Managing patients with sickle cell disease in primary care.

Sickle cell disease (SCD) is a group of disorders affecting the hemoglobin in erythrocytes. SCD is associated with significant morbidity and mortality and occurs most commonly among people of African ancestry. In 2014, the National Heart, Lung, and Blood Institute updated its guidelines for the management of SCD. These guidelines were implemented to provide evidence-based recommendations to assist primary care clinicians in the proper management of patients with SCD. This article reviews the current practice guidelines for SCD, with attention to health maintenance and hydroxyurea.

Arpón quirúrgico vs. semilla de iodo (125I) en la localización de lesiones no palpables malignas de mama. Resultados preliminares / Surgical clips vs. iodine-125 (125I) seeds for marking the location of nonpalpable malignant breast lesions: preliminary results

OBJETIVOS: Evaluar los resultados de la cirugía radioguiada mediante semillas de 125I como alternativa al arpón quirúrgico en pacientes con lesiones no palpables malignas de mama. MATERIAL Y MÉTODOS: Se incluyeron pacientes con diagnóstico anatomopatológico de cáncer de mama, con lesiones no palpables, candidatas a tratamiento quirúrgico durante 2015-2016. Las pacientes fueron asignadas de manera aleatoria al marcaje prequirúrgico con arpón metálico (grupo A) o con semilla (grupo B). En ambos grupos, el procedimiento fue guiado mediante ecografía y/o mamografía en función de las características de la lesión radiológica. Durante la cirugía se utilizó una sonda gammadetectora y, posteriormente, se comprobó mediante radiología la presencia de las semillas en las piezas quirúrgicas. Se realizó el análisis histológico de las piezas, considerando márgenes libres la ausencia de tumor en la tinta. Las variables analizadas fueron la edad de las pacientes y varias características de la lesión (lateralidad, tamaño medido por resonancia magnética y en la pieza quirúrgica, tipo radiológico y presencia de márgenes quirúrgicos libres). RESULTADOS: En el grupo A (n=53), los subtipos histológicos más frecuentes fueron el carcinoma ductal infiltrante (CDI, 84,9%) y el luminal A (LA, 49,1%); el tamaño medio lesional (TML=1,8cm). En el grupo B (n=45), los resultados fueron CDI=82,2%, LA=46,5%, TML=1,5 cm. En el grupo A, la tasa de márgenes afectados fue del 13,2% y la tasa de reintervenciones, de un 13,2% (p = 0,7), y en el grupo B, la tasa de márgenes afectados fue 11,4% y la tasa de reintervenciones, del 7,5% (p = 0,5). Los volúmenes de las piezas quirúrgicas fueron significativamente menores en el grupo B (V=128,68 cm3) que en el grupo A (V=189,37 cm3) (p <0,05). CONCLUSIONES: La utilización de semillas de 125I se ha mostrado como una técnica factible en la localización de lesiones no palpables de mama, mostrando diferencias significativas en el tamaño de las piezas quirúrgicas respecto al arpón

OBJECTIVES: To assess the usefulness of iodine-125 (125I) seeds as an alternative to surgical clips for marking the location of nonpalpable malignant breast lesions for surgery. MATERIAL AND METHODS: We included patients with histologically confirmed nonpalpable malignant lesions treated by surgery in 2015 or 2016. Patients were randomly assigned to presurgical marking with metallic clips (Group A) or with 125I seeds (Group B). In both groups, marking was guided by ultrasound and/or mammography depending on the radiologic characteristics of the lesion. During surgery, a gamma probe was used and afterward the presence of seeds in the surgical specimen was checked radiologically. In the histological analysis, the absence of tumor in the stain was considered free margins. We analyzed the following variables: age, lesion characteristics (laterality, mean size on MRI and in the surgical specimen, radiological type), and presence/absence of free margins. RESULTS: In Group A (n=53), the most common histologic subtypes were infiltrating ductal carcinoma (IDC, 84.9%) and luminal A (LA, 49.1%); the mean size of the lesions was 1.8cm. In Group B (n=45), the most common histologic subtypes were IDC (82.2%) and LA (46.5%); the mean size of the lesions was 1.5cm. In Group A, 13.2% had involved margins and 13.2% underwent a second surgical intervention. In Group, B 11.4% had involved margins and 7.5% underwent a second surgical intervention. The differences between groups were not significant (p = 0.7 for involved margins and p = 0.5 for reintervention). The volume of the surgical specimens was significantly lower in Group B than in Group A (128.68cm3 vs. 189.37cm3; p < 0.05). CONCLUSIONS: Using 125I seeds was feasible and enabled significantly smaller surgical specimens than using metallic clips

