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Biomedical subjects

A Boucher

Publications and source records attributed to A Boucher.

At least 19 recordsLinked to original sources
PubMed2006

Cytomegalovirus infection in kidney transplant recipients: Evolution of approach through three eras.

Cytomegalovirus (CMV) prophylaxis is recommended for high-risk patients, while preemptive therapy is considered acceptable for patients at moderate/low risk. After reviewing kidney transplant patients from 1992-1995 and 1996-1999, we decided to replace prophylaxis by preemptive therapy. Herein we have presented our data. From 1996-1999 we treated 129 patients with ganciclovir prophylaxis for 3 months if D+/R- or if they received depleting antibodies. The incidence of CMV was 13.2% versus 3.7% in the 1992-1995 cohort. The increase was associated with mycophenolate mofetil (MMF) use (P = .002). Forty-two percent of the D+/R- developed an infection with 89% of bouts occurring in the first month after cessation of prophylaxis. From 2002-2004, we never gave prophylaxis to 129 patients except when they received thymoglobulin. High-risk D+/R- patients were monitored by polymerase chain reaction (PCR) CMV for 3 months. The incidence of CMV was 17.1% with 54% of the D+/R- developing CMV. CMV infection occurred mostly during the first trimester posttransplantation. Creatinine at 1 year posttransplantation was worse in the presence of CMV infection (154.3 mumol/L-1.75 mg % versus 130.2 mumol/L-1.47 mg %, P = .03). Time to cure CMV infection was longer when MMF was discontinued: 36.7 days versus 69.9 days (P = .026). Our results indicated that CMV incidence is increasing: 3.7% (1992-1995) --> 13.2% (1996-1999) -->17.1% (2002-2004) and that it impairs 1 year graft function. Recovery was faster among patients still receiving MMF compared with those discontinuing MMF. Although MMF inhibits synthesis of anti-CMV IgM, it increases the anti-herpes virus effect of ganciclovir and may protect against chronic allograft nephropathy. Based on our experience, we plan to reintroduce prophylaxis in high-risk patients and to continue MMF when treating CMV infection.

Acyclovir↗
PubMed2003

Diabetes mellitus in transplantation: 2002 consensus guidelines.

Diabetes mellitus is a serious complication following organ transplantation that is underdiagnosed, possibly due to the inadequate definitions used in published literature and the lack of standardized screening. Diabetes in transplantation amplifies the already increased risk of cardiovascular disease among transplant patients, and increases the risk of graft loss and death. Patients at risk of developing diabetes in transplantation should therefore be prospectively identified and given individualized immunosuppressive therapy to minimize the risk of developing this disease. These guidelines are intended to: (1) help identify patients at risk for diabetes after transplantation; (2) set down a standard definition of posttransplant diabetes mellitus (PTDM); (3) create a standard monitoring protocol for the diagnosis of PTDM; and (4) optimize the management of patients at risk of developing or who develop diabetes after transplantation. With improved diagnosis, individualization of therapy, and proper early management, the incidence of diabetes in transplantation, and the accompanying additional burden of illness the disease carries, may be diminished. In turn, this will help achieve the therapeutic goals of reducing the risk of graft complications, improving quality of life, and reducing postoperative morbidity and mortality in transplant patients.

Consensus↗
PubMed2002

Abnormal interleukin-1 receptor type II gene expression in the endometrium of women with endometriosis.

