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Biomedical subjects

P Philippe

Publications and source records attributed to P Philippe.

At least 37 records · Page 2Linked to original sources

The scale-invariant spatial clustering of leukemia in San Francisco.

This study tests the hypothesis of scale-invariant self-similar clustering of childhood leukemia cases over the San Francisco spatial area. The spatial distribution of leukemia cases has been investigated over seven scales of observation. A power-law relation of the variance to the mean of aggregates (quadrats) was used to detect possible scale-invariant self-similar clustering. The spatial distribution of leukemia cases (incidence from 1946 to 1964) was well fitted by a power-law function. The follow-up of clustering from the first years of case notification (1946) confirmed a scale-invariant self-similar spatial pattern with a stable power-law slope from 1952 onward. This pattern was shown to pertain specifically to school-age leukemia cases. Younger cases had a random distributional pattern over space. Observation and simulations of the distributional patterns revealed memory-keeping of historical (the pre-1953 era) fractal-like conditions. Based on a comparison of the leukemia fractal dimension with that of the city residential data, it is speculated that the current scale-invariant self-similar spatial clustering of the leukemia cases reflects the onset of the historical fractal patterning of the city residences at a particular time point in the past.

Child↗

[Causal research epistemology and epidemiology of complex systems].

Epidemiology now meets with the crisis of its most fundamental paradigm. The biomedical paradigm of the search for individual-level disease risk factors opposes the public-health paradigm of the search for contextual-level disease risk factors. The public-health paradigm exacerbates the causal research of disease risk factors in that it must now count on a hierarchy of scales of observation. This underlines the need to take into account nonlinear relationships among scales and variables as well as the dynamic aspect of the phenomena. It is concluded that the complex conceptualization required by the public-health paradigm will entail epidemiologists to develop new theories and to familiarize themselves with approaches more akin to those used in the study of complex systems.

Causality↗

Electrophoretic analyses in a case of monoclonal gamma chain disease.

Abnormal low molecular weight immunoglobulin heavy chain can be detected in serum samples from patients with heavy chain disease. In this paper, we report the characterization of a gamma heavy chain in a patient suffering from a lymphoplasmocytic disorder, using immunofixation analysis and two-dimensional polyacrylamide gel electrophoresis. We demonstrate that the combination of serum protein agarose electrophoresis and two-dimensional electrophoresis (three-dimensional electrophoresis) can be used to further characterize abnormal protein bands detected by immunofixation.

Electrophoresis, Gel, Two-Dimensional↗

[Splenic abscess caused by Coxiella burnetti in the absence of endocarditis].

INTRODUCTION: The most frequent clinical expression of chronic Q fever is culture-negative endocarditis. Other localizations are rare. EXEGESIS: We report a documented case of chronic Q fever that occurred in a 47-year-old immunocompetent man and was associated with spleen abscess, in the absence of detectable endocarditis. The spleen abscess was a complication of either a preexisting cyst or a calcified hematoma. Splenic infection with Coxiella burnetii was documented with cultures, polymerase chain reaction and immunohistochemistry. The outcome was favorable after splenectomy and a 21-month antibiotherapy. CONCLUSION: Chronic Q fever may develop in the absence of endocarditis, when a preexisting vascular lesion such as aortic aneurysm exists. A splenic cyst may have played a similar role for this patient.

Abscess↗

Nonlinearity in the epidemiology of complex health and disease processes.

The challenges posed by chronic illness have pointed out to epidemiologists the multifactorial complex nature of disease causality. This notion has been referred to as a web of causality. This web extends theoretically beyond risk markers. It includes determinants of emergence/non-emergence of disease. This web of determinants is a form of complex system. Due to its complexity, the determinants within such system are not linked to each others in a linear, predictable manner only. Predictability is possible only on a short-term basis, and unpredictability sets in over the long run. Understanding such a system of determinants calls for articulation and testing of complex models which synthesize our knowledge of multiple determinants at many scales, both biological and otherwise. Given the complexity of this web and existing knowledge about the nonlinearity of such systems, the following question is posed: Can the challenge of studying causality be adequately addressed if emphasis continues to be placed on using tools and methods that are geared towards looking at such system from a linear paradigm? Or is it time to add to the epidemiologic research agenda the notion of nonlinearity and its relevant form of analytical approaches that are being tested in other disciplines? Furthermore, the question posed here applies as well to the study of determinants of health. Addressing determinants of heath adds further complexity to our task.

Causality↗

Interphase cytogenetics and competitive RT-PCR for residual disease monitoring in patients with chronic myeloid leukaemia during interferon-alpha therapy.

