Biomedical subjects

R Pelletier

Publications and source records attributed to R Pelletier.

At least 19 recordsLinked to original sources

PubMed2003

Misregulation of histone acetylation in Sertoli cell-only syndrome and testicular cancer.

In many species, including humans, chromatin remodelling during spermiogenesis is initiated with a marked increase in histone acetylation in elongating spermatids. We have investigated whether this process is disturbed when spermatogenesis is defective or in human testicular tumours. For this purpose, the presence of highly acetylated histone H4 was detected on testicular sections from men with a severe impairment of spermatogenesis of several origins, as well as in different types of testicular tumours. In most tubules devoid of germinal cells (including SCO, Sertoli cell only syndromes) or lacking spermatocytes and spermatids, the Sertoli cells' nuclei showed a global increase in histone H4 acetylation. A similar observation was made in the peritumoral seminiferous tubules of testicular tumour tissues, whenever they were lacking germinal cells, with carcinoma in situ (CIS) cells being hypoacetylated. The global hyperacetylation of elongating spermatids during spermatogenesis could be part of an intercellular signalling pathway involving Sertoli cells and germinal cells, which could be disturbed in cases of severe spermatogenesis impairment, as well as in tubes surrounding germ cells in testicular tumours.

Acetylation↗

PubMed2003

Multilaboratory comparison of proficiencies in susceptibility testing of Helicobacter pylori and correlation between agar dilution and E test methods.

Susceptibility testing was performed at seven Canadian microbiology laboratories and the Helicobacter Reference Laboratory, Halifax, Nova Scotia, Canada, to assess susceptibility testing proficiency and the reproducibility of the results for clarithromycin and metronidazole and to compare the Epsilometer test (E test) method to the agar dilution reference method. Control strain Helicobacter pylori ATCC 43504 (American Type Culture Collection) and 13 clinical isolates (plus duplicates of four of these strains including ATCC 43504) were tested blindly. The National Committee for Clinical Laboratory Standards (NCCLS) guidelines for agar dilution testing were followed, and the same suspension of organisms was used for agar dilution and E test. Antimicrobials and E test strips were provided to the investigators. Methods were provided on a website (www.Helicobactercanada.org). Each center reported MICs within the stated range for strain ATCC 43504. Compared to the average MICs, interlaboratory agreements within 2 log(2) dilutions were 90% (range, 69 to 100%) for clarithromycin by agar dilution, with seven very major errors [VMEs], and 85% (range, 65 to 100%) by E test, with three VMEs. Interlaboratory agreements within 2 log(2) dilutions were 83% (range, 50 to 100%) for metronidazole by agar dilution, with six VMEs and eight major errors (MEs), and 75% (range, 50 to 94%) by E test, with four VMEs and four MEs. At lower and higher concentrations of antibiotic, E test MICs were slightly different from agar dilution MICs, but these differences did not result in errors. When a standardized protocol based on NCCLS guidelines was used, most participants in this study correctly identified clarithromycin- and metronidazole-susceptible and -resistant strains of H. pylori 93% of the time by either the agar dilution or E test method, and the numbers of errors were relatively equivalent by both methods.

Clarithromycin↗

PubMed2002

Polyploidy in large-headed sperm: FISH study of three cases.

BACKGROUND: Macrocephalic or large headed sperm with multiflagella is a rare abnormality often associated with infertility. Sperm chromosomal abnormalities could be associated with this specific morphological abnormality. METHODS: The cytogenetic content of large-headed sperm was assessed by dual and three-colour fluorescence in-situ hybridization in three patients carrying this specific morphological abnormality. RESULTS: In all patients nearly all sperm contained at least one copy of each sex chromosome, and in more than half of them at least two copies of either chromosome 1 or 18 were identified. In some sperm a tetraploidy was found. CONCLUSIONS: These observations suggested that both meiotic I and II divisions were affected by incomplete partition of homologous chromosomes during meiosis I and of sister chromatids during meiosis II associated with a failure of nuclear cleavage. Furthermore, they provide evidence for a clear relationship between a specific morphological abnormality of the sperm and their abnormal cytogenetic content. The treatment of infertility using ICSI would probably be unsuccessful and have a high genetic risk in these cases.

