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Biomedical subjects

R Du Bois

Publications and source records attributed to R Du Bois.

At least 19 recordsLinked to original sources
PubMed2005

Clinical response to morphine in cancer patients and genetic variation in candidate genes.

Morphine is the analgesic of choice for moderate to severe cancer pain; however, 10-30% of patients do not tolerate morphine. This study evaluated genetic variation in the mu-opioid receptor, betaarrestin2, stat6 and uridine diphosphate-glucuronysltransferase 2B7 (UGT2B7) genes, in patients who responded to morphine vs those who were switched to alternative opioids. We prospectively recruited and genotyped 162 Caucasian patients (117 controls, 39 switchers). Switchers, were more likely to carry the common allele at 1182 G/A, 5864 G/A, 8622T/C and 11143 G/A in the betaarrestin2 gene (P = 0.021, 0.043, 0.013, 0.043, respectively). Switchers had increased carriage of the T allele (-1714 C/T) and a significant difference in the allelic frequency at 9065 C/T (chi(2) = 3.86, P = 0.049) in the stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in the mu-opioid receptor gene or UGT2B7 gene. This study presents novel data suggesting that variation in genes involved in mu-opioid receptor signalling influence clinical response to morphine.

Alleles↗
PubMed2000

CC chemokine receptor gene polymorphisms in Czech patients with pulmonary sarcoidosis.

Genes for the chemokine receptors CCR5 and CCR2 are characterized by polymorphisms resulting in a nonfunctional receptor expression. Ligands for CCR2 and CCR5 (chemokines monocyte chemotactic protein-1 [MCP-1] and RANTES) are implicated in the pathogenesis of sarcoidosis. We have, therefore, analyzed polymorphisms of CCR5 (32-bp deletion in CCR5 gene [Delta32]) and of CCR2 (replacement of valine by isoleucine in CCR2 gene [64I]) in 66 Czech patients with sarcoidosis in comparison with a representative sample of Czech normal population. The frequencies of CCR5Delta32 and CCR2-64I polymorphisms in patients with sarcoidosis were different from that in control subjects. CCR5Delta32 allelic frequency was significantly increased in patients. By contrast, the CCR2-64I allele was more frequent in control subjects; however, the difference did not attain significance. Interestingly, the CCR5Delta32 allele was associated with clinically more apparent disease: it was present in 39.1% of patients requiring corticosteroids but only in 16.7% patients who did not need therapeutic intervention (odds ratio [OR] = 2.9). When patients requiring corticosteroids were compared with control subjects, the differences in the CCR5Delta32 frequencies were enhanced (p < 0.01). In conclusion, the observed association of CCR5Delta32 and CCR2-64I with sarcoidosis implicates a role for these polymorphisms in disease susceptibility and protection.

Adolescent↗
PubMed1998

HLA associations in three mutually exclusive autoantibody subgroups in UK systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by the presence of autoantibodies, mostly IgG, which target a limited set of nuclear proteins. These antinuclear antibodies (ANA) associate with disease subgroups and specific organ involvement. Here we show that there is mutual exclusivity of individual ANA in 130 UK SSc patients, confirm clinical associations with antibody profile and extend the analysis to include genetic data. The ANA mutual exclusivity observed leads to the possibility that SSc, in these patients, is in fact three separate diseases. An alternative explanation for exclusivity relates to the fact that optimal production of IgG antibody requires T-cell help, a process restricted by the HLA class II presentation of antigen peptide. If each autoantibody has a different and tight MHC restriction, then there is a possibility that these groups arose from a common pathway and were modified by genetics into the mutually exclusive groups observed, making the separate disease theory less tenable. In order to answer this question, we have determined MHC class II restriction precisely using high-resolution HLA genotyping (SSP) coupled with an amino acid analysis program in our 130 UK SSc patients. DRB1*11 was associated with anti-topoisomerase-I antibody (ATA)-positive patients (P = 0.007) and when combined with ATA (RR = 15.82), dcSSc (RR = 11.45), or both (RR = 21.9), represented the strongest risk factor for pulmonary fibrosis. Patients with antibodies to RNA polymerases I, II and III were associated with DQB1*0201. At the amino acid level, 20 positions in DRB1 and 20 positions in DQB1 showed some significant correlation with an ANA group. Clearly, however, the linkages to MHC class II alleles are not nearly strong enough to explain the mutually exclusive nature of the autoantibody groups and our results support, but do not prove, the separate disease theory.

