Burden of illness among patients with severe aplastic anemia who have had insufficient response to immunosuppressive therapy: a multicenter retrospective chart review study

Annals of Hematology - This study assessed treatment patterns and healthcare resource utilization (HRU) of patients with severe aplastic anemia (SAA) with insufficient response to immunosuppressive...     

Perforated colorectal neoplasms: correlation of clinical, contrast enema, and CT examinations

Results of clinical, contrast enema (CE), and computed tomographic (CT) examinations in 39 patients with perforated colorectal neoplasms were retrospectively reviewed. Twenty patients were toxemic at initial presentation, but in only four patients was the diagnosis of perforated colorectal neoplasm initially suspected clinically. CE study was performed in 22 patients and enabled the diagnosis of perforated neoplasm in 11 cases, neoplasm alone in eight, and neither neoplasm nor perforation in three. CT was performed in 38 patients and enabled the diagnosis of perforated neoplasm in 36; pericolic phlegmon but no mass lesion was evident in two. In 16 patients, CT also demonstrated metastatic disease. Because of its reliability in establishing the diagnosis and staging the extent of the inflammatory and neoplastic disease, CT is indicated in cases of suspected or proved perforated colorectal neoplasm and in cases in which CE study findings are indeterminate or suggestive of perforated neoplasm.     

The efficacy and limitations of percutaneous endoscopic gastrostomy.

We analyzed 64 percutaneous endoscopic gastrostomy procedures performed by us between 1986 and 1990. Thirty patients had neurologic disease; 16 had head and neck cancers; eight had other malignancies; two had acquired immunodeficiency syndrome; and eight had other problems. Seven patients died within 30 days of complications (n = 4) or the primary illness (n = 3). Mean follow-up was 6 months; an additional patient died of aspiration and eight others died of their underlying illness. There were 19 complications (32%). Four wound complications occurred. Nine patients developed aspiration pneumonia within 3 days of the procedure, four of whom died in the hospital. Of the 24 patients with a history of aspiration, nine experienced aspiration during or after percutaneous endoscopic gastrostomy. Patients with a history of aspiration were more likely to have perioperative aspiration pneumonia, and patients who experienced aspiration were more likely to die.     

Epidermal growth factor receptors and adenylate cyclase activity in human thyroid tissues

Thyroid stimulating hormone (TSH) and epidermal growth factor (EGF) are growth factors for some thyroid cells in cultures. We have previously found more EGF receptors in neoplastic human thyroid tissues than in normal thyroid tissues. We have also found a higher TSH-stimulated adenylate cyclase (AC) activity in neoplastic human thyroid tissues than in normal thyroid tissues. To clarify the relationship between the effect of EGF and TSH on thyroid tissue, we measured the binding of EGF and TSH and the basal, TSH-stimulated and forskolin-stimulated adenylate cyclase activity in 49 normal, hyperplastic and neoplastic human thyroid tissues (5 normal, 2 Hashimoto thyroiditis, 5 Graves' disease, 14 multinodular goiters, 9 follicular adenomas, S follicular carcinomas, 8 papillary carcinomas, and 1 undifferentiated carcinoma). Specific binding of EGF and TSH were measured by radioreceptor assays using competitive inhibition of radio-labeled ligand by unlabeled ligand. Basal, maximally (300 mU/ml) TSH-stimulated, and maximally (100 mM) forskolin-stimulated adenylate cyclase activities were also measured in the same membrane particulate fractions from the thyroid tissues. We found: neoplastic thyroid tissues bind more labeled EGF than nonneoplastic thyroid tissues; follicular adenomas and carcinomas have higher EGF binding than other thyroid tissues; a weak but significant correlation between specific EGF binding and specific TSH binding, and between specific EGF binding and TSH-stimulated adenylate cyclase activity of the thyroid membrane preparations. These findings are consistent with the hypothesis that TSH stimulates an increase in thyroid EGF receptors by increasing intracellular cAMP. The higher binding of EGF and the higher TSH-stimulated AC activity may explain why thyroid neoplasms grow to a larger size than normal thyroid tissues.

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Resumen La hormona estimuladora de tiroides (TSH) y el factor de crecimiento epidermal (EGF) son factores de crecimiento para algunas células tiroideas en cultivo tisular. Previamente hemos informado el hallazgo de más receptores de EGF en tejidos tiroideos neoplásicos humanos que en tejidos tiroideos normales. Con el objeto de clarificar la relación entre el efecto del EGF y de la TSH sobre el tejido tiroideo, realizamos la determinacion de la ligación del EGF y de la TSH y de la actividad basai y de la actividad estimulada por TSH y forskolina de la adenilato-ciclasa (AC) en 49 especímenes de tejido tiroideo humano (5 normales, 2 tiroiditis de Hashimoto, 5 enfermedad de Graves, 14 bocios multinodulares, 9 adenomas foliculares, 5 carcinomas foliculares, 8 carcinomas papilares, y 1 carcinoma indiferenciado). La ligadura especifica del EGF y de la TSH fue medida mediante determinaciones de receptores utilizando inhibición competitiva radiomarcada. También se determinó la actividad basai y la actividad estimulada por forskolina de la adenilato-ciclasa en las mismas fracciones de tejidos tiroideos. Se registraron los siguientes hallazgos: los tejidos neoplásicos ligan más EGF marcado que los tejidos tiroideos no neoplásicos; los adenomas foliculares y los carcinomas poseen una capacidad de ligación del EGF mayor que los otros tejidos tiroideos; hay una débil pero significativa correlación entre la ligación especifíca del TGF y la de la TSH, y entre la ligación específica del EGF y la actividad estimulada por TSH de la adenilato-ciclasa en las preparaciones de membrana tiroidea. Estos hallazgos aparecen consistentes con la hipótesis de que la TSH estimula un aumento en los receptores de EGF mediante el incremento de la cAMP intracelular. La aumentada ligación de EGF y la incrementada actividad estimulada de TSH pueden explicar el por qué los neoplasmas tiroideos crecen hasta un tamaño mayor que los tejidos tiroideos normales.

