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Biomedical subjects

G Pelletier

Publications and source records attributed to G Pelletier.

At least 91 records · Page 5Linked to original sources

Prolonged distress and clinical deterioration before pericardial drainage in patients with cardiac tamponade.

OBJECTIVE: To determine whether patients with cardiac tamponade are subject to delays and clinical deterioration before undergoing echocardiography and pericardial drainage. DESIGN: Retrospective study. SETTING: The Montreal Heart Institute, Montreal, Quebec, a cardiology referral centre. PATIENTS: The charts of 50 patients who presented with tamponade were reviewed. Intervals between the appearance of symptoms, consultation, echocardiography and drainage were noted. The presence of clinical deterioration before drainage was evaluated. Causes for delays were investigated. RESULTS: Previous cardiac surgery (74%) was the most common etiology of tamponade. Symptoms were present 6.6+/-5.8 days before consultation. The delay between consultation and echocardiography was 1.2+/-2.0 days (range 0 to 12), and that between echocardiography and drainage was 0.8+/-0.9 days (range 0 to four). Patients underwent drainage 1. 9+/-2.5 days (range 0 to 16) after the initial consultation. Deterioration of the clinical status was noted in 34% of patients before pericardial drainage. An error in the initial diagnosis was present in 36% of patients; the majority of these were incorrectly diagnosed with heart failure. Another 44% of patients had no mention of either a working diagnosis in the chart at admission or the desire to rule out tamponade on the request for echocardiography. CONCLUSION: The proper diagnosis does not appear to be initially considered in up to 80% of patients who present with cardiac tamponade. Clinical deterioration occurs in approximately a third of patients during the interval between consultation and pericardial drainage.

Adult↗

Effect of mycophenolate mofetil in heart transplantation.

OBJECTIVE: To study the effect of mycophenolate mofetil (MMF), a new immunosuppressive drug that acts by inhibiting de novo pathways of purine synthesis, and rabbit antithymocyte globulin (RATG) on the lymphocyte subpopulation after heart transplantation. DESIGN: A review of clinical and laboratory records. SETTING: The Montreal Heart Institute. PATIENTS: Thirty-one patients who underwent heart transplantation. In 9 patients, neoral cyclosporine, prednisone and azathioprine were administered (group 1). In 14 patients RATG was added during the first 3 postoperative days (group 2) and in 8 patients RATG and combination immunosuppression was given, but MMF was used instead of azathioprine (group 3). The demographic characteristics of donors and recipients were similar among the 3 groups. MAIN OUTCOME MEASURES: The proportion of CD2, CD4 and CD8 receptor-positive lymphocytes, expressed as a mean (and standard deviation) percentage of the total lymphocyte population, measured at 7, 15 and 30 days and 6 months after transplantation. RESULTS: At 7 days after transplantation, CD2 lymphocytes averaged 55% (18%), 16% (15%) and 14% (11%) in groups 1, 2 and 3 respectively (p < 0.05), CD4 averaged 36% (11%), 9% (12%) and 7% (8%) in groups 1, 2 and 3 (p < 0.05), and CD8 averaged 14% (6%), 4% (3%) and 4% (3%) in groups 1, 2 and 3 (p < 0.05). At 15 days after transplantation CD2 averaged 69% (10%), 42% (16%) and 47% (20%) in groups 1, 2 and 3 respectively (p < 0.05), and CD8 averaged 16% (7%), 16% (6%) and 19% (7%) (p = NS). At 30 days after transplantation the percentages of CD2, CD4 and CD8 lymphocytes were similar among the groups. The freedom rate from acute rejection averaged 22% (14%), 9% (8%) and 50% (18%) (p < 0.05) in groups 1, 2 and 3 at 6 months after transplantation, and the freedom rate from infection averaged 56% (17%), 36% (13%) and 38% (17%) for the 3 groups at this time period (p = NS). CONCLUSIONS: A short course of RATG causes severe, transitory depletion of CD2, CD4 and CD8 lymphocyte subpopulations. MMF decreases the incidence of early acute rejection after heart transplantation without affecting the lymphocyte subpopulation when compared with azathioprine.

Animals↗

ERP differences in visual attention processing between attention-deficit hyperactivity disorder and control boys in the absence of performance differences.

