Search

Background: Fludarabine-containing combination chemotherapy regimens are increasingly used in the treatment of indolent lymphoid malignancies, with the associated risk of infection being the major toxicity. Predictors of infection during fludarabine-containing combination therapy are poorly defined and optimal strategies for infection prophylaxis are not known. The authors analyzed their experience with patients treated with the fludarabine-mitoxantrone (FM) or fludarabine-cyclophosphamide (FC) regimens to develop a predictive model for infections., Methods: Ninety-two patients with indolent lymphoid malignancies were treated with FM (n = 29) or FC (n = 63). Baseline variables including age, gender, regimen, disease histology, previous therapy, time from diagnosis to current treatment, performance status, renal function, absolute neutrophil count (ANC), lymphocyte count, and immunoglobulin G levels were examined retrospectively for their association with risk of infectious complications during or within 4 weeks of therapy., Results: Six risk factors were associated with infectious complications: age > 60 years, > or = 3 previous therapies, previous fludarabine exposure, time from diagnosis to current treatment of > 3 years, performance status > or = 2, and baseline ANC < 2.0 x 10(9)/L. Compared with patients with 0-2 risk factors, patients with > or = 3 risk factors had higher infection rates (26% vs. 7% per cycle, P < 0.0001), more Grade 4 neutropenia (41% vs. 8% per cycle, P < 0.0001), and more neutropenic sepsis (15% vs. 1% per cycle, P < 0.0001)., Conclusions: Infection risk during fludarabine-containing combination chemotherapy was predicted with a model comprising six baseline risk factors. Patients predicted to be at high risk of infection were an appropriate group for consideration of prophylactic strategies.

Background: Preclinical data have supported the use of fludarabine and cyclophosphamide (FC) in combination for the treatment of indolent lymphoid malignancies. Previously reported schedules were highly effective, but were complicated by significant myelotoxicity and infectious complications. In the current study, the authors analyzed their experience with an attenuated dose regimen to determine whether equivalent efficacy could be achieved with reduced toxicity., Methods: Sixty-four patients with indolent lymphoid malignancies were treated with intravenous fludarabine at a dose of 25 mg/m(2) and cyclophosphamide at a dose of 250 mg/m(2), each given on Days 1-3 for a median of 4 cycles. The median age of the patients was 60 years. Nineteen percent of the patients were previously untreated, and 45% had refractory disease; the patients had received a median of 2 prior therapies. With regard to histology, 41% of the patients had chronic lymphocytic leukemia or its variants, whereas the remainder of patients had low-grade non-Hodgkin lymphoma, predominantly follicule center cell lymphoma., Results: A total of 237 cycles were delivered. The principal toxicities reported were neutropenia (NCI CTC Grade 4 in 17% of cycles) and infection (Grade >/= 3 in 6% of cycles). The overall response rate and complete response rate were 86% and 29%, respectively. No significant difference could be discerned with regard to response rates for patients with untreated, recurrent, or refractory disease., Conclusions: The FC schedule used in the current study was found to be highly effective in patients with indolent lymphoid malignancies. Toxicity was lower compared with higher dose schedules, whereas efficacy appeared to be equivalent., (Copyright 2004 American Cancer Society.)

The recent World Health Organization (WHO) classification recognizes three subtypes of marginal zone lymphoma (MZL): extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL and nodal MZL. As a group, MZL share morphological and immunophenotypic features similar to that of the marginal zone B-cell in secondary B-follicles, the postulated common cell of origin. There is, however, increasing information about molecular heterogeneity between the types of MZL, suggesting different aetiology and highlighting our current incomplete understanding of this evolving entity. We describe the presentation and clinical course of three patients with MZL who do not fit the currently recognized WHO categories, and best fit the putative category of MZL, leukaemic subtype. We review the current literature on this newly described entity, highlighting the importance of its recognition.

Four experiments compare the effect of familiarity on item, associative, and plurality recognition on self-paced and speeded tests. The familiarity of test items was enhanced by presenting a prime that matched the subsequent test item. On item and plurality recognition tests, participants were more likely to respond "old" to primed than to unprimed test items. In associative recognition, priming increased the proportion of old responses on a speeded test, but not on a self-paced test. This suggests that familiarity plays a larger role in item and plurality recognition than in associative recognition on self-paced tests. On speeded tests, priming has a similar effect on item, associative, and plurality recognition. Results suggest that item and associative recognition rely differentially on familiarity and recollection. They are also consistent with recent evidence suggesting that different processes underlie plurality and associative recognition.

