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G Mann

Publications and source records attributed to G Mann.

At least 37 records · Page 2Linked to original sources

Initial clinical and demographic predictors of swallowing impairment following acute stroke.

Swallowing impairment (dysphagia) is a frequent sequela of acute stroke; however, the ability to accurately detect dysphagia at the bedside and predict which patients may be at risk of dysphagic complications, such as aspiration, remains limited. Despite this, clinical assessment batteries continue to be the first point of assessment for acute dysphagia. We examined the predictive value of clinical factors suggestive of swallowing dysfunction in an attempt to identify the important independent clinical signs at initial presentation that are associated with dysphagia, aspiration, and the combined variable aspiration and/or penetration (ASPEN) in acute stroke patients. For the purposes of this study, dysphagia was defined as a disorder of bolus flow. Aspiration was defined as entry of swallowed material below the level of the true vocal cords which was not expectorated. The clinical items identified as independent predictors of dysphagia (measured radiographically) at initial presentation were age > 70 years, male gender, disabling stroke (Barthel score < 60), palatal weakness or asymmetry, incomplete oral clearance, and impaired pharyngeal response (cough/gurgle). The clinical predictors of aspiration (determined radiographically) at initial presentation were delayed oral transit and incomplete oral clearance. Incorporating clinical signs, such as those identified by this study, into clinical assessments of swallowing impairment may increase their predictive utility.

Acute Disease↗

High expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood acute lymphoblastic leukaemia.

Childhood acute lymphoblastic leukaemia (ALL) is a malignancy with the potential to infiltrate the liver, spleen, lymph nodes and brain. Such extramedullary presentation is important for understanding the biology of childhood ALL and also for developing new prognostic parameters. A potential mechanism in the trafficking of leukaemia cells is the interaction of the chemokine receptor CXCR4, which is expressed on ALL cells, and its ligand stromal cell-derived factor-1 (SDF-1), produced by stromal cells in bone marrow and extramedullary organs. Functionality of CXCR4 was demonstrated by a high correlation between cell surface density of CXCR4 and transendothelial migration of leukaemia blasts towards a gradient of SDF-1 (r = 0.73, P = 0.001). Inhibition of SDF-1-induced migration by an anti-CXCR4 monoclonal antibody (78.33 +/- 23.86% inhibition) evidenced the specificity of CXCR4 to SDF-1. In order to evaluate clinical significance of CXCR4 expression, lymphoblasts from the bone marrow of 73 patients with and without extramedullary organ infiltration were compared. Multiparameter flow cytometry revealed that lymphoblasts from patients with high extramedullary organ infiltration, defined as ultrasonographically measured enlargement of liver or spleen, expressed the CXCR4 receptor at higher fluorescence intensity (median 66.12 +/- 66.17) than patients without extramedullary organ infiltration (median 17.56 +/- 19.29; P < 0.001). Consequently, high expression of CXCR4 was strongly predictive for extramedullary organ involvement, independently of the peripheral lymphoblast count. Highest CXCR4 expression was seen in mature B ALL (median 102.74 +/- 92.13; P < 0.003), a disease characterized by a high incidence of extramedullary bulky disease. As high expression of the chemokine receptor CXCR4 predicts extramedullary organ infiltration in childhood ALL, we suggest that CXCR4 and its ligand play an essential role in extramedullary invasion.

Antibodies, Monoclonal↗

Collapsing the tibial bone tunnel in hamstring autograft reconstruction of the anterior cruciate ligament.

The use of double staples is an accepted method for fixation of hamstring anterior cruciate ligament (ACL) grafts at the distal tibial site. In the last year, we have modified the 2-staple technique that we have been using for distal tibial fixation of our double loop hamstring ACL autografts. Previously, we had impacted the graft with 2 toothed staples onto the cortex distal to the opening of the tibial tunnel. The modification we report here involves driving the proximal staple into the tibial tunnel roof, thus collapsing the tunnel onto the tendon during fixation. The distal staple is introduced in the usual manner. Clinical follow-up including subjective and objective KT-1000 arthrometry has indicated no difference in the early results compared with the former staple technique. Radiologic follow-up showed tunnel obliteration and filling in the area of the proximal staple, suggesting early graft incorporation in callus. While early results are encouraging, long-term follow-up and pullout studies will be reported. It would appear that collapsing the bony tunnel by the proximal staple may be a simple method of providing fracture callus to increase the stiffness of the tibial graft fixation, with no major or minor complications. Animal experiments are being carried out to objectively define the mechanical advantage of the graft incorporation by callus.

Animals↗

And the sun keeps shining.

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Antineoplastic Combined Chemotherapy Protocols↗

[Vaccinations in sports and recommendations for immunization against flu, hepatitis A and hepatitis B].