Interleukin 1 (IL-1) is a major proinflammatory cytokine that is believed to play a central role in the pathophysiology of endometriosis. The IL-1 receptor type II (IL-1RII) is known to bind to IL-1 and to inhibit its biological effects. In our previous studies, we showed that human endometrium expresses IL-1RII, and we observed reduced expression of the protein in women with endometriosis. The aim of this study was to investigate IL-1RII mRNA in the endometrial tissue of normal women (n = 26) and of patients with various degrees of endometriosis (n = 53). In situ hybridization showed that IL-1RII mRNA expression was significantly decreased in endometriosis, particularly during the early stages of the disease (stages I and II). This was quite obvious in both glandular and stromal cells, and it was corroborated by reverse transcription-polymerase chain reaction analysis of IL-1RII mRNA in the endometrial tissue of women with (n = 10) and without (n = 8) endometriosis. The reduced levels of IL-1RII mRNA in the endometrium of women suffering from endometriosis reveals a profound defect in IL-1RII gene expression and, consequently, a reduced capability of endometrial tissue to down-regulate IL-1 activity. Defective IL-1RII gene expression during the early stages of endometriosis (stages I and II) may contribute to the etiology of the disease.

Adult↗
PubMed2001

Cycle-dependent expression of interleukin-1 receptor type II in the human endometrium.

Cytokines such as interleukin-1 (IL-1) play a major role in the reparative and inflammatory-like processes that occur in human endometrium during every menstrual cycle, but they also seem to be implicated in critical reproductive events such as ovulation and implantation. Interleukin-1 is tightly regulated in the body by a complex network of control systems. In the present study, we examined the expression of IL-1RII, a natural specific inhibitor of IL-1, in the human endometrium and found an interesting distribution and temporal pattern of expression throughout the menstrual cycle. Immunoreactive IL-1RII was found in stromal as well as epithelial cells, but it was predominant within the lumen of the glands and the apical side of surface epithelium. In situ hybridization and reverse transcription-polymerase chain reaction (RT-PCR) analyses showed higher levels of mRNA in epithelial than in stromal cells. The IL-1RII cellular and luminal secretion followed a regulated cycle phase-dependent pattern of expression. Although elevated in the late proliferative/early secretory phase of the menstrual cycle, IL-1RII luminal secretion significantly decreased in the midsecretory phase, reaching its lowest levels at Day 21, before augmenting markedly again during the late secretory phase. This pattern of expression was less obvious at the level of cellular staining, as examined by immunohistochemistry, but it was corroborated by Western blot analysis of IL-1RII protein and semiquantitative RT-PCR of IL-1RII mRNA in the whole endometrial tissue and separated glandular epithelial cells. The reduced expression of IL-1RII within the implantation window suggests the existence of accurate regulatory mechanisms that, by down-regulating IL-1RII expression, alleviate IL-1 inhibition during this crucial period and facilitate IL-1 proimplantation actions. The elevated expression of IL-1RII observed during the late secretory phase suggests an involvement of IL-1RII in control of the proinflammatory state that takes place in the endometrium during the premenstrual and menstrual periods.

Adult↗
PubMed2000

Neutron polarization induced by radio frequency radiation

We have measured that an unpolarized ultracold neutron beam gets polarized through its interaction with a resonant radio frequency field. Both spin components pass through the field and end up in one single spin state. We present a simple description for this surprising effect together with first experimental results.

Journal Article↗
PubMed2000

Effect of hormonal agents on monocyte chemotactic protein-1 expression by endometrial epithelial cells of women with endometriosis.

OBJECTIVE: To assess whether hormonal agents used in the medical treatment of endometriosis, such as danazol and GnRH agonist, exert direct regulatory action on monocyte chemotactic protein-1 (MCP-1) expression by endometrial epithelial cells. DESIGN: Primary cultures of epithelial cells isolated from human endometrium were exposed to different concentrations of cytokines and steroid hormone analogs. Expression of MCP-1 was analyzed at the levels of protein and messenger RNA. SETTING: Gynecology clinic and laboratory of endocrinology of reproduction. PATIENT(S): Women presenting for infertility or pelvic pain in whom endometriosis was diagnosed by using laparoscopy. INTERVENTION(S): Endometrial tissue biopsy performed at laparoscopy. MAIN OUTCOME MEASURE(S): Secretion of MCP-1 protein was measured by using enzyme-linked immunosorbent assay, and mRNA steady-state levels were measured by performing Northern blot analysis. RESULT(S): Buserelin acetate, a GnRH agonist (0.1-10 ng/mL), had no significant effect on MCP-1 expression, whereas danazol (10(-7)-10(-5) M), a testosterone analog, and dexamethasone, an anti-inflammatory glucocorticoid hormone (10(-12)-10(-6)M), showed a direct and a dose-dependent inhibitory effect on MCP-1 expression. This effect occurred at the level of protein and mRNA. CONCLUSION(S): The findings of the study may affect understanding of the mechanisms by which hormonal treatments act on endometriosis and influence its clinical manifestations.

