A case of severe refractory thrombotic thrombocytic purpura responding to treatment with 13-cis retinoic acid.
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Adult↗
Biomedical subjects
T Schlenker
Publications and source records attributed to T Schlenker.
[Medical aspects of fitness to be remanded in custody or be imprisoned].
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Alcohol Withdrawal Delirium↗
Blastocyst score affects implantation and pregnancy outcome: towards a single blastocyst transfer.
OBJECTIVE: To determine the relationship between blastocyst score and pregnancy outcome. DESIGN: Retrospective review of blastocyst transfer in an IVF clinic. SETTING: Private assisted reproductive technology unit. PATIENT(S): 107 patients undergoing blastocyst culture and transfer of two embryos. INTERVENTION(S): Culture of all pronucleate embryos in sequential media to the blastocyst stage (day 5), followed by transfer of two blastocysts. MAIN OUTCOME MEASURE(S): Implantation rates, pregnancy rates, and twinning were analyzed. RESULT(S): When a patient received two top-scoring blastocysts (64% of patients), implantation and pregnancy rates were 70% and 87%, respectively. The twinning rate in this group was 61%. When only one top-quality blastocyst was available for transfer (21% of patients), the implantation and pregnancy rates were 50% and 70%. The twinning rate for this group was 50%. In contrast, when only low-scoring blastocysts were available for transfer (15% of patients), implantation and pregnancy rates were 28% and 44%, and the twinning rate was 29%. No monozygotic twins were observed in this group of patients. CONCLUSION(S): The ability to transfer one high-scoring blastocyst should lead to pregnancy rates greater than 60%, without the complication of twins.
Adult↗
Functional interactions between oxidative stress, membrane Na(+) permeability, and cell volume in rat hepatoma cells.
BACKGROUND & AIMS: Oxidative stress leads to a rapid initial loss of liver cell volume, but the adaptive mechanisms that serve to restore volume have not been defined. This study aimed to evaluate the functional interactions between oxidative stress, cell volume recovery, and membrane ion permeability. METHODS: In HTC rat hepatoma cells, oxidative stress was produced by exposure to H(2)O(2) or D-alanine plus D-amino acid oxidase (40 U/mL). RESULTS: Oxidative stress resulted in a rapid decrease in relative cell volume to 0.85 +/- 0.06. This was followed by an approximately 100-fold increase in membrane cation permeability and partial volume recovery to 0.97 +/- 0.05 of original values. The volume-sensitive conductance was permeable to Na(+) approximately K(+) >> Tris(+), and whole-cell current density at -80 mV increased from -1.2 pA/pF at 10(-5) mol/L H(2)O(2) to -95.1 pA/pF at 10(-2) mol/L H(2)O(2). The effects of H(2)O(2) were completely inhibited by dialysis of the cell interior with reduced glutathione, and were markedly enhanced by inhibition of glutathione synthase. CONCLUSIONS: These findings support the presence of dynamic functional interactions between cell volume, oxidative stress, and membrane Na(+) permeability. Stress-induced Na(+) influx may represent a beneficial adaptive response that partially restores cell volume over short periods, but sustained cation influx could contribute to the increase in intracellular [Na(+)] and [Ca(2+)] associated with cell injury and necrosis.
Alanine↗
[Ulcers of the colon in association with nonsteroidal anti-inflammatory drugs (NSAID)--a rare cause of gastrointestinal bleeding? Report of 3 cases].
Although adverse side effects of nonsteroidal anti-inflammatory drugs (NSAID) can affect the whole gastrointestinal tract, most reports refer to upper gastrointestinal tract complications. We report on 3 patients with lower gastrointestinal bleeding (patient 1 and 2) respectively detectable fecal blood loss (patient 3) after the use of NSAID. Patient 1 and 3 were taking NSAID over at least 6 months for the treatment of rheumatic diseases while patient 2 reported a single use of 2 g acetylsalicylic acid. Colonoscopy showed a single ulcer of the colon in patients 1 and 2. Due to acute bleeding patient 1 required interventional endoscopic treatment. Colonoscopy of patient 3 revealed multiple colonic ulcerations. Gastroduodenoscopy also detected adverse NSAID-effects on the upper gastrointestinal tract in patient 1 and 3 (ulcers of the stomach, erosive duodenitis). NSAID-medication was discontinued in all patients and, additionally, mesalazine was administered to patient 3. Consecutively, symptoms and lesions disappeared. Our cases stress the clinical importance of NSAID-toxicity distal to the small intestine which may exist concomitantly to lesions of the upper gastrointestinal tract and is not obligatory dose-dependent.