Intensive physical training in elite athletes can have an adverse effect on the immune system, and can increase the susceptibility to infectious diseases. The insult to the immune system includes the cellular, humoral and phagocitic pathways. The increased incidence of viral infections (in particularly of the upper respiratory tract) occurs mainly during periods of intense exercise training and competitions due to the combination of physiological and psychological stress. Other factors that may contribute to the decreased immunity and increased susceptibility to infections include eating disorders and nutritional deficiencies, jet lag, sleep deprivation, and lack of proper hygiene in shared food and sleeping quarters. For elite athletes, even a mild viral infection can be devastating due to loss of important training hours and/or compromise of competitive performance. Therefore, in addition to the goal of improving the athletes performance, another important responsibility/obligation of the staff working with athletes (physicians, nutritionists, physiotherapists, and psychologists), is to emphasize preventive medicine and maintenance of good health. In this article we define athletes, and especially elite athletes, as a population at risk of various infections, and recommend immunization against hepatitis A and B and a yearly immunization against influenza.

Hepatitis A↗

Modeling protein-small molecule interactions: structure and thermodynamics of noble gases binding in a cavity in mutant phage T4 lysozyme L99A.

The complexes of phage T4 lysozyme L99A with noble gases have been studied by molecular dynamics simulation. In a long simulation of the complex with one Xe atom, the structure was found to undergo global conformation change involving a reversible opening and closing of the entrance to the substrate-binding site, during which the conformations of the N and C-terminal domains varied little. The distributions of Xe positions sampled in dynamics simulations were refined in terms of anisotropic Gaussian distributions via least-squares minimization of the difference between Fourier transforms. In addition, molecular transformation simulations have been applied in order to calculate the binding free energies of Xe, Kr and Ar relative to a standard state at a pressure of 1 bar. A single bound Xe is found to assume an equilibrium distribution over three adjacent preferred sites, while in a two-Xe complex, the two Xe atoms preferentially occupy two of these. The positions of the three sites agree closely with the positions of bound Xe determined in the refined crystal structure of a complex formed at a pressure of 8 bar Xe, and the calculated affinities agree well with the observed partial occupancies. At a pressure of 8 bar, a mixture of one-Xe and two-Xe complexes is present, and similarly for complexes with Kr and Ar, with single occupancy relatively more prevalent with Kr and Ar. (Binding of a third Xe atom is found to be quite unfavorable.) A comparison with simulation results for the binding of benzene to the same site leads to the conclusion that binding of Xe within cavities in proteins is common because of several favorable factors: (1) Xe has a large atomic polarizability; (2) Xe can be applied at a relatively high pressure, i.e. high chemical potential; (3) an unfavorable entropic term related to the need to orient the ligand in the binding site is absent. Finally, it is found that the model's binding energy of a water molecule in the cavity is insufficient to overcome the unfavorable binding entropy.

Amino Acid Substitution↗

Precursor B-cell lymphoblastic lymphoma in childhood and adolescence: clinical features, treatment, and results in trials NHL-BFM 86 and 90.

BACKGROUND: Precursor B-cell lymphoblastic lymphoma (PBLL) is a rare subtype of childhood non-Hodgkin lymphoma (NHL). The purpose of our study was to investigate frequency and clinicopathological features of PBLL in children and to test prospectively the efficacy of an ALL-type therapy for treatment of these patients. PROCEDURE: From October, 1986, to March, 1995, 1,075 patients up to 18 years of age suffering from all kinds of NHL were registered in the two consecutive multicenter studies NHL-BFM 86 and 90. Of these, 27 patients were diagnosed with PBLL. Twenty-one PBLL patients were treated according to a BFM-ALL-type protocol: an eight-drug induction over 9 weeks was followed by an 8-week consolidation including methotrexate 5 g/m(2) x4. Patients in stages I and II continued with maintenance up to a total therapy duration of 24 months, whereas patients in stages III and IV received an additional eight-drug intensification and cranial radiotherapy (12 Gy for prophylaxis) after consolidation. Six PBLL patients were treated according to the BFM-protocol for B-NHL, stratified according to stage and tumor load and consisiting of two to six 5-day courses of chemotherapy. RESULTS: The median age of the 27 patients with PBLL (18 boys, 9 girls) was 6.2 (range 0.7-15) years. Stages (St. Jude) were: I (n = 3), II (n = 7), III (n = 9), and IV (n = 8). Twenty-one PBLL patients had nodal disease, 6 patients had subcutaneous manifestations, and 8 patients had bone marrow disease (<25% blasts). All patients achieved remission. With a median follow-up time of 4. 25 years, the estimated probability for event-free survival (pEFS) at 10 years for the total group was 0.73 (SE 0.10). Five patients (2, 1, 1, and 1 patients at stages I, II, III, and IV, respectively) relapsed: 2 of 21 patients who were treated according to the ALL strategy and 3 of 6 who were treated according to the B-NHL-protocol. CONCLUSIONS: PBLL accounts for 2.5% of childhood NHL. An ALL-type therapy strategy appears to be superior to a short-pulse B-NHL protocol.