Adult↗
PubMed2000

Ovarian hormones modulate monocyte chemotactic protein-1 expression in endometrial cells of women with endometriosis.

Endometriosis, a frequent oestrogen-dependent disease believed to result from an aberrant proliferation of endometrial tissue outside the uterine cavity, is associated with an increased expression of monocyte chemotactic protein-1 (MCP-1) in the intrauterine endometrium. This makes it plausible that migrating endometrial cells are intrinsically able to initiate monocyte chemoattraction and activation, a phenomenon which has been consistently observed in the peritoneal cavity of patients and recently in their eutopic endometrium. To elucidate the mechanisms involved in the regulation of MCP-1 expression in eutopic endometrial cells, we studied the effects of ovarian hormones and found that oestradiol (10(-9) and 10(-8) mol/l) markedly increased MCP-1 mRNA steady-state levels and protein secretion by endometrial cells in response to interleukin-1beta (IL-1beta) (0.1 ng/ml). The IL-1beta-induced MCP-1 expression was even higher following pretreatment of cells with both oestradiol (10(-9) mol/l) and progesterone (5x10(-8) mol/l). This did not seem to be due to increased MCP-1 mRNA stability, but rather to a higher level of gene transcription. Our results provide evidence that ovarian steroids regulate, indirectly, the synthesis and the secretion of a potent chemotactic and activating factor for monocytes/macrophages by endometrial cells of women with endometriosis and reveal a new mechanism for oestradiol action.

Adult↗
PubMed2000

Estradiol amplifies interleukin-1-induced monocyte chemotactic protein-1 expression by ectopic endometrial cells of women with endometriosis.

Endometriosis, one of the most frequently occurring gynecological disorders, is estrogen dependent and is often associated with immunological changes. These include increased macrophage activation and infiltration into the endometriotic implants themselves as well as the peritoneal cavity where the implants often develop. Despite the critical role estrogens play in the development of endometriosis, the biochemical mechanisms of their action remain unclear. In the present study we report that estradiol (E2) enhances endometriotic cell responsiveness to the proinflammatory cytokine interleukin-1beta by up-regulating interleukin-1-induced monocyte chemotactic protein-1 (MCP-1) expression at the level of both protein secretion and messenger ribonucleic acid (mRNA) synthesis, whereas progesterone had no significant effects. According to mRNA half-life experiments, E2 action does not seem to be due to increased MCP-1 mRNA stability but, rather, to a higher level of transcription, as shown by run-on analysis. Interestingly, immunohistochemical analysis of MCP-1 expression in endometriotic tissue showed intense immunostaining in both epithelial glands and stroma regardless of the menstrual cycle phase, which is consistent with the cell culture data and indicates that MCP-1 expression is not subject to cyclic variation. The findings of the present study for the first time provide evidence that E2 up-regulates, although in an indirect way, the expression of a potent chemotactic and activating factor by ectopic endometrial cells, which may occur locally in the inflammatory site and contribute to peritoneal macrophage recruitment and activation, and reveal a new means of E2 action in the pathophysiology of endometriosis.

Adult↗
PubMed2000

Physiological tremor: does handedness make a difference?

