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Biomedical subjects

E Stevens

Publications and source records attributed to E Stevens.

At least 19 recordsLinked to original sources
PubMed2006

Surgical technique and complications during laparoscopic repair of diaphragmatic hernias.

Diaphragmatic hernias can present as retrocostoxiphoid hernias (RCXH) or diaphragmatic dome hernias. The RCXH include the Larrey hernia (LH), the Morgagni hernia (MH), and the Larrey-Morgagni hernia (LMH). These congenital hernias are usually asymptomatic, and the diagnosis is simplified by two exams: chest X-ray, and thoraco-abdominal computed tomography (CT) scan. The potential risk in this condition is small-bowel incarceration in the hernia defect and subsequent obstruction. We report two cases of LH and one case of LMH treated by laparoscopy between February 2004 and October 2005, with a review of the surgical techniques. Two different laparoscopic techniques were used: the tension-free technique, and resection of the hernia sac with closure of the defect and reinforcement by prosthesis. One patient presented a postoperative cardiac tamponade due to a clip-induced bleeding of an epicardial artery at the inferior surface of the heart. Treatment by laparoscopy is feasible, but a consensus regarding the best laparoscopic repair is needed.

Adolescent↗
PubMed2003

Haptoglobin directly affects T cells and suppresses T helper cell type 2 cytokine release.

T helper cell type 1 (Th1) and type 2 (Th2) immune responses are characterized by a different pattern of cytokine expression following T-cell activation. Alterations of the ratio of Th1 to Th2 cells are important determinants of susceptibility to viral and parasitic infections, allergies, anti-tumour responses, and autoimmunity. In this work we bring new evidence for an effect of haptoglobin (Hp), a positive acute-phase protein, on T-lymphocyte functions. We show that Hp specifically interacts with both resting and activated CD4+ and CD8+ T cells. This specific binding results in a strong suppression of induced T-cell proliferation. In addition, Hp exhibits a strong in vitro inhibitory effect on Th2 cytokine release, while the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2) is only slightly inhibited at high Hp doses. As a result, the presence of Hp promotes Th1 activation over Th2 activation in vivo as evidenced in Hp-deficient mice. Anti-CD3 monoclonal antibody injection indeed resulted in predominant IL-4 production in Hp-/- mice, in contrast to predominant IFN-gamma production in Hp+/+ mice. We conclude that Hp plays a modulating role on the Th1/Th2 balance by promoting a dominant Th1 cellular response. This points to a role of acute-phase proteins in balancing immune responses.

Adjuvants, Immunologic↗
PubMed2000

Daclizumab (Zenapax) inhibits early interleukin-2 receptor signal transduction events.

Daclizumab, a humanized antibody against the interleukin-2 (IL-2) receptor (R) alpha-chain, is a promising new immunosuppressant in transplantation. As its exact mechanism of action has remained unclear, we examined its short-term effects on primary human T lymphocytes expressing the high-affinity IL-2R. Daclizumab exposure for 20 min neither affected T cell viability nor their surface expression of the IL-2R alpha-, beta-, or gamma-chains. However, after IL-2 stimulation (200 U/ml, 20 min), immunoblots of cell lysates demonstrated attenuation of the IL-2-induced tyrosine phosphorylation of 65-75 kDa proteins by Daclizumab, but not by isotype controls. Since this is the molecular weight of the IL-2R beta- and gamma-chains, which are both tyrosine-phosphorylated by IL-2, we next examined the effect of Daclizumab on their IL-2-induced tyrosine phosphorylation. In immunoblots of IL-2R beta- and gamma-chain-immunoprecipitates the tyrosine phosphorylation of both chains by IL-2, but not by IL-15, was attenuated in the presence of Daclizumab. Furthermore, co-immunoprecipitation experiments showed that Daclizumab inhibited the IL-2-induced association of these chains, a prerequisite for their mutual tyrosine phosphorylation. Lastly, we demonstrated that Daclizumab inhibits the receptor-downstream induction of the IL-2-activated DNA-binding protein STAT5 in gel shift assays. We conclude that Daclizumab directly and specifically interferes with IL-2 signaling at the receptor level by inhibiting the association and subsequent phosphorylation of the IL-2R beta- and gamma-chains induced by ligand binding. Under our experimental conditions, Daclizumab had no effects on cell viability, and it did not modulate the surface expression of the IL-2R alpha-, beta-, or gamma-chains.

