Fusobacterium pneumonia and death following uvulo-palato-pharyngoplasty

A case with a fatal outcome caused by infection with Fusobacterium species was seen in a patient recently operated on for heavy snoring with uvulo-palato-pharyngoplasty (UPPP). The mechanism of infection is discussed. It is concluded that a febrile episode seen in patients less than 2 weeks postoperatively should be considered a serious symptom and be treated intensively after thorough examination. © 1994 John Wiley & Sons, Inc.     

Absence of restricted diffusion in adipose tissue capillaries.

Capillary permeability in adipose tissue for 57Co-cyanocobalamin (57Co-B12) was determined by the single injection, external registration method. The capillary diffusion capacity, CDC, (the permeability-surface area product, PS) was 1.1 ml/100 g-min at a capillary extraction of 0.21 and a plasma flow of 6.7 ml/100 g-min. Results were compared to 51Cr-EDTA data from a previous study with similar method and preparation. As CDC(51Cr-EDTA)/CDC(57Co-B12) was 1.81 and as D(51Cr-EDTA)/D(57Co-B12), the ratio between the free diffusion coefficients in water at 37 degrees C, was 1.79, it is concluded that restricted diffusion does not occur in cutaneous tissue for 57Co-B12 as compared to 51Cr-EDTA, i.e., 51Cr-EDTA and 57Co-B12 diffuse across the capillary membrane of adipose tissue at rates proportional to their respective free diffusion coefficients in water. The Pappenheimer equivalent pore radius estimate of 30 A and the Karnovsky interendothelial 40 A slit width are both defective in explaining the experimental data. The transendothelial channel system of fused vesicles (Simionescu, Simionescu and Palade 1975) is a possible structural equivalent for the present findings. The results support the hypothesis that capillaries of continuous type exhibit similar permeation characteristics regardless of the tissue in which they are located.     

Systemic hematologic effects of PEG-rHuMGDF-induced megakaryocyte hyperplasia in mice

PEG-rHuMGDF injected daily in normal mice causes a rapid dose-dependent increase in megakaryocytes and platelets. At the same time that platelet numbers are increased, the mean platelet volume (MPV) and platelet distribution width (PDW) can be either decreased, normal, or increased depending on the dose and time after administration. Thus, PEG-rHuMGDF at a low dose causes decreases in MPV and PDW, MGDF at an intermediate dose causes an initial increase followed by a decrease in MPV and PDW, and PEG-rHuMGDF at higher doses causes an increase in MPV and PDW followed by a gradual normalization of these platelet indices. In addition to the expected thrombocytosis after 7 to 10 days of daily injection of high doses of PEG-rHuMGDF, a transient decrease in peripheral red blood cell numbers and hemoglobin is noted accompanied in the bone marrow by megakaryocytic hyperplasia, myeloid hyperplasia, erythroid and lymphoid hypoplasia, and deposition of a fine network of reticulin fibers. Splenomegaly, an increase in splenic megakaryocytes, and extramedullary hematopoiesis accompany the hematologic changes in the peripheral blood and marrow to complete a spectrum of pathologic features similar to those reported in patients with myelofibrosis and megakaryocyte hyperplasia. However, all the PEG-rHuMGDF-initiated hematopathology including the increase in marrow reticulin is completely and rapidly reversible upon the cessation of administration of PEG-rHuMGDF. Thus, transient hyperplastic proliferation of megakaryocytes does not cause irreversible tissue injury. Furthermore, PEG-rHuMGDF completely ameliorates carboplatin-induced thrombocytopenia at a low-dose that does not cause the hematopathology associated with myelofibrosis.     

Inverse Association Between Birth Weight,Birth Length and Serum Total Cholesterol in Adulthood

Objectives - To investigate whether impaired fetal growth, measured by low birth weight and short birth length, is linked with raised levels of serum lipids and increased risk and mortality of coronary heart disease. Design - The association between birth length, birth weight, Ponderal Index and total serum cholesterol was examined in 545 Danish men and women aged 31 to 51 years who participated in the Ebeltoft Health Promotion Project in Denmark. Results - No associations were found in women. For men, a negative association was found between birth weight and serum total cholesterol, with a fall in mean serum total cholesterol from 6.03 mmol/l at birth weight below 3300 g to 5.64 mmol/l at birth weight above 4000. A similar association was found between birth length and serum cholesterol, with a mean value of 6.23 mmol/l at birth length below 51 cm and a mean value of 5.56 mmol/l at birth length above 54 cm. No associations were found for Ponderal Index. Between 3% and 8% of the variance in serum total cholesterol could be explained by the statistical models used in this study. Conclusion - Our findings support the hypothesis of a negative association between birth weight, birth length and elevated serum cholesterol in adult life, but only in men.     

How Do We Define Congenital Heart Defects for Scientific Studies?

Estimates of the prevalence of congenital heart defects (CHD) have been published over many years and from many regions. As they are based on different definitions of which cases to include in the CHD prevalence, published prevalence estimates vary substantially. With the increasing use of echocardiography in neonatal intensive care, a patent ductus arteriosus (PDA) or flow over the atrial septum will often be visible. These findings may be coded as CHD at discharge and in this way falsely increase the CHD prevalence in the population. There are several purposes for which population‐based data on CHD may be used: etiology, planning of treatment, or obtain information on outcome, including mortality. For etiology studies, it is important to include terminations of pregnancy as well as all births with CHD. For mortality studies in live births, inclusion of preterm born infants with PDA will increase overall mortality of CHD. The Danish Register of Congenital Heart Disease is based on hospital discharge diagnoses and diagnoses from outpatient visits. To increase the validity of these data, extensive data cleaning has been carried out based on record review and knowledge on the discharge coding practice. We include PDA and atrial septal defects as CHD cases if these defects are still open 2 months after birth. International consensus on how to define CHD would improve the validity and comparability of epidemiological studies on CHD.     

