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Nolan (1991) sees a moral ambiguity in our treatment of these embryos that is difficult to rationally justify neurontin 100mg generic medications overactive bladder. Specifically buy 300mg neurontin visa medicine allergic reaction, we justify germline genetic engineering as an extension of clinical medicine with “the ostensible goal of providing therapy for these ‘patients purchase neurontin now medicine prescription drugs,’“ while at the same time we seem “quite comfortable with pursuing germline genetic research that would itself entail substantial destruction of embry- onic life” (Nolan, 1991, p. In no other area of clinical medicine or research medicine do we permit the destruction of failed patients. This objection can be answered by noting an ambiguity in the use of the term “patient,” as applied to the eight-cell embryo. Morally speaking, the embryo is not a patient in the same sense that an infant is a patient. What this signals is a therapeutic attitude toward that embryo, as opposed to a merely experimental attitude. If we have genet- ically engineered an embryo and implanted it, and then in the third month of ges- tation some environmental factor causes terrible damage to the fetus, then this mother has the moral right to choose abortion, especially if it is her judgment that this is in the best interests of the fetus who would otherwise face a seriously com- promised life of unmitigated suffering. By way of contrast, if this same genetically engineered embryo is born, but some serious medical disorder emerges after birth that is an unexpected consequence of the genetic engineering, then we would have a strong societal obligation to do everything medically reasonable to correct or ame- liorate that disorder. Note that we have in mind here a crippling disorder, perhaps one that would be very costly to correct or ameliorate, as opposed to a fatal disor- der where heroic medical intervention could only prolong a painful dying process. So long as this moral commitment is in place, we do not see a strong moral objec- tion to germline engineering on the grounds of embryonic destruction. Threats to Health Care Justice A fifth objection we need to consider is an argument from justice. This is a complex objection that has many dimensions to it and that is very sensitive to empirical matters of a political and economic sort. That is, if this were foreclosed as a therapeutic research option by social choice, would we have violated any key moral rights that individuals have, especially future individuals afflicted with specific genetic disorders who could have been spared those disorders if the research had been allowed to go forward? The objector’s response to these questions is, in effect, that no one has a just claim to germline genetic engineering. That is, as many have argued, there are an indefinitely large array of therapeutic medical technolo- gies that are possible; but, given limited resources for meeting medical needs in any society, only some fraction of these can be actualized and deployed (Callahan, 1990). If everyone is thereby denied access to these technologies, and if virtually everyone could potentially benefit from them, then all are treated impartially and fairly. That is, it is regrettable and unfortunate that many future individuals will be afflicted with serious genetic disorders they could have been spared, but, morally speaking, it is not unjust. This is a line of argument we have already addressed at great length in another publication (Fleck, 1994). Briefly, if we have only limited resources for meeting vir- tually unlimited health needs, then those needs must be fairly prioritized. One way of thinking about this problem is from the perspective of protecting fair equality of opportunity for all over the course of a life (as opposed to looking at this as a problem of justice at a point in time) (Daniels, 1985). We can imagine that by the year 2003 we will have developed and deployed a totally implantable artificial heart with annual costs of $52 billion ($1997) for 350,000 people per year. By the year 2010 we will imagine we have the capacity to do germline genetic engineering. Everyone today is mindful of intense political and business pressures to control health care costs. While it is generally true that no one’s moral rights are violated if a society chooses not to develop and deploy a new medical technol- ogy, in this case there is a justice-based argument that would warrant the conclusion that germline genetic resources should command societal resources before ongoing expenditures for artificial hearts. A key element of that argument is that roughly 70% of those artificial hearts would go to individuals over age 65, that is, individu- als who would have had the opportunity to lead a full life of reasonable quality. What germline genetic engineering would offer is that same opportunity to other individuals who were at the very beginning of life. Along these same lines, there is a comparable argument that might be made regarding somatic cell gene therapy. That is, like the artificial heart, somatic cell gene therapy may prove to be another very expensive “half-way” technology. This means that the intervention does not really cure the medical problem; instead, the problem is substantially ameliorated through repeated application of the technology.

