Accuracy of single-time, multilevel registration in image-guided spinal surgery.

BACKGROUND CONTEXT: Computerized frameless stereotactic image-guidance has been used in recent years to improve the accuracy and safety of pedicle screw placement during spine surgery. Because the possibility of intervertebral motion exists, and because the patient is usually in a different position when preoperative imaging is performed compared with the operative position, it has been suggested that the imaging model of the complete lumbar spine and the surgically exposed lumbar spine may be significantly discordant. Consequently, current protocols suggest registering each spinal level (single-level registration) separately before pedicle screw placement at that level, a time-consuming process. PURPOSE: To assess the accuracy of single-time multilevel registration for multilevel pedicle screw placement during image-guided, computer-assisted spine surgery, in the setting of degenerative disorders of the lumbar spine. STUDY DESIGN/SETTING: This is a prospective clinical and radiological study of 45 patients with degenerative disorders of the lumbar spine who underwent instrumented fusion with the use of single-time multilevel registration computer-assisted, image-guided tomography. The accuracy of the pedicle screws placement was confirmed on the basis of a protocol that included intraoperative spontaneous electromyographic (EMG) recordings, direct pedicle visualization, and computer tomography (CT) scans when clinically indicated during the follow-up period. PATIENT SAMPLE: Forty-five consecutive patients who fulfilled the criteria of computer-assisted, image-guided tomography pedicle screw placement for degenerative lumbar spine disease without overt instability. OUTCOME MEASURES: The principal outcome measure was the accuracy of pedicle screw placement with single-time multilevel registration for multilevel pedicle screw placement during image-guided, computer-assisted spine surgery; postoperative CT performed for clinical indications during the follow-up course was used for the assessment of pedicle screw placement. METHODS: Patients were assessed clinically before and after the operation. Data from 45 consecutive cases of image-guided, computer-assisted lumbar spinal fusion were statistically analyzed to determine the relationship between the number of levels registered during single-time registry and the mean registration error (MRE). Intraoperative spontaneous EMG, direct visualization, and postoperative CT scans were used to assess the accuracy of pedicle screw insertion. RESULTS: None of the patients involved in this study experienced clinical sequelae of improper pedicle screw placement. MREs after surface mapping and after point merge were small (less than 1.00 mm and less than 3.00 mm, respectively). During the intraoperative assessment of the pedicle screws placement, no significant spontaneous EMG activity was recorded and the pedicular walls were found intact in direct visualization. The postoperative CT scans showed in 10 patients accurate placement in 55 of the 57 pedicle screws with expansion of the medial wall in two screws. CONCLUSIONS: Single-time, multilevel registration may decrease operative time relative to repeated, single-level registrations, without compromising the increased accuracy of pedicle screw placement afforded by this technique in the setting of degenerative disorders of the lumbar spine. Despite the advantages in computer-guided image surgery, cautious application in the individual patient is recommended until more comprehensive data can be gathered in specific degenerative pathology with overt instability; thus the knowledge of the anatomy remains crucial.     

Prognostic importance of human papillomavirus type 16 DNA in cervical cancer.

Human papillomavirus (HPV) type 16 DNA is frequent in invasive cervical cancers. Among 43 patients with invasive cervical cancer, HPV-16-positive tumors spread to the parametrial and pelvic lymph nodes significantly more often than did HPV-16-negative tumors (P less than 0.05). Demonstration of HPV-16 DNA in invasive cervical cancers may be an additional prognostic factor for this disease.     

Somatostatin Receptor Localization of Pancreatic Endocrine Tumors

n = 39) than conventional imaging studies (MRI, n = 25; CT, n = 13); 23 of 24 patients had positive octreotide scintigraphy, 17 of 24 had positive MRI-scans, and 12 of 24 patients had positive CT scans. It was concluded that ¹¹¹ In-octreotide scintigraphy combined with conventional imaging improves the preoperative localization of presumably tumorous lesions in patients with gastroenterohepatic endocrine tumors.     

Comparison of LCx with other current viral load assays for detecting and quantifying human immunodeficiency virus type 1 RNA in patients infected with the circulating recombinant form A/G (CRF02)

LCx was compared to other assays in measuring human immunodeficiency virus type 1 (HIV-1) CRF02 viremia. LCx showed significant but low correlation with the other methods. Values of <2.60 log(10) cp/ml were observed in 29.6% of specimens with LCx and in only 14.8% with bDNA and PCR, suggesting suboptimal performance of LCx with CRF02.     

