Combined interferon and vinblastine treatment of advanced melanoma: evaluation of the treatment results and the effects of the treatment on immunological functions

Summary Thirteen patients with metastatic malignant melanoma received interferon -2a (Roferon-A) and vinblastine. The interferon dosage was increased from 3×10⁶ IU to 9×10⁶ IU daily in 10 weeks and thereafter 9×10⁶ IU was administered three times weekly intrasmuscularly. Vinblastine (0.075–0.15 mg/kg) was given every third week intravenously. One of the ten evaluable patients had partial remission (PR) (11%) for 10 months. The diseases was stabilized (NC) in three patients (30%) for 3, 6 and 9 months. Progression (PD) occurred in six patients. The treatment time varied from 5 weeks to 44 weeks. The median survial time from the beginning of this combination treatment was 5 months. The most common side-effects were fever, fatigue, loss of taste, weight loss and neutropenia.The mitogen response to phytohemagglutinin and purified protein derivative of tuberculin decreased in all patients. The response to concanavalin A decreased less and began to increase again in the patients with PR and NC. The natural killer cell activity in PD patients decreased more than in the patients with PR and NC. The ratio of T4/T8-positive cells was restored in PR + NC patients but rose in PD patients indicating a difference in the immunomodulatory effect of the combination or of the advanced disease itself on T-cell function in PD patients.This combination of daily interferon and vinblastine did not prove to be effective in melanoma. The depression of immunological functions, which was more marked in patients with PD, might indicate that vinblastine in this combination counteracts the immunostimulatory effect of interferon.     

Surgical treatment of the epicanthal fold

A surgical technique is described for the correction of the epicanthal fold. Indications for its use are noted and emphasis is placed on its advantages. The procedure is simple to perform and uniformly gives good results.     

Placebo in the treatment of pain

Placebo is the use of the substance or procedure without specific activity for the condition that is trying to be healed. In medicine, benefits of placebo effect are used since 1985 and 1978 placebo effect was first scientifically confirmed. It was found that placebo induced analgesia depends on the release of endogenous opiates in the brain and that the placebo effect can be undone using the opiates antagonist naloxone. Functional magnetic resonance imaging of the brain showed that placebo analgesia was obtained regarding the activation and increased functional relationship between ant. cingulate, prefrontal, orbitofrontal, and insular cortex, nucleus accumlens, amygdala, periaqueduktalne gray matter and spinal cord. Placebo also facilitates descending inhibition of nociceptive reflexes through periacvaeductal gray substance. Placebo effect can be achieved in several ways: by using pharmacological preparations or simulation of operating or other procedures. This phenomenon is associated with perception and expectation of the patient. To achieve the effect of placebo it is essential degree of the suggestions of the person who prescribe a placebo, and the degree of belief of the person receiving the placebo. Expected effect of placebo is to achieve the same effect as the right remedy. Achieved placebo effect depends on the way of presentation. If a substance is presented as harmful, it may cause harmful effects, called 'nocebo" effect. Placebo effect is not equal in all patients, same as the real effect of the drug is not always equal in all patients. Application of placebo in terms of analgesia will cause a positive response in 35% of patients. Almost the same percentage (36%) of patients will respond to treatment with morphine in medium doses (6-8 mg). Therefore, one should remember that response to placebo does not mean that a person simulates the pain and then it is unethical to withhold the correct treatment especially in light of findings that the prefrontal cortex is activated expecting liberation of pain and how this action reduce activities in brain regions responsible for sensation of pain (thalamus, somatosensory cortex and other parts of the cortex). However, the use of placebos is ethically, legally and morally very dubious. The basis for the placebo effect is deception. It undermines honest relationship and trust between doctor and patient which is extremely important for successful treatment. Consciously giving placebos to patients for a condition that can be adequately treated, with prejudice the right of patients to the best care possible, opens up many bioethical issues. Despite all the current knowledge level, placebo effect remains still a scientific mystery.     

Immunotherapy in the treatment of lymphoma

Relapsed or refractory non-Hodgkin's lymphomas, especially diffuse large B-cell lymphoma as well as relapsed or refractory Hodgkin lymphomas are hard-to-treat diseases. Patients who do not respond to initial therapy or experience relapse are treated with salvage regimens, and if eligible for aggressive therapy, treatment is continued with high-dose chemotherapy and autologous stem cell transplantation. Current therapy options can cure substantial numbers of patients, however for some it is still an uncurable disease. Numerous new drugs and cell therapies are being investigated for the treatment of relapsed or refractory lymphomas. Different types of immunotherapy options have shown promising results, and some have already become the standard of care. Here, we review immunotherapy options for the treatment of lymphoma and discuss the results, positions, practical aspects, and future directions of different drugs and cellular therapies for the treatment of this disease.