Manejo de las extravasaciones de contraste yodado, mediante una intervención térmica. Prueba piloto / Management of iodate contrast extravasations, through a thermal intervention. Pilot test

Objetivo. Analizar la eficacia de la aplicación del calor seco y del frío seco para la resolución de las extravasaciones de contraste yodado administrado mediante una bomba inyectora. Método. Estudio experimental. Se ha realizado una prueba piloto, para de-finir el protocolo de actuación y recogida de datos de un estudio comparativo multicéntrico. Se han evaluado 6 casos de extravasación recogidos en el periodo de marzo a junio de 2017, aplicando de forma aleatoria seco o calor seco como primera intervención. Resultados. En todos los casos se produjo una reacción inflamatoria generalizada de la extremidad afectada pasadas 24h. En los casos tratados con frío seco se pudo delimitar y medir la extravasación tras este intervalo de tiempo, sin embargo en los casos tratados con calor seco como primera intervención no se pudieron definir los contornos pasadas estas 24h. El dolor remitió de forma similar con ambas intervenciones. Conclusiones. La ausencia de con-torno definido y medible de la extravasación pasadas 24h, en las que fueron tratadas con calor seco como primera intervención, puede ser con-secuencia de una mejor absorción y distribución del contraste extravasado comparado con el frío seco. Lo que podría determinar que el calor seco es una intervención térmica positiva para la resolución de éstas ex-travasaciones

Objective. To analyse the efficacy of the application of dry heat and dry cold for the resolution of iodinated contrast extravasations administered by means of an injection pump. Method. Experimental study. A pilot test has been carried out to define the protocol for action and data collection of a comparative multicentre study. We have evaluated six cases of extravasation that occurred during the period of March to June 2017, randomly applying dry cold or dry heat as the first intervention. Results. In all cases, there was a generalized inflammatory reaction of the affected limb after 24h. In the cases treated with dry cold, it was possible to delimit and measure the extravasation after this time interval, however in the cases treated with dry heat as the first intervention, the contours could not be defined after these 24h. Pain returned similarly with both interventions. Conclusions. The absence of a defined and measurable contour of the extravasation after 24h, in which they were treated with dry heat as the first intervention, may be a consequence of a better absorption and distribution of extravasated contrast compared to dry cold. What could determine that dry heat is a positive thermal intervention for the resolution of these extravasations

Association between thyroid function and lipid profiles, apolipoproteins, and high-density lipoprotein function.

BACKGROUND: Thyroid hormone regulates lipid metabolism. In particular, it has been reported to regulate plasma high-density lipoprotein cholesterol (HDL-C) levels and the activity of molecules involved in HDL metabolism. OBJECTIVE: We investigated changes in the concentrations of lipids and apolipoproteins and in the function of HDL according to acute dynamic changes in thyroid function. METHODS: Concentrations of plasma lipids and apolipoproteins, paraoxonase-1 activity, and cholesterol efflux were measured in 27 patients with differentiated thyroid carcinoma who underwent total thyroidectomy and radioactive iodine (RAI) treatment, at 3 distinct times: After surgery (baseline subclinical hyperthyroid state), on the day of undergoing RAI treatment (overt hypothyroid state), and 3 months post-RAI treatment (subclinical hyperthyroid state). RESULTS: The mean free T4 and thyroid-stimulating hormone concentrations were 0.24 ± 0.06 ng/dL and 91.2 (77.8-118.2) µIU/mL, respectively, on the day of RAI treatment. Total cholesterol, triglyceride, low-density lipoprotein cholesterol, and apoB levels, and the apoA-I/II ratio were significantly increased in the overt hypothyroid state and recovered to baseline values with levothyroxine replacement. HDL-C and apoE levels were persistently elevated despite levothyroxine replacement. Paraoxonase-1 activity, corrected for apoA-I, decreased in the overt hypothyroid state but recovered with levothyroxine replacement (P = .009). Cholesterol efflux also decreased significantly in the overt hypothyroid state (21.5 ± 5.1% vs 18.9 ± 2.9%, P = .005), but remained low despite recovery of thyroid function. CONCLUSION: Changes in thyroid function are associated not only with changes in the concentrations of various plasma lipid components but also with changes in HDL function.

