Highlights from the combined Society of Urodynamics and Female Urology, and International Society of Pelvic Neuromodulation annual meeting.
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Humans↗
Biomedical subjects
Christopher Smith
Publications and source records attributed to Christopher Smith.
Retinoid signaling determines germ cell fate in mice.
Germ cells in the mouse embryo can develop as oocytes or spermatogonia, depending on molecular cues that have not been identified. We found that retinoic acid, produced by mesonephroi of both sexes, causes germ cells in the ovary to enter meiosis and initiate oogenesis. Meiosis is retarded in the fetal testis by the action of the retinoid-degrading enzyme CYP26B1, ultimately leading to spermatogenesis. In testes of Cyp26b1-knockout mouse embryos, germ cells enter meiosis precociously, as if in a normal ovary. Thus, precise regulation of retinoid levels during fetal gonad development provides the molecular control mechanism that specifies germ cell fate.
Animals↗
Endovascular treatment of an abdominal aortic pseudoaneurysm as a late complication of inferior vena cava filter placement.
Pseudoaneurysms of abdominal aorta after inferior vena cava (IVC) filter placement are uncommon, with associated morbidity and mortality. We report a case in which an abdominal aortic pseudoaneurysm resulted from erosion of a Bird's Nest (Cook, Bloomington, IN) IVC filter into the wall of the abdominal aorta. A 64-year-old woman with an IVC filter placed 10 years prior presented to the emergency department complaining of abdominal pain. A computed tomography scan of the abdomen and pelvis showed a 1.4-cm x 2.0-cm infrarenal aortic pseudoaneurysm adjacent to the IVC filter site. A Zenith endograft (Cook) was used via an open femoral artery exposure to successfully treat the pseudoaneurysm.
Abdominal Pain↗
The case for bladder botulinum toxin application.
Botulinum toxin (BoNT) has been shown to be and effective agent in suppressing detrusor overactivity due to neurogenic causes. Recently, BoNT has been extended to patients who have idiopathic detrusor overactivity. This article reviews the use of BoNT to treat disorders of neurogenic detrusor overactivity and establishes BoNT as a therapeutic modality to treat idiopathic bladder overactivity. It is important to remember that the application of BoNT in the lower urinary tract is not approved by the regulatory agencies and caution should be applied until larger randomized clinical studies are completed.
Administration, Intravesical↗
Allocation of deceased donor kidneys for transplantation: opinions of patients with CKD.
BACKGROUND: Deceased donor kidney allocation schemes are designed to balance optimal utility with equity of access. The aim of this single-center survey is to seek patient opinion about the relative importance of factors used to determine the optimal transplant recipient in kidney allocation schemes. METHODS: In each of 8 scenarios, participants were invited to select which 1 of 2 hypothetical patients should receive a kidney. RESULTS: Two hundred thirty-two of 295 invited patients (78.6%) completed the questionnaire: 104 of 153 invited hemodialysis patients (68.0%) and 128 of 142 invited patients with functioning transplants (90.1%). Only 6.0% of participants agreed with current UK Transplant (UKT) and United Network for Organ Sharing (UNOS) allocation to a patient not yet on dialysis therapy who had been on the transplant waiting list longer than a patient already on dialysis therapy. Only 24.6% of participants agreed with the UKT and UNOS schemes that the transplant survival advantage associated with HLA matching warranted allocation of a kidney to a patient who had been waiting 2 years in preference to a patient waiting 7 years. Participants also were opposed to the use of recipient age and balance of exchange agreements (that reward centers with high rates of organ retrieval). The majority agreed with UKT and UNOS that recipient sex should not be used to allocate kidneys and allocation should favor recipients who have waited longer. CONCLUSION: Patients disagreed with several aspects of current allocation systems. Analysis of patient opinion should be taken into consideration when attempting to optimize the use of this scarce health resource.
Adolescent↗
Re: secondary malignancies in different forms of urinary diversion using isolated gut.
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Humans↗
Characterization of a transplantable hormone-responsive human prostatic cancer xenograft TEN12 and its androgen-resistant sublines.
BACKGROUND: Models for human prostate cancer can facilitate the study of resistance to endocrine therapy, aid drug discovery, and pre-clinical assessment. METHODS: Characteristics thought relevant to the growth in athymic nude mice of TEN12, an androgen-dependent transplantable prostatic cell line derived from a primary prostate carcinoma, and its two androgen-independent sublines, TEN12F and TEN12C, have been assessed immunocytochemically. RESULTS: The xenografts of the parental TEN12 line are moderately differentiated with both papillary and glandular regions, pleomorphic nuclei and abundant mitotic figures and are extremely vascular. The cells express androgen receptor (AR), PSA, VEGF, EGFR, c-erbB2, and TGFalpha. Both TEN12F and TEN12C xenografts possessed a more anaplastic morphology and displayed significantly lower growth rates, reduced blood vessel density (BVD), decreased MIB-1 antigen and E-cadherin expression and increased cytoplasmic AR and HSP90 staining. Elevated EGFR (membrane) but not c-erbB2 expression was demonstrated in the TEN12F line only. Castration of mice bearing TEN12 xenografts rapidly induced the appearance of cytoplasmic AR in the cells, PSA levels decreased initially but recovered to below pre-castration levels whilst reduced TGFalpha and loss of VEGF expression was seen in the long-term castrates. CONCLUSIONS: TEN12 and its sublines offer additional in vivo models to study the factors involved in the progression of prostatic cancer to androgen-independence.
