Comparative study of monoclonal antibody scan in diagnosing orthopaedic infection

When clinical data are insufficient to diagnose infection of bone or joints, nuclear scanning becomes crucial in making an accurate diagnosis. The efficacy of (99m)technetium antigranulocyte monoclonal antibody Fab' fragment (LeukoScan) is prospectively compared with (111)indium white blood cell and (99m)technetium methylene diphosphonate bone scans in 74 patients with suspected musculoskeletal infections. They were grouped according to site of suspected infection: 33 long bones, 23 prosthetic joints, and 18 diabetic feet. Sixty-two of these 74 patients had surgical verification with histopathology or culture. The remaining 12 patients had clinical followup as proof of absence of infection. The overall sensitivity of LeukoScan, (111)indium white blood cell, and (99m)technetium methylene diphosphonate bone scans was 93%, 85% and 92%, respectively. Specificity was 89%, 75% and 52%, and accuracy was 90%, 79% and 74%, respectively. The conclusion from this study is that LeukoScan is more accurate in detecting osteomyelitis, with better sensitivity and specificity in prosthetic joints. Compared with (111)indium white blood cell scans, LeukoScan++ gives superior images, and results are obtained in 1 to 6 hours without biohazard risk from handling blood products.     

Cost-effectiveness of preoperative localization studies in primary hyperparathyroid disease

OBJECTIVE: To evaluate the effect of preoperative localization studies on the surgical management of patients with primary hyperparathyroid disease (PHPT). SUMMARY BACKGROUND DATA: Reported cure rates of initial surgical exploration for PHPT are close to 95%. Preoperative localization studies are frequently obtained to improve surgical success and decrease operative time. METHODS: Initial cervical exploration was performed in 113 patients with PHPT from 1981 to 1993. Twenty-four patients (21%) had surgery without preoperative localization studies. The remaining 89 patients (79%) had 132 noninvasive preoperative localization studies. Success of the localization studies in tumor localization, pathologic findings, postoperative serum calcium levels, and operative times were compared. Patient costs of the studies were calculated. RESULTS: Disease was identified during operation in 23 of 24 patients (96%) having cervical exploration without preoperative localization studies, and they had normal calcium levels after surgery. Eighty-seven of 89 patients (98%) having preoperative localization studies were surgically cured. The highest sensitivity rate (60%) and highest positive predictive value (79%) of the localization studies were found with thallium-technetium scintiscanning. Average cost of the localization studies was $901 per patient. Combination studies were obtained in 32 patients at an average cost of $1,314 per patient without improving sensitivity. Mean operating time did not differ for localized and nonlocalized patients. CONCLUSIONS: Preoperative localization studies did not improve parathyroid localization or cure rate and did not substantially shorten operating time in initial cervical exploration for PHPT. The economic burden of routine preoperative localization studies in these patients is not justified.     

Arterial reactivity is enhanced in genetic males taking high dose estrogens

OBJECTIVES: We sought to assess whether high dose estrogen treatment is associated with enhanced arterial reactivity in genetic males. BACKGROUND: Although estrogens have been shown to enhance arterial reactivity in women, and are thereby thought to confer cardiovascular benefit, the vascular effects of long-term estrogen therapy in genetic males is unknown. METHODS: We studied the arterial physiology of 30 genetic males--15 male to female transsexuals receiving long-term high dose estrogen therapy and 15 healthy male control subjects matched for age, smoking history and vessel size. Using external vascular ultrasound, brachial artery diameter was measured at rest, after flow increase (causing endothelium-dependent dilation [EDD]) and after nitroglycerin (GTN), an endothelium-independent dilator. Blood pressure, cholesterol and testosterone levels were also measured in each subject. RESULTS: Total testosterone and free testosterone index levels were lower in the transsexuals compared with the control subjects (p < 0.001). In contrast, EDD was significantly higher in the transsexuals than in the control males (mean [+/-SD] 7.1 +/- 3.1% vs. 3.2 +/- 2.8%, p = 0.001), as was the GTN response (21.2 +/- 6.7% vs. 14.6 +/- 3.3%, p = 0.002). Total and high density lipoprotein cholesterol, blood pressure levels and baseline vessel size were similar in the two groups. On multivariate analysis, enhanced EDD was associated independently with estrogen therapy (p = 0.02) and with low total cholesterol (p = 0.04). An enhanced GTN response was also significantly associated with estrogen therapy (p = 0.03). CONCLUSIONS: Long-term treatment with high dose estrogens is associated with enhanced arterial reactivity in genetic males, which may be due to the effects of estrogen excess or androgen deprivation, or both.     

