Primary hyperaldosteronism caused by adrenocortical carcinoma

Since the syndrome of primary hyperaldosteronism was described by Jerome Conn in 1955, over 300 patients with this disorder have been identified in the medical centers of Vanderbilt University and the University of Michigan. The most frequent cause of this endocrinopathy has been a solitary adenoma of the adrenal cortex (72%); bilateral adrenocortical hyperplasia has been the cause of primary hyperaldosteronism in 27% of cases; less frequently, the cause has been multiple and/or bilateral adenomas (1%). During the last 4 years in these 2 medical centers, we have encountered 3 patients who have had biochemically proven primary hyperaldosteronism due to adrenocortical carcinoma. Each of these unusual cases is summarized with review of the recent literature.

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Resumen Desde la descripción del síndrome de hiperaldosteronismo primario por Jeremo Conn en 1955, más de 300 pacientes con esta entidad han sido identificados en nuestros 2 centros médicos, la Universidad de Vanderbilt (Nashville) y la Universidad de Michigan (Ann Arbor). La causa más frecuente de esta endocrinopatía ha sido el adenoma solitario de la corteza suprarrenal (72%); la hiperplasia adrenocortical bilateral ha sido la causa del hiperaldosteronismo primario en 27% de los casos; con menor frecuencia se han presentado los adenomas multiples y/o bilaterales (1%). En los 4 últimos años hemos encontrado 3 pacientes con hiperaldosteronismo primario comprobado bioquímicamente producido por carcinoma adrenocortical. Se presenta cada uno de estos casos poco usuales junto con una revisión de la literatura reciente.

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Résumé Depuis que le syndrome d'hyperaldostéronisme primitif a été décrit par Jerôme Conn en 1955 plus de 300 sujets qui en étaient victimes ont été identifiés à la Vanderbilt University de Nashville et à l'University of Michigan de Ann Arbor. La cause la plus fréquente de cette endocrinopathie répond à un adénome solitaire de la cortico-surrénale (72%) alors que l'hyperplasie corticale des 2 surrénales est plus rarement à son origine (27%), les adénomes multiples et/ou bilatéraux étant rarissimes (1%). Au cours des 4 dernières années 3 cas d'hyperaldosteronisme dû à un cancer de la cortico-surrénale ont été observés dans les 2 centres. Chacun de ces cas exceptionnels est exposé cependant que la littérature récente concernant l'hyperalderosteronisme est analysée.

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Presented at the International Association of Endocrine Surgeons in Paris, September 1985.     

Lack of concordance of growth rates of primary and recurrent breast cancer

The degree of concordance of growth rates of primary tumors with corresponding recurrences was investigated by using data from 184 patients with breast cancer with measurable recurrences. For conduction of this examination, the detection processes of both the primary tumor and the recurrence were explored. The probability of detection of a recurrence per unit time was found to be nearly proportional to the tumor's diameter. Approximately 60,000 cells initiated the recurrence, and the distribution of doubling times of the recurrences was exponential, with a mean of 2.1 months. The probability of detection of the primary tumor per unit time was approximately proportional to its volume. The distribution of doubling times of primary tumors was nearly exponential; from other evidence, we inferred that the mean doubling time was also close to 2.1 months. Several techniques to measure growth rate agreement between the primary and recurrent tumors within individuals were developed, and all of them yielded the result that the growth rates are nearly unrelated.     

Wound matrix attachment regulates actin content and organization in cells of the granulation tissue

Actin cytoskeletal polymerization is associated with a pro-proliferative, pro-survival state. We hypothesized that the actin polymerization of wound cells is increased in the presence of wound matrix attachment and is decreased after disruption of this attachment. Musculocutaneous flap and wound splinting models were used to investigate the effect of wound matrix attachment on the actin cytoskeleton. Disruption of wound matrix attachment was accomplished by incision of the wound matrix/dermis interface (wound matrix release) and/or desplinting. Polymerized actin was assayed with phalloidin labeling of wound specimens 24 hours after disruption of attachment and a method to quantify the content and organization of polymerized actin in granulation tissue was used. Disruption of wound matrix attachment decreased the content of polymerized actin, the actin staining intensity, and the actin fiber organization in the granulation tissue of both the flap and splint models. Disruption of wound matrix attachment decreased actin polymerization and fiber organization in the granulation tissue. Our data support the concept that the state of wound matrix attachment regulates the actin cytoskeleton of wound cells.     

The relation between syntactic and morphological recovery in agrammatic aphasia: A case study

