Interleukin-8 and monocyte chemotactic protein-1 mRNA expression in perinatally infected and asphyxiated preterm neonates.

BACKGROUND: Inflammation due to perinatal infection (PI) and perinatal asphyxia (PA) may cause damage to various tissues and very often to the immature brain of the fetus and the newborn. Previously, we have shown that the neonatal immune system has the ability to produce increased chemokine protein levels in the serum during the inflammatory response caused by PI and PA. AIM: The aim of our present study was to investigate mRNA levels of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) in peripheral blood leukocytes from infected and asphyxiated neonates. METHODS: Forty-two premature neonates were studied; 11 with PI, 16 with PA and 15 without PA and PI, were used as controls. IL-8 and MCP-1 mRNA levels were investigated in whole blood and in phytohemagglutinin-activated lymphocytes using semi-quantitative polymerase chain reaction and real-time polymerase chain reaction, respectively. RESULTS: IL-8 mRNA levels were significantly increased in whole blood both during PA and PI, while MCP-1 mRNA levels were not. In vitro activated lymphocytes expressed significantly increased IL-8 mRNA levels during PI, whereas no increase was observed during PA. MCP-1 mRNA levels were significantly increased in activated lymphocytes during PA, while no increase was observed during PI. CONCLUSIONS: Our data show that chemokine mRNA levels expressed by activated lymphocytes during inflammation caused by PIs are different to those expressed during PAs. These findings might have important implications during the administration of specific chemokine antagonists in order to prevent or reduce tissue damage caused by inflammation.

Inflammatory mediators in perinatal asphyxia and infection.

AIM: To determine serum levels of interleukin-6 (IL-6), IL-1beta, tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1) and C-reactive protein (CRP) in asphyxiated neonates and compare these inflammatory factors with those found in neonates with perinatal infection. METHODS: 88 neonates were studied, of whom 36 were asphyxiated, 18 were infected and the remaining 34 were controls. Peripheral blood samples were obtained on the 1st, 3rd and 5th postnatal days. RESULTS: Cytokines IL-6 and IL-1beta as well as sICAM-1 serum levels did not differ between asphyxiated and infected neonates; however, at most time periods, their values were significantly higher than controls. TNF-alpha was similar in the three groups of neonates. CRP serum values were significantly higher in the infected neonates than in the asphyxiated or control subjects. Among the 54 asphyxiated and infected neonates, 15 were considered as severe cases and 39 as mild. The severe cases, at most time periods, had significantly higher IL-6, IL-1beta and sICAM-1 levels compared with the mild ones. Through receiver operating characteristic curves the cut-off points, sensitivities, and specificities for distinguishing neonates at risk or at high risk for brain damage were established. CONCLUSION: Similar increases in serum levels of IL-6, IL-1beta and sICAM-1 were found in perinatally asphyxiated and infected neonates. As these increases correlated with the severity of the perinatal insults, neonates at high risk for brain damage might be detected.

Model-based technique for the measurement of skin thickness in mammography.

A model-based method is proposed for the measurement of breast skin thickness from digitised mammograms that takes into account both the geometric and radiographic properties of the skin region. The method initially identifies a salient feature that discriminates the skin from the other anatomical structures of the breast. Its identification is based on a multi-scale grey-level gradient estimation, using a wavelet decomposition of the image. The spatial distribution of this feature is organised as a graph, with each of its nodes associated with a binary set of interpretation labels. A Markov random field is defined on the set of labels, and the best graph labelling is finally determined with a maximum a posteriori (MAP) probability criterion. The method was applied on 11 mammograms with improved contrast characteristics at the breast periphery, obtained by an exposure equalisation technique during image acquisition. The validation of the approach was performed by calculating the root mean square (RMS) error between the detected skin thickness and manual measurements performed on each of the films. The resulting error values ranged from 0.1 mm to 0.2 mm for normal cases and reached a maximum of 0.5mm in pathological cases with advanced skin thickening.

Early markers of brain damage in premature low-birth-weight neonates who suffered from perinatal asphyxia and/or infection.

