The hippocampus is not necessary for a place response but may be necessary for pliancy

Rats with kainate-colchicine hippocampal lesions (HL) and controls (C) were initially trained in the Morris water maze with procedures that deterred their prepotent thigmotaxic response. Training began with an escape platform that occupied nearly the entire pool. The area to which the rats could escape was made smaller by substituting smaller platforms as training progressed. In contrast to standard procedures, HL rats and C rats showed comparable performance during acquisition and preferentially searched the goal quadrant on probe trials during which the platform was removed. In a follow-up experiment, the platform was moved to a random position along the wall, which required a switch to a thigmotaxic response for most effective escape. HL rats that were thigmotaxic before place training did not switch to a thigmotaxic response as readily as did controls, behavior consistent with the view that hippocampal damage reduces pliancy.     

Effects of hemipancreatectomy on insulin secretion and glucose tolerance in healthy humans

Pancreatic tissue obtained by hemipancreatectomy from healthy living related donors has been transplanted into recipients with Type I diabetes mellitus. To determine the metabolic consequences of this procedure for the donors, we carried out oral glucose-tolerance testing and 24-hour monitoring of serum glucose levels and urinary C-peptide excretion as a measure of insulin secretion in 28 donors, both before and one year after hemipancreatectomy. The mean fasting serum glucose level was significantly higher one year after the procedure (mean +/- SD, 5.4 +/- 0.9 vs. 4.9 +/- 0.5 mmol per liter; P less than 0.003), as was the serum glucose value two hours after the administration of glucose (8.7 +/- 2.9 vs. 6.5 +/- 1.0 mmol per liter; P less than 0.001). The fasting serum insulin level was significantly lower one year after hemipancreatectomy (33.0 +/- 21.6 vs. 38.4 +/- 21.6 pmol per liter; P less than 0.05), as was the area under the insulin curves during the oral glucose-tolerance test (52,554 +/- 22,320 vs. 76,230 +/- 33,354 pmol per liter per minute; P less than 0.04). The mean 24-hour serum glucose-profile value was higher at one year, and the 24-hour urinary C-peptide excretion was lower in the 17 donors who underwent these studies. Seven of the 28 donors had abnormal glucose tolerance one year after hemipancreatectomy; however, insulin secretion in these 7 donors was indistinguishable from that in the 21 donors who had normal glucose tolerance. All 28 donors had fasting serum glucose concentrations lower than 7.8 mmol per liter, and their mean 24-hour plasma glucose levels remained within the normal range. We conclude that in healthy donors hemipancreatectomy results in a deterioration of insulin secretion and glucose tolerance, as measured one year later. Further study is required to ascertain whether the development of clinical diabetes mellitus is a risk inherent in hemipancreatectomy.     

Airway inflammation in chronic obstructive pulmonary disease: comparisons with asthma

Chronic obstructive pulmonary disease (COPD) is a progressive syndrome of expiratory airflow limitation caused by chronic inflammation of the airways and lung parenchyma. The airway inflammatory response in COPD is initiated by smoking in the overwhelming majority of cases, and chronic exposure to cigarette smoke initiates a series of events that causes damage to central airways, peripheral airways, and terminal airspaces, leading to physiologic and clinical abnormalities. Although COPD shares some clinical features with asthma, another prevalent airway inflammatory disease, there are distinct differences in the phenotypic characteristics of airway inflammation between COPD and asthma. The eosinophil is the most prominent inflammatory cell in asthma, with mast cells, lymphocytes, and macrophages playing important but less prominent roles. In COPD the cellular composition of the airway inflammatory infiltrate differs, with neutrophils, macrophages, and lymphocytes assuming prominence and the eosinophil playing a minor role, except in the setting of exacerbations. The contrasting inflammatory phenotypes of asthma and COPD have important implications for clinical and physiologic manifestations of disease, as well as for therapy.     