Adult↗

PubMed2001

Risk of trisomy 21 in offspring of patients with Klinefelter's syndrome.

Intracytoplasmic sperm injection (ICSI) has given some patients with Klinefelter's syndrome (ie, men with an XXY sex-chromosome profile) the chance to become fathers, but the genetic makeup of the spermatozoa used for the injection is a concern. We studied the segregation of the sex chromosomes and chromosomes 1 and 21 by multicolour fluorescence in-situ hybridisation in a patient with non-mosaic Klinefelter's syndrome who was a candidate for ICSI. As other workers have found, we saw a higher rate of 24,XX and 24,XY spermatozoa in the patient than in controls. However, we also found a much higher frequency of disomy 21 in the spermatozoa of this patient than in controls (6.2 vs 0.4%). Any child conceived by ICSI using this man's sperm will thus have a proportionally higher risk of trisomy 21.

Chromosome Aberrations↗

PubMed2001

Cis-elements governing trinucleotide repeat instability in Saccharomyces cerevisiae.

Trinucleotide repeat (TNR) instability in humans is governed by unique cis-elements. One element is a threshold, or minimal repeat length, conferring frequent mutations. Since thresholds have not been directly demonstrated in model systems, their molecular nature remains uncertain. Another element is sequence specificity. Unstable TNR sequences are almost always CNG, whose hairpin-forming ability is thought to promote instability by inhibiting DNA repair. To understand these cis-elements further, TNR expansions and contractions were monitored by yeast genetic assays. A threshold of approximately 15--17 repeats was observed for CTG expansions and contractions, indicating that thresholds function in organisms besides humans. Mutants lacking the flap endonuclease Rad27p showed little change in the expansion threshold, suggesting that this element is not altered by the presence or absence of flap processing. CNG or GNC sequences yielded frequent mutations, whereas A-T rich sequences were substantially more stable. This sequence analysis further supports a hairpin-mediated mechanism of TNR instability. Expansions and contractions occurred at comparable rates for CTG tract lengths between 15 and 25 repeats, indicating that expansions can comprise a significant fraction of mutations in yeast. These results indicate that several unique cis-elements of human TNR instability are functional in yeast.

Endodeoxyribonucleases↗

PubMed2001

Prevalence and antifungal susceptibility of 442 Candida isolates from blood and other normally sterile sites: results of a 2-year (1996 to 1998) multicenter surveillance study in Quebec, Canada.

During a 2-year surveillance program (1996 to 1998) in Quebec, Canada, 442 strains of Candida species were isolated from 415 patients in 51 hospitals. The distribution of species was as follows: Candida albicans, 54%; C. glabrata, 15%; C. parapsilosis, 12%; C. tropicalis, 9%; C. lusitaniae, 3%; C. krusei, 3%; and Candida spp., 3%. These data, compared to those of a 1985 survey, indicate variations in species distribution, with the proportions of C. glabrata and C. parapsilosis increasing by 9 and 4%, respectively, and those of C. albicans and C. tropicalis decreasing by 10 and 7%, respectively. However, these differences are statistically significant for C. glabrata and C. tropicalis only. MICs of amphotericin B were > or =4 microg/ml for 3% of isolates, all of which were non-C. albicans species. Three percent of C. albicans isolates were resistant to flucytosine (> or =32 microg/ml). Resistance to itraconazole (> or =1 microg/ml) and fluconazole (> or =64 microg/ml) was observed, respectively, in 1 and 1% of C. albicans, 14 and 9% of C. glabrata, 5 and 0% of C. tropicalis, and 0% of C. parapsilosis and C. lusitaniae isolates. Clinical data were obtained for 343 patients. The overall crude mortality rate was 38%, reflecting the multiple serious underlying illnesses found in these patients. Bloodstream infections were documented for 249 patients (73%). Overall, systemic triazoles had been administered to 10% of patients before the onset of candidiasis. The frequency of isolation of non-C. albicans species was significantly higher in this group of patients. Overall, only two C. albicans isolates were found to be resistant to fluconazole. These were obtained from an AIDS patient and a leukemia patient, both of whom had a history of previous exposure to fluconazole. At present, it appears that resistance to fluconazole in Quebec is rare and is restricted to patients with prior prolonged azole treatment.