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The isthmus or intermediate zone is identified as a constriction between the ventriculus and the proventricu- lus purchase neurontin 100 mg with amex medicine for diarrhea. The vessels on the surface of the proventriculus are easily identified and avoided purchase neurontin 800mg otc medications bad for kidneys. The proventriculotomy incision is initiated at the isthmus and extends orad into the body of the proventriculus best 100mg neurontin medicine to increase appetite. Hemorrhage from the cut edge of the proventriculus may be controlled using radiocoagu- lation. Thumb forceps may be used to gently clamp the cut edge to occlude the vessel, allowing it to be identified and appropriately coagulated. A combination of irri- gation and suction is useful to com- pletely evacuate the proventriculus and ventriculus. A small diameter flexible endoscope may be used per os, or through the proventriculotomy to assure that all foreign objects have been removed. The proventriculotomy is closed us- ing a simple continuous appositional d) Radiosurgical forceps should be used only for controlling hemorrhage and not for making incisions into viscera. A midline, flap or transverse celiotomy may be ous or interrupted inverting pattern such as a Cush- appropriate, depending on the location of the lesion. The inverting pattern should In most circumstances, microsurgical technique is extend beyond the actual incision to ensure an ade- indicated due to the extremely thin nature of the quate seal. The blood supply to the small intes- using an orogastric tube to insufflate the proven- tine is via the celiac artery (to the duodenum) and the triculus with air or sterile saline. The technique used to anastomose the bowel requires Food and water should be offered in the immediate microsurgical manipulation of 6-0 to 10-0 monofila- postoperative period. Side-to-side anastomosis may prove to be less one intends to withhold food until wound more appropriate in birds and is easier to perform. Incisional leakage of gastric contents Enteral feeding tubes may be indicated for a variety occurs with some frequency in birds. Meticulous attention to proper closure is tional supplementation to anorectic and debilitated vital to prevent leakage. A variety of medical and surgical conditions should be used with a continuous suture pattern to including crop infections, impaction, injury or in- provide the best seal. If the proventricular wall ap- flammation, esophageal perforation or laceration, pears thin and friable, the potential for postoperative proventricular dilatation, beak disorders, pharyngeal incisional leakage may warrant placement of a duo- disorders and any condition resulting in hypophagia denal feeding tube. This will allow enteral alimenta- or anorexia places a nutritional demand on the pa- tion of the patient while bypassing the gastric incision. Proper attention to the patient’s nitrogen balance The ventriculus is best approached through a can make the difference between success and failure proven-triculotomy incision. The opening into the ventriculus can be gently dilated to A technique for placement of a duodenostomy tube allow the introduction of instruments appropriate for has been described in domestic pigeons. Some surgeons sug- five catheterized birds had minor weight loss after 14 gest that a ventriculotomy (transverse abdominal days of total nutritional support through the enteros- approach) is easier than a proventriculotomy (left tomy tube (4% to 10%). The lighter-colored, elliptical area removal, all the birds had regained their normal of the ventriculus, where the muscle is thin and the weight. The ascending duodenum is easily identified The incision is made transversely across the muscle by its close association with the pancreas (see Anat- fibers into the lumen. A “through-the-needle” catheter (in- placed close together to prevent leakage, because a dwelling jugular catheter) is used with the needle serosal seal cannot be created by using an inverting passing first through the left abdominal wall, then suture pattern. The catheter diameter should be less than one-third the diameter of the intestine. One or two sutures are midline celiotomy or to debride necrotic bowel secon- placed between the left body wall and the duodenum dary to constrictions caused by adhesions (see Color at the entry site of the catheter to secure the intestine 14). The midline celiotomy is closed ture on either side of the cloaca; however, when the routinely. If mattress sutures are used, they must The catheter is secured to the outside left abdominal allow for the passage of droppings.

