Synthesis and biological activities of phenyl piperazine-based peptidomimetic growth hormone secretagogues

A new class of potent, orally active phenyl piperazine-based GH secretagogues have been discovered from attempts to mimic the arrangement of the phenyl substituent in the spiroindanyl piperidine and spiroindoline sulfonamide privileged structures of 4 and 1, respectively. The best of these compounds, 18 (EC50 = 2.8 nM) is nearly as potent as MK-0677 for releasing GH from rat pituitary cells.     

Hodgkin's disease: impact on childbearing

Although Hodgkin's disease is considered one of the "curable" cancers, the high cure rates associated with this disease are not accomplished without risk of potentially severe, immediate, and late side effects. Because the predominant histologic subtype of Hodgkin's disease found in the United States generally affects the 15- to 25-year-old age group, the disease, its treatment, and the side effects of treatment will affect many women of childbearing age. The treatment and its effects on the patient and offspring, including posttreatment fertility, are key issues for perinatal nurses.     

Recycling of disposable medical devices (medical device products)

Modern medicine uses large amounts of one-way-devices. This includes mass articles as well as technically sophisticated ones, all of them in accordance with GMP (Good-manufacturing-practice) guidelines. Recycling of selected one-way devices in technically possible and economically useful. Prerequisite for recycling is the inclusion of legal, economic and ecologic points of view. In addition the validation of processes and agreement on installation of continuous quality control is necessary to minimise risks. We suggest admission of recycling and reuse of one-way devices and suggest to proceed stepwise: 1. Principal decision to permit recycling 2. Appointment of an interdisciplinary Federal Board "Medical Devices" for coordination and channelling of activities 3. Selection of products for recycling 4. Principal decision for the systematics of the process together with: process control, product control during a pre-testing stage, random tests in prospective, multi-centre studies for the control of production and use. 5. Introduction of internal quality control systems to allow internal and external control of routine work.     

What is "special" about face perception?

There is growing evidence that face recognition is "special" but less certainty concerning the way in which it is special. The authors review and compare previous proposals and their own more recent hypothesis, that faces are recognized "holistically" (i.e., using relatively less part decomposition than other types of objects). This hypothesis, which can account for a variety of data from experiments on face memory, was tested with 4 new experiments on face perception. A selective attention paradigm and a masking paradigm were used to compare the perception of faces with the perception of inverted faces, words, and houses. Evidence was found of relatively less part-based shape representation for faces. The literatures on machine vision and single unit recording in monkey temporal cortex are also reviewed for converging evidence on face representation. The neuropsychological literature is reviewed for-evidence on the question of whether face representation differs in degree or kind from the representation of other types of objects.     

Psychiatric diagnosis and nosological theory: studies on the individual diagnostic schema of the physician

This study is concerned with the diagnostic process of psychiatrists. Two concepts are investigated; the internalized nosological theory and the psychiatric diagnostic scheme. If patients or diseases are judged on predefined lists of symptoms (e.g. AMDP-list), we assume that judgments are based on the first one. If the psychiatrist, however, is free in the choice of relevant attributes in judging patients or diseases, we assume that his judgments are based on his individual diagnostic scheme. Results show high agreement in internalized nosological theories, but strong individual differences in diagnostic schemes. Interindividual agreement in internalized nosological theories is still greater than intraindividual agreement between diagnostic scheme and nosological theory. This proves that distinguishing the two concepts is meaningful. Structural components of both concepts, e.g., their dimensions, pregnant structures, and their metric, were analyzed by multidimensional scaling. We assume that the psychiatric diagnostic scheme determines the clinical diagnosis in everyday practice, whereas the internalized nosological theory is of importance mainly in research. The differences between both concepts suggest that lists of symptoms are not very helpful in analyzing clinical diagnosis. Thus, in order to achieve greater agreement in diagnosis, further and detailed analysis of individual "implicit" theories which determine the greater part of diagnostic schemes is necessary.     