There is a need for fast and sensitive methods to evaluate the response of patients with chronic myeloid leukaemia (CML) to interferon-alpha (IFN-alpha) therapy to complement cytogenetic analysis of Philadelphia (Ph) chromosome-positive metaphases. We have used interphase FISH (fluorescence in situ hybridization) and competitive RT-PCR (reverse transcriptase-polymerase chain reaction) techniques for detection of BCR-ABL-positive cells to measure suppression of leukaemic clone in a series of 51 follow-up samples from 24 CML patients undergoing IFN-alpha treatment. Interphase FISH analysis of the malignant clone in bone marrow using BCR and ABL probes was found to be highly correlated to conventional G-banding metaphase examination (r = 0.98). RT-PCR quantification of BCR-ABL mRNA transcripts in blood also showed a high degree of concordance with the proportion of Ph-positive metaphases (r = 0.93). In addition, the degree of cytogenetic response did not influence the equivalence between karyotype analysis and molecular methods. We concluded that interphase FISH and competitive RT-PCR provide reliable information on residual tumour burden and response to IFN-alpha in CML patients. These molecular methods may significantly improve the efficiency of residual disease monitoring during IFN-alpha therapy of CML.

Antineoplastic Agents↗

Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat pancreas during embryonic and fetal life.

The expression of functional receptors for nerve growth factor in insulin-producing cell lines grown in vitro has recently been demonstrated. The possible importance of signals transduced via these receptors in the control of islet maturation has been proposed based on data obtained using an in vitro culture system. To further support this hypothesis, we have studied the expression of Trk-A, the high-affinity receptor for NGF, in vivo during the embryonic and fetal development of the rat pancreas. We have also examined the expression of NGF during the same period. Immunohistological analysis shows that at embryonic day 11 (E11), Trk-A is expressed by the epithelial cells of the presumptive pancreas. The few pancreatic endocrine cells present at that stage express Trk-A. At E12 and E16, Trk-A expression was detected in the developing ductal network. The endocrine cells located in the ducts express Trk-A while those that have migrated into the surrounding mesenchyme now stain negative for Trk-A. By E20, Trk-A expression by ductal cells has considerably decreased and can be detected only in small ducts closely associated with islet-like structures. These islet-like structures stain negative for Trk-A. After birth, insulin-positive cells arranged into islets re-express Trk-A. During the same period, NGF mRNA is found to be expressed in the developing pancreas. The expression of Trk-A and its ligand NGF in the pancreas during embryonic and fetal life suggests that NGF and its receptor could play an important role in the development of the pancreas.

Animals↗

[Cold agglutinins and cryoglobulinemia in a patient with hepatitis C].

OBJECTIVES: Cold agglutinins and cryoglobulins are uncommon in the same patient as observed in our case. CASE REPORT: A 74-year-old patient suffered repeated episodes of hemolytic anemia for one year and had hepatitis C anti-virus antibodies. Mixed cryoglobulinemia was found at levels which increased during episodes of acute hemolysis in addition to anti-I cold agglutinins. Two-dimensional electrophoresis revealed identical oligoclonal cold agglutinins and cryoglobulins. DISCUSSION: Unlike mixed cryoglobulinemia, cold agglutinins are not known to occur subsequent to hepatitis C infection. The identical immunoglobulins observed in our patient suggest a common origin. Chronic anti-I cold oligoclonal agglutinins are rarely observed and could be an intermediary step towards monoclonal lymphopathy as has been described in prolonged hepatitis C infection.

Aged↗

[Hemophagocytic syndromes].

Hemophagocytic syndromes are the clinicobiological translation of an unconnected macrophagic activity with hemophagocytosis. Their physiopathology is related with a deregulation of the T lymphocytes and an excessive production of cytokines. Acquired hemophagocytic syndromes are mostly associated with underlying pathology which they can reveal: immunodeficiency, infections (mostly of viral origin), hemopathies and cancers, auto-immune diseases. The main clinicobiological features are fever, hepatosplenomegaly and peripheric bicytopeny. In the majority of cases, the diagnosis is confirmed by a myelogram which shows the presence of benign histiocytes, actively phagocyting the hematopoietic cells. The pejorative prognosis of hemophagocytic syndromes (actual mortality rate 30 to 45%) requires an early therapy which associates etiological treatment of the underlying affection with pathogenic treatment (pulse of corticosteroids, immunoglobulins, immunosuppressors, or plasmapheresis).

Adult↗

[Spatial distribution of cancer incidence by anatomic site in Quebec].

