Correlation of leukocyte interleukin-1 production with the stimulation of prostaglandin and tissue factor synthesis by human umbilical vein endothelial cells

Human leukocyte suspensions (neutrophils 80–85%, monocyte 15–20%) were incubated alone or with cultured human umbilical vein endothelial cells. Leukocytes were either directly added to the endothelial cell cultures or separated from them by a 0.4 micron insert filter. Supernatants or cell lysates were obtained at 0.5, 1, 2, and 4 hours of incubation. Supernatants were assayed for the prostacyclin (PGI₂) metabolite 6-keto prostaglandin F₁ and prostaglandin E₂ (PGE₂) by radioimmunoassay and for interleukin-1 (IL-1) by the thymocyte co-mitogen assay. Cell lysates were analyzed for cell-associated procoagulant activity (PCA). Co-incubation of endothelial cells with leukocytes stimulated the synthesis of PGI₂, PGE₂, and PCA. These biochemical changes correlated partially with the release of IL-1 beta. The results suggest that IL-1 released in monocyte/neutrophil co-cultures can produce prothrombotic (increased PCA expression) and inflammatory changes (increased synthesis of vasodilatory and permeability enhancing PGI₂ and PGE₂) in endothelial cells. Neutrophils may represent a source of the released IL-1 and/or may act to stimulate monocyte release of this cytokine and thus play an important role in vascular pathology by a mechanism unrelated to their more direct cytotoxic activity.     

Baroreceptor control of heart rate in the conscious toad Bufo marinus

Perivascular balloons were used to elicit heart rate (HR) responses to imposed changes in mean arterial pressure (Pa) in conscious unrestrained toads (Bufo marinus). It is clear that functional baroreceptors lie in the pulmocutaneous arteries of B. marinus, and that these can elicit compensatory heart rate responses to perturbations of blood pressure. Functional baroreceptors were not present in the carotid circulation and are probably absent from the lateral aortae and conus arteriosus as well. Normalized gain of the baroreceptor-heart rate reflex (delta HR%/delta Pa) in five toads was 13%/kPa, which is considerably less than that found in other vertebrates to date.     

Interaction of peripheral and central respiratory drives in cats I. Effects of sodium cyanide as a peripheral chemoreceptor stimulus at different levels of CSF pH

In cats anesthetized with chloralose-urethane, the central respiratory chemoreceptors were exposed to mock CSF of pH 7.02, 7.20, or 7.57. The right carotid body was simultaneously stimulated by intracarotid injections of 40, 80, or 160 μg sodium cyanide in 200 μl Ringer solution. The left carotid nerve and, in some animals, both vagosympathetic truncs were dissected. It could be demonstrated the the increase in ventilation produced by application of NaCN to the peripheral chemoreceptors is significantly larger at high than at low mock CSF pH (i.e. at low than at high central stimulus intensity). In vagotomized cats the responses of V_T and gelai to NaCN similarly depend upon CSF pH; they are somewhat larger, though, than in intact animals. These results are discussed as compared with results reported by different authors. Supported by the Deutsche Forschungsgemeinschaft (Be 477)     

Axonal projections of single bulbospinal inspiratory neurons revealed by spike-triggered averaging and antidromic activation

Activity was recorded extracellularly from 26 inspiratory bulbospinal neurons in anesthetized, paralyzed, artificially ventilated cats. All but one were located in the ventral respiratory group. A neuron was classified as either I alpha or I beta by comparing its firing pattern during inspiratory cycles with lung inflation to its pattern when lung inflation was withheld during the central inspiratory phase (2, 14, 15). In this study, the projection and conduction velocity of these axons were determined using two methods: antidromic activation (AA) of the bulbospinal neurons and spike-triggered averaging (STA) of the extracellular field potentials. These methods have been compared directly because the same electrode was used both for stimulating the axon of the bulbospinal neuron and recording its axonal potential in the same location. Axonal projections from these neurons were mapped in the contralateral spinal cord with a mobile electrode by determining where the lowest stimulus threshold occurs for AA and greatest axonal potential can be recorded with STA. The locations of these axons were in the ventral and lateral funiculi. Each method determined a similar location for an axon. Positions of 10 axons were determined at both the third (C3) and fourth (C4) cervical segments. Single axons maintained their positions in either descending tract from rostral C3 to mid-C4. In five of six cases where two "neighboring" medullary units were characterized, the axons of each pair projected together within 350 micron of each other in the cervical spinal cord. Estimates of mean axonal conduction velocity (CV) from antidromic activation from a single stimulus site, "single-point AA," were as much as 42% less than corresponding estimates from STA extracellular field potentials at that point (P less than 0.001). Such single-point estimates were less than determinations that were calculated from the difference in conduction time and the difference in conduction distance from two points in the spinal cord. These two-point determinations averaged 55.4 +/- 13.1 m/s (using AA) and 53.3 +/- 13.1 (using STA) for 10 neurons. These values were not significantly (P greater than 0.2) different from each other and are greater than most earlier reports, which used the single-point AA method. Either method, AA or STA, can be used to determine axonal position and CV. The advantages and disadvantages of each method are discussed.(ABSTRACT TRUNCATED AT 400 WORDS)     

Screening and genetic counselling for relatives of patients with breast cancer in a family cancer clinic.

