Effect of complete response on outcome following autologous stem cell transplantation for myeloma

We studied the effect of complete response (CR) among 126 consecutive patients who underwent stem cell transplantation (SCT) for myeloma. The CR rate with SCT was 33%. Median overall survival (OS) from diagnosis of myeloma was 56 months. OS following SCT was 22 months. Progression-free survival (PFS) was 12 months. OS was not different between patients who achieved CR and those who did not, median survival 25 vs 24 months, P = 0.5. Corresponding median times for PFS were 15 and 11 months, P = 0.2. The plasma cell labeling index (PCLI) was high (> or = 1%) in 36% (high risk group) and was associated with poor OS and PFS (P < 0.001). Achieving CR did not influence OS or PFS in either the high or the low risk group. In contrast, OS and PFS were significantly influenced by high PCLI both in patients who achieved CR and those who did not. OS was poor (< 30 months) in high risk patients regardless of CR status and in low risk patients who did not achieve CR, compared to low risk patients achieving CR (57 months), making them candidates for novel post-transplant treatment options. Outcome following SCT is dependent more on biological variables such as the PCLI than on CR status.     

Association between mutations in Plasmodium falciparum chloroquine resistance transporter and P. falciparum multidrug resistance 1 genes and in vivo amodiaquine resistance in P. falciparum malaria-infected children in Nigeria

This study investigated the association between Plasmodium falciparum chloroquine resistance transporter (pfcrt) T76 and P. falciparum multidrug resistance gene 1 (pfmdr1) Y86 alleles and in vivo amodiaquine (AQ) resistance, as well as the clearance of parasites harboring these two alleles in children treated with AQ in southwest Nigeria. One hundred one children with acute uncomplicated P. falciparum malaria infections were treated with the standard dosage of AQ and followed-up for 28 days. Blood samples were collected on filter paper samples at enrollment and during follow-up for identification of parasite genotypes and pfcrt and pfmdr1 mutations using polymerase chain reaction and restriction fragment length polymorphism approaches. Parasitologic assessment of response to treatment showed that 87% and 13% (RI) of patients were cured and failed treatment, respectively. Although infections in patients were polyclonal (as determined by merozoite surface protein 2 genotyping), the presence of both mutants pfcrtT76 and pfmdr1Y86 alleles in parasites is associated with in vivo AQ resistance (odds ratio = 7.58, 95% confidence interval = 1.58-36.25, P = 0.006) and is selected by the drug in children who failed AQ treatment. Treatment failure with the combination of mutant pfcrtT76 and pfmdr1Y86 alleles as well as the ability of patients to clear these resistant parasites is dependent on age, suggesting a critical role of host immunity in clearing AQ-resistant P. falciparum. The combination of mutant pfcrtT76 and pfmdr1Y86 alleles may be useful markers for monitoring the development and spread of AQ resistance, when combining this drug with other antimalarials for treatment of malaria in Africa.     

Napping facilitates word learning in early lexical development

Little is known about the role that night‐time sleep and daytime naps play in early cognitive development. Our aim was to investigate how napping affects word learning in 16‐month‐olds. Thirty‐four typically developing infants were assigned randomly to nap and wake groups. After teaching two novel object–word pairs to infants, we tested their initial performance with an intermodal preferential looking task in which infants are expected to increase their target looking time compared to a distracter after hearing its auditory label. A second test session followed after approximately a 2‐h delay. The delay contained sleep for the nap group or no sleep for the wake group. Looking behaviour was measured with an automatic eye‐tracker. Vocabulary size was assessed using the Oxford Communicative Development Inventory. A significant interaction between group and session was found in preferential looking towards the target picture. The performance of the nap group increased after the nap, whereas that of the wake group did not change. The gain in performance correlated positively with the expressive vocabulary size in the nap group. These results indicate that daytime napping helps consolidate word learning in infancy.     

Arterial endothelial function in a porcine model of early stage atherosclerotic vascular disease

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States and is projected to become the leading cause of mortality in the world. Atherosclerosis is the most important single factor contributing to this disease burden. In this study, we characterize relationships between endothelial dysfunction and vascular disease in an animal model of diet-induced, early-stage atherosclerotic vascular disease. We tested the hypothesis that hypercholesterolaemia induces vascular disease and impairs endothelium-dependent relaxation (EDR) in conduit arteries of adult male Yucatan pigs. Pigs were fed a normal fat (NF) or high fat cholesterol (HFC) diet for 20-24 weeks. Results indicate that, while the HFC diet did not alter EDR in femoral or brachial arteries, EDR was significantly decreased in both carotid and coronary arteries. Sudanophilic fatty streaks were significantly present in the abdominal aorta and common carotid artery. Histopathology revealed increased intima-media thickness (IMT) and foam cell accumulation in Stary Stage I-III lesions in the abdominal aorta, common carotid artery and femoral arteries. In the coronary arteries, the accumulation of foam cells in Stary Stage I and II lesions resulted in a trend for increased IMT. There was no evidence of vascular disease in the brachial arteries. These results indicate that early stages of CVD (Stary Stage I-III) precede decreases in EDR induced by HFC diet, because femoral arteries exhibited foam cell accumulation and an increased IMT but no change in endothelial function.     