Surgical salvage after radiation for laryngeal cancer

From January, 1962, through December, 1973, 1,084 patients with cancer of the intrinsic larynx were treated at the Mayo Clinic. Of the 1,084 patients, 136 were retreated after radiation therapy failed to cure their cancer (105 glottic, 30 supraglottic, and one subglottic cancers). Recurrence of glottic cancer was generally recognized later than recurrences in the supraglottic area; likewise, glottic cancers were more advanced at recurrence than supraglottic growths. When feasible, conservation surgery was carried out on both glottic and supraglottic growths. Unfortunately, many growths were too advanced for conservation surgery by the time recurrence was recognized. The concept of "radiate-and-watch" for early glottic and supraglottic cancers is designed to save larynges. The concept is not supported by this study.     

beta-Actin is confined to structures having high capacity of remodelling in developing and adult rat cerebellum

Neurons undergo complex morphological changes during differentiation and in cases of plasticity. A major determinant of cell morphology is the actin cytoskeleton, which in neurons is comprised of two actin isoforms, non-muscle gamma- and beta-actin. To better understand their respective roles during differentiation and plasticity, their cellular and subcellular localization was examined in developing and adult cerebellar cortex. It was observed that gamma-actin is expressed at a constant level throughout development, while the level of beta-actin expression rapidly decreases with age. At the light microscopic level, gamma-actin staining is ubiquitous and the only developmental change observed is a relative reduction of its concentration in cell bodies and white matter. In contrast, beta-actin staining almost completely disappears from the cytoplasm of cell bodies, primary dendrites and axons. In young cerebellar cultures, gamma-actin is found in the cell body, neurites and growth cones, while beta-actin is mainly found in growth cones, as previously reported in other primary neuronal culture systems [Kaech et al. (1997), J. Neuroscience, 17, 9565-9572; Bassell et al., (1998), J. Neuroscience, 18, 251-265]. Electron microscopy of post-embedding immunogold-labelled tissue confirms the widespread distribution of gamma-actin, and also reveals an increased concentration of gamma-actin in dendritic spines in the adult. During development, beta-actin accumulation is observed in actively growing structures, e.g., growth cones, filopodia, cell bodies and axonal tracts. In the adult cerebellar cortex, beta-actin is preferentially found in dendritic spines, structures which are known to retain their capacity for morphological modifications in the adult brain. This differential subcellular localization and developmental regulation of the two actin isoforms point to their different roles in neurons.     

The emerging diversity of the electrophoretic types of Vibrio cholerae in the Western Hemisphere

Since the Latin American cholera epidemic began in 1991, 447 isolates of Vibrio cholerae O1 from the Western Hemisphere have been assayed by multilocus enzyme electrophoresis (MEE) to determine allelic variation among 16 enzyme-encoding genes. Two electrophoretic types (ETs) were identified among toxigenic isolates from Latin America: 323 were ET 4, the ET associated with the Latin American epidemic, and 29 were ET 3. Twenty-three of these ET 3 isolates had a distinctive antimicrobial resistance pattern also seen in isolates imported into the United States from Latin America and Southeast Asia. These resistant isolates had an identical ribotype and nearly identical pulsed-field gel electrophoresis (PFGE) patterns. Most nontoxigenic isolates analyzed were not precursors or descendants of toxigenic epidemic strains. MEE provided a population genetic frame-work for the interpretation of PFGE and ribotype data from the isolates in this study. All three methods identified 2 distinct strains of toxigenic V. cholerae O1 currently epidemic in Latin America.     

Legal issues in sharing the benefits of biodiversity prospecting

The National Cancer Institute (NCI) is the US Government's principal agency for research on the prevention, diagnosis and treatment of cancer. A critical component of the Institute's mission is the identification and development of new and promising treatments for cancer and AIDS. For many years these efforts have included a program to investigate natural products for potential new therapeutic agents. In 1986, with the advent of new screening techniques, the National Cancer Institute stepped up its exploration of natural products and began world-wide collections of plants in tropical and subtropical regions. In recognition of the principles of the Biodiversity Treaty, NCI appreciates that continued access to the natural products of these countries depends on the Institute's ability to recognize the contributions of these source countries and their indigenous peoples, and to provide them adequate incentives to conserve their natural resources for the purposes of drug discovery. Accomplishing this goal presented several legal issues for the National Cancer Institute. As an agency of the US government, the NCI has an adjunct statutory mission to facilitate the transfer of technology developed through the Institute's programs into the private sector for further development and commercialization, and NCI operates under a national policy to use the patent system to transfer Federally supported research to the private domestic sector. Reliance on patent law may limit the Institute's ability to recognize the rights of source countries and their indigenous people and provide compensation for their contributions. However, other legal instruments, such as contracts, can serve as interim measures to provide compensation to source countries and indigenous populations. The National Cancer Institute's Letter of Collection agreement (LOC, formerly the "Letter of Intent'), is an example of an alternative means that "fills-in the gaps' created by patent law and through which source countries may share in the benefits of natural product development.