Amphotericin B↗

PubMed2000

Evidence for a genetic predisposition towards acute rejection after kidney and simultaneous kidney-pancreas transplantation.

BACKGROUND: In vitro production of tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), interleukin 10 (IL-10), and transforming growth factor-beta (TGF-beta) correlate with their respective genetic polymorphisms. We analyzed the relationship between these genetic polymorphisms and posttransplant outcome. METHODS: Using DNA polymerase chain reaction (PCR) technology, polymorphisms for TNF-alpha, IFN-gamma, IL-10, and TGF-beta were determined for 82 kidney (K) and 19 simultaneous kidney-pancreas (SKP) recipients. These results were analyzed with regard to the incidence of acute rejection (AR), and the timing and severity of the first AR episode. RESULTS: A high TNF-alpha production phenotype correlated with recurrent acute rejection (AR) episodes (P<0.026). Compared with the low TNF-alpha production phenotype, more patients with the high production phenotype had a post-AR serum creatinine >2.0 mg/dl, but this was not statistically significant (64 vs. 35%, P=0.12). There was no relationship between TNF-alpha genotype and the time to first AR episode or incidence of graft loss. IFN-gamma production phenotype showed no correlation with any of these clinical outcome parameters. There was an increase in AR incidence as the IL-10 production phenotype increased (low, intermediate, high), but only in low TNF-alpha producer phenotypes (P=0.023). CONCLUSIONS: Patients with a polymorphic cytokine genotype putatively encoding for high in vivo TNF-alpha production, and to a lesser extent IL-10 cytokine genotypes putatively encoding for higher levels of in vivo IL-10 production, had a worse clinical outcome regarding AR episodes. These data support the hypothesis that the strength of alloimmune responsiveness after transplantation in part is genetically determined.

Acute Disease↗

PubMed2000

Genome organization in the human sperm nucleus studied by FISH and confocal microscopy.

The sperm nucleus has a unique chromatin structure where the DNA is highly condensed and associated with specific proteins, the protamines. It is a nondividing cell which is also transcriptionally inactive. After fusion with an oocyte, the sperm nucleus undergoes decondensation and, in the same time, starts replication and transcription. It has been suggested that somatic chromosomes during interphase are organized in territories which display a cell type and cell cycle specific distribution. The purpose of this work was to investigate whether chromosomes would also have a specific distribution in the sperm nucleus, which could be related to its inactive state, and have implications on the early stages of fertilization. In the present study, centromeric and telomeric sequences were detected by fluorescent techniques performed on human decondensed spermatozoa. Chromosome painting probes were used to detect the chromosome X and chromosome 13 on interphase sperm nuclei. The fluorescent signals were captured in 3D with a confocal microscope. For each of these chromatin structures, the volume, position, and distribution of the signals were analyzed in samples of 30 nuclei with the help of image analysis software. The centromeres appeared grouped in several foci that were randomly distributed within the sperm nucleus. The telomeres gave an approximately haploid number of small signals, evenly distributed throughout the nucleus. The chromosomes X and 13 occupied 4.7% and 3. 7% of the total nuclear volume, respectively. Interestingly, the X chromosome territory showed a preferential position in the anterior half of the volume of the nucleus, whereas chromosome 13 had a random position. This work shows a particular distribution of chromosome territories in the human sperm nucleus that could be related to mechanisms implicated in its specific functions. The analysis of more chromosomes and chromosomal structures, including the Y chromosome, would help to understand the structure of the human sperm chromatin, and its fundamental and clinical implications.

