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Biomedical subjects

A Fleming

Publications and source records attributed to A Fleming.

At least 55 records · Page 3Linked to original sources

Kinetics of anti-CD4-induced T helper cell depletion and inhibition of function. Activation of T cells by the CD3 pathway inhibits anti-CD4-mediated T cell elimination and down-regulation of cell surface CD4.

In vivo treatment with anti-CD4 antibody profoundly suppresses a number of T cell-dependent responses and is clinically useful in the treatment of certain mouse models of autoimmune disease. Treatment with anti-CD4 antibody will inactivate and can deplete CD4 T cells, but the mechanisms responsible for these effects are incompletely understood. When mouse spleen cells were exposed in vitro to both SRBC and monoclonal anti-CD4, there was 55% reduction of the anti-SRBC response. If cultures were preincubated with anti-CD4 for 48 h before in vitro challenge, the reduction was greater than 80%. When unfractionated spleen cells were cultured with anti-CD4 for 96 h, there was actual elimination of CD4 cells in these cultures since virtually all CD3+ cells were CD8+. Activation of T cells by exposure to anti-CD3 rendered them resistant to antibody-mediated CD4 depletion. This resistance to CD4 depletion was seen even in cultures that were pretreated with anti-CD4 for as long as 24 h before anti-CD3 exposure. In cultures of purified T cells, anti-CD4 did not eliminate CD4 T cells. However, culture of T cells with macrophage-rich adherent cells and anti-CD4 resulted in elimination of CD4 T cells. Thus, it appears that macrophages play a role in anti-CD4-induced T cell elimination. While anti-CD4 did not eliminate CD4 cells from a population of purified T cells, there was profound down-regulation of cell surface CD4. Activating T cells with immobilized anti-CD3 before addition of anti-CD4 prevented down-regulation of CD4. These experiments demonstrate that T cell activation by anti-CD3 renders the activated cells resistant to antibody-induced CD4 down-regulation and to antibody-induced CD4 T cell depletion. These findings may have relevance to the application of anti-CD4 therapy in human diseases that are mediated by activated Th cells.

Antigen-Antibody Reactions↗

Prospective trial of supranormal values as goals of resuscitation in severe trauma.

We prospectively tested the effect of the early postinjury attainment of supranormal values of cardiac index (> or = 4.52 L/min per square meter), oxygen delivery (> or = 670 mL/min per square meter), and oxygen consumption (> or = 166 mL/min per square meter) on outcome in traumatized patients with an estimated blood loss of 2000 mL or more. The goals in control patients were to attain normal values for all hemodynamic measurements. During the 6-month period, 33 protocol patients and 34 control patients with similar vital signs, estimated blood losses, and severity of injuries were enrolled in the study. Eight (24%) protocol patients died, while 15 (44%) control patients died. The protocol patients had fewer mean (+/- SEM) organ failures per patient (0.76 +/- 1.21 vs 1.59 +/- 1.60), shorter stays in the intensive care unit (5 +/- 3 vs 12 +/- 12), and fewer mean days requiring ventilation (4 +/- 3 vs 11 +/- 10) than did the control patients (P < .05 for each). We conclude that attaining supranormal circulatory values improves survival and decreases morbidity in the severely traumatized patient.

Adolescent↗

Evaluation of a comprehensive algorithm for blunt and penetrating thoracic and abdominal trauma.

The objective was to develop a single branched-chain decision tree for both blunt and penetrating thoracic and abdominal trauma and to test its feasibility to track clinical decisions. The algorithm consisted of 14 specific patient management loops and 31 decision nodes. During a 4-month period, the management decisions and clinical course of 434 trauma patients were prospectively observed. Thirty-four patients had no signs of life on arrival to the emergency department (ED) and were excluded from the statistical evaluation; the remaining 400 patients constituted the study group. The mean Injury Severity Score (ISS), Penetrating Abdominal Trauma Index (PATI), and Trauma Score (TS) scores in the series were 21 +/- 10, 34 +/- 12, and 13 +/- 3. The overall patient mortality of the study group was 17 per cent; it was 61 per cent in those patients with major deviations from the algorithm and 6 per cent in patients who complied with the algorithm. The ISS, PATI, and TS scores were 29 +/- 9, 32 +/- 12, and 13 +/- 2 in patients with deviations and 20 +/- 10, 37 +/- 12, and 14 +/- 2 in patients who complied with the algorithm. Of the 37 patients who died with major deviations from the algorithm, the deviation was directly contributory to death in 21 cases (57%) and probably contributory in another 14 cases (38%). There were 108 patients with ISS scores between 20 and 50. In this group, mortality was 55 per cent when a major deviation occurred and 5 per cent without major deviations from the algorithm. The authors conclude that the survival of trauma patients may be improved by following the specific management criteria outlined by the algorithm.

