The role of radiotherapy in endocrine orbitopathy

The treatment of Graves' ophthalmopathy is symptomatic because the etiology remains unknown though evidence supports an aberrant immune response. Orbital radiotherapy, combined with corticosteroids, is indicated for rapidly progressive ophthalmopathy and troublesome soft tissue symptoms. In case of sight-threatening manifestations operative decompression is the method of choice. However, radiotherapy seems to be a safe and effective method as a good to excellent response in 60-70% of patients can be expected. The treatment results of 15 patients with a long term follow-up are presented.     

CCK-2/gastrin receptor-targeted tumor imaging with (99m)Tc-labeled minigastrin analogs.

The aim of this study was to evaluate 3 new (99m)Tc-labeled minigastrin analogs modified with open chain tetraamines at the N-terminus for their suitability in the CCK-2/gastrin-R-targeted imaging of tumors (CCK-2/gastrin-R = cholecystokinin subtype 2/gastrin receptor). METHODS: The [(D)Glu(1)]minigastrin sequence was assembled on the solid support and the respective tetraamine precursors coupled at the N-terminus. Purified peptide conjugates were labeled with (99m)Tc under alkaline conditions. Saturation binding experiments were performed for (radio)metallated peptides [(99m)Tc/(99g)Tc]Demogastrin 1-3 in rat acinar pancreatic AR4-2J cell membranes. Internalization was studied in AR4-2J cells at 37 degrees C. Radiopeptide stability was tested in murine plasma, urine, and kidney homogenates. Tissue distribution of the peptides was compared in healthy mice and athymic mice bearing AR4-2J tumors. RESULTS: Peptide conjugates were obtained in 10%-30% overall yields by solid-phase techniques. Radiolabeling afforded >98% pure [(99m)Tc]Demogastrin 1-3 species in specific activities of approximately 37 GBq/mumol. Radiopeptides retained a high affinity for the CCK-2/gastrin-R in vitro (50% inhibitory concentration values of approximately 1 nmol/L) and internalized rapidly in CCK-2/gastrin-R-positive cells. After injection in mice they displayed rapid, high, and specific localization in the CCK-2/gastrin-R-expressing tissues (stomach and AR4-2J tumor) and were excreted from the body via the kidneys in the form of hydrophilic metabolites. CONCLUSION: The promising characteristics of [(99m)Tc]Demogastrin 1-3 both in vitro and in animal models illustrate their suitability for CCK-2/gastrin-R-targeted tumor imaging. These qualities could be confirmed for [(99m)Tc]Demogastrin 2, which provided excellent delineation of tumor deposits in a first patient with metastatic medullary thyroid cancer.     

Prognostic evaluation of specific cutaneous infiltrates in B-chronic lymphocytic leukemia

The relationship between numerous histologic variables and survival was investigated in 54 consecutive lesions of specific skin infiltrates of B-cell chronic lymphocytic leukemia (B-CLL) from 27 patients (16 males and 11 females, mean age 65 years, range 42–83 years). All patients were followed for up to 204 months or until death. Histopathologically, the infiltrates showed a patchy perivascular (35%), diffuse (31.5%), nodular (31.5%) or band-like (1.9%) pattern. In 28% of the cases, an admixture of reactive cells within the infiltrate including eosinophils, histiocytes, neutrophils and plasma cells was observed. Cytomorphologically, small B-lymphocytes with condensed chromatin predominated in most infiltrates. However, some biopsies showed a small but significant number of medium- or large-sized neoplastic cells of the B-lymphocyte lineage with variable cytomorphological features. In a multivariate analysis, several histologic parameters within the infiltrates were found to show a significant association with long survival, namely, an infiltrate of moderate density, a nodular pattern, involvement of the lower dermis only, and presence of predominantly small B-lymphocytes (more than 95%) with condensed chromatin. Histologic variables that independently correlated with relatively short survival included an infiltrate of severe intensity, a diffuse pattern, epidermal changes (especially acanthosis and ulceration), medium-sized and large B-lymphocyte (more than 5%), and reactive cells within the infiltrate (neutrophils, eosinophils, and plasma cells). Overall analysis of our results showed two histologic patterns with a significant prognostic impact (p<0.01; z=5.4). Pattern I (33 biopsies) correlated with relatively long survival (2-year survival rate; 97%) and consisted of infiltrates showing predominantly small B-lymphocytes (more than 95%) without reactive cells or epidermal changes. Pattern II (21 biopsies) indicated short survival (2-year survival rate; 49%) and included all the rest of the biopsies i.e., infiltrates with medium- and large-sized B-lymphocytes (more than 5%), admixture of reactive cells, and epidermal changes. Results from our study suggest that histologic features in specific skin infiltrates of B-chronic lymphocytic leukemia may be helpful in identifying prognostically different subgroups of patients and planning therapeutic schedules.     