Appendix 100mg neurontin with mastercard symptoms ulcerative colitis, [Drawings of permanent and primary teeth which are labeled (with letters) to highlight features of each tooth]; Appendix page 1-10 cheap 800 mg neurontin fast delivery medicine 773. Blickdiagnostik: Compactatlas der klinischen Inspektion und Diferenzialdiagnostik buy neurontin american express medicine journal. Sample Citation and Introduction to Citing Contributions to Books Te general format for a reference to a contribution to a book, including punctuation: Examples of Citations to Contributions to Books Contributions are found when a book has an overall editor or editors and the individual chapters or other components of the book are written by various authors, usually called contributors. Because a reference should start with the individual or organization responsible for the intellectual content of the publication, begin a reference to a contribution with the author and title of the contribution, followed by the word "In:" and information about the entire book. Medical texts frequently contain charts, fgures, and other illustrative material that have been reproduced with permission from other sources. Citation Rules with Examples for Contributions to Books Components/elements are listed in the order they should appear in a reference. An R afer the component name means that it is required in the citation; an O afer the name means it is optional. Author/Editor (R) | Author Afliation (O) | Title (R) | Connective Phrase (R) | Book Information (R) | Location (Pagination) (R) | Part (R) 266 Citing Medicine Author/Editor of a Contribution to a Book (required) General Rules for Author/Editor • List names in the order they appear in the text • Enter surname (family or last name) frst for each author • Capitalize names and enter spaces within surnames as they appear in the document cited on the assumption that the author approved the form used. To simplify rules for English-language publications, this rule ignores some conventions used in non- English languages ⚬ Treat letters marked with diacritics or accents as if they are not marked Å treated as A Ø treated as O Ç treated as C Ł treated as L à treated as a ĝ treated as g ñ treated as n ü treated as u Box 132 continues on next page... Names in non-roman alphabets (Cyrillic, Greek, Arabic, Hebrew, Korean) or character-based languages (Chinese, Japanese). Romanization, a form of transliteration, means using the roman (Latin) alphabet to represent the letters or characters of another alphabet. Tis rule ignores some conventions used in non-English languages to simplify rules for English-language publications. An organization such as a university, society, association, corporation, or government body may be an author. International Union of Pure and Applied Chemistry, Organic and Biomolecular Chemistry Division. American College of Surgeons, Committee on Trauma, Ad Hoc Subcommittee on Outcomes, Working Group. American Academy of Pediatrics, Committee on Pediatric Emergency Medicine; American College of Emergency Physicians, Pediatric Committee. Tis rule ignores some conventions used in non-English languages to simplify rules for English-language publications. Separate the surname from the given name or initials by a comma; follow initials with a period; separate successive names by a semicolon and a space. If you abbreviate a word in one reference in a list of references, abbreviate the same word in all references. Marubini E (Istituto di Statistica Medica e Biometria, Universita degli Studi di Milano, Milan, Italy), Rebora P, Reina G. Tis rule ignores some conventions used in non-English languages to simplify rules for English-language publications. Moskva becomes Moscow Wien becomes Vienna Italia becomes Italy Espana becomes Spain Examples for Author Affiliation 8. Contributed chapter with author address included Title of a Contribution to a Book (required) General Rules for Title • Enter the title of the chapter or other contribution as it appears in the original document, in the original language • Capitalize only the frst word of a title, proper nouns, proper adjectives, acronyms, and initialisms • Use a colon followed by a space to separate a title from a subtitle unless some other form of punctuation (such as a question mark, period, or an exclamation point) is already present • Follow non-English titles with a translation whenever possible; place the translation in square brackets • End a title with a period unless a question mark or exclamation point already ends it Specific Rules for Title • Titles not in English • Titles in more than one language • Titles containing a Greek letter, chemical formula, or another special character Box 144. Diagnostika i kompleksnoe lechenie osnovnykh gastroenterologicheskikh zabolevanii: klinicheskie ocherki. Tis rule ignores some conventions used in non-English languages to simplify rules for English-language publications. Base molecular de la expresion del mensaje genetico [Molecular basis of gene expression]. Diagnostika i kompleksnoe lechenie osnovnykh gastroenterologicheskikh zabolevanii: klinicheskie ocherki [Diagnosis and complex treatment of basic gastrointestinal diseases: clinical studies]. If a chapter or other contribution is presented with equal text in two or more languages, as ofen occurs in Canadian publications: • Give all titles in the order in which they are found on the title page • Place an equals sign with a space on either side between the titles • List all the languages, separated by commas, afer the pagination • End the list with a period Example: Le genome: avancees scientifques et therapeutiques et consequences sociales = Te genome: scientifc and therapeutic developments and social consequences. Contributed chapter with a title beginning with a lower-case letter or containing a special symbol or character 10. Contributed chapter with a non-English title Connective Phrase for a Contribution to a Book (required) General Rules for Connective Phrase • Place a space and the word "In" afer the title of the contribution • Follow "In" with a colon and a space Examples for Connective Phrase 1. Standard reference to a contributed chapter Book Information (required) General Rules for Book Information • Cite the book in which the contribution appears according to Chapter 2A Entire Books but omit the Pagination Examples for Book Information 12. Contributed chapter in one volume of a multivolume book Location (Pagination) for a Contribution to a Book (required) General Rules for Location (Pagination) • Begin location with "p.