We studied 57 low-birth-weight premature neonates, of whom 29 suffered from perinatal asphyxia and/or infection, while the remaining 28 did not and served as controls. We measured peripheral nucleated red blood cell (NRBC) absolute numbers as well as interleukin (IL)-1beta, IL-6 and tumour necrosis factor (TNF)-alpha cytokine serum levels at 24 h postnatally and on days 3 and 7 following birth. Fourteen of the asphyxiated/infected neonates and 12 controls had neurologic assessments at the corrected postnatal age of 18 months. We found NRBC absolute numbers and serum IL-1beta and IL-6 cytokine levels at 24 h postnatally to be significantly higher in neonates with perinatal asphyxia/infection than in the controls (p = 0.022, p = 0.036 and p = 0.037, respectively). TNF-alpha levels did not differ. Neurologic examination at the corrected postnatal age of 18 months showed 8 out of the 14 children who had been asphyxiated/infected as neonates to have abnormal findings, while 12 children who were used as controls during their neonatal period were normal. Abnormal neurologic findings correlated with high NRBC counts and IL-1beta and IL-6 levels at 24 h postnatally. In conclusion, increased NRBC counts and proinflammatory cytokine levels in asphyxiated/infected neonates represent early markers for subsequent neurologic impairment.

Annocherin and (2,4)-cis- and trans-annocherinones, monotetrahydrofuran Annonaceous acetogenins with a C-7 carbonyl group from Annona cherimolia seeds.

The new cytotoxic monotetrahydrofuran Annonaceous acetogenins, annocherin (1) and a mixture of (2,4)-cis- and trans-annocherinones (2 and 3), were isolated from the bioactive methanolic extract of Annonacherimolia seeds. Compounds 1-3 each possess an unusual 7-carbonyl group. Their structures were established on the basis of chemical and spectral evidence. Compounds 1-3 showed significant toxicity in the brine shrimp lethality test and cytotoxicity for six human solid tumor cell lines, with selectivity for the renal cell line (A-498) at potencies equivalent to Adriamycin.

Robust moving averages, with Hopfield neural network implementation, for monitoring evoked potential signals.

This technical note describes a robust version of moving averages, that enables reliable monitoring of the evoked potential (EP) signals. A cluster analysis (CA) procedure is introduced to robustify the signal averaging (SA). It is implemented via a Hopfield neural network (HNN), which performs selection of the trials forming a cluster around the current state of the EP signal. The core of this cluster serves as an estimate of the instantaneous EP. The effectiveness of the method, indicated by application to real data, and its computation efficiency, due to the use of simple matrix operations, makes it very promising for clinical observations.

An intelligent system for the tracking--localization of changes & exploratory analysis--of long-term ECG.

An interactive methodology for the analysis of long-term ECG is introduced. It is an anthropomimetic technique and consists of three parts. At the first stage, the clinicians' scan of the ECG traces is imitated and changes in the shape of QRS are quantified. In the sequel, a clinician involves in the interpretation of the most prominent changes providing the patient-dependent prototypes for the subsequent machine learning procedure. Finally, a classification scheme incorporates the portion of medical knowledge needed to explore the whole patient's ECG. This scheme, being very robust to noise, presents excellent generalization properties and can serve as a reliable automation in a future examination of the certain subject.

Vaginal hysterectomy: technique and results in the last twenty years.

The objective of this work was to describe patient characteristics and the effect of vaginal hysterectomy in a University hospital in the last two decades. A retrospective review of women undergoing vaginal hysterectomy was performed. The type of hysterectomy and complications were determined. From 1974 to 1994, a total of 6420 hysterectomies were performed. The vaginal route was used for 1530 patients. In the last decade, the Heaney method was used. A comparison of the periods 1974-1984 and 1984-1994 revealed that with the Heaney technique, we had significantly fewer complications, including less febrile morbidity, bleeding requiring transfusion, and injuries. Vaginal hysterectomy, specially using the Heaney method, is a rewarding challenge for any gynecologic surgeon. There are a low postoperative morbidity rate and a low mortality rate, which is well below the average mortality rate associated with abdominal hysterectomy.

Data dependent weighted averages for recording of evoked potential signals.

Two new filters are proposed to replace conventional on-line artifact rejection routines. They are based on an algorithm that computes a weight for each trial according to its similarity to the rest. The robustness of the two filters and their capacity to reduce recording time significantly were verified experimentally.

Tumor cell growth inhibition by several Annonaceous acetogenins in an in vitro disk diffusion assay.

The cell inhibition activities of several Annonaceous acetogenins, covering the three major structural classes of bis-adjacent, bis-non-adjacent, and single tetrahydrofuran (THF) ring compounds and their respective ketolactone rearrangement products, were tested in an in vitro disk diffusion assay against three murine (P388, PO3, and M17/Adr) and two human (H8 and H125) cancerous cell lines as well as a non-cancerous immortalized rat GI epithelial cell line (I18). The results demonstrate a dose-dependent inhibition of cancerous cell growth, while non-cancerous cell growth is not inhibited by the same dosages. All of the acetogenins, irrespective of their various structural types, inhibit the growth of adriamycin resistant tumor cells and non-resistant tumor cells at the same levels of potency. These results show that the Annonaceous acetogenins are an extremely potent class of compounds, and their inhibition of cell growth can be selective for cancerous cells and also effective for drug resistant cancer cells, while exhibiting only minimal toxicity to 'normal' non-cancerous cells.