The revelation effect refers to the tendency to call an item on a recognition test old if it is preceded by a cognitive task that involves the processing of a similar stimulus (Watkins & Peynircioğlu, 1990). It has been proposed that the revelation effect occurs because of an increase in the familiarity of the test items in the revelation condition (Luo, 1993; Westerman & Greene, 1998). In the present experiments, the revelation effect was investigated in recognition tasks that were not based solely on the familiarity of the test items but, also, on a recall-like retrieval process. A revelation effect was not found on an associative-recognition task or on a plurality recognition task. The results of this study show that the revelation effect does not occur when the contribution of familiarity to recognition decisions is reduced by factors that encourage the recollection of the study episode.

We report a case of fatal disseminated fungal infection by Scedosporium prolificans which occurred in a patient with acute leukemia during induction chemotherapy. Rapid clinical deterioration despite high-dose empirical amphotericin B highlights both the pathogenicity of this fungus in immunocompromised hosts and its resistance to standard antifungal therapy.

Background: To define a maximum tolerated dose (MTD) for the combination of epirubicin and cyclophosphamide with filgrastim (r-met-HuG-CSF) in patients with advanced solid tumors and non-Hodgkin's lymphoma (NHL)., Patients and Methods: Thirty-five patients with advanced solid tumors were enrolled in stages I and II. Twenty-one patients were treated in stage I in sequential cohorts of at least three patients at increasing dosage levels of cyclophosphamide and epirubicin, for up to six cycles every 21 days. At the completion of stage I, a MTD for epirubicin was established. Fourteen patients were treated in stage II, in cohorts of three or more. The epirubicin dose remained constant at the MTD dosage from stage I. Cyclophosphamide was further dose-escalated to establish its MTD. Twenty-one patients with previously untreated non-Hodgkin's lymphoma were treated in stage III with the MTD established in the prior stages., Results: The MTD in stage I was epirubicin 150 mg/m2 and cyclophosphamide 1500 mg/m2 with cumulative neutropenia as the dose-limiting toxicity (DLT). Cumulative thrombocytopenia prevented further dose-escalation of cyclophosphamide in stage II. The stage III regimen consisted of six, 21-day cycles of epirubicin 150 mg/m2, cyclophosphamide 1500 mg/m2, vincristine 2 mg, and prednisolone 100 mg for five days with filgrastim support. Nineteen of twenty-one patients (90%) completed six cycles of treatment, eight (38%) without dose reduction. Common toxicity criteria (CTC) grade 4 neutropenia (neutrophil nadir < 0.5 x 10(9)/l) was documented in 85 of 118 cycles (72%). Neutropenic fever was documented in 17 of 21 patients (81%) on at least one occasion. Severe thrombocytopenia (< 25 x 10(9)/l) was seen in fourteen of 118 cycles (12%) and increased with cycle number. There was no significant non-hematological toxicity., Conclusion: Significant dose-escalation of epirubicin and cyclophosphamide was possible with filgrastim support. The MTD achieved was approximately double that of standard-dose therapy. This study forms the basis of an ongoing randomized study evaluating dose-intensification in intermediate grade NHL.

Objective: To assess the value of routine bone marrow biopsy (BMB) in adult patients less than 65 years of age with suspected idiopathic thrombocytopenic purpura (ITP)., Design: Retrospective analysis. Data were collected from hospital medical records and laboratory results., Setting: Large tertiary-level metropolitan teaching hospital, Victoria., Participants: Sixty-six patients who had undergone BMB for investigation of isolated thrombocytopenia between January 1992 and May 1997, according to defined eligibility criteria., Results: Sixty-one of the 66 patients had BMB findings consistent with ITP (i.e., normal or increased numbers of megakaryocytes and other haemopoietic lineages normal). Three of these patients' biopsies incidentally showed reduced or absent iron stores. In the remaining five patients, BMB in four showed mild hypocellularity and the subsequent course in these patients was consistent with chronic ITP. The fifth patient had neutrophil hypersegmentation and giant band cells on BMB, the cause of which was unclear. The subsequent course in this patient has also been consistent with chronic ITP., Conclusions: Our data suggest that the routine performance of BMB for the diagnosis of ITP is not useful, provided that a thorough clinical history and physical examination are undertaken and that the blood count and peripheral blood smear show no abnormalities apart from thrombocytopenia.

