The Differentiation of Intestinal-Failure-Associated Liver Disease from Nonalcoholic Fatty Liver and Nonalcoholic Steatohepatitis.

Intestinal failure-associated liver disease (IFALD), formerly known as parenteral nutrition-associated liver disease has often been listed in textbooks as an example of nonalcoholic fatty liver disease (NAFLD). However, the etiology, pathophysiology, epidemiology, histology, and progression differ substantially between the conditions defined as NAFLD and the disease, IFALD. Therefore, IFALD should not be defined or considered as a type or a cause of nonalcoholic fatty liver or nonalcoholic steatohepatitis, but rather as a distinct disease.

Development of a general and efficient iron-catalyzed epoxidation with hydrogen peroxide as oxidant.

The development of inexpensive and practical iron catalysts for the environmentally benign epoxidation of olefins with hydrogen peroxide as terminal oxidant is described. By systematic variation of ligands, metal sources, and reaction conditions, it was discovered that FeCl3 x 6 H2O in combination with pyridine-2,6-dicarboxylic acid and different amines shows high reactivity and excellent selectivity towards the epoxidation of aromatic olefins and moderate reactivity towards that of aliphatic olefins.

Using teams and committees effectively.

In a corporate setting, the term "team" usually refers to members of a group with different responsibilities and/or skills working together to achieve a common goal or objective. The major reason why a company desires group as opposed to individual involvement is to derive sounder decisions. Two essential issues to resolve in establishing teams or committees are 1) who should be a member or representative; and 2) what is the charter or mandate for the group.

The many faces of reality.

Reality has many faces, depending on who is judging or describing a situation or event. A person's view of reality is strongly influenced by his or her perceptions, values, biases and beliefs, and reality is therefore a relative term. Even the ability to determine the reality of an object through objective instruments and measures is limited.

Developing a pharmaceutical perspective.

A variety of focuses are used in this article to discuss four types of perspectives; these focuses are self, others, drugs/issues and company/industry. There is a hierarchy of concern about the topics one deals with. This hierarchy ranges from identifying whether there is a question to address or whether the topic is more serious and there is an issue to consider.

Creating standards for basic, medical and market research.

Different types of standards that can be created are ideal, realistic, desirable and minimally acceptable. A different approach to viewing types of standards is to view them as existing along a spectrum from very formal to informal. Basic research, medical research and market research can each develop and use standards that are entirely formal or informal or that exist at any stage along that spectrum.

Differentiating between current fashions and major innovations.

Every professional discipline has current fashions. Certain ideas or topics are promoted by those who are most closely associated with the idea. These people often have a great deal to gain when ideas are accepted.

Applying pharmaceutical lessons: learning lessons from the past.

Systematic evaluation of a project, product or other successes, and failures, is an important method for improving the performance of a company, as well as that of an individual. One should evaluate and determine if lessons learned can be applied to the systems and procedures being used in the company. Even if the company does not have to adjust its strategies, procedures, portfolio or systems as a result of lessons it has learned, there may be pointers to communicate to staff.

The importance of pharma sense and pharma think.

Pharma sense refers to a general understanding of pharmaceutical principles and concepts. Pharma think is an active process that occurs when a person uses his or her pharma sense to think about a question, issue or problem and identifies a solution, an action plan or series of options. As a direct result of greater use of pharma sense and pharma think, the quality of decisions made in a company will increase.

Quality and quantity of data.

When collecting data, deciding what type and how much to obtain will depend in large measure on how the data will be used and the group(s) that will be given the data, as well as the risk-taking or risk-averse position adopted. Among the most important issues involving the quality of data are knowing what plans and activities will lead to obtaining high-quality data and recognizing whether the data obtained achieve one's goals. Factors to consider in deciding on the quality and quantity of data to collect include the following: robustness of data required for extrapolatability; potential use of the data; degree of bias that is acceptable; the quantity of data that must be collected in a study or trial which must be considered separately from the quantity to be submitted in a regulatory dossier; practicality of the study; cost of the study; and time available and necessary to complete the study.

Reducing pharmaceutical risk.

This article describes several types of risk encountered in drug discovery, development and marketing, as well as the overall business risks in the pharmaceutical industry. Discovery risk refers to the risk companies face if they are partly or totally dependent on discovering new drugs; many avenues are presented for companies to pursue in order to decrease discovery risk. Development risk is defined as the risk that drug discoveries that enter development will not reach the market and become commercially viable drugs.

Pharmaceutical tangents: the good, the bad and the ugly.

In this article a "tangent" means a change from the plans or path one has agreed to follow in drug discovery, development, production or marketing. There are positive and negative tangents. It is important for companies to have a method for approving tangents in a systematic way.

Teaching courses in clinical trial research methods.

This article describes nine separate elements that are part of any course: 1) the teachers, 2) the students, 3) expectations and attitudes of the teachers, 4) expectations and attitudes of the students, 5) a strategy of how to achieve the expectations, 6) materials to use, 7) types of presentations, 8) organizing the individual sessions, and 9) time and place for the course and each of its sessions. The relationship of each of these elements to a course on clinical-trial research methods is discussed. Approaches to use for designing an overall curriculum for a school, company, or regulatory authority also are discussed.

Validation of the phenomenon of regression of seizure frequency in epilepsy.

A phenomenon known as regression of seizure frequency toward the median was observed in a previous clinical study performed in patients with partial seizures. Regression of seizure frequency is a situation in which patients with a frequency of seizures above the median value for the group during an initial period have a tendency to have frequency of seizures decrease during a subsequent period, and other patients with a lower frequency of seizures during the initial period increase their frequency during a subsequent period. To investigate this further, eight published sets of clinical data obtained in epileptic patients with various seizure types were identified by a literature search.

A double-blind crossover study of cinromide versus placebo in epileptic outpatients with partial seizures.

Cinromide was evaluated versus placebo as add-on therapy in a double-blind crossover study in epileptic outpatients with partial seizures at three sites. Four-week base lines were used before, between, and after the two 12-week treatment periods of the crossover. An operational definition was used to classify each partial seizure as Type A, B, or C.

Drug interference with measurement of metanephrines in urine.

The influence of 35 commonly used drugs on measurement of metanephrines in urine was evaluated. Two concentrations of drugs were chosen for study based on usual doses and the percent of dose excreted unchanged in the urine. At "medium" drug concentrations, only phenylephrine falsely elevated metanephrine levels, whereas at a 10-fold higher drug concentration, guanethidine, hydrocortisone, imipramine, isoetharine, levodopa, phenobarbital, and phenylephrine caused positive interference.

Practical considerations in planning and conducting clinical trials with investigational or marketed drugs.

A system is presented to increase efficiency in planning, initiating, conducting, and analyzing the results of a clinical trial. The procedures to be used are designed to assist clinical investigators of sponsored or unsponsored studies, as well as drug corporations and other sponsors of drug studies. The series of checklists and steps to follow may be easily modified for individual trials.