Comparative in vivo evaluation of technetium and iodine labels on an anti-HER2 affibody for single-photon imaging of HER2 expression in tumors.

In vivo diagnosis with cancer-specific targeting agents that have optimal characteristics for imaging is an important development in treatment planning for cancer patients. Overexpression of the HER2 antigen is high in several types of carcinomas and has predictive and prognostic value, especially for breast cancer. A new type of targeting agent, the Affibody molecule, was described recently. An Affibody dimer, His6-(ZHER2:4)2 (15.4 kDa), binds to HER2 with an affinity of 3 nmol/L and might be used for the imaging of HER2 expression. The use of 99mTc might improve the availability of the labeled conjugate, and Tc(I)-carbonyl chemistry enables the site-specific labeling of the histidine tag on the Affibody molecule. The goals of the present study were to prepare 99mTc-labeled His6-(ZHER2:4)2 and to evaluate its targeting properties compared with the targeting properties of 125I-4-iodobenzoate-His6-(ZHER2:4)2 [125I-His6-(ZHER2:4)2]. METHODS: The labeling of His6-(ZHER2:4)2 with 99mTc was performed with an IsoLink kit. The specificity of 99mTc-His6-(ZHER2:4)2 binding to HER2 was evaluated in vitro with SK-OV-3 ovarian carcinoma cells. The comparative biodistributions of 99mTc-His6-(ZHER2:4)2 and 125I-His6-(ZHER2:4)2 in tumor-bearing BALB/c nu/nu mice were determined. RESULTS: The labeling yield for 99mTc-His6-(ZHER2:4)2 was approximately 60% (50 degrees C), and the radiochemical purity was greater than 97%. The conjugate was stable during storage and under histidine and cysteine challenges and demonstrated receptor-specific binding. The biodistribution study demonstrated tumor-specific uptake levels (percentage injected activity per gram of tissue [%IA/g]) of 2.6 %IA/g for 99mTc-His6-(ZHER2:4)2 and 2.3 %IA/g for 125I-His6-(ZHER2:4)2 at 4 h after injection. Both conjugates provided clear imaging of SK-OV-3 xenografts at 6 h after injection. The tumor-to-nontumor ratios were much more favorable for the radioiodinated Affibody. CONCLUSION: The use of Tc(I)-carbonyl chemistry enabled us to prepare a stable, site-specifically labeled 99mTc-His6-(ZHER2:4)2 conjugate that was able to bind to HER2-expressing cells in vitro and in vivo. The indirectly radioiodinated conjugate provided better tumor-to-liver ratios. The labeling of Affibody molecules with 99mTc should be investigated further.     

Treatment of cremaster synkinesias with botulinum toxin A: a video case report.

Synkinesias secondary to nerve lesions and aberrant re-innervation are well-known phenomena especially after lesions of the facial nerve. Synkinesias can successfully be treated with botulinum toxin A (BTx A). Synkinesias of the cremaster muscle have not been described or treated to date. We present the case of a 62-year-old man who developed synkinesias of both cremaster muscles after extensive laparatomy for esophageal cancer. Treatment of synkinesias with various oral medications had been unsuccessful. Electromyography-guided injections of BTx A in both cremaster muscles (15 MU on the right and 10 on the left) led to significant symptom relief for an average of 8 weeks. We present the case including pre- and posttreatment video clips.     

Mapping scores onto stages: mini-mental state examination and clinical dementia rating.

OBJECTIVE: Although the clinical course of Alzheimer disease (AD) is gradual, it is useful for a number of reasons to distinguish between different levels of severity. The Clinical Dementia Rating (CDR) has demonstrated high validity and reliability for this purpose, but it requires a considerable amount of data to be collected both from the patient and from an informant. In the present study, the authors mapped Mini-Mental State Examination (MMSE) scores onto CDR categories to determine how well the MMSE performs as a surrogate of the CDR as a timesaving method of staging dementia. METHOD: Eight hundred sixty-three probands, including 524 patients with probable AD, 92 patients with questionable dementia, and 247 with memory complaints but no objective cognitive impairment, were included. Cutoff scores were identified on one-half of the sample using a receiver operating characteristic analysis. The cutoff values were then applied to the other half of the sample, and the agreement between MMSE score ranges and CDR stages was determined by calculating Cohen's kappa. RESULTS: The MMSE discriminated well between CDR stages 0.5, 1, 2, and 3 but performed poorly in the separation between CDR stages zero and 0.5. The MMSE ranges were 30 for no, 26-29 for questionable, 21-25 for mild, 11-20 for moderate, and 0-10 for severe dementia. Substantial agreement between the two instruments was obtained for the categories mild (kappa=0.62, p<0.001, N=115), moderate (kappa=0.69, p<0.001, N=114), and severe dementia (kappa=0.76, p<0.001, N=39), whereas the agreement was moderate for no (kappa=0.44, p<0.001, N=120) and only fair for questionable dementia (kappa=0.28, p<0.001, N=42). CONCLUSION: The MMSE can be used as a surrogate measure for the CDR for the staging of dementia in AD.     

