High-dose etoposide and cyclophosphamide without bone marrow transplantation for resistant hematologic malignancy

Seventy-five patients with resistant acute leukemia or lymphoma received high-dose cyclophosphamide and etoposide to explore the activity of this combination in resistant hematologic malignancies, and to determine the maximum doses of these drugs that can be combined without bone marrow transplantation. Etoposide was administered over 29 to 69 hours by continuous infusion corresponding to total doses of 1.8 g/m2 to 4.8 g/m2. Cyclophosphamide, 50 mg/kg/d, was administered on 3 or 4 consecutive days total 150 to 200 mg/kg ideal body weight). At all dose levels myelosuppression was severe but reversible. Mucosal toxicity was dose-limiting with the maximum tolerated dose level combining etoposide 4.2 g/m2 with cyclophosphamide 200 mg/kg. Continuous etoposide infusion produced stable plasma levels that were lower than would be achieved after administration by short intravenous infusion, and this could explain our ability to escalate etoposide above the previously reported maximum tolerated dose. There were 28 complete (35%) and 12 partial (16%) responses. Median duration of complete response (CR) was 3.5 months (range 1.1 to 20+). Seventeen of 40 patients (42%) with acute myelogenous leukemia (AML) achieved CR, including 6 of 20 (30%) with high-dose cytosine arabinoside resistance. We conclude that bone marrow transplantation is not required after maximum tolerated doses of etoposide and cyclophosphamide. This regimen is active in resistant hematologic neoplasms, and the occurrence of CR in patients with high-dose cytosine arabinoside-resistant AML indicates a lack of complete cross-resistance between these regimens.     

Münzkopfschmerz

Background

Subcutaneous peripheral nerve field stimulation (sPNFS) is an established procedure for the treatment of chronic localized neuropathic pain of peripheral origin. The treatment of nummular headache primarily focuses on conservative methods with limited prospects of success. The role of sPNFS in the treatment of nummular headache has not been investigated as yet.

Question

Is the sPNFS an option in the management of nummular headache?

Materials and methods

In addition to a summary of established methods in the treatment of nummular headache, sPNFS as a possible form of therapy is discussed.

Results

A positive effect of sPNFS in terms of the treatment of nummular headache is shown.

Discussion

sPNFS stimulates free subcutaneous nerves and transmits a pleasant form of paraesthesia in the area of pain. If regular conservative therapy has already been exhausted, then sPNFS might be an effective new option in the treatment of nummular headache. sPNFS is a minimally invasive and low-risk procedure. However, the high treatment cost and restrictions regarding fitness to undergo MRI are points of criticism. Further studies are needed to define its potential and role in the treatment of nummular headache.

     

Comparison of culture and serology for the diagnosis of cytomegalovirus infection in kidney and liver transplant recipients

This study compared culture, including the shell vial procedure, with serology, including IgM cytomegalovirus (CMV) antibody testing, for the diagnosis of CMV infection in 42 subjects undergoing cadaveric renal or liver transplantation. Of 35 subjects who developed active CMV infection, 31 had positive cultures, while IgM CMV antibodies were detected in 29. Subjects with symptomatic CMV infection were more likely than asymptomatic subjects to have positive cultures of leukocytes (17/18 vs. 9/17, P = .01). In contrast, symptomatic and asymptomatic subjects did not differ in their IgG or IgM CMV antibody test responses. In subjects with symptomatic infection, viral shedding typically began early in the course of infection, often preceding symptoms, while the serologic response usually followed the appearance of symptoms. With the use of the shell vial procedure to facilitate detection of positive cultures, symptomatic CMV infections following kidney or liver transplantation can be recognized earlier and more reliably using viral culture than by serologic testing.     

The macrophage adherence inhibition test in Wistar rats bearing Jensen tumors. II. Macrophage adherence inhibition test after intravenous administration of spores of the CNRZ 528 strain of Clostridium butyricum and incubation with clostridial antigens

The tumor-specificity of tumor-clostridia-phenomenon in the model of Jensen-sarcoma of the white rat was detected with the help of humoral and cell-mediated immune reactions of the host towards intravenous application of 5 X 10(8) spores of clostridia, which do not dissolve the tumor. Contrary to weak responses in Widal-agglutination the MAI showed characteristic values of inhibition of peritoneal-cell-adherence in tumor-bearing animals after incubation with soluble clostridia antigens.     

Successful strategy to improve the specificity of electronic statin–drug interaction alerts

Purpose  

A considerable weakness of current clinical decision support systems managing drug–drug interactions (DDI) is the high incidence of inappropriate alerts. Because DDI-induced, dose-dependent adverse events can be prevented by dosage adjustment, corresponding DDI alerts should only be issued if dosages exceed safe limits. We have designed a logical framework for a DDI alert-system that considers prescribed dosage and retrospectively evaluates the impact on the frequency of statin–drug interaction alerts.     

Tolcapone improves sleep in patients with advanced Parkinson's disease (PD)

Efficacy of the long-acting catechol-O-methyltransferase (COMT)-inhibitor, tolcapone on sleep quality was studied in 61 patients with advanced PD in a prospective open-label multicenter non-interventional trial. Main outcome measures were the PD sleep scale (PDSS). Further outcome measures were global clinical impression of change (GCI-C), daily off-time, activities of daily living (UPDRS part II), quality of life (EuroQoL-5D), Epworth sleepiness scale (ESS) and adverse events reports. All efficiency and safety parameters were assessed 4 weeks after the switch to tolcapone and compared to baseline. The mean ± S.D. daily dose of tolcapone was 294.2 ± 36.9 mg/day at the final assessment. The mean PDSS scores significantly improved from 21.6 ± 8.1 at baseline to 16.3 ± 7.7 at final assessment (p < 0.0001). Consistently, daytime sleepiness was significantly reduced as reflected by lower scores on the ESS (p = 0.0057). Further efficacy parameters including GCI-C, daily off-time, activities of daily living, and quality of life were also significantly improved. Tolcapone was in general well tolerated and safe. This observational study provides first evidence that tolcapone improves sleep quality and reduces daytime sleepiness in patients suffering from advanced PD.     

Rippling muscle disease: Variable phenotype in a family with five afflicted members

We report a family with rippling muscle disease (RMD) who had an autosomal dominant mode of inheritance. The father, mother, and one daughter proved to be heterozygous, and two sons were homozygous for the A92T mutation of the caveolin‐3 gene. The cardinal features of RMD, particularly percussion‐induced rapid contractions, muscle mounding, and muscle rippling, varied considerably among these subjects. Moreover, all examined individuals showed muscle weakness; however, the patterns were inconsistent. Muscle Nerve, 2010