Intraoperative examination of sentinel lymph nodes by ultrarapid immunohistochemistry

The recently developed method of ultrarapid immunohistochemistry (IHC) was applied to the intraoperative examination of sentinel lymph nodes (SLNs) in breast cancer patients. In a prospective study of 50 patients with invasive breast carcinomas, a total of 60 SLNs were studied. Among them, 33 SLNs from 30 patients were studied intraoperatively using a direct immunoperoxidase method with anticytokeratin antibody clone MNF116. This technique has a turnaround time of less than 20 minutes. Ultrarapid IHC revealed 15 positive SLNs compared to 14 positive SLNs using hematoxylin and eosin (H and E) frozen sections. The one SLN missed in H and E frozen sections presented with cytokeratin-positive isolated tumor cells in the lymph node sinus. After paraffin embedding, H and E-stained serial step sections of the SLN specimens detected another two patients with isolated tumor cells. We also examined the remaining axillary lymph nodes (ALNs) by H and E-stained serial step paraffin sections. From 17 of the 30 patients with positive SLNs, 6 patients also had metastatic involvement of the ALNs of level I or II. Thus ultrarapid IHC was a very sensitive and rapid technique for the intraoperative detection of metastatic involvement of SLNs in breast cancer patients. This technique may be a useful complementary tool for the intraoperative study of SLNs, particularly in tumors that are a diagnostic challenge, such as lobular carcinoma.     

Cognitive impairment in SCA-19

The autosomal dominant cerebellar ataxias (ADCAs) are a heterogeneous group of neurodegenerative disorders characterised by progressive cerebellar dysfunction in combination with various associated features. Since 1993, ADCAs have been increasingly characterised in terms of their genetic mutation and are currently referred to as spinocerebellar ataxias (SCAs). The discovery of genetic abnormalities offers the opportunity to study the possible interaction between the identified gene mutation and cognitive function. In this study, we focus on the neuropsychological abnormalities in a Dutch ADCA family, in which a new locus was recently identified (SCA-19). The family members showed frontal-executive dysfunction, with global cognitive impairment occurring in some of the more severely affected patients. Interestingly, the neuropsychological profile of this new family seems to overlap that of individuals with various other SCAs. Apparently, similar pattern of neuronal degeneration in various SCA subtypes accounts for the neuropsychological dysfunction, which is thus not genotype specific.     

The serum protein alpha 2-Heremans-Schmid glycoprotein/fetuin-A is a systemically acting inhibitor of ectopic calcification

Ectopic calcification is a frequent complication of many degenerative diseases. Here we identify the serum protein alpha2-Heremans-Schmid glycoprotein (Ahsg, also known as fetuin-A) as an important inhibitor of ectopic calcification acting on the systemic level. Ahsg-deficient mice are phenotypically normal, but develop severe calcification of various organs on a mineral and vitamin D-rich diet and on a normal diet when the deficiency is combined with a DBA/2 genetic background. This phenotype is not associated with apparent changes in calcium and phosphate homeostasis, but with a decreased inhibitory activity of the Ahsg-deficient extracellular fluid on mineral formation. The same underlying principle may contribute to many calcifying disorders including calciphylaxis, a syndrome of severe systemic calcification in patients with chronic renal failure. Taken together, our data demonstrate a critical role of Ahsg as an inhibitor of unwanted mineralization and provide a novel therapeutic concept to prevent ectopic calcification accompanying various diseases.     

Potential Relevance of Agmatine as a Virulence Factor of Helicobacter pylori

The polyamine agmatine is able to increasegastric acid secretion. Therefore, we investigatedwhether Helicobacter pylori is able to form and releaseagmatine in vitro and in the human stomach in vivo , and if so, whether a relationship exists amongagmatine concentration in gastric juice, H. pyloriinfection, and gastroduodenal lesions. Agmatine wasdetermined by means of HPLC. In the supernatant of H. pylori cultures, agmatine concentrations up to1500 ng/ml (~12 M) were determined, depending on thenumber of the bacteria in the individual cultures.Agmatine concentration in gastric juice from H. pylori-positive patients was higher than inthat from H. pylori-negative patients. Gastrin in bloodwas elevated in H. pylori-positive patients comparedwith H. pylori-negative patients. Agmatine concentration in gastric juice and serum gastrin levelappeared to be related. In conclusion, H. pylori is ableto form and to release agmatine in vitro and in vivo.This may be assumed to be relevant in vivo, since higher amounts of agmatine are present ingastric juice from H. pylori-positive than from H.pylori-negative patients. Accordingly, agmatine producedby H. pylori may be a virulence factor of this bacterium and may be involved in the pathogenesis ofgastroduodenal lesions.     