Family history is the major risk factor in the aetiology of breast cancer. Breast screening is currently available to women from the age of 50 to 64 through the National Breast Screening Programme. There is, however, an equivalent risk of developing breast cancer below 50 for first degree relatives of women diagnosed with breast cancer premenopausally. We have estimated the risk of breast cancer for relatives of women affected at different ages and used these to establish a family cancer clinic offering breast screening based on individual risk. In three years we have seen 851 patients. Compliance for annual radiology was in excess of 83% over this period and of five cancers detected one had a lump at presentation, two developed interval breast lumps, and two were asymptomatic.     

Epitope-selective, monoclonal-antibody-based immunoradiometric assays of predictable specificity for differential measurement of choriogonadotropin and its subunits

Knowing the epitope specificities of our monoclonal antibodies (MCA) to human choriogonadotropin (hCG), we could design three classes of two-site immunoradiometric assays (IRMA): a combination of two MCA recognizing two separate alpha-epitopes (alpha-MCA) provides a system (i.e., an alpha-IRMA) that measures holo-hCG plus free alpha-subunits plus follitropin, lutropin, and thyrotropin, whereas a beta-IRMA, consisting of two beta-MCA, quantifies holo-hCG plus free beta-subunits. The amount of either of the two subunits can be calculated by subtracting the amount of holo-hCG determined in parallel in a holo-hCG-IRMA. In the latter, one of the alpha- or beta-MCA may be either cross-combined or, preferably, paired with an MCA specific for a conformational epitope. These analytical specificities, predicted from our previously established epitope map of hCG, could be experimentally verified. With these IRMAS we could demonstrate that in certain choriocarcinoma cell lines the earliest and quantitatively predominant tumor marker is the free alpha-subunit. Similar results showing an unbalanced secretion of hCG and its subunits were obtained for patients with related tumors. These findings challenge the present diagnostic practice of relying solely on "beta-hCG" radioimmunoassays and at the same time offer a novel analytical strategy.     

Recovery and regression in concentration camp survivors: a psychodynamic re-evaluation

This paper focuses on the adaptive capacity of survivors, and, by reframing the psychodynamics of the "survivor syndrome", employing Object Relations theory and Self Psychology, attempts to shed light on the recovery process and the subsequent regressive responses in later life. Historically, an understanding of the survivor syndrome was impeded by the severity and uniqueness of the trauma. Survivors demonstrated symptoms that were not always congruent with the established diagnosis "traumatic neurosis", and conventional psychoanalytic psychotherapy which aimed at lifting the repression of the persecution often failed. Despite reports of "late" physiologic sequelae, recent work has focused on the survivor's capacity to recover. Survival during the persecution entailed maintaining perceptual defences, maintaining an attachment to the world and the objects in it, and despite the fragmenting effect of these two sets of mechanisms, maintaining an integrated sense of self. Three clinical vignettes are presented to demonstrate that during the recovery process a degree of reversal of the survival mechanisms was necessary. This required taking into oneself or acknowledging the anger evoked by the persecution, which, associated with the fragmenting effect of the persecution on the sense of self, often resulted in guilt and self-loathing, and affected the vicissitudes of the survivor's personal story. Often the self-selfobject function required bolstering by particular relationships. The triggers for later regression responses in survivors are events that evoke rage or serve as a symbolic bridge to memories of the persecution, and life changes that generate altered relationships that had served a self-selfobject function.(ABSTRACT TRUNCATED AT 250 WORDS)     

Capsulotomy with the diathermy scalpel (2)

Temperatures were measured with a newly designed bipolar electrode ("Cap-Stamp"). Since the results were satisfactory it was possible to introduce the new method in extracapsular cataract surgery on human. Initial clinical results are reported, the advantages of the new instrument are discussed and the "Cap-Stamp" is compared with conventional instruments.     

Regional medical practice variation in high-cost healthcare services

The European Journal of Health Economics - Magnetic resonance imaging (MRI) is a popular yet cost-intensive diagnostic measure whose strengths compared to other medical imaging technologies have...