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P Fontaine

Publications and source records attributed to P Fontaine.

At least 19 recordsLinked to original sources
PubMed1996

[Results of sub-inguinal revascularization in the treatment of diabetic ischemic foot].

From January 1993 to August 1995, we performed 60 revascularizations of the lower limb using 65 bypasses in 55 patients (32 men, 23 women, mean age 66.6 yars) with diabetes. Trophic lesions of the foot existed in 57 of the revascularizations, and in 3 cases pain was provoked by the supine position. Supra-articular femoropopliteal bypass was performed in 8 cases, subarticular femoropopliteal bypasses in 25, femorotibial bypasses in 14 and paramalleolar bypasses in 18. There were 6 post-operative deaths. Six major amputations were required including 2 despite patent bypasses. Twenty-nine minor amputations were required for trophic disorders. There were 5 deaths after the postoperative period in which 4 major amputations were required despite patent bypasses in 2 cases. Retarded cicatrization was seen in 13 of the amputation stumps of areas of atrophism. Actuarial survival at 2 years was 77 +/- 6% with primary patency of 53 +/- 9.5% and secondary patency of 74 +/- 7%. The rate of success in saving the lower limb was 80.5 +/- 5.6%. Bypass revascularization has been effective in the treatment of the diabetic ischemic foot. Operative mortality was high, resulting from associated cerebral vascular events and coronary heart disease.

Aged↗
PubMed1995

Immunodominant minor histocompatibility antigens expressed by mouse leukemic cells can serve as effective targets for T cell immunotherapy.

Numerous minor histocompatibility antigens (MiHAs) show tissue-specific expression and can induce vigorous T cell responses. They therefore represent attractive targets for leukemia immunotherapy mediated by adoptive transfer of T cells. The main objective of this work was to determine whether MiHAs expressed by normal hematopoietic cells were present on leukemic cells and whether they could trigger lysis by cytotoxic T lymphocytes (CTLs). CTL assays showed that mouse leukemic cells of both lymphoid and myeloid lineages were sensitive to CTLs targeted toward some but not all MiHAs. In four out of four strain combinations in which we primed CTLs against immunodominant MiHAs, effectors killed leukemic blasts, whereas no cytotoxicity was observed when CTLs were targeted toward four immunorecessive MiHAs. Testing of HPLC fractions obtained from normal and leukemic cells provided molecular evidence that leukemic blasts expressed only some of the MiHAs found on normal mouse hematopoietic cells. Decreased density of H-2 class I molecules at the surface of leukemic cells suggests that down-regulation of genes encoding either class I molecules or proteins involved in antigen processing played a role in the aberrant expression of MiHAs. In vivo resistance to the leukemic cells by various strains of mice correlated with in vitro CTL activity. These results show that leukemic cells express only some (immunodominant) MiHAs and suggest that this subset of MiHAs represent prime targets for adoptive immunotherapy.

Animals↗
PubMed1994

T lymphocyte responses to multiple minor histocompatibility antigens generate both self-major histocompatibility complex-restricted and cross-reactive cytotoxic T lymphocytes.

