Dosing considerations with transdermal formulations of fentanyl and buprenorphine for the treatment of cancer pain

Tracy L Skaer College of Pharmacy, Washington State University, Spokane, WA, USA Abstract: Opioids continue to be first-line pharmacotherapy for patients suffering from cancer pain. Unfortunately, subtherapeutic dosage prescribing of pain medications remains common, and many cancer patients continue to suffer and experience diminished quality of life. A large variety of therapeutic options are available for cancer pain patients. Analgesic pharmacotherapy is based on the patient's self-report of pain intensity and should be tailored to meet the requirements of each individual. Most, if not all, cancer pain patients will ultimately require modifications in their opioid pharmacotherapy. When changes in a patient's medication regimen are needed, adequate pain control is best maintained through appropriate dosage conversion, scheduling immediate release medication for withdrawal prevention, and providing as needed dosing for breakthrough pain. Transdermal opioids are noninvasive, cause less constipation and sedation when compared to oral opioids, and may improve patient compliance. A relative potency of 100:1 is recommended when converting the patient from oral morphine to transdermal fentanyl. Based on the limited data available, there is significant interpatient variability with transdermal buprenorphine and equipotency recommendations from oral morphine of 75:1–110:1 have been suggested. Cancer patients may require larger transdermal buprenorphine doses to control their pain and may respond better to a more aggressive 75–100:1 potency ratio. This review outlines the prescribing of transdermal fentanyl and transdermal buprenorphine including how to safely and effectively convert to and use them for those with cancer pain. Keywords: opioids, analgesic pharmacotherapy, immediate release medication, pain treatment modification, breakthrough pain, opioid withdrawal, equipotency rati

The absorption of fat by the mammalian stomach

Approved 3/24/1914, C.W. Greene."Typescript.Illustrations pasted in.Tables folded to fit in text block.A proper analysis of the function of the stomach in alimentation involves not only those factors which produce chemical and mechanical changes in the foods during its stay in the gastric cavity; but also, the extent to which the products of digestion are absorbed. This paper confines itself to an investigation of the absorption of fats by the stomach. Especial attention has been given to those fats naturally occurring in the emulsified form; although some non-emulsified fats, neutral oil and neutral fat, were also tested.Includes bibliographical references

Tip cells: Master regulators of tubulogenesis?

AbstractThe normal development of an organ depends on the coordinated regulation of multiple cell activities. Focusing on tubulogenesis, we review the role of specialised cells or groups of cells that are selected from within tissue primordia and differentiate at the outgrowing tips or leading edge of developing tubules. Tip or leading cells develop distinctive patterns of gene expression that enable them to act both as sensors and transmitters of intercellular signalling. This enables them to explore the environment, respond to both tissue intrinsic signals and extrinsic cues from surrounding tissues and to regulate the behaviour of their neighbours, including the setting of cell fate, patterning cell division, inducing polarity and promoting cell movement and cell rearrangements by neighbour exchange. Tip cells are also able to transmit mechanical tension to promote tissue remodelling and, by interacting with the extracellular matrix, they can dictate migratory pathways and organ shape. Where separate tubular structures fuse to form networks, as in the airways of insects or the vascular system of vertebrates, specialised fusion tip cells act to interconnect disparate elements of the developing network. Finally, we consider their importance in the maturation of mature physiological function and in the development of disease

Tip Cells Act as Dynamic Cellular Anchors in the Morphogenesis of Looped Renal Tubules in Drosophila

SummaryTissue morphogenesis involves both the sculpting of tissue shape and the positioning of tissues relative to one another in the body. Using the renal tubules of Drosophila, we show that a specific distal tubule cell regulates both tissue architecture and position in the body cavity. Focusing on the anterior tubules, we demonstrate that tip cells make transient contacts with alary muscles at abdominal segment boundaries, moving progressively forward as convergent extension movements lengthen the tubule. Tip cell anchorage antagonizes forward-directed, TGF-β-guided tubule elongation, thereby ensuring the looped morphology characteristic of renal tubules from worms to humans. Distinctive tip cell exploratory behavior, adhesion, and basement membrane clearing underlie target recognition and dynamic interactions. Defects in these features obliterate tip cell anchorage, producing misshapen and misplaced tubules with impaired physiological function