Event-related potentials (ERPs) were recorded during a visual two-choice reaction time (RT) task in attention-deficit hyperactivity disorder (ADHD) and control boys selected using strict inclusion and exclusion criteria. No group differences were found in mean RT and correct responses. Although early occipital ERPs were not affected in the ADHD group, the peak latency of early anterior ERPs (N1, P1, N2) was significantly delayed. ADHD showed a larger effect of stimulus type on the frontal negativity (N530) and the posterior late negativity (nSW) and a smaller effect of stimulus type on anterior N2 and posterior P3b amplitude. The development of N530 and P450 amplitude across blocks of five trials was analyzed using orthogonal polynomial trend analysis of variance software. In the control group, P450 amplitude to "frequent" stimuli reduced across blocks. In the ADHD group, N530 amplitude increased for "rare" stimuli across blocks. It is suggested that the ADHD group showed a lack of automatization of the categorization process with increasing time on task for which they compensated by controlled attentional processes.

Attention↗

Expression of integrin alpha5beta1 and MMPs associated with epithelioid morphology and malignancy of uveal melanoma.

PURPOSE: Altered expression of the alpha5beta1 integrin and matrix metalloproteinases (MMPs) is recognized as a hallmark of invasive tumor cells. The purpose of the present study was to investigate the expression of integrin subunit alpha5, its corresponding ligand fibronectin (FN), and the expression pattern for MMPs in four highly proliferative human choroidal melanomas (TP17, TP31, SP8.0, and SP6.5) to evaluate whether any correlation can be established between these markers and cell tumorigenicity. METHODS: Cell tumorigenicity was evaluated by subcutaneous injection of uveal melanoma cell lines in immunodeficient nude mice. Anchorage dependency was evaluated by growth assays in soft agar. The invasive ability of each cell type was also determined using a modified Boyden chamber. Expression of both the alpha5 integrin subunit and FN was determined at the mRNA level by RT-PCR. The protein level (for alpha5) was determined by flow cytometry and inhibition of adhesion assays by using an antibody directed against the alpha5 subunit. Expression of MMPs was determined by standard gelatin zymography. RESULTS: Assays in nude mice provided evidence that the cell lines possess a range of tumorigenic ability of TP17>TP31>SP8.0>SP6.5. Antibody inhibition of cell adhesion and flow cytometry demonstrated that TP17 cells have no detectable membrane-bound alpha5beta1, whereas low levels are found in primary cultured melanocytes, as well as in SP6.5, SP8.0, and TP31 cells. RT-PCR analyses provided evidence that both FN and alpha5 expression may be regulated at the transcriptional level. Gelatin zymography revealed that all cell lines, as well as normal melanocytes, express MMP-2 at varying levels but that only the highly invasive TP17 cell line secretes a distinctive MMP with a high molecular weight of 117 kDa. CONCLUSIONS: Among the four melanoma cell lines selected for the completion of this study, TP17 exhibited the most aggressive phenotype, which also correlated with the mostly epithelioid morphology of these cells. The cell morphology of the TP17 cell line could be related to the loss of alpha5beta1, whereas its invasive properties are more likely related to the expression of the 117-kDa MMP.

Aged↗

[Late biliary complications after endoscopic sphincterotomy for common bile duct stones in patients older than 65 years of age with gallbladder in situ].

UNLABELLED: The aim of this retrospective study was to evaluate the nature and the frequency of biliary complications after endoscopic retrograde cholangiography for common bile duct stones in elderly patients with gallbladder in situ. METHODS: Between 1991 and 1993, 169 consecutive patients with gallbladder in situ, older than 65 years (79 +/- 8) had an endoscopic retrograde cholangiography with sphincterotomy for choledocholithiasis. Information on the early (<1 month) and late biliary complications, treatment and mortality were obtained by mail or phone calls from patients and general practitioners. Long-term data were obtained for 139 patients (82%). Mean follow-up was 56.5 months (80 months for patients still alive at the end of the study). RESULTS: Early complications occurred in 13 patients (10.8%). Seven patients had acute cholecystitis, present before the procedure in all cases; all were treated by surgery. Other early complications included cholangitis (n =7), mild acute pancreatitis (n =3), bleeding (n =1), perforation (n =1), biliary colic (n =1), pneumopathy (n =1) and bradycardia (n =1), all treated medically. Forty patients underwent early cholecystectomy, and 5 died during the first month without biliary disease. Late complications were thus assessed in 94 patients and occurred in 13 (14%), i.e around 2% per year. Complications were acute cholangitis (n=4), biliary pain (n =4), cholecystitis (n =2), abdominal pain (n =2) and jaundice due to sphincterotomy stenosis (n =1). Five patients had cholecystectomy, 1 a radiological drainage and 7 were treated medically. No death due to a biliary complication was observed. The presence of gallstones, the absence of gallbladder opacification at cholangiography were not prognostic factors for the recurrence of biliary symptoms. 65 patients (50%) died without biliary disease during the follow-up (actuarial death rate 10.5% per year). CONCLUSION: Late biliary complications after endoscopic retrograde cholangiography for choledocholithiasis in patients with gallbladder in situ are rare (2% per year). Prophylactic cholecystectomy after sphincterotomy does not seem warranted in elderly patients, because of rare recurrent biliary symptoms, low mortality rate, and limited life expectancy.