Selected RD1 Peptides for Active Tuberculosis Diagnosis: Comparison of a Gamma Interferon Whole-Blood Enzyme-Linked Immunosorbent Assay and an Enzyme-Linked Immunospot Assay

We recently set up a gamma interferon (IFN-γ) enzyme-linked immunospot assay (ELISPOT), using selected early secreted antigenic target 6 (ESAT-6) peptides, that appears specific for active tuberculosis (A-TB). However, ELISPOT is difficult to automate. Thus, the objective of this study was to determine if the same selected peptides may be used in a technique more suitable for routine work in clinical laboratories, such as whole-blood enzyme-linked immunosorbent assay (WBE). For this purpose, 27 patients with A-TB and 41 control patients were enrolled. Our WBE, using the already described selected peptides from ESAT-6 plus three new ones from culture filtrate protein 10, was performed, and data were compared with those obtained by ELISPOT. Using our selected peptides, IFN-γ production, evaluated by both WBE and ELISPOT, was significantly higher in patients with A-TB than in controls (P < 0.0001). Statistical analysis showed a good correlation between the results obtained by WBE and ELISPOT (r = 0.80, P < 0.001). To substantiate our data, we compared our WBE results with those obtained by QuantiFERON-TB Gold, a whole-blood assay based on region of difference 1 (RD1) overlapping peptides approved for TB infection diagnosis. We observed a slightly higher sensitivity with QuantiFERON-TB Gold than with our WBE (89% versus 81%); however, our test provided a better specificity result (90% versus 68%). In conclusion, results obtained by WBE based on selected RD1 peptides significantly correlate with those generated by ELISPOT. Moreover, our assay appears more specific for A-TB diagnosis than QuantiFERON-TB Gold, and thus it may represent a complementary tool for A-TB diagnosis for routine use in clinical laboratories.     

Increasing proportion of late diagnosis of HIV infection among patients with AIDS in Italy following introduction of combination antiretroviral therapy

We analyzed trends over time and determinants of late diagnosis of HIV infection among people diagnosed with AIDS in 1986 to 1998 in a tertiary care center in Rome, Italy. Information on the date of a first HIV test was collected prospectively, in addition to data routinely collected for AIDS reporting. Patients with AIDS were defined as "late testers" if the time interval between first positive HIV test result and AIDS diagnosis was < or = 3 months. Overall, 503 people with AIDS of 1977 included in the analysis (25.4%) were late testers. the proportion of late testers decreased from 62.5% in 1986 to 16% in 1995. Thereafter, this proportion increased to 20.5% in 1996, 33.7% in 1997, and 36.6% in 1998. In multivariate analysis, the following variables were significantly associated with late testing: AIDS diagnosis in years 1986 to 1993 or 1997 to 1998 compared with 1995, male gender, age > or = 45 years, men who have sex with men, heterosexual contacts, or having unknown transmission mode compared with intravenous drug users, and being born outside Italy. Since 1996, the overall number of AIDS cases diagnosed at our center began to decrease whereas the number of late-testing AIDS patients did not decrease, resulting in an increasing proportion of late testers during the last 3 years of the study. This findings may reflect the effect of combination antiretroviral therapy in slowing progression to AIDS of HIV-infected persons aware of their status. A relevant number of people still discover their HIV infection late and may therefore miss treatment opportunities. New testing strategies are needed to reach more people who engage in high-risk behaviors, especially those at risk for sexual transmission, and those born outside Italy.     

A novel inhibitor of the alternative complement pathway prevents antiphospholipid antibody-induced pregnancy loss in mice