Serum calcium as an early indicator for surgical treatment of hyperparathyroidism after renal transplantation

In an attempt to find out if a particular group of patients with hyperparathyroidism after renal transplantation (HRT) are at risk of developing complications, 14 patients with overt untreated HRT who had at least 1 serum calcium determination 12 mg/100 ml were evaluated and compared retrospectively with 11 normocalcemic transplant recipients at 6 and 30± 8 months after successful renal allografting. Serum calcium was 12 mg/100 ml within 6 months of transplantation in 13 of the 14 HRT patients. At 6 months significant differences were found between HRT and controls in mean serum calcium (11.6 versus 9.2 mg/100 ml) and alkaline phosphatase (228 versus 120 U/l). At 30±8 months differences were found in serum calcium (10.2 versus 9.4 mg/100 ml), phosphate (2.8 versus 4.8 mg/100 ml), and alkaline phosphatase (180 versus 88 U/l). Serum creatinine levels were similar in the 2 groups. A significant correlation was found between early and late determinations of alkaline phosphatase when all 25 patients were studied as a single group (r=0.72, p<0.001). Bone pain and/or radiological evidence of hyperparathyroid bone disease were significantly associated with HRT (8 versus 1 and 7 versus 0, respectively). A higher but not significant incidence of vascular calcifications (5 versus 1) and acute pancreatitis (2 versus 0) was found in HRT. Patients who develop moderate to severe HRT as defined by at least 1 serum calcium determination 12 mg/100 ml do so within 6 months of renal transplantation, have increased morbidity, particularly involving the skeleton, and might benefit from early subtotal parathyroidectomy.

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Resumen Con el propósito de determinar si el grupo particular de pacientes con hiperparatiroidismo después de transplante renal (HTR) posee riesgo de desarrollar complicaciones, se realizó la evaluación de 14 casos definidos de HTR no tratados y que presentaban por lo menos un valor de calcio sérico 12 mg/100 ml, los cuales fueron comparados con 11 recipientes normocalcémicos de transplante renal a los 6 y 30 ±8 meses después de un aloinjerto renal exitoso. El calcio sérico apareció en 12 mg/100 ml dentro de los primeros 6 meses de efectuado el transplante en 13 de 14 pacientes con HTR. A los 6 meses se hallaron diferencias significativas entre los pacientes con HTR y los controles en el valor promedio del calcio sérico (11.6 vs. 9.2 mg/100 ml) y de la fosfatasa alcalina (228 vs. 120 U/l). A los 30±8 meses se hallaron diferencias en el calcio sérico (10.2 vs. 9.4 mg/100 ml), fosfato (2.8 vs. 4.8 mg/100 ml) y fosfatasa alcalina (180 vs. 88 U/l). Los niveles de creatinina sérica aparecieron similares en los 2 grupos. Se encontró una correlación significativa entre las determinaciones tempranas y las tardías de la fosfatasa alcalina cuando la totalidad de los 25 pacientes fue estudiada como grupo único (r= 0.72, p<0.001). El dolor óseo y/o la evidencia radiológica de enfermedad ósea paratiroidea aparecieron en asociación significativa con el HTR (8 vs. 1 y 7 vs. 0, respectivamente). Una incidencia mayor, aunque no significativa, de calcificaciones vasculares (5 vs. 1) y de pancreatitis aguda (2 vs. 0) fue hallada en el HTR. Los pacientes con HTR severo definido como el hallazgo de por lo menos una determinación de calcio sérico 12 mg/100 ml, lo desarrollan dentro de los 6 meses siguientes al transplante renal, presentan morbilidad aumentada, especialmente con afección esquelética, y es posible que se beneficien de paratiroidectomía subtotal.

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Résumé Dans le but de déterminer les risques de complications chez un groupe de malades ayant présenté un hyperparathyroïdisme après transplantation rénale les auteurs ont comparé une série de 14 cas où le taux de calcium avait été au moins une fois supérieure à 12 mg/100 ml et une série de 11 receveurs où le taux de calcium était normal et ce 6 et 30±8 mois après allogreffe rénale. Au bout de 6 mois le taux de calcium fut supérieur à 12 mg/100 ml chez 13 des 14 malades qui avaient subi une transplantation rénale. Des différences significatives furent constatées entre les transplantés et les sujets appartenant au groupe de contrôle aussi bien en ce qui concerne le calcium sérique (11.6 contre 9.2 mg/100 ml) et la phosphatase alcaline (228 contre 120 U/l). Au terme de 30±8 mois des différences furent également constatées pour le calcium (10.2 contre 9.4 mg/100 ml), pour le phosphore (2.8 contre 4.8 mg/100 ml) et pour la phosphatase alcaline (180 contre 88 U/l). Les taux de créatinine sérique étaient identiques dans les 2 groupes. Une corrélation significative fut constatée entre les déterminations précoces et tardives de la phosphatase alcaline chez les 25 sujets rassemblés en un seul groupe (r=0.72, p<0.001). La douleur osseuse et/ou des signes radiologiques évidents d'atteinte osseuse d'origine hyperparathyroïdienne allaient de pair significativement chez les transplantés (8 contre 1 et 7 contre 0 respectivement). Chez ceux-ci fut constatée une fréquence supérieure mais non significative de calcifications vasculaires (5 contre 1) et de pancréatite aiguë (2 contre 0). Les opérés qui ont développé un hyperparathyroïdisme modéré ou intense (un taux supérieur à 12 mg/100 ml, au moins une fois) au cours des 6 mois qui suivirent la transplantation rénale, en particulier lorsqu'ils présentèrent une atteinte du squelette, devraient bénéficier d'une parathyroïdectomie subtotale.