Animals↗
PubMed1999

Spontaneous T-cell proliferation in the non-obese diabetic mouse to a peptide from the unique class II MHC molecule, I-Ag7, which is also protective against the development of autoimmune diabetes.

AIMS/HYPOTHESIS: Major histocompatibility complex class II molecules present antigenic peptides to T-cells and have an important role in T-cell thymic education. The mechanism by which major histocompatibility complex alleles confer a high genetic risk for autoimmune diabetes is not known. One hypothesis is that during positive thymic selection, the peripheral T-cell repertoire is modelled by major histocompatibility complex-restricted presentation of self major histocompatibility complex molecule-derived peptides, some of which mimic tissue autoantigens. The sequence similarity between a known T-cell epitope of glutamic acid decarboxylase-65, 509:VPPSLRTLED and the non-obese diabetic mouse class II major histocompatibility complex molecule I-Ag7 86:VPTSLRRLEQ is consistent with this. METHODS: We measured spontaneous proliferation of peripheral T-cells from non-obese diabetic mice and other, non-diabetes-prone strains, to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, binding of these peptides to intact I-Ag7 and assessed the effect of tolerance induction on diabetes development, by injecting young non-obese diabetic mice with high doses of peptide. RESULTS: T-cells from non-obese diabetic, but not other mice strains, spontaneously proliferate to the I-Ag7 86-101 and glutamic acid decarboxylase-65(509-524) peptides, but not control peptides. Both test peptides bind I-Ag7. Tolerance induction prolongs diabetes-free survival in non-obese diabetic mice when either the I-Ag7 86-101 or glutamic acid decarboxylase-65(509-524) peptide, but not control peptide, is used. CONCLUSION/INTERPRETATION: A peptide from the unique class II major histocompatibility complex, diabetes-susceptibility molecule, I-Ag7, presented by I-Ag7 is a target of T-cell responses in diabetes-prone nonobese diabetic mice and tolerance induction against the peptide offers appreciable protection against the development of diabetes.

Amino Acid Sequence↗
PubMed1999

Treatment for postdural puncture headache associated with late postpartum eclampsia.

Postdural puncture headache (PDPH) is the most common complication of accidental or deliberate dural puncture. It also occurs after epidural or spinal analgesia for labor and delivery. Treatment may be conservative with analgesics and/or caffeine. Definitive treatment can be accomplished with an epidural blood patch (EBP). We present a case of postpartum convulsions which were temporally related to a caffeine infusion and an EBP.

Acetaminophen↗
PubMed1998

Determinants of mortality in elderly patients with heart failure: the role of angiotensin-converting enzyme inhibitors.

BACKGROUND: Despite randomized controlled trials demonstrating mortality reduction, many studies have documented persistent low rates of prescription of angiotensin-converting enzyme inhibitors (ACE-I) in patients with heart failures; the reasons for this pattern remain poorly defined. In addition, some authors have argued that the results of carefully controlled clinical trials do not translate well into the uncontrolled world of clinical practice, and the mortality benefits of ACE-I may not extend into special populations such as the elderly. OBJECTIVES: To understand the reasons for failure to prescribe ACE-I to Medicare patients with heart failure and to assess the impact of this failure on mortality. METHODS: We obtained data by reviewing charts of Medicare patients discharged from 7 Colorado hospitals with a diagnosis of heart failure during 1994. RESULTS: We identified a diagnosis of heart failure in 1016 patients without a contraindication to ACE-I. Three hundred seventy-eight of these patients were receiving ACE-I at the time of admission. Of the 638 remaining, 257 had their left ventricular systolic function assessed and 92 had diminished function. Of these 92, 50 (54.3%) were discharged on a regimen of ACE-I. The only significant difference in baseline comorbidity or demographic variables between those given and those not given ACE-I was that patients not prescribed ACE-I were older. Using multivariate analysis, younger age and cardiology consultation predicted ACE-I prescription (P = .02). By life-table analysis, mortality at 1 year following discharge from the index hospitalization was lower in those treated with ACE-I than in those not so treated (P = .03). The Deyo index of comorbidity, prescription of an ACE-I, site of treatment, and presence or absence of cardiology consultation were significantly associated with 1-year mortality by multivariate analysis (P<.001). CONCLUSIONS: Underinvestigation and undertreatment of chronic heart failure persists. Failure to treat elderly patients with ACE-I is associated with a mortality that appears to be greater than that seen in the placebo arms of large clinical trials of ACE-I therapy. Within the population studied, older patients are less likely to be treated. Failure of age to significantly add to prediction of mortality implies that the apparent bias against treating older patients with chronic heart failure with ACE-I is not justified. Because mortality is dependent on provider and site of treatment, further reductions in mortality from chronic heart failure may require intensive and selective local efforts, or development of regional heart failure centers.

