The management of dyspepsia: a systematic review.
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Anti-Ulcer Agents↗
Biomedical subjects
P Barton
Publications and source records attributed to P Barton.
Economic analysis of low-dose heparin vs the low-molecular-weight heparin enoxaparin for prevention of venous thromboembolism after colorectal surgery.
BACKGROUND: Low-dose heparin and low-molecular-weight heparin are effective strategies for preventing venous thromboembolism in colorectal surgery. The economic attractiveness of these 2 strategies in North America is unknown. We conducted an economic analysis of low