Dealing with Down syndrome occurrence risk

There were 28,600 deliveries of 500 g or more to women at the Rotunda Hospital between January 1st 1985 and December 1st 1989. Of these, 595 were to women aged 40 years and over. Thirty-five variables of clinical significance were analyzed, comparing those of 40 years of age and more with those under 40. The older group had significant increases in gestational diabetes, ante-partum hemorrhage, fetal distress, prematurity, low birth weight and perinatal mortality. Chromosome congenital abnormalities were significantly higher, particularly Down syndrome. There were significantly increased rates of induction and cesarean section in the older women. Some evidence of interaction of age with other factors was found, however these were difficult to separate out in the clinical setting. We therefore recommend it wiser to manage all elderly gravidas in a high risk manner dealing with cases individually within this framework. Intervention should, however, need to be justified in the older as in the younger woma

Focal adhesion kinase (FAK) expression in normal and neoplastic lymphoid tissues

Focal adhesion kinase (FAK) is a protein tyrosine kinase essential for intracellular regulatory events, such as cell growth, differentiation, migration and tumor metastasis. The aim of this study was to analyze the expression of FAK protein in a series of normal and neoplastic lymphoid tissues

The circadian rhythm of biochemical markers of bone resorption is normally synchronized in breast cancer patients with bone lytic metastases independently of tumor load

BACKGROUND: Bone metastases are devastating events resulting in disruption of local bone remodeling processes. Physiological bone turnover has a circadian rhythm. No data are available on the circadian pattern of bone turnover markers in patients with bone metastases. METHODS: Twenty post-menopausal women with breast cancer (BC) at first disease relapse and at least one bone metastasis were consecutively recruited. Twenty healthy women served as controls. Patients were free from concomitant chemotherapy/endocrine therapy. Throughout a 24-h period, urine samples were collected at 4-h intervals, and blood samples were collected at 4-h intervals between 08:00 and 24:00, and at 2-h intervals between 24:00 and 08:00. Serum osteocalcin (OC), total and bone-alkaline phosphatase (tALP and bALP, respectively) and C-terminal telopeptide of type I collagen (CTX), and urinary NTX and free deoxypyridinoline (fDPD) were measured together with serum parathyroid hormone (PTH) and serum and urinary calcium and phosphorus. Temporal variations of measured analytes were assessed by ANOVA and the COSINOR model. RESULTS: At 08:00, patients had higher levels of bone resorption indices (NTX, CTX and fDPD) than controls (p<0.0001). tALP and bALP, but not OC, were higher in patients than controls (p<0.001). PTH, serum and urinary calcium and urinary phosphorus did not differ between groups; serum phosphorus was higher in controls (p<0.0001). A circadian rhythm was evident for CTX and fDPD values in both patients and controls. A circadian rhythm in NTX, OC, phosphorus and PTH was apparent in controls only. However, it was detected also in patients when percent changes from MESOR were considered. Serum phosphorus showed a circadian rhythm, while no rhythm was detected for tALP, bALP, serum and urinary calcium. The rhythmicities in cancer patients were normally synchronized, and rhythmic parameters were independent of tumor load in the skeleton, age and menopausal status. CONCLUSIONS: This is the first study to yield information on the maintenance of the temporal program of bone turnover in bone metastatic cancer patients. Whether administration of bisphosphonates in the nighttime leads to a different outcome with respect to the current administration in the morning is a matter of future researc

CIRCADIAN RHYTHM OF BONE TURNOVER MARKERS INBREAST CANCER PATIENTS WITH METASTATIC BONE DISEASE ANDIN CONTROL SUBJECTS

Circadian rhythmicity is an essential feature of bone metabolism. The assessment of diurnal variation in bone resorption and formation markers in cancer patients with bone metastases could provide further insights on tumor induced derangement in bone turnover. Twenty-one ambulatory breast cancer patients with bone metastases and 20 agematched control subjects entered the study. Breast cancer patients were assessed at baseline conditions before starting any antineoplastic treatment of metastatic disease. After fasting from 10.00 pm the evening before experimentation, blood specimens in both patients and controls were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 2.00 am, 4.00 am, 6.00 am and 8.00 am to determine alkaline phosphatase (ALP), calcium (Ca), albumin, and cortisol. Urine samples were collected at 8.00 am, 12.00 am, 4.00 pm, 8.00 pm, 12.00 pm, 4.00 am and 8.00 am to determine the excretion of deoxypyridinolines (DPD) and N-telopeptide (NTX). Serum cortisol showed a marked circadian rhythm either in control subjects: MESOR 116 ng/dl, amplitude 60.9 ng/dl, acrophase at 6.00 am (P < 0.001) or in cancer patients: MESOR 103.1 ng/dl, amplitude 54.8 ng/dl, acrophase at 11.00 am (P < 0.001). Also albumin showed a rhythm in both subsets: MESOR 4.1 g/l, amplitude 0.21 g/l, Acrophase at 5.50 pm (P = 0.04) and MESOR 3.8 g/l, amplitude 0.40 g/l, acrophase at 4.50 pm (P < 0.001), respectively. Neither serum ALP nor serum calcium showed a significant circadian rhythm. Urinary DPD showed a significant circadian rhythm either in patients: MESOR 6.6 mmol, amplitude 0.96 mmol, acrophase at 8.30 am (P = 0.002) or in controls: MESOR 9.0 mmol, amplitude 1.36 mmol, acrophase at 9.50 am (P = 0.01); whereas urinary NTX showed a diurnal rhythm in control subjects MESOR 37.4 nmol BCE/mmol, amplitude 12 nmol BCE/mmol, acrophase at 7.45 am (P < 0.0001), but only a trend (not significant) was observed in cancer patients. These data indicate that bone resorption markers maintain a circadian rhythmicity in cancer patients. The determination of DPD and NTX in urine collected over a 4 h time span could account for the low amplitude observed. Data on serum cross laps will be provided at the meeting

Novel markers of normal and neoplastic human plasmacytoid dendritic cells

Plasmacytoid dendritic cells (pDCs) are involved in innate immunity (eg, by secreting interferons) and also give rise to CD4(+)CD56(+) hematodermic neoplasms. We report extensive characterization of human pDCs in routine tissue samples, documenting the expression of 19 immunohistologic markers, including signaling molecules (eg, BLNK), transcription factors (eg, ICSBP/IRF8 and PU.1), and Toll-like receptors (TLR7, TLR9). Many of these molecules are expressed in other cell types (principally B cells), but the adaptor protein CD2AP was essentially restricted to pDCs, and is therefore a novel immunohistologic marker for use in tissue biopsies. We found little evidence for activation-associated morphologic or phenotypic changes in conditions where pDCs are greatly increased (eg, Kikuchi disease). Most of the molecules were retained in the majority of pDC neoplasms, and 3 (BCL11A, CD2AP, and ICSBP/IRF8) were also commonly negative in leukemia cutis (acute myeloid leukemia in the skin), a tumor that may mimic pDC neoplasia. In summary, we have documented a range of molecules (notably those associated with B cells) expressed by pDCs in tissues and peripheral blood (where pDCs were detectable in cytospins at a frequency of < 1% of mononuclear cells) and also defined potential new markers (in particular CD2AP) for the diagnosis of pDC tumors