Recent exposure to general-information facts creates a tendency to claim that the facts had been known prior to their exposure. In Experiment 1, this "illusory knowledge effect" occurred even when participants did not have to demonstrate their knowledge by recalling part of the fact. In Experiment 2, the effect was found for both true and false facts. These findings suggest that the tendency to claim that recently presented facts had been previously known is caused by their enhanced familiarity. Accounts that would attribute this effect entirely to an underestimation of participants' knowledge of the new facts or to participants' intentional inflation of their prior knowledge states are not supported by these results.

The revelation effect is the tendency to call an item on a recognition test "old" if it is preceded by a different task interpolated between study and test. Seven experiments explored the generality of the revelation effect across a number of interpolated tasks. A revelation effect emerged when a variety of tasks preceded recognition test items; the effect was found for test items that followed a memory-span task, a synonym-generation task, and a letter-counting task. The compatibility between the test stimuli and the stimuli that composed the interpolated task was found to be a critical factor. With words as stimuli on a recognition test, a revelation effect was found when the stimuli in the interpolated task were words and letters. However, when numbers were the stimuli in the interpolated task, no revelation effect was found.

Two experiments investigate the nature of the verbal-overshadowing effect-the finding that recognition performance for certain stimuli is impaired if it is described verbally (Schooler & Engstler-Schooler, 1990). Impairment on a face-recognition task was found, although participants produced not a verbal description of the target but, instead, a description of another object (a car) presented in the study phase. These results support the idea that the verbal-overshadowing effect reflects a general shift in the processes involved in face recognition rather than a specific impairment for the described stimulus. Results also support the notion that the impairing effect of verbalization is unique to certain types of stimuli; verbalization impaired recognition of a face but not of a car.

Seven experiments demonstrate the robustness of the revelation effect, which is the tendency to call recognition test items old if they are distorted when they initially appear and if they are revealed before the recognition judgment. With anagrams as the distortion, a revelation effect was found in within- and between-subjects designs, in a frequency-judgment task, in a list-discrimination task, when new items were used as targets, when the study list and the test were presented in different modalities, and when the word that was revealed did not match the word that was recognized. These results challenge accounts that attribute the revelation effect either to an increase in the familiarity of the revealed test word or to a positive response bias.

Hyperalgesia and allodynia, lasting for months or even years, occurs in the form of post-herpetic neuralgia in approximately 70% of adults previously infected with the varicella herpes zoster virus. The present study aimed at testing the analgesic desensitising actions and reversibility of repeated application of topical capsaicin on disordered polymodal nociceptors and peptidergic sensory fibres mediating warm and pain sensation. Cutaneous nociceptor desensitisation was measured using the Glasgow automated thermal threshold test (Medelec TTT). For normal subjects (n = 69) the mean forearm warm threshold was 0.15 +/- 0.07 degrees C and the cold threshold was 0.14 +/- 0.10 degrees C. A variable degree of partial desensitisation of herpes-affected skin was found in 15 patients with post-herpetic neuralgia before capsaicin treatment where the mean threshold elevation for warm detection was 1.19 degrees C and 0.7 degrees C for cold detection, compared with the corresponding normal skin. In preliminary studies of 15 patients with post-herpetic neuralgia, good pain relief averaging 30% or 77% occurred in the affected dermatome(s) after 3 to 4 weeks of 0.01% or 0.05% capsaicin cream respectively, applied 3-4 times daily. The warm thresholds, after chronic capsaicin treatment, increased between 0.1 and 7.60 degrees C, the average elevation being 3.69 degrees C. By contrast cold thresholds after capsaicin altered inconsistently and by only an average of 0.08 degrees C. The results suggest that elevation of the warm threshold may indicate the desensitisation achieved by capsaicin treatment of skin polymodal nociceptors. Cold detection, being dependent upon A-delta cold fibre function, is unaffected by capsaicin treatment. There was a poor correlation between pain relief and elevation of warm detection in response to capsaicin treatment. Generally, it was found that those patients with less initial desensitisation to warm detection as a consequence of post-herpetic neuralgia experienced better pain relief after capsaicin was applied. The method used permits determination of the minimum effective desensitising dose of capsaicin, enables patient compliance and progress to be monitored and should allow the prediction of patients likely to achieve the best response to treatment.

