Biomedical subjects
Publications and source records attributed to D Nunez.
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OBJECTIVE: To compare intraoperative findings and/or angiography with color-flow duplex scan. DESIGN: This prospective double-blind study was performed on all stable patients with zone 1, 2, or 3 penetrating neck trauma. Results of angiographic or intraoperative findings were compared with the results of duplex ultrasonographic scans. MAIN OUTCOME MEASURES: Fifty-five patients were studied over a 2-year period in which the distribution of injuries included 23 stab wounds (42%), 30 gunshot wounds (54%), and 2 motor vehicular lacerations (4%). There were 42 patients (76%) with normal ultrasonographic results and 13 patients (24%) with abnormal ultrasonographic results. The true-negative rate was 100%; however, there were 2 false positives resulting in 100% sensitivity and 85% specificity. CONCLUSIONS: Duplex ultrasonography provides an excellent diagnostic modality with cost-saving, patient-friendly characteristics and a low rate of morbidity. It should be instituted as the primary diagnostic procedure of choice for penetrating neck trauma.
Diagnostic peritoneal lavage (DPL) and computed tomography (CT) are the primary diagnostic modalities used in the evaluation of patients with suspected blunt abdominal trauma (BAT). DPL is fast and accurate but is associated with complications. CT is also accurate, yet requires stability and transportability of the patients. Ultrasound (US) has been suggested as an aid in evaluating BAT. We evaluated US in the initial assessment of BAT in 1000 patients. Patients were eligible for the study if they met specified trauma criteria and had suspected BAT. We then followed the outcome of the patients and their further work-up. US showed a sensitivity of 88%, a specificity of 99%, and an accuracy of 97% for detecting intraabdominal injuries. We conclude that emergency ultrasound may be used as the initial diagnostic modality for suspected blunt abdominal trauma.
The working patterns of clinical postgraduate trainees are being scrutinised in preparation for the implementation of new, structured and shortened postgraduate specialist training programmes. Current practice in the National Health Service dictates, in all branches of surgery, the evaluation of elective admissions undergoing procedures under general anaesthetic by a junior trainee (SHO or HO) who then arranges the appropriate preoperative investigations. This doctor acts as a "generalist' in that he is primarily concerned with the patient's general fitness for the operation as well as with the specific condition to be treated. The anaesthetist also evaluates the patient prior to the operation. In his case his sole concern is to whether or not the patient is fit for a general anaesthetic. This prospective study investigated the extent of duplication in preoperative elective patient assessment by both the otolaryngology trainee and the anaesthetist in order to answer the question: are both assessments necessary? The medical records of 100 consecutive adult elective admissions to the Leicester Royal Infirmary Otolaryngology Department which provides inpatient services to a catchment population of 900,000 were reviewed. The case histories obtained by clinicians blind to the study were classified as positive or negative for relevant features. The case histories obtained by the otolaryngology trainee and anaesthetist showed a level of disagreement which was 9 per cent greater than chance. It appears that there is a low level of duplication in preoperative elective otolaryngology patient assessment and both otolaryngology trainee and anaesthetic examination are of value.
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Diagnostic peritoneal lavage (DPL) and computed tomography (CT) are the primary diagnostic modalities in the evaluation of patients with suspected blunt abdominal trauma (BAT). Diagnostic peritoneal lavage is fast and accurate but associated with complications. Computed tomography is also accurate, yet requires that patients be stable and transportable. A prospective study was designed to determine the utility of emergency ultrasound (US) studies in the initial assessment of BAT. Two hundred acutely injured patients with suspected BAT were evaluated with US. Patients were eligible for the study if they met trauma criteria and had suspected BAT. Subsequently, without knowledge of the US results, DPL or CT was performed. Ultrasound showed a sensitivity of 83%, a specificity of 100%, and an accuracy of 97% in detecting intra-abdominal injuries. Six injuries were missed but only one was felt to be significant. If US had been used in all 200 patients, 199 would have had appropriate care. We conclude US is reliable in the detection of free intraperitoneal fluid and may be used in place of DPL or CT.