Cell Nucleus↗

PubMed2000

Regulated hyperacetylation of core histones during mouse spermatogenesis: involvement of histone deacetylases.

Here we report a detailed analysis of waves of histone acetylation that occurs throughout spermatogenesis in mouse. Our data showed that spermatogonia and preleptotene spermatocytes contained acetylated core histones H2A, H2B and H4, whereas no acetylated histones were observed throughout meiosis in leptotene or pachytene spermatocytes. Histones remained unacetylated in most round spermatids. Acetylated forms of H2A and H2B, H3 and H4 reappeared in step 9 to 11 elongating spermatids, and disappeared later in condensing spermatids. The spatial distribution pattern of acetylated H4 within the spermatids nuclei, analyzed in 3D by immunofluorescence combined with confocal microscopy, showed a spatial sequence of events tightly associated with chromatin condensation. In order to gain an insight into mechanisms controlling histone hyperacetylation during spermiogenesis, we treated spermatogenic cells with a histone deacetylase inhibitor, trichostatin A (TSA), which showed a spectacular increase of histone acetylation in round spermatids. This observation suggests that deacetylases are responsible for maintaining a deacetylated state of histones in these cells. TSA treatment could not induce histone acetylation in condensing spermatids, suggesting that acetylated core histones are replaced by transition proteins without being previously deacetylated. Moreover, our data showed a dramatic decrease in histone deacetylases in condensing spermatids. Therefore, the regulation of histone deacetylase activity/concentration appears to play a major role in controling histone hyperacetylation and probably histone replacement during spermiogenesis.

Acetylation↗

PubMed2000

Follicular development and atresia in the B6.Y(TIR) sex-reversed mouse ovary.

The B6.Y(TIR) mouse fails to develop normal testes despite transcription of Sry, the primary testis-determining gene on the Y chromosome. Consequently, B6.Y(TIR) fetuses with bilateral ovaries develop into apparently normal but infertile females. This infertility can be mainly attributed to oocyte incompatibility for postfertilization development. In addition, abnormality in preovulatory follicles and rapid loss of oocytes have been observed in XY ovaries. This study examined the effect of gonadotropins on follicular development and atresia in B6.Y(TIR) prepubertal females. The results show that untreated XY females had fewer late preantral follicles and their frequency of atresia was lower. No other difference was found when they were compared with XX females. After treatment with gonadotropins for 24 h, frequency of atresia decreased in both XX and XY ovaries. After 48 h, most preovulatory follicles in XY ovaries were nonatretic, but the oocytes often were denuded. Immunocytochemical staining for connexin 43 detected punctate foci along the oocyte plasma membrane. The density of these foci changed during follicular development, which was similar in XX and XY ovaries. In conclusion, follicular development and atresia under the control of gonadotropins is not influenced by defective oocytes until the preovulatory phase.

Animals↗

PubMed2000

Emergence of resistance of Candida albicans to clotrimazole in human immunodeficiency virus-infected children: in vitro and clinical correlations.

