Utility of MRI versus tumor markers for post-treatment surveillance of marker-positive CNS germ cell tumors

Patients with marker-positive central nervous system (CNS) germ cell tumors are typically monitored for tumor recurrence with both tumor markers (AFP and b-hCG) and MRI. We hypothesize that the recurrence of these tumors will always be accompanied by an elevation in tumor markers, and that surveillance MRI may not be necessary. We retrospectively identified 28 patients with CNS germ cell tumors treated at our institution that presented with an elevated serum or cerebrospinal fluid (CSF) tumor marker at the time of diagnosis. We then identified those who had a tumor recurrence after having been in remission and whether each recurrence was detected via MRI changes, elevated tumor markers, or both. Four patients suffered a tumor recurrence. Only one patient had simultaneously elevated tumor markers and MRI evidence of recurrence. Two patients had evidence of recurrence on MRI without corresponding elevations in serum or CSF tumor markers. One patient had abnormal tumor markers with no evidence of recurrence on MRI until 6 months later. We conclude that in patients with marker-positive CNS germ cell tumors who achieve complete remission, continued surveillance imaging in addition to measurement of tumor markers is indicated to detect recurrences.     

Multicenter, noncomparative study of caspofungin in combination with other antifungals as salvage therapy in adults with invasive aspergillosis

BACKGROUND: Caspofungin inhibits synthesis of beta-1,3-glucan, an essential component of the Aspergillus cell wall. This echinocandin has demonstrated efficacy (45% success) as salvage monotherapy of invasive aspergillosis (IA). Interest remains as to whether caspofungin, in combination with other antifungal classes, can improve the efficacy against IA. METHODS: The study involved 53 adults with documented IA who were refractory to or intolerant of standard antifungal therapy and received caspofungin and 1 other mold-active antifungal agent (at the investigator's discretion). Efficacy was assessed by signs, symptoms, and radiographs at the end of combination therapy and Day 84 after combination therapy initiation. Favorable (complete or partial) responses required significant clinical and radiographic improvement. Diagnoses and outcomes were assessed by an independent expert. RESULTS: Among the 53 patients enrolled the most common underlying diseases were acute leukemia (53%), lymphoma (11%), and chronic leukemia (6%). Pulmonary aspergillosis (81%) was the most common site, and most patients (87%) were refractory to prior therapy. Success at the end of combination therapy and Day 84 was 55% (29/53) and 49% (25/51), respectively. Fifty-seven percent of patients with neutropenia and 54% who received an allogeneic hematopoietic stem cell transplant responded favorably. Survival at Day 84 was 55%. Combination therapy, dosed on average for 31.3 days, was well tolerated. Two (4%) serious drug-related adverse events, both attributed to voriconazole, occurred. None of the patients discontinued caspofungin due to toxicity. CONCLUSIONS: Caspofungin in combination with a triazole or polyene was an effective alternative as salvage therapy for patients with recalcitrant Aspergillus infections.     

A phase II study of biweekly pemetrexed and gemcitabine in patients with metastatic breast cancer

Purpose

Pemetrexed (PEM) is a novel folate antimetabolite which inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. This phase II study was designed to assess the efficacy of Gemcitabine (GEM) and PEM given in a novel schedule in metastatic breast cancer (MBC) patients.

Methods

Eligible patients had MBC and received one prior chemotherapy regimen for metastatic disease; Performance status (PS) 0–2; measurable disease (RECIST criteria). PEM(500 mg/m²) was administered intravenously (IV) over 10 min prior to GEM(1,500 mg/m²) IV given over 30 min on day 1 every 14 days.

Results

Median age of the 16 patients in the study was 54 years (range 33–77). Fourteen patients had a PS of 0/1 and were evaluable for response. There were no reported complete or partial responses, seven patients with stable disease, six patients with disease progression and one patient with unknown response. Most common toxicities were skin rash: Grade 1/2(8) and Grade 3/4(1). Grade 3/4 non-hematological toxicities were fatigue(1); anorexia(1); pneumonia(1); peripheral ischemia(1) and elevation of liver transaminases(1). Three patients experienced febrile neutropenia (FN). This study did not meet the predefined criteria to proceed with additional accrual.

Conclusions

This regimen of PEM and GEM showed no clinical activity in the dose and schedule tested.     

Antifungal agents in hematopoietic stem cell transplantation

Invasive fungal infections are major complications of stem cell transplantation associated with significant morbidity and mortality. Allogeneic stem cell transplant recipients are at a significantly greater risk for fungal infection than recipients of autologous transplantation. Although with the wide use of fluconazole prophylaxis the incidence and associated mortality of invasive candidiasis has been minimized, mold diseases remain a significant complication during periods of prolonged immunosuppression for graft versus host disease. Posaconazole prophylaxis during periods of high risk was recently demonstrated to be effective in preventing fungal infections and associated mortality. Preemptive strategy employing laboratory markers and serial CT scans to identify mold infection at an early stage is promising. However its efficacy has to be validated in clinical trials. Several new antifungal agents have been introduced lately, characterized by improved safety profile and broader antifungal spectrum. Voriconazole has become the standard of care for the treatment of invasive aspergillosis. Finally there has been increasing interest on combination therapy for invasive aspergillosis due to the high rate of failure of the currently available antifungals, especially in the profoundly immunocompromised host.     