Studies in gene-targeted mice have demonstrated that factor B of the alternative complement pathway plays an important role in several disease models, but an exogenous inhibitor of factor B has not previously been available. We have developed an inhibitory monoclonal antibody directed against a critical epitope on mouse factor B and have tested it in a model of antiphospholipid (aPL) antibody (Ab)-induced fetal loss. Gene-targeted factor B-deficient mice (fB-/-) were injected with a fusion protein comprised of the second and third short consensus repeat (SCR) domains of mouse factor B linked to a mouse IgG1 Fc domain. Hybridomas were made from splenocytes of the immunized mouse. One mAb, designated 1379, produced an IgG1 antibody that inhibited alternative pathway activation in vitro and in vivo by preventing formation of the C3bBb complex. Strikingly, this mAb inhibited alternative pathway activation in serum from mice, rats, humans, monkeys, pigs and horses. Fab fragments made from this mAb also inhibited alternative pathway activation. Epitope mapping demonstrated that this antibody binds to factor B within the third SCR domain. When mAb 1379 was administered to mice that also received human IgG containing antiphospholipid antibodies, it provided significant protection from antiphospholipid antibody-induced complement activation and fetal loss. Thus, this mAb to factor B has broad species reactivity and effectively inhibits alternative pathway activation. The mAb protects mice in an in vivo model of antiphospholipid antibody syndrome, demonstrating the therapeutic potential for the inhibition of factor B in this disease.     

Comparative studies of purified subviral component vaccines and formalin-treated mammary tumor viruses from four inbred strains of mice

Formalin-treated virus vaccines were prepared from purified murine mammary tumor viruses (MuMTV) from 4 inbred strains of mice: RIII/Imr, GR/Imr, C3H/Imr, and A/Imr. In addition, subviral components were isolated from these 4 strains and purified to homogeneity. The inactivated viruses, their major envelope glycoproteins (gp50-gp55), and their major internal core protein (p28) were emulsified in complete Freund's adjuvant and used as vaccines for prevention of mammary tumors in mice. All 4 Formalin-treated virus vaccines reduced significantly the incidence of mammary tumors in "virus-free" C57BL and BALB/c mice when inoculated prior to challenge with live MuMTV. The RIII-, GR-, and A-MuMTV strains showed extensive heterologous cross-protection, whereas the C3H-MuMTV strain showed significant protection only against C3H- and A-MuMTV challenge. The major viral glycoproteins gp50-gp55 reduced significantly the tumor incidence when mice were challenged with isologous infectious virus after immunization, although these glycoproteins showed different degrees of cross-protection than did the same virus strains used as "intact" but Formalin-treated preparations. RIII-gp55 and GR-gp55 cross-protected against each other but not against challenge with C3H- and A-MuMTV strains; the A-gp50 protected against challenge with A- and RIII-MuMTV strains; C3H-gp55 demonstrated limited activity against C3H-MuMTV challenge only. The internal viral core proteins (p28) were ineffective in all systems studied. The same vaccines were tested in MuMTV-positive, high-tumor-incidence strains from which they were derived. At best, the appearance of spontaneous tumors was delayed in a few experimental sets; eventually, all mice developed mammary tumors. The foster-nursed C3HfC57BL strain of mice, which is not exposed to exogenous MuMTV during suckling and which develops mammary tumors after activation of the endogenous virus genome later in life, was responsive only when the heterologous GR-MuMTV Formalin-treated vaccine was used. The association between the ability of virus vaccines to protect a mouse strain and the degree of natural virus expression in that strain is discussed.     

Immunologic studies with mouse mammary tumor viruses: comparative studies with spontaneous mammary tumor cell vaccines from five inbred mouse strains

Vaccines were prepared from cells of primary spontaneous mammary tumors (MT) of RIII/Imr, GR/Imr, C3H/Imr, A/Imr, and C3HfC57BL/Imr mice. Each vaccine was used to immunize "murine mammary tumor virus (MuMTV)-free" BALB/c/Imr and C57BL/Imr mice before challenge with infectious RIII-MuMTV, GR-MuMTV, C3H-MuMTV, and A-MuMTV. RIII-MT and C3H-MT cells protected mice against tumorigenesis by all four MuMTV's; GR-MT cells protected against all but the RIII-MuMTV challenge; A-MT cells were ineffective against challenge by all four MuMTV's and significantly enhanced development of A-MuMTV-induced tumors. The activity of the C3H-MT cells was not seen when C3HfC57BL cells, free of the standard C3H-MuMTV, were used. The same cell vaccines were inoculated into the five donor strains of mice in attempts to prevent spontaneous MT in these high-incidence strains, which are naturally infected with MuMTV at birth. None of the vaccines prevented tumorigenesis in these mouse strains although delays in the appearance of tumors were observed in RIII and GR mice inoculated with either isologous MT cells or C3Hf-MT cells. The role of viral antigens acting alone or in concert with cellular antigens is discussed.