Adolescent↗

Allogeneic bone marrow transplantation for juvenile myelomonocytic leukaemia: a single centre experience and review of the literature.

Juvenile myelomonocytic leukaemia (JMML) is a rare paediatric disease and allogeneic stem cell transplantation is the only curative approach. The roles of pretransplant treatment, conditioning regimen and graft-versus-host disease (GVHD) are still unclear. Eleven children with JMML underwent allogeneic BMT in our institution. Donors were matched unrelated (n = 6) matched siblings (n = 4) and one mismatch family donor. Transplant-related mortality (TRM) was 36%. Three patients relapsed after transplantation. Two of three patients with relapse are in continuous remission after donor lymphocyte infusion or second BMT, respectively. To evaluate the role of pretransplant treatment, conditioning regimen and GVHD, we have summarised our series with other published single centre reports and give an overview on a total of 65 patients with JMML who underwent allogeneic BMT. No significant correlation between pretransplant treatment, conditioning regimen and TRM could be observed. Overall relapse rate is high (47%). TBI is associated with a significantly higher relapse rate (P = 0.012). Other conditioning modalities, intensive chemotherapy and splenectomy prior to stem cell transplantation do not seem to have a significant impact on relapse rate. Patients with or without GVHD showed no significant difference in relapse rate (58% vs 45%). In the event of relapse after transplantation withdrawal of immunosuppression, donor lymphocyte infusion or second transplant was successful in 6/11 patients. Graft-versus-leukaemia effect seems to play an essential role in bone marrow transplantation for JMML.

Antineoplastic Combined Chemotherapy Protocols↗

Expression of tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors and sensitivity to TRAIL-induced apoptosis in primary B-cell acute lymphoblastic leukaemia cells.

Because tumour necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) (Apo2 ligand) preferentially kills malignant cells while sparing normal cells, it may be therapeutically useful against cancers, including those of haematopoietic origin. Although the activity of TRAIL has been studied in tumour cell lines and in a limited number of different primary tumours, its overall activity in a large number of uniform cases of primary tumours is not known. We therefore studied the activity of TRAIL in 29 primary precursor B-cell acute lymphoblastic leukaemia (ALL) samples. TRAIL was found to have a modest activity as it killed a maximum of 29% of ALL cells within 18 h compared with killing 75% of Jurkat cells. The sensitivity to TRAIL did not correlate with the pattern of TRAIL receptor expression or FLIP expression, as determined by Western blot analysis. The CD40 receptor, which can transduce survival signals in mature malignant B cells, was less frequently expressed on ALL cells, but incubation with an exogenous soluble CD40 ligand trimer did not rescue them from spontaneous apoptosis and did not mediate their resistance to TRAIL. Further, although ALL cells expressed TRAIL protein, they failed to kill target Jurkat cells in a TRAIL-dependent manner. Our data delineate major biological differences between mature and precursor malignant B cells and suggest a limited therapeutic role for TRAIL as a single agent in primary B-cell ALL.

Adolescent↗

Spondylolysis as a cause of low back pain in swimmers.

Low back pain (LBP) has recently become a common complaint in swimmers. The differential diagnosis of LBP in swimmers includes muscle and ligament sprains, Scheuerman disease, herniated disc, facet joint injury, tumors, infections, and spondylolysis. Although spondylolysis or listhesis is a frequent injury in the athlete, mainly in weightlifters, wrestlers, gymnasts, divers and ballet dancers, it is infrequently reported in swimmers. We have recently encountered four adolescent elite swimmers who complained of low back pain and were diagnosed as having spondylolysis. Three of the patients were either breast-strokers or butterfly swimmers. Plain radiography demonstrated the lesion in two patients. Increased uptake in bone scan was noted in all patients. CT was performed only in two patients and revealed the lesion in both. One patient was diagnosed within two weeks, and the diagnosis in the others was deferred for 2-7 months. The patients were treated successfully by reducing the intensity of their training program and the use of a corset for at least three months. Repeated hyperextension is one of the mechanisms for spondylolysis in athletes as is the case in breast-strokers and butterfly style swimmers. LBP in swimmers should raise the suspicion of spondylolysis. Plain radiography and bone scan should be performed followed by SPEC views, CT, or MRI as indicated. If the case is of acute onset as verified by bone scan, a Boston or similar brace should be used for 3 to 6 months in conjunction with activity modification and optional physical therapy. Multidisciplinary awareness of low back pain in swimmers, which includes trainers, sport medicine physicians, and physical therapists, should lead to early diagnosis and appropriate treatment.