The linkage of glucose to tiazofurin decreases in vitro uptake into rat glioma C6 cells

The aim of this study was to analyse the uptake of the synthetic nucleoside tiazofurin and glucoso-linker-tiazofurin conjugate (GLTC) into rat C6 glioma cells in vitro. Results indicated that C6 cells accumulated [3H] tiazofurin slowly with time and that accumulation was reduced by the presence of unlabelled GLTC in the medium which implies that GLTC competes with tiazofurin for transport sites. Uptake of [14C] 2 deoxy-glucose into these cells was very rapid and was not affected by the presence of unlabelled GLTC. To prove the true rate of uptake, the HPLC analysis of cellular extract was performed. After the 360 min of incubation in medium that contained 0.15 mM of tiazofurin, the sum of the concentration of tiazofurin and it's metabolite thiazole-adenine dinucleotide (TAD) in the cells was a total of approximately 4.8% of the amount added to each flask. After the same period of incubation in medium which contained 0.15 mM of GLTC, the sum of concentrations of conjugate, free tiazofurin and TAD represented less than 1/3 of the total concentration measured after the incubation with free tiazofurin and was further reduced in the presence of dipyridamole. Therefore, it can be concluded that GLTC shows some affinity for the nucleoside transporter, but the actual rate of uptake is low.     

Electronic fall surveillance system model

Of primary concern to health care facilities today is the reduction of preventable injuries such as patient falls that often lead to serious and fatal injuries and result in increased lengths of stays, resource demands, costs, and lawsuits. Although all patients have the capacity to fall, a major challenge is to identify the presence of key risk factors exhibited by a patient as soon as possible to reduce the likelihood of an adverse fall event. Currently, fall risk assessment and prevention practices focus on nurses identifying the risk factors for falls with a limited use of technology. This article introduces a preliminary falls risk assessment and prevention model that uses standardized clinical and operational performance indicators linked through the Web to the patient's electronic health record to produce an electronic Fall Surveillance System. The use of an integrated Fall Surveillance System linked directly to the electronic health record allows for the implementation of quick "real-time" preventive intervention that would dramatically improve the quality and costs of patient care.     

Immunogenicity and protection against Haemophilus parasuis infection after vaccination with recombinant virulence associated trimeric autotransporters (VtaA)

Haemophilus parasuis is the etiological agent of Glässer's disease in swine, characterized by fibrinous polyserositis, polyarthritis and meningitis. The lack of a vaccine against a broad spectrum of strains has limited the control of the disease. Recently, virulence associated trimeric autotransporters (VtaA) were described as antigenic proteins of H. parasuis. In this study 6 VtaA were produced as recombinant proteins and used to immunize snatch-farrowed, colostrum-deprived piglets. Immunized animals developed specific systemic and mucosal antibodies. The protective capacity of the anti-VtaA antibodies was evaluated by the inoculation of 3 × 10⁸ or 6 × 10⁶ colony forming units (CFU) of the highly virulent strain Nagasaki. Vaccinated animals had a delayed course of disease and 33 or 57%, respectively, of the animals survived the lethal challenge. The partial protection achieved with the recombinant VtaA supports their potential as candidates to be included in future vaccine formulations against H. parasuis.     

Ovarian serous tumors of low malignant potential (serous borderline tumors). The relationship of exophytic surface tumor to peritoneal "implants".

A series of 98 ovarian serous tumors of low malignant potential (LMP) was studied to test the validity of the implantation theory of extraovarian peritoneal spread of tumor by assessing the association between exophytic tumor on the ovarian surface and synchronous peritoneal implants. Patient's ages ranged from 17 to 77 years (mean, 37.8 years). The ovarian tumors were bilateral in 39 cases (40%). Exophytic tumor was present in 47 (48%) cases and involved at least one ovary in 82% of bilateral tumors. Exophytic tumor was found in 29 of 31 patients (94%) with peritoneal implants, but in only 18 of 67 patients (27%) without peritoneal implants. Moreover, 29 of 47 patients (62%) with exophytic tumor had peritoneal implants compared with only 2 of 51 patients (4%) without exophytic tumor. The utility of exophytic tumor as a marker of synchronous peritoneal implants had a diagnostic sensitivity of 94%, a diagnostic specificity of 73%, and an efficiency of 80%. Because of the strongly positive correlation between exophytic tumor and peritoneal implants, the implantation theory remains as a highly likely explanation for extraovarian spread of ovarian serous LMP tumors. The multicentric "field effect" theory, however, cannot be entirely excluded and may be operative in some cases.     

Premedication with metoclopramide decreases the frequency of methohexital induced hiccup

Metoclopramide is one of many drugs that have been recommended for the treatment of intractable hiccup. Methohexital may produce hiccup during induction of general anesthesia. 211 women received methohexital for induction and maintenance of general anesthesia for short gynaecological procedures. All the patients were premedicated with fentanyl, diazepam and atropine. 109 patients were randomly selected to receive metoclopramide before induction of anesthesia; the remaining 102 patients served as a control group, and were anesthetized without metoclopramide premedication. The frequency of hiccup was compared between the two groups. 7 patients had hiccup in the metoclopramide premedicated group, as compared to 17 patients in the control group. This difference was statistically significant. We conclude that metoclopramide reduces the frequency of methohexital induced hiccup, and recommend that metoclopramide be routinely used for the premedication of methohexital injection.(Stav A, Weksler N, Berman M: premedication with metcoclopramide decreases the frequency of methohexital induced hiccup. J Anesth 6: 17–20, 1992)     

Influencing physician prescribing

The drug use process suffers from problems related to quality and cost that have not responded well to administrative or educational interventions. In many cases, attempts to improve the quality of physician prescribing have been clumsy, often based on intuition. This article begins by describing the drug use process and the role of prescribing in that process. In the following section, we describe what is known about how physicians make drug choice decisions. The paper concludes with suggestions, based on evidence, about the design of strategies for influencing prescribing.