Abdominal Injuries↗

The relationship between ARDS, pulmonary infiltration, fluid balance, and hemodynamics in critically ill surgical patients.

Hypervolemia from fluid overload with resultant pulmonary edema is thought to be a frequent cause of Adult Respiratory Distress Syndrome (ARDS). However, ARDS may also occur as a result of the hypovolemic shock of surgery or trauma. To develop an appropriate rationale for fluid therapy in high-risk surgical patients, the relationship between fluid balance, hemodynamics, the onset of ARDS by physiologic criteria (shunt greater than or equal to 20%, and/or PaO2/FiO2 ratio less than 250) and the onset of pulmonary infiltration (PI) associated with ARDS were examined. Fifty patients were prospectively followed from admission throughout their hospitalizations; 38 (76%) had trauma and 12 (24%) were postoperative. Cardiac index, central venous pressure (CVP), wedge pressure (WP), and shunt (Qsp) were measured. All chest x rays were read by one staff radiologist who was blinded to the patients' identities. PI was graded from "0" to "4" (0 = no PI, 4 = maximum PI). The first x ray reading of "2" or greater was used as the time of onset of PI. ARDS by physiologic criteria occurred in 29 of 50 (58%) patients; 27 of these 29 (94%) also developed +2 or greater PI. The mean onset times of ARDS and of +2 PI were 40 +/- 41 hours and 40 +/- 38 hours, respectively. The ARDS patients had a significantly smaller net positive fluid balance than the non-ARDS patients over the first 40 hours after admission (+6,831 ml +/- 4,909 ml vs 12,440 ml +/- 7,817 ml, (P less than 0.01)).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Information-seeking and maternal self-definition during the transition to motherhood.

The self-definitional processes accompanying the transition to motherhood were examined in this study. A cross-sectional sample of more than 600 women who were planning to get pregnant within 2 years, pregnant, or in the postpartum stage completed extensive questionnaires pertaining to their experiences of pregnancy and motherhood. On the basis of the assumption of the "self-socialization" perspective that individuals actively construct their identities in response to life transitions, our analyses focused on the role of information-seeking in the developing self-definitions of women becoming mothers. As predicted, (a) women actively sought information in anticipation of a first birth, (b) they used this information to construct identities incorporating motherhood, and (c) after the birth the determinants of their self-definitions shifted from indirect sources of information to direct experiences with child care. Hence, consistent with the self-socialization perspective, information-seeking did play an important role in the women's developing self-conceptions during this life transition. Mechanisms by which information gathered may alter self-conception are discussed.

Adolescent↗

Contact allergy to gold after systemic administration of gold for rheumatoid arthritis.

A patient with seropositive, nodular rheumatoid arthritis (RA) developed contact allergy to gold jewellery following a severe skin rash which occurred after 13 weeks of treatment with sodium aurothiomalate. Patch testing confirmed that the contact allergy was due to gold. This is the first proved case of contact allergy to gold or any other compound initiated by systemic administration of the allergen.

Arthritis, Rheumatoid↗

Australian mortality statistics for rheumatoid arthritis 1950-81: analysis of death certificate data.

An analysis of mortality related to rheumatoid arthritis (RA) in Australia for the period 1950 to 1981 was undertaken based on information recorded in death certificates. These data include every death over a 32 year period where RA was considered to be the underlying cause. Death from RA was commonly reported (0.17% of all deaths). The mean age at death from RA in both sexes exceeded that of the general population for most of the period. There was little difference between patients dying of RA and the general population for age at death in the over 50 years' age group. There was a significant decrease in mortality for women dying of RA over the age of 75. RA accounted for more deaths in women than in men (in a ratio of 2.2:1). Men tended to die at a younger age from RA than did women. The impact of RA remained relatively constant in relation both to the total causes of death and to deaths due to other musculoskeletal diseases. There was a significant decline, however, in female RA deaths as a percentage of deaths due to all musculoskeletal diseases. Cohort analysis does not indicate any marked effect from extrinsic factors on mortality due to RA.

Age Factors↗

Chondrosarcoma of the calcaneum and massive soft tissue calcification in a patient with hereditary and acquired connective tissue diseases.

We describe the first case of the coexistence of the hereditary connective tissue disorder multiple exostoses (HME) and an acquired connective tissue disorder manifest by the overlap of dermatomyositis (DM), scleroderma (PSS), high titre speckled pattern antinuclear antibodies, and increased antibodies to double stranded deoxyribonucleic acid (DNA). Furthermore this patient developed chondrosarcoma of the calcaneum (an unusual site for this malignancy) and massive soft tissue calcification (an unusual feature of PSS, adult DM, and systemic lupus erythematosus (SLE)).

Bone Neoplasms↗

A double-blind crossover trial of diflunisal and naproxen in osteoarthritis.

