Diamon Gangji

Leukoencephalopathy and elevated levels of myelin basic protein in the cerebrospinal fluid of patients with acute lymphoblastic leukemia.

AS the survival of patients with acute lymphoblastic leukemia has improved, increased attention has focused on the potential toxicity and adverse long-term sequelae of antileukemic therapy. In part...

Transient expansion of peptide‐specific lymphocytes producing IFN‐γ after vaccination with dendritic cells pulsed with MAGE peptides in patients with mage‐A1/A3‐positive tumors

Assessment of T‐cell activation is pivotal for evaluation of cancerimmunotherapy. We initiated a clinical trial in patients with MAGE‐A1and/or ‐A3 tumors using autologous DC pulsed with MAGE peptides aimedat analyzing T‐cell‐derived, IFN‐γ secretion by cytokine flowcytometry and ELISPOT. We also tested whether further KLH additioncould influence this response favorably. Monocyte‐derived DC weregenerated from leukapheresis products. They were pulsed with therelevant MAGE peptide(s) alone in group A (n=10 pts) andadditionally with KLH in group B (n=16 pts). A specific buttransient increase in the number of peripheral blood T lymphocytessecreting IFN‐γ in response to the vaccine peptide(s) was observed in6/8 patients of group A and in 6/16 patients of group B. We concludethat anti‐tumor vaccination using DC pulsed with MAGE peptides inducesa potent but transient anti‐MAGE, IFN‐γ secretion that is notinfluenced by the additional delivery of a nonspecific, T‐cellhelp.

Influence of fluoxetine on olanzapine pharmacokinetics

Conventional antidepressant treatment fails for up to 30% of patients with major depression. When there are concomitant psychotic symptoms, response rates are even worse. Thus, subsequent treatment often includes combinations of antidepressants or augmentation with antipsychotic agents. Atypical antipsychotic agents such as olanzapine cause fewer extrapyramidal adverse effects than conventional antipsychotics; for that reason, they are an advantageous augmentation strategy for treatment-resistant and psychotic depression. The purpose of this study was to assess the potential for pharmacokinetic interaction between olanzapine and fluoxetine, a popular antidepressant that is a selective serotonin reuptake inhibitor. The pharmacokinetics of 3 identical single therapeutic doses of olanzapine (5 mg) were determined in 15 healthy nonsmoking volunteers. The first dose of olanzapine was taken alone, the second given after a single oral dose of fluoxetine (60 mg), and the third given after 8 days of treatment with fluoxetine 60 mg, qd. Olanzapine mean C max was slightly higher (by about 18%) and mean CL/F was slightly lower (by about 15%) when olanzapine was coadministered with fluoxetine in single or multiple doses. Olanzapine mean t 1/2 and median t max did not change. Although the pharmacokinetic effects of fluoxetine on olanzapine were statistically significant, the effects were small and are unlikely to modify olanzapines safety profile. The mechanism of influence is consistent with an inhibition of CYP2D6, which is known to control a minor pathway of olanzapine metabolism.

Therapeutic Effect of Human Recombinant Interferon-Alpha-2C in Essential Thrombocythaemia

Human recombinant interferon-alpha 2C was given to 4 patients with essential thrombocythaemia. Three patients achieved a complete remission on day 19 +/- 1 and the 4th achieved a partial remission. After 4 weeks of induction therapy, a maintenance therapy of twice weekly intramuscular injections of 5 X 10(6) or 10 X 10(6) IU was instituted but did not maintain the remission.

Amiodarone-induced thyrotoxicosis suggestive of thyroid damage

Amiodarone-induced thyrotoxicosis (AIT) is generally believed to result from increased hormonal synthesis related to the iodine overload. Thyroid damage has recently been incriminated as a pathophysiological mechanism. We report 3 cases of AIT associated with clinical and/or biochemical features consistent with thyroid damage. This hypothesis was supported by a painful thyroid (case 1 ), transient high serum Tg (case 2), a transient (case 2) or persistent (case 3) hypothyroid phase and an undetectable technetium thyroid uptake during the hypothyroid period (case 3). These clinical observations support the previous histological data indicating that thyroid follicular disruption might contribute to the pathogenesis of AIT.

Acute pancreatitis as presenting symptom and sole manifestation of small cell lung carcinoma.

SummaryA 58-year-old man with no sign of pulmonary disease and a normal chest x-ray presented with acute pancreatitis resistant to conventional medical management and a mass in the head of the pancreas. The presumptive diagnosis was pancreatic cancer with tumor-induced pancreatitis. However, endoscopic retrograde cholangiopancreatography suggested metastatic rather than primary tumor, so that an extrapancreatic primary was actively sought. Further lung work-up demonstrated a small cell carcinoma of the lung. This case indicates that metastasis-induced acute pancreatitis can be the presenting symptom and sole manifestation of lung cancer.

Trisomy 11 in preleukemia

The clinical and cytogenetic findings of a patient with a preleukemic state and trisomy 11 are reported. Trisomy 11 was present as the sole karyotypic alteration at the time of overt leukemia. Trisomy 11 presents an additional chromosomal abnormality not previously described in preleukemia.

Misonidazole blood and cerebrospinal fluid kinetics in monkeys following intravenous and intrathecal administration

Abstract Misonidazole (NSC 261037) (RO 070582) blood and cerebrospinal fluid (CSF) levels were studied in the rhesus monkey following 100 and 200 mg/kg intravenous i.v. and 0.9 mg/kg intrathecal i.t. administration. After a 200 mg/kg i.v. dose the plasma half life (4.8 hr) was increased in comparison to that following a 100 mg/kg dose, suggesting possible saturation of metabolic pathways. Levels of desmethylmisonidazole (the major metabolite) were observed in the plasma 5 min after administration and were approximately 45% of those of the parent compound 4.5 hr later. Misonidazole and the desmethylated metabolite measured in 24-hr urine collections accounted for 4.8 and 19.3% of the total dose administered, respectively. Following i.v. bolus administration misonidazole levels were detected in the CSF at 5 min and rapidly achieved equilibrium with plasma levels within 90 min. Elimination of misonidazole from the CSF occurred at the same rate as that from the plasma. The metabolite was measurably in CSF approximately 1.5 hr after administration and ranged from 33 to 82% of plasma levels. Following i.t. injection, misonidazole disappearance occurred in a biexponential manner with mean-disappearance half times of 15 min and 38 min for the fast and slow phases, respectively.

Malignant Fibrous Histiocytoma of the Heart: Case Report and Literature Review

A case report of a 57-year-old woman with malignant fibrous histiocytoma of the heart is presented. The clinical presentation was suggestive of a benign atrial myxoma. Careful pathologic study is necessary to differentiate the myxoid variant of malignant fibrous histiocytoma of the heart from the more common benign atrial myxoma. Usually, the evolution of malignant fibrous histiocytoma of the heart is rapidly fatal. Clinical aspects of this patients case are discussed in conjunction with a review of the available literature.

Mechanisms of Neurotoxicity and Experimental Models

The mechanisms of action underlying the neurotoxicity caused by chemotherapeutic drugs can be related to the mechanism by which the drug exerts its anticancer activity, but may also be totally different. In order to be able to study these mechanisms, the development and use of in-vitro and in-vivo test models are indispensable. In addition, the models may provide a preclinical tool to test possible methods for prevention and treatment of drug-related neurotoxicity. In the first place, it can be stated that the number of available models is small, whereas most of the existing models can be strictly applied only to a specific class of anticancer drugs. Another aspect, of equal importance, is the often underestimated influence of pharmacological parameters, such as the route of administration, the kinetics of the drug and drug interactions.