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Biomedical subjects

L A Lee

Publications and source records attributed to L A Lee.

At least 73 records · Page 4Linked to original sources
PubMed1995

Severe illness in African children with diarrhoea: implications for case management strategies.

To identify clinical disorders associated with severe illness in African children with diarrhoea, we studied a group of under-5-year-olds with diarrhoea who had been brought to a large public hospital in central Cote d'Ivoire. The general condition of children with diarrhoea was assessed and classified according to criteria recommended by WHO, and then used as a nonspecific indicator of severity. Of the 264 children with diarrhoea who were enrolled in the study, 196 had nonsevere illness and 68 severe illness. Children with severe illness were significantly more likely than those with nonsevere illness to be dehydrated (45% versus 11%), moderate-to-severely wasted (47% versus 29%), bacteraemic (26% versus 9%), severely anaemic (haemoglobin level <6 g/dl; 15% versus 6%), have Plasmodium falciparum parasitaemia (27% versus 14%), and have two or more of these five conditions (60% versus 14%). Nontyphoidal Salmonella spp. were present in 68% of the blood isolates but were not associated with seropositivity to human immunodeficiency virus (HIV). The study demonstrates the need for a more comprehensive approach to assessment and management of children with diarrhoea that ensures prompt recognition of bacteraemia, anaemia, wasting and malaria, as well as dehydration. Simple nonspecific observational criteria, such as those recommended by WHO for assessing and classifying general condition, are useful for identifying children with diarrhoea who are at high risk of having life-threatening clinical disorders, and can readily be used by health workers whose clinical training and access to diagnostic laboratory facilities are both limited.

Case Management↗
PubMed1994

Specific tolerance across a discordant xenogeneic transplantation barrier.

Successful induction of tolerance across disparate (discordant) species barriers could overcome the organ shortage that presently limits clinical transplantation. We demonstrate here that xenogeneic swine thymic transplants can induce tolerance to swine antigens in mice, while positively selecting functional host CD4+ T cells. Immunologically normal C57BL/10 mice were thymectomized and depleted of T and natural killer cells; then they received transplants of fetal pig thymus and liver fragments. Mature mouse CD4+ T cells developed in the pig thymus grafts and migrated to the periphery. Swine grafts grew markedly and no anti-pig IgG response was produced. Mixed lymphocyte reactions confirmed that the new T cells were functional and were tolerant to pig antigens.

Animals↗
PubMed1994

The importance of nonimmune factors in reconstitution by discordant xenogeneic hematopoietic cells.

Bone marrow transplantation has been shown to induce donor-specific tolerance in rodent models. This approach could potentially be applied to xenotransplantation across discordant species barriers. To evaluate host factors resisting hematopoietic cell engraftment, we have developed two model systems utilizing the combination of swine into severe combined immunodeficient (SCID) mice. SCID mice lack functional B and T lymphocytes, and can therefore be used to evaluate nonimmune factors resisting marrow engraftment, and for adoptive transfer studies to test the role of immune cells and antibodies. First we transplanted swine bone marrow cells into SCID mice conditioned with whole-body irradiation (4 Gy). For nine weeks following the intravenous administration of 10(8) swine bone marrow cells, up to 3.8% of peripheral blood leukocytes were of swine origin, as determined by flow cytometry (FCM). These cells were all of the myeloid lineage. Swine IgG was also detectable in the serum for up to 14 weeks. The bone marrow of the reconstituted mice contained low percentages of swine myeloid cells, and swine myeloid progenitors could be detected for up to 20 weeks after bone marrow transplantation. In a second model, we grafted thymus and liver tissue from 45-69-day-old swine fetuses under the kidney capsule of 4 Gy-irradiated SCID mice. A suspension containing 10(8) swine fetal liver cells (FLC) was also administered i.p. Long-term repopulation with swine T cells was observed, with up to 1.5% swine T cells detected in the WBC, peritoneum, and spleen for at least 5.5 months postgrafting. These T cells expressed either CD4 or CD8, whereas up to 17.6% of cells in the thymic grafts expressed both CD4 and CD8. The i.p. FLC suspension was required for optimal long-term graft maintenance. Our studies show that (1) low level myeloid and B lymphocyte reconstitution can be achieved by transferring adult swine BMC to irradiated SCID recipients; (2) swine myeloid progenitors were detectable long-term in BMC of these mice, suggesting that stem cell engraftment was achieved; and (3) T cell reconstitution of SCID mice by swine progenitors requires cotransplantation of a swine stromal environment, as is provided by fetal swine thymus/liver grafts. We conclude that nonimmune factors such as those provided by species-specific stromal environments are important for reconstitution of some lineages by discordant hematopoietic stem cells.

