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...     

Skin problems after a tsunami

BACKGROUND: On December 26, 2004, the biggest earthquake for 40 years, measuring 9.0 on the Richter scale, triggered a tsunami that pounded the coastal areas of South Asia and East Africa. The effects of the tsunami on skin conditions have not been evaluated. OBJECTIVE: To determine the influence of the tsunami on skin conditions by evaluating the skin problems of patients presenting at hospitals after the tsunami. METHODS: Between 5 and 25 January 2005, two dermatologists evaluated patients who complained of skin problems at an outpatient clinic and emergency room of a general hospital in Banda Aceh, Aceh Province, Indonesia. RESULTS: The total number of patients that presented during the study period was 235 (131 males and 104 females), and they had a total of 265 skin problems. In terms of age distribution, most subjects were in their fourth decade (23.0%), followed by the third (22.6%) and fifth decade (16.6%). The most prevalent skin problems were infections-infestations (32.5%), followed by eczemas (29.8%) and traumatic skin disorders (29.4%). In males, traumatic skin disorders were most common. The great majority of infection-infestation cases involved superficial fungal infections. Contact dermatitis accounted for three-quarters of eczema cases, and mainly involved the arms (40.0%) and legs (27.1%). The majority of traumatic skin disorders were lacerations, punctures and penetrations, and the feet (44.7%) and hands (18.8%) were most frequently affected. CONCLUSIONS: Unhygienic conditions, exposure to a hazardous environment and contact with various objects during and after the tsunami probably increased the prevalence of infections-infestations, traumatic skin disorders and contact dermatitis. To prevent these problems and associated secondary bacterial infections, health-related education and early medical management are required.     

The in vitro pharmacological profile of KR31080, a nonpeptide AT1 receptor antagonist

Summary— KR31080 (2-butyl-5-methyl-6-(1-oxopyridin-2-yl)-3-[[2'-(1H-tetrazol-5-yl) biphenyl-4-yl]methyl]-3H-imidazo[4,5-b] pyridine) is a potent inhibitor of angiotensin type 1 (AT₁) receptors in rabbit aorta and human recombinant AT₁ receptors. In the isolated rabbit thoracic aorta, KR31080 caused a nonparallel shift to the right of the concentration-response curves to angiotensin II (All) with decreased maximal response (pD'₂ = 10.1 ± 0.1), but had no effect on the contractile response induced by norepinephrine. KR31080 inhibited specific [¹²⁵I]AII binding to rabbit aortic membranes (AT, receptors) and [¹²⁵I][Sar¹, Ile⁸]AII binding to human recombinant AT₁ receptors in a concentration-dependent manner with IC₅₀ values of 0.84 ± 0.08 nM and 1.92 ± 0.15 nM, respectively, but did not inhibit specific [¹²⁵I)AII binding to bovine cerebellum membranes (ÀT₂ receptors). In the Scatchard analysis, KR31080 interacted with rabbit aortic AT₁ receptors in a competitive manner, similar to losartan. These results demonstrate that KR31080 is a potent and AT₁ selective angiotensin receptor antagonist which exerts a competitive antagonism in the [¹²⁵I]AII binding assay and insurmountable AT₁ receptor antagonism in the functional study.     

Overexpression/amplification of HER-2/neu is uncommon in hepatocellular carcinoma

BACKGROUND： Hepatocellular carcinoma （HCC） is one of the most prevalent fatal cancers in the world. Despite advances in early diagnosis and improvements in surgical techniques, the survival of patients with HCC even after resection is poor because of the high incidence of recurrences. Therefore, the identification of prognostic factors may be helpful in the development of new treatment protocols. AIMS： To investigate HER-2/neu status in HCC by immunohistochemistry （IHC） and fluorescence in situ hybridisation （FISH）, and to explore the possibility of using trastuzumab in the treatment of HCC. METH ODS： Eight hundred and sixty eight surgical samples from patients with primary HCC were examined for their HER-2/neu status. IHC for HER-2/neu was performed with the HercepTest kit; FISH analysis was performed with the PathVysion HER-2 DNA probe kit. The correlations between HER-2/neu overexpression and clinicopathological characteristics were analysed statistically. RESULTS： HER-2/neu overexpression was detected in 21 （2.42%） of the 868 primary HCCs. Only one specimen showed HER-2/neu gene amplification by FISH. No significant associations were found between HER-2/neu overexpression and the clinicopathological parameters. CONCLUSIONS： There is a low frequency of HER-2/neu overexpression/amplification in HCC. There appears to be no role for HER-2/neu as a prognostic marker and no benefit of anti-HER-2/neu trastuzumab treatment in patients with HCC.     

Evaluation of four elastomeric interocclusal recording materials

Background: The fabrication of dental prosthesis requires the transfer of interocclusal records from patient's mouth to semiadjustable articulators using different kinds of recording media. Any inaccuracy in these interocclusal records leads to occlusal errors in the final prosthesis. This study was conducted to evaluate the dimensional changes occurring in the interocclusal recording material over a given period of time and the material's resistance to compression during the cast mounting on the articulator.     

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.     

LIPOPROTEIN(α) IN HEALTH AND DISEASE

SUMMARY Elevated plasma levels of Lp(a) do seem to influence the progression of atherosclerosis. Evidence is emerging that certain apo(a) isoforms may be more atherogenic than others, and in transgenic mice free apo(a) has been shown to be associated with accelerated atherosclerosis. Currently it is not known whether treating elevated Lp(a) levels will reduce progression of atherosclerosis and, as therapeutic options are limited, mass screening of Lp(a) levels in populations is not indicated. The presence of raised Lp(a) levels, however, warrants aggressive treatment to reduce other cardiovascular risk factors. Continuing research to investigate the relationship of the apo(a) gene to other genes, including the plasminogen gene and apo(a)-related genes, will add further information pertaining to the evolution, function, regulation and clinical implications of Lp(a).