Actuarial Analysis↗

The restorer Rfo gene acts post-translationally on the stability of the ORF138 Ogura CMS-associated protein in reproductive tissues of rapeseed cybrids.

This paper describes the analysis of the effect of the restorer gene Rfo on the expression of the ORF138 protein associated with Ogura cytoplasmic male sterility (CMS) which has been engineered in rapeseed by protoplast fusion. We show that the presence of the Rfo gene in the genome of the plants decreases the amount of ORF138 protein in floral buds, this effect being the most dramatic in anthers at the stage of development when the sterile phenotype is normally expressed. However, the amount of orf138 transcripts is not affected by the Rfo gene in the same organs at the same stages. Total polysome analyses of buds and anthers show that the orf138 transcripts are translated with the same efficiency in sterile and restored plants. From these results we infer that the Rfo gene product acts on the post-translational stability of the ORF138 protein, leading to a decrease in the accumulation of the protein and a restoration of fertility.

Brassica↗

Isolation of rapeseed genes expressed early and specifically during development of the male gametophyte.

A cDNA subtraction and differential hybridization strategy was used to isolate cDNAs expressed early during male gametophyte development in the important crop species Brassica napus. Three cDNAs, corresponding to genes highly and specifically expressed at the tetrad and microspore stages, are presented here. The analysis of one of them, named BnM3.4, by in situ hybridization, showed that it is expressed specifically and at a high level in the rapeseed microspore. The specificity in its profile of expression is most likely transcriptionally controlled as a similar pattern of expression was also observed in Arabidopsis thaliana plants transformed by the BnM3.4 promoter fused to the reporter GUS-coding sequence. The putative BnM3.4 promoter contains three dispersed copies of a motif described previously in the promoters of several genes expressed in the male gametophyte. The BnM3.4 gene encodes a predicted novel proline-rich protein of 23.4 kDa which may interact with cytoskeletal components or have a structural role in the cell wall.

Arabidopsis↗

Effects of ageing and dehydroepiandrosterone administration on pro-opiomelanocortin mRNA expression in the anterior and intermediate lobes of the rat pituitary.

There is still controversy about the influence of ageing on the activity of the hypothalamo-pituitary-adrenocortical (HPA) axis in the rat. The first objective of the present study was to evaluate the influence of ageing on the activity of the HPA axis by measuring pituitary proopiomelanocortin (POMC, the precursor of ACTH and alphaH) mRNA levels in the anterior and intermediate lobes in young (50-55-day old) and aged (18-month-old) rats of both sexes. The second goal of the study was to evaluate the effect of 2.5 day administration of dehydroepiandrosterone (DHEA), a steroid precursor which has been shown to improve some ageing-associated deficits. In the young male anterior pituitary, DHEA induced a 17.5% increase in POMC mRNA levels. In aged males, anterior pituitary POMC mRNA levels were 22% lower than those detected in young animals. DHEA treatment produced a 26% increase, then completely restoring mRNA levels when compared to those found in young vehicle-treated males. In the young female, DHEA did not induce any changes in anterior pituitary POMC mRNA. In aged females a 24% reduction in the hybridization signal was observed. This reduction was completely reversed by DHEA which induced a 45% increase over the levels observed in vehicle-treated aged animals. In the intermediate lobe, the results were very similar to those obtained in the anterior lobe, although the observed effects induced by ageing and DHEA were less striking. These results together with previous ones indicating an age-related decrease in corticotropin-releasing hormone (CRH) neuronal activity suggest that ageing is associated with a decrease in HPA axis activity. They also demonstrate that a short-term DHEA treatment can exert a beneficial influence by reversing the decrease in pituitary POMC mRNA expression which occurs as a consequence of ageing.

Aging↗

The EMB 506 gene encodes a novel ankyrin repeat containing protein that is essential for the normal development of Arabidopsis embryos.