Animals↗
PubMed1994

Concentration of autoantibodies to native 60-kd Ro/SS-A and denatured 52-kd Ro/SS-A in eluates from the heart of a child who died with congenital complete heart block.

OBJECTIVE: To determine the serologic specificity of acid eluates from tissues of a child who died with congenital complete heart block (CCHB). METHODS: Tissues were extracted, acid eluted, and the IgG and antibody titers determined on the eluates by enzyme-linked immunosorbent assay. RESULTS: Antibodies to native 60-kd and denatured 52-kd Ro/SS-A were found to be enriched only in the heart eluate, and not in the eluates from brain, kidney, and skin. CONCLUSION: These findings indicate a major role for anti-native 60-kd Ro/SS-A in the immunopathogenesis of CCHB.

Adult↗
PubMed1994

Outbreaks of Salmonella enteritidis infections in the United States, 1985-1991.

The spread of Salmonella enteritidis infections in the United States was tracked to identify potential risk factors and preventive measures. Isolation rates and information regarding outbreaks of S. enteritidis from 1985 through 1991 were determined by reports to the national Salmonella surveillance system and through the foodborne disease outbreak surveillance system. From 1985 through 1991, 380 outbreaks were reported involving 13,056 ill persons and 50 deaths. The proportion of Northeast outbreaks fell from 81% in 1985 to 55% in 1991 as the number of outbreaks in other areas increased. Grade A shell eggs were implicated in 82% of outbreaks. Case-fatality rates in nursing homes and hospitals were 70 times higher than in other settings. Cultures of environmental or animal specimens from all farms tested yielded S. enteritidis. Eggborne S. enteritidis infections are a major public health problem. Preventive measures, including educating consumers about proper handling of eggs, using pasteurized eggs, and controlling infections on egg farms, may stem the impact of this disease.

Disease Outbreaks↗
PubMed1994

Increase in antimicrobial-resistant Salmonella infections in the United States, 1989-1990.

To assess factors associated with antimicrobial-resistant Salmonella infections and trends in resistance, a prospective study of patients with culture-confirmed salmonellosis was done in 1989-1990. Patients with resistant infections were more likely than those with susceptible infections to be hospitalized (P = .006), to be < 1 year old (P = .003), to be black (P = .013), and to have recently been treated with an antimicrobial agent (P = .085). Compared with data from a similar study in 1979-1980, increases were seen in the percentage of patients with resistant infections (from 17% to 31%), in the resistance to ampicillin (10% to 14%), and in the frequency of isolates found in blood (1% to 11%). These data show that treatment of Salmonella infections may be complicated by growing resistance to clinically important antimicrobial agents and by an increasing frequency of extraintestinal complications. Antimicrobial agents with little demonstrated resistance should be considered for patients with complicated illness and at high risk of having a resistant infection.

Adolescent↗
PubMed1994

Autoantibodies of neonatal lupus erythematosus.