The purpose of this study was to quantify with precision the characteristics of normal physiological tremor in the dominant and nondominant hand of a group of right-handed females. Twenty-two right-handed females (aged 20 to 40) gave informed consent to participate. Manual dominance determined with a questionnaire had to be equal to, or above 90%, for subjects to be accepted in the study. While the subjects kept their eyes closed, tremor was recorded simultaneously in the two extended index fingers during 40 s. Preceding the recording of postural tremor there was a period during which the subjects were asked to relax (control condition); to exert a pressure with the two index fingers on two strain gauges (static condition); or to press on and off with both index fingers on two strain gauges (dynamic condition). Each condition was recorded twice with two helium neon velocity lasers. This procedure was repeated after permutation of the lasers, thus a total of twelve sweeps of data were recorded. Seven parameters were used to analyze the tremor signal including measures of harmonicity, median frequency, proportional power in the 7-12 Hz range, amplitude, waveform morphology, entropy, and nonlinearity. Significant differences between hands were found in three parameters (median frequency, power in 7-12 Hz and entropy) but not in tremor amplitude (RMS). In addition, significant differences were found in five out of seven characteristics between conditions. These results suggest that neuromotor activity preceding the recording of tremor has a significant influence on tremor characteristics and that some of these characteristics are significantly different between the right and left hand in right-handed females.

Adult↗
PubMed1998

Safety and tolerability of cyclosporine and cyclosporine microemulsion during 18 months of follow-up in stable renal transplant recipients: a report of the Canadian Neoral Renal Study Group.

BACKGROUND: There has been concern that the increased drug exposure associated with treatment with cyclosporine microemulsion (CsA-ME) would lead to an increase in adverse events. METHODS: The long-term safety and tolerability of conventional cyclosporine (CsA) and CsA-ME were compared in a randomized, multicenter, pharmacoepidemiologic study involving 1097 stable renal transplant patients after 18 months of follow-up. RESULTS: No significant difference was seen in change in serum creatinine or calculated creatinine clearance between the two groups. Episodes of deterioration in renal function (change in serum creatinine > or = 20%) were categorized with the following results for CsA-ME versus CsA, respectively: acute rejection, 4.5% vs. 4.5%; chronic rejection, 8% vs. 11%; CsA nephrotoxicity, 12% vs. 7% (P=0.008); transient changes, 17% vs. 12%; other causes, 4% vs. 6%. During the first 6 months of the study, a transient increase in the incidence of gastrointestinal and neurological adverse events was seen in the CsA-ME group compared with the CsA group. Up to 18 months, patients in the CsA group reported significantly fewer hearing and vestibular disorders, but more cardiovascular problems than those in the CsA-ME group (P=0.035). CONCLUSIONS: Tolerance to CsA and CsA-ME was similar. Renal function over 18 months was not adversely affected by the increased drug exposure with CsA-ME, although there was a transient increase in nephrotoxicity. The frequency of acute and chronic rejection did not change.

Administration, Oral↗
PubMed1997

Ammonium acid urate crystal formation in adult North American stone-formers.

Although ammonium acid urate (AAU) stones are endemic in Asia, pure AAU calculi have almost disappeared from industrialized countries and clinical pathophysiologic relevance of sporadic stones containing AAU crystals is currently unknown. We reviewed 1,396 crystallographic stone analyses performed in our institution over a 10-year period. Prevalence of stones containing AAU crystals and predominantly AAU stones were 3.1% and 0.2%, respectively. In more than two thirds of cases, AAU crystals represented less than 10% of stone crystal composition. No pure AAU stone was found. According to crystalline predominance, 42%, 35%, and 12% of these calculi were uric acid, infectious, and calcium oxalate stones, respectively. AAU crystals were detected as discrete intercrystalline or peripheral deposits in 74.4% of stones. In only one calculus was AAU crystals detected in the nucleus. The hospital charts of 37 patients who presented with 43 calculi containing AAU crystals were also reviewed. The mean age was 53.1 +/- 16.6 years. Fifty-seven percent of calculi were upper urinary tract stones and 43% were bladder stones. Upper urinary tract calculi were more frequently uric acid stones, followed by infectious and calcium oxalate stones. Lower urinary tract calculi were more frequently infectious stones, followed by uric acid stones. Upper urinary tract stones were passed spontaneously in 13 patients and removed surgically in nine patients. Nine of these subjects were idiopathic recurrent stone formers who had passed other calculi with no trace of AAU crystal. Fifty-seven percent of lower urinary tract stones were associated with documented bladder dysfunction. In conclusion, although AAU-containing urolithiases are occasionally seen in our population, predominantly or primarily AAU stones are exceptional. AAU crystal formation usually appears as a minor and secondary phenomenon of no primary pathophysiologic relevance in stone formation.