Ventilatory responses to carbon dioxide (Sco2) were measured in 15 asymptomatic asthmatic patients in whom CO2 retention had been documented during a previous attack of acute asthma. At the time when Sco2 was measured, the patients had normal or only mildly impaired ventilatory function (vital capacity (VC) 3,5 +/- 0,19 I, 98,7 +/- 4% of predicted (mean +/- SE); forced expiratory volume in 1 second (FEV1) 2,37 +/- 0,161, 83,8 +/- 5,2% of predicted; and FEV1/VC 68 +/- 2,5%). Fifteen control subjects without lung disease were also studied (VC 4,38 +/- 0,28 I, 103 +/- 2,6% of predicted; FEV1 3,76 +/- 0,23 I, 112 +/- 4,4% of predicted; FEV1/VC 86 +/- 7,8%). Sco2 in the patients (1,21 +/- 0,14 l/min/mmHg, range 0,62 - 2,81) was significantly different (P less than 0,001) from that in controls (2,13 +/- 0,17 l/min/mmHg, range 1,13 - 3,17). Sco2 in a subgroup of 5 patients with normal pulmonary function was also significantly different from that in controls. Correction for lung size (Sco2/VC) did not detract from the significance of the difference between patients and controls, suggesting that inherently low respiratory centre sensitivities to CO2 may have played a role in the development of hypercapnia during severe asthma in these patients.

The magnitude of the asthma problem in Cape Town, as reflected by cases presenting to a large hospital, is described. The need for better facilities to treat acute asthma and to provide supervised interval therapy is discussed. A plea is made for the more widespread use of well-established simple beside aids in the assessment of the severity of asthma and the response to therapy.

Thirty-nine asthmatic patients required mechanical ventilation (IPPV) for status asthamticus over a seven and a half year period. We reviewed their clinical records with particular emphasis on the events leading to intermittent positive pressure ventilation (IPPV) and the long-term courses of those patients who survived IPPV. Long delays by patients before seeking medical attention, incomplete assessment of acute attacks, underuse of corticosteroids prior to admission and overuse of sedation were important factors often influencing the necessity for IPPV. Four patients died during IPPV. Of the 35 who survived, 32 were regularly followed in our Respiratory Clinic. Nine patients subsequently died, eight undoubtedly from asthma. Serial measurements of forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV1) were retrospectively analyzed to determine patterns of asthma. Of the 23 patients still alive, 14 have well controlled asthma, five have a pattern of persistent airflow obstruction, two have markedly labile asthma, and two have gradually deteriorating airflow obstruction. By contrast, seven patients who died sufficiently long after IPPV to enable categorization of their patterns showed either markedly labile asthma or gradually deteriorating airflow obstruction. None had relatively constant ventilatory function at either normal or suboptimal levels. We suggest that patterns of asthma are useful guides in detecting patients at high-risk. Patterns characterized by markedly labile asthma or gradually deteriorating airflow obstruction appear to be associated with an increased risk of sudden death from asthma.

The effect of prospective payment system (PPS) on reducing cost and quality of care is still unknown. Fifty-two patients (mean +/- SD, 82.0 +/- 6.5 years) with hip fracture classified as DRG 210 (hip and femur procedures except major joint, age greater than 69 years and/or complication and/or comorbidity), treated by compression nail were separated into four groups: Group I--no comorbidity, no complications; Group II--no comorbidity but had complications; Group III--with comorbidity but no complications; and Group IV--with both comorbidity and complications. Compared to length of stay (LOS) in Groups I, II and III (mean 26 days), Group IV had significantly increased LOS (mean, 61.5 days) and 81% of the 16 who were day outliers (L.O.S. greater than 40 days). Patients without comorbidity (I & II) even if they did develop complications were not financial losers. Those with comorbidity appear to be high-cost patients as they invariably end up with complications (78%), and reimbursement for Group IV was significantly less, resulting in net loss of this DRG. Our finding demonstrates the importance of preventing complications in patients with comorbidity. Present DRG reimbursement guidelines do not provide sufficient attention to LOS implications of both comorbidity and complications. Ideally, they should be considered as separate factors within the DRG category.

A patient with obstructive sleep-induced apnoea due to bilateral incomplete recurrent laryngeal nerve palsies is described. The sleep apnoea syndrome is briefly reviewed and the potentially fatal complications are emphasized.

This report describes a patient with acute airways obstruction and respiratory failure secondary to a large endotracheal metastasis from a primary ovarian carcinoma first detected seven years previously. Associated airflow obstruction due to mucus impaction contributed significantly to the development of respiratory failure. The tumor responded to radiotherapy, and radiologic evidence for tracheal obstruction was no longer present five months after irradiation.