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Résumé La thyroid stimulating hormone (TSH) et l'epidermal growth factor (EGF) sont des facteurs de croissance agissant sur certaines cellules thyroïdes en culture. Nous avons trouvé qu'il y avait plus de récepteurs EGF dans le tissu thyroïde humain néoplasique que dans le tissu thyroïdien normal. Nous avons également montré qu'il y avait plus d'activité d'adenylate cyclase stimulée par la TSH dans le tissu thyroïden néoplasique par rapport au tissu normal. Pour clarifier le rapport entre les effets de l'E.GF et la TSH sur le tissu thyroïden, nous avons mesuré l'activité de liaison d'EGF, de TSH et l'activité adénulate cyclase de base, stimulée par la TSH, et par la forskoline chez 49 patients ayant du tissu normal, hyperplasique ou néoplasique (5 normaux, 2 thyroïdites de Hashimoto, 5 maladies de Basedow, 14 goîtres multinodulaires, 9 adénomes folliculaires, 5 cancers folliculaires, 8 cancers papillaires, et 1 cancer indifférencié). Les liaisons spécifiques d'EGF et de TSH ont été mesurées par le dosage des récepteurs nucléaires par la méthode de déplacement des ligands marqués par des ligands froids (non marquées). Les activités adénylate cyclase de base, maximale (300 mU/mL), stimulée par la TSH (300 mU/mL) et la forskoline (100 mM) ont été également mesurées dans les mêmes fractions de particules membranaires provenant des tissus thyroïdens. Nous avons trouvé que: les tissus néoplasiques se liaient davantage avec l'EGF que les tissus non néoplasiques; les adénomes folliculaires et les cancers avaient un index de liaison plus élevé que les autres tissus thyroïdens; et il y avait une corrélation faible mais significative entre la liaison spécifique EGF et TSH, et entre la liaison spécifique EGF et l'activité adénylate cyclase des préparations de membrane thyroïdienne. Ces résultats sont en faveur de l'hypothèse selon laquelle la TSH provoque une augmentation des récepteurs EGH de la thyroïde en augmentant la concentration intracellulaire d'AMP cyclique. Le degré de liaison d'EGF élevé, et l'augmentation de l'activité stimulée par la TSH peuvent expliquer la croissance accélérée des tissus néoplasiques par rapport à celle des tissus normaux.

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Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.

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Supported in part by the Medical Research Service of the Veterans Administration Medical Center, San Francisco, California and the Affirmative Action Faculty Development Grant of the University of California, San Francisco, California.     

Molecular and Serological Evidence for Anaplasma platys and Babesia sp. Infection in a Dog,Imported in Belgium,from Southern Spain

This case report describes a dog suffering from a co‐infection with Babesia and Anaplasma parasites. Anaplasma platys was found to be responsible for the anaplasmosis by molecular biology techniques, while microscopical and serological evidence was found for a coexistent babesiosis, although this could not be confirmed by polymerase chain reaction. Moreover, the possible risk of import of exotic pathogens is highlighted.     

Frequent ongoing T-cell receptor rearrangements in childhood B- precursor acute lymphoblastic leukemia: implications for monitoring minimal residual disease

Crosslineage T-cell receptor delta (TCR delta) rearrangements are widely used as tumor markers for the follow up of minimal residual disease in childhood B-precursor acute lymphoblastic leukemia (ALL) by polymerase chain reaction (PCR). The major drawback of this approach is the risk of false-negative results due to clonal evolution. We investigated the stability of V delta 2D delta 3 rearrangements in a group of 56 childhood B-precursor ALL patients by PCR and Southern blot analysis. At the PCR level, V delta 2D delta 3-to-J alpha rearranged subclones (one pathway for secondary TCR delta recombination) were demonstrated in 85.2% of V delta 2D delta 3-positive patients tested, which showed that small subclones are present in the large majority of patients despite apparently monoclonal TCR delta Southern blot patterns. Sequence analysis of V delta 2D delta 3J alpha rearrangements showed a biased J alpha gene usage, with HAPO5 and J alpha F in 26 of 32 and 6 of 32 clones, respectively. Comparison of V delta 2D delta 3 rearrangement status between diagnosis and first relapse showed differences in seven of eight patients studied. In contrast, from first relapse onward, no clonal changes were observed in six patients studied. To investigate the occurrence of crosslineage TCR delta rearrangements in normal B and T cells, fluorescence-activated cell sorter-sorted peripheral blood CD19+/CD3- and CD19-/CD3+ cell populations from three healthy donors were analyzed. V delta 2D delta 3 rearrangements were detected at low frequencies in both B and T cells, which suggests that V delta 2-to-D delta 3 joining also occurs during normal B-cell differentiation. A model for crosslineage TCR delta rearrangements in B-precursor ALL is deduced that explains the observed clonal changes between diagnosis and relapse and is compatible with multistep leukemogenesis of B-precursor ALL.