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Somatic Cells as Nuclear Donors Initially purchase neurontin amex medicine hollywood undead, intestinal cells from Xenopus laevis feeding tadpoles were used as donor nuclei discount neurontin 600mg overnight delivery medications management. A small fraction of the nuclear transplantation embryos developed to the swimming tadpole stage discount neurontin 800mg free shipping medications lexapro. In these experiments, seven embryos completed meta- morphosis to produce normal adult males and females. The adult clones were fertile, demonstrating the completeness of the nuclear reprogramming. Therefore, not only could differentiated somatic cell nuclei undergo reprogramming, but tumor cells could also be recruited to participate in normal embryonic development following nuclear transplantation. Nonetheless, rates of development of embryos were reduced greatly when “dif- ferentiated” cells were used as nuclear donors compared to blastula or gastrula endodermal cells. Restrictions in the extent of development was most apparent in the Mexican axolotl. Therefore, the vast majority of notochord nuclei were severely restricted in their developmental capac- ity. Failure of development following nuclear transplantation was associated with the presence of chromosomal abnormalities, which included ring chromosomes, anaphase bridges, chromosome fragments, and variable numbers of chromosomes. From these results, Briggs and co-workers (1964) concluded: “The central question therefore concerns the origin of these chromosomal abnormalities. Are they to be regarded as artifacts, or do they indicate a genuine restriction in the capacity of the somatic nuclei to function normally following transfer into egg cytoplasm? In subsequent experiments, primary cultures were used as a source of nuclei in an effort to provide more uniform populations. Also, “serial nuclear transplanta- tion” gained favor to improve rates of development beyond the blastocyst stage. Serial nuclear transplantation involved a first round of nuclear transfer to produce partially cleaved blastocysts. The positive effects of serial nuclear transplantation were not improved by additional rounds of nuclear transplantation, suggesting that sequential nuclear reprogramming was not taking place. Using serial nuclear transplantation, partial or complete blastulae were obtained at rates of 22 to 31% using cultures of kidney, lung, heart, testis, and skin from adult frogs as donor nuclei for serial nuclear transplantation. Swimming tadpoles devel- oped when nuclei for the initial transfers were from adult kidney, lung, and skin but not heart. Based on these results, it would appear that <10% of cells from the primary nuclear transplant embryos were able to undergo successful genetic repro- gramming and direct successful development of tadpoles. It is also important to note that some developmental abnormalities were evident in tadpoles derived from nuclear transplantation. The descriptions were not extensive, but anal and cardiac edema were reported and resulted in subsequent death. Since a relatively small proportion of donor nuclei were able to form even blastocysts following nuclear transplantation, it remained possible that embryos resulted only from a subpopulation of cells that retained stem cell-like characteris- tics. To rule out this possibility, primary cell cultures were established from foot- web explants and were shown to be differentiated by the expression of keratin in >99. Although no first-transfer embryos developed beyond early cleavage embryos, serial transplantation resulted in swimming tadpoles with well- differentiated organs. Attempts to confirm these results in Drosophila yielded development of larvae but no adults. This result was extended by Schubiger and Schneiderman (1971) when it was shown that preblastoderm nuclei could be transplanted into oocytes, then develop 8 to 10 days when placed in a mature female. These implants were retrieved, then dissociated, and the nuclei were again used for serial nuclear transplantation. The serial nuclear transplant embryos were transferred into developing larvae where they underwent metamorphosis along with their hosts to form adult tissues. Therefore, extensive genetic reprogramming of donor nuclei was possible but required serial nuclear transplantation similar to that used in amphibia. Conclusions The work with amphibia clearly demonstrated that nuclear transplantation could be used to efficiently generate multiple cloned individuals using blastomeres from early cleavage embryos. Although rates of development were diminished when more highly differentiated cell types were used as donors for nuclear transplanta- tion, it was possible to generate live offspring. Therefore, differentiation was reversible and developmental fates were subject to reprogramming under appro- priate conditions.

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