Aged↗
PubMed1998

Severe hyperthermia during tetrabenazine therapy for tardive dyskinesia.

We recently observed a 45-year-old patient with a history of psychiatric illness who presented with severe hyperthermia (rectal temperature above 41 degrees C) with intense rhabdomyolysis and liver cytolysis during tetrabenazine therapy for neuroleptic tardive dyskinesia. In addition to tetrabenazine, this patient took lorazepam and two antidepressant drugs: clomipramine, a potent serotonin-reuptake inhibitor, and mianserin. Hyperthermia responded to parenteral sodium dantrolene and oral bromocriptine administration. The significant role of tetrabenazine (a central nervous system dopamine-depleting drug) and the contribution of antidepressants to the mechanism of this neuroleptic malignant syndrome - like hyperthermia are discussed.

Anti-Anxiety Agents↗
PubMed1998

Clinical spectrum associated with positive ANCA titres in 94 consecutive patients: is there a relation with PR-3 negative c-ANCA and hypergammaglobulinaemia?

OBJECTIVE: To calculate the positive predictive value (ppv) of cytoplasmic antineutrophil cytoplasmic antibodies (c-ANCAs) and anti-proteinase 3 (PR 3) antibodies for Wegener's granulomatosis (WG) and to evaluate their association with other diseases. METHODS: The clinical files of all 94 patients who had a positive c- or perinuclear (p)-ANCA test, or both, in the laboratory of the University Hospital, Leuven between April 1995 and March 1996 and who attended the Internal Medicine Department of the hospital were retrospectively studied. RESULTS: Of the 94 patients with ANCAs (fluorescence titre > or = 1/40), 57 were c-ANCA positive and 45 p-ANCA positive (eight were simultaneously c- and p-ANCA positive). Of the 57 c-ANCA positive patients, 23 had WG. The ppv for WG thus was 40%. This value did not increase by defining a higher threshold for a positive ANCA. There was not a good relation between ANCA titres and disease activity in the WG patients, nor was there a relation between anti-PR 3 antibody levels and WG disease activity. The ppv of anti-PR 3 antibodies for WG however was very high (85%). There was a positive correlation between the level of (hyper) gammaglobulinaemia and c-ANCA titres in those patients with final diagnoses not known to be associated with c-ANCA. Forty five patients had positive p-ANCAs. The largest group were those with inflammatory bowel disease (n = 20, of whom the majority had colitis ulcerosa or primary sclerosing cholangitis, or both); the great majority of these patients had no anti-myeloperoxidase antibodies. Vasculitis was present in eight patients, of whom two had WG (both were also c-ANCA positive). CONCLUSION: There is a low ppv of c-ANCAs for WG, caused by a high percentage of PR 3 negative, positive c-ANCA determinations, possibly related to hypergammaglobulinaemia. Anti-PR 3 antibodies have a high ppv for WG. However, neither c-ANCA titre, nor the level of anti-PR 3 antibodies correlated with the activity of the disease.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1997

Counterimmunoelectrophoresis with serum prediffusion: an improved method for the detection and identification of antibodies against extractable nuclear and cytoplasmic antigens.