Implantable Micropump System for Augmented Liver Perfusion

Liver cirrhosis, a worldwide health problem, decreases the blood flow through the liver. This in turn leads to dangerous portal hypertension and decreased metabolic function within the liver. To improve this situation, a new concept is proposed which involves introducing a microaxial blood pump into the portal vein. This device is intended to increase blood flow through the liver and to enhance hepatic function. Furthermore, high pressures will be reduced to physiological levels. The microaxial pump with its single stage impeller is powered by a proximally integrated microelectric motor. The pump unit is completely immersed within the blood vessel. Heat caused by electrical and mechanical losses will be transported into the blood. In vitro optimization of the pump design was accomplished using both hydraulic and hemolysis tests.     

Experience with the iodine-123 and technetium-99m labelled anti-granulocyte antibody MAb47: a comparison of labelling methods

Four different methods of radiolabelling the anti-granulocyte monoclonal antibody MAW were compared and their influence on diagnostic value studied. The best clinical images were obtained following labelling with iodine-123 by the Iodogen method and direct labelling with technetium-99m after tris-(carboxyethyl)-phosphine treatment of MAW to achieve disulphide bridge reduction.^99mTc labelling using a specific ligand (MAb47-mtp), or a second method involving direct reduction with mercaptoethanol, led to an increased background activity in clinical studies, thus impeding the diagnosis of chronic disease. Fresh infections were clearly localized by all four preparations. The elimination of the activity from the blood was slower in the case of the iodinated MAb47, while the collected urine samples showed an excrection of about 10% of the injected activity per day independent of the labelling method. The results in terms of sensitivity and specificity were rather similar for all labelling methods and ranged from 90% to 99%.     

Renal recovery from acute tubular necrosis requiring renal replacement therapy: a prospective study in critically ill patients.

BACKGROUND: Data on the incidence of end-stage renal disease (ESRD) resulting from irreversible acute tubular necrosis (ATN) are controversial. This prospective cohort study was designed to assess the need for short- and long-term dialysis in critically ill patients with severe ATN and to define risk factors for lack of renal recovery. METHODS: 433 consecutive patients with clinically diagnosed severe ATN necessitating renal replacement therapy were enrolled. Eight patients were excluded because renal biopsy revealed another cause of acute renal failure. None of the remaining 425 patients had pre-existing chronic renal insufficiency. Primary outcome criteria were recovery of renal function at discharge and ESRD status at 1 year follow-up. RESULTS: The overall in-hospital mortality of the cohort was 47%. At discharge, 57% of the 226 surviving patients had normal renal function, 33% had mild to moderate renal failure (serum creatinine: 1.3-3 mg/dl) and 10% had severe renal failure (serum creatinine: 3-6 mg/dl). Multivariate analysis showed that neither patient characteristics (age, gender, comorbid conditions), severity of illness (APACHE III, number of failed organs) nor mode and duration of renal replacement therapy were related to recovery of renal function. After 1 year, 76 of the surviving patients had died and in one patient chronic renal failure had progressed to ESRD. CONCLUSIONS: If critically ill patients with normal renal function prior to the renal insults survive the precipitating cause of ATN, the overwhelming majority will recover sufficient renal function.     

Evaluation of the McPeek postoperative outcome score in three trials

Background Postoperative outcome of patients is determined by recovery characteristics and self-reported quality of life. The first can be assessed with the McPeek score which values three aspects of recovery: mortality, postoperative critical care and duration of hospitalization.Materials and methods We calculated the McPeek score of 669 patients in three trials: (1) colorectal cancer surgery, (2) antihistamine/volume loading in various operations, and (3) cholecystectomy. Beforehand, the average of intensive care unit treatment and duration of hospitalization were determined for the different operations to define McPeek score points. The score was tested on reliability, validity, and sensitivity. In addition, clinical applicability was assessed in a survey.Results The score was reliable with similarly distributed score points in the three trials at different institutions. Inter-rater reliability was high (97% overlap). Validity was proven by moderate high correlation to convergent criteria such as complications (trial I to III r=0.43, r=0.38, r=0.60), preoperative American Society of Anesthesiologists class (ASA) (r=0.24, r=0.28, r=0.57), and age (r=0.23, r=0.32, r=0.31). The score was different between patients with and without neoplasms (P<0.001, trial II) and between elective or emergency patients (P<0.001, trial III). In a survey, investigators reported that the score was easy to assess and more comprehensive than four other scores.Conclusions The McPeek score values the postoperative outcome on a nonlinear scale. A priori, the average duration of hospitalization and critical care for a specific operation has to be defined. Our validation suggests that it is a reliable, valid, sensitive, and practical instrument for outcome analysis after anesthesia and surgery.     

Factors that affect influenza vaccine uptake among staff of long-term care facilities.

A survey of directors and employees of 36 long-term care facilities in Hesse, Germany, revealed that influenza vaccine uptake among staff was less than 30% in 30 and greater than 50% in 6. The study identified policies and practices associated with vaccination uptake at long-term care facilities and factors associated with the decision of staff to get vaccinated.