The most common manifestations of neonatal lupus erythematosus (NLE) are cutaneous lupus and congenital heart block. Autoantibodies to Ro/SSA occur in almost all cases of NLE. The autoantibody response to Ro/SSA is complex, and antibodies may be detected to 60-kD Ro/SSA, 52-kD Ro/SSA, La/SSB, and U1 ribonuclear protein in anti-Ro/SSA-positive sera. Which of these anti-Ro/SSA-related autoantibody specificities are important in the clinical expression of NLE is not conclusively established. We examined the autoantibody specificities in 20 maternal NLE sera to determine whether autoantibody specificities correlate with the clinical findings and to evaluate the relative importance of autoantibodies to the different Ro/SSA-associated proteins. Autoantibodies were examined using immunodiffusion, immunoblotting, and enzyme-linked immunosorbent assay. Eleven babies had NLE skin disease, 11 had heart block, and two had both skin disease and heart block. All 20 maternal sera had antibodies to 60-kD Ro/SSA. Eighteen of the 20 had antibodies to 52-kD Ro/SSA, nine had antibodies to La/SSB, and one had antibodies to U1 ribonuclear protein. The prevalence of anti-La/SSB was the same in the skin-disease and heart-block subsets of NLE. Titers of anti-60-kD Ro/SSA were significantly (p < 0.02) lower in NLE skin disease maternal sera than in the NLE heart-block maternal sera. These results point out the importance of 60-kD Ro/SSA as a potential target in NLE. We speculate that the lower titers of anti-60-kD Ro/SSA in the sera from mothers of babies with skin disease may be due to substantial deposition of antibodies in the mothers' and babies' skin, leading to lower circulating titers, or may reflect a lower threshold for development of skin disease than for heart block.

Antibodies, Antinuclear↗
PubMed1994

The autoantibody response to Ro/SSA in cutaneous lupus erythematosus.

BACKGROUND AND DESIGN: Seventeen patients with subacute cutaneous lupus erythematosus (SCLE) were compared with 15 patients with discoid lupus erythematosus (DLE) to evaluate the relationship of 60- and 52-kd Ro/SSA autoantibodies to the clinical diagnosis and to evaluate assays for anti-Ro/SSA. RESULTS: All serum samples from patients with SCLE had precipitating anti-Ro/SSA antibodies in immunodiffusion, and all had high titer anti-60-kd Ro/SSA in enzyme-linked immunosorbent assay. Immunoblotting was inadequately sensitive for detecting anti-60-kd Ro/SSA. Fifteen patients with SCLE had anti-52-kd Ro/SSA (11 high titer, four low titer). Only one of the 15 patients with DLE had precipitating, high-titer anti-Ro/SSA. Nine other patients with DLE had low-titer anti-60-kd Ro/SSA, and four had low-titer anti-52-kd Ro-SSA. Low-titer anti-Ro/SSA did not confer an increased risk for photosensitivity in the DLE group. CONCLUSIONS: High-titer, precipitating antibodies to Ro/SSA are typical of SCLE and unusual in DLE. Low-titer, nonprecipitating antibodies to Ro/SSA are common in DLE and could be an indication of pathogenic factors shared with SCLE. However, low titers of anti-Ro/SSA do not confer a significant risk for SCLE skin lesions. For the purpose of clinical evaluation of skin disease, immunodiffusion assays for anti-Ro/SSA are cost-effective and informative.

Autoantigens↗
PubMed1993

Antimicrobial-resistant Salmonella spp isolated from healthy broiler chickens after slaughter.