Aged↗
Blastocyst culture and transfer: analysis of results and parameters affecting outcome in two in vitro fertilization programs.
OBJECTIVE: To determine whether previously described advanced blastocyst development and high implantation rates are confirmed in an expanded multicenter trial. DESIGN: Retrospective review. SETTING: Two private assisted reproductive technology units. PATIENT(S): One hundred seventy-four patients who underwent blastocyst culture and transfer. INTERVENTION(S): Culture of all pronucleate embryos in sequential media to the blastocyst stage (day 5) followed by ET. MAIN OUTCOME MEASURE(S): The number and percentage of blastocysts developed, implantation rates, pregnancy rates, and parameters that affected outcome were analyzed. RESULT(S): Only 3 of 174 patients failed to achieve blastocyst-stage ET. The mean blastocyst development rate was 48%. The ongoing pregnancy rate was 66.3% per oocyte retrieval, with a mean (+/-SE) of 2.2 +/- 0.05 blastocysts transferred and an implantation rate of 48% per blastocyst transferred. CONCLUSION(S): Blastocyst culture and transfer is an effective means of treating patients who respond well to gonadotropins. High pregnancy rates can be accomplished with low numbers of embryos transferred. Patients who failed to achieve ET were rare.
Adult↗
Improving vaccination coverage through accelerated measurement and feedback.
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Child↗
Culture and transfer of human blastocysts increases implantation rates and reduces the need for multiple embryo transfers.
OBJECTIVE: To determine whether the transfer of blastocysts on day 5, developed in sequential culture media, resulted in an increase in implantation rate compared with embryos transferred on day 3. DESIGN: Comparative study of embryo culture regimes. SETTING: Private practice assisted reproductive technology center. PATIENT(S): Twenty-three patients undergoing routine IVF cycles. INTERVENTION(S): Culture of embryos to day 3 in either standard culture conditions or a serum-free chemically defined medium. One hundred one embryos were subsequently cultured from day 3 to day 5 in a second serum-free medium specifically designed to support development of the blastocyst. MAIN OUTCOME MEASURE(S): Embryo cell number and quality on day 3. Blastocyst development on day 5. Implantation rate (determined by fetal heart) and ongoing pregnancy rate (PR). RESULT(S): Implantation rates for embryos transferred at the blastocyst stage of development were twice that observed for embryos transferred on day 3, around the eight-cell stage. Significantly more embryos were required for transfer on day 3, compared with day 5, to establish similar PRs. CONCLUSION(S): Viable human blastocysts can be obtained in sequential culture media in the absence of coculture and serum. Transfer of blastocysts in IVF will facilitate high PRs while limiting the number of embryos transferred and therefore minimizes the risk of multiple gestation.
Adult↗
Stimulation of cyclic guanosine monophosphate production by natriuretic peptide in human biliary cells.
BACKGROUND & AIMS: Guanosine 3',5'-cyclic monophosphate (cGMP), whose production is stimulated by the interaction of nitric oxide, natriuretic peptides, and guanylin with their respective guanylate cyclases, activates secretion through ion channels in several epithelia. Cl- channels have been identified in the apical membrane of biliary epithelial cells. The aim of this study was to investigate the production of cGMP and its effects on Cl- permeability in biliary epithelial cells. METHODS: Halide efflux measurement, whole-cell patch clamp recording, radioimmunoassay, and reverse-transcription polymerase chain reaction using two human biliary cell lines (H69 and Mz-ChA-1) were performed. RESULTS: In cells equilibrated with 125I, bromo-cGMP stimulated halide efflux by 22%. In whole-cell patch clamp recordings, the addition of cGMP intracellularly, or of atrial natriuretic peptide extracellularly, stimulated inward currents at negative membrane potentials, consistent with Cl- efflux through open channels. In H69 cells, atrial and C-type natriuretic peptides stimulated production of cGMP. Mz-ChA-1 responded only to atrial natriuretic peptide. Both cell lines expressed messenger RNA for the guanylate cyclase type A receptor and the guanylate cyclase free-clearance receptor. CONCLUSIONS: These data suggest that natriuretic peptide stimulates cGMP production in human biliary epithelial cells, which in turn may regulate ductular bile formation through the opening of Cl- channels.