Synaptic-like microvesicles of neuroendocrine cells originate from a novel compartment that is continuous with the plasma membrane and devoid of transferrin receptor

We have characterized the compartment from which synaptic-like microvesicles (SLMVs), the neuroendocrine counterpart of neuronal synaptic vesicles, originate. For this purpose we have exploited the previous observation that newly synthesized synaptophysin, a membrane marker of synaptic vesicles and SLMVs, is delivered to the latter organelles via the plasma membrane and an internal compartment. Specifically, synaptophysin was labeled by cell surface biotinylation of unstimulated PC12 cells at 18 degrees C, a condition which blocked the appearance of biotinylated synaptophysin in SLMVs and in which there appeared to be no significant exocytosis of SLMVs. The majority of synaptophysin labeled at 18 degrees C with the membrane-impermeant, cleavable sulfo-NHS-SS-biotin was still accessible to extracellularly added MesNa, a 150-D membrane-impermeant thiol-reducing agent, but not to the 68,000-D protein avidin. The SLMVs generated upon reversal of the temperature to 37 degrees C originated exclusively from the membranes containing the MesNa-accessible rather than the MesNa-protected population of synaptophysin molecules. Biogenesis of SLMVs from MesNa-accessible membranes was also observed after a short (2 min) biotinylation of synaptophysin at 37 degrees C followed by chase. In contrast to synaptophysin, transferrin receptor biotinylated at 18 degrees or 37 degrees C became rapidly inaccessible to MesNa. Immunofluorescence and immunogold electron microscopy of PC12 cells revealed, in addition to the previously described perinuclear endosome in which synaptophysin and transferrin receptor are colocalized, a sub-plasmalemmal tubulocisternal membrane system distinct from caveolin-positive caveolae that contained synaptophysin but little, if any, transferrin receptor. The latter synaptophysin was selectively visualized upon digitonin permeabilization and quantitatively extracted, despite paraformaldehyde fixation, by Triton X-100. Synaptophysin biotinylated at 18 degrees C was present in these subplasmalemmal membranes. We conclude that SLMVs originate from a novel compartment that is connected to the plasma membrane via a narrow membrane continuity and lacks transferrin receptor.     

NG2 proteoglycan and the actin-binding protein fascin define separate populations of actin-containing filopodia and lamellipodia during cell spreading and migration

The transmembrane proteoglycan NG2 is able to interact both with components of the extracellular matrix and with the actin cytoskeleton. An examination of the distribution of NG2 during cell spreading suggests that NG2 can associate with two distinct types of actin-containing cytoskeletal structures, depending on the nature of the stimulus derived from the substratum. On fibronectin-coated dishes, cell surface NG2 associates exclusively with stress fibers developing within the cell. On poly-L-lysine-coated dishes, cell surface NG2 is associated with radial processes extending from the cell periphery. Spreading on fibronectin/poly-L-lysine mixtures, as well as on matrix components such as laminin, tenascin, and type VI collagen, produces cells with mosaic characteristics, i.e., NG2 is associated with both types of structures. NG2-positive radial processes are distinct from a second population of radial structures that contain fascin. NG2-positive extensions appear to be individual self-contained units (filopodia), whereas fascin is associated with actin ribs within sheets of membrane (lamellipodia). NG2- and fascin-positive structures are often localized to opposite poles of spreading cells, suggesting a possible role for the two classes of cellular extensions in the establishment of cell polarity during morphogenesis or migration. Time lapse imaging confirms the presence of lamellipodia on the leading edges of migrating cells, while numerous filopodia are present on trailing edges.     

The D2 autoreceptor agonists SND 919 and PD 128483 decrease stereotypy in developing rats

Although stereotyped behavior in adult rats is partly regulated by dopamine (DA) D2 autoreceptors, previous attempts to demonstrate D2 autoreceptor regulation of stereotypy in developing rats have been unsuccessful. In the present study, two highly selective D2 autoreceptor agonists were used to demonstrate D2 autoreceptor regulation of spontaneous stereotyped behavior in developing rats. Both SND 919 and PD 128483 produced significant dose-dependent decreases in the stereotypy counts of 21-day-old, 35-day-old, and adult rats. There was a 51% decrease in the stereotypy counts of 21-day-old rats injected with SND 919, 0.05 mg/kg, compared to a 36% decrease in the counts of rats pretreated with haloperidol. Similarly, PD 128483 significantly decreased the stereotypy counts of 21-, 35-day-old, and adult rats in a dose-dependent fashion. There was a 58% decrease in the stereotypy counts of 21-day-old rats injected with PD 128483, 0.1 mg/kg, compared to a 17% decrease in counts when the rats were first treated with haloperidol. The effect of haloperidol plus PD 128483 was significantly different from the effect of PD 128483 alone. Injection of SND 919 or PD 128483 had no significant effects on the stereotypy counts of 10-day-old rats. The results suggest that DA D2 autoreceptor-mediated regulation of spontaneous stereotyped behavior is functional at 21, but not 10, days of age.