BACKGROUND: Production of grammatical morphology is typically impaired in agrammatic aphasic individuals, as is their capacity to produce the syntactic structure responsible for licensing that morphology. Whether these two impairments are causally related has been an issue of long-standing debate. If morphological deficits are a side-effect of underlying syntactic ones, as has been claimed (Friedmann & Grodzinsky, 1997; Izvorski & Ullman, 1999), therapy which improves the syntactic deficit should remediate the morphological deficit as well. This paper reports a case study of one individual with such co-occurring impairments and describes their recovery in response to linguistically-motivated treatment targeting his syntactic deficits. METHODS #ENTITYSTARTX00026; PROCEDURES: MD is a 56 year-old male diagnosed with non-fluent Broca's aphasia subsequent to a left-hemisphere CVA, with limited capacity to produce syntactically complex utterances and grammatical morphology. He was enrolled in therapy using Treatment of Underlying Forms (TUF; Thompson & Shapiro, 2005), targeting production of sentences involving Wh-movement (object relative clauses). MD participated in twice-weekly treatment sessions for approximately two months, with daily probes assessing his production of treated and untreated sentence types. In addition, probes assessing his grammatical morphology and sentence production were administered pre- and post-treatment. OUTCOMES #ENTITYSTARTX00026; RESULTS: Pre-treatment scores in tests of grammatical morphology and sentence production indicated deficits in both domains. During treatment, MD successfully acquired production of a variety of sentence with Wh-movement, though this did not generalize to sentences involving a grammatically distinct movement operation (NP-movement). Post-treatment scores also indicated a lack of improvement in production of grammatical morphology. CONCLUSIONS: The dissociation between MD's morphological and syntactic recovery indicates that the recovery of syntactic and morphological processes in aphasia may occur independently. This result is thus surprising under approaches in which morphological and syntactic impairments are strongly and causally related in aphasia, such as the Tree-Pruning Hypothesis (Friedmann, 2001; Friedmann & Grodzinsky, 1997). Further, these results reinforce the conclusion that aphasia treatment can lead to generalization, but only to linguistic material which is in a subset relation to trained structures (Thompson, Shapiro, Kiran & Sobecks, 2003).     

P63Stem Cell and Immunotherapy Services, NHS Blood and Transplant, Birmingham, UK

Over 20 years ago, the Birmingham Blood Centre established a facility for the cryopreservation of bone marrow (BM) for patients in the West Midlands suffering from haematopoietic disorders and for whom a bone marrow transplant was indicated. Today, the use of mobilised peripheral blood (PBSC) has overtaken bone marrow as the source of stem cells for transplantation and the numbers of patients benefitting and the diversity of conditions being treated has increased enormously. Allogeneic transplants, using stem cells from healthy donors, have become increasingly successful as a result of an improving understanding of the complexities of the HLA histocompatibility system. Additionally umbilical cord blood (HUC), which in the 1980s was recognised as a source of stem cells, can now be collected and used for transplantation. As scientific knowledge and the clinical management of patients has advanced, so too have laboratory methods for manipulating cell products to enrich or deplete certain cell populations (e.g. by CD34+cell selection) in order to minimise potentially fatal graft-versus-host disease (GVHD) or to eliminate tumour cells in the case of autologous patients. Donor lymphocytes (DLI) may also be collected and used to aid a graft-versus-leukaemia (GVL) effect. The laboratory is currently developing protocols for immunotherapy using virus-specific T cells which can be prepared and infused to combat potentially fatal CMV disease post-transplant. Clinical trials of vaccines employing tumour specific dendritic cells for treating patients with hepatocellular carcinoma (HCC) and metastatic melanoma (MM), which do not respond to conventional treatments, are also underway. The advances and expansion in the Stem Cell and Immunotherapy (SCI) service in Birmingham over the last 10 year period are reflected in the table below:
 

     

Mapping brain size and cortical gray matter changes in elderly depression.

BACKGROUND: In elderly depression, volumetric brain imaging findings suggest abnormalities of the frontal lobe, particularly the orbitofrontal cortex, and the hippocampus. No studies to date have mapped cortical abnormalities over the entire brain surface in major depression. Here, we conducted detailed spatial analyses of brain size and gray matter within the cortical mantle in elderly patients with major depression. METHODS: High-resolution, three-dimensional, structural magnetic resonance imaging data and cortical pattern matching methods were used in 24 depressed elderly patients and 19 group-matched controls to measure local brain size and proportions of gray matter at thousands of homologous cortical surface locations. RESULTS: Prominent brain size reductions were observed in the depressed subjects in the orbitofrontal cortex bilaterally. Cortical gray matter measurements revealed significant gray matter increases in the orbitofrontal cortex, adjacent to focal trend level significant decreases of gray matter in the same region. Depressed patients also exhibited significant gray matter increases in parietal cortices, as well as the left temporal cortex. CONCLUSIONS: Complex cortical changes may contribute to the brain size reduction of the orbitofrontal cortex and to the gray matter abnormalities detected in orbitofrontal cortex and temporoparietal cortices, thereby providing a potentially new window into the pathophysiology of elderly depression.     

Diet and premenopausal bilateral breast cancer: A case-control study

We investigated associations between diet and premenopausal bilateral breast cancer in a familial matched case-control study. We studied 140 cases from population-based registries in Los Angeles County (California) and Connecticut, and from the major hospitals in the southern parts of the Province of Quebec. Unaffected sisters of the cases served as matched controls (222 total). Dietary intake were assessed with a food frequency questionnaire. Total fat, monounsaturated fat, polyunsaturated fat, oleic acid, and linoleic acid intake was inversely associated with premenopausal bilateral breast cancer risk. Consumption of carbohydrates (and sweetened beverages) was associated with an increased risk. We observed no associations for dietary fiber, antioxidants, or major food groupings, but we did observe inverse associations for intake of low fat dairy products and tofu. These findings suggest that monounsaturated and polyunsaturated fats, as well as soy foods, might reduce the risk of premenopausal bilateral breast cancer.