Animals↗
Sensitive sulphur-specific detection of omeprazole metabolites in rat urine by high-performance liquid chromatography/inductively coupled plasma mass spectrometry.
The use of high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICPMS) with sulphur-specific detection was investigated as a method for obtaining metabolite profiles for the drug omeprazole administered as a 1:1 mixture of (32)S- and (34)S-labelled material. Analysis based on the monitoring of the chromatographic eluent at either m/z 32 or 34 was not successful due to insufficient sensitivity caused by interferences from polyatomic ions. However, reaction of sulphur with oxygen in the hexapole collision cell, combined with monitoring at m/z 48 (for (32)S) or m/z 50 (for (34)S), provided a facile method for metabolite profiling. Detection of m/z 48 was superior in sensitivity to detection of m/z 50.
Animals↗
Unexpected observation of ion suppression in a liquid chromatography/atmospheric pressure chemical ionization mass spectrometric bioanalytical method.
Ion suppression is a well-known phenomenon in electrospray ionization (ESI) mass spectrometry. These suppression effects have been shown to adversely affect the accuracy and precision of quantitative bioanalytical methods using ion spray. Such suppression effects have not been as well defined in atmospheric pressure chemical ionization (APCI) and there is some debate whether these effects actually occur in the ionization process using APCI. Here an example is described where clear ion suppression was observed during studies on a model compound and three metabolites using APCI liquid chromatography/tandem mass spectrometry (LC/MS/MS).
Amino Alcohols↗
High-performance liquid chromatography/inductively coupled plasma mass spectrometry and tandem mass spectrometry for the detection of carbon-containing compounds.
High-performance liquid chromatography (HPLC) combined with inductively coupled plasma mass spectrometry (ICPMS) has been studied as a means for the detection of carbon to provide a 'universal' method for detecting organic compounds in chromatographic eluents. Carbon is particularly difficult to ionise and the amount of carbon present in normal chromatographic systems leads to high backgrounds, making detection a challenge. Novel separation approaches were therefore employed, using either entirely aqueous eluents (at temperatures of 60 and 160 degrees C, dependent on the column used) to eliminate the organic modifier completely, or isotopically enriched solvents. For the aqueous eluents, detection limits for sulphanilamide were found to be 2.26 microg, corresponding to 1.13 micromol (0.47 micromol of carbon), injected on a conventional 4.6 mm i.d. column. The use of a narrow bore column with highly isotopically enriched 12C-methanol (99.95 atom%) as organic modifier for the mobile phase enabled the detection of 86 micromol for 13C-triple-labelled caffeine and 79 micromol for 13C-double-labelled phenacetin. The sensitive detection of 12C-compounds with 13C-enriched methanol as organic modifier proved impractical due to a lower level of isotopic enrichment (99 atom%) of this solvent, with the residual 12C-methanol resulting in significant interference.
Antipyrine↗
Over-the-head CPR.
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Cardiopulmonary Resuscitation↗
Polypyrimidine tract binding protein modulates efficiency of polyadenylation.
Polypyrimidine tract binding protein (PTB) is a major hnRNP protein with multiple roles in mRNA metabolism, including regulation of alternative splicing and internal ribosome entry site-driven translation. We show here that a fourfold overexpression of PTB results in a 75% reduction of mRNA levels produced from transfected gene constructs with different polyadenylation signals (pA signals). This effect is due to the reduced efficiency of mRNA 3' end cleavage, and in vitro analysis reveals that PTB competes with CstF for recognition of the pA signal's pyrimidine-rich downstream sequence element. This may be analogous to its role in alternative splicing, where PTB competes with U2AF for binding to pyrimidine-rich intronic sequences. The pA signal of the C2 complement gene unusually possesses a PTB-dependent upstream sequence, so that knockdown of PTB expression by RNA interference reduces C2 mRNA expression even though PTB overexpression still inhibits polyadenylation. Consequently, we show that PTB can act as a regulator of mRNA expression through both its negative and positive effects on mRNA 3' end processing.
Base Sequence↗
An asymmetric synthesis of aza analogues of the tricyclic skeleton of daphnane and the ABC ring system of phorbol.
An asymmetric synthesis of aza analogues of the ABC ring system of phorbol and related compounds containing the 5-7-6-fused framework of daphnane involved construction of the central seven-membered ring by a regioselective reduction of a chiral imide and cyclization with trifluoromethanesulfonic acid. Subsequent demethylation and oxidative dearomatization of ring C afforded an enantiopure dienone 20 with the same relative and absolute configuration at the 9- and 10-positions of the phorbol skeleton.