The EMB 506 gene of Arabidopsis, required for the normal development of the embryo beyond the globular stage, has been cloned. The gene encodes a protein of predicted size 35 kDa that contains five ankyrin (ANK) repeats within the C terminal moiety. ANK repeats are conserved domains of 33 amino acids involved in specific recognition of protein partners. The EMB 506 protein was detected at different stages of silique development but accumulated preferentially in the mature cauline leaves. The rescue of homozygous emb 506 embryos by complementation with the wild-type sequence cDNA demonstrated that the emb mutation is a consequence of the T-DNA insertion and that integration and expression of the transgene occurred during gametogenesis and/or early embryo development. In addition to the drastic effect of the emb 506 mutation during embryo development, complementation experiments revealed another effect of the gene: emb 506 plants transformed with the wild-type EMB 506 sequence were able to produce viable seeds but showed a reduction of apical dominance and the presence of adventitious buds or bracts along the stem. This result supports the idea that genes essential for embryogenesis may also be required at other stages of the plant life cycle.

Amino Acid Sequence↗

The BANYULS gene encodes a DFR-like protein and is a marker of early seed coat development.

Mutations in the BANYULS (BAN) gene lead to precocious accumulation of anthocyanins in immature seed coat in Arabidopsis. The ban -1 allele has been isolated from a collection of T-DNA transformants and found to be tagged by the integrative molecule. The sequencing of wild-type and two independent mutant alleles confirmed the identity of the gene. Analysis of the full-length cDNA sequence revealed an open reading frame encoding a 342 amino acid protein which shared strong similarities with DFR and other enzymes of the phenylpropanoid biosynthesis pathway. BAN expression was restricted to the endothelium of immature seeds at the pre-globular to early globular stages of development as predicted from the maternal inheritance of the phenotype, and therefore represents a marker for early differentiation and development of the seed coat. BAN is probably involved in a metabolic channelling between the production of anthocyanins and pro-anthocyanidins in the seed coat.

Alleles↗

Immunocytochemical localization and biological activity of hydroxysteroid sulfotransferase in the frog brain.

Biosynthesis of the neuroactive steroids pregnenolone sulfate (delta5PS) and dehydroepiandrosterone sulfate (DHEAS) is catalyzed by the enzyme hydroxysteroid sulfotransferase (HST), which transfers the sulfonate moiety from 3'-phosphoadenosine 5'-phosphosulfate (PAPS) on the 3-hydroxy site of steroids. Although high concentrations of delta5PS and DHEAS have been detected in the rat brain, the anatomical localization of HST in the CNS has never been determined. Using an antiserum against rat liver HST, we have investigated the distribution of HST-like immunoreactivity in the CNS of the frog Rana ridibunda. Two populations of HST-immunoreactive neurons were observed in the hypothalamus, and several bundles of positive nerve fibers were visualized in the telencephalon and diencephalon. Incubation of frog brain homogenates with [35S]PAPS and [3H]pregnenolone yielded the formation of several 3H,35S-labeled compounds, including delta5PS and testosterone sulfate. When [3H]dehydroepiandrosterone and [35S]PAPS were used as precursors, one of the 3H,35S-labeled metabolites coeluted with DHEAS. Neosynthesis of [3H]delta5PS and [3H]DHEAS was reduced significantly by 2,4-dichloro-6-nitrophenol, a specific inhibitor of sulfotransferases. The present study provides the first immunocytochemical mapping of HST in the brain. Our data also demonstrate for the first time that biosynthesis of the highly potent neuroactive steroids delta5PS and DHEAS occurs in the CNS of nonmammalian vertebrates.

Animals↗

Cellular localization of estrogen receptor beta messenger ribonucleic acid in cynomolgus monkey reproductive organs.