Personalized Medicine Based on Theranostic Radioiodine Molecular Imaging for Differentiated Thyroid Cancer.

Molecular imaging based personalized therapy has been a fascinating concept for individualized therapeutic strategy, which is able to attain the highest efficacy and reduce adverse effects in certain patients. Theranostics, which integrates diagnostic testing to detect molecular targets for particular therapeutic modalities, is one of the key technologies that contribute to the success of personalized medicine. Although the term "theranostics" was used after the second millennium, its basic principle was applied more than 70 years ago in the field of thyroidology with radioiodine molecular imaging. Differentiated thyroid cancer, which arises from follicular cells in the thyroid, is the most common endocrine malignancy, and theranostic radioiodine has been successfully applied to diagnose and treat differentiated thyroid cancer, the applications of which were included in the guidelines published by various thyroid or nuclear medicine societies. Through better pathophysiologic understanding of thyroid cancer and advancements in nuclear technologies, theranostic radioiodine contributes more to modern tailored personalized management by providing high therapeutic effect and by avoiding significant adverse effects in differentiated thyroid cancer. This review details the inception of theranostic radioiodine and recent radioiodine applications for differentiated thyroid cancer management as a prototype of personalized medicine based on molecular imaging.

A novel molecular probe 131I-K237 targeting tumor angiogenesis in human prostate cancer xenografts.

Specific molecular probes are essential for the early diagnosis of prostate cancer. In addition, peptides have been shown to have numerous uses as diagnostic and therapeutic molecular probes. The K237 peptide binds to the vascular endothelial growth factor receptor with high affinity and specificity, and was predicted to have potential use as a probe in tumor angiogenesis. The overall aim of the present study was to assess the diagnostic potential of 131I­K237 as a molecular probe for prostate cancer. The K237 peptide was radiolabeled with 131I using an Iodogen method. The radiolabeling efficiency and radiochemical purity were found to be 73.7 ± 3.2 and 96.7 ± 0.6%, respectively, which were determined using thin layer chromatography and high performance liquid chromatography in vitro. Cellular uptake and competition binding experiments were used to identify the affinity of 131I­K237 to LNCaP prostate cancer cells. The binding ratio of 131I­K237 to LNCaP cells in the experimental group was 95.8 ± 1.5%, whereas the binding ratios in the 5 kBq Na131I, 10 kBq Na131I, 15 kBq Na131I and PBS groups were 8.2 ± 0.4, 8.3 ± 0.2, 8.5 ± 0.2 and 0.0%, respectively. In addition, the binding ratio of 131I­K237 to LNCaP significantly decreased with the increased dose of unlabeled K237. A total of 40 male BALB/c mice with LNCaP xenografts were used for biodistribution and single photon emission computed tomography imaging analysis. An image was obtained and tumors were visible from 2 h post injection of 131I­K237. In conclusion, the results of the present study showed that 131I­K237 had a high affinity for LNCaP cells and may be considered as a candidate diagnostic molecular probe for prostate cancer.

The role of ¹²³I imaging in the evaluation of infants with mild congenital hypothyroidism.

BACKGROUND/AIMS: Controversy exists regarding the diagnosis and treatment of mild congenital hypothyroidism (MCH). We studied the value of (123)I imaging in patients with MCH. METHODS: Retrospective chart review of infants and children <4 years of age who underwent (123)I imaging: group 1 = MCH [thyroid-stimulating hormone (TSH) <25 µIU/ml, normal free T4/T3], group 2 = severe congenital hypothyroidism (TSH ≥25 µIU/ml), and group 3 = MCH in infancy imaged after treatment withdrawal at age 3 years. Data collected included 4- and 24-hour (123)I uptake, TSH, free T4/total T3 at imaging, age at imaging, and levothyroxine (L-T4) dose at 1 year of. RESULTS: Thirty-six patients underwent (123)I imaging. In group 1 (n = 20, median TSH: 8.49 µIU/ml), 85% had abnormal imaging consistent with dyshormonogenesis. Two patients were referred after 1 year of age. The median age at imaging for the remaining 18 patients was 54 days. Median L-T4 dose at 1 year of age for these 18 patients was 2.8 µg/kg, which is consistent with dyshormonogenesis. Ninety-one percent of group 2 (n = 11, median TSH: 428.03 µIU/ml) had abnormal imaging. The median age at imaging was 13 days. Four patients in group 3 had abnormal (123)I imaging and restarted treatment. CONCLUSION: (123)I imaging is a valuable tool for evaluation, diagnosis, and treatment of MCH.