Oropharyngeal candidiasis (OPC) is a common opportunistic infection in human immunodeficiency virus (HIV)-infected patients and other immunocompromised hosts. Clotrimazole troches are widely used in the treatment of mucosal candidiasis. However, little is known about the potential contribution of clotrimazole resistance to the development of refractory mucosal candidiasis. We therefore investigated the potential emergence of resistance to clotrimazole in a prospectively monitored HIV-infected pediatric population receiving this azole. Adapting the National Committee for Clinical Laboratory Standards M27-A reference method for broth antifungal susceptibility testing of yeasts to clotrimazole, we compared MICs in macrodilution and microdilution assays. We further analyzed the correlation between these in vitro findings and the clinical response to antifungal therapy. One isolate from each of 87 HIV-infected children was studied by the macrodilution and microdilution methods. Two inoculum sizes were tested by the macrodilution method (10(3) and 10(4) CFU/ml) in order to assess the effect of inoculum size on clotrimazole MICs. The same isolates also were tested using a noncolorimetric microdilution method. Clotrimazole concentrations ranged from 0.03 to 16 microg/ml. Readings were performed after incubation for 24 and 48 h at 35 degrees C. For 62 (71.2%) of 87 clinical isolates, the MICs were low (< or =0.06 microg/ml). The MIC for 90% of the strains tested was 0.5 microg/ml, and the highest MIC was 8 microg/ml. There was no significant difference between MICs at the two inoculum sizes. There was 89% agreement (+/-1 tube) between the microdilution method at 24 h and the macrodilution method at 48 h. If the MIC of clotrimazole for an isolate of C. albicans was > or =0.5 microg/ml, there was a significant risk (P < 0.001) of cross-resistance to other azoles: fluconazole, > or = 8 microg/ml (relative risk [RR] = 8.9); itraconazole, > or =1 microg/ml (RR = 10). Resistance to clotrimazole was highly associated with clinically overt failure of antifungal azole therapy. Six (40%) of 15 patients for whom the clotrimazole MIC was > or =0.5 microg/ml required amphotericin B for refractory mucosal candidiasis versus 4 (5.5%) of 72 for whom the MIC was <0.5 microg/ml (P = 0.001; 95% confidence interval = 2.3 to 22; RR = 7.2). These findings suggest that an interpretive breakpoint of 0.5 microg/ml may be useful in defining clotrimazole resistance in C. albicans. The clinical laboratory's ability to determine MICs of clotrimazole may help to distinguish microbiologic resistance from the other causes of refractory OPC, possibly reducing the usage of systemic antifungal agents. We conclude that resistance to clotrimazole develops in isolates of C. albicans from HIV-infected children, that cross-resistance to other azoles may develop concomitantly, and that this resistance correlates with refractory mucosal candidiasis.

AIDS-Related Opportunistic Infections↗

PubMed2000

Seeking medical advice if HIV symptoms are suspected. Qualitative study of beliefs among HIV-negative gay men.

OBJECTIVE: To identify beliefs associated with seeking medical advice promptly when symptoms of HIV infection are suspected among HIV-negative gay men. DESIGN: Qualitative study of beliefs among focus group participants. SETTING: Quebec city, Que, metropolitan area. PARTICIPANTS: Referred sample of 20 HIV-negative gay men 18 to 45 years old who attended bars, university, or gay associations in Quebec city. METHOD: Three focus groups of five to seven subjects were formed and each 2-hour session was tape-recorded. MAIN OUTCOME FINDINGS: Participants thought that seeking medical advice promptly when symptoms of HIV are suspected would help them be informed about their health status and would eliminate unnecessary anxiety and fear, but would force them to face reality and make major changes. Barriers were the quality of the relationship with their physicians and concern about discussing their sexual lives. Normative beliefs were sought from members of community groups, circles of close friends, health providers, and the media. CONCLUSIONS: Several beliefs could influence the motivation of seronegative gay men to seek medical advice promptly when symptoms of HIV infection are suspected. These beliefs should be integrated into programs promoting early consultation with physicians and into clinical counseling, as integration could facilitate early treatment and care. Physicians should give special attention to establishing relationships of trust with these patients.

Adolescent↗

PubMed1999

Functional genomic mapping of an early-activated centromeric mammalian origin of DNA replication.