Contact-induced Phonological Mergers: Transfer or Approximation

Sound changes in a language are considered nearly inevitable consequences of language death. The literature on sound change in obsolescencing languages has focused on whether the changes are internally or externally motivated, between convergent and divergent change and, therefore, the difference between categorical sound shifts and gradient phonetic effects has been overlooked. This paper examines the acoustic correlates of voicing distinctions in the Kurmanji language that investigate the subphonemic variation within a category. The results of a cross-generational acoustic study of Kurmanji showed that unaspirated initial voiceless stops have undergone phonetic change convergent with Persian, the dominant language. This paper argues that sound change in obsolescing languages may manifest substitution or approximation/expansion of phonological categories in the moribund languag

bloated tubules (blot) Encodes a Drosophila Member of the Neurotransmitter Transporter Family Required for Organisation of the Apical Cytocortex

AbstractWe have identified a novel member of the vertebrate sodium- and chloride-dependent neurotransmitter symporter family from Drosophila melanogaster. This gene, named bloated tubules (blot), shows significant sequence similarity to a subgroup of vertebrate orphan transporters. blot transcripts are maternally supplied and during embryogenesis exhibit a complex and dynamic pattern in a subset of ectodermally derived epithelia, notably in the Malpighian tubules, and in the nervous system. Animals mutant for this gene are larval lethals, in which the Malpighian tubule cells are distended with an enlarged and disorganised apical surface. Embryos lacking the maternal component of blot expression die during early stages of development. They show an inability to form actin filaments in the apical cortex, resulting in impaired syncytial nuclear divisions, severe defects in the organisation of the cortical cytoskeleton, and a failure to cellularise. For the first time, a neurotransmitter transporter-like protein has been implicated in a function outside the nervous system. The isolation of blot thus provides the basis for an analysis of the relationship between the function of this putative transporter and epithelial morphogenesis

Multiple Signalling Pathways Establish Cell Fate and Cell Number in Drosophila Malpighian Tubules

AbstractA unique cell, the tip mother cell, arises in the primordium of each Drosophila Malpighian tubule by lateral inhibition within a cluster of achaete-expressing cells. This cell maintains achaete expression and divides to produce daughters of equivalent potential, of which only one, the tip cell, adopts the primary fate and continues to express achaete, while in the other, the sibling cell, achaete expression is lost (M. Hoch et al., 1994, Development 120, 3439–3450). In this paper we chart the mechanisms by which achaete expression is differentially maintained in the tip cell lineage to stabilise cell fate. First, wingless is required to maintain the expression of achaete in the tubule primordium so that wingless mutants lack tip cells. Conversely, increasing wingless expression results in the persistence of achaete expression in the cell cluster. Second, Notch signalling is restricted by the asymmetric segregation of Numb, as the tip mother cell divides, so that achaete expression is maintained only in the tip cell. In embryos mutant for Notch tip cells segregate at the expense of sibling cells, whereas in numb neither daughter cell adopts the tip cell fate resulting in tubules with two sibling cells. Conversely, when numb is overexpressed two tip cells segregate and tubules have no sibling cells. Analysis of cell proliferation in the developing tubules of embryos lacking Wingless after the critical period for tip cell allocation reveals an additional requirement for wingless for the promotion of cell division. In contrast, alteration in the expression of numb has no effect on the final tubule cell number

Unveiling Consonant Harmony: Nonlexical reduplication in English

There is a lack of strong diachronic evidence in English phonology to demonstrate consonant harmony (hereafter CH) in reduplication (Fikkert et al. 2005; Goad & Buckley 2006; Hale & Reiss 2008; Pater & Werle 2003; Rose 2000; Wolfram & Johnson 1982). In the present study, we investigated CH in synchronic settings wherein native English speakers were asked to produce a euphonious pseudo reduplicant from a nonce base in uncontrolled and controlled experiments. The results of the experiments indicated that, in English, consonantal assimilations might have a hierarchical structure when CH is present in the synchronic formation of a rhyming reduplicant. Taken holistically, these findings suggest that the rate of coronal assimilation exceeds that of labial assimilation. The occurrence of dorsal assimilation may be restricted even further by the scarcity of word-initial dorsal onsets that meet the requirements for rhyming reduplication