Adult↗
PubMed1996

A randomized, prospective multicenter pharmacoepidemiologic study of cyclosporine microemulsion in stable renal graft recipients. Report of the Canadian Neoral Renal Transplantation Study Group.

BACKGROUND: The safety, tolerability, and pharmacokinetics of conventional cyclosporine (ConCsA) and cyclosporine microemulsion (MeCsA) were compared under conditions of normal clinical practice in a prospective, randomized, concentration-controlled, pharmacoepidemiologic study. METHODS: Between September 1994 and March 1995, 1097 stable renal transplant recipients in 14 Canadian centers were randomized 2:1 to treatment with MeCsA or ConCsA. Patients were commenced on each study drug at a dose equal to their previous therapy with ConCsA, and the dose was adjusted to maintain predose whole blood cyclosporine concentrations within the therapeutic range established for each center. Prednisone and azathioprine were continued unless dose adjustment was required for clinical reasons. RESULTS: The mean cyclosporine concentration was comparable in both treatment groups at all time points throughout the 6 months of follow-up. The mean dose of cyclosporine was 3.6 mg/kg/day in both treatment groups at entry to the study, and declined by 0.3% and by 2.8% in patients receiving ConCsA and MeCsA, respectively. The nature and severity of adverse events were similar in both treatment groups, but there was a transient increase in neurological and gastrointestinal complications in the group receiving MeCsA within the first month after conversion (P<0.05). Serum creatinine and creatinine clearance did not change in either treatment group throughout the study. Biopsy-proven acute rejection occurred in three patients (0.8%) receiving ConCsA and in seven patients (0.9%) receiving MeCsA, with non-histologically proven acute rejection in an additional three patients (0.8%) receiving ConCsA and five patients (0.6%) receiving MeCsA (P=NS). Serum creatinine rose transiently in 35 patients (9.8%) receiving ConCsA and 138 patients (18.7%) receiving MeCsA (P<0.05) and resolved either spontaneously or after a reduction in the cyclosporine dose. One graft was lost in the MeCsA group due to irreversible rejection, and seven patients died, three in the group receiving ConCsA and four of those receiving MeCsA (P=NS). Absorption of cyclosporine was more rapid and complete from MeCsA than from ConCsA during the first 4 hr of the dosing interval, resulting in almost 40% greater exposure to the drug (P<0.001). There was close correlation between area under the time-concentration curve (AUC) over the first 4 hr of the 12-hr dosage interval and AUC over the entire 12-hr dosage interval for both formulations, making AUC over the first 4 hr a good predictor of total cyclosporine exposure. Using this parameter, patients with low absorption randomized to receive MeCsA showed a marked increase in drug exposure by months 3 and 6, whereas there was no change in those who continued on ConCsA. A limited sampling strategy utilizing samples at the predose and postdose trough levels provided an excellent correlation with drug exposure, particularly for patients receiving MeCsA (r2=0.94 MeCsA vs. r2=0.89 ConCsA). CONCLUSIONS: MeCsA appears to be a safe and effective therapy in stable renal transplant patients and provides superior and more consistent absorption of cyclosporine when compared with ConCsA. Transient toxicity after conversion to MeCsA occurs in some patients, and may reflect the increased exposure to cyclosporine. Use of a limited sampling approach combining trough and 2-hr postdose concentrations may provide an effective way to monitor this exposure.

Adolescent↗