MONICA: a compact,portable dual gamma camera system for mouse whole-body imaging

IntroductionWe describe a compact, portable dual-gamma camera system (named “MONICA” for MObile Nuclear Imaging CAmeras) for visualizing and analyzing the whole-body biodistribution of putative diagnostic and therapeutic single photon emitting radiotracers in animals the size of mice.MethodsTwo identical, miniature pixelated NaI(Tl) gamma cameras were fabricated and installed “looking up” through the tabletop of a compact portable cart. Mice are placed directly on the tabletop for imaging. Camera imaging performance was evaluated with phantoms and field performance was evaluated in a weeklong In-111 imaging study performed in a mouse tumor xenograft model.ResultsTc-99m performance measurements, using a photopeak energy window of 140 keV±10%, yielded the following results: spatial resolution (FWHM at 1 cm), 2.2 mm; sensitivity, 149 cps (counts per seconds)/MBq (5.5 cps/μCi); energy resolution (FWHM, full width at half maximum), 10.8%; count rate linearity (count rate vs. activity), r²=0.99 for 0–185 MBq (0–5 mCi) in the field of view (FOV); spatial uniformity, <3% count rate variation across the FOV. Tumor and whole-body distributions of the In-111 agent were well visualized in all animals in 5-min images acquired throughout the 168-h study period.ConclusionPerformance measurements indicate that MONICA is well suited to whole-body single photon mouse imaging. The field study suggests that inter-device communications and user-oriented interfaces included in the MONICA design facilitate use of the system in practice. We believe that MONICA may be particularly useful early in the (cancer) drug development cycle where basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors, e.g., limited imaging space, portability and, potentially, cost are important.     

Changes in neurons,neuroendocrine cells and nerve fibres in the lamina propria of irradiated bowel

Summary Damage to bowel often complicates radiotherapy for abdominal and pelvic malignancy. The symptoms of chronic irradiation enteropathy, which often include intractable diarrhoea, are generally attributed to vascular injury. We have examined specimens of bowel resected from patients who had been therapeutically irradiated to assess the extent of injury to the enteric nerve plexuses. To facilitate visualisation of nerve fibres and cells of neural or neuroendocrine origin, sections were immunostained with antibodies to neuronspecific enolase or PGP 9.5, widely used markers of nerves and neurons. Electron microscopy was performed in selected cases. In 27 out of 33 specimens the number of nerve fibres in the lamina propria was obviously increased compared to that in control material. Scattered cells with the histological, immunohistochemical and ultrastructural features of ganglion cells were noted within the lamina propria in 23 of the specimens, and in 18 cases so-called neuroendocrine cells, not normally seen in this location, were also present. These radiation-induced changes in the innervation of the bowel may contribute to the symptoms of chronic radiation enteropathy.     

Long-term outcomes in patients with atrioventricular block undergoing septal ventricular lead implantation compared with standard apical pacing

Aims: Left ventricular function may be altered by right ventricularapical pacing. The aims of the study were to compare the long-termcourse of different parameters of left ventricular dysfunctionin patients undergoing implantation of a dual-chamber pacemakerwith the ventricular lead in a septal position vs. in a standardapical position. Methods: We randomized 98 patients with atrioventricular block (AV-block)undergoing pacemaker implantation to positioning the ventricularlead in the high or mid septum (n = 53) or in the apex (n =45) of the right ventricle. N-terminal pro-brain natriueticpeptide (BNP) levels, left ventricular ejection fraction (LVEF),and exercise capacity were analysed 3 days, 3 months, and 18months after the implantation. The primary endpoints were thechanges of these parameters from baseline to 18 months. Results: Changes of BNP levels, LVEF, and exercise capacity from baselineto 18 months were statistically not different between septaland apical stimulation. The clinical occurrence or deteriorationof overt heart failure was similar in both treatment arms. Conclusion: With regard to different parameters of congestive heart failure,a septal stimulation site is not superior to conventional apicalpacing in unselected patients undergoing pacemaker implantationfor AV-block.     

Healthy young and middle age adults: What will it take to vaccinate them for influenza?

Starting in 2010, healthy adults age 19–49 will be recommended for annual influenza vaccination. Because they were not previously targeted, little is known about their vaccine-related attitudes and behaviors. Using nationally representative survey data from 2009 to 2010, we found that adults newly recommended for influenza vaccination (as compared to previously recommended groups) are less likely to believe flu vaccines are safe (44% vs. 63%), to have ever been vaccinated (36% vs. 64%), to be vaccinated following a healthcare provider recommendation (44% vs. 52%), and to visit a doctor's office during vaccination season (41% vs. 69%). To boost rates of influenza vaccination in this population, new and untraditional strategies aimed at encouraging first-time vaccination are needed.     

Implant-supported denture in a patient with Huntington's disease: interdisciplinary aspects

Patients with extrapyramidal diseases often cannot maintain independent, efficient oral hygiene due to restricted motor ability of the upper extremities and lack of coordination. The hermetic closure of the mouth and lips, and the associated ability to keep liquid and toothpaste in the mouth, can become so weak that effective oral hygiene cannot be maintained. Over a period of many years, this illness leads to loss of teeth and the need for complete prosthodontic care. Dyskinesia and hyperkinesia of the tongue and the peri-oral musculature, combined with xerostomia and pooling of saliva, make it impossible for the patient to wear a conventional complete denture, despite an anatomically-adequate bearing area. In such cases, an implant-supported prosthesis is a better therapeutic measure, although some aspects of oral hygiene must initially be disregarded. Two ITI^TM implants were inserted into the anterior mandibular region of a patient with Huntington's chorea, because a complete denture could not be retained on the alveolar ridge, despite adequate vestibule depth, due to tongue dyskinesia. A bar joint was used to anchor this mucosal-borne denture. This implant-supported complete denture led to a clear improvement in the patient's chewing function when observed over a period of a year.