The use of recombinant-activated factor VII in von Willebrand disease: a case series.

Spontaneous and surgery-associated bleeding in patients with von Willebrand disease (vWD) cannot always be controlled with desmopressin or replacement therapy. This paper presents results on the use of recombinant-activated factor VII (rFVIIa) in patients with vWD included in the internet registry Haemostasis.com. Twenty-eight reports on the use of rFVIIa in vWD were identified from the database and included in this analysis. The bleeding episodes were classified as mild (n = 7), moderate (n = 16), or severe (n = 2), and were unspecified in three cases. The median dose of rFVIIa administered was 94 microg/kg body weight (40-127.3 microg/kg). Bleeding stopped in 23 of 27 evaluable patients (85%) and markedly decreased in three patients; the total response rate was 96% (26/27 patients). Response did not correlate with the type of vWD, the site or severity of the initial bleed, or the rFVIIa dose. Other replacement therapies were infrequently used, and their use was similar in the 24 h before and after rFVIIa administration. Eighteen patients also received antifibrinolytic treatment, but its impact on response was not recorded. Only one adverse event (mild fever) was observed. These cases suggest a role for rFVIIa as a safe and effective therapy for vWD.     

Results of a 2-year examination of patients with essential hypertension and left ventricular hypertrophy

A study of 52 middle-aged males with essential hypertension, unaccompanied by cardiovascular disorders, is reported. The patients were divided into 2 groups with respect to the type of treatment they received: 30 patients on beta-adrenoblockers and 22 patients on methyldopa. The patients were treated continuously for 2 years under one-dimensional echocardiographic control. The greatest drop in arterial blood pressure and ventricular septum thickness was seen within the first 6 months of treatment, while posterior-wall hypertrophy disappeared altogether. Although there was no further drop in blood pressure after 6 months, the thickness of the ventricular septum remained reduced for at least 2 years. Regression of left-ventricular hypertrophy was not accompanied with any deterioration of left-ventricular performance, nor was it related to additional use of vasodilators.     

Characterization of a highly polymorphic marker adjacent to the SLC4A1 gene and of kidney immunostaining in a family with distal renal tubular acidosis.

BACKGROUND: Mutations in the human SLC4A1 (AE1/band 3) gene are associated with hereditary spherocytic anaemia and with distal renal tubular acidosis (dRTA). The molecular diagnosis of AE1 mutations has been complicated by the absence of highly polymorphic genetic markers, and the pathogenic mechanisms of some dRTA-associated AE1 mutations remain unclear. Here, we characterized a polymorphic dinucleotide repeat close to the human AE1 gene and performed an immunocytochemical study of kidney tissue from a patient with inherited dRTA with a defined AE1 mutation. METHODS: One CA repeat region was identified in a phage P1-derived artificial chromosome (PAC) clone containing most of the human AE1 gene and the upstream flanking region. We determined its heterozygosity value in multiple populations by PCR analysis. Genotyping of one family with dominant dRTA identified the AE1 R589H mutation, and family member genotypes were compared with the CA repeat length. AE1 and vH(+)-ATPase polypeptides in kidney tissue from an AE1 R589H patient were examined by immunocytochemistry for the first time. RESULTS: This CA repeat, previously reported as D17S1183, is approximately 90 kb upstream of the AE1 gene and displayed considerable length polymorphism, with small racial differences, and a heterozygosity value of 0.56. The allele-specific length of this repeat confirmed co-segregation of the AE1 R589H mutation with the disease phenotype in a family with dominant dRTA. Immunostaining of the kidney cortex from one affected member with superimposed chronic pyelonephritis revealed vH(+)-ATPase-positive intercalated cells in which AE1 was undetectable, and proximal tubular epithelial cells with apparently enhanced apical vH(+)-ATPase staining. CONCLUSIONS: The highly polymorphic dinucleotide repeat adjacent to the human AE1 gene may be useful for future studies of disease association and haplotype analysis. Intercalated cells persist in the end-stage kidney of a patient with familial autosomal dominant dRTA associated with the AE1 R589H mutation. The absence of detectable AE1 polypeptide in those intercalated cells supports the genetic prediction that the AE1 R589H mutation indeed causes dominant dRTA.     

The effect of partial hepatectomy on the genotoxicity of aflatoxin B1

The influence of partial hepatectomy on the genotoxic effect of aflatoxin B1 (AFB1) mycotoxin in male Chinese hamsters (Cricetulus griseus) was studied after application of a single i.p. dose of 1.0 mg AFB1/kg. Changes in the fractions of proliferating bone marrow cells, values of the mitotic index of liver cells and morphologic changes in liver tissue were also monitored. Partial hepatectomy reduced significantly the mutagenic activity of AFB1 measured by the frequency of chromosome aberrations in bone marrow cells during 5 days. In hepatectomized animals AFB1 cytotoxicity was significantly reduced as evaluated by changes in the values of proliferating bone marrow cell fractions. There were no important morphologic changes in the liver. In hepatectomized AFB1 treated animals mitotic activity in liver tissue was substantially lower than in hepatectomized but AFB1 untreated animals.     

Parallel image reconstruction using B-spline approximation (PROBER).

A new reconstruction method for parallel MRI called PROBER is proposed. The method PROBER works in an image domain similar to methods based on Sensitivity Encoding (SENSE). However, unlike SENSE, which first estimates the spatial sensitivity maps, PROBER approximates the reconstruction coefficients directly by B-splines. Also, B-spline coefficients are estimated at once in order to minimize the reconstruction error instead of estimating the reconstruction in each pixel independently (as in SENSE). This makes the method robust to noise in reference images. No presmoothing of reference images is necessary. The number of estimated parameters is reduced, which speeds up the estimation process. PROBER was tested on simulated, phantom, and in vivo data. The results are compared with commercial implementations of the algorithms SENSE and GRAPPA (Generalized Autocalibrating Partially Parallel Acquisitions) in terms of elapsed time and reconstruction quality. The experiments showed that PROBER is faster than GRAPPA and SENSE for images wider than 150x150 pixels for comparable reconstruction quality. With more basis functions, PROBER outperforms both SENSE and GRAPPA in reconstruction quality at the cost of slightly increased computational time.     

