Maternal fish consumption, hair mercury, and infant cognition in a U.S. Cohort

Fish and other seafood may contain organic mercury but also beneficial nutrients such as n-3 polyunsaturated fatty acids. We endeavored to study whether maternal fish consumption during pregnancy harms or benefits fetal brain development. We examined associations of maternal fish intake during pregnancy and maternal hair mercury at delivery with infant cognition among 135 mother-infant pairs in Project Viva, a prospective U.S. pregnancy and child cohort study. We assessed infant cognition by the percent novelty preference on visual recognition memory (VRM) testing at 6 months of age. Mothers consumed an average of 1.2 fish servings per week during the second trimester. Mean maternal hair mercury was 0.55 ppm, with 10% of samples > 1.2 ppm. Mean VRM score was 59.8 (range, 10.9-92.5). After adjusting for participant characteristics using linear regression, higher fish intake was associated with higher infant cognition. This association strengthened after adjustment for hair mercury level: For each additional weekly fish serving, offspring VRM score was 4.0 points higher [95% confidence interval (CI), 1.3 to 6.7]. However, an increase of 1 ppm in mercury was associated with a decrement in VRM score of 7.5 (95% CI, -13.7 to -1.2) points. VRM scores were highest among infants of women who consumed > 2 weekly fish servings but had mercury levels 相似文献   

Sequential cyclophosphamide-prednisone and vincristine-bleomycin (CPOB). An effective, schedule-dependent treatment for advanced diffuse histiocytic lymphoma

In an Eastern Cooperative Oncology Group non-Hodgkin's lymphoma clinical trial, 90 patients with Stage III or IV diffuse histiocytic lymphoma (DHL) were treated with one of four chemotherapy regimens. All patients were previously untreated with chemotherapy, and careful restaging was required to document responses. Each treatment included cyclophosphamide, vincristine and prednisone (COP) plus Adriamycin (COPA), BCNU (BCVP) or bleomycin (COPB and CPOB). The two bleomycin-containing regimens differed only in the schedule of drug administration. CPOB-treated patients received cyclophosphamide on day 1, prednisone on days 1 to 5 and vincristine and bleomycin on day 15 of each 21-day cycle. COPB-treated patients received the same four drugs in the same dosage; however, the schedule was changed so that vincristine and bleomycin were given on day 1. Treatment of responders was continued for 8 cycles. Those with a complete response (CR) were randomized to maintenance therapy with BCVP or no treatment. Treatment with CPOB yielded a CR rate of 55% compared to 25% for COPB (P = 0.07). In contrast to COPB, treatment with CPOB was associated with a significantly longer median duration of CR (26.5 versus 5.7 months; P less than 0.05) and median survival (27.7 versus 11.2 months; P less than 0.02). The CR rate was 31% for BCVP and 45% for COPA, and the median survivals were 10.7 months and 14.4 months, respectively. One half of the CPOB-treated patients who achieved CR remained alive in continuous CR after 30 to 72 months. No advantage for maintenance therapy was observed. Myelotoxicity was greater with CPOB than COPB, but comparable to COPA. This trial demonstrated that the results of treatment of DHL with COP plus bleomycin were strikingly dependent upon the schedule of administration of bleomycin and vincristine. Bleomycin effectively combined with COP, as in CPOB, yielded results comparable to those obtained when Adriamycin was added to COP. CPOB appears to be an effective treatment for DHL that should be considered as an alternative to other regimens, particularly for patients who cannot receive Adriamycin.     

Invasive ductal carcinoma with fibrotic focus: mammographic and sonographic findings with histopathologic correlation

OBJECTIVE: We sought to define the imaging findings of invasive ductal carcinoma with fibrotic focus and its associated histopathologic correlation. CONCLUSION: Radiologists should be aware of the imaging characteristics of this newly described entity because of the significant prognostic implications and perhaps to prompt the pathologist to assess for the presence of a fibrotic focus at excision.     

Methylphenidate increases the motor effects of L-Dopa in Parkinson's disease: a pilot study

We determined whether methylphenidate, a dopamine transporter blocker, modifies motor, cognitive, or affective responses to L-Dopa in Parkinson's disease (PD). Five patients who reported benefit from L-Dopa/carbidopa and motor fluctuations were admitted and withdrawn from their usual antiparkinsonian medications. On 3 consecutive days in a randomized double-blinded fashion, they took 0.2 mg/kg oral methylphenidate or placebo followed 30 minutes later by a 1-hour intravenous L-Dopa (2 mg/kg per h) or placebo infusion. Vital signs, tapping, walking, dyskinesias, mood, anxiety, concentration, and arousal were monitored every 30 minutes. Cognitive testing was performed before and following the infusion. Methylphenidate combined with L-Dopa led to greater peak right-hand tapping speed than either alone. Dyskinesia severity increased most when methylphenidate and L-Dopa were co-administered. There were no differences between conditions on the Stroop test, digit ordering, simple reaction time, or covert orienting of attention validity effect. Methylphenidate alone led to improvement in choice reaction time. Change in self-assessed analogue ratings of mood, anxiety, arousal, or concentration did not differ between conditions. Methylphenidate increased the motor effects of L-Dopa with minimal effects on cognitive or affective functions, suggesting a physiologic role for the dopamine transporter in patients with PD with motor fluctuations.     

