Avoiding problems in clinical practice after the pill scare

The publications of 1995 and 1996 on the risk of venous thrombosis associated with the use of the combined oral contraceptive pill (COC) suggested that the risks were lower than previous estimates. The debate, which ensued, ensured that the safety of the COC with regard to arterial and venous disease was reassessed. This review details the importance of contraception for public health. It reassesses critically current prescribing practice in the light of the new publications on Factor V Leiden, arterial and venous disease. Methods of communicating information about the COC are assessed, and the difficulties of transmitting complex scientific data to health care professionals and the general public are debated. The importance of attempting to quantify the benefits and risks of the COC and explaining them in the context of other life events is emphasized.     

Development of allergy in children. I. Association with virus infections.

Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process.     

Effects of selective depletion of L3T4+ T-lymphocytes on herpes simplex virus encephalitis

The L3T4 surface molecule defines a subset of murine lymphocytes which are homologous to CD4+ lymphocytes in humans, and are functionally characterized as "helper/inducer" cells. To determine the role of helper/inducer lymphocytes in the host defense against herpes simplex virus type 1 (HSV-1) encephalitis, we utilized a monoclonal antibody to selectively deplete L3T4+ lymphocytes from BALB/c mice prior to experimental HSV infection. Susceptibility to HSV was only minimally increased by the depletion of L3T4+ cells, although mice receiving anti-L3T4 were profoundly immunosuppressed; splenic lymphocytes did not respond to stimulation by virus antigen in vitro, and L3T4+ lymphocyte-depleted mice failed to produce antibodies to HSV-1. However, mice receiving anti-L3T4 had a prolonged increase in natural killer cell activity following HSV infection as compared to controls. These data demonstrate that L3T4+ lymphocytes contribute minimally to host resistance to acute neural HSV infection, even though elimination of these lymphocytes markedly inhibits the genesis of immune responses.     

Immune deficiency following thermal trauma is associated with apoptotic cell death

Thermal injury-associated specific immune deficiency occurs despite indicators of systemic activation of the lymphoid compartment. We investigated the possibility that postburn immune failure and T cell activation are causally related through activation-induced (apoptotic) cell death. The relationship between the cellular immune response and cell mortality was examined in cultures of peripheral blood mononuclear cells (PBMC) from 14 immunosuppressed patients with extensive burns (35–90% total body surface area). Impaired cellular immunity coincided with significantly reduced cell viability as ascertained by propidium iodide staining and dye reduction assays. Following stimulation with the mitogenic lectin, phytohemagglutinin (PHA), the majority of DNA in patient cultures was fragmented, suggesting the occurrence of apoptotic cell death. Even without stimulation a portion of patient cells was apoptotic as indicated by oligonucleosomal bands on agarose gel electrophoresis. Exogenous interleukin-2 or phorbol ester markedly reduced constitutive as well as PHAinduced DNA fragmentation.In situ demonstration of DNA strand breaks in freshly isolated patient PBMC, by a TdT-based labeling technique, confirmed that a larger fraction (up to 60%) of circulating lymphocytes was undergoing apoptosis on the periphery. These novel observations suggest that apoptosis may play a major role in thermal injury-related cellular immunodeficiency.     

Evidence for central reorganization of ventilatory chemoreflex pathways in the cat during regeneration of visceral afferents in the carotid sinus nerve

There are two sets of peripheral arterial chemoreceptors in the cat, the carotid bodies innervated by the carotid sinus nerve and the aortic bodies with afferents in the aortic depressor nerves. Reflex stimulation of ventilation in response to hypoxia is abolished acutely after interrupting the sensory pathway from the carotid body chemoreceptors in the cat even though the reflex pathway from the aortic body chemoreceptors is intact. However, in chronically maintained preparations, there is a restoration of the hypoxic response which is mediated by the aortic chemoreflex pathway. It was proposed that restoration was due to a ‘central reorganization’ of chemoreflex pathways which followed interruption of the sensory pathway from the carotid bodies and that the reorganization enhanced the efficacy of the aortic ventilation chemoreflex. This proposal was tested in the present experiments by measuring reflex ventilatory and cardiovascular responses to electrical stimulation of the sensory nerves containing aortic and carotid chemoreceptor afferents following bilateral interruption of carotid sinus nerves and carotid body resection. Responses measured acutely (1–6 h) after interruption were compared with those measured 60–80 and 110–140 days later. At 60–80 days, a chemoreflex response (increase in tidal volume of ventilation) to stimulation of the interrupted carotid sinus sensory pathway was markedly attenuated while the response to stimulation of the uninterrupted pathway in aortic depressor nerves was enhanced. At 110–140 days, the tidal volume response to carotid sinus nerve stimulation was greatly enhanced while the aortic depressor nerve response declined from the elevated level. There were significant but less pronounced changes in the response of other ventilatory and cardiovascular variables to aortic depressor nerve and carotid sinus nerve stimulation.The results support the idea that there is a ‘central reorganization’ of chemoreflex pathways which is reflected functionally by changes in the efficacy of reflexes evoked from aortic depressor nerve and carotid sinus nerve. The changes are analagous to those occurring in somatic reflexes during regeneration of sensory nerves. It is suggested that the changes in efficacy of carotid sinus nerve reflexes are due to a degenerative loss of synapses of the central projections of interrupted carotid sinus nerve sensory axons (degenerative atrophy) and subsequent regenerative like changes (regenerative proliferation) in the central projections. The changes in the efficacy of aortic depressor nerve reflexes may be attributed to formation of new synapses by converging central projections of this uninterrupted pathway (reactive synaptogenesis) and subsequent regression of the newly formed synapses.     

