Reevaluation of procarbazine for the treatment of recurrent malignant central nervous system tumors

Ninety-nine patients with primary recurrent malignant tumors of the central nervous system were treated with procarbazine as a single agent. Procarbazine was not given as a specified protocol, but for patients who were ineligible or refused other protocols. All patients had been treated previously with radiotherapy and 96 patients had also received previous chemotherapy. Twenty-five patients were treated at the first progression of their tumor, 47 were treated at the second progression, and 27 were treated at the third progression of their tumor. For the aggregate, the response plus stabilization rate was 27% for glioblastoma multiforme with median time to tumor progression of 30 weeks, and 28% for other anaplastic gliomas with a median time to tumor progression of 49 weeks. With respect to the percent of patients who responded or stabilized to treatment, these results are inferior to those reported previously for patients treated with procarbazine at recurrence. With respect to duration of response and stabilization, the data are comparable.     

Relationship Between Exhaled Carbon Monoxide and Airway Hyperresponsiveness in Asthmatic Patients

The study objectives were to analyze the changes in exhaled carbon monoxide (COex) induced by histamine provocation challenge in asthmatic patients and to evaluate the relationship between COex and airway sensitivity and reactivity. Levels of COex were measured in 105 nonsmoking mildly asthmatic subjects before and after histamine provocation challenge. Dose-response curves were characterized by their sensitivity (PD₂₀) and reactivity. Dose-response slope (DRS), continuous index of responsiveness (CIR), and bronchial reactivity index (BRI) were determined as reactivity indices. Bronchial challenge was positive for 47 subjects and negative for 58. The COex levels rose significantly after bronchial challenge in the positive response group (4.49 ± 0.4 vs. 5.74 ± 0.57 ppm, p = 0.025) and in the negative response group (2.84 ± 0.25 vs 4.00 ± 0.41 ppm, p = 0.000). An inverse relation between basal COex and PD₂₀ was found (r = - 0.318, p = 0.030). In all subjects, a proportional direct relationship between COex and DRS (r = 0.214, p = 0.015), CIR (r = 0.401, p = 0.000), and BRI (r = 0.208, p = 0.012) was observed. On stepwise multiple linear regression analysis, COex only significantly correlated with CIR (multiple r² = 0.174, p = 0.000). In conclusion, exhaled CO determination is a noninvasive inflammatory marker of the respiratory tract, which shows an acceptable association with airway hyperresponsiveness.     

Hypothalamic hamartoma associated with Laurence-Moon-Biedl syndrome. Case report and review of the literature.

A rare case of a patient with Laurence-Moon-Biedl syndrome associated with hypothalamic hamartoma is described. The English-language literature contains no cases of patients with this association. The clinical manifestations of this syndrome, those of hypothalamic hamartomas, and the appearance of the tumors on magnetic resonance images are discussed.     

Cerebrospinal Fluid Penetration and Pharmacokinetic/Pharmacodynamic Parameters of Intravenously Administered Colistin in a Case of Multidrug-Resistant <Emphasis Type="Italic">Acinetobacter baumannii</Emphasis> Meningitis

Described here is a case of meningitis caused by multidrug-resistant Acinetobacter baumannii susceptible only to colistin, which was treated successfully with intravenous colistin sulfomethate sodium (5 mg/kg/day). The levels of colistin in serum and cerebrospinal fluid and the pharmacokinetic/pharmacodynamic parameters of colistin were determined. In this case, intravenously administered colistin penetrated cerebrospinal fluid (25% of serum levels) at levels sustaining bactericidal concentrations. Electronic Publication     

Sense of coherence and burnout in nursing home workers during the COVID-19 pandemic in Spain

Care staff in nursing homes work in a challenging environment, and the COVID-19 pandemic has exacerbated those challenges in an unprecedented way. On the other hand, the sense of coherence (SOC) is a competence that could help these professionals perceive the situation as understandable, manageable and meaningful. This study aims to analyse the extent to which potential risk and protective factors against burnout have affected nursing home workers during the COVID-19 pandemic and to assess the contribution of these factors to their burnout. Three hundred forty professionals who worked in nursing homes in Spain completed a survey and reported on their sociodemographic characteristics and their organisational characteristics of the job related to COVID-19, SOC and burnout. Multiple linear regression analyses were performed. The results showed that the SOC is highly related to the dimensions of burnout and is a protective factor against this. In addition, the increase in hours has a negative effect, facilitating inadequate responses to stressful situations; and whereas perceived social support and availability of resources have a protective effect, the deterioration in mental and physical health is the most important risk factor. This study could help better understand the psychological consequences of the effort that nursing home workers and can also help design mental health prevention and care interventions for workers that provide them with resources and supports that foster their coping skills.     