Minor histocompatibility antigens (MiHA) may represent ideal targets for cancer immunotherapy since (1) the expression of many MiHA is tissue specific and (2) they can trigger potent T lymphocyte responses. A primary objective of our research program is to characterize T cell responses to cells displaying multiple incompatible MiHA. Early in the course of this work, we observed in various stimulator/responder combinations that immunization versus multiple MiHA generated cytotoxic effectors that killed not only stimulator cells but also a large panel of MHC-identical and MHC-different targets. To characterize the cells responsible for this cytotoxic activity and their specificity, we expanded polyclonal and clonal CD3+ CD4- CD8+ LP anti-C57BL/6 effectors. LP anti-C57BL/6 polyclonal effectors (LPTc cell line) showed strong cytotoxic activity when tested against several H-2b and non-H-2b targets, but displayed, respectively, weak or absent cytotoxicity against MHC class I-deficient cells and syngeneic cells. When used as cold targets, C57BL/6 cells inhibited the lysis of all H-2b and non-H-2b cells. Some H-2b, but no H-2d or H-2k, cold targets inhibited the lysis of C57BL/6 targets. With the exception of LP and C57BL/6, all types of H-2b cells (A.BY, D1.LP and C3H.SW) showed complete reciprocal inhibition of lysis. The same observation was made for non-H-2b targets. The cytotoxicity profile of 12/14 LP anti-C57BL/6 clones was identical to that of the LPTc cell line, while 2/14 clones recognized only H-2b cells. Cytotoxicity was inhibited by incubation of effector cells with anti-CD3 or anti-CD8 antibodies and by incubation of target cells with specific anti-MHC class I antibodies. These results show that immunization against multiple MiHA in the context of self-MHC generates 2 types of CTL: some are strictly self-MHC restricted while others are strongly cross-reactive and recognized MHC-peptide complexes on allogeneic MHC-different targets. This observation has significant implications concerning the use of anti-MiHA T cells in cancer immunotherapy.

Animals↗
PubMed1994

The role of MHC-associated self-peptides in transplantation and immunosurveillance.

The antigen-binding site of most major histocompatibility complex (MHC) class I and II antigens is occupied by self-peptides that are derived from the proteolysis of endogenous proteins following instructions provided by the molecules of the MHC themselves. Together with MHC proteins, self-peptides define our immunological self and shape the repertoire of both T cells that recognize "nonself," and NK cells that may recognize "no self." Endogenous proteins of all cell compartments (nucleus, cytosol, organelles, surface membrane) can yield self peptides whose expression may be either ubiquitous or lineage-specific. Their expression allows the binary recognition mechanism of T and NK cells to check the integrity of the cell genome. A better understanding of the molecular bases of the distinction between self and nonself permits us to anticipate the possibility of modifying their expression and/or their recognition in order to: (i) make the nonself acceptable as self, thereby establishing specific transplantation tolerance, (ii) reestablish tolerance of the self lost in autoimmune diseases, and (iii) induce the rejection as nonself of neoplastic cells. These objectives are particularly pertinent to the area of bone marrow transplantation, where the ultimate goal is aimed at modulating host cell allorecognition in such a way as to both potentiate the graft-versus-leukemia reaction and prevent GVHD.

Animals↗
PubMed1994

The safety of dorsal penile nerve block for neonatal circumcision.

BACKGROUND: Dorsal penile nerve block (DPNB) was first described for use in neonatal circumcision in 1978. Since then, many studies have documented its effectiveness in alleviating pain in newborns undergoing circumcision. In 1989, the American Academy of Pediatrics acknowledged that DPNB may relieve the pain and stress of circumcision but stopped short of endorsing its routine use in this procedure, citing lack of data on its safety. METHODS: To determine the types and rates of complications from DPNB used for neonatal circumcision, the authors conducted a retrospective review of hospital records of 1358 circumcised male infants delivered at an urban medical center during a 1-year period. RESULTS: Of the 1358 records reviewed, 1222 (90%) had sufficient documentation to be included in the study. DPNB was used in 1022 (84%) of the circumcisions. Complications occurred in 12 cases (11 with small ecchymoses at injection sites and one with excessive bleeding from the needle stick), for a rate of 1.2%. No cases of lidocaine toxicity, voiding delay, or vascular compromise were noted. There was a trend toward increased incidence of injection-site hematomas with the Plastibell as compared with the Gomco technique (P = .07). There were no significant differences in complication rates for DPNB performed by less experienced operators (eg, medical students and residents) compared with more experienced operators (staff physicians). CONCLUSIONS: This study corroborates findings of smaller case studies, indicating that DPNB is associated with a low rate of minor complications.