Atrial Natriuretic Factor↗
A prospective randomized trial of blastocyst culture and transfer in in-vitro fertilization.
The effectiveness of blastocyst culture and transfer in human in-vitro fertilization (IVF) was evaluated in a prospective randomized trial in patients having a moderate to good response to gonadotrophin stimulation. Embryos were transferred either on day 3 after culture to around the 8-cell stage in Ham's F-10 medium supplemented with fetal cord serum, or on day 5 after culture to the blastocyst stage in the sequential serum-free media G 1.2 and G 2.2. The pregnancy rates after transfer on day 3 or day 5 were equivalent, 66 and 71% respectively; however, significantly more embryos were transferred on day 3 (3.7) than on day 5 (2.2). The number of blastocysts transferred did not affect the implantation rate, and pregnancy rates when either two or three blastocysts were transferred were 68 and 87% respectively. The implantation rate of the blastocysts (50.5% fetal heart beat) was significantly higher compared to the cleavage stage embryos transferred on day 3 (30.1%). The percentage of blastocyst development was not affected by the number of 2-pronuclear embryos, or by maternal age. Irrespective of the number of blastocysts formed, pregnancy rates were similar. Furthermore, the pregnancy rate following blastocyst transfer in patients with 10 or more follicles at the time of human chorionic gonadotrophin administration was not affected by patient age. More than 60% of patients having blastocyst culture and transfer had supernumerary embryos for cryopreservation. The establishment of a pregnancy following thaw and transfer confirmed the viability of cryopreserved blastocysts cultured in the absence of serum or co-culture. The ability to transfer just two blastocysts while maintaining high pregnancy rates will therefore help to eliminate high order multiple gestations and improve the overall efficiency of human IVF.
Adult↗
Cytosolic Ca2+ and protein kinase Calpha couple cellular metabolism to membrane K+ permeability in a human biliary cell line.
Cholangiocytes represent an important target of injury during the ischemia and metabolic stress that accompanies liver preservation. Since K+ efflux serves to minimize injury during ATP depletion in certain other cell types, the purpose of these studies was to evaluate the effects of ATP depletion on plasma membrane K+ permeability of Mz-ChA-1 cells, a model human biliary cell line. Cells were exposed to dinitrophenol (50 microM) and 2-deoxyglucose (10 mM) as the standard model of metabolic injury. Whole-cell and single K+ channel currents were measured using patch clamp techniques; and intracellular [Ca2+] ([Ca2+]i) was estimated by calcium green-1 fluorescence. Metabolic stress increased [Ca2+]i, and stimulated translocation of the alpha isoform of protein kinase C (PKCalpha) from cytosolic to particulate cell fractions. The same maneuver increased membrane K+ permeability 40-70-fold as detected by (a) activation of K+selective whole cell currents of 2,176+/-218 pA (n = 34), and (b) opening of apamin-sensitive K+ channels with a unitary conductance of 17.0+/-0.2 pS. PKCalpha translocation and channel opening appear to be related since stress-induced K+ efflux is inhibited by chelation of cytosolic Ca2+, exposure to the PKC inhibitor chelerythrine (25 microM) and downregulation of PKC by phorbol esters. Moreover, K+ currents were activated by intracellular perfusion with recombinant PKCalpha in the absence of metabolic inhibitors. These findings indicate that in biliary cells apamin-sensitive K+ channels are functionally coupled to cell metabolism and suggest that cytosolic Ca2+ and PKCalpha are selectively involved in the response.
2,4-Dinitrophenol↗
Improved controlled ovarian hyperstimulation in poor responder in vitro fertilization patients with a microdose follicle-stimulating hormone flare, growth hormone protocol.