There is now evidence that the recently identified estrogen receptor (ER) beta is more widely distributed in the body than is ER-alpha. In order to gain more information about the role of ER-beta in reproduction, we have investigated by in situ hybridization the localization of mRNA expression of this ER subtype in adult monkey reproductive organs. In the pituitary gland of animals of both sexes, in both the anterior and intermediate lobes, a large number of cells were positive. No specific signal was observed in the posterior lobe. In the ovary, granulosa cells in primary and growing follicles highly expressed ER-beta mRNA. The theca interna cells were also strongly labeled. In some corpora lutea, the luteal cells were strongly labeled, while in other ones, the signal was weak. A hybridization signal was also detected in the ovarian surface epithelium. In the uterus, ER-beta mRNA was found in high concentration in glandular epithelial cells and stromal cells of the endometrium, while weaker labeling was consistently observed in smooth muscle cells. In the mammary gland, labeling was detected in the epithelial cells of acini and interlobular ducts as well as stromal cells. In the testis, specific labeling was detected in the seminiferous epithelium whereas the interstitial Leydig cells were unlabeled. Although it was not possible to clearly identify all the positive cell types, it appears that Sertoli cells as well as the vast majority of germinal cells express ER-beta mRNA. In the prostate, the secretory epithelial cells exhibited a specific autoradiographic reaction while the stromal cells did not show mRNA expression. The epithelial cells of the prostatic urethra showed a strong labeling. No hybridization signal was detected in the seminal vesicles. It then appears quite clear that ER-beta is expressed in a cell-specific manner in all the monkey reproductive organs studied. In the female, the wide distribution of these receptors in the ovary and uterus suggests that ER-beta may play an important role in the mediation of the known effects of estrogen in reproduction functions. In the male testis and prostate, ER-beta has been found in cells that contain very little or no ER-alpha. The role of circulating or locally produced estrogens in the male reproductive system remains to be clarified.

Animals↗

Prediction of common bile duct stones by noninvasive tests.

OBJECTIVE: To define accurate and useful predictors of common bile duct stones (CBDS). SUMMARY BACKGROUND DATA: The ability to predict CBDS with noninvasive tests can avoid unnecessary, costly, or risky procedures. METHODS: All patients referred for examination for CBDS by endoscopic ultrasonography (EUS) from 1993-1996 were prospectively entered in a database. In a first sample selected randomly from the whole population, predictors of CBDS were determined by univariate analysis and logistic regression. Predictors were subsequently tested in that sample and in the rest of the population. A separate analysis was done for patients planned for cholecystectomy. RESULTS: Eight hundred and eighty patients (328 men, 552 women), aged 57.8 +/- 17 years (range 16-94), were included. The prevalence of CBDS was 18.8%. Age, serum levels of bilirubin, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase (GGT), and alkaline phosphatase, and the existence of jaundice and fever, a dilated bile duct, and a pathologic gallbladder were found to be associated with CBDS. Logistic regression was undertaken separately for patients younger than 70 years (predictors: GGT >7 x normal; pathologic gallbladder; dilated bile duct) and older than 70 years (predictors: GGT >7 x normal; fever > 38 degrees C; dilated bile duct). Odds ratios were 3 to 6.7. The model was satisfactorily applicable to the second sample; age <70 years: chi2 = 3.3 (NS); age >70 years: chi2 = 3.8 (NS). In patients younger than age 70 and planned for cholecystectomy, the combination of the level of GGT and dilated bile duct predicted CBDS accurately. CONCLUSIONS: A simple screening of patients at risk for CBDS can be achieved with three predictive criteria adapted for the patient's age.

Adolescent↗

Use of magnetic resonance cholangiography in the diagnosis of choledocholithiasis: prospective comparison with a reference imaging method.

BACKGROUND: Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract. AIM: To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods. PATIENTS/METHODS: 70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cholangiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations. RESULTS: 49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%. CONCLUSIONS: Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones.

Adult↗

Immunocytochemical localization of type 5 17beta-hydroxysteroid dehydrogenase in human reproductive tissues.

17beta-hydroxysteroid dehydrogenase (17beta-HSD) controls the last step in the formation of all androgens and all estrogens. At least six 17beta-HSD isoenzymes have been identified. The recently cloned Type 5 17beta-HSD transforms 4-dione into testosterone. To gain a better understanding of the role of this enzyme in reproductive tissues, we immunocytochemically localized the enzyme in human male and female reproductive organs. In the ovary of adult premenopausal women (25-40 years of age), immunostaining was found in corpus luteum cells. In the uterus, staining was detected only in the epithelial cells of the endometrium. Immunolabeling was also detected in the mammary gland, a positive reaction being detected in epithelial cells of acini and intralobular ducts as well as in the surrounding stromal cells. In the testis, strong staining was seen in the Leydig cells, and a weak but specific reaction was occasionally detected in Sertoli and germ cells. In the prostate, specific labeling was observed in alveoli and stromal fibroblasts. In alveoli, all the basal cells were generally labeled, whereas the luminal cells exhibited variations in immunoreactivity. In all the reproductive organs examined, specific staining was routinely detected in the walls of blood vessels, including the endothelial cells. These results indicate a cell-specific localization of Type 5 17beta-HSD in the different human reproductive organs, thus suggesting new mechanisms of local androgen and estrogen formation that may play an important physiological role.

