Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer

Insulin-like growth factor 1 (IGF-1) is a potent mitogen for human breast-cancer cells in vitro. In circulation, most of IGF-1 is bound to IGF-binding protein 3 (IGFBP-3). This high-affinity binding is thought to have an important limiting effect on the availability of IGF-1 for biological activity. To assess the availability of IGF-1 for receptor binding, we determined serum levels of IGF-1 and IGFBP-3 and IGF-1/IGFBP-3 ratios. In a case-control study, 150 women aged 38 to 75 years presenting with stage-l or-II breast cancer were investigated just prior to surgery (n = 76), or to irradiation one month after surgery (n = 74). The population-based control group consisted of 441 women of the same age having no breast cancer. Women reporting diabetes mellitus or other hormonal abnormalities were excluded. Premenopausal cases showed elevated IGF-1 serum concentrations, decreased IGFBP-3 levels and increased IGF-1/IGFBP-3 ratios. The IGF-1/IGFBP-3 ratio was a significant breast-cancer risk factor, also after adjustment for age, family history, height, body-mass index, body-fat distribution, and serum levels of C-peptide. The relative risk was 7.34 for the highest compared with the lowest quintile of IGF-1/IGFBP-3. The presence or absence of tumor had no influence on these results. Increased levels of available IGF-1 in the circulation of pre-menopausal women may contribute to the development of breast cancer. © 1995 Wiley-Liss Inc.     

Cytogenetic and comparative genomic hybridization findings in four cases of breast cancer after neoadjuvant chemotherapy

To assess a potential common pattern of genetic alterations in chemotherapy-resistant tumors we analyzed four tumors from breast cancer patients (patients 1-4) after neoadjuvant chemotherapy, by comparative genome hybridization (CGH) and conventional chromosome banding analysis. All patients showed structural aberrations involving chromosomes 1, 5, 11, 16, and 17. In CGH analysis, the patients showed typical imbalances for ductal breast cancer: gains of 1q (3 patients), 5q (2 patients), 8q (3 patients), and X (4 patients) and losses of 1p33 approximately p36 (3 patients), 16q (3 patients), 17p (3 patients), 19 (4 patients), and 22q (4 patients). Other recurrent imbalances of atypical pattern for ductal breast cancer were gain of 4q21 approximately q32 (2 patients), 20q21 approximately q22 (2 patients), and 21 (2 patients) and loss of 20p (3 patients). Three patients showed involvement of several regions bearing genes of drug resistance (MDR1 [HUGO symbol: ABCB1], BCRP [HUGO symbol: ABCG2], MRP1 [HUGO symbol: ABCC1], RFC1); the fourth patient displayed an amplification in the region of MYC (alias c-myc), thus providing--at the level of the light microscope--an explanatory background for the ability of their tumors to survive anthracycline-, taxane- and cyclophosphamide-based chemotherapy. Conventional cytogenetic analysis and CGH displayed highly coincidental findings in the tumors of four patients after neoadjuvant chemotherapy for breast cancer.     

In Vitro and In Vivo Interactions of Haemophilus ducreyi with Host Phagocytes

We investigated the phagocytosis of Haemophilus ducreyi both in vitro and in vivo. Human granulocyte and monocyte phagocytosis of opsonized and nonopsonized, fluorescence-labeled H. ducreyi was assessed by flow cytometry. Both Escherichia coli and noncapsulated H. influenzae were included as controls. The maximal percentage of granulocytes taken up by H. ducreyi was 35% after 90 min. In contrast, 95% of H. influenzae bacteria were phagocytosed by granulocytes after 30 min. These results indicated that H. ducreyi phagocytosis was slow and inefficient. Bacterial opsonization by using specific antibodies increased the percentage of granulocytes phagocytosing H. ducreyi from 24 to 49%. The nonphagocytosed bacteria were completely resistant to phagocytosis even when reexposed to granulocytes, indicating that the H. ducreyi culture comprised a mixture of phenotypes. The intracellular survival of H. ducreyi in granulocytes, in monocytes/macrophages, and in a monocyte cell line (THP-1) was quantified after application of gentamicin treatment to kill extracellular bacteria. H. ducreyi survival within phagocytes was poor; approximately 11 and <0.1% of the added bacteria survived intracellularly after 2 and 20 h of incubation, respectively, while no intracellular H. influenzae bacteria were recovered after 2 h of incubation with phagocytes. The role of phagocytes in the development of skin lesions due to H. ducreyi was also studied in vivo. Mice that were depleted of granulocytes and/or monocytes and SCID mice, which lacked T and B cells, were injected intradermally with approximately 10⁶ CFU of H. ducreyi. Within 4 days of inoculation, the granulocyte-depleted mice developed lesions that persisted throughout the experimental period. This result reinforces the importance of granulocytes in the early innate defense against H. ducreyi infection. In conclusion, H. ducreyi is insufficiently phagocytosed to achieve complete eradication of the bacteria. Indeed, H. ducreyi has the ability to survive intracellularly for short periods within phagocytic cells in vitro. Since granulocytes play a major role in the innate defense against H. ducreyi infection in vivo, bacterial resistance to phagocytosis probably plays a crucial role in the pathogenesis of chancroid.     