Evidence for the involvement of receptors for fibronectin in the promotion of chick tail segmentation

Summary In the chick embryo the paraxial mesoderm forms about 50–53 pairs of somites, the precise number depending on the extent to which segmentation proceeds along the tail. However, the terminal mesoderm of the tail fails to segment despite the fact that it appears to contain a reservoir of potential somites. Why does this mesoderm not segment? Some clues can be obtained by comparing this non-segmenting region with the segmental plate in the trunk. We and others have shown that in the trunk region of the chick, cell adhesion plays a major role in somitogenesis and that this increased cell adhesion is associated with compaction of segments of mesoderm immediately prior to segmentation. This compaction can be brought about prematurely by fibronectin and by the specific adhesion peptide GRGDS. The terminal mesoderm in the tail resembles the segmental plate mesoderm in the trunk in undergoing compaction in response to fibronectin and GRGDS. The tail mesoderm differs from the segmental plate mesoderm in that it can also respond to peptides closely related to GRGDS. The response suggests that, whereas the integrin receptors for fibronectin and GRGDS appear to be specific in the presomitic trunk mesoderm, responding only to the specific adhesion-peptide GRGDS, the tail mesoderm may contain more heterogeneous sets of receptors within the integrin/VLA family that respond to a wider variety of ligands. Coincident with these differences is the phenomenon of regional cell death in the tail bud mesoderm. All of these factors are thought to play a role in the extent of segmentation in the paraxial mesoderm of the embryonic chick.     

A framework for measuring costs to society of IgE-mediated food allergy

Both immunoglobulin E (IgE)-mediated food allergy and food intolerance can lead to many changes in personal behaviour and health care resource use which have important economic consequences. These costs will impact directly, indirectly and intangibly on both individuals and society in general. It is important to measure the cost of illness (COI) of food allergy as a first step in developing and evaluating measures to reduce and control the burden of illness. This paper outlines a framework for assessing COI of food allergy from different viewpoints. It offers a structure for identifying the different cost impacts on allergic and nonallergic consumers, food producers and society as a whole, and for scoping, measurement and valuation of relevant costs. Within this structure, the existing literature is reviewed. This review illustrates the lack of information and clear methodology for assessing costs of food allergy. The paper concludes that there is a need for a more structured research programme to generate data essential for future evaluations of procedures and technologies for the diagnosis, treatment and management of food allergy.     

Distinct T-cell subtypes induced with whole cell and acellular pertussis vaccines in children.

Recent clinical trials have demonstrated that new generation acellular pertussis vaccines can confer protection against whooping cough. However, the mechanism of protective immunity against Bordetella pertussis infection induced by vaccination remains to be defined. We have examined cellular immune responses in children immunized with a range of acellular and whole cell pertussis vaccines. Immunization of children with a potent whole-cell vaccine induced B. pertussis-specific T cells that secreted interferon-gamma (IFN-gamma), but not interleukin-5 (IL-5). In contrast, T cells from children immunized with acellular pertussis vaccines secreted IFN-gamma and/or IL-5 following stimulation with B. pertussis antigens in vitro. These observations suggest that protective immunity conferred by whole-cell vaccines, like natural immunity, is mediated by type 1 T cells, whereas the mechanism of immune protection generated with acellular vaccines may be more heterogeneous, involving T cells that secreted type 1 and type 2 cytokines.     

Face processing in adolescents with and without epilepsy.

Children with temporal lobe epilepsy frequently suffer memory deficits, often marked in face processing. To determine the neural correlates of this dysfunction, we investigated face processing in adolescents with intractable epilepsy compared to typically developing controls. The M170 and M220 MEG event-related fields (ERFs) were recorded while the adolescents completed an n-back task on blocks of upright and inverted faces. Source analyses of the ERF data were performed using an event-related beamforming technique that allowed the detection of multiple sources. The control adolescents showed the expected waveforms and inversion effects, although there were differences in source localization, compared to the adult literature. The participants with epilepsy had poor performance on the tasks. The adolescents with extra-temporal lobe epilepsy showed both the M170 and M220 but the source localizations were highly atypical. The patients with right temporal lobe epilepsy had an absent or highly atypical M220, a component related to face recognition processes. We hypothesize that the children with extra-temporal lobe epilepsy have difficulty with face encoding processes while the patients with right temporal lobe epilepsy have specific difficulty with face recognition.     

Sex differences in the relationship between activity and weight loss in the rat

Access to a running wheel combined with restricted feeding produced body weight loss at an equivalent rate in male and female litter-mate rats (Experiment 1). Thus, despite weighing less and running more, females were not more vulnerable to this procedure. When factors influencing weight loss were varied, no sex difference was found in adaptation to a new feeding schedule or in the effect of single versus group housing (Experiment 2). The apparent critical difference was that body weight loss increased running in males but not in females (Experiment 3). In all rats, rapid recovery of body weight occurred when food access was no longer restricted (Experiment 1), suggesting that "activity-based anorexia" is a misnomer for weight loss by rats in a running wheel.