Structural modification of receptor-binding technetium-99m complexes in order to improve brain uptake

Low brain uptake is a generally accepted problem in developing technetium-99m brain receptor imaging agents. For a class of potential 5-HT_2A receptorbinding agents we tried to improve the original low brain uptake of 0.4% injected dose (ID) in rats 5 min p.i. by modifying the lipophilic properties of the molecules. Because of the presence of a protonable nitrogen, which according to the pK _a value leads to ionization of the molecule at blood pH, the pK _a value was considered to be the parameter most suitable for adjustment of lipophilicity. Insertion of ether-oxygen in the molecule of five candidates lowers the apparent pK _a value from 10.0 to 8.3 and dramatically increases the brain uptake to 1.3% ID at 5 min. The direct relationship between brain uptake and apparent pK _a cannot be simply explained by the increase in the pK _a-governed proportion of the neutral species.     

Reconstruction of plantar defects

Plantar defects are a challenge for the plastic surgeon; from 1984–1995 59 operations were performed in 57 patients. The radial forearm flap and the latissimus dorsi (LD) flaps were mainly used depending on the amount of tissue loss. Local flaps such as dorsalis pedis and instep flaps were used for smaller defects. The radial forearm flap is ideal in terms of thickness and stability for the sole but limited in its size. The LD flap is a safe procedure especially for severe injuries and osteitis, but has the disadvantage of being bulky and debulking procedures are frequently performed. For nerve reconstruction deep sensibility seems to be sufficient in order to obtain stable postoperative results. In this report the different operative methods are evaluated. Since 1991, the patients were monitored with static and dynamic foot pressure measurements and gait analysis to assess the postoperative result and prevent pressure ulcers, scar irritation and hyperkeratosis. Preoperative investigations may contribute to an optimal schedule for planning and stabilization of the operative regimen.     

Synthetic Colloids Attenuate Leukocyte-Endothelial Interactions by Inhibition of Integrin Function

Background: It has been suspected that synthetic colloids may interfere with leukocyte adhesion by down-regulation of endothelial cell adhesion molecules. Although inhibition of endothelial inflammation might reduce leukocyte-related tissue injury, the same mechanism may be detrimental for host defense during severe infection. Regarding the widespread use of colloids, the authors performed a laboratory investigation to determine the mechanisms by which synthetic colloids interfere with leukocyte-endothelial interactions.

Methods: Adhesion molecule expression on native and cytokine-activated endothelium from umbilical veins was measured after pretreatment with gelatin and various preparations of dextran or hydroxyethyl starch. Inhibition of neutrophil adhesion to activated endothelium was examined in a flow chamber by perfusion of untreated and colloid-treated neutrophils over colloid-pretreated endothelium at 2 dyn/cm2. Comparisons were made between untreated controls, colloid-pretreated endothelium, and colloid-cotreated neutrophils.

Results: Intercellular adhesion molecule 1, vascular cell adhesion molecule 1, E-selectin, and P-selectin were not attenuated by any colloid. Accordingly, colloid pretreatment of endothelium alone did not reduce neutrophil adhesion. In contrast, when neutrophils were cotreated by addition of colloids to the perfusate immediately before perfusion, adhesion decreased by 31-51% (P < 0.05) regardless of the colloid type. As indicated by the twofold increased rolling fractions, this reduction was due to an inhibition of neutrophil integrins.     

Lymphoscintigraphy as a predictor of lymphatic drainage from cutaneous melanoma

Background: If cutaneous lymphoscintigraphy (CL) is accurate in predicting the draining lymph node basins at risk from primary axial melanomas, then regional metastases should only occur in those lymph node basins identified by CL. Methods: This study is a retrospective review of patients undergoing CL for primary axial melanomas from June 1, 1985, until June 31, 1992. Data retrieved included age, gender, number of basins identified, location of basins identified, management of basins, recurrence in lymphatics, development of distant disease, and long-term follow-up. Results: A total of 181 patients underwent elective LND, and 48 patients (27%) had melanoma in the nodes within the dissected basin. Of these 181 patients, seven developed nodal metastases as their site of first recurrence. All seven recurrences were seen at sites dissected or at sites indicated by CL, which the primary surgeon elected not to treat initially. Of the 116 patients observed, 16 (14%) developed lymph node metastases as their first site of recurrence. Fifteen of these 16 patients had their site of lymph node metastases predicted by CL. In this study, CL predicted 98.6% of all lymph node metastases. Conclusions: The high overall reliability of CL as demonstrated by long-term follow-up indicates that the information obtained by CL can be reliably used to guide intervention. Initial evaluation of patients with high-risk cutaneous melanomas at sites with ambiguous lymphatic drainage must include CL in order to determine the draining lymph node basins and to plan therapy. Presented at the 47th Annual Cancer Symposium of The Society of Surgical Oncology, Houston, Texas, March 17–20, 1994.     

A survey of pre-placement urinalysis drug findings.

In December, 1989, the Department of Transportation (DOT) in conjunction with the Federal Aviation Administration (FAA) mandated an extensive urine drug testing program for selected positions within the airline industry. At the end of 1 year we have tested 7,872 applicants under these rules, with a positive finding rate of 0.17%. We have also tested 32,157 applicants, including those applying for DOT-covered positions, with a positive rate of 2.82%. Considering only the two major drugs of abuse--marijuana and cocaine--we found the positive rate to be an order of magnitude greater than the rate discovered under the DOT program. We present these data together with a discussion of some of the possible reasons for this major disparity. We also present findings for barbiturates and benzodiazepines which are not tested under the DOT program, but which have safety implications related to the aviation industry.     

Fluorescence immunohistochemistry and confocal scanning laser microscopy

We have developed a reliable technique for labeling and examining neural structures in soft tissues associated with articular joints and have tested it in human wrist joints under various specimen-related conditions. The labeling protocol employs an immunohistochemical process with a panneuronal marker (PGP 9.5) as the primary antibody and Alexa Fluor 488 as the fluorescing secondary antibody. Imaging was done using a confocal laser scanning microscope, which produced exceptionally detailed three-dimensional images of nerve endings and transiting nerve fibers from thick sections of wrist joint ligaments obtained from human cadavers. The protocol provided a practical postmortem window for specimen acquisition and processing without significant apparent worsening of image quality. The images produced are resistant to fading with repeated exposure to a fluorescent light source, which gives many opportunities for observation. Background staining is minimal, producing high contrast labeling of target tissues, which, in turn, enhances image analysis.     

Assessment of immunization as a technique to extend the chilled storage life of vacuum‐packaged lamb

The growth at — 1.5°C of Lactobacillus delbrueckii, a meat spoilage organism, was evaluated on vacuum‐packaged lamb legs obtained from animals immunized against that organism. Growth was significantly lower than that on similarly treated legs obtained from non‐immunized lambs. These findings suggest that immunization against spoilage organisms may contribute toward increasing the chilled storage life of fresh meat.     

Pneumococcaemia as a presenting sign in 3 cases of multiple myeloma

Multiple myeloma was diagnosed in 3 patients following episodes of pneumococcaemia associated with neutropenia and decreased serum concentration of normal immunoglobulins. Severe pneumococcal infection is commonly encountered during the course of multiple myeloma, but has not been stressed as a presenting feature of the disease.