Lymphocyte depletion during treatment with intensive chemotherapy for cancer

Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.     

Characterization of colony-stimulating activity produced by human monocytes and phytohemagglutinin-stimulated lymphocytes

Human colony-stimulating activity (CSA) may support the proliferation of both human and murine granulocyte-macrophage progenitor cells (CFU- C) or, in the case of human urinary CSA, may only stimulate murine bone marrow CFU-C. CSA produced in the culture media of monocytes and macrophages and phytohemagglutinin-stimulated lymphocytes from human peripheral blood was characterized for both human and mouse marrow CFU- C stimulating activities. During the initial phase of a long-term cultures of monocytes, both human- and mouse-active CSA (MnCM-HM) were produced. In later phases of culture, however, only mouse-active CSA (MnCM-M) was produced. Fractionation on Sephadex G-150 revealed two functionally distinct species from MnCM-HM and lymphocytes conditioned medium, a high molecular weight factor (MW greater than 150,000) which stimulated mouse but not human colony formation, and a low molecular weight species (MW 25,000-35,000) which was active against both mouse and human target cells. However, MnCM-M revealed only one high molecular weight species (greater than 150,000), active only on mouse marrow. The possible biologic significance of such an activity is discussed.     

Quantifying the effects of absorbed dose from radioembolisation on healthy liver function with [99mTc]TcMebrofenin

European Journal of Nuclear Medicine and Molecular Imaging - To quantify the effects of absorbed radiation dose on healthy liver parenchyma following radioembolisation (RE) using...     

Characterization of mice expressing Ins1 gene promoter driven CreERT recombinase for conditional gene deletion in pancreatic β-cells

Gene manipulation using Cre-loxP recombination has proven to be an important approach for studying the impact of gene expression on pancreatic β-cell biology. We report the generation of a transgenic mouse line that enables a highly specific system for conditional gene manipulation within β-cells and achieve tissue specific and temporally regulated deletion of the Ctnnb1 (β-catenin) gene in pancreatic β-cells. cDNA encoding Cre recombinase fused to modified estrogen receptor (CreERT) under control of mouse insulin 1 gene promoter (Ins1) was used to construct the mouse line Tg(Ins1-Cre/ERT)1Lphi, also termed MIP1-CreERT. In a cross of MIP1-CreERT with a ROSA26/LacZ reporter strain, tamoxifen [Tmx] - dependent β-galactosidase expression occurred within pancreatic β-cells but not in other organ systems. Intraperitoneal glucose tolerance tests and glucose-stimulated changes in β-cell cytoplasmic calcium concentration were not adversely affected in adult MIP1-CreERT. A mouse line with floxed Ctnnb1 gene (Ctnnb1f/f) was crossed with the MIP1-CreERT line to generate a mouse model for inducible β-cell specific deletion of β-catenin gene (Ctnnb1f/f:MIP1-CreERT). Ctnnb1f/f:MIP1-CreERT mice and Ctnnb1f/f littermate controls, were injected with Tmx as adults to knock down β-catenin production in the majority of pancreatic β-cells. These mice showed normal glucose tolerance, islet cyto-architecture and insulin secretion. A novel protein fraction of 50Kd, immunoreactive with anti-β-catenin was observed in islet extracts from Ctnnb1f/f:MIP1-CreERT[Tmx] mice but not MIP1-CreERT-negative Ctnnb1f/f[Tmx] controls, indicating possible presence of a cryptic protein product of recombined Ctnnb1 gene. The MIP1-CreERT mouse line is a powerful tool for conditional manipulation of gene expression in β-cells.     

Hypoxic hepatitis in children after cardiac surgery

<正>To the Editor: Hypoxic hepatitis(HH), also known as ischemic hepatitis or shock liver, is a liver injury characterized by necrosis of centrilobular hepatocytes with a rapid increase in serum aminotransferase levels. The incidence rate of HH among patients in the intensive care unit(ICU) was found to be 0.9%-11.9% [1]. Occurrence of HH appears to have a significant impact on the clinical outcome.     

Recombinant LH supplementation to recombinant FSH during the final days of controlled ovarian stimulation for in vitro fertilization. A multicentre, prospective, randomized, controlled trial

BACKGROUND: The purpose of this multicentre, multinational trial was to study whether rLH supplementation to recombinant FSH (rFSH) during the late follicular phase increased pregnancy rates. METHODS: After down-regulation with nafarelin, 526 women were randomized on Day 1 of stimulation to use either rFSH (Gonal-F) alone (n = 261) or to continue after Day 6 of stimulation with both rFSH (Gonal-F) and rLH (Luveris) (n = 265) from Day 6. The starting dose of rFSH was 150-225 IU/day according to age below or above 35 years. RESULTS: Ongoing pregnancy rate at week 10-12 was 28.7% after rFSH alone and 27.2% after rFSH + rLH. This showed no evidence of a difference. Administration of rLH significantly (P< 0.001) increased serum LH. Ongoing pregnancy rates in patients with low LH levels (<33 percentile) on Days 1 and 6 of stimulation showed no difference between the group treated with rFSH only (23.9% low Day 1 LH; 22.1% low Day 6 LH) versus rFSH + rLH (25.0% low Day 1 LH; 28.9% low Day 6 LH). CONCLUSIONS: Supplementing rFSH with daily doses of 75-150 IU of rLH during the second half of the follicular phase showed no evidence of increasing the ongoing pregnancy rates in the general population. (ClinicalTrials.gov, trial number: KF02-035/03).