Experimental evaluation of radioiodinated sennoside B as a necrosis-avid tracer agent.

Necrosis-avid agents are a class of compounds that selectively accumulate in the necrotic tissues after systemic administration, which can be used for in vivo necrosis imaging and targeted therapies. In order to search for a necrosis-avid tracer agent with improved drugability, we labelled iodine-131 on sennoside B (SB) as a naturally occurring median dianthrone compound. The necrosis targetability and clearance properties of (131)I-SB were evaluated in model rats with liver and muscle necrosis. On SPECT/CT images, a "hot spot" in the infarcted liver lobe and necrotic muscle was persistently observed at 24 h and 72 h post-injection (p.i.). Gamma counting of the tissues of interest revealed a radioactivity ratio of necrotic to viable liver at 4.6 and 3.4 and of necrotic to viable muscle at 7.0 and 8.8 at 24 h and 72 h p.i., respectively. The good match of autoradiographs and fluoromicroscopic images with corresponding histochemical staining suggested preferential uptake of (131)I-SB in necrotic tissue. Pharmacokinetic study revealed that (131)I-SB has an elimination half-life of 8.6 h. This study indicates that (131)I-SB shows not only prominent necrosis avidity but also favourable pharmacokinetics, which may serve as a potential necrosis-avid diagnostic agent for assessment of tissue viability.

Increased TRAb and/or low anti-TPO titers at diagnosis of graves' disease are associated with an increased risk of developing ophthalmopathy after onset.

Patients with low thyroid peroxidase antibodies (anti-TPO) and increased TSH-receptor antibodies (TRAb) at diagnosis of Graves' disease (GD) have been suggested to have an increased risk to develop Graves' ophthalmopathy (GO). The aim was to evaluate if GO development can be predicted.This is an observational study with registration of possible GD and GO risk factors.399 patients with GD were registered 2003-2008 in Malmö, Sweden and out of these 310 were retrospectively followed up to 6 years. The main outcome measures were anti-TPO titer, TRAb titer, smoking habits, radioiodine treatment and GO development.TRAb was assessed with a third generation assay at GD diagnosis in 231 patients. The proportion of patients with GO increased above the median 6.3 IU/L both at diagnosis of GD (p=0.001) and at follow-up (p=0.0001).The distribution of GO patients anti-TPO above or below 20 kIU/L at diagnosis of GD was similar between groups (p=0.239). However at follow-up anti-TPO<20 kIU/L was associated with an increased proportion of newly developed GO as compared to the cohort with anti-TPO>20 kIU/L (p=0.018).87% of patients who developed GO after GD diagnosis had TRAb above 6.3 IU/L and/or anti-TPO below 20 kIU/L. The proportion of GO was doubled in GD patients treated with radioiodine but could not explain the described findingsAnti-TPO<20 kIU/L and/or TRAb>6.3 IE/L at the time of GD diagnosis were associated with an increased risk to develop GO after diagnosis of GD.

Changes of regulatory T and B cells in patients with papillary thyroid carcinoma after 131I radioablation: a preliminary study.