Antibodies, Antinuclear↗
PubMed1995

Reactive pulmonary lymphoid disorders.

The two main reactive pulmonary lymphoid disorders are lymphoid interstitial pneumonia and follicular bronchitis/bronchiolitis, both pathological entities with a variety of aetiologies. We reviewed the morphological and immunohistochemical features of 26 cases with one or other of these two diagnoses, to explore the possibility that they represented overlapping patterns of hyperplasia of the bronchopulmonary immune system. The polymerase chain reaction was used to determine the clonality of the infiltrates. Histologically, there was a spectrum of changes with two main components. An interstitial infiltrate of mainly T lymphocytes, plasma cells and histiocytes predominated in lymphoid interstitial pneumonia, whilst lymphoid follicles predominated around airways in follicular bronchitis/bronchiolitis. Classification of the disorder rested on which component the pathologists believed to be dominant. In two cases, histology and immunohistochemistry suggested lymphoma, and in one of these cases this diagnosis was confirmed by the polymerase chain reaction. One case of lymphoid interstitial pneumonia produced three bands. The remainder produced polyclonal patterns when samples were adequate. Clinically, there was no clear difference between patients with the two disorders, or patients with pathological features of both.

Adolescent↗
PubMed1993

L-arginine infusion has no effect on systemic haemodynamics in normal volunteers, or systemic and pulmonary haemodynamics in patients with elevated pulmonary vascular resistance.

1. The evidence that the infusion of L-arginine, the precursor of endothelium-derived relaxing factor (EDRF)/nitric oxide (NO), may reduce systemic blood pressure, via the generation of intracellular cyclic guanosine-3,5-monophosphate(cGMP), in normotensive volunteers is controversial. In the first part of the study we investigated the effect of an L-arginine infusion on systemic blood pressure and plasma cGMP in healthy volunteers. 2. Patients with systemic sclerosis have widespread endothelial damage which, by reducing the release of NO, could contribute to the raised pulmonary vascular resistance (PVR) often found in this condition. We hypothesised that if there were a failure of NO synthesis this might be overcome by infusing L-arginine into the pulmonary artery, thereby lowering PVR. In the second part of the study we investigated the effect of L-arginine infusion on systemic and pulmonary haemodynamics, and on plasma cGMP levels in patients with pulmonary hypertension and systemic sclerosis. 3. L-arginine (500 mg kg-1) was infused over 30 min into five normotensive volunteers and five patients with systemic sclerosis and pulmonary hypertension. Blood pressure, heart rate and skin temperature were measured non-invasively in the volunteers and systemic and pulmonary haemodynamics recorded via radial artery cannulae and balloon-tipped, flow directed, pulmonary artery catheters in the patients with systemic sclerosis. 4. L-arginine had no significant effect on blood pressure, heart rate or skin temperature in the normotensive volunteers nor on systemic or pulmonary haemodynamics in the systemic sclerotic group. Cyclic-GMP levels did not significantly change in either group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Problems in the daily management of delusional and hallucinogenic experiences in juvenile schizophrenic patients--experiences with long-term inpatient psychotherapy].