Radiation doses deriving from patients undergoing 111In-DTPA-d-Phe-1-octreotide scintigraphy

The purpose of this study was to estimate the radiation doses to nursing staff, other patients, accompanying persons and family members deriving from patients undergoing ¹¹¹In-DTPA-d-Phe-1-octreotide (¹¹¹In-OCT) scintigraphy. Dose rates were measured from 16 patients who had received an intravenous injection of 140±40 MBq ¹¹¹In-OCT. The measurements were performed at three different distances (0.5, 1 and 2 m) at 10–20 min, 5–7 h and 24 h (and in some cases, up to 48 h) after administration of ¹¹¹In-OCT. The effective half-lives of the biexponential decrease of the dose rates were estimated to be 2.94±0.27 h (T ₁) and 65.17±0.58 h (T ₂). The calculated maximum dose to other persons in the waiting area was 27.2 μSv, to family members 61.5 μSv, to nursing staff in a ward 24.1 μSv and to neighbouring patients in the ward 69.5 μSv. Our results clearly demonstrate that the calculated maximum radiation exposure to accompanying persons, personnel, family members and other patients is well below the maximum annual dose limit for non-professionally exposed persons. Received 20 May and in revised form 9 July 1997     

CD15 (LeuM1) immunoreactivity: Prognostic factor for sporadic and hereditary medullary thyroid cancer?

Patients treated for sporadic and hereditary medullary thyroid carcinoma (MTC) have varying rates of persistent disease, recurrence, and survival. The aim of this study was to correlate the immunoreactivity of the monoclonal antibody CD15 (LeuM1) to initial clinical findings and the outcome of treatment. The primary tumors of 75 patients with sporadic MTC, 7 with hereditary disease, and 3 members of MEN 2A families were studied. Of these subjects 74 (87%) showed no or little immunoreactivity (<15% positive cells; score 0) in most tumors. The remaining 13% had surgery for tumors with more than 15% cells with positive staining (score I). There was no correlation between LeuM1 immunoreactivity and sex, age, and type of MTC. There was, however, a significant correlation with the pTNM classification and UICC staging. The prognosis for patients with score 0 was significantly better than score 1 patients. CD15 immunoreactivity appears to be a predictive factor in sporadic and hereditary MTC. Lymph node dissection seems to be more successful in patients with score 0 tumors than in those with score 1 tumors. The question of reoperation in patients with recurrence of disease (especially with biochemical recurrence or persistence) should be discussed on the basis of CD15 immunoreactivity.

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Resumen Los pacientes tratados para carcinoma medular, esporádico y hereditario, de la glándula tiroides (CMT) exhiben grandes variaciones en las tasas de enfermedad persistente, recidiva y sobrevida. El propósito del presente estudio fue establecer la correlación entre la inmunorreactividad del anticuerpo CD15 (LeuM1) y los hallazgos clínicos iniciales, así como con el resultado final del tratamiento.Se estudiaron los tumores primarios de 75 pacientes con CMT esporádico, de siete con enfermedad hereditaria y de 3 miembros de familias con síndrome NEM2A.Setenta y cuatro pacientes (87%) exhibieron ninguna o muy baja inmunorreactividad (menos de 15% de células positivas; puntaje 0) en la mayoría de los tumores. El 13% restante fue sometido a cirugía por tumores con más de 15% de las células con coloración positiva (puntaje 1). No se evidenció correlación entre la inmunorreactividad LeuM1 y el sexo, edad o tipo del CMT. Sin embargo, sí apareció una correlación significativa con la clasificiación pTNM y la estadificación de la UICC. El pronóstico de los pacientes con puntaje 0 resultó significativamento mejor que el de los pacientes con puntaje 1.La inmunorreactividad CD15 parece ser un factor de predicción de pronóstico en el CMT esporádico y familiar. La disección ganglionar parece ser más exitosa en pacientes con tumores de puntaje 0 que en los que portan tumores con puntaje 1.El interrogante en cuanto a reoperación en pacientes con recidiva de la enfermedad (especialmente cuando hay recidiva o persistencia bioquímica) debe ser considerada con base en la inmunorreactividad CD15.

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Résumé Les taux de maladie persistante, de récidive et de survie chez des patients traités pour cancer médullaire sporadique et héréditaire de la thyroïde (CMT) sont très variables. Le but de cette étude a été de corréler l'immunoréactivité des anticorps monoclonaux CD15 (LeuM1) à des données cliniques initiales et l'évolution finale du traitement des CMT. On a étudié 75 patients ayant un CMT primitif, sept ayant une maladie héréditaire, et trois membres d'une famille MEN 2A. Soixante quatre patients (87%) avaient peu ou pas d'immunoréactivité (moins de 15% de cellules positive: score = 0). Les 13% restants ont eu une chirurgie pour les tumeurs ayant un pourcentage > 15 (score = 1). Il n'y avait aucune corrélation entre l'immunoréactivité LeuM1 et le sexe, l'âge et le type de CMT. Il y avait, en revanche, une corrélation significative entre la classification pTMN et le stage UICC. Le pronostic des patients ayant un score = 0 était significativement meilleur que celui des patients ayant un score = 1. L'immunoréactivité CD15 apparaît comme étant un facteur pronostique des CMT. Le curage lymphatique

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