Introduction. Lymphocytic infiltration and specific lymphocytes subsets may play important roles in papillary thyroid carcinoma (PTC) progression and prognosis. In this study, we try to understand the influence of (131)I radioablation on the important lymphocytes subtypes of regulatory T and B cells (Tregs and Bregs). Methods. Peripheral blood mononuclear cells from 30 PTC patients before and after (131)I therapy, and 20 healthy donors were collected. The expression of Tregs (CD4(+)CD25(+)CD127(-/low)) and B cell (CD5(+)CD19(+)) and production and secretion of interleukin 10 (IL-10) were analyzed by FACS and ELISA assay, respectively. Results. For Tregs percentage in peripheral blood lymphocytes, there was no difference between pretreatment and control and between posttreatment and control. Compared with pretherapy, increased Tregs infiltration was noted in posttherapy (P < 0.05). Although no difference was between pretreatment and control, compared with these two groups, decreased CD19(+) and CD5(+)CD19(+) B cell percentage in posttreatment was observed (P < 0.05). Among these groups, no significant difference was displayed in intracellular IL-10 production and extracellular IL-10 secretion. Conclusions. (131)I Radioablation increased Tregs and decreased CD19(+) and CD5(+)CD19(+) B cells percentage after treatment. However, it has no effect on IL-10 and lymphocytes in peripheral blood. Therefore, longer follow-up of Tregs and Bregs should be further investigated.

Necrosis affinity evaluation of 131I-hypericin in a rat model of induced necrosis.

Cancers are often with spontaneous or therapeutic necrosis that could be utilized as a generic target for developing new treatments. The purpose of this study was to investigate the biodistribution and pharmacokinetics of radioiodinated hypericin (Hyp), a naturally occurring compound, after intravenous (i.v.) injection in a rat model of liver and muscle necrosis (n = 42), and evaluate its necrosis affinity. Hyp was labeled with (131)I with labeling efficiency >99%. After incubating in solution/rat plasma for 8 days, radiochemical purity of (131)I-Hyp remained 98.1 and 97.1%, respectively, indicating good in vitro stability. SPECT-CT images at 24 h after i.v. injection of (131)I-Hyp in rats with induced liver and muscle necrosis showed obvious tracer absorption in necrotic tissues. Biodistribution studies revealed that the percentage of the injected dose per gram of tissue (%ID/g) evolved from 1.9 %ID/g at 6 h, through a maximum 3.0 %ID/g at 12 h, to 1.0 %ID/g at 192 h in necrotic liver. Pharmacokinetics studies revealed that the terminal elimination half-life, total body clearance and area under the curve of (131)I-Hyp were 32.7 h, 9.2 L/h/kg and 1.6 MBq/L*h, respectively. These results demonstrated that (131)I-Hyp features a long blood circulation in animals and persistent retention in necrotic tissues. Therefore, (131)I-labeled Hyp could be a broad-spectrum anti-tumor agent with a cost much cheaper relative to the biological agents such as monoclonal antibodies.

Controversies about radioactive iodine-131 remnant ablation in low risk thyroid cancers: are we near a consensus?

Well differentiated thyroid cancers (WDTC), including papillary (80%) and follicular (10%) types, are the most common endocrine cancers globally. Over the last few decades most the diagnosed cases have fallen into low risk categories. Radioactive iodine-131 (RAI) has an established role in reducing recurrence and improving the survival in high risk patients. In patients with primary tumor size <1 cm, RAI is not recommended by many thyroid societies. However, low risk WDTC has been an arena of major controversies, most importantly the role and dose of adjuvant RAI for remnant ablation to minimize chances of recurrence and improving survival. This review is an attempt to update readers about the previous and existing practice based on results of non- randomized trials and evolving trends fueled by recently published randomized studies.

In vivo distribution of avidin-conjugated MX35 and (211)At-labeled, biotinylated poly-L-lysine for pretargeted intraperitoneal α-radioimmunotherapy.

PURPOSE: Avidin-coupled monoclonal antibody MX35 (avidin-MX35) and astatine-211-labeled, biotinylated, succinylated poly-l-lysine ((211)At-B-PL(suc)) were administered in mice to assess potential efficacy as an intraperitoneal (i.p.) therapy for microscopic tumors. We aimed to establish a timeline for pretargeted radioimmunotherapy using these substances, and estimate the maximum tolerable activity. METHODS: (125)I-avidin-MX35 and (211)At-B-PL(suc) were administered i.p. in nude mice. Tissue distributions were studied at various time points and mean absorbed doses were estimated from organ uptake of (211)At-B-PL(suc). Studies of myelotoxicity were performed after administration of different activities of (211)At-B-PL(suc). RESULTS: We observed low blood content of both (125)I-avidin-MX35 and (211)At-B-PL(suc), indicating fast clearance. After sodium perchlorate blocking, the highest (211)At uptake was found in kidneys. Red bone marrow (RBM) accumulated some (211)At activity. Mean absorbed doses of special interest were 2.3 Gy/MBq for kidneys, 0.4 Gy/MBq for blood, and 0.9 Gy/MBq for RBM. An absorbed dose of 0.9 Gy to the RBM was found to be safe. These values suggested that RBM would be the key dose-limiting organ in the proposed pretargeting scheme, and that blood data alone was not sufficient for predicting its absorbed dose. CONCLUSIONS: To attain a favorable distribution of activity and avoid major toxicities, at least 1.0 MBq of (211)At-B-PL(suc) can be administered 24 hours after an i.p. injection of avidin-MX35. These results provide a basis for future i.p. therapy studies in mice of microscopic ovarian cancer.

