Modulating mechanisms of neuroendocrine cell activity: the LHRH pulse generator

1. Luteinizing hormone-releasing hormone (LHRH), synthesized in specialized neurons in the hypothalamus, is the prime regulator of reproduction. In its absence, reproductive development is arrested and disorders of LHRH secretion result in several reproductive dysfunctions. 2. The LHRH neuronal network plays a paramount role in the regulatory loop controlling gonadal homeostasis. LHRH input to the pituitary gland maintains gonadotropin secretion, which, in turn, is responsible for gonadal trophism. Steroidal and peptidergic hormones from the gonad close the regulatory system by establishing negative (male and females) and positive (females) feedback loops. 3. Interestingly, LHRH input to the pituitary is intermittent rather than continuous. In fact, continuous exposure to LHRH results in paradoxical hypogonadism. Several studies in animals have provided direct evidence for episodic secretion of LHRH into the hypophyseal portal system. However, the nature of the system(s) responsible for the generation of the LHRH pulsatile profile is not currently known. The recent observation that immortalized LHRH neurons secrete LHRH in a pulsatile manner suggests that the pulse generating mechanism resides within the LHRH neuronal network. 4. In this overview, we compile several lines of evidence supporting this notion and put this characteristic of LHRH neurons in perspective with gonadal influences both internal and external to the LHRH neuronal network. Some recent data regarding the site of action of gonadal steroids on the LHRH neuronal system, the functional significance of galanin colocalization with LHRH, and the role of nitric oxide in the pulse generating mechanism are also discussed.     

Radial echo-planar imaging

A new ultrafast magnetic resonance imaging pulse sequence named radial echo-planar imaging (rEPI) is introduced. The sequence is based on a modification of the echo-planar imaging (EPI) sequence to scan k-space radially, in an attempt to combine the speed of EPI with the benefits of radial sampling. Like in EPI, all the desired lines in k-space are scanned consecutively in opposite directions. The unique feature of this new sequence, however, is that the orientation of the readout gradient is incrementally rotated, so that all the echoes are refocused through the center of k-space. Therefore, rEPI data are acquired in a polar grid, and image reconstruction can be done either by means of filtered back-projection or by regridding the data to a Cartesian matrix followed by 2D Fourier transform. First results show that rEPI images can be acquired with the same speed and signal-to-noise ratio of EPI images. rEPI images are also shown to be less sensitive to off-resonance effects than EPI images. Further studies are underway to investigate the usefulness of rEPI for spectroscopic imaging and applications affected by motion.     

Low predictive value of intrinsic fibroblast radiosensitivity for fibrosis development following radiotherapy for breast cancer

Nearly 4 million women in the United States were physically hurt by their husbands or boyfriends in 1994. The health and well-being of these women and their children, as well as the women who are overlooked in these statistics, are jeopardized by past and current experiences with abuse within intimate relationships. Strategies for nurses in women's health care settings to screen women for current or past abuse within their intimate personal relationships, guidelines for effective responses to disclosure of abuse, and supportive interventions are described.     

Effect of capsaicin-containing red pepper sauce suspension on upper gastrointestinal motility in healthy volunteers

Afferent nerves play a major role in the regulation of gastrointestinal motility. The questions remains if specific food ingredients can selectively activate such fibers. The aim of the study was to investigate the effect of intraesophageal application of a capsaicin-containing red pepper sauce (Tabasco) suspension on upper gastrointestinal motility in a controlled trial. After a baseline recording [esophageal motility, balloon distension, electrogastrogram (EGG)], red pepper or saline solution was infused intraesophageally in seven healthy volunteers. At 30 min gastric emptying and orocecal transit time were determined using a [13C]acetate and H2-lactulose breath test. Infusion of red pepper sauce suspension significantly increased the amplitudes (65.8 +/- 3 to 78.5 +/- 4.7 mm Hg, P < 0.05) and propagation velocity (2.9 +/- 0.3 to 4.25 +/- 0.3 sec, P < 0.05) of esophageal pressure waves and LES pressure (17.8 +/- 1.4 to 23.7 +/- 2.6 mm Hg, P < 0.05). It significantly decreased perception and discomfort threshold of intraesophageal balloon distension, reduced the percentage of normal electrical activity in the EGG, and delayed gastric emptying (saline: T(1/2) 42.9 +/- 12.0 min vs red pepper: T(1/2) 66.8 +/- 19.0 min, P < 0.05). Despite the prolongation of gastric emptying, orocecal transit time was not altered, indicating an actual increase of intestinal transit. Esophageal application of capsaicin-containing red pepper sauce suspension had profound changes on upper gastrointestinal motility, which could improve clearance and protection of the esophagus and could lead to retention of the irritant in the stomach and faster transit through the small bowel.     

Therapy of cancer metastasis by tumoricidal activation of tissue macrophages using liposome-encapsulated immunomodulators

Published results of hepatic cryotherapy are now available for almost 900 patients. Its safety is well established and its clinical role in treating patients with unresectable hepatoma or liver metastases from colorectal carcinoma is well supported by tumour marker and survival data; the results in the treatment of neuroendocrine liver metastases are promising. Its role as an alternative to liver resection is not yet well supported by long-term data. Although different adjuvant treatment protocols have been used following the cryotherapy of colorectal liver metastases, the effect of adjuvant treatment on recurrence or survival has not been assessed in prospective studies. Laparoscopic hepatic cryotherapy is feasible in selected patients with suitable tumour locations. However, the proportion of patients who might be usefully treated with this technique is not yet well established. The mechanisms of tissue destruction by freezing are reviewed.     

Potent inhibitors of the MAP kinase p38

The MAP kinase p38 plays a key role in the biosynthesis of the inflammatory cytokines TNF-alpha and IL-1. We have developed a novel series of potent p38 inhibitors that could lead to new methods of treatment for inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease.     

Reduction in new metastases in breast cancer with adjuvant clodronate treatment

We report an unusual case of peripheral primitive neuroectodermal tumor (pPNET) in an infant presenting with congenital cutaneous nodules and a t(7;22)(p21;q11.2). The biologic behavior of the tumor diverged over time from a slowly growing tumor with multiple cutaneous nodules to a more aggressive neoplasm characterized by pulmonary metastases and a soft tissue mass showing additional cytogenetic alterations.