Adolescent↗

[Seroconversion study of Biken CAM-70 measles vaccine formulations].

OBJECTIVES: To compare seroconversion rates induced by Biken CAM-70 measles vaccines at different viral concentrations. METHODS: Healthy children aged 9 to 18 months from a primary health care unit in Rio de Janeiro, Brazil, and whose guardians agreed with their participation, were randomly assigned to receive one of the following vaccine formulations: 5,000, 1,000 or 200 CCID50 (50% Tissue Culture Infective Dose). The research team, participants, and data analysts were blinded to the type of vaccine administered. Pre- and post-vaccination antibody levels were assessed through Plaque Reduction Neutralization Test. Two interim data analyses were planned to assess unequivocal evidence of the superiority of one of the vaccine types. RESULTS: From 223 recruited children, 84% completed the whole course. Of them, 79% were less than 10 months of age, and 93% did not show detectable measles antibodies in pre-vaccination serum. Seroconversion (four-fold increase in antibody levels) in groups vaccinated with 5,000, 1,000 or 200 CCID50, were 82%, 55%, and 37% (p<0.0000), respectively. Differences in the mean concentration of post-vaccination antibodies were also substantial and statistically significant (p<0.000). Seroconversion rates (pooling data from all vaccine formulations) were 73% to children aged 10 months or more, and 53% in those below 10 months. CONCLUSIONS: Vaccines with concentrations below 5,000 CCID50 did not produce satisfactory seroconversion rates. The vaccine performance by age was consistent with that seen in other studies using Biken CAM-70 strain in which a sizable proportion of 9-month-old children failed to achieve full immunological response.

Analysis of Variance↗

A telemedical approach to the screening of diabetic retinopathy: digital fundus photography.

OBJECTIVE: The importance of screening for diabetic retinopathy has been established, but the best method for screening has not yet been determined. We report on a trial of assessment of digital photographs by telemedicine compared with standard retinal photographs of the same fields and clinical examination by ophthalmologists. RESEARCH DESIGN AND METHODS: A total of 129 diabetic inpatients were screened for diabetic retinopathy by slit-lamp biomicroscopy performed by an ophthalmologist and by two-field 50 degrees non-stereo digital fundus photographs assessed by six screening centers that received the images by electronic mail. Conventional 35-mm transparencies of the same fields as the digital photographs were assessed by a retinal specialist and served as the reference method for detection of diabetic retinopathy. Slit-lamp biomicroscopy was the reference method for the detection of macular edema. RESULTS: The prevalence of any form of diabetic retinopathy was 30% (n = 35); of sight-threatening retinopathy including macular edema, the prevalence was 6% (n = 7). The assessment of digital images by the six screening centers resulted in a median sensitivity of 85% and a median specificity of 90% for the detection of moderate nonproliferative or sight-threatening diabetic retinopathy. Clinically significant macular edema (n = 4) was correctly identified in 15 of the 24 grading reports. An additional seven reports referred the patients for further investigation because of concurrent diabetic retinopathy. CONCLUSIONS: Telescreening for diabetic retinopathy by an assessment of two-field 50 degrees non-stereo digital images is a valid screening method. Although detection of clinically significant macular edema using biomicroscopy is superior to digital or standard non-stereo photographs, only few patients with sight-threatening diabetic retinopathy are missed.

Computer Communication Networks↗

Detection of residual disease in pediatric B-cell precursor acute lymphoblastic leukemia by comparative phenotype mapping: method and significance.

The present review summarizes our efforts in developing a novel immunologic approach ("Comparative Phenotype Mapping") targeted at assessing minimal residual disease (MRD) in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) patients. The method relies on quantitatively aberrant, leukemia-associated antigen expression patterns which allow to discriminate leukemic from normal BCP using a limited panel of antibody combinations and multidimensional flow cytometry. In an analysis of 63 follow up bone marrow samples of patients with BCP-ALL we show that this approach enables to efficiently detect MRD. Further clinical observation revealed that the patients which were MRD-positive by flow cytometry (although in morphological remission) had a very high probability of early disease recurrence compared to the good chances of a relapse-free survival (RFS) in the MRD-negative cohort (RFS 0.0 vs. 0.76 at 3 years). Comparative Phenotype Mapping thus proves to be a reliable method for MRD detection in BCP-ALL. Concluding remarks relate to the optional applications of the method as well as to future perspectives. An ongoing large prospective study which we are now conducting on the basis of Comparative Phenotype Mapping will clarify the clinical significance of MRD detection in ALL patients by this method, and will determine its value compared to related as well as molecular-genetic techniques.

Adolescent↗