Knowledge of the spatial distribution of diseases provides useful information in etiologic research and in implementation of preventive activities in community health. Spatial autocorrelation analysis is one of the various methods that enables to determine spatial clustering of diseases. This method has not been applied to lung, stomach and colon cancer in Québec. These cancers are frequent and are associated with environmental factors. The objectives of the study are to determine spatial distribution of incidence rates of these cancer sites by sex and to help generate etiologic hypotheses. Community health departments (CHDs) of residence are considered as risk markers since their population and environment may be related to the selected cancer sites. Data were obtained from Québec Cancer Registry. Rates were standardized by the direct method. Autocorrelation analysis was done through BW coefficient and Moran's coefficient I for correlograms. Results of standardized rates were compared to those of non standardized rates. Rates yielded the same results for the BW coefficient. Conversely, results were quite different for the correlograms. This implies that results from standardized rates should be kept since the age structure of CHD populations are different. Important variation in the level of spatial autocorrelation was found among the six sex-specific cancer sites. For male lung cancer and male stomach cancer first-order neighbouring CHDs showed similar incidence rates according to a geographic gradient. Female lung cancer exhibited spatial autocorrelation. Absence of spatial autocorrelation for colon cancer suggests that CHD is not the appropriate scale for study of this cancer and allows use of conventional epidemiologic methods. These results are discussed in relation to current etiologic hypotheses.(ABSTRACT TRUNCATED AT 250 WORDS)

Cluster Analysis↗

Serum erythropoietin and reticulocyte counts in inflammatory process.

The role of erythropoietin in the pathogenesis of anaemia associated with inflammatory disorders is unclear. We studied serum erythropoietin levels in patients with inflammatory process of varying aetiologies. Serum erythropoietin levels and reticulocyte counts were prospectively measured in 40 patients with inflammatory syndromes and compared with values obtained in 20 patients with myelodysplastic syndromes. Significant inverse correlation between erythropoietin levels and haemoglobin concentration were noted in the 2 groups. The slope of the regression line for patients with inflammatory disorders was lower as compared with that for the myelodysplastic syndromes. In all cases, when the erythropoietin response in relation to degree of anaemia is compared with that which occurs in patients with myelodysplastic syndromes, the inadequate erythropoietin response in patients with chronic inflammatory process becomes evident. In patients with inflammatory process, a relationship between erythropoietin levels and reticulocyte counts were only noted in patients with mildly anaemia (haemoglobin concentration higher than 10.5 g/dl). This study suggests blunted erythropoietin production and impaired marrow response to this hormone in the anaemia which occurs in inflammatory syndromes and supports the hypothesis that these disorders may contribute to the development of the anaemia associated with inflammatory disorders.

Adult↗

Sartwell's incubation period model revisited in the light of dynamic modeling.

The objective is to look into the well-known robustness of Sartwell's disease incubation period (IP) lognormal model. A new approach is proposed that embeds the pathogenesis of infection into the framework of percolation theory derived from the physical sciences. A two-step model of the individual disease process is proposed. The first step has a stochastic basis: it is aimed at establishing the threshold position of subjects bound to be diseased. Agent and host factors entertain and help the process reach the threshold. They include all the biologic risk factors (age, exposure dose and intensity, route of inoculation, etc.) to which Sartwell's model is usually found robust. The threshold is the point of no return of the disease process. The threshold provides the initial conditions of the second step. The second step traces the evolution of the pathologic process until disease onset: it is based on a nonlinear deterministic model that progressively unfolds the individual fates. As a chaotic regime is embedded into the model and as chaos unavoidably develops at some time entailing disease onset, the IP distribution becomes independent of the initial conditions laid out at the threshold. Unpredictable disease time courses and onsets are obtained. Biological examples supporting the model are provided. A simulation of 1000 pathologic processes is undertaken according to a simple birth-and-death process of microorganisms or cancer cells. As expected, a lognormal fits the IP distribution over a wide range. A lack of lengthy IPs is, however, observed. A simple multiplicative process coincides exactly with a lognormal model, but a multiplicative-competitive process such as that which is embedded in the nonlinear deterministic model has a narrower distribution. Large sample sizes are, however, needed to uncover this departure from the lognormal. Biologically, at least two phases of the empiric IP should be told apart: lengthy IPs should be distinguished from short and median IPs. Lengthy IPs emphasize interaction (complexity) between the disease progression and the immunological defenses of the host. Simulated distributions involving process complexity closely fit selected cancer data sets. Process complexity of the host pathologic unfolding can actually be recognized and quantified.

Disease↗

Hereditary complement factor I deficiency.