Fifty patients with osteoarthritis were studied in a double-blind, crossover trial of diflunisal (1000 mg daily) and naproxen (750 mg daily). In the 45 patients who completed the study, no significant difference was noted between the drugs in most of the parameters studied, including evening pain intensity and effectiveness rating by patient and investigator. There was a trend towards greater patient preference for diflunisal, although this trend did not reach statistical significance. Naproxen produced significantly fewer side-effects, although side-effects with both drugs were mild.

Adult↗

Selective management of posterior stab wounds.

Selective management of 473 patients with stab wounds limited to the posterior abdomen was reviewed. This group was composed of predominantly young, healthy men. Laporotomy was based primarily on clinical findings. Tenderness, not localized to the area of injury, or absent or rare bowel sounds best identified patients with serious injuries. Omental protrusion was frequently associated with significant organ injury. Peritoneal lavage and local wound exploration were used infrequently. All patients with fatal injuries were operated on or died within four hours of admission. Diagnosis was delayed in five serious injuries: one diaphragmatic, three retroperitoneal colon perforations and one duodenal injury, all of which were identified and treated successfully in the initial hospital admission without any complications. Seventy-six percent of the patients never required surgery. Sixteen percent of all patients had significant organ injury, and six percent had "nonessential" laporotomy. Overall morbidity was 12 percent and mortality was 1.1 percent. The colon, liver, diaphragm, and kidneys were the most common organs injured. Thus, clinical assessment alone is a reliable means of selectively managing patients with posterior abdominal stab wounds.

Abdominal Injuries↗

The effects of early rearing environments on maternal behavior in adult female rats.

The purpose of this study was to determine the effect of presence of siblings and exposure to colony cues during early life on the onset of maternal behavior at 20 and 75 days of life, and on subsequent emotional behavior in juvenile and adult female rats. Different groups of animals were reared either with a large number or a small number of siblings (sibling factor), or in the colony room or in a room apart from other mothers with pups (colony factor). Animals were tested for latency (in days) to show maternal behavior at either 20 or 75 days of age, and for emotional behavior (using the open field apparatus) at either 20-40 or 80-100 days of age. Exposure to colony sensory cues significantly reduced latencies for pup retrieval and nest-building in adults, but not in juveniles. Exposure to a large number of siblings reduced the latencies, in both adults and juveniles, to nest build; in juveniles, to lie over 75% of the litter; and in adults, to adopt a nursing posture. Consistent with prior research, juveniles had longer latencies than adults for a number of pup-directed behaviors including: latency to become maternal, latency to retrieve pups, latency to adopt a lactating posture, latency to lick/genital lick, and latency to nest-build. In the emotionality tests, the young animals scored as less emotional than the adults, an effect which was further exaggerated by early colony exposure. Overall results indicated that manipulation of early rearing environments does have a significant positive effect on later responses to young pups by both juvenile and adult female rats.

Age Factors↗

Facial rash with scarring due to granulomatous vasculitis in rheumatoid disease.

A 60-year-old man with destructive rheumatoid disease, multiple nodules, and vasculitis developed a facial rash with ulceration and scarring. Histology showed granulomatous vasculitis. The rash was rapidly controlled with oral corticosteroids. Granulomatous vasculitis has not previously been reported as causing this clinical picture in the absence of concomitant necrobiosis and palisading.

Arthritis, Rheumatoid↗

Clinical features and followup study of HLA-B27 positive patients presenting with peripheral arthritis.

A comparison was made between HLA-B27 positive patients with peripheral arthritis and patients with ankylosing spondylitis (AS). The distribution of peripheral joint involvement in HLA-B27 positive seronegative arthritis was not the same as that in AS; significant differences were also noted in the sex ratio and incidence of uveitis. Followup of the patients with peripheral arthritis revealed that 25% had developed a further criterion for Reiter's syndrome, 45% had persistent seronegative arthritis and in 55% the arthritis had resolved.

Adolescent↗

Pericardial mesothelioma presenting as systemic lupus erythematosus.

A case of mesothelioma of the pericardium with many features of systemic lupus erythematosus (SLE) is described. We stress that satisfaction of the American Rheumatism Association's classification criteria for SLE does not confirm the diagnosis, even though their diagnostic sensitivity and specificity has recently been improved.

Diagnosis, Differential↗

Salivary scanning in rheumatoid arthritis with sicca syndrome.

Forty-nine patients were studied prospectively by salivary scanning to assess the value of this investigation in possible Sjögren's syndrome (SS). Twenty-three had rheumatoid arthritis (RA) with sicca symptoms and a positive Schirmer's test. Fifteen had RA with no sicca symptoms and a negative Schirmer's test. Eleven had osteoarthrosis (OA) with no sicca symptoms and a negative Schirmer's test. Scanning differentiated only poorly between the three groups. We conclude that it has only limited application in the diagnosis of SS associated with RA.

Adult↗