Contrast-induced nephropathy: are there differences between low osmolar and iso-osmolar iodinated contrast media?

It is acknowledged that high osmolar contrast media are more nephrotoxic than low (LOCM) or iso-osmolar contrast media (IOCM). However, it remains contentious whether the IOCM are less nephrotoxic in comparison with LOCM. This article reviews published clinical studies that investigated this issue and demonstrates there are no conclusive data to indicate that there is a definite difference in renal tolerance between LOCM and IOCM. All these agents are potentially nephrotoxic in patients with advanced renal impairment. In these patients the smallest possible dose of IOCM or LOCM should be used in addition to adequate hydration to minimize the risk of contrast nephropathy.

Imaging characteristics of DHOG, a hepatobiliary contrast agent for preclinical microCT in mice.

RATIONALE AND OBJECTIVES: This study was performed to assess the imaging characteristics and pharmacokinetics of 1,3-Bis-[7-(3-amino-2,4,6-triiodophenyl)-heptanoyl]-2-oleoyl glycerol (DHOG, Fenestra LC), a hepatobiliary contrast agent for microCT. MATERIALS AND METHODS: We investigated the abdomen of 18 female C3H mice in a MicroCAT II microCT scanner before contrast agent injection and at multiple time points up to 48 hours after intravenous injection of DHOG (1 g I/kg body weight). The contrast agent effect was determined quantitatively and dynamically by measuring pre- and postcontrast Hounsfield units (HU) of the liver, aorta, spleen, and kidneys. Based on additional phantom measurements, the reproducibility of lesion detection was estimated for different lesion sizes. RESULTS: DHOG caused a marked early postcontrast enhancement of blood in the aorta and a very high enhancement of the spleen, both slowly declined after 90 minutes. The liver parenchyma showed a slow contrast agent accumulation and clearly increased HU data between 3 and 7 hours after injection. No significant renal parenchymal enhancement or excretion was noticed. At early time points after administration, DHOG exhibits characteristics of a macromolecular contrast agent by demonstrating a blood pool effect. At later time points, DHOG provides a prolonged, marked liver enhancement on microCT images due to its specific liver uptake. For a lesion size of 1 mm diameter, the variability in between two scans was 27.7 HU (P < .05) and the variability for different planes of one scan was 19.8 HU (P < .05). CONCLUSIONS: DHOG yields a very good visualization of the liver and delineation of the surrounding structures with a long plateau. It is a very suitable contrast agent for liver imaging in mice for microCT imaging. The presented protocol provides a high reproducibility for lesion detection with a relatively low radiation dose.

Estrogen effects on thyroid iodide uptake and thyroperoxidase activity in normal and ovariectomized rats.

Sex steroids interfere with the pituitary-thyroid axis function, although the reports have been controversial and no conclusive data is available. Some previous reports indicate that estradiol might also regulate thyroid function through a direct action on the thyrocytes. In this report, we examined the effects of low and high doses of estradiol administered to control and ovariectomized adult female rats and to pre-pubertal females. We demonstrate that estradiol administration to both intact adult and pre-pubertal females causes a significant increase in the relative thyroid weight. Serum T3 is significantly decreased in ovariectomized rats, and is normalized by estrogen replacement. Neither doses of estrogen produced a significant change in serum TSH and total T4 in ovariectomized, adult intact and pre-pubertal rats. The highest, supraphysiological, estradiol dose produced a significant increase in thyroid iodide uptake in ovariectomized and in pre-pubertal rats, but not in control adult females. Thyroperoxidase activity was significantly higher in intact adult rats treated with both estradiol doses and in ovariectomized rats treated with the highest estradiol dose. Since serum TSH levels were not significantly changed, we suggest a direct action of estradiol on the thyroid gland, which depends on the age and on the previous gonad status of the animal.