We describe four cases (from three families) of hereditary factor I deficiency, bringing the total number of cases now reported to 23. In one family there are two affected siblings: one has suffered recurrent pyogenic infections; the other is asymptomatic. In the second family, the patient had recurrent pyogenic infections and a self-limiting vasculitic illness; in the third family, the patient suffered recurrent pyogenic and neisserial infections. All four patients had markedly reduced concentrations of C3 in the serum (family 1 propositus: 28%; family 1 asymptomatic sibling: 15%; family 2: 31%; and family 3: 31% normal human serum) which was in the form of C3b. Low IgG2 levels may occur in primary C3 deficiency, and a reduction in IgG2 concentration to 1.14 g/l (normal: 1.30-5.90 g/l) was found in the patient from family 2. Using radioligand binding assays, we demonstrated increased binding of C3b to erythrocytes in a patient with factor I deficiency. This C3b could not be cleaved by autologous serum but could be cleaved by normal serum or purified factor I. We review and compare the published cases of C3, factor H and factor I deficiency.

Adolescent↗

[Percutaneous drainage nephrostomy in patients over 70 years of age. Apropos of 98 nephrostomies in 74 patients].

From 1985 to 1992, 98 ultrasound-guided percutaneous drainage nephrostomies were performed in 74 patients with a mean age of 77 years (range: 70-88 years). The diversion was indicated because of upper urinary tract obstruction (87% of cases), urinary fistula (4%) or secondary displacement of the first PCN (9%). The initial disease was benign in 29 patients (42.5%, including 48% of renal and ureteric stones), malignant in 39 cases (53%, including 79% of pelvic cancers) and not specified in 6 cases (4.5%). PCN was performed successfully in 93% of patients and allowed improvement in renal failure and/or treatment of the initial infectious syndrome in the majority of cases. The following complications were observed: secondary displacement of the drain (13 cases), infection (3 cases), renal subcapsular haematoma (1 case). The outcome of the patients was directly related to the initial disease: 28 of the 29 patients diverted for a benign disease were still alive and the PCN drain was able to be removed in 96% of cases after curative treatment; 95% of the patients diverted for cancer had died within 13 months after PCN. Patients with previously untreated prostatic cancer had the best prognosis, as androgen suppression allowed removal of the PCN without any additional procedure, in some cases. Drainage of the upper urinary tract by percutaneous nephrostomy under local anaesthesia has a limited morbidity and a low failure rate and therefore appears to be a technique of choice, particularly in elderly patients.

Aged↗

Competing stochastic models of the incubation period: an investigation of age-at-diagnosis of familial and sporadic retinoblastoma.

This study is based on the assumption that the distribution of age-at-diagnosis (a synonym for the incubation period) of a disease can convey information with respect to its pathogenetic mechanisms. To this end, an analysis of 3 retinoblastoma (RB) international data sets was undertaken. The molecular and cellular basis of RB is well understood and may serve our purpose well. RB is broken down into familial bilateral, unilateral, and sporadic unilateral forms. Survival and hazard functions were computed. Several competing stochastic models (up to 9 per RB form) were fit. Each conveyed a meaningful pathogenetic mechanism. Between-model discrimination was achieved by examining chi-square goodness-of-fit values to select the best fitting model. Well-known survival models, such as the simple exponential and the lognormal (Sartwell model) were ruled out. Age-at-diagnosis of familial RB proved to be best explained by 2 interfering exponentials (a diffonential function); the logistic was retained as the best adjusted model of the incubation period of sporadic cases of RB. As to familial unilaterals, both the diffonential and the logistic models fit equally well. The 3 data sets are consistent in these results, ruling out the less well-fit competing models. The results suggest the existence of 2 opposing but independent balancing internal mechanisms at the origin of familial RB. Sporadic RB appears to be due to a single host-dependent self-limiting cellular mechanism. Familial unilaterals which share both of these component mechanisms would involve a lower retinoblast turnover rate. The cellular implications of these findings are discussed with regard to the relative importance of endogenous and exogenous induction factors in RB. It is concluded that, according to the RB form, RB occurrence results from 2 cellular interfering forces of different strength and organization.

Age Factors↗

Lineage promiscuity in leukemia studies of T-cell receptor and immunoglobulin genes.

Using appropriate DNA probes, the configurations of the T-cell receptor beta-chain genes and immunoglobulin heavy-chain genes were studied in patients diagnosed as having the following malignancies: 7 chronic myeloid leukemia, 13 acute myeloblastic leukemia, 9 acute lymphocytic leukemia and 20 chronic lymphocytic leukemia. Rearrangements not corresponding to the immunotype were unexpectedly found in lineage neoplasias.

Burkitt Lymphoma↗