Reflex Cardiorespiratory Effects of Nociceptive Oesophageal Distension in the Decerebrate Rat

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.     

The Disablement Experienced by Traumatically Brain-Injured Adults Living in the Community

The disablement that occurs following traumatic brain injury (TBI) can be extensive and severe and consequently has been difficult to report on in a comprehensive and thorough manner. We were able to address this difficulty by analysing a sub group of data from the Canadian Health and Activity Limitation Survey (HALS) using the theoretical framework of disablement developed by the World Health Organization, the International Classification of Impairment, Disability and Handicap (ICIDH). There were 454 survey respondents (representing 12290 in the Canadian population) with disability resulting from a TBI and a mean time post-injury of 13 years. Three handicaps identified in the ICIDH were the focus of the study: physical independence, work, social integration. The prevalence of long term handicap was very high with 66% of the sample reporting the need for ongoing assistance with some activities of daily living, 75% not working, and 90% reporting some limitations or dissatisfaction with their social integration. Multivariate regression analysis was used to investigate the determinants of the handicaps. The determinants included: age, gender, level of education, living alone, physical environment, and specific disabilities. The implications of these findings are discussed in relation to rehabilitation issues, the usefulness of the ICIDH as a model to investigate outcomes, and directions for future research.     

TGFβ-1 regulation of VEGF production by breast cancer cells

Background: Angiogenesis is essential for tumor growth and metastasis. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor identified to date. TGFβ-1 acts as an indirect angiogenic agent. Methods: VEGF and TGFβ-1 were measured in the serum of breast cancer patients and agematched controls and in tumor tissue of cancer patients by ELISA. VEGF protein and mRNA expression by breast tumor cell lines were examined, and the effect of TGFβ-1 on VEGF production in these cells was assessed. Results: VEGF levels were significantly higher (P=.03) in the serum of patients with breast cancer compared to age-matched controls. A positive correlation was found between serum (r=0.539) and tumor tissue (r=0.688) levels of VEGF and TGFβ-1. Metastatic MDA-MB-231 breast cancer cells produce more VEGF than do the primary BT474 cells. TGFβ-1 significantly (P<.05) increased production of VEGF. Conclusions: Breast cancer cells constitutively produce VEGF protein and mRNA. There is a relationship between VEGF and TGFβ-1 levels in breast cancer patients, and TGFβ-1 regulates VEGF expression by breast cancer cells. Presented at the 50th Annual Cancer Symposium of the Society of Surgical Oncology, Chicago, Illinois, March 20–23, 1997.     

Cognitive rehabilitation in the elderly: overview and future directions.

This study provides an overview of the papers emanating from the experimental trial that evaluated a new cognitive rehabilitation program in older adults who were experiencing normal cognitive decline. The main features of the design are summarized, along with evidence that the training produced long-lasting improvement in memory performance, goal management, and psychosocial status. The benefits were attributed to several factors, including the program's emphasis on techniques that promoted efficient strategic processing. Limitations of the program and directions for future research are discussed.     

Relationship of AIDS-related attitudes to sexual behavior changes in adolescents.

The impact of the acquired immunodeficiency syndrome (AIDS) epidemic on a group of adolescents was investigated by surveying 197 sexually active, predominantly African-American, urban high school students. Reported sexual behavior changes were evaluated in relation to AIDS-related knowledge and attitudes. Over 50% of the students decreased their frequency of sexual activity, increased their condom use, and/or decreased their number of partners. These students had significantly higher scores on a measure of worry about vulnerability to human immunodeficiency virus (HIV) infection than those whose behavior had not changed. AIDS knowledge, AIDS beliefs, and AIDS-related anxiety interacted with gender to affect sexual behavior change. Male students reporting decreased frequency of sexual activity, for example, had more accurate beliefs about AIDS than males reporting no decrease. Among female students, however, those reporting decreased frequency had less accurate beliefs than those reporting no decrease. These results highlight the importance of considering gender and specific sexual behaviors when designing AIDS education interventions.     

3(S)-hydroxy-leukotriene B4 is a potent granulocyte chemotaxin in the guinea pig dermis

Inflammation Research -     

Antiinflammatory effects of second-generation leukotriene B4 receptor antagonist,SC-53228: Impact upon Leukotriene B4- and 12(R)-HETE- mediated events

Leukotriene B₄ (LTB₄) and 12(R)-hydroxyeicosatetraenoic acid [12(R)-HETE] are proinflammatory products of arachidonic acid metabolism that have been implicated as mediators in a number of inflammatory diseases. When injected intradermally into the guinea pig, LTB₄ and 12(R)-HETE elicit a dose-dependent migration (chemotaxis) of neutrophils (PMNs) into the injection sites as assessed by the presence of a neutrophil marker enzyme myeloperoxidase. SC-41930 {7-[3-(4-acetyl-3-methoxy-2-propylphenoxy)propoxyl]-3,4-dihydro-8-propyl-2H-1-benzopyran-2-carboxylic acid}, a first-generation LTB₄ receptor antagonist, inhibited the chemotactic actions of LTB₄ when given orally with an ED₅₀ value of 1.7 mg/kg. The second-generation LTB₄ receptor antagonist, SC-53228 [(+)-(S)-7-(3-{2-(cyclopropylmethyl)-3-methoxy-4-[(methylamino)carbonyl]phenoxy} propoxy)-3,4-dihydro-8-propyl-2H-1-benzopyran-2-propanoic acid], inhibited LTB₄-induced chemotaxis when given intragastrically with an ED₅₀ value of 0.07 mg/kg. Furthermore, SC-53228 inhibited 12(R)-HETE-induced granulocyte chemotaxis with an oral ED₅₀ value of 5.8 mg/kg. When dosed orally over a range of 0.03–100 mg/kg, SC-53228 gaveC _max plasma concentrations of 0.015–41.1g/ml. SC-53228 inhibited LTB₄-primed membrane depolarization of human neutrophils with an IC₅₀ value of 34 nM. As a potent LTB₄ receptor antagonist, SC-53228 may well have application in the medical management of disease states such as asthma, rheumatoid arthritis, inflammatory bowel disease, contact dermatitis, and psoriasis, in which LTB₄ and/or 12(R)-HETE are implicated as inflammatory mediators.     

Immunocyto-adherence by spleen cells and tissue antigens in normal and carbon tetrachloride-treated rats

The immunocyto-adherence test with sheep red cells coated with rat liver mitochondrial antigen shows that rat spleen cells form more rosettes with the coated cells than with sheep cells alone. The rise in the anti-tissue antibody level after carbon tetrachloride (CC1₄) injection is accompanied by an increase in the number of rosette forming cells. This evidence adds substantial support to the likely immune nature of the anti-tissue antibody response.