131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission.

In an attempt to improve outcomes for patients with acute myeloid leukemia (AML) after allogeneic hematopoietic cell transplantation (HCT), we conducted a phase 1/2 study in which targeted irradiation delivered by 131I-anti-CD45 antibody was combined with targeted busulfan (BU; area-under-curve, 600-900 ng/mL) and cyclophosphamide (CY; 120 mg/kg). Fifty-two (88%) of 59 patients receiving a trace 131I-labeled dose of 0.5 mg/kg anti-CD45 murine antibody had higher estimated absorbed radiation in bone marrow and spleen than in any other organ. Forty-six patients were treated with 102 to 298 mCi (3774-11 026 MBq) 131I, delivering an estimated 5.3 to 19 (mean, 11.3) Gy to marrow, 17-72 (mean, 29.7) Gy to spleen, and 3.5 Gy (n = 4) to 5.25 Gy (n = 42) to the liver. The estimated 3-year nonrelapse mortality and disease-free survival (DFS) were 21% and 61%, respectively. These results were compared with those from 509 similar International Bone Marrow Transplant Registry patients who underwent transplantation using BU/CY alone. After adjusting for differences in age and cytogenetics risk, the hazard of mortality among all antibody-treated patients was 0.65 times that of the Registry patients (95% CI 0.39-1.08; P = .09). The addition of targeted hematopoietic irradiation to conventional BU/CY is feasible and well tolerated, and phase 2 results are sufficiently encouraging to warrant further study.

Improved effect of 131I-MIBG treatment by predosing with non-radiolabeled MIBG in carcinoid patients, and studies in xenografted mice.

BACKGROUND: 131I-meta-iodobenzylguanidine (MIBG) has been used with success for the palliation of metastatic carcinoid. To qualify more patients for this treatment, we evaluated the effect of predosing with non-radiolabeled MIBG on 131I-MIBG tumour targeting in carcinoid patients and in mice with BON human carcinoid xenografts. PATIENTS AND METHODS: Ten carcinoid patients with a faint tumour imaging on a diagnostic 131I-MIBG scan (1 mCi = 37 MBq, 5 mg MIBG) received non-radiolabeled MIBG prior to a second scintigraphy. In case of improved tumour targeting patients were treated with 200 mCi (7.4 GBq) 131I-MIBG following a pharmacological predose of 20-40 mg/m2 MIBG. RESULTS: In six patients. highly increased 'tumour/non-tumour' ratios were seen due to reduced levels in normal tissues and increased tumour accumulation. The combined treatment applied in five patients, considerably improved symptoms in all (duration 6-12 months), accompanied by biochemical response in three. In BON carcinoid xenografted mice, MIBG was injected intraperitoneally followed by intravenous 125I-MIBG with similar findings: increased 'tumour/non-tumour' radioactivity ratios by 1.5-3-fold. CONCLUSION: Predosing with non-radiolabeled MIBG resulted in improved 131I-MIBG tumour targeting, prolonged palliation and encouragingly often biochemical responses in carcinoid.

[Improvement of visual acuity of intensely myopic patients during their eye-cure stay at Bad Hall (author's transl)]. / Anderung der Sehschärfe bei Patienten mit höhergradiger Myopie während ihres Kuraufenthaltes in Bad Hall/Oberösterreich.

Intensely myopic patients in the Eye Department of the Paracelsus-Institute in Bad Hall (Upper Austria) were subjected to visual acuity tests whereby the conditions of examination were held constant (optotype-projector, panoramic visual range, exactly defined break-off criteria). Results showed that 33% of the patients, who had completed combined iodine treatments and ophthalmo-iontophoresis, showed an improvement in visual acuity of 3 or more optotypes, corresponding to an average increase thereof of 0,13 from the initial visual power. Side effects of intense myopia (dilatation tension and degenerative changes at the posterior eye pole) should thus be regarded as an indication of the successful application of the combined balneotherapy, mineral water treatment and eye-cure in Bad Hall.