Proliferative potential and prognostic evaluation of low-grade astrocytomas

Summary Despite their histological similarity, low-grade astrocytomas vary widely in their clinical behavior. To elucidate this variable behavior, we measured the proliferative potential of 69 primary and 18 recurrent low-grade astrocytomas and correlated the results with the clinical characteristics and outcome. Each patient received an intravenous infusion of bromodeoxyuridine (BUdR); BUdR-labeled nuclei in excised tumor specimens were identified by immunoperoxidase staining. The BUdR labeling index (LI), or S-phase fraction, ranged from <1 to 9.3%; the LI was < 1% in 64 (74%) patients and 1% in 23 patients (26%). The LI did not appear to be associated with age, sex, tumor location, or whether the tumor was primary or recurrent. A Cox proportional-hazards analysis of the influence of the LI and other variables (age, sex, tumor location, extent of surgery, primary versus recurrent tumor) on survival showed that the LI and extent of surgery (total resection, subtotal resection, biopsy) were significant in predicting both survival and progression-free survival for all patients and for patients with primary tumors. The LI was also significant in predicting progression-free survival for patients with recurrent tumors. The correlation between the BUdR LI and both survival and time to recurrence suggests that the outcome of low-grade astrocytomas varies according to the proliferative potential. The growth rate of these histologically similar tumors should be assessed individually in order to select specific treatment.Deceased January 28, 1993     

High dose oral tamoxifen and subcutaneous interferon alpha-2a for recurrent glioma

Chemotherapeutic regimens in present use for recurrent glioma have substantial toxicity. Activity against recurrent gliomas has been reported for both tamoxifen and interferon alpha, agents that have more acceptable toxicity profiles and that can be administered in an outpatient setting. We tested the efficacy and toxicity of the combination of high-dose tamoxifen and interferon alpha in adults with recurrent glioma in a phase II trial. Eligible patients had radiographically measurable recurrent gliomas of any grade after initial radiation therapy. Interferon-alpha (6 × 10⁶ U subcutaneously three times per week) and tamoxifen (240 mg/m²/day orally) were administered continuously. Treatment response was assessed at 6 week intervals using clinical and radiographic criteria. Eighteen patients (11 males and 7 females) were enrolled. Median age was 41 years (range 23–61 years). All patients had gliomas that progressed after radiation therapy and nitrosourea chemotherapy. The histologic diagnosis of the original tumor was glioblastoma multiforme in 8 patients, anaplastic astrocytoma in 5 patients, astrocytoma in 4 patients and mixed malignant glioma in 1 patient. Reversible moderate to severe neurological toxicity manifested by dizziness and unsteady gait was seen at tamoxifen doses of 240 mg/m²/day. Although the initial tamoxifen dose was reduced to 120 mg/m²/day, moderate neurotoxicity was noted at this dose as well and the trial was closed early. The combination of oral tamoxifen (120 to 240 mg/m²/day) and subcutaneous interferon-alpha (6 × 10⁶ U three times per week) was associated with significant neurotoxicity in this group of recurrent glioma patients, resulting in early study closure. Of 16 evaluable patients, 12 had progressive disease after one cycle of treatment, 3 had stable disease, and there was one minor response. Gradual dose escalation may be required if similar patients are to be treated with high dose tamoxifen in conjunction with interferon.     

Phase I trial of tipifarnib in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs: a North American Brain Tumor Consortium Study.

PURPOSE: To determine the maximum-tolerated dose (MTD), toxicities, and clinical effect of tipifarnib, a farnesyltransferase (FTase) inhibitor, in patients with recurrent malignant glioma taking enzyme-inducing antiepileptic drugs (EIAEDs). This study compares the pharmacokinetics and pharmacodynamics of tipifarnib at MTD in patients on and off EIAEDs. PATIENTS AND METHODS: Recurrent malignant glioma patients were treated with tipifarnib using an interpatient dose-escalation scheme. Pharmacokinetics and pharmacodynamics were assessed. RESULTS: Twenty-three assessable patients taking EIAEDs received tipifarnib in escalating doses from 300 to 700 mg bid for 21 of 28 days. The dose-limiting toxicity was rash, and the MTD was 600 mg bid. There were significant differences in pharmacokinetic parameters at 300 mg bid between patients on and not on EIAEDs. When patients on EIAEDs and not on EIAEDs were treated at MTD (600 and 300 mg bid, respectively), the area under the plasma concentration-time curve (AUC)(0-12 hours) was approximately two-fold lower in patients on EIAEDs. Farnesyltransferase inhibition was noted at all tipifarnib dose levels, as measured in peripheral-blood mononuclear cells (PBMC). CONCLUSION: Toxicities and pharmacokinetics differ significantly when comparing patients on or off EIAEDs. EIAEDs significantly decreased the maximum concentration, AUC(0-12 hours), and predose trough concentrations of tipifarnib. Even in the presence of EIAEDs, the levels of tipifarnib were still sufficient to potently inhibit FTase activity in patient PBMCs. The relevance of these important findings to clinical activity will be determined in ongoing studies with larger numbers of patients.