Child, Preschool↗
PubMed1993

[Endocrine and metabolic consequences of massive obesity].

Massive obesity is always accompanied by insulin resistance with hyperinsulinaemia in proportion to the amount of visceral fat, which has repercussions on oxidative and non-oxidative glucose metabolism. The increase of free fatty acids in direct relation to the adipocytic mass reduces the hepatic insulin uptake; it increases the suprahepatic glucose flow and the production of very low density lipoproteins. The adipose tissue exerts a feminizing effect in men and a masculinizing effect in women. Women have disorders of ovulation and hirsutism, with increase of free testosterone and elevation of luteotropic hormone levels. Men have hypoandrism due to excessive aromatization of androgens and oestrogens. The adipose tissue accelerates the turnover of cortisol and facilitates cortisone production, which stimulates ACTH secretion and maintains stimulation of the adrenal cortex. Hyperinsulinism and resistance to insulin also intervene in hormonal regulation. They elevate the insulin-like growth factor 1 (IGF-1) which inhibits the production of growth hormone and reduces its plasma half-life; hyperinsulinism and IGF-1 facilitate ovarian androgen production; hypothalamic disturbances occur by diminution of sensitivity to hypoglycaemia, and there are abnormalities in monoaminergic and serotoninergic control. Bone tissue density is preserved for a long time, as it is in proportion to the fatty mass and to the oestrogen and IGF-1 levels, but it may be gradually reduced by secondary hyperparathyroidism. Thyroid function and thyrotropic regulations are unaffected.

Endocrine System Diseases↗
PubMed1993

Plasma lipid response and nutritional adequacy in hypercholesterolemic subjects on the American Heart Association Step-One Diet.

OBJECTIVES: To determine the efficacy of the American Heart Association Step-One Diet for lowering blood lipid levels and to assess its nutritional adequacy in younger (< 50 years old) and older (> or = 50 years old) subgroups. STUDY DESIGN: A prospective cohort study; 383 subjects were instructed in the American Heart Association Step-One Diet. Adherence to the diet was assessed at 6 weeks. Eighty-seven subjects continued the diet for an additional 12 weeks. SETTING: General community participants: volunteers from community cholesterol screening programs and chart reviews at family practice clinics. STUDY PARTICIPANTS: Men and women, aged 20 to 70 years, with baseline low-density lipoprotein cholesterol levels between the 50th and 95th percentile, and excluded if receiving any medications that affect blood lipid levels or if there was a history of diabetes, gout, peptic ulcer, or liver disease. INTERVENTION: Instruction by a registered dietitian and adherence to the American Heart Association Step-One Diet for 6 (n = 383) and 18 weeks (n = 87). This diet involves an intake of total fat not to exceed 30% of calories, saturated fatty acids not to exceed 10% of calories, and dietary cholesterol limited to 300 mg/d. RESULTS: Subjects aged 50 to 70 years averaged a reduction in total cholesterol level and low-density lipoprotein cholesterol level of 4% after 6 weeks. At the end of 18 weeks, mean total cholesterol and low-density lipoprotein cholesterol levels in subjects younger than 50 years exceeded their baseline levels, and in those older than 50 years returned to baseline lipid levels. Inadequate intake of several micronutrients were reported, notably, zinc, calcium, and vitamins A, D, and E. CONCLUSIONS: When recommending the American Heart Association Step-One Diet to persons with hyperlipidemia, baseline dietary behavior should be assessed to determine whether that diet offers therapeutic advantage over the persons's self-selected diet. Follow-up should include monitoring of lipid response and nutritional adequacy. Special emphasis should be placed on selection of foods with appropriate micronutrient content.

Adult↗
PubMed1992

[Congenital cysts and fistulae of the face and the neck].

