Respuesta histológica completa a la neoadyuvancia en cáncer gástrico avanzado / Histological complete response after neoadjuvant therapy in advanced gastric cancer

Introduction: this article describes the first case in Peru where a patient with an advanced gastric cancer showed pathologic complete response to neoadjuvance indicated due an extensive involvement of paraaortic and celiac trunk lymph nodes. Clinical case: 51 year old female patient, after 4 cycles of chemotherapy, the former with epirubicin, cisplatin and capecitabine and the remaining three with epirubicin, cisplatin and 5-fluorouracil, a complete response was obtained from the tomographic point of view. Later patient underwent total gastrectomy with D2 lymphadenectomy. Microscopic examination of the surgical specimen verified only scar tissue without evidence of malignancy in both, the stomach and the lymph nodes removed. Further we present a review of the relevant medical literature to date.

Introducción: el presente artículo describe el primer caso en el Perú en el que una paciente con cáncer gástrico avanzado ha mostrado respuesta completa histopatológica a neoadyuvancia. Caso clínico: paciente mujer de 51 años con cáncer gástrico con un extenso compromiso ganglionar para-aórtico y a nivel del tronco celíaco. Luego de 4 ciclos de quimioterapia, el primero con epirrubicina, cisplatino y capecitabina y los 3 restantes con epirrubicina, cisplatino y 5-fluoruracilo, se obtiene una respuesta completa desde el punto de vista tomográfico, por ello la paciente fue sometida a gastrectomía total con linfadenectomía D2 verificándose en el examen microscópico de la pieza operatoria sólo tejido cicatricial sin evidencias de neoplasia maligna tanto en el estómago como en los ganglios linfáticos resecados. A propósito del caso se hace una revisión de la literatura médica relevante actualizada.

Thermodynamic and spectroscopic studies of lanthanides(III) complexation with polyamines in dimethyl sulfoxide.

The thermodynamic parameters of complexation of Ln(III) cations with tris(2-aminoethyl)amine (tren) and tetraethylenepentamine (tetren) were determined in dimethyl sulfoxide (DMSO) by potentiometry and calorimetry. The excitation and emission spectra and luminescence decay constants of Eu3+ and Tb3+ complexed by tren and tetren, as well as those of the same lanthanides(III) complexed with diethylenetriamine (dien) and triethylenetetramine (trien), were also obtained in the same solvent. The combination of thermodynamic and spectroscopic data showed that, in the 1:1 complexes, all nitrogens of the ligands are bound to the lanthanides except in the case of tren, in which the pendant N is bound. For the larger ligands (trien, tren, tetren) in the higher complexes (ML2), there was less complete binding by available donors, presumably due to steric crowding. FT-IR studies were carried out in an acetonitrile/DMSO mixture, suitably chosen to follow the changes in the primary solvation sphere of lanthanide(III) due to complexation of amine groups. Results show that the mean number of molecules of DMSO removed from the inner coordination sphere of lanthanides(III) is lower than ligand denticity and that the coordination number of the metal ions increases with amine complexation from approximately 8 to approximately 10. Independently of the number and structure of the amines, linear trends, similar for all lanthanides, were obtained by plotting the values of DeltaGj degrees, DeltaHj degrees, and TDeltaSj degrees for the complexation of ethylenediamine (en), dien, trien, tren, and tetren as a function of the number of amine metal-coordinated nitrogen atoms. The main factors on which the thermodynamic functions of lanthanide(III) complexation reactions in DMSO depend are discussed.

Soporte nutricional artificial en la infección por HIV: reporte de un caso / Artificial nutritional support in hiv infection: report of one case

El presente trabajo describe el primer caso de infección por HIV admitido a terapia nutricional en una unidad de soporte nutricional artificial multidisciplinaria en el Perú y es el primero en su género publicado en el país. Se presenta el caso de una adolescente de 16 años con severo trastornos gastrointestinales y nutricionales como complicaciones de la infección por HIV y que requirió nutrición parenteral total por un período de 21 días. Durante el período de tratamiento no se evidenció complicación alguna derivada de la intervención nutricional, apreciándose más bien una gran mejoría clínica y una adecuada respuesta nutricional determinada a través de los parámetros bioquímicos más reconocidos y a través de la utilización de una técnica nueva para nuestro país como es el análisis de composición corporal por impedanciometría.