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

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Supported by a grant from the Fondo de Investigaciones Sanitarias de la Seguridad Social. Ministerio de Sanidad, Spain.     

Pancreas and islet transplant registry data

From December 16, 1966, to June 30, 1983, some 337 pancreas transplants in 316 diabetic patients from 305 cadaveric and 32 living related donors were performed at 46 institutions throughout the world. A total of 60 pancreas transplants in 56 patients were performed prior to July 1, 1977, with only 2 functioning for more than 1 year. Therefore, the present era includes 277 pancreas trans-plants performed in 262 patients at 39 institutions. Seventy-four of these were done in 1982, while 72 were performed in the first 6 months of 1983 with 11 new institutions reporting. Of the 262 patients in the present era, 74 (28%) have died with 48 (18%) of these dying within the first 3 months of transplantation. Of the 190 pancreas transplants performed up to December, 1982, and available for evaluation of 1-year graft function, 31 (16%) are currently functioning; another 8 (4%) functioned for 1 year but then failed (7) or the recipient died (1). Of the 72 transplants done in the first 6 months of 1983, there are 26 (37%) still functioning. Results are expressed according to technique of handling the ductal drainage, association with kidney transplantation, and association with the type of immunosuppression. Seventeen non-diabetic patients (13 with chronic pancreatitis, 4 with adenocarcinoma) had autotransplantation of a segment of the pancreas after pancreatectomy. Thirteen were said to function but follow-up data are incomplete. There were 73 islet tissue allografts reported as of June 30, 1980, but none of the patients achieved insulin independence. Since then an additional 86 islet tissue allografts have been reported without any insulin independence achieved to make a total of 159 performed without normoglycemia. A total of 79 pancreatectomized patients have received islet tissue autografts with 50% being reported as insulin independent, but the results are difficult to interpret.

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Resumen En el périodo comprendido del 16 de diciembre de 1966 al 30 de junio de 1983, 316 diabéticos han sido sometidos a 337 transplantes pancreáticos (305 cadavéricos y 32 de donantes vivos) en 46 instituciones. En el périodo antes del 1 de julio de 1977 un total de 60 transplantes pancreáticos se ejecutaron en 56 pacientes y solamente 2 funcionaron más de un año. Por consiguiente la actual epoca incluye 277 transplantes pancreáticos ejecutados en 262 pacientes en 39 instituciones. En 1982 se ejecutaron 74 y en los primeros seis meses del 1983 se reportaron 72 nuevos transplantes pancreáticos e incluyó 11 instituciones nuevas. Durante la actual época 74 de 262 pacientes (28%) han muerto y 48 (18%) de estos murieron durante los primeros tres meses del transplante. De los 190 transplantes de páncreas ejecutados hasta diciembre de 1982 y evaluables en relación a su función al año, 31 (16%) estan actualmente funcionando y 8 (4%) funcionaron por un año y fracasaron más tarde (7) o el recipiente murió (1). De los 72 transplantes ejecutados en los primeros 6 meses del 1983, 26 (37%) mantienen buena función. Los resultados son expresados de acuerdo a la tenica utilizada para el drenaje del conducto pancreático, su asociación con transplante renal y el tipo de inmunosupresión utilizado. Diecisiete pacientes no diabéticos recibieron autotransplante de páncreas parcial (13 con pancreatitis crónica y 4 con adenocarcinoma). Trece se han reportado con función, pero la información es incompleta. Hasta el 30 de junio de 1980 se reportaron 73 aloinjertos de tejido de islotes y ninguno logró la insulinoindependencia. Otros 86 injertos de islotes se han reportado desde esa fecha, pero ninguno ha logrado la insulinoindependencia, lo que hace un total de 159 aloinjertos de islotes sin obtener normoglicemia. Setenta y nueve pacientes con autoinjertos de islotes han sido reportado y supuestamente la mitad son insulinoindependientes aunque estos resultados son difïciles de interpretar.