Biochemical investigation with regard to infection and immunity of Eimeria acervulina in the fowl

Summary Biochemical investigation of the fluid surrounding the sporocysts in the oocysts (oocyst fluid) showed the presence of the common amino acids, -isoaminobutyric acid, glycerol, an unidentified carbohydrate and proteins.Incubation experiments with D-glucose-¹⁴C (U) revealed the presence of enzymes able to convert glucose into lactic acid and other acids. Inside the sporocysts the common amino acids, glycerol and the unidentified carbohydrate were also present, but -isoaminobutyric acid did not occur. The carbohydrate binding protein carboglutelin, carbohydrate phosphate and small amounts of glucose and fructose were mainly found inside the sporocysts.Incubation experiments of oocyst fluid mixed with sporocysts with D-glucose-C¹⁴ (U) demonstrated an interchange between the fluid and the sporocysts. In the oocyst fluid lactic acid was formed, but inside the sporocysts the conversion appeared to stop mainly with formation of carbohydrate phosphate.Incubation experiments of intestinal pieces both from immunized and not-immunized birds with oocyst fluid, sporocysts and labelled glucose showed that a stronger reaction took place in immunized birds than in not-immunized ones.Similar experiments were performed with not-immunized birds at different days after a primary infection. The reaction of the intestinal wall, which seemed quite normal again since day 19 after infection, was comparable with that observed in immunized birds.Finally the hypothesis is given, that in the first part of the intestine of immunized birds compounds are present originating from the first infection. These compounds might enhance the reaction between the oocyst fluid and the present feed to such an extent that the pH decreases and much epithelial cells are pushed off possibly together with the sporocysts. Then leakage of serum proteins might occur.     

Induction of apoptosis/necrosis in various human cell lineages by Haemophilus ducreyi cytolethal distending toxin.

We investigated the impact of highly purified Haemophilus ducreyi cytolethal distending toxin (HdCDT) on the apoptosis and necrosis of various human cells; including myeloid cells, epithelial cells, keratinocytes, and primary fibroblasts. The levels of apoptosis and necrosis induced in these cells were compared to those induced by HdCDT in human T cells and in the Jurkat T cell line. Levels of caspase-3 activity were measured, and membrane changes like phosphatidylserine (PS) translocation was evaluated after double-staining with the fluorescein isothiocyanate (FITC)-labeled annexin V and propidium iodide (PI) using flow cytometry. HdCDT induced various degrees of apoptosis and necrosis in dose- and time-dependent manners in cells of various lineages. Early and late apoptosis (annexin V-stained cells) were induced in more than 90% of T cells and monocytes after treatment with 100 ng/ml HdCDT for 24 and 48 h, respectively. The corresponding numbers for epithelial cells, keratinocytes, and fibroblasts were 26-32% after treatment with 100 ng/ml HdCDT for 48 h. HdCDT appears to eliminate effectively by inducing apoptosis those cells that are involved in immune responses. Epithelial cells, keratinocytes and fibroblasts, which are important for the healing of chancroid ulcers, are eliminated by apoptosis or necrosis after contact with HdCDT, albeit slower and to a lesser extent than T cells.     