[ARTIFICIAL NUTRITIONAL SUPPORT IN HIV INFECTION: REPORTOF ONE CASE] / Soporte Nutricional artificial en la Infecciónpor HIV: Reporte de un Caso.

The present work describes the first case of HIV infected patient admitted to nutritional therapy in a multidisciplinary Nutritional Support Unit in Perú, and is the first of this type published in Perú. We show the case of a teen-ager patient with severe gastrointestinal and nutritional alterations as a complication of HIV infection, who required parenteral total nutrition for 21 days. During this treatment period we did not observe any complication as result of nutritional intervention; on the contrary, we observed a great clinical improvement and an adecuated nutritional response trough the most recognized biochemical parameters and using Body composition by Impedanciometry, a new technic for our country.

The anatomy of an OPTI: Part 2. The CORE system. Ohio Osteopathic Hospital Association. Ohio Association of Osteopathic Medical Directors. Ohio Osteopathic Association.

In July 1995, the American Osteopathic Association (AOA) Board of Trustees passed new regulations regarding the accreditation of osteopathic graduate medical education (GME) by establishing the Osteopathic Postdoctoral Training Institutions (OPTI) system. This system must be phased in by July 1999. The principal changes resulting from the OPTI system include establishing requirements for college cosponsorship of GME programs and for the number of residency programs, interns, and residents to be trained by the OPTI. In essence, OPTI is an osteopathic acronym for consortium. Each OPTI must include at least one college of osteopathic medicine (COM) and one AOA-accredited hospital. The OPTIs will be subject to interval AOA inspections and will be required to demonstrate a governing system, mission statement, organizational structure, and the presence of faculty development programs. The first article in this two-part series, published in the October JAOA, provided a general blueprint for OPTI building and presented both positive and negative issues germane to the formation of OPTIs. Part 2 reinforces the considerations outlined in Part 1 by describing the formation of a large OPTI--the Ohio University College of Osteopathic Medicine (OU-COM) Centers of Osteopathic Regional Education (CORE) system. Key features are described, including the mission statement, organizational structure, committee system, governance, GME programs, operations, and budget.

Anatomy of an OPTI: Part I. Form, function, and relationships.

In July 1995, the American Osteopathic Association (AOA) Board of Trustees passed new regulations for the accreditation of osteopathic graduate medical education (GME) programs by establishing the Osteopathic Postdoctoral Training Institutions (OPTI) system, to be implemented over 4 years. The resulting changes include requirements for college cosponsorship of GME programs and the establishment of standards for the minimum number of residency programs, interns, and residents. The OPTIs will be subject to AOA inspections at least every 5 years. Proponents of the OPTI system claim it will strengthen the profession by promoting educational collaboration, raising academic standards, and requiring appropriate resources to support osteopathic medical education. Opponents fear that it will be too resource intensive, create an additional layer of unnecessary bureaucracy, and have a negative impact on small colleges, hospitals, and states. Despite the controversy, a process for applying for OPTI status has been developed by the AOA, and a number of hospitals and colleges are already developing OPTIs. This article, the first in a two-part series, identifies issues and barriers to be considered in the formation of OPTIs and articulates principles underlying successful collaborations. In Part 2 these issues, principles, and barriers will be reinforced by describing the process used to form a large OPTI--the Ohio University College of Osteopathic Medicine (OU-COM) Centers for Osteopathic Regional Education (CORE) System.

An osteopathic prescription for medical education reform: Part 1. Curriculum and infrastructure.

Medical education has not kept pace with the evolving healthcare system. Criticism from industry and policy observers focuses on four major areas requiring reform: the curriculum, the fragmented educational infrastructure, the specialist-to-generalist mix, and the alienation from community and public health. The dominance of managed care organizations in the delivery and financing of healthcare is forcing a new set of physician competencies to the fore and changing projections of physician manpower and specialty needs. The authors address the four major criticisms from a uniquely osteopathic point-of-view. In this first of two articles, the authors describe the evolving osteopathic medical education model, and then employ a medical analogy to diagnose the causes of and propose treatments for curricular issues and infrastructure fragmentation. In the second article of the pair, they explore the causes of and propose strategies to address the generalist-to-specialist imbalance and the alienation of medicine from community and public health; the article also explores the role of technology in support of reform. In each article, the authors propose treatments to correct the problems in the osteopathic medical education model, and conclude that the profession is well-positioned to lead medical education reform.