Ors12, a mammalian autonomously replicating sequence (812 bp), was previously isolated by extrusion of African green monkey (CV-1 cells) nascent DNA from active replication bubbles. It contains a region of alpha-satellite extending 168-bp from the 5'-end, and a nonrepetitive portion extending from nucleotide position 169 to nucleotide 812 that is present in less than nine copies per haploid genome. Ors12 is capable of transient autonomous DNA replication in vivo and in vitro, associates with the nuclear matrix in a cell cycle-dependent manner, and hybridizes at the centromeric region of six CV-1 cell chromosomes as well as a marker chromosome. To demonstrate that DNA replication initiates at ors12 at a native chromosomal locus, a 14.2 kb African green monkey genomic clone was isolated and sequence information was obtained that allowed us to generate eight sets of PCR primers spanning a region of 8 kb containing ors12. One set of primers occurred inside ors12. These primers were used to amplify nascent DNA strands from asynchronously growing CV-1 and African green monkey kidney (AGMK) cells, using noncompetitive and competitive PCR-based mapping methodologies. Both assays showed that DNA replication in vivo initiates preferentially in a 2.3 kb region containing ors12, as well as at a second site located 1.7 kb upstream of ors12. This study provides the first demonstration of genomic function for a centromeric mammalian origin of DNA replication, originally isolated by nascent strand extrusion.

Animals↗

PubMed1999

Identification of initiation sites for DNA replication in the human dnmt1 (DNA-methyltransferase) locus.

Vertebrates have developed multiple mechanisms to coordinate the replication of epigenetic and genetic information. Dnmt1 encodes the maintenance enzyme DNA-methyltransferase, which is responsible for propagating the DNA methylation pattern and the epigenetic information that it encodes during replication. Direct sequence analysis and bisulfite mapping of the 5' region of DNA-methyltransferase 1 (dnmt1) have indicated the presence of many sequence elements associated with previously characterized origins of DNA replication. This study tests the hypothesis that the dnmt1 region containing these elements is an origin of replication in human cells. First, we demonstrate that a vector containing this dnmt1 sequence is able to support autonomous replication when transfected into HeLa cells. Second, using a gel retardation assay, we show that it contains a site for binding of origin-rich sequences binding activity, a recently purified replication protein. Finally, using competitive polymerase chain reaction, we show that replication initiates in this region in vivo. Based on these lines of evidence, we propose that initiation sites for DNA replication are located between the first intron and exon 7 of the human dnmt1 locus.

Chromosome Mapping↗

PubMed1999

Carboxy-substituted cinnamides: a novel series of potent, orally active LTB4 receptor antagonists.

A series of carboxy-substituted cinnamides were investigated as antagonists of the human cell surface leukotriene B4 (LTB4) receptor. Binding was determined through measurement of [3H]LTB4 displacement from human neutrophils. Receptor antagonism was confirmed through a functional assay, which measures inhibition of Ca2+ release in human neutrophils. Potent antagonists were discovered through optimization of a random screening hit, a p-(alpha-methylbenzyloxy)cinnamide, having low-micromolar activity. Substantial improvement of in vitro potency was realized by the attachment of a carboxylic acid moiety to the cinnamide phenyl ring through a flexible tether, leading to identification of compounds with low-nanomolar potency. Modification of the benzyloxy substituent, either through ortho-substitution on the benzyloxy phenyl group or through replacement of the ether oxygen with a methylene or sulfur atom, produced achiral antagonists of equal or greater potency. The most potent compounds in vitro were assayed for oral activity using the arachidonic acid-induced mouse ear edema model of inflammation. Several compounds in this series were found to significantly inhibit edema formation and myeloperoxidase activity in this model up to 17 h after oral administration. Representatives of this series have been shown to be potent and long-acting orally active inhibitors of the LTB4 receptor.

Administration, Oral↗

PubMed1999

Inhibition of FEN-1 processing by DNA secondary structure at trinucleotide repeats.

The mechanism by which trinucleotide expansion occurs in human genes is not understood. However, it has been hypothesized that DNA secondary structure may actively participate by preventing FEN-1 cleavage of displaced Okazaki fragments. We show here that secondary structure can, indeed, play a role in expansion by a FEN-1-dependent mechanism. Secondary structure inhibits flap processing at CAG, CGG, or CTG repeats in a length-dependent manner by concealing the 5' end of the flap that is necessary for both binding and cleavage by FEN-1. Thus, secondary structure can defeat the protective function of FEN-1, leading to site-specific expansions. However, when FEN-1 is absent from the cell, alternative pathways to simple inhibition of flap processing contribute to expansion.