Posttraumatisches septisches Abdomen

Abdominal infection has the fifth highest incidence of all posttraumatic infections but has the second highest mortality rate with 25%,pneumonia,with 29%, being the only posttraumatic infection that is more frequently lethal.Posttraumatic abdominal sepsis, on the other hand, has a mortality rate of almost 50%.This rate cannot be reduced except by prompt identification of the correct diagnosis of the underlying injury or complication.This means that delayed laparotomy is strikingly detrimental in these patients, with 46% mortality as opposed to 11% in patients who undergo laparotomy promptly. In parallel with this, the mortality of fresh-onset and localized peritonitis is 14%,whereas that of diffuse purulent peritonitis is up to a devastating 42%.     

Rekonstruktion und Stabilisierung nach fehlverheilten Frakturen und Pseudarthrosen im Femurbereich mit Marknagel und anderen Osteosyntheseverfahren (LISS-System)

Malunion and nonunion after fracture present many difficulties in trauma surgery. Selection of the best therapy and operative techique requires careful analysis of the complications. Hyperthrophic nonunion of the femur shaft is mostly best treated with locking reamed nails. Significant differences in torsions after nailing can be corrected by repositioning of the distal interlocking screws if recognized sufficiently early. After fracture healing an open rotation osteotomy is necessary; stabilization can be achieved by means of medullary nails or a condylar plate. How a malalignment of the bone axis is corrected depends on the position of a malunion, the functional deficit caused, and the biomechanical demands on the joint. Condylar plates can often solve the problems in this region. There are also guidelines for ¶the treatment of atrophic and infected nonunions (recommended procedures are ¶aggressive debridement, autologous cancellous bone graft, and biological osteosynthesis), but the treatment of individual cases requires a exhaustive knowledge of and experience in this special field. It is quite common for even well-established procedures to fail. When the bone is biologically reduced and this is the reason for malunion newly developed techniques of internal fixation can be applied. The less invasive stabilization system (LISS), combined with autologous cancellous bone grafting if necessary, can result in healing even in a worst-case scenario.     

Risk of acquiring influenza A in a nursing home from a culture-positive roommate.

Influenza A was cultured in 62 double rooms. The roommate was infected in 12 (19.4%). During 3,294 resident-seasons, influenza was cultured in 208 single rooms (6.3%). Those who lived in double rooms with a culture-positive roommate had a 3.07 relative risk (CI95, 1.61-5.78) of acquiring influenza.     

Parent satisfaction with paediatric day-surgery: a questionnaire-based study

Potential advantages of paediatric day-surgery are cost saving, improved utilization of staff and hospital facilities, and reduction of stress for the paediatric patient and their family. A successful programme requires careful case selection, full operating and anaesthetic facilities and good follow-up. Current practice is reviewed with regard to initial assessment, preparation for surgery and overall management during the day admission. To provide information on how patients and their parents experience essential aspects of daycare paediatric surgery, a questionnaire-based study on parental satisfaction of paediatric day-surgery was performed. Most children were back to normal, within a few days. Recovery from paediatric day-surgery was rapid and the overall level of parent satisfaction was high.     

Parvalbumin 3 is an Abundant Ca2+ Buffer in Hair Cells

Ca2+ signaling serves distinct purposes in different parts of a hair cell. The Ca2+ concentration in stereocilia regulates adaptation and, through rapid transduction-channel reclosure, underlies amplification of mechanical signals. In presynaptic active zones, Ca2+ mediates the exocytotic release of afferent neurotransmitter. At efferent synapses, Ca2+ activates the K+ channels that dominate the inhibitory postsynaptic potential. A copious supply of diffusible protein buffer isolates the three signals by restricting the spread of free Ca2+ and limiting the duration of its action. Using cDNA subtraction and a gene expression assay based on in situ hybridization, we detected abundant expression of mRNAs encoding the Ca2+ buffer parvalbumin 3 in bullfrog saccular and chicken cochlear hair cells. We cloned cDNAs encoding this protein from the corresponding inner-ear libraries and raised antisera against recombinant bullfrog parvalbumin 3. Immunohistochemical labeling indicated that parvalbumin 3 is a prominent Ca2+-binding protein in the compact, cylindrical hair cells of the bullfrog's sacculus, and occurs as well in the narrow, peanut-shaped hair cells of that organ. Using quantitative Western blot analysis, we ascertained that the concentration of parvalbumin 3 in saccular hair cells is approximately 3 mM. Parvalbumin 3 is therefore a significant mobile Ca2+ buffer, and perhaps the dominant buffer, in many types of hair cell. Moreover, parvalbumin 3 provides an early marker for developing hair cells in the frog, chicken, and zebrafish.     

Doxorubicin in experimental and clinical heart failure.

Doxorubicin-induced heart failure is a rare but serious illness due to the well-known treatment difficulties. Prevention strategies have not demonstrated the expected success and unfortunately, this specific type of heart failure does not respond to the usual medical therapy as other kinds of heart failure. Therefore, surgical procedures may be necessary in some patients. Cardiac transplantation is performed in most cases but it requires the cure of the neoplastic disease. This usually requires a recurrence-free interval of several years which is associated with a high attrition rate in these patients due to their cardiac disease. Therefore, other conservative and surgical treatment concepts were developed during the last years. This review presents the most common procedures and discusses their efficacy as well as their clinical applicability.