A retrospective personal case study of 43 long-term in-patient treatments of adolescents suffering from first onset schizophrenia with a prolonged course is introduced. 5 criteria were selected combining psychopathological aspects and typical problems of everyday therapeutic management--one criterium being the occurrence of hallucinations and delusions. Only less than half the patients (n = 19), however, suffered from delusions to such a degree that repercussions and consequences on the course and kind of treatment were noticeable. This fact pointed to peculiarities of juvenile schizophrenia in comparison with adult schizophrenia, in which paranoid and hallucinatory phenomena are more prominent, consistent and elaborated. 4 types of delusional and hallucinatory experience with certain ensuing therapeutic reactions are distinguished: Type 1: pseudonormality and denial of delusions, type 2: overlapping of reality and delusion and frantic attempts to separate the two realms, type 3: hallucinatory absorption and trance-like states, type 4: dramatic delusional play and "happy" hallucinations in regressive psychoses. Theories about the perception of reality during the cognitive development in childhood and about altered states of consciousness are discussed and related to different therapeutic approaches.

Adolescent↗
PubMed1985

[X-ray computed tomography in fractures of the acetabulum].

Radiographic assessment of these fractures remains difficult. Conventional techniques according to Letournel show the lesions but not to the best advantage, for instance the "congruency" of femoral head with acetabulum. 54 CT scan were performed (1982-1984) every time a doubt was persisting. Incarcerations of fragments, impactions of the acetabulum, sacro-iliac joint disjunctions, congruency and lesions of femoral head are much better seen with scanner. In planing the surgical therapy (or orthopedic), CT scan add a great deal to the information and dramatically improves the results.

Acetabulum↗
PubMed1982

Identification of human CML target. HLA-B locus (B12) antigen variants defined by CTL generated between B locus-identical (B12) responder-stimulator pairs.

The genetics of human CML targets were studied by seven CTL generated in combinations iun which the responder/stimulator difference was limited to one (or two) HLA-A, -B, or -C antigens. Unstimulated peripheral blood lymphocytes were used as targets. CTL sensitized against antigens A11, Aw31, or B17 lysed all cells bearing the respective target from a large panel of cells from unrelated individuals. Hence, at least one CTL clone was directed against the HLA antigen molecule. However, all CTL also exerted cross-kill to cells not sharing the stimulating HLA antigen. For two CTL, the target of the cross-kill was not clarified. Five CTL were found where the cross-kill was directed against antigen HLA-B12 (Bw44 and Bw45). All these cTL were generated in R/S pairs identical for B locus antigens (Bw44/Bw35 heterozygotes). The individual CTL lysed different parts of the panel of B12-positive target cells. The interpretation is that these CTL detect subtypes of HLA antigens, but alternative possibilities are also considered. Four B12 subtypes are described, tentatively designated as B12-related CML targets. Identification of HLA-B-related CML targets represent CML "typing" of HLA-antigen differences that were not detected serologically. The subtypes can now be tested for their possible functional significance.

B-Lymphocytes↗
PubMed1982

[The barbarism of the body].

The body appears as a place of wordless experience. Between this anonymous feeling and the subject takes place the difficult barrier of language and alterity. This barbaric body, somewhere between autopsy and psychoanalysis, neither lesion nor neurosis, is on all sides in danger of being managed: from an organical point of view managed as a lesion; from a psychological point of view undergoing other sense-making discourses.

Attitude to Health↗
PubMed1976

Permeability of artificial membranes to a pluridisperse solution of 125I-polyvinylpyrrolidone.

The validity of the transport equation for uncharged macromolecules across a porous membrane developed by Verniory et al. (1973, J. Gen. Physiol. 62:489) has been tested on several types of artificial membranes (Amicon PM-30, XM-50, and XM-100 Diaflo ultrafilters) using a pluridisperse solution of polyvinylpyrrolidone as filtrand. The influence of the filtration pressure on the shape of the sieving curve predicted by the theory has been verified. A mean pore radius and the width of the pore demonstrated that the method used previously to determine the effective filtration pressure in the glomerulus from sieving data is valid. The transport equation previously proposed by Renkin (1954, J. Gen. Physiol. 38:225) gives results that are less consistent than those obtained with the new transport equation.

