Phase I study of high-dose cytosine arabinoside and etoposide in patients with advanced malignancies

Summary Cytosine arabinsodie (ara-C) and etoposide (VP-16) display synergy in the laboratory. Twenty-six patients participated in a phase I study of high-dose ara-C in combination with VP-16. The dose of VP-16 was held constant at 50 mg/m² as an intermittent infusion over 33 h; escalating doses of ara-C were given as infusions during hours 9–12 and 21–24. Myelosuppression was the dose-limiting toxicity and occurred with doses considerably less than those expected from studies of the two drugs as single agents. The suggested initial doses for phase II trials with this schedule are 750 mg/m²×2 doses of ara-C and 50 mg/m² of VP-16. Nonhematologic toxicity was minimal; therefore, further dose escalation is feasible in patients in whom myelosuppression is acceptable.Supported in part by grants from the National Cancer Institute (CA-12197 and CA-09422) and the American Cancer Society CF-85-182     

Quantitative assessment of ALZ-50 immunoreactivity in Alzheimer's disease.

A quantitative assay for ALZ-50 immunoreactivity was evaluated in samples of superior temporal gyrus taken at autopsy from 13 Alzheimer patients and 11 controls. The assayable immunoreactivity appears to be stable for at least 24 hours postmortem but was lost with formalin fixation. The mean value of the Alzheimer patients was tenfold higher than that of the controls (P less than .002). The values of four Alzheimer samples overlapped with the low levels seen in controls, but no controls had elevated levels. In this sample population, therefore, the assay had a sensitivity of 69% and specificity of 100%.     

Scar sign of renal oncocytoma: Magnetic resonance imaging appearance and lack of specificity

This case report illustrates the magnetic resonance imaging (MRI) appearance of a typically asymptomatic renal oncocytoma as a homogeneous mass of medium signal with a stellate central region of decreased signal, representing the central scar. The MRI was correlated with computed tomography (CT), ultrasound (US), and gross pathologic appearance. The appearance of a central scar is not specific for oncocytoma and does not exclude renal cell carcinoma, as illustrated by a second case.     

Association between the HOXA1 A218G polymorphism and increased head circumference in patients with autism.

BACKGROUND: The HOXA1 gene plays a major role in brainstem and cranial morphogenesis. The G allele of the HOXA1 A218G polymorphism has been previously found associated with autism. METHODS: We performed case-control and family-based association analyses, contrasting 127 autistic patients with 174 ethnically matched controls, and assessing for allelic transmission disequilibrium in 189 complete trios. RESULTS: A, and not G, alleles were associated with autism using both case-control (chi(2) = 8.96 and 5.71, 1 df, p <.005 and <.025 for genotypes and alleles, respectively), and family-based (transmission/disequilibrium test chi(2) = 8.80, 1 df, p <.005) association analyses. The head circumference of 31 patients carrying one or two copies of the G allele displayed significantly larger median values (95.0th vs. 82.5th percentile, p <.05) and dramatically reduced interindividual variability (p <.0001), compared with 166 patients carrying the A/A genotype. CONCLUSIONS: The HOXA1 A218G polymorphism explains approximately 5% of the variance in the head circumference of autistic patients and represents to our knowledge the first known gene variant providing sizable contributions to cranial morphology. The disease specificity of this finding is currently being investigated. Nonreplications in genetic linkage/association studies could partly stem from the dyshomogeneous distribution of an endophenotype morphologically defined by cranial circumference.     

Contralateral reinnervation of midline muscles in nonidiopathic facial palsy.

The purpose of this study was to analyze contralateral reinnervation of the facial nerve in eight patients with complete facial palsy after surgery or trauma and seven healthy volunteers. All patients had contralateral reinnervation of facial muscles as demonstrated by electrical nerve stimulation versus none of the control subjects. Four patients had facial muscle movements at the site of the damaged nerve. In one patient this was entirely the result of contralateral reinnervation, whereas the other three patients had innervation both ipsilaterally and contralaterally. This implies that renewed facial muscle activity should be examined considering the origin of the reinnervation, either contralateral or ipsilateral. Contralateral reinnervation is a common phenomenon after total facial palsy and can occur alongside ipsilateral reinnervation. It can be mistaken for adequate reinnervation of the damaged nerve, causing postponement of dynamic reconstruction therapy.     

MR imaging of extraabdominal desmoids: differentiation from other neoplasms.

A retrospective review of MR images of 36 patients with histologically proved extraabdominal desmoids was done to define the MR characteristics of these tumors and to determine if MR could be used to differentiate desmoids from other benign and malignant soft-tissue neoplasms. The desmoids evaluated included eight primary and 30 recurrent lesions. Our study was conducted in parallel with another study in which the MR appearance of 95 benign and malignant soft-tissue masses was evaluated, and the MR images of these masses were compared with our findings. The four desmoids from that study are included in our data. The signal intensity of the tumor on T1- and T2-weighted images was graded relative to the intensities of muscle and fat. Homogeneity, margin, neurovascular and bone involvement, and fibrosis (low-signal regions within the tumor on both T1- and T2-weighted images) were evaluated. On MR imaging, the desmoids showed inhomogeneous signal (97%), poor margination (89%), neurovascular involvement (58%), and bone involvement (37%). Fibrosis was present in 88% of primary desmoids and 90% of recurrent ones, and intermediate signal (greater than that of muscle and less than that of fat) was present in 75% and 50% of these, respectively. Our results show that the MR features of desmoids have characteristics that are commonly found in malignant tumors (inhomogeneous signal, poor margination, and neurovascular involvement). MR features of desmoids that distinguish them from malignant neoplasms are the presence of fibrosis and intermediate signal in the regions of the tumor.