients with atrial fibrillation and in reducing frequency and/or severity of ventricular extrasystoles.

Since 1989, grapefruit juice is reported to modify, with clinical implications, the pharmacokinetic of a series of drugs such as calcium channel blockers that are dihydropyridine derivates and/or some HMGCoA reductase inhibitors. All these drugs are metabolized to a large extent by the most abundant human isoform of cytochrome P450, CYP3A4. Grapefruit inhibits the cytochrome P450 3A4 enzyme system responsible for the oxidative metabolism of many orally administered drugs. The most important compounds of GFJ considered to be involved in the pharmacokinetic interaction are flavonoids (naringin, naringenin, narirutin, quercetin, kaempferol, hesperidin, neohesperidin, didymin, and poncirin), furanocoumarins (6',7'-dihydroxy-bergamottin, bergamottin, bergamottin-6',7'-epoxide, bergapten, epoxy-bergamottin) and sesquiterpens (noot-katone).The experimental researches had as object the comparative study of total content of flavonoidic compounds, like naringin in different fruit juices: citric fruit (white, pink and red grapefruit), apples, pears--industrial or laboratory prepared juices (by squeezing). They praised a different content in flavonoidic compounds for citric and for the rest of analyzed fruits.For grapefruit juices the concentrations in flavonoidic compounds are higher in total fruit juice: 143.86 mg/100 mL in red, 131.47 mg/100 mL in pink and 84.21 mg/100 mL in white grapefruit juice. In juice prepared from fruit pulp, the concentrations were 81.92 mg/100 mL, 108.23 mg/100 mL and 65.76 mg/100 mL, respectively. The content in naringin, the most important flavanone in citrus fruit, varied between 1.98 and 51.2 mg/100 mL juice.

During the virus C infection the presence of cirrhosis is the major risk factor for the development of hepatocellular carcinoma. In the absence of cirrhosis the estimated prevalence hepatocellular carcinoma ranged from 6.7% to 50.1%. We present the case of a 64 year-old-man admitted to the hospital with 3-days history of nespecific symptomatology. Screening abdominal ultrasound showed an enlarged liver with 4 parenchimatous nodules in the right lobe and malignant thrombosis of the inferior vena cava. Chest CT revealed multiple metastasis in both lungs and left pulmonary arterial thrombosis. The patient died 5 weeks later. The particularity of the case is the presence of the end-stage hepatocellular carcinoma in a patient with asymptomatic C virus infection.

Context. The complex of symptoms in pancreatic cancer is vague, which often delays presentation and diagnosis. Thrombophlebitis is an unusual presentation of pancreatic cancer, which appears more frequent in the cancer of the body and tail of the pancreas. Case report. We present a case of a 52–years–old woman who was admitted to the hospital for a superficial thrombophlebitis. At the abdomen ultrasound screening, multiple liver masses, relatively well defined, with a hypo–echoic center and a hyper–echoic periphery, were identified. The head of the pancreas was normal, the body and the tail could not be seen very well due to flatulence. After computed tomography, the diagnosis was ‘Pancreatic tumor with multiple hepatic metastases (stage Ⅳ)’. After the histopathological examination, 1,250mg/m2 of Gemcitabine was started on day 1 and 8 every 28 days, plus 100mg/day of Erlotinib (Tarceva), every day. At the end of the seventh month of treatment, the patient suffered an irreversible ischemic cardiac event. Conclusion. Superficial thrombophlebitis can be the initial manifestation of the pancreatic cancer. Gemcitabine and erlotinib is now a FDA approved regimen for patients with metastatic pancreatic cancer. While the search for the best gemcitabine based backbone for advanced pancreatic cancer continues, studies of anti–angiogenic agents alone or in combination with traditional chemotherapy, should be undertaken, as they may improve overall survival in this group of poor prognosis patients.