17-Hydroxysteroid Dehydrogenases↗

Localization of type 5 17beta-hydroxysteroid dehydrogenase, 3beta-hydroxysteroid dehydrogenase, and androgen receptor in the human prostate by in situ hybridization and immunocytochemistry.

An important source of androgens in the human prostate are those synthesized locally from the inactive adrenal precursor dehydroepiandrosterone (DHEA) and its sulfated derivative DHEA-S. Three beta-HSD (hydroxysteroid dehydrogenase) converts DHEA into androstenedione (4-dione), whereas type 5 17beta-HSD catalyzes the reduction of 4-dione into testosterone in the human prostate and other peripheral intracrine tissues. In the present study, we have used two complementary approaches, namely in situ hybridization and immunocytochemistry, to identify the cells that contain the type 5 17beta-HSD messenger RNA and enzyme in human benign prostatic hyperplasia (BPH). Localization of 3beta-HSD and of the androgen receptor (AR) was also investigated by immunostaining in the same tissue. To find out whether there are any differences between BPH and normal prostate tissue, the localization of type 5 17beta-HSD was reexamined by immunocytochemistry in the normal human prostate samples and also in normal prostate epithelial cell line (PrEC). The in situ hybridization results obtained with a tritiated uridine triphosphate (3H-UTP)-labeled type 5 17beta-HSD riboprobe are in agreement with the immunostaining data obtained with a specific antibody to the enzyme. The immunostaining results obtained from normal prostate tissue and BPH were found to be similar. Thus, in the glandular epithelium, basal cells highly express the messenger RNA and the enzyme, whereas luminal cells show a much lower and variable level of expression. In the stroma and walls of blood vessels, fibroblasts and the endothelial cells lining the blood vessels show positive staining. Similar results are observed when the cellular distribution of 3beta-HSD is investigated. AR immunoreactivity, however, shows a different distribution because, in the epithelium, most of the nuclei of basal cells are negative, whereas the majority of nuclei of the luminal cells show positive staining. A strong reaction for AR is also found in most stromal cell nuclei and in the nuclei of most endothelial cells, as well as in some other cells of the walls of blood vessels. In conclusion, human type 5 17beta-HSD, as well as 3beta-HSD, are highly expressed, not only in the basal epithelial cells and stromal fibroblasts but also in the endothelial cells and fibroblasts of the blood vessels. AR, on the other hand, is highly expressed in the luminal cells. The present data suggest that DHEA is transformed in the basal cells of the glandular epithelium into 4-dione by 3beta-HSD and then into testosterone by type 5 17beta-HSD, whereas dihydrotestosterone is synthesized in the luminal cells after diffusion of testosterone from the underlying layer of basal cells. The potential role of androgen formation and action in blood vessels is unknown and opens new avenues of investigation for a better understanding of the multiple roles of androgens.

17-Hydroxysteroid Dehydrogenases↗

Alternative therapy use in neurologic diseases: use in brain tumor patients.

BACKGROUND: The extent of alternative therapy use in brain tumor patients is unknown, but it may be frequent and seems important to those who use it. OBJECTIVE: To characterize alternative therapy use in brain tumor patients. METHODS: Prospective questionnaire-based survey of 167 brain tumor patients who attended a cancer center in Southern Alberta. Physicians completed forms describing clinical information such as disease status. RESULTS: The response rate was 91% (167/184). Twenty-four percent of patients used alternative therapies and often more than one therapy at the same time. Motivation to use these therapies was influenced by the desire for patient-focused treatment and a perceived need to take charge. Alternative therapy users were younger (p = 0.04) and more likely to be on sick or disability leave (p = 0.02), to come in for repeat visits (p = 0.05), and to have received conventional treatments (p = 0.01). Users tended to have lower quality of life with respect to physical well-being, functional well-being, and a specific brain tumor subscale. Clinical variables, such as disease status, tumor type, and Karnofsky Performance Score, were not related to alternative therapy use. Major changes in number and types of alternative therapy use occurred during the study period. No major side effects or tumor responses were seen with alternative therapies. CONCLUSIONS: Alternative therapy use in brain tumor patients is common and may reflect unmet patient needs with respect to their cancer care within the current model of health care delivery.

Adult↗