In an earlier study (Miwa, M., Hill, C., Kumar, R., Sugatani, J., Olson, M. S., and Hanahan, D. J. (1987) J. Biol. Chem. 262, 527-530) it was shown that an inhibitor of platelet-activating factor (PAF), a powerful endogenous mediator of platelet aggregation, was present in freeze-clamped perfused livers. Subsequently, we determined that this substance was a mixture of unsaturated free fatty acids (FFA). Among these FFA, oleic acid between 10 and 100 microM was found to be a potent inhibitor of PAF-induced platelet aggregation and serotonin secretion. Consequently, in order to understand the molecular mechanism of oleic acid action, we investigated the effects of this FFA on several biochemical events associated with platelet aggregation induced by PAF. The effect of oleic acid and/or PAF on the level of [32P]phosphatidylinositol 4-phosphate (PIP) and [32P]phosphatidylinositol 4,5-bisphosphate (PIP2) was examined by using platelets labeled with [32P]phosphate. Oleic acid induced a dose-dependent decrease in the levels of [32P]PIP and [32P]PIP2; a maximal decrease in [32P]PIP and [32P]PIP2 of approximately 50 and 25%, respectively, was observed within seconds after the addition of 20 microM oleic acid and persisted for at least 15 min. Oleic acid did not induce the formation of [3H]inositol phosphates in platelets prelabeled with [3H]inositol, suggesting that the decrease in [32P]PIP and [32P]PIP2 was not due to a stimulation of phospholipase C. In contrast to oleic acid, PAF induced a dose-dependent increase in the [32P]PIP level, reaching a maximum of approximately 200% 3 min after the addition of 1 nM PAF to the platelets. This increase in [32P]PIP was accompanied by platelet aggregation and secretion, and a close correlation was established between the [32P]PIP level and the degree of aggregation. Oleic acid and PAF, when added together to the platelets, interacted by affecting the level of [32P]PIP and [32P]PIP2 in an opposite way since the decrease in the level of [32P]PIP and [32P] PIP2 induced by oleic acid was partially reversed by an excess of PAF. The decrease in the levels of [32P] PIP and [32P]PIP2 caused by oleic acid was associated with an inhibition of platelet aggregation induced by PAF. Interestingly, oleic acid did not block [3H]PAF binding to platelets but inhibited the PAF-induced phosphorylation of platelet proteins of 20 kDa and 40 kDa. These results suggest that inhibition of the PAF response by oleic acid may be at one of the steps in the signal transduction.(ABSTRACT TRUNCATED AT 400 WORDS)
Zinc ions in the micromolar range exhibited a strong inhibitory activity toward platelet activating factor (PAF)-induced human washed platelet activation, if added prior to this lipid chemical mediator. The concentration of Zn2+ required for 50% inhibition of aggregation (IC50) was inversely proportional to the concentration of PAF present. The IC50 values (in microM) for Zn2+ were 8.8 +/- 3.9, 27 +/- 5.8, and 34 +/- 1.7 against 2, 5, and 10 nM PAF, respectively (n = 3-6). Zn2+ exhibited comparable inhibitory effects on [3H]serotonin secretion and the IC50 values (in microM) were 10 +/- 1.2, 18 +/- 3.5, and 35 +/- 0.0 against 2, 5, and 10 nM PAF, respectively (n = 3). Under the same experimental conditions, aggregation and serotonin secretion induced by ADP (5 microM), arachidonic acid (3.3 microM), or thrombin (0.05 U/ml) were not inhibited. Introduction of Zn2+ within 0-2 min after PAF addition not only blocked further platelet aggregation and [3H]serotonin secretion but also caused reversal of aggregation. Analysis of [3H]PAF binding to platelets showed that Zn2+ as well as unlabeled PAF prevented the specific binding of [3H]PAF. The inhibition of [3H]PAF specific binding was proportional to the concentration of Zn2+ and the IC50 value was 18 +/- 2 microM against 1 nM [3H]PAF (n = 3). Other cations, such as Cd2+, Cu2+, and La3+, were ineffective as inhibitors of PAF at concentrations where Zn2+ showed its maximal effects. However, Cd2+ and Cu2+ at high concentrations exhibited a significant inhibition of the aggregation induced by 10 nM PAF with IC50 values being five- and sevenfold higher, respectively, than the IC50 for Zn2+, and with the IC50 values for inhibition of binding of 1 nM [3H]PAF being 5 and 19 times higher, respectively, than the IC50 for Zn2+. The specific inhibition of PAF-induced platelet activation and PAF binding to platelets suggested strongly that Zn2+ interacted with the functional receptor site of PAF or at a contiguous site.
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The aggregation of washed human platelets with paf-acether (paf) and [3H]paf binding were inhibited in a concentration- and time-dependent manner by three chemically defined ginkgolides (BN 52020, BN 52021, BN 52022) and their mixture, BN 52063 (molar ratio: 2:2:1). The IC50 values for aggregation correlated well with the IC50 values for [3H]paf binding (R-square 0.971). BN 52021, BN 52020 and BN 52063 (6 microM), as well as unlabelled paf (50 nM), displaced platelet-bound [3H]paf. Specific binding (total minus non-specific binding) in the presence of BN 52020 and BN 52063 was saturated but that observed in the presence of BN 52022 was not. However all ginkgolides shifted the dose-dependent paf-induced platelet aggregation curve rightwards. BN 52063 failed to modulate paf metabolism either in plasma or in the presence of platelets. The present results suggest that the ginkgolide mixture, BN 52063, acts at the paf binding level and the close correlation between ginkgolide effects on aggregation vs. paf binding illustrates the functional relevance of the putative paf platelet receptor.