The human growth hormone transgene: expression in hemizygous and homozygous mice.

Female transgenic mice carrying the mouse metallothionein-I/human growth hormone (hGH) fusion gene are sterile. Transmission of the transgene has been limited to the male germ line, resulting in the production of hemizygous (He) progeny containing only a single (paternal) copy of the gene. Using ovary transfer, we have developed procedures for producing homozygous (Ho) TG mice, viz., male TG mice were mated with control (non-TG) females carrying ovaries donated by female TG mice. In both He and Ho TG animals, serum levels of hGH were higher (1.5-fold) in males than in females, tended to decrease with age of the animal, and were increased (about 5-fold) by zinc induction. However, in comparison to He animals of the same sex, the Ho TG mice attained a greater body weight and had more than 2-fold higher levels of liver hGH-mRNA and serum hGH, both under basal conditions and in response to zinc induction. That is, the expression of the transgene was qualitatively similar in He and Ho TG mice, but the level of transgene activity was greater in the Ho animals. We interpret this to indicate that both copies (maternal and paternal) of the transgene were active and expressed additively (or cooperatively) in the Ho TG animal.

Stress-induced secretion of human growth hormone in transgenic mice.

The effect of stress on human growth hormone (hGH) secretion was studied in transgenic mice. Experiments were conducted on fourth, fifth, and sixth generation male mice carrying a fusion gene, consisting of the promoter sequence of the mouse metallothionein I gene ligated to the hGH structural gene (mMT-I/hGH). In animals adapted to a controlled photoperiod, basal (unstimulated) levels of plasma hGH exhibited a diurnal cycling, with peak values occurring during the later half of the light period (15.5 +/- 1.0 vs 10.7 +/- 0.9 ng/ml, mean +/- SE, light versus dark, respectively). Food deprivation (5 days) led to elevated levels of plasma hGH (11.0 +/- 0.7 vs 32.0 +/- 4.2 ng/ml, preversus post-fast, respectively) accompanied by weight loss (49.5 +/- 0.8 vs 34.3 +/- 0.7 g), and hypoglycemia (7.8 +/- 0.2 vs 5.0 +/- 0.3 mM); glucose administration (5% drinking solution ad libitum) blocked the changes in levels of plasma hGH (12.2 +/- 1.1 vs 13.8 +/- 0.8 ng/ml) and plasma glucose (7.4 +/- 0.3 vs 7.9 +/- 0.5 mM), although the animals still sustained significant weight loss (44.9 +/- 1.6 vs 35.2 +/- 1.1 g). Vigorous exercise (swimming, 4 hr) produced a small but significant increase in plasma hGH, 12.1 +/- 1.1 ng/ml (1 hr pre-swim) vs 16.7 +/- 0.6 ng/ml (immediately post-swim). These findings indicate that the mMT-I/hGH transgene is responsive to the physiologic status of the host animal. Taken together with information regarding the heterologous components of the fusion gene, these data are consistent with the view that the hGH (structural) sequence may play a role in the response to stress.

Histochemical characteristics of soleus muscle in hGH transgenic mice.

Histochemical characteristics of soleus muscle were compared in human growth hormone (hGH) transgenic mice vs their nontransgenic littermates. Plasma of transgenic mice contained hGH (7.1 +/- 0.7 and 6.7 +/- 0.4 ng/ml, mean +/- SE, at 5 and 11 months of age, respectively); hGH was not detectable in plasma of nontransgenic littermates. Body and soleus weights were greater (approximately 55 and 25%, respectively) and both type I and type IIA fibers were larger in transgenic animals. Most significantly, fiber type composition of the soleus muscle was different in hGH-transgenic animals, i.e., the percentage of type I fibers was significantly greater than in nontransgenic mice (77.2 +/- 5.1% vs 58.4 +/- 2.5%). It is generally believed that skeletal muscle fiber composition is determined predominantly by neural influences (1, 2). These data suggest hormonal factors, growth hormone, also affect the phenotype of skeletal muscle myosin.