In the technique of counterimmunoelectrophoresis (CIE) with serum prediffusion (SPD) serum is allowed to diffuse freely into the gel before pouring the antigenic extract in its trough (or wells) and starting the electrophoresis. Both the immunoprecipitations and the interactions with reference sera are strongly intensified by SPD, leading to higher sensitivity and specificity for the detection of anti-SSA/Ro, anti-SSB/La, anti-U1RNP, anti-Sm, anti-Jo1 and even anti-Scl-70 antibodies. We found that the optimal SPD time was 2 h. To evaluate the relevance of SPD for the clinical laboratory, 92 antinuclear antibody (ANA) positive sera were tested on CIE without SPD and with 2 h SPD in identification tests with SSA/Ro, SSB/La, Sm, U1RNP and Jo1 reference sera (rsa). The precipitation lines and their interactions were evaluated by three independent observers. It was observed that SPD considerably improved the efficiency of CIE for antibody identification. The mechanisms underlying the intensification of the precipitation lines by SPD are discussed as are the characteristics of the CIE in comparison with other test systems such as the enzyme linked immunosorbent assay (ELISA) and immunoblot.

Animals↗
PubMed1996

Human immunodeficiency virus in plasma and genital secretions during the menstrual cycle.

Six human immunodeficiency virus (HIV)-positive women were studied weekly over 8 weeks to detect HIV RNA in plasma and cervical secretions and proviral DNA in cervical, vaginal, and cervicovaginal lavage samples by polymerase chain reaction (PCR) amplification techniques. In cervical swab samples, cell-free HIV RNA was detected more frequently than cell-associated HIV proviral DNA (22/48 vs. 7/48, respectively). Cervical HIV RNA was consistently detected in 2 women with plasma HIV RNA > 100,000 copies/mL but was not detected in 2 women with plasma HIV RNA < 10,000 copies/mL, regardless of menstruation status. HIV-specific IgA was detected in the plasma of 2 women and in at least 1 cervicovaginal lavage sample from all 6 women. Thus, quantitation of cervical HIV RNA can be accomplished by PCR techniques and may be useful in evaluation genital viral shedding.

Adult↗
PubMed1996

Deficient nitric oxide responsible for reduced nerve blood flow in diabetic rats: effects of L-NAME, L-arginine, sodium nitroprusside and evening primrose oil.

1. This study examined the potential role of impaired nitric oxide production and response in the development of endoneurial ischaemia in experimental diabetes. Rats were anaesthetized (Na pentobarbitone 45 mg kg-1, diazepam 2 mg kg-1) for measurement of sciatic nerve laser Doppler flux and systemic arterial pressure. Drugs were administered into the sciatic endoneurium via a microinjector attached to a glass micropipette. 2. In two separate studies comparing diabetic rats (streptozotocin-induced; 8-10 wk duration) with controls, nerve Doppler flux in diabetic rats (Study 1, 116.6 +/- 40.4 and Study 2, 90.1 +/- 34.7 (s.d.) in arbitrary units) was about half that measured in controls (219.6 +/- 52.4 and 212.8 +/- 95.5 respectively; P < 0.005 for both). There were no significant differences between the two in systemic arterial pressure. 3. Inhibition of nitric oxide production by microinjection of 1 nmol L-NAME into the endoneurium halved flux in controls (to 126.3 +/- 41.3 in Study 1 and 102.1 +/- 38.9 in Study 2; both P < 0.001), with no significant effect in diabetic rats, indicating markedly diminished tonic nitric oxide production in the latter. D-NAME was without effect on nerve Doppler flux. 4. L-Arginine (100 nmol), injected after L-NAME, markedly increased flux in controls (by 65.8% (P < 0.03) and 97.8% (P < 0.01) in the two studies) and by proportionally similar amounts in diabetic rats [75.8% (P < 0.001) and 60.2% (P < 0.02)]. The nitro-donor, sodium nitroprusside (SNP; 10 nmol) had similar effects to L-arginine in both groups (increases of 66.0% in controls and 77.5% in diabetics; both P < 0.002). 5. A second diabetic group, treated with evening primrose oil performed exactly like control rats in respect of responses to L-NAME, L-arginine and SNP. 6. These findings implicate deficient nitric oxide in nerve ischaemia of diabetes and suggest correction thereof as a mechanism of action of evening primrose oil.