OBJECTIVE: To assess the efficacy of a novel protocol-microdose GnRH agonist (GnRH-a), FSH, and GH, for the stimulation of IVF patients who were canceled previously on a standard luteal GnRH-a, FSH, GH protocol. DESIGN: Prospective evaluation using the patient's previous IVF stimulation attempt as historic controls. SETTING: Private practice assisted reproductive technology center. PARTICIPANT(S): Thirty-two patients who had prior ovulation induction cycles canceled using luteal phase GnRH-a suppression followed by exogenous gonadotropins and GH. INTERVENTION(S): Precycle treatment with oral contraceptives followed by follicular phase administration of 40 micrograms leuprolide acetate every 12 hours beginning on cycle day 3 and FSH supplemented with GH beginning on cycle day 5. MAIN OUTCOME MEASURE(S): Paired analysis of E2 day 5, number of follicles, ampules of FSH required, and cancellation rate. The number of oocytes, embryos, embryo quality, implantation rate, and pregnancy rate (PR) were determined for completed cycles on the microdose GnRH-a, FSH, GH protocol. RESULT(S): Controlled ovarian hyperstimulation was superior during microdose GnRH-a, FSH, GH stimulation when compared with the prior luteal GnRH-a cycle. Specifically, there was a higher E2 response, more oocytes, fewer cycle cancellations, and no premature LH surge or luteinization. The microdose GnRH-a, FSH, GH protocol produced an average of 10 oocytes and a 50% ongoing PR. CONCLUSION(S): The microdose GnRH-a, FSH, GH protocol is superior to standard protocols for the treatment of patients with decreased ovarian reserve undergoing controlled ovarian hyperstimulation for IVF.
Adult↗
Regulation of biliary secretion through apical purinergic receptors in cultured rat cholangiocytes.
To evaluate whether ATP in bile serves as a signaling factor regulating ductular secretion, voltage-clamp studies were performed using a novel normal rat cholangiocyte (NRC) model. In the presence of amiloride (100 microM) to block Na+ channels, exposure of the apical membrane to ATP significantly increased the short-circuit current (Isc) from 18.2 +/- 5.9 to 52.8 +/- 12.7 microA (n = 18). The response to ATP is mediated by basolateral-to-apical Cl- transport because it is inhibited by 1) the Cl- channel blockers 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (1 mM), diphenylanthranilic acid (1.5 mM), or 5-nitro-2-(3-phenylpropylamino)benzoic acid (50 or 100 microM) in the apical chamber, 2) the K+ channel blocker Ba2+ (5 mM), or 3) the Na(+)-K(+)-2Cl- cotransport inhibitor bumetanide (200 microM) in the basolateral chamber. Other nucleotides stimulated an increase in Isc with a rank order potency of UTP = ATP = adenosine 5'-O-(3)-thiotriphosphate, consistent with P2u purinergic receptors. ADP, AMP, 2-methylthioadenosine 5'-triphosphate, and adenosine had no effect. A cDNA encoding a rat P2u receptor (rP2uR) was isolated from a liver cDNA library, and functional expression of the corresponding mRNA in Xenopus laevis oocytes resulted in the appearance of ATP-stimulated currents with a similar pharmacological profile. Northern analysis identified hybridizing mRNA transcripts in NRC as well as other cell types in rat liver. These findings indicate that exposure of polarized cholangiocytes to ATP results in luminal Cl- secretion through activation of P2u receptors in the apical membrane. Release of ATP into bile may serve as an autocrine or paracrine signal regulating cholangiocyte secretory function.
Adenosine Triphosphate↗
A model for the incorporation of intracytoplasmic sperm injection into a private practice in vitro fertilization program.
OBJECTIVE: To describe a method for the training of personnel and the implementation of intracytoplasmic sperm injection (ICSI) into an IVF program. The results of the first 75 cycles are reviewed. DESIGN: Retrospective review of the first 75 consecutive ICSI procedures. SETTING: Private, community-based IVF program. MAIN OUTCOME MEASURES: The fertilization rate, damage rate, ongoing pregnancy rate (PR), and implantation rate were measured. RESULTS: Nine percent of the injected oocytes were damaged. The fertilization rate was 60%, and the cleavage rate was 98%. Fifty-nine percent of the cycles resulted in an ongoing pregnancy, and the implantation rate per embryo was 26%. CONCLUSIONS: A high initial PR can be obtained with ICSI using a systematic training regimen.
Adult↗
Ca(2+)-activated C1- channels in a human biliary cell line: regulation by Ca2+/calmodulin-dependent protein kinase.