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Résumé Du 16 décembre 1966 au 30 juin 1983, quelque 337 transplantations pancréatiques ont été pratiquées avec des greffons provenant de 305 cadavres et 32 donneurs vivants apparentés, sur 316 patients diabétiques dans 46 établissements à travers le monde. Soixante greffes de pancréas au total ont été faites chez 56 patients avant le 1^er juillet 1977, dont 2 seulement ont fonctionné plus d'un an; c'est pourquoi la revue ci-dessous concerne 277 greffes pratiquées sur 262 malades dans 39 établissements. Soixante-quatorze ont été faites en 1982, tandis que 72 ont été rapportées dans les 6 premiers mois de 1983, dans 11 nouveaux établissements. Sur les 262 patients passés en revue, 74 (28%) sont morts, dont 47 (18%) dans les 3 mois après la greffe. Sur les 190 transplantations pancréatiques réalisées jusqu'à décembre 1982 et pour lesquelles on dispose de résultats de tests pratiqués après un an de fonction du greffon, 31 (16%) sont actuellement fonctionelles et 8 autres (4%) ont échoué après plus d'un an de fonction (7) ou leur receveur est mort(1). Parmi les 72 greffes réalisées dans le premier semestre de 1983, 26 (37%) sont encore fonctionnelles. Les résultats sont classés d'après la méthode de drainage des sécrétions exocrines, l'association ou non à une greffe rénale, et le type de traitement immunosuppresseur associé à la greffe. Dix-sept patients n'étaient pas diabétiques (13 atteints de pancréatite chronique, 4 d'adénocarcinome) mais ont subi une auto-transplantation segmentaire de pancréas; parmi eux, 13 auraient un greffon fonctionnel, mais les données sur l'évolution des sujets sont incomplètes. Soixante-treize hétérogreffes d'îlots ont été rapportées jusqu'au 30 juin 1980, sans qu'une seule entraîne de sevrage définitif de l'insulinothérapie. Depuis lors, 86 hétérogreffes d'îlots ont été rapportées sans entraîner de sevrage insulinique, soit un total de 159 greffes qui ont été pratiquées sans entraîner de retour à la normoglycémie; 79 patients au total ont recu des autogreffes d'îlots et 50% d'entre eux sont décrits comme n'ayant plus besoin d'insuline, mais ces résultats sont difficiles à interprêter.

     

Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo-Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo-Ia difference on such islets, pretreatment of the islets with anti-Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo-Ia antigens can lead to a stronger anti-class I rejection response.     

Psycholinguistic features,design attributes,and respondent-reported cognition predict response time to patient-reported outcome measure items

Purpose

Patient-reported outcome measures (PROMs) vary in their psycholinguistic complexity. This study examined whether response time to PROM items is related to psycholinguistic attributes of the item and/or the self-reported cognitive ability of the respondent.

Methods

Baseline data from Wave 2 of the Quality of Life in Neurological Disorders (Neuro-QoL) development study were reanalyzed. That sample contained 581 adults with neurological disorders and whose self-reported cognitive abilities were quantified by the Neuro-QoL v2.0 Cognitive Function Item Bank. 185 Neuro-QoL items were coded for several psycholinguistic variables and design attributes: number of words and syllables, mean imageability of words, mean word frequency, mean age of word acquisition, and response format (e.g., about symptom frequency or task difficulty). Data were analyzed with linear and generalized linear mixed models.

Results

Main effects models revealed that slower response times were associated with respondents with lower self-reported cognitive abilities and with PROM items that contained more syllables, less imageable (e.g., more abstract) words, and that asked about task difficulty rather than symptom frequency. Interaction effects were found between self-reported cognition and those same PROM attributes such that people with worse self-reported cognitive abilities were disproportionately slow when responding to items that were longer (more syllables), contained less imageable words, and asked about task difficulty.

Conclusion

Completing a PROM requires multiple cognitive skills (e.g., memory, executive functioning) and appraisal processes. Response time is a means of operationalizing the amount or difficulty of cognitive processing, and this report indicates several aspects of PROM design that relate to a measure’s cognitive burden. However, future research with better experimental control is needed.