Animals↗
PubMed1995

Targeted delivery of nerve growth factor via fibronectin conduits assists nerve regeneration in control and diabetic rats.

This study examined the influence of fibronectin conduits joining two halves of a sectioned sciatic nerve, with and without preimpregnation with nerve growth factor, on regeneration in rats with streptozotocin-induced diabetes mellitus. Regeneration, measured morphometrically in fibres containing immunoreactivity to calcitonin gene-related peptide (CGRP) and GAP-43, was significantly less (P < 0.0001 for all comparisons) in diabetic rats with fibronectin mat grafts without nerve growth factor compared to similarly treated controls. Regeneration distances in diabetic rats were reduced to 43% (CGRP-reactive fibres) and 44% (GAP-43-reactive fibres) of controls, and the total amounts of immunoreactivities in the conduits were also reduced, though by lesser amounts (55 and 61% of controls respectively). Impregnation of the conduits with nerve growth factor before implantation increased the distance and amounts of regenerating immunoreactivity in both control and diabetic rats for both CGRP and GAP-43, such that these regeneration parameters were similar in nerve growth factor-treated diabetic rats to those in control rats implanted with untreated fibronectin mat conduits. These findings implicate impaired neurotrophic support in the defective regeneration characteristic of diabetic. neuropathy.

Animals↗
PubMed1994

Recognition of tyrosinase by tumor-infiltrating lymphocytes from a patient responding to immunotherapy.

The observation that allogeneic melanoma cells matched for particular HLA class I alleles stimulate T-cells isolated from patients suggests that widely shared antigens exist on these tumors. A transient expression system was developed for screening a melanoma complementary DNA library using the highly transfectable human kidney cell line 293. Using this system, large numbers of complementary DNA clones can be rapidly screened for the expression of antigens which stimulate T-cells. Tumor-infiltrating lymphocytes from patient 888, which recognized melanoma in the context of HLA-A24, were used to screen a complementary DNA library made from the autologous melanoma. Our results demonstrate that these tumor-infiltrating lymphocytes recognize tyrosinase, a gene previously shown to be recognized by T-cells only in the context of HLA-A2. These data demonstrate that a single antigen can be recognized in the context of two different class I HLA alleles. In addition, this study suggests that recognition of tyrosinase by antigen-specific T-cells may be involved in tumor rejection.

Antigens, Neoplasm↗
PubMed1994

After the intensive care nursery experience: families' perceptions of their well being.

This article describes family well being after a child's intensive care nursery experience. Thirty families of children who were graduates of intensive care nurseries participated in the study. Fifteen families of children with identifiable disabilities and 15 families of children with no identifiable disabilities were interviewed and completed standardized questionnaires. A comparison of family well being was done across three dimensions: the child's characteristics and caregiving needs, the family's support resources and needs, and the family's values and beliefs regarding their child's hospitalization and resulting special needs. Both groups of families had realized a renewed sense of meaning concerning family, children, and life itself due to their child's medical crises or disability. Families of children with disabilities, however, noted their financial concerns, burdens with their child's caregiving, and their difficulty in locating services for their child. These families' experiences underscore the need for a coordinated transition from the hospital to the community for the family and child.

Adult↗
PubMed1993

Recurrent meningococcal infections in a patient with congenital C5 deficiency.

A congenital C5 deficiency was the cause of recurrent meningococcal disease in a 27-year-old man. The lack of serum bactericidal activity accounts for the higher incidence and the different course of Neisseria infections in patients with a deficiency of the late complement components. Early antibiotic treatment and vaccination with a capsular polysaccharide meningococcal vaccine (A,C,Y,W-135) should be considered.

Adult↗