Review on special emphasis of bortezomib on relapsed/refractory myeloma

Refractory or relapsed Multiple Myeloma (MM) is a plasma cell neoplasia characterized by paraproteins in the urine or serum and a bone marrow plasmacytosis of over 10%. Multiple/refractory myeloma is a neoplasm of plasma cells and exact cause of multiple myeloma is remain unidentified, it is characterized by accumulation of malignant plasma cells in the bone marrow, leading to bone marrow failure, anemia, skeletal destruction, renal failure, increased susceptibility to infection and hypercalcemia. The survival time for the patients with refractory or multiple myeloma can be prolonged with treatment of newer and more target specific approach. The proteasome inhibitors are an important class of anti-myeloma drugs that have efficacy to disrupt the proteolytic structure of tumor cells and enhancing their susceptibility to apoptosis. Bortezomib has a significant clinical efficacy against refractory multiple myeloma. Bortezomib is the most commonly used and clinically tested proteasome inhibitor and which is effective in prolonging the overall survival in several trials. Bortezomib combinations with other drugs such as dexamethasone and cyclophosphamide are the choice of treatment for standard risk patients following the mSMART guidelines. The success with lower dosage of bortezomib in elderly patient’s proven efficacious subcutaneous usage and its useful proteasome inhibitor to enhance patient’s compliance and reduces toxicity and costs of therapy. This review discusses on special emphasis of bortezomib on relapsed/refractory multiple myeloma as front-line treatment.

First time pregnant women's experiences in early pregnancy

Background: There are few studies focusing on women's experiences of early pregnancy. Medical and psychological approaches have dominated the research. Taking women's experiences seriously during early pregnancy may prevent future suffering during childbirth. Aim: To describe and understand women's first time experiences of early pregnancy. Method: Qualitative study using a phenomenological hermeneutic approach. Data were collected via tape-recorded interviews in two antenatal care units in Sweden. Twelve first time pregnant women in week 10–14, aged between 17 and 37 years participated. Results: To be in early pregnancy means for the women a life opening both in terms of life affirming and suffering. The central themes are: living in the present and thinking ahead, being in a change of new perspectives and values and being in change to becoming a mother. Conclusions: The results have implications for the midwife's encounter with the women during pregnancy. Questions of more existential nature, instead of only focusing the physical aspects of the pregnancy, may lead to an improvement in health condition and a positive experience for the pregnant woman

Defining the characteristics and expectations of fluid bolus therapy : A worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes. (C) 2016 Elsevier Inc. All rights reserved.Peer reviewe

Defining the characteristics and expectations of fluid bolus therapy: a worldwide perspective

Purpose: The purpose of the study is to understand what clinicians believe defines fluid bolus therapy (FBT) and the expected response to such intervention. Methods: We asked intensive care specialists in 30 countries to participate in an electronic questionnaire of their practice, definition, and expectations of FBT. Results: We obtained 3138 responses. Despite much variation, more than 80% of respondents felt that more than 250 mL of either colloid or crystalloid fluid given over less than 30 minutes defined FBT, with crystalloids most acceptable. The most acceptable crystalloid and colloid for use as FBT were 0.9% saline and 4% albumin solution, respectively. Most respondents believed that one or more of the following physiological changes indicates a response to FBT: a mean arterial pressure increase greater than 10 mm Hg, a heart rate decrease greater than 10 beats per minute, an increase in urinary output by more than 10 mL/h, an increase in central venous oxygen saturation greater than 4%, or a lactate decrease greater than 1 mmol/L. Conclusions: Despite wide variability between individuals and countries, clear majority views emerged to describe practice, define FBT, and identify a response to it. Further investigation is now required to describe actual FBT practice and to identify the magnitude and duration of the physiological response to FBT and its relationship to patient-centered outcomes.Facultad de Ciencias Médica

An evaluation of serial blood lactate measurement as an early predictor of shock and its outcome in patients of trauma or sepsis