Preparation of enriched populations of corticotrophs from goldfish rostral pars distalis.

A mammalian isolated adrenal cell system was validated as a bioassay for goldfish ACTH; the log dose-response curve for the goldfish hormone is parallel to that for synthetic mammalian ACTH1-24, and the two ACTHs induce the same maximum rate of corticosterone production. Using this assay, it was observed that (1) there is a marked and consistent biphasic change in pituitary ACTH content as related to the length of time the fish are held in laboratory aquaria, and (2) the absolute and relative (to tissue wt) ACTH content of the rostral pars distalis is considerably greater than that of the proximal portion of the gland. Using a trypsin technique, isolated pituitary cells were prepared from both (rostral and proximal) portions of the gland; bioassay data indicate that cell suspensions prepared from the rostral pars distalis are enriched with respect to corticotrophs. The implications of these findings with regard to formulating an advantageous in vitro system for studying ACTH secretion are discussed.

Dibutyryl cyclic AMP-induced phosphorylation of specific proteins in adenohypophysial cells.

The objective of this work was to identify the natural substrates of cyclic AMP-dependent protein kinase in pituitary cells. Studies were performed using 2 systems: intact pituitary cells stimulated with dibutyryl cyclic AMP (DBC) after preincubation with [gamma-32P]. Phosphorylation of proteins was analyzed by two-dimensional gel electrophoresis, followed by autoradiography. In intact cells, the only clear and reproducible effect of DBC stimulation is increased phosphorylation of 3 proteins (termed A, B, and C), each with a molecular weight of about 20 000 dalton. The time-course and dose-dependence of phosphorylation of A, B and C are generally similar to that for DBC-induced hormone secretion, which is consistent with a role for these proteins in the secretory mechanism. When [gamma-32P]ATP is added to cell extracts, proteins A, B, and C are not measurably phosphorylated, either in the absence or presence of cyclic AMP. This observation suggests that proteins A, B and C may not be directly phosphorylated by cyclic AMP-dependent protein kinase, but may be phosphorylated indirectly by a second kinase. On the other hand, growth hormone and prolactin are readily phosphorylated in cell extracts by cyclic AMP-dependent protein kinase (although they are not phosphorylated in vivo). This finding makes clear the need for caution in interpreting results from broke cell systems.

Effect of glucocorticoid levels in vivo on growth hormone biosynthesis.

The rate of growth hormone (GH) biosynthesis in pituitary cells prepared from rats with different histories of glucocorticoid exposure was analyzed by a dual-labeling acrylamide-gel technique. Glucocorticoid deficiency, produced by adrenalectomy, reduces GH synthesis by approximately 50%. GH synthesis adrenalectomized rats treated with either natural or synthetic glucocorticoids, is restored to normal or above normal levels. Acute exposure (1 h) of cells to corticosterone in vitro does not produce a significant increase in GH synthesis. Adrenalectomized rats treated with steroid for one day show a small but detectable increase in GH synthesis, while treatment for 3--6 days results in progressively larger stimulatory effects. All of these results are similar to previous findings regarding glucocorticoid stimulation of GH synthesis in vitro.

Effect of cordycepin on CRF stimulation and steroid inhibition of ACTH secretion by rat pituitary cells.

Isolated pituitary cells prepared from adrenalectomized rats secrete ACTH in response to CRF, and this response is inhibited by corticosterone. Both the stimulation of release by CRF and the inhibition of release by corticosterone are antagonized by cordycepin (3'-deoxyadenosine). Inhibition of CRF-stimulated secretion by cordycepin is apparently not related to inhibition of RNA synthesis, since high doses of actinomycin D do not affect ACTH secretion. More likely, cordycepin's inhibition of secretion stems from its inhibition of adenylate cyclase activity. Inhibition of corticosterone action by cordycepin is qualitatively similar to that previously reported actinomycin D. This effect of both drugs is probably due to inhibition of RNA synthesis. Significantly, a low dose of cordycepin has a greater inhibitory effect on corticosterone action than on total cellular RNA synthesis. Cordycepin is reported to preferentially inhibit messenger RNA synthesis, and low dose preferentially inhibits appearance of cytoplasmic RNA in pituitary cells. These data suggest that corticosterone-induced RNA is a cytoplasmic (messenger) RNA.