Biliary epithelial cells contribute to bile formation through absorption and secretion of fluid and electrolytes. Recent studies indicate that membrane Cl- permeability is regulated in part by increases in intracellular Ca2+ concentration. The purpose of these studies was to evaluate the effects of intracellular Ca2+ on channel activity, using the human Mz-ChA-1 cholangiocarcinoma cell line as a model, and to assess the possible roles of Ca(2+)-dependent kinases in channel regulation. Exposure to ionomycin (1 microM) activated ion channels in the cell-attached configuration in 63 of 74 attempts, increasing open probability (NPo) from 0 to 0.26 +/- 0.15 (n = 17). Multiple channels were present in each patch, and the effects of ionomycin were reversed by subsequent addition of ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'- tetraacetic acid (2 mM) to the bath. With Cl(-)-containing solutions, channels had a slope conductance of 14 +/- 4 pS (n = 11), and the mean open time was estimated to be 5.3 +/- 1.8 ms. These channels were anion selective, and currents were carried by efflux of Cl- at the resting potential. Exposure to the Ca2+/calmodulin-dependent protein kinase II (CaMKII) antagonist calmidazolium (100 microM) decreased NPo in ionomycin-stimulated cells to 0.02 +/- 0.06 (n = 19). The protein kinase C antagonist chelerythrine (50 microM) was without effect. In parallel studies in subconfluent cell monolayers, CaMKII antagonists were also potent inhibitors of ionomycin-stimulated 125I efflux. These findings indicate that Ca(2+)-dependent increases in membrane Cl- permeability are related in part to opening of 14.pS anion channels through a mechanism that depends on both Ca2+ and CaMKII. These channels represent a potential target for pharmacological modulation of biliary cell transport and function.
Bile Ducts↗
In vitro fertilization in women age 40 and older: the impact of assisted hatching.
PURPOSE: To assess the impact of assisted hatching on in vitro fertilization (IVF) outcome in women age 40 and older. METHODS: A retrospective analysis was performed to compare 28 cycles of IVF without assisted hatching to 38 cycles of IVF with assisted hatching. All patients in both groups were age 40 or older and the mean age was similar. RESULTS: The delivery rate per oocyte retrieval was significantly higher in the assisted hatching group (18/38; 48%) compared to the nonhatched controls (3/28; 11%, P = 0.0003). The implantation rate of hatched embryos (40/175; 22%) was clearly enhanced, compared to the nonhatched embryos (7/126; 6%, P < 0.001). The fertilization rate, number of oocytes and the number of embryos per patient were comparable in the two groups. CONCLUSIONS: Assisted hatching dramatically improves embryonic implantation and term pregnancy rates in women age 40 and older undergoing IVF.
Adult↗
Effect of ursodeoxycholic acid on biochemical parameters, hepatocyte proliferation and liver histology in galactosamine hepatitis in the rat.
The effect of oral administration of ursodeoxycholic acid (UDCA) on biochemical parameters, liver histology and liver cell proliferation was investigated in rats with galactosamine hepatitis. Treatment with UDCA led to a decrease of aminotransferases, but did not show any significant changes in liver histology or liver cell proliferation. The improvement of liver enzymes without change of histology in this animal model of hepatitis following treatment with UDCA is in agreement with results obtained from clinical trials with UDCA in patients with chronic viral hepatitis.
Alanine Transaminase↗
Ursodeoxycholate increases cytosolic calcium concentration and activates Cl- currents in a biliary cell line.
BACKGROUND & AIMS: Ursodeoxycholate (UDC) stimulates a bicarbonate-rich choleresis, but the cellular mechanisms involved are not fully established. Because ductular secretion also increases biliary HCO3-concentration, the purpose of this study was to evaluate whether UDC has direct effects on duct cells by measuring intracellular calcium concentration ([Ca2+]i) and membrane Cl- permeability in Mz-ChA-1 human cholangiocarcinoma cells. METHODS: Intracellular calcium levels were measured using fura-2 fluorescence. Membrane Cl- permeability was assessed in subconfluent monolayers using 125I efflux and in individuals cells using whole-cell patch clamp techniques. RESULTS: Exposure to UDC (2.5 mmol/L) increased [Ca2+]i from 180 +/- 25 to 639 +/- 84 nmol/L due to release of Ca2+ from intracellular stores and stimulated 125I efflux approximately threefold above basal levels. Exposure to extracellular (1.25 mmol/L) or intracellular (100 mumol/L) UDC activated currents carried by Cl- ions; intracellular UDC increased current density from 4.7 +/- 1.3 to 32.5 +/- 8.8 pA/pF. UDC-stimulated currents were inhibited by chelation of intracellular calcium. CONCLUSIONS: UDC in pharmacological concentrations increases [Ca2+]i and stimulates Cl- efflux through opening of Cl- channels in biliary cells. We speculate that UDC could increase bile flow by direct stimulation of ductular secretion and may be of therapeutic benefit to patients with cystic fibrosis who have impaired adenosine 3',5'-cyclic monophosphate-dependent biliary secretion.
Bile Duct Neoplasms↗