Context: Attainment of hemodynamic parameters to within a normal range may leave patients in compensatory shock. In such patients, serial blood lactate evaluation can be useful in predicting shock. Aims: To ascertain the role of serum lactate as a predictor of shock and its outcome in patients of trauma and sepsis. Settings and Design: A prospective, non-interventional study. Materials and Methods: The study included 50 patients (5 to 60 years old) of trauma admitted within 12 hours of injury and patients of suspected or proven sepsis. Those with chronic medical illnesses, alcohol intoxication, or poisoning were excluded. Blood lactate levels were analyzed at admission and 12, 24, and 36 hours of inclusion with records of corresponding hemodynamic variables, investigations, and interventions. The outcome was recorded as survival or non-survival. Statistical Analysis Used: Statistical analysis was done with a student′s t test and repeated measure ANOVA (Analysis of Variance). Results: An analysis revealed higher mean lactate levels in non-survivors as compared with survivors. Mean lactate levels in non-survivors did not attain normal levels, while that of survivors reached normal levels by 24 hrs in trauma patients and 36 hrs in sepsis patients. The predicted mortality rates by a lactate level> 40 mg/dl at admission, 12, 24, and 36 hours were 52.6%, 61.5%, 83.3%, and 100%, respectively for both the subgroups combined. Non-survivors had a higher incidence of MODS (Multi Organ Dysfunction Syndrome). Conclusions: Serial lactate values followed over a period of time can be used to predict impending complications or grave outcome in patients of trauma or sepsis. Interventions that decrease lactate values to normal early may improve chances of survival and can be considered effective therapy. Lactate values need to be followed for a longer period of time in critical patients

An evaluation of serial blood lactate measurement as an early predictor of shock and its outcome in patients of trauma or sepsis

Context: Attainment of hemodynamic parameters to within a normal range may leave patients in compensatory shock. In such patients, serial blood lactate evaluation can be useful in predicting shock. Aims: To ascertain the role of serum lactate as a predictor of shock and its outcome in patients of trauma and sepsis. Settings and Design: A prospective, non-interventional study. Materials and Methods: The study included 50 patients (5 to 60 years old) of trauma admitted within 12 hours of injury and patients of suspected or proven sepsis. Those with chronic medical illnesses, alcohol intoxication, or poisoning were excluded. Blood lactate levels were analyzed at admission and 12, 24, and 36 hours of inclusion with records of corresponding hemodynamic variables, investigations, and interventions. The outcome was recorded as survival or non-survival. Statistical Analysis Used: Statistical analysis was done with a student′s t test and repeated measure ANOVA (Analysis of Variance). Results: An analysis revealed higher mean lactate levels in non-survivors as compared with survivors. Mean lactate levels in non-survivors did not attain normal levels, while that of survivors reached normal levels by 24 hrs in trauma patients and 36 hrs in sepsis patients. The predicted mortality rates by a lactate level> 40 mg/dl at admission, 12, 24, and 36 hours were 52.6%, 61.5%, 83.3%, and 100%, respectively for both the subgroups combined. Non-survivors had a higher incidence of MODS (Multi Organ Dysfunction Syndrome). Conclusions: Serial lactate values followed over a period of time can be used to predict impending complications or grave outcome in patients of trauma or sepsis. Interventions that decrease lactate values to normal early may improve chances of survival and can be considered effective therapy. Lactate values need to be followed for a longer period of time in critical patients

2-(Quinolin-4-ylthio)-1,3,4-oxadiazole derivatives: Design, synthesis, antibacterial and antifungal studies

1318-1324A series of novel <span style="mso-bidi-font-weight: bold">hybrid 2-(7-chloroquinolin-4-ylthio)-5-(substituted)-1,3,4-oxadiazole derivatives have been designed, synthesized which contains different pharmacophores like quinoline and 1,3,4-oxadiazole linked via sulfur atom. All the newly synthesized derivatives have been characterized by IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, All the final synthesized scaffolds have been subjected to in vitro antimicrobial activity against several bacteria (E.coli<span style="mso-bidi-font-weight: bold">, P.aeruginosa, S.aureus, S.pyogenus) and fungi (C.albicans, A.niger, A.clavatus) using broth dilution technique. Among the compounds tested, compounds 3f substituted with coumarin analogue and 3b with amine group at second position of phenyl to oxadiazole moiety are found to be most potent. </span