Latency measurement improvement of P100 complex in visual evoked potentials by FMH filters.

The ensemble average of Pattern Shift Visual Evoked Potentials (PSVEP) signals is seriously affected by random latency variations encountered in each individual sweep which is modeled as a continuous signal with linear segments and well-shaped triangular peaks. This effect is causing the smoothed peaks of the averaged PSVEP waveforms. It is our objective to restore the degraded peaks and provide accurate information about their exact location. The method used is based on nonlinear filtering of the FIR-Median Hybrid (FMH) type and is recommended as a postfiltering process to the well-known averaging methods of recovering PSVEP signals from noise by time-locking to stimuli. The new technique, tested in signals from clinical observations, has proven very promising.

Application of cancer procoagulant as an early detection tumor marker.

BACKGROUND: In spite of many advances in the analytical reagents (antibodies), analytical systems, and the clinical application of tumor markers, the present markers do not detect early stage cancer. Preliminary data with an antigen specific to tumor tissue, cancer procoagulant (CP), suggest its possible role in the detection of early stage cancer. This study was aimed at determining the clinical use of CP as an early stage tumor marker. METHODS: An improved enzyme-linked immunosorbent assay (ELISA) was developed to measure CP concentration in serum. A panel of 817 blinded serum samples were examined from three groups of people: 573 cancer, 106 benign, and 139 normal. RESULTS: The sensitivity of all samples analyzed from cancer patients was 80%. The CP ELISA was able to detect ovarian, colon, and kidney cancer at a sensitivity greater than 85%; breast, prostate and small cell lung cancer was detected at a sensitivity of 80-85%. Particularly interesting was the observation that early stage cancers, regardless of site, were detected effectively. In some groups, the CP assay correctly identified 100% of the patients with stage I and II cancer. The assay was able to identify correctly noncancer patient sera at a specificity of 83% for those with benign disease and 82% for the normal individuals. CONCLUSIONS: The CP assay has potential as an aid in diagnosing early stage malignancies and thereby may significantly improve the survival rate of cancer patients.

Effects of variation in physical effort on frontalis EMG activity.

The physiological mechanisms underlying forehead muscle biofeedback for stress reduction are not well understood. A common hypothesis considers the frontales to be "key muscles" uniquely indexing the degree of tension present in the general musculature. We tested this hypothesis under conditions ranging from relaxation to maximum physical effort. The hypothesis was not supported. Changes in forehead muscle activity were limited primarily to reflecting changes in head and neck muscle tension.

The impact of mastectomy on self-concept and social function: a combined cross-sectional and longitudinal study with comparison groups.

Self-concept and social function following radical, modified radical or simple mastectomy for Stage I or II breast cancer, breast biopsy for benign breast disease, cholecystectomy or no operative procedure were measured across a fifteen-month period in a cross-sectional design and across a twelve-month period in a repeated measures design. Women selected for study were without other preexisting mental or physical illness. The degree of disability observed following mastectomy was considerably less than previously reported in uncontrolled studies, with the incidence of actual disturbance extremely small. Women receiving adjuvant therapies following mastectomy, but not women treated by mastectomy alone, reported significantly more body-image dissatisfaction and feminine self-image concerns than the comparison groups. The findings refute previously published impressions of severe psychosocial maladjustments following mastectomy. The study suggests that post-mastectomy women vulnerable to poorer outcome would be those with lower expectations of good quality social support, other present life stressors, other pre-existing chronic diseases, and a disposition to believe in life outcomes as less under their own control.

'Prolymphocytoid' cells in chronic lymphocytic leukaemia and their prognostic significance.

The morphology of lymphocytes in blood and bone marrow smears from 103 patients with chronic lymphocytic leukaemia (CLL) was studied. Special attention was paid to the finding of immature cells with the morphological features of prolymphocytes (prolymphocytoid cells -PLC). Subsequently the prognostic significance of these cells was examined. It was found that in 85 cases no PLC were found (Group I); in 8 cases the percentage was less than or equal to 10% (Group II) and in 10 cases the PLC were greater than 10% (Group III). The cases with PLC, especially in group III, fell in advanced stages of the disease (III-IV) and presented with increased lymphocytosis. In 8 patients of group III, who were followed till death, the disease became refractory to any treatment and the survival was short. We suggest that 'prolymphocytoid' transformation is a bad prognostic sign in CLL.