DNA↗

PubMed1999

Calcium-dependent actin filament-severing protein scinderin levels and localization in bovine testis, epididymis, and spermatozoa.

We assessed the levels and localization of the actin filament-severing protein scinderin, in fetal and adult bovine testes, and in spermatozoa during and following the epididymal transit. We performed immunoblots on seminiferous tubules and interstitial cells isolated by enzymatic digestion, and on bovine chromaffin cells, spermatozoa, aorta, and vena cava. Immunoperoxidase labeling was done on Bouin's perfusion-fixed testes and epididymis tissue sections, and on spermatozoa. In addition, immunofluorescence labeling was done on spermatozoa. Immunoblots showed one 80-kDa band in chromaffin cells, fetal and adult tubules, interstitial cells, spermatozoa, aorta, and vena cava. Scinderin levels were higher in fetal than in adult seminiferous tubules but showed no difference between fetal and adult interstitial cells. Scinderin levels were higher in epididymal than in ejaculated spermatozoa. Scinderin was detected in a region corresponding with the subacrosomal space in the round spermatids and with the acrosome in the elongated spermatids. In epididymal spermatozoa, scinderin was localized to the anterior acrosome and the equatorial segment, but in ejaculated spermatozoa, the protein appeared in the acrosome and the post-equatorial segment of the head. In Sertoli cells, scinderin was detected near the cell surface and within the cytoplasm, where it accumulated near the base in a stage-specific manner. In the epididymis, scinderin was localized next to the surface of the cells; in the tail, it collected near the base of the principal cells. In Sertoli cells and epididymal cells, scinderin may contribute to the regulation of tight junctional permeability and to the release of the elongated spermatids by controlling the state of perijunctional actin. In germ cells, scinderin may assist in the shaping of the developing acrosome and influence the fertility of the spermatozoa.

Animals↗

PubMed1998

Prophylactic cholecystectomy is not indicated following renal transplantation.

BACKGROUND: The appropriate management of gallstones in patients undergoing renal transplantation is controversial. Screening for gallstones and subsequent prophylactic cholecystectomy has been recommended by some authors for kidney transplant candidates. Our program does not practice routine pretransplant screening for gallstones, and we reviewed our data to determine the outcome of our management approach. METHODS: We reviewed the records of the 1,364 currently followed patients who have undergone kidney transplant at our institution since 1985 in order to evaluate the morbidity and mortality of biliary disease in the post-transplant period. We attempted to contact all patients by telephone or mail survey for the presence of biliary tract disease or operations. RESULTS: Six hundred and sixty-two patients were fully evaluated. Fifty-two (7.85%) required cholecystectomy for stone disease. Seven patients underwent incidental cholecystectomy during other operations, 2 patients developed acalculus cholecystitis, and 14 patients with asymptomatic cholelithiasis are being followed up. Surgical indications included 38 biliary colic, 9 acute cholcystitis, 3 gallstone pancreatitis, and 2 patients who were asymptomatic. Fifty-two patients underwent 30 laparoscopic cholecystectomies, 20 open cholecystectomies, and 2 conversions. Surgery occurred from 7 days to 9.6 years following transplantation. Overall, the median hospital stay (no postoperative stay) was 4 days (range 1 to 57). Patients undergoing laparoscopy had a median stay of 2 days compared with 7 days for those undergoing an open procedure. Complications were seen in 6 patients (11.5%) with no morbidity and no graft loss. The 1-, 2-, and 5-year graft survival was 98%, 96%, and 85%, respectively, in patients undergoing cholecystectomy. CONCLUSIONS: Transplant patients are not at an increased risk for developing biliary tract disease compared with nontransplant patients. Gallstone disease does not have a negative impact on graft survival. Treatment of gallstones has a low risk and does not represent an increased risk of complications in patients following renal transplantation.

Adult↗