The authors review the embryological, clinical and therapeutic aspects of congenital facial and cervical cysts (C) and fistulae (F), based on a personal series of 85 cases (facial: 18, latero-cervical: 29, mediocervical: 38) observed during a 5-year period. The facial forms are the result of an incomplete coalescence of the facial buds and most often present as helical F (17/18). Laterocervical C and F are due to abnormal evolution of branchial clefts; the main clinical forms are related to anomalies of the 2nd branchial cleft (24/29), usually presenting as sinus localized at the anterior border of the lower third of the sternocleidomastoid muscle (8) and amygdaloid cysts. Thyroglossal duct cysts are the most frequent of the medio-cervical C and F (35/38); they usually present as a mediocervical cyst in the thyro-hyoid space which may be revealed by an infection or a fistulization. The only appropriate treatment of congenital facial and cervical C and F is surgery providing that the resection is meticulous with complete resection of the fistula in order to avoid relapse. Complete resection also suppresses the risk of secondary malignant degeneration of amygdaloid and thyroglossal duct cysts.

Adolescent↗
PubMed1991

Evaluation of in vitro cytotoxic T lymphocyte assays as a predictive test for the occurrence of graft vs host disease.

The potential value of in vitro cytotoxic T lymphocyte (CTL) assays for predicting the occurrence of graft vs host disease (GVHD) following allogeneic bone marrow transplantation was evaluated in 12 mouse donor-host combinations associated with various degrees of GVHD. These donor-host combinations were selected after evaluation of GVHD triggered by minor histocompatibility antigens (MiHA) in 24 allogeneic strain combinations derived from six strains of H-2b mice. Recipients (n = 475), previously submitted to total body irradiation (9.5 Gy), were transplanted with 10(7) bone marrow cells along with 5 x 10(7) spleen cells. While lethal GVHD was observed in half of the strain combinations, it was possible to select 12 donor-host combinations characterized by severe, mild, or absent GVHD. When levels of anti-host CTL activity were assessed following in vivo priming and in vitro boosting, strong CTL-mediated cytotoxicity was observed in all combinations whether they developed GVHD or not. CTL frequency measured by limiting dilution analysis (LDA) ranged from 1/16880-1/306. The Spearman rank test revealed no positive correlation between GVHD intensity and donor anti-host CTL activity assayed either in bulk culture experiments or in LDA conditions. These results indicate that MiHA capable of triggering potent CTL responses in vitro do not necessarily initiate GVHD, and that in vitro measurement of donor CTL activity against host-type Con A blasts is not a predictive assay for anti-MiHA GVHD. However, the possibility to recruit CTL populations targeting host MiHA expressed specifically on hematopoietic cells suggests a novel therapeutic strategy for the cure of hematopoietic malignancies. Indeed, transplantation of donor hematopoietic stem cells supplemented with T cells aimed at MiHA specifically expressed by host hematopoietic cells, could possibly potentiate the desirable graft vs leukemia effect without increasing the risk of GVHD.

Animals↗
PubMed1991

The effects of social support on women's health during pregnancy, labor and delivery, and the postpartum period.

This review of the literature on social support and its relationship to maternal health indicates that emotional, tangible, and informational support are positively related to mothers' mental and physical health around the time of childbirth. The importance of various types of support changes with the changing needs of women as they move from pregnancy to labor and delivery, and then to the postpartum period. During pregnancy, emotional and tangible support provided by the spouse and others is related to the expectant mother's mental well-being. In addition, informational support in the form of prenatal classes is related to decreased maternal physical complications during labor and delivery, and to improved physical and mental health postpartum. Mothers who have the support of a companion during labor and delivery experience fewer childbirth complications and less postpartum depression. Mothers' postpartum mental health is related to both the emotional support and practical help (eg, housework and child care activities) provided by the husband and others. Health care providers are in a unique position to educate prospective parents about the importance of social support around the time of childbirth and may play a critical role in mobilizing support systems for new mothers.

Delivery, Obstetric↗
PubMed1991

Dorsal penile nerve block for newborn circumcision.