Interferon-alpha protects myeloma cell lines from dexamethasone-induced apoptosis.

Because of the increasing use of IFN-alpha in both induction and maintenance therapy for multiple myeloma (MM), its effect on growth and apoptosis of myeloma cells is important to consider. To investigate the role of IFN-alpha on the growth of myeloma cells, we have studied its effects on the response of interleukin 6 (IL-6)-dependent myeloma cell line (ANBL6) and IL-6-independent myeloma cell line (C2E3) in the presence of IL-6 and dexamethasone (Dex). We found that although IFN-alpha is a potent inhibitor of proliferation, it has only a minimal effect on induction of apoptosis. Moreover, we found IFN-alpha as well as IL-6 can significantly suppress dexamethasone-induced apoptosis. The suppression of apoptosis is concurrent with the induction of both AP-1 and STAT binding activity. We also found that IL-6 but not IFN-alpha up-regulates Bcl-X(L) expression. However, IL-6-mediated Bcl-X(L) expression is suppressed in the presence of Dex. Therefore, the expression of Bcl-X(L) does not account for the protection of Dex-induced apoptosis by IFN-alpha and IL-6. Taken together, our results suggest that IFN-alpha may counteract the beneficial effects of corticosteroids or perhaps other apoptosis inducing agents in the treatment of myeloma.     

Refined chromosome analysis as an independent prognostic indicator in de novo myelodysplastic syndromes

In a study of 56 consecutive adult patients with de novo myelodysplastic syndromes (MDS), all cases were successfully analyzed with two refined chromosome banding techniques. Most patients (44 of 56, 79%) were found to have a chromosome defect. The majority of these patients had a recurrent loss of chromosomal material rather than a reciprocal translocation or inversion, as commonly found in acute leukemia. The three largest chromosomal categories found were associated with a wide range of survival. Twelve patients (21%) had normal chromosomes, a stable clinical course, and long survival (median follow-up time of 49 months, with all patients alive). Nine patients had in common a single chromosome defect resulting in either monosomy 7 or deletion 7q. They had a median survival of 12 months, and four died of acute nonlymphocytic leukemia (ANLL). Of 12 patients with complex defects, 11 had a complete or partial loss of a chromosome 5 and a complete or partial loss of the long arm of a chromosome 7 or 20. They had a poor median survival of four months, and six patients died of ANLL. Although the French-American-British (FAB) classification was also found to have some prognostic value, FAB subgroups were chromosomally heterogeneous and showed less dramatic differences in median survival than the larger chromosomal subgroups. We have shown, for the first time, that a refined chromosomal analysis is an independent prognostic indicator in de novo MDS and may be helpful in establishing therapeutic approaches in this difficult group of heterogeneous disorders.     

High-dose lymphoblastoid interferon in advanced renal cell carcinoma: an Eastern Cooperative Oncology Group Study

This report describes a phase II Eastern Cooperative Oncology Group (ECOG) study of high-dose lymphoblastoid interferon (IFN alpha-n1) in 39 patients with measurable, advanced renal cell carcinoma. The original treatment plan was 30 X 10(6) units/m2 (30 mU) of IFN alpha-n1 im daily X 10 days; treatments were repeated every 21 days. This dose and schedule proved intolerable, with none of seven patients able to complete greater than 10 days of therapy because of fever, lassitude, hepatic dysfunction, and myelosuppression. Patients were subsequently treated with the following regimen: 3 mU/m2 on Day 1; 5 mU/m2 on Day 2; 10 mU/m2 on Day 3; and 20 mU/m2 on Days 4-10. Thirty-three new patients received this regimen and two patients received this schedule after having received 30 mU/m2. Using this second regimen, 30% of the patients were able to complete two cycles of treatment without dose reduction or interruption. Five patients (13%) had partial response (ECOG criteria) of measurable tumor. Median time to response was 140 days. Responses were documented in lung metastases in four patients and in a pelvic soft tissue mass in the fifth. Response rates and survival times are similar to those seen in prior ECOG phase II trials in advanced renal cell carcinoma. Eight of 39 patients are still alive greater than 2 years after beginning therapy. Only two of these patients had had an objective response, however. Such prolonged survival is more frequent than has been seen in previous ECOG studies. The relative contribution of patient selection and interferon therapy to this survival is uncertain.