Silicon photodiodes with high photoconductive gain at room temperature.

Silicon photodiodes with high photoconductive gain are demonstrated. The photodiodes are fabricated in a complementary metal-oxide-semiconductor (CMOS)-compatible process. The typical room temperature responsivity at 940 nm is >20 A/W and the dark current density is ≈ 100 nA/cm2 at 5 V reverse bias, yielding a detectivity of ≈ 10(14) Jones. These photodiodes are good candidates for applications that require high detection sensitivity and low bias operation.

Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia.

Alemtuzumab (anti-CD52; Campath-1H) is effective in fludarabine-refractory chronic lymphocytic leukemia (CLL), but is associated with infection and early onset neutropenia. To reduce toxicity, filgrastim (G-CSF) was administered concurrently with alemtuzumab. In total, 14 CLL patients (median age 59) with a median of 3.5 prior regimens (range 1--12) received i.v. alemtuzumab, stepped up from 3 to 30 mg the first week, then 30 mg thrice weekly for 12 weeks. Filgrastim 5 microg/kg was administered daily 5 days before and throughout alemtuzumab therapy. Six patients developed cytomegalovirus (CMV) reactivation 3--6 weeks into treatment; six patients developed fever, three neutropenia, and one pneumonia. The patient with CMV pneumonia died; ganciclovir cleared CMV in the other patients. Five patients developed early neutropenia (weeks 2--5). Four patients developed delayed neutropenia (weeks 10--13) unassociated with CMV reactivation. Nine patients ceased therapy because of infectious and hematologic toxicity. Five partial responses were noted, all in patients with lymph nodes>cm, lasting a median of 6.5 months (range 5--13). Filgrastim and alemtuzumab were given concurrently with manageable infusion toxicity and clinical activity, but the efficacy of this regimen was limited by delayed neutropenia of unclear etiology and CMV reactivation. Filgrastrim should not be administered prophylactically during alemtuzumab therapy outside clinical trials.

Rimantadine for treatment of hepatitis C infection in liver transplant recipients.

Hepatitis C recurrence after liver transplantation is a serious problem, leading to increased graft loss and morbidity in some individuals. Treatment with interferon and other agents is controversial and not highly efficacious. The use of an effective antiviral agent to reduce or eliminate viral burden is desirable. To this end, we performed an open-label pilot trial to determine if rimantadine would show antiviral activity against hepatitis C virus (HCV) in the posttransplantation setting. Eleven patients with recurrent post-liver transplantation disease, characterized by transaminase level abnormality and HCV RNA in serum and liver biopsy specimens consistent with HCV infection were offered enrollment onto the study. Patients were treated for 12 weeks with rimantadine, 100 mg orally twice daily, and followed up after treatment for up to 8 additional weeks. Serum was collected at 2-week intervals to assess transaminase and HCV RNA levels. Nine patients completed the planned course of therapy. There was no significant change in serum alanine aminotransferase levels during treatment. No patients cleared HCV RNA from the serum, and fluctuations in the viral titer were not clearly associated with the initiation and completion of the active-treatment phase. Rimantadine was well tolerated, with only one patient who stopped therapy for perceived side effects. We conclude that rimantadine monotherapy has no role in the management of recurrent hepatitis C after liver transplantation.

Cutaneous necrosis associated with interferon alpha-2b.

Cutaneous necrosis may occur as a complication of treatment with interferon. Here we report the first case of cutaneous necrosis developing in a patient receiving interferon alpha-2b for the treatment of chronic hepatitis C viral infection. The patient developed two necrotic lesions while receiving high doses of interferon. We suggest that discontinuation of treatment may be necessary to permit healing of such lesions. Although the exact mechanism involved in cutaneous necrosis remains unknown, our observations support earlier findings suggesting that intraarterial injection may be a factor.

Suppressor cells and T cell synergy in the primary MLR: interleukin-2 is required for the maintenance of rat CD8+ suppressor cells.

The requirements for maintenance of allospecific CD8+ Ts cells generated in the rat primary MLR were investigated. Allospecific CD8+ Ts cells rapidly lose their activity over 72 hr in secondary culture with media alone, whereas low concentrations of rIL-2 (less than 1 U/ml) are able to maintain potent CD8+ Ts cell activity. This Ts cell activity is maintained at rIL-2 concentrations which do not result in significant cell proliferation. Therefore, cell proliferation per se is not a requirement to maintain Ts cell activity, although the CD8+ Ts cells can proliferate to rIL2 in a concentration-dependent manner. An anti-IL-2 receptor monoclonal antibody significantly inhibited the maintenance of Ts cell activity. Two-color flow cytometric analysis demonstrated that Ts cells cultured in rIL-2 maintain upregulation of their high-affinity IL-2 receptor. Although allospecific Ts cells maintained in secondary culture with rIL-2 for 48 hr maintained antigen specificity, there is also the induction of an antigen-nonspecific population. After 168 hr in secondary culture the Ts cells have lost allospecificity, although Ts activity can be maintained with rIL2 in continuous culture for up to 4 weeks.

A radioimmunoassay for 5-methyltetrahydrohomofolate.

A radioimmunoassay for 5-methyltetrahydrohomofolate has been developed by using antibody induced in rabbits by 5-methyltetrahydrohomofolate-bovine serum albumin conjugates. The labeled drug was prepared by condensing it with [3H]histamine or [125I]histamine. The assay employing either isotope was simple and reproducible and had identical sensitivities. The specificity of the antibody was characterized by comparing the effectiveness of various related compounds in displacing labeled 5-methyltetrahydrohomofolate from the binding site of the antisera. At concentrations up to 1000 microgram/ml, homofolate acid, tetrahydrohomofolic acid, folic acid and methotrexate showed no competition for the binding. 5-methyltetrahydrofolic acid and 5-formyltetrahydrofolic acid cross-reacted with the antisera; the concentrations producing 50% binding inhibition were 2.8 and 24 microgram, respectively, as compared to 0.01 microgram for 5-methyltetrahydrohomofolate. The assay can be used for measuring the drug in plasma and tissues. This study supports its usability for clinical pharmacologic studies.