Staphylococcus epidermidis protease EcpA can be a deleterious component of the skin microbiome in atopic dermatitis

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Response rate,durability of response,and survival after thalidomide therapy for relapsed multiple myeloma

OBJECTIVE: To assess response rate, duration of response, progression-free survival, and toxicity of thalidomide in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Thirty-two patients with relapsed multiple myeloma were entered into the study between April 29, 1999, and June 20, 2000. They were given oral thalidomide at a dosage of 200 mg/d for 2 weeks, which was then increased as tolerated to a maximum of 800 mg/d. The primary end point of the study was response rate. RESULTS: The median age of the patients was 67 years (range, 36-78 years). Prior chemotherapy had failed in all patients, and stem cell transplantation had failed in 5 patients (16%). There were 10 confirmed responses, yielding a response rate of 31%. In addition, there was 1 unconfirmed partial response and 7 minimal responses with no complete responses. The median duration of response was 11.9 months (range, 3.7-203 months). Overall, 20 patients have died, and 26 patients have experienced disease progression. The median follow-up of surviving patients was 28.5 months (range, 193-34.0 months), with a median progression-free survival of 8.6 months (95% confidence interval [CI], 4.7-16 months). The median progression-free survival among the responding patients was 15.7 months (95% CI, 8.6-25.6 months). The median overall survival for the entire group was 22 months (95% CI, 10.6-35.9 months). The most common treatment-related nonhematologic toxic effects (grade >3) were neuropathy (16%), sedation (13%), febrile neutropenia (6%), and constipation (6%). CONCLUSIONS: Thalidomide is useful in the treatment of patients with relapsed multiple myeloma and produced durable response in approximately one third of patients, with median response duration of nearly 1 year.     

Pulmonary marginal zone lymphoma of MALT type as a cause of localised pulmonary amyloidosis

AIM: To describe six patients with pulmonary marginal zone lymphoma in whom amyloid deposition was identified. Marginal zone lymphoma is a recently recognised type of low grade non-Hodgkin's lymphoma. METHODS: A computerised search was performed of all patients seen at the Mayo Clinic with a diagnosis of pulmonary amyloidosis. Six patients with pulmonary amyloidosis who had biopsy confirmed extranodal marginal zone lymphoma of mucosa associated lymphoid tissue type were identified. All were women, ranging in age from 45 to 85 years. RESULTS: Five patients had amyloid deposition in conjunction with pulmonary marginal zone lymphoma at the time of the original diagnosis. One patient was referred for evaluation of localised pulmonary amyloidosis and was found to have coexisting pulmonary marginal zone lymphoma. Clinical presentation was limited to pulmonary symptoms (two of the six) or constitutional symptoms (two), or was asymptomatic (two). In all six cases, initial findings of nodular densities on screening chest roentgenograms led to further evaluation and eventual lobectomy; these findings included multiple pulmonary nodules (four), single nodule (one), and single nodule with diffuse bilateral interstitial infiltrates (one). Bone marrow was examined in five patients and was normal in all. Protein studies performed in four patients revealed no monoclonal protein. No patients had manifestations of systemic amyloidosis, such as renal, neurological, or cardiac involvement, at a median follow up of 50 months. Four of the six patients remain alive at a median of five years. CONCLUSIONS: Pulmonary marginal zone lymphoma may be found in association with localised amyloid deposition and should be considered in the differential diagnosis of localised pulmonary amyloidosis.     

Primary mucinous adenocarcinoma of the thymus: a case report and review of the literature

Primary thymic mucinous adenocarcinoma is extremely rare; to our knowledge, only 2 cases have been reported to date. We describe a third case of primary mucinous adenocarcinoma of the thymus in a 41-year-old man who presented with an anterior mediastinal mass with subsequent metastasis to the lung. The initial diagnosis was of metastatic mucinous adenocarcinoma, but extensive clinical workup of the patient failed to reveal a primary tumor elsewhere in the body. The specific identification of mucinous adenocarcinoma as a primary thymic neoplasm can be difficult or impossible. Morphologic and immunophenotypic similarities to mucinous adenocarcinomas of the gastrointestinal tract can pose diagnostic challenges for surgical pathologists, especially in small biopsy specimens.