Of 105 Salmonella organisms of any serotype selected from a sample of 1,824 serotyped salmonellae isolated during a nationwide bacteriologic survey of healthy broiler chickens after slaughter, 60 (57%) were resistant to 1 or more antimicrobial agents and 47 (45%) were resistant to 2 or more agents. Highest resistance was to tetracycline (45%), streptomycin (41%), sulfisoxazole (19%), gentamicin (10%), and trimethoprim/sulfamethoxazole (8%). Additional isolates of S typhimurium, heidelberg, agona, and enteritidis were selected from the sample of 1,824 isolates for testing because of the high frequency with which these 4 serotypes are isolated from human patients. The highest frequency of resistance among 104 isolates of S heidelberg, 92 isolates of S typhimurium, and 30 isolates of S agona was to streptomycin (33 to 57%), sulfisoxazole (33 to 50%), tetracycline (26 to 50%), and gentamicin (13 to 40%); 51 to 63% of these isolates were resistant to 1 or more agents and 37 to 59% were resistant to 2 or more agents. Resistance to ampicillin among these 3 serotypes was uncommon (0 to 4%). In contrast, 15 of 19 tested isolates (79%) of S enteritidis were resistant to ampicillin and 13 of the 19 isolates (68%) were resistant only to ampicillin. This pattern of resistance was associated with a specific bacteriophage type and indicated the potential role of bacterial clones in determining the frequency and patterns of antimicrobial resistance in populations of broiler chickens. Resistance to gentamicin and trimethoprim/sulfamethoxazole was higher than that previously reported and is of public health concern because of the frequency with which these drugs are used to treat bacterial infections in human patients.

Animals↗
PubMed1993

Neonatal lupus erythematosus.

Neonatal lupus erythematosus (NLE) is an autoimmune disease whose major findings are subacute cutaneous lupus erythematosus (SCLE) skin lesions and congenital heart block. Babies have maternal anti-Ro/SSA, anti-La/SSB, or anti-U1RNP autoantibodies. Anti-Ro/SSA are the predominant autoantibodies, having been found in about 95% of cases. The autoantibodies pass through the placenta from mother to child. Skin disease resolves at about the time that maternal autoantibodies can no longer be detected in the baby. NLE therefore provides the strongest clinical evidence that autoantibodies are involved in at least some manifestations of lupus erythematosus, but there is as yet no definitive evidence implicating autoantibodies in the disease process. Skin disease usually begins after birth, is transient, and does not result in scarring. Cardiac disease begins in utero, and the heart block is almost always permanent. Many babies require pacemakers, and about 10% die from complications related to cardiac disease. In some cases, transient liver disease or thrombocytopenia have been observed. Individuals who had NLE usually have healthy childhoods but may develop autoimmune disease in adulthood. Whether the later development of autoimmune disease is a common or an unusual event is not yet known. Mothers of babies with NLE may be asymptomatic initially, but with time usually develop symptoms of autoimmune disease. The most typical constellation of symptoms in our group of approximately 30 mothers of babies with NLE is that of Sjögren's syndrome. Most babies exposed to anti-Ro/SSA autoantibodies during gestation will not develop NLE. There is no test to determine prospectively which babies will be affected. Treatment during gestation is still controversial and, if attempted, should be reserved for fetuses with potentially life-threatening disease. Treatment after birth consists of topical management for skin disease and pacemaker implantation, if necessary, for heart block. Systemic steroids may be given for serious internal disease.

Adult↗
PubMed1993

Neonatal lupus liver disease.

Neonatal lupus erythematosus (NLE) is an autoimmune disease characterized by complete congenital heart block and/or transient skin lesions of subacute cutaneous lupus erythematosus. We report that in approximately 10% of cases of NLE with heart block or skin disease, liver disease also occurs (4 of 35 cases in our series). Cholestasis was the major feature in our cases. Although the cholestasis may be severe, the disease process appears to be transient and surviving babies have been healthy on follow-up. In one liver examined for antibody deposition, IgG antibody deposits, presumably of maternal origin, were present. Three maternal sera were examined for autoantibodies, including liver-specific autoantibodies. No liver-specific autoantibodies were found. Rather, the maternal autoantibodies too were the ubiquitous Ro/SSA-associated autoantigens. The autoantibodies bound the 60 kDa SSA/Ro ribonuclear protein (three of three sera), the 52 kDa SSA/Ro protein (two of three sera) and the SSB/La ribonuclear protein (two of three sera).