Aza Compounds↗
Theoretical studies on C-heteroatom bond formation via reductive elimination from group 10 M(PH3)2(CH3)(X) species (X = CH3, NH2, OH, SH) and the determination of metal-X bond strengths using density functional theory.
Density functional calculations have been used to investigate C-C, C-N and C-O bond forming reactions via reductive elimination from Group 10 cis-M(PH3)2(CH3)(X) species (X = C-I3, NH2, OH). Both direct reaction from the four-coordinate species and a three-coordinate mechanism involving initial PH3 loss have been considered. For the four-coordinate pathway the ease of reductive elimination to give M(PH3)2 and CH3-X follows the trend M = Pd < Pt < Ni. The reaction of the cis-M(PH3)2(CH3)(NH2) species is promoted by the formation of methylamine adducts. Non-planar transition states are located and the C-heteroatom bond forming processes are characterised by migration of CH3 onto the cis-heteroatom ligand. For a given ligand, X, activation energies follow the trend M = Ni < Pd < Pt. Formation of the three-coordinate M(PH3)(CH3)(X) species is promoted by a labilisation of the cis-PH3 ligand in the four-coordinate reactants when X = NH2 or OH. For the three-coordinate pathway the energy change for reductive elimination to give M(PH3) and CH3-X again follows the trend M = Pd < Pt < Ni and in all cases the initial product is an M(PH3)(XCH3) adduct. The three-coordinate transition states again involve migration of the CH3 ligand onto the cis-X ligand and for X = NH2 or OH activation energies follow the trend Ni > Pd < Pt. For a given metal activation energies in both the four- and three-coordinate pathways increase along the series CH3 < NH2 < OH. These trends in activation energy can be rationalised in terms of the strength of M-CH3/M-X bonding as long as the extent of geometrical distortion required to obtain the transition state geometry is taken into account. Further calculations on cis-Pd(PH3)2(CH3)(SH) suggest that the more common experimental observation of C(sp3)-S compared to C(sp3)-O reductive elimination arises from the greater kinetic accessibility of the former process rather than an intrinsic thermodynamic preference for C-S bond formation. By comparison, the calculations indicate that C(sp3)-N reductive elimination should be feasible from Ni and Pd systems. DF calculations are shown to reproduce the relative homolytic bond strengths determined experimentally for Pt-X bonds. In the cis-M(PH3)2(CH3)(X) systems the M-CH3 homolytic bond strength increases down the group while for M-NH2 and M-OH bonds the trend is M = N approximately equal to Pd < Pt. M-NH2 and M-OH are considerably stronger than M-CH3 bonds and the presence of a heteroatom ligand serves to weaken M-CH3 bonds even further.
Journal Article↗
Colorectal cancer screening and familial risk: a survey of internal medicine residents' knowledge and practice patterns.
OBJECTIVE: Risk stratification is essential to the appropriate use of colorectal cancer screening recommendations. The principal objective of this study was to assess the knowledge and screening behavior of internal medicine (IM) residents regarding familial colorectal cancer. METHODS: We conducted a survey of IM residents in their second and third year of postgraduate training from two university-based programs (n = 127). The survey instrument assessed physician knowledge of screening recommendations and current practices for individuals with a family history of colorectal cancer, adenomatous polyps, familial adenomatous polyposis, and hereditary nonpolyposis colorectal cancer. The instrument also elicited data regarding familial risk assessment, documentation, and notification of at-risk family members. RESULTS: Eighty-one IM eligible residents (81%) completed the survey. Most respondents identified a family history of colorectal cancer as an important factor in assessing colorectal cancer risk and appropriately implemented relevant screening recommendations. However, for patients with a family history of adenomatous polyps diagnosed before age 60 yr, knowledge and adherence to recommendations advocating screening at age 40 was relatively poor. More importantly, for patients with familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer, respondents lacked the necessary risk assessment skills and knowledge to appropriately implement current recommendations. There were no consistent differences in knowledge or screening behavior when stratified on the basis of program site or postgraduate year status. CONCLUSION: Many IM residents are deficient in their knowledge, risk assessment skills, and screening practices for patients at familial risk of colorectal cancer. Effective educational strategies that promote awareness regarding familial risk, risk assessment skills, and appropriate use of relevant screening guidelines are needed.
Colorectal Neoplasms↗
Epsilon-sarcoglycan mutations found in combination with other dystonia gene mutations.
Myoclonus-dystonia is a movement disorder associated with mutations in the epsilon-sarcoglycan gene (SGCE) in most families and in the DRD2 and DYT1 genes in two single families. In both of the latter families, we also found a mutation of SGCE. The molecular mechanisms through which the detected mutations may contribute to myoclonus-dystonia remain to be determined.
Base Sequence↗