Starting in 1988, 72 patients with advanced human immunodeficiency virus (HIV) infection were enrolled in a phase I study of didanosine at the National Cancer Institute. Beginning in 1992, patients ...with decreases in CD4 cell counts could switch to a combination of zidovudine and didanosine. The estimated median survival for all patients was 28 months (95% confidence interval, 23–46). However, for patients whose entry CD4 cell counts were 100–300/mm3, the estimated 4-year survival was 80%. Baseline CD4 and CD8 cell counts, hemoglobin, lymphocytes, sedimentation rates, diagnosis of AIDS, and fever were significant predictors of overall survival. Principal toxicities were pancreatitis and peripheral neuropathy; no new toxicities were seen with extended didanosine treatment that had not been observed in shorter-term studies. This 5-year follow-up shows that didanosine can be tolerated for >4 years in some patients with advanced HIV infection and may have particular long-term utility in patients with moderately advanced immunosuppression.
A variety of drugs have been used to treat B-lymphocyte neoplasms, including both cell cycle-specific (CCS) and non-cell-cycle-specific drugs. Although the therapy for such cancers is complex and can ...include both types of drugs, the efficacy of these drugs in inducing cell death remains unclear. In this paper we have concentrated on specific CCS drugs and have examined their ability to induce programmed cell death (apoptosis) in Burkitt's lymphoma cell lines derived from patients. The CCS drugs chosen were hydroxyurea and aphidicolin (active in late G1, early S phase), the topoisomerase poisons camptothecin and etoposide (S, early G2phase) and vincristine and Taxol (late G2, M phase). These choices allow comparison of two drugs with differing modes of action for each of the various phases of the cell cycle. Our results indicate that the variation in apoptosis between drugs that act at the same phase of the cell cycle is negligible. Both S/G2and G2/M blockers are very potent at inducing apoptosis whereas G1/S blockers are ineffective in the induction of apoptosis. In addition, marked kinetic variations in the rate of apoptosis induction were observed, etoposide and camptothecin being more rapid in their action than the other agents. The order of effectiveness in inducing apoptosis on a kinetic basis was S/G2agents ⪢ G2/M agents ⪢ G1/S agents. In this study we have also found that growth inhibition was induced by all the CCS agents chosen and by anti-IgM in various Burkitt's lymphoma lines. Furthermore c-mycwas down-regulated under similar conditions. Since apoptosis was only selectively induced by some of the CCS agents, it implies c-mycexpression is associated with growth regulation and c-myc down-regulation is an insufficient condition for the induction of apoptosis. In addition, cotreatments using the CCS and other agents revealed the following: Cotreatment using two CCS drugs which act at the same stage in the cell cycle showed either no change or only additivity to the effects seen with either agent alone. However, cotreatment with CCS drugs showed that an inhibitory effect is found between G1/S and G2/M drugs or S/G2and G2/M drugs. No effect was found between G1/S and S/G2drugs. Anti-IgM, which by itself was capable of inducing apoptosis, was observed to augment apoptosis induced by very low concentrations of G2/M-acting drugs but it has little effect on G1/S or the S/G2drugs. The inhibitory effect of anti-CD40 or TNF-α on anti-IgM-induced apoptosis did not carry over to an effect on apoptosis induction by the CCS agents. Thus specific combinations of agents may lead to either enhancement, inhibition, or no interactive effect on apoptosis.
The equilibrium constants for complexation of C
60 with naphthalene, phenanthrene and pyrene in toluene have been determined by UV/visible spectroscopy. The magnitude of the equilibrium constants was ...found to increase with decreasing ionization potential of the donor. Values for complexation enthalpy have been determined for the first time for C
60/aromatic hydrocarbons. Well-defined charge transfer (C-T) bands have been observed for complexes of C
60 with a variety of aromatic hydrocarbons, with C-T band maxima moving to higher frequency with increasing donor ionization potential.
The equilibrium constants for complexation of C60 with naphthalene, phenanthrene and pyrene in toluene have been determined by UV visible spectroscopy. The magnitude of the equilibrium constants was ...found to increase with decreasing ionization potential of the donor. Values for complexation enthalpy have been determined for the first time for C60/aromatic hydrocarbons. Well-defined charge transfer (C-T) bands have been observed for complexes of C60 with a variety of aromatic hydrocarbons, with C-T band maxima moving to higher frequency with increasing donor ionization potential.
Stereotactic radiosurgery serves as an important primary and adjuvant treatment option for patients with many types of intracranial meningiomas. This is particularly true for patients with parasellar ...meningiomas. In this study, the authors evaluated the outcomes of Gamma Knife surgery (GKS) used to treat parasellar meningiomas.
The study is a retrospective review of the outcomes in 138 patients with meningiomas treated at the University of Virginia from 1989 to 2006; all patients had a minimum follow-up of 24 months. There were 31 men and 107 women whose mean age was 54 years (range 19-85 years). Eighty-four patients had previously undergone resection. The mean pre-GKS tumor volume was 7.5 ml (range 0.2-54.8 ml). Clinical and radiographic evaluations were performed, and factors related to favorable outcomes in each case were assessed.
The mean follow-up duration was 84 months (median 75.5 months, range 24-216 months). In 118 patients (86%), the tumor volume was unchanged or had decreased at last follow-up. Kaplan-Meier analysis demonstrated radiographic progression-free survival at 5 and 10 years to be 95.4% and 69%, respectively. Fourteen patients (10%) developed new cranial nerve palsies following GKS. Factors associated with tumor control included younger age, a higher isodose, and smaller tumor volume. A longer follow-up duration was associated with either a decrease or increase in tumor volume. Fourteen patients (10%) experienced new or worsening cranial nerve deficits after treatment. Factors associated with this occurrence were larger pretreatment tumor volume, lower peripheral radiation dose, lower maximum dose, tumor progression, and longer follow-up.
Gamma Knife surgery offers an acceptable rate of tumor control for parasellar meningiomas and accomplishes this with a low incidence of neurological deficits. Radiological control after radiosurgery is more likely in those patients with a smaller tumor volume and a higher prescription dose.
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