Antibodies, Antinuclear↗
PubMed1992

Left ventricular mechanics in the preterm infant and their effect on the measurement of cardiac performance.

The effects of the transition from fetal to postnatal circulation on left ventricular geometry, wall motion, and echocardiographic measurements of function in the human preterm infant are largely unknown. To determine whether abnormalities in left ventricular geometry are present in the normal preterm infant after birth and, if so, for how long, and to examine possible contributing factors and their effect on the measurement of cardiac performance, we obtained serial echocardiograms of 14 healthy preterm infants (gestational age, 33 +/- 2 weeks; birth weight, 1940 +/- 470 gm) at 9.5 +/- 3.5 days of age (time 1) and again at 51 +/- 16 days (time 2). Left ventricular shape and wall motion were measured and estimates of wall stress and mass were made. Performance was assessed by standard M-mode shortening fraction and by transverse two-dimensional area shortening. At time 1 septal flattening caused distortion of left ventricular shape. As the patients grew older, septal flattening resolved and the left ventricle tended to assume a circular cross-sectional shape. Wall-motion analysis demonstrated poor motion of the midseptum and anterior free wall at time 1, which improved at time 2 (p = 0.06). Left ventricular mass increased from 24 +/- 5 to 41 +/- 7 gm/m2 (p = 0.0001) and wall stress decreased from 49 +/- 21 to 38 +/- 13 gm/cm2 (p = 0.005) between time 1 and time 2. Shortening fraction was lower at time 1 than at time 2 (18% +/- 7% vs 28% +/- 8%; p = 0.001; normal limit = 28% to 45%); however, there was no significant difference in area shortening between time 1 and time 2 (49% +/- 10% vs 53% +/- 8%; normal limit = 45% to 65%). We conclude that the preterm newborn infant has distorted left ventricular shape and abnormal wall motion, which alter measurements of shortening fraction and persist for the first weeks of life. Area shortening may be necessary to assess left ventricular performance during the first weeks of life in the premature infant.

Echocardiography↗
PubMed1992

Clinical, histologic, and immunofluorescent distinctions between subacute cutaneous lupus erythematosus and discoid lupus erythematosus.

Subacute cutaneous lupus erythematosus (SCLE) was originally described and distinguished from discoid lupus erythematosus (DLE) on the basis of clinical examination of the skin, but subsequent reports have questioned the concept of SCLE as a marker of a unique subset of LE patients. We classified 27 lupus patients, on the basis of cutaneous exam, as having discoid lupus skin lesions, subacute cutaneous skin lesions, or systemic lupus erythematosus (SLE) without DLE or SCLE lesions. Clinical features most characteristic of SCLE rather than DLE were superficial, non-indurated, non-scarring lesions, and photosensitivity, with lack of induration being the single most helpful finding. Histologic examination of lesional skin showed a relatively sparse, superficial infiltrate in SCLE and a denser, deeper infiltrate in DLE. A distinctive pattern of staining with direct immunofluorescence, particulate epidermal IgG deposition, was found in seven of seven SCLE patients (all anti-Ro/SSA positive) and none of the other patients. This distinctive pattern can be reproduced experimentally when anti-Ro/SSA autoantibodies are infused into human skin-grafted mice. Particulate dermal-epidermal junctional staining was the pattern seen in the patients who did not have SCLE. Clinically defining SCLE as a superficial inflammatory form of cutaneous lupus (i.e., considering lesions to be DLE if they are indurated) results in a meaningful segregation of SCLE and DLE patient groups. The epidermal IgG deposits unique to SCLE provide independent evidence that the clinical findings that were used to identify the patient groups actually identify distinctive cutaneous lupus subsets. The observation that antibodies are present in a different location in the skin in SCLE than in DLE indicates that SCLE and DLE are likely to have different pathomechanisms.

Antibodies, Antinuclear↗