Dorsal penile nerve block with lidocaine is safe and effective for reducing the pain associated with newborn circumcision. Administering the anesthesia adds little time or expense to the overall routine. Complications are minor, limited to local bleeding and hematoma formation. Family physicians performing circumcision should be prepared to use penile nerve block and to advocate it to parents who choose newborn circumcision.

Circumcision, Male↗
PubMed1990

A causal model describing the relationship of women's postpartum health to social support, length of leave, and complications of childbirth.

Recovery from childbirth is a complex process that may involve not only the gynecological organs, but also the cardiovascular, respiratory, musculo-skeletal, urologic, gastrointestinal, endocrine, and nervous systems. The process of postpartum recovery may span several months and is related to a variety of personal, family, and social variables. This paper presents a model that describes changes in women's health over the first postpartum year and the relationship between health changes and other variables. The model's dependent variables--mothers' mental and physical health--have a reciprocal effect on one another. The independent variables within the model include length of maternity leave, social support, complications of childbirth, baby's health, mother's use of cigarettes and alcohol, and demographic characteristics. This model is proposed as a research tool for future investigations in postpartum health, and as a conceptual framework to enhance our understanding of the relationship between postpartum health and other important variables.

Adult↗
PubMed1990

Studies of immunologic tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation in mice.

We showed previously that transplantation of 10(7) unmanipulated C57BL/6 marrow cells to irradiated LP mice yields healthy (B6-LP) chimeras showing no signs of rejection or graft-versus-host disease (GVHD). The aim of this work was to gain more insight into the mechanism(s) responsible for tolerance to host minor histocompatibility antigens following allogeneic bone marrow transplantation (BMT). (B6-LP) chimeras showed very good immune reconstitution when studied in vitro for proliferative response to mitogens and alloantigens and generation of T cell cytotoxic activity. In co-culture experiments their spleen cells showed no natural suppressor activity. When used as cell donors, their capacity to initiate GVHD in four strains of mice presenting H-2 differences was normal when compared to C57BL/6 donors. However, they provoked no GVHD in the three strains of H-2 compatible mice studied. Re-irradiated (B6-LP) chimeras rapidly died of GVHD following injection of C57BL/6 marrow + spleen cells. (B6-LP.R111) chimera cells appeared tolerant to LP minor antigens presented in the context of H-2r or H-2b. No anamnestic anti-idiotypic suppressor response was noted when stable (B6-LP) chimeras were stimulated with naive C57BL/6 cells. These findings suggest that in BMT chimeras transplanted across minor histocompatibility barriers: (1) both host and donor-derived antigen-presenting cells can present host antigens to donor T cells whose numbers in the marrow inoculum will determine if GVHD or tolerance will ensue, (2) GVHD can be triggered by only a limited number of 'dominant' minor antigens, and (3) we found no evidence for the presence of natural suppressors, veto cells or anti-idiotypic suppressor T cells.

Animals↗
PubMed1989

Distinctive features of procoagulant response of monocytes from diabetic patients.

The procoagulant activity (PCA) of disrupted monocytes was examined in 32 diabetic patients (26 with insulin-dependent and 6 with non-insulin-dependent diabetes) versus 30 control subjects. Diabetes monocytes exhibited a weak PCA before any incubation, associated in 10 cases with a significant amount of factor VII activity. Incubation led to a significant rise in PCA in diabetes cells, when stimulated with lipopolysaccharide or not, and in control cells only after stimulation. In incubated diabetes cells, PCA was prothrombinase-like when factor VII was associated with the freshly isolated cells, and tissue factor-like (as in the controls) when no factor VII was associated with the cells. The characteristics of PCA were not correlated with clinical features or with the type of diabetes. Our study suggests that diabetes monocytes exhibit a higher level of PCA than control ones, possibly corresponding to an in vivo stimulation, or at least a higher responsiveness to stimuli occurring in vitro.

Adult↗