Colorectal cancer extracellular acidosis decreases immune cell killing and is partially ameliorated by pH-modulating agents that modify tumor cell cytokine profiles

Tumor cells upregulate myriad proteins that are important for pH regulation, resulting in the acidification of the extracellular tumor microenvironment (TME). Abnormal pH is known to dampen immune function, resulting in a worsened anti-tumor immune response. Understanding how extrinsic alterations in pH modulate the interactions between immune cells and tumors cells will help elucidate opportunities for new therapeutic approaches. We observed that pH impacts the function of immune cells, both natural killer (NK) and T cells, which is relevant in the context of a highly acidic TME. Decreased NK and T cell activity was correlated with decreasing pH in a co-culture immune cell-mediated tumor cell-killing assay. The addition of pH-modulating drugs cariporide, lansoprazole, and acetazolamide to the co-culture assay was able to partially mitigate this dampened immune cell function. Treatment of colorectal cancer (CRC) cells with NHE1 inhibitor cariporide increased CRC cell-secreted cytokines involved in immune cell recruitment and activation and decreased cytokines involved in epithelial-mesenchymal transition (EMT). Cariporide treatment also decreased CRC cell shed TRAIL-R2, TRAIL-R3, and PD-L1 which is relevant in the context of immunotherapy. These experiments can help inform future investigations into how the pH of the tumor microenvironment may be extrinsically modulated to improve anti-tumor immune response in solid tumors such as colorectal cancer.     

Combined doxorubicin and paclitaxel in advanced breast cancer: Effective and cardiotoxic

BACKGROUND:: Pacitaxel has shown activity in metastatic breast cancer, includinganthracycline-resistant breast cancer. The efficacy, toxicityand optimal scheduling of the combina tion of the two drugsneeds to be defined. PATIENTS AND METHODS:: Thirty women with advanced breast cancer who had undergone atmost one prior adjuvant chemotherapy regimen, were treated atthree different dose levels with doxorubicin (50, 60 and 60mg/m²) followed 30 minutes later by paclitaxel (155, 175 and200 mg/m², respectively) every 3 weeks. RESULTS:: The overall response rate was 83% (95% CI: 64–94), with24% of patients achieving CR. The median response duration forcomplete responders was 11 months (range 4–14+) and mediansurvival 18 months (range 3–28+). Two hundred sixty-fivetreatment courses were given (median 9, range 3–13) andthe median cumulative dose of doxorubicin was 369 mg/m² (range114–550). The main toxicities were neutropenia, parestesia,nausea/vomiting, alopecia, myalgia and cardiotoxicity. Fifteenpatients (50%) had reductions of left ventricular ejection fractionto below normal levels and 6 of these patients (20%) developedcongestive heart failure. CONCLUSIONS:: The combination of doxorubicin and paclitaxel is highly active,but is accompanied by the dose-limiting toxic effects of neutropenia,neuropathy and cardiotoxicity. advanced breast cancer, cardiotoxicity, doxorubicin, paclitaxel     

Epirubicin or epirubicin and cisplatin as first-line therapy in advanced breast cancer. A phase III study

Purpose: To compare the efficacy and toxicity of epirubicin to that of the combination of epirubicin and cisplatin in patients with advanced breast cancer. Patients and methods: A total of 155 patients were randomized to receive either epirubicin (70 mg/m²) days 1 and 8 every 4 weeks or epirubicin (60 mg/m²) days 1 and 8 plus cisplatin (100 mg/m²) day 1 every 4 weeks. Epirubicin was continued until disease progression or to a cumulative dose of 1000 mg/m². Cisplatin was discontinued after six cycles. In 45 premenopausal women an oophorectomy was performed. None of the evaluable patients had received chemotherapy for metastatic disease. Results: Among evaluable patients (74 in the epirubicin group and 65 in the epirubicin plus cisplatin group) there were 19% vs 29% complete responses, and 42% vs 37% partial responses, with no significant difference. In the epirubicin plus cisplatin group the response rate was significantly higher in previously untreated patients as compared with patients who had received adjuvant chemotherapy (74% vs 55%, P=0.002). Median times to disease progression were 8.4 months in the epirubicin group and 15.3 months in the epirubicin plus cisplatin group (P=0.045). Median survival times were 15.1 and 21.5 months, respectively (P=0.41). In the epirubicin plus cisplatin group leukopenia and thrombocytopenia were significantly more frequent, 29% of the patients developed mild to moderate peripheral neurotoxicity, 34% reported tinnitus and hearing changes, 6 patients developed nephrotoxicity (one died due to nephrotic syndrome), and 3 patients developed leukaemia (two died of this cause). Congestive heart failure occurred in six patients in the epirubicin group and three patients in the epirubicin plus cisplatin group. Conclusion: Cisplatin plus epirubicin is an active, although highly toxic regimen when used as first-line therapy in advanced breast cancer. The time to disease progression was significantly longer in the cisplatin plus epirubicin group (increased by 82%). Due to toxicity, the combination regimen cannot be recommended. However, the study indicated a very high activity of cisplatin in advanced breast cancer. Studies of first-line therapy in advanced breast cancer including cisplatin or other platin derivatives in combination with, for example, the taxanes are suggested. Received: 8 December 1999 / Accepted: 17 July 2000