Iodine Radioisotopes↗
PubMed1975

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. II. A physiological study in the normal dog.

The two theoretical models proposed previously to calculate the intracapillary and transcapillary glomerular pressure gradients from the sieving of macromolecules such as PVP have been used to analyse in 22 normotensive dogs the sieving curve relating the sieving coefficients, phi, to molecular size (phi: glomerular clearance of PVP fractions/GFR). Neither the "local c2" model-filtrate unmixed at the outer face of the capillaries walls--nor the constant c2 model-filtrate well mixed--allowed to obtain realistic values for the hemodynamical parameters. Indeed with the local c2 model, the best fit between calculated and experimental sieving curves could be obtained only by reversing the intracapillary pressure gradient; conversely the constant c2 model obliged to decrease the intracapillary pressure so abruptly along the capillaries, that retrofiltration took place in the distal parts of the vessels. This difficulty has been overcome by combining the two models; the so-called "hybrid model" considers that the filtrate is well mixed in the vicinity of the urinary pole only. The following results were obtained: 1. PGCa and PGCe (intracapillary pressures at the afferent and efferent extremities of the capillaries) equal to 49.7 +/- 1.03 and 41.8 +/- 1.00 mm Hg respectively. 2. Pressure equilibrium is generally reached at the efferent extremity of the vessels. 3. The slope of PGC (see article) varies inversely to FF. (filtration fraction). 4. The model, however, does not allow to rule out the possibility of retrofiltration.

Animals↗
PubMed1975

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. I. A mathematical model.

Determination of glomerular intracapillary and transcapillary pressure gradients from sieving data. A biomathematical model is described to calculate the intracapillary and transcapillary glomerular pressure gradients from the sieving coefficients (phi: fractional clearances/GFR) of macromolecules such as polyvinylpyrrolidone (PVP). Two differential equations have been developed. The first one calculates local values for GFR in terms of local values for PGC (intracapillary hydrostatic pressure) and pi (oncotic pressure). The second equation calculates the clearance of PVP equimolecular fractions, the sieving equations previously described (24) being used to derive the concentrations of PVP in the filtrate (c2). Two variants of the second equation have been considered, assuming the filtrate in contact with the membrane either "well stirred" or "unstirred" (constant c2 and local c2 gradient models respectively). Computer simulations have been used to illustrate how the sieving curve is modified when the five parameters on which depends the shape of the curve are changed one by one. The sieving curve relates phi to a(s) (hydrodynamically equivalent molecular radius). The determining parameters are: GFP, the mean effective glomerular filtration pressure, epsilon, the slope of the intracapillary pressure, FF, the filtration fraction, Cp0, the protein concentration in arterial plasma and r, the pore radius which is the only structural parameter involved when one assumes the glomerular membrane crossed by cylindrical pores of uniform size and length. The shape of the sieving curve is modified significantly enough by changing GFP, FF and r within reasonable limits, to make it possible to derive GFP and r from experimental sieving data for macromolecules such as PVP or dextrans.

Capillaries↗
PubMed1975

A model for sieving of macromolecules by the glomerular membrane of the kidney.

The transport of water and of macromolecules across the glomerular membrane of the kidney depends on the membrane parameters (radius, length and number of pores) as well as on the hydrostatic and oncotic pressures on either side of the membrane. The filtration pressure decreases along the capillary loops from afferent to efferent end. Water and solute flows are thus given by a system of two differential equations. The sieving coefficient of the macromolecules is the ratio of solute to water flow. In the program described the differential equations are solved by the Runge-Kutta method (fourth order). Rosenbrock's method of minimization is used to adjust the theoretical to the experimental sieving coefficients. The pore radius, total pore area per unit of path length and conductance of the membrane, as well as the intracapillary hydrostatic pressure and its gradient can thus be determined.

Biological Transport↗