PAF-acether (PAF) is a newly formed mediator not normally present in circulating blood. A compound exhibiting all of its biological characteristics but coeluting with phosphatidylcholine (PC) in high-pressure liquid chromatography (HPLC) was unveiled ('peak X') in normal human plasma. A second HPLC run of peak X HPLC fractions revealed the presence of PAF itself with concomitant disappearance of peak X. Beside PAF, immunoreactive apolipoproteins A-I and E were found in peak X. Also lipoproteins (Ls) purified using either ultracentrifugation or immunoaffinity chromatography yielded peak X and, in a second HPLC run, authentic PAF. L-free plasma was devoid of peak X. Finally, after preincubation with plasma, labeled PAF was found associated with Ls. Thus in human blood preformed PAF is bound in high amounts to Ls, a result of interest given the role of Ls and platelets in vascular diseases and the present knowledge on PAF biosynthesis.
Circulating precursors of mucosal immunoglobulin A plasma cells and T-cell immunoblasts migrate selectively into mucosal sites from the blood, but the mechanisms controlling this selective trafficking have not been determined. One possibility is that the site-specific extravasation of circulating effector cell populations is determined by organ-specific endothelial cell recognition mechanisms. Here we have assessed the ability of isolated mouse gut intraepithelial lymphocytes to recognize and bind to mucosal versus nonmucosal lymphoid organ high endothelial venules, vessels that support high levels of lymphocyte traffic in vivo. In an in vitro assay of lymphocyte interaction with high endothelial venules in frozen sections, intraepithelial leukocytes bind well to high endothelial venules in Peyer's patches but, unlike most circulating B and T lymphocytes, are unable to interact with peripheral lymph node high endothelial venules. Furthermore, we show by in situ immunohistology and in cell suspension immunofluorescence studies that intraepithelial leukocytes fail to stain with a monoclonal antibody, MEL-14, against putative lymphocyte receptors for lymph node high endothelial venules. Thus, they lack a cell surface glycoprotein required for homing to peripheral nodes. The demonstration of organ-specific recognition of endothelial cells by a normal mucosal effector lymphocyte population suggests that selective interactions with endothelium may play an important role in controlling the distribution of effector cells in vivo. The utilization of organ-specific endothelial cell recognition mechanisms by circulating precursors of mucosal effector cells could explain both the unification of immune responses in diverse mucosal sites and the physiologic segregation of mucosal from nonmucosal immune mechanisms.
gp140, the C3d/EBV receptor (CR2), previously isolated and characterized from human B lymphocytes, was identified on human platelets: by measuring the specific binding of either polyclonal anti-gp140 IgG and monoclonal anti-C3d/EBVR antibodies, as OKB-7 and HB-5, or human C3d; by isolating gp140 from solubilized platelet components with polyclonal anti-gp140 IgG or monoclonal OKB-7, using immunoprecipitation and electro-immunoblotting assays; by inducing specific activation of human platelets. Cross-linking of this receptor by polyclonal anti-gp140 IgG induced aggregation of human platelets and stimulated ATP release. Absence of lactate dehydrogenase release and inhibition by EDTA and prostacyclin of anti-gp140-induced aggregation, support strongly active aggregation and absence of lysis. Platelet aggregation by anti-gp140 required metabolic activities and was modulated by fibrinogen, paf-acether or thrombin. OKB-7 triggered human platelet aggregation when cross-linked by anti-mouse second-step antibodies. In the same way, platelet activation by C3d fragment was detected, in presence of fibrinogen, only when C3d was cross-linked on the cell surface by anti-C3d F(ab')2 fragments.
The Duhamel operation of retrorectal transanal pull-through is a widely used technique in the treatment of Hirschsprung's disease. Modifications of the technique have been made with the introduction of stapling instruments. The construction of a side-to-side colorectal anastomosis has been facilitated with the introduction of the GIA linear anastomosing instrument. The advent of the EEA stapling device has allowed us to perform a modified Duhamel operation in a 9-month-old boy with Hirschsprung's disease using mechanical sutures entirely. The technique for the procedure is described.
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The metabolite of molsidomine, 3-morpholino-syndnonimine (SIN-1) is a vasodilator and an inhibitor of platelet activation induced by adenosine-5'-diphosphate (ADP), arachidonic acid (AA) and thrombin. We present the results of SIN-1 on platelet aggregation induced by paf-acether and on the biosynthesis of this mediator by washed rabbit platelets. SIN-1 inhibits submaximal platelet aggregation induced by 50 pM paf-acether. This inhibition is dose-dependent (SIN-1 IC50: 37 +/- 10 nM, n = 3). SIN-1 also inhibits submaximal aggregations induced by ADP (IC50: 13 +/- 11 nM) and AA (IC50: 26 +/- 12 nM) (n = 3-5). Finally, SIN-1 inhibits dose-dependently the formation of lyso paf-acether (the precursor of paf-acether) and of thromboxane A2, and AA freeing by thrombin-stimulated platelets. Thus SIN-1 has a wide spectrum activity on platelets. He is both capable of inhibiting platelet aggregation induced by all used agonists and to inhibit the formation of paf-acether and thromboxane A2, two powerful mediators of platelet aggregation.