Development of a geometrically accurate imaging protocol at 3 Tesla MRI for stereotactic radiosurgery treatment planning.

The purpose of this study is to develop a geometrically accurate imaging protocol at 3 T magnetic resonance imaging (MRI) for stereotactic radiosurgery (SRS) treatment planning. In order to achieve this purpose, a methodology is developed to investigate the geometric accuracy and stability of 3 T MRI for SRS in phantom and patient evaluations. Forty patients were enrolled on a prospective clinical trial. After frame placement prior to SRS, each patient underwent 3 T MRI after 1.5 T MRI and CT. MR imaging protocols included a T1-weighted gradient echo sequence and a T2-weighted spin echo sequence. Phantom imaging was performed on 3 T prior to patient imaging using the same set-up and imaging protocols. Geometric accuracy in patients and phantoms yielded comparable results for external fiducial reference deviations and internal landmarks between 3 T and 1.5 T MRI (mean ≤ 0.6 mm; standard deviation ≤ 0.3 mm). Mean stereotactic reference deviations between phantoms and patients correlated well (T1: R = 0.79; T2: R = 0.84). Statistical process control analysis on phantom QA data demonstrated the stability of our SRS imaging protocols, where the geometric accuracy of the 3 T SRS imaging protocol is operating within the appropriate tolerance. Our data provide evidence supporting the spatial validity of 3 T MRI for targeting SRS under imaging conditions investigated. We have developed a systematic approach to achieve confidence on the geometric integrity of a given imaging system/technique for clinical integration in SRS application.

An octapeptide analogue of HIV gp120 modulates protein tyrosine kinase activity in activated peripheral blood T lymphocytes.

Following infection with HIV, patients exhibit lymphocyte dysfunction before the loss of CD4+ T cells. The major HIV surface glycoprotein, gp120, can modulate lymphocyte function in vitro; however, the mechanism by which gp120 affects T lymphocyte signal transduction is controversial. We have used Peptide T, a synthetic octapeptide derived from a conserved, CD4 binding region of gp120, to examine gp120-related modulation of lymphocyte signal transduction. Activation of lymphocytes through the T cell receptor (TCR) in collaboration with cell surface accessory molecules results in rapid increases in tyrosine phosphorylation, probably through the recruitment and activation of src-family protein tyrosine kinases (PTK) such as lck and fyn which have been implicated in mediating the proximal signalling events mediated through the TCR. To identify potential mechanisms by which gp120 could modulate the function of T lymphocytes, we determined the effect of Peptide T on normal, activated peripheral blood lymphoblasts. Treatment of normal, activated peripheral blood lymphoblasts with Peptide T (10(-9) M) for 60 min transiently reduced levels of protein tyrosine phosphorylation (ptyr). Reduction in levels of cellular ptyr was associated with transient inhibition of the activity of total cellular and CD4-associated p56lck kinase activity (80%). Peptide T also induced a small delayed reduction in the p59fyn activity (up to 42%). Despite the decrease in total cellular ptyr levels, pp60c-src kinase activity was increased 11-fold following treatment with Peptide T. Peptide T pretreatment also induced tyrosine phosphorylation of a 48-kD CD4-associated protein, indicating that Peptide T may have multiple effects. Peptide T did not alter the levels of total cellular p56lck enzyme, nor did it directly inhibit the activity of purified p56lck. These results are consistent with a Peptide T-dependent modulation of PTK regulation, and support the potential of gp120 to interfere with T lymphocyte signal transduction in activated T lymphocytes.

Using serial observations to identify predictors of progression to AIDS in the Toronto Sexual Contact Study.

The Toronto Sexual Contact Study comprises a cohort of 249 male sexual contacts of men with HIV disease which has been followed every 3 months for almost 5 years. On enrollment 143 were seropositive and 16 seroconverted during the follow-up period. By 31 December 1989, 41 of the 159 seropositive cohort members had developed AIDS. Using Cox relative risk regression models, we investigated the association of a number of laboratory and clinical variables and progression to AIDS. Fixed covariate models examined laboratory variables from the enrollment visit of cohort members, with time calculated from this date. In models assessing time dependent covariates, time was calculated from the estimated date of HIV infection. In the univariate models of either fixed or time dependent covariates, many variables were significantly associated with risk of progression to AIDS (T4 cell count, T4/T8 ratio, blastogenic responses to phytohemagglutinin, concanavalin A, and pokeweed mitogen, serum IgA, appearance of p24 antigen, and the development of oral hairy leukoplakia, thrush, or herpes zoster). Appearance of persistent generalized lymphadenopathy was not associated with increased risk of progression. In the multivariate model which evaluated fixed laboratory covariates, T4/T8 ratio, IgA level, and PHA response at enrollment were significantly associated with elevated risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Detection of incident HIV infection by PCR compared to serology.