Cognitive disorders in patients with occlusive disease of the carotid artery: a systematic review of the literature

We present a systematic review of the literature on the prevalence, nature, severity, course, and causes of cognitive deficits in patients with occlusive disease of the carotid artery prior to surgery (if surgery was under discussion). Searches were carried out on Medline and Psychlit from 1980 to 1999 using neurovascular and psychological index terms, and papers and books were checked for further references. Studies describing neuropsychological assessment of groups of patients with carotid obstruction were included. Eighteen studies were found. We extracted from the papers data on study design, demographic characteristics of patients, clinical diagnosis, carotid obstruction, cerebral imaging, time interval between ischemic episode and neuropsychological assessment, neuropsychological asessment procedures, integration and interpretation of test performances, and conclusions of authors. Fourteen studies concluded that there are cognitive deficits both in patients with symptomatic and in those with asymptomatic carotid obstruction; four studies denied cognitive impairment. There were no differences in patient characteristics, study design, or neuropsychological assessment procedures between the 14 studies that found deficits and the 4 that did not. There are indications for a mild, diffuse, detrimental effect of carotid occlusive disease on cognitive functioning. However, methodological problems prevent a definitive conclusion. Further research is needed to confirm these findings and to ascertain the neurovascular risk factors for and the natural course of cognitive impairment in patients with carotid occlusive disease. Received: 12 July 1999/Received in revised form: 10 November 1999/Accepted: 26 January 2000     

Epidemiologic and Genomic Analysis of SARS-CoV-2 Delta Variant Superspreading Event in Nightclub,the Netherlands,June 2021

We report a severe acute respiratory syndrome coronavirus 2 superspreading event in the Netherlands after distancing rules were lifted in nightclubs, despite requiring a negative test or vaccination. This occurrence illustrates the potential for rapid dissemination of variants in largely unvaccinated populations under such conditions. We detected subsequent community transmission of this strain.     

Validity of Two Self-care Instruments for the Elderly

The aim of this study was to address concurrent and construct validity of two instruments, the Self-care Ability Scale for the Elderly (SASE) and the self-report form of the Appraisal of Self-care Agency Scale (ASA-A), by testing them with home-dwelling, elderly Swedish patients. The two self-report instruments, including some additional new questions, were mailed to an age-stratified random sample of 420 elderly subjects and were finally completed by 125 of them. Bivariate and multivariate statistical methods were used in the analyses. An analysis of the non-respondents revealed no significant differences between them and the respondents. Standardized regression coefficients for reported abilities/activities on the scores were 0.71 for SASE (p < 0.0001) and for ASA-A 0.51 (p < 0.0001). SASE and ASA-A were found to measure related but not identical concepts (r = 0.69). Sensitivity and specificity ratings for managing without any help from official and unofficial caregivers were 68% and 72% respectively for SASE, and 50% and 64% for ASA-A. Individuals of 80+ years of age had lower scores than younger respondents on the SASE (p < 0.001) and ASA-A (p < 0.05) scales. Respondents living independently had higher scores on both scales than those living in institutions (p < 0.001). Lower scores on both scales were found for respondents who were not in good health compared with those who were in good health (p < 0.001). A five-factor solution for SASE explained 70.2% of the variances, and an eight-factor solution explained 67.9% of the variances for ASA-A. The results of this study confirm that the SASE and ASA-A assessments substantially measured what they were intended to measure in the studied group of lucid, elderly subjects.     

Prolonged thromboprophylaxis with Dalteparin during immobilization after ankle fracture surgery: a randomized placebo-controlled, double-blind study

Background Skeletal trauma and immobilization are well-known risk factors for deep vein thrombosis (DVT) and pulmonary embolism (PE). While prophylaxis against thromboembolic complications has become routine after major orthopedic surgery, whether or not prophylaxis after minor surgery and lower limb immobilization is necessary is still under debate.

Methods In a double-blind, placebo-controlled study, 272 consecutive patients were randomized to receive either thromboprophylaxis with Dalteparin (n = 136) or placebo (n = 136) for 5 weeks after ankle fracture surgery. All patients received 1 week of initial treatment with Dalteparin before randomization. A unilateral phlebography was performed when the cast was removed.

Results The overall incidence of DVT was 21% (95% CI: 13-29%) in the Dalteparin group and 28% (CI: 19- 37%) in the placebo group (risk ratio = 0.8, CI: 0.6-1.1; p = 0.3). The incidence of proximal DVTs was 4% and 3%, respectively. No major bleeding occurred.

Interpretation We found no significant difference in the incidence of DVT between the 2 treatment groups and our results do not support prolonged thromboprophylaxis. The overall incidence of DVT was high, reflecting the potential risk of PE and post-thrombotic syndrome after ankle fracture surgery. Most of the DVTs were asymptomatic, however, and were located in distal veins.