In order to determine the most sensitive method for the early detection of HIV infection, polymerase chain reaction (PCR) and serology were compared using matched peripheral blood mononuclear cells (PBMC) and serum samples taken sequentially at 3-month intervals on 17 HIV seroconverters. All samples from the time of enrollment in the study to the time of seroconversion were studied. [There were only two of the 17 cases where PCR and antigen positivity preceded EIA detectable seroconversion.] Initially, one of these cases was found to be PCR positive 11 months prior to seroconversion, however DNA fingerprinting techniques indicated that the early positive specimen did not belong to the subject in question. In a single subject, PCR was negative at the time of serologic evidence of infection but was positive at the next sampling 3 months later. In the remaining 14 cases, PCR was positive at the same sample time as full or partial seroconversion as determined by three EIA screening tests and Western blot. EIA antibody screen tests showed variability in detection of early HIV antibodies. We found no evidence for prolonged HIV infection prior to seroconversion. PCR offers little if any advantage over serology in the early detection of HIV infection in adults.

Allopurinol sensitivity in a patient with chronic tophaceous gout: success of intravenous desensitization after failure of oral desensitization.

Sensitivity to allopurinol, which occurs in 10-15% of patients, can seriously limit the drug's use in chronic tophaceous gout. Oral allopurinol desensitization has been advocated for sensitive patients in whom use of the drug is warranted. We report the successful use of intravenous allopurinol desensitization in a patient with chronic tophaceous gout in whom oral desensitization had previously failed.

Cofactors of progression to acquired immunodeficiency syndrome in a cohort of male sexual contacts of men with human immunodeficiency virus disease.

In a cohort of 249 male sexual contacts of men with acquired immunodeficiency syndrome (AIDS) or an AIDS-related condition in Toronto, Ontario, Canada, 143 cohort members were seropositive on enrollment and 16 seroconverted between initial recruitment in July 1984 to July 1985 and December 1988. Data on age, smoking and drinking status, recreational drug use, and history of sexually transmitted diseases and other diseases were obtained from interviews at induction and during follow-up on the cohort members every 3 months. Cox relative risk regression models, in which time was calculated from estimated date of human immunodeficiency virus (HIV) infection for seroprevalent cohort members and from 90 days prior to the first positive test for seroconverters, examined the potential effect of use of a variety of recreational drugs and the occurrence of selected infections on the risk of development of AIDS. Thirty-five cohort members developed AIDS while under study. No significant association with risk of progression to AIDS was noted for use of various recreational drugs (singly or in combination), history of specific infections, age at enrollment, or smoking and drinking status at enrollment. Only estimated duration of HIV infection appeared to be associated with increasing risk of development of AIDS.

Autofluorescence of alveolar macrophages: problems and potential solutions.

Despite recent advances in immunofluorescence technology, the study of alveolar macrophage cell surface proteins is hampered by the presence of autofluorescence. We suggest several approaches that might overcome this problem and enable specific immunofluorescent detection of cellular proteins and automated analysis of alveolar macrophages.

The effect of chemotherapeutic agents on chemotaxis and random migration of human leukocytes.

Chemotherapeutic agents (CTAs) used for treatment of neoplastic and other diseases may influence defense mechanisms of the patient, altering various humoral and cellular immunologic functions. Herein we report the influence of 16 CTAs on random migration and chemotaxis of human polymorphonuclear cells (PMNCs), using two methods, under-agarose migration and double-filter Boyden chambers with 51Cr-PMNCs. Random migration was inhibited by vinblastine only (P less than .01). BCNU and daunorubicin inhibited random migration only when used in high concentrations. In under-agarose migration, only BCNU and vinblastine inhibited chemotaxis (P less than .01) in therapeutic concentrations. Inhibition was also observed when higher concentrations of vincristine were tested. In the Boyden method, marked inhibition of chemotaxis (P less than .01) was caused by BCNU, vinblastine, vincristine, daunorubicin, and doxorubicin. Inhibition of chemotaxis could not be reversed by washing the cells after preincubation. CTAs per se did not have chemoattractant activity. This study shows that some chemotherapeutic agents inhibit random and directed migration of human PMNCs. It also supports the evidence that Boyden chamber method may detect chemotactic abnormalities that escape recognition by the under-agarose migration method. Suppression of locomotion of PMNCs should be taken into consideration in patients treated with CTAs.

Sex steroids imprinting and prostatic growth.

Sex steroids exposure to rats castrated at birth during the neonatal or prepubertal period permanently modified certain morphologic features of the accessory sex organs in adulthood. Similar treatment of intact rats failed to induce these changes. Hypophysectomy in adulthood did not abolish the neonatally androgen-induced imprinting of the growth response of the rat accessory sex organs in adulthood, which suggests that the effects of neonatal androgen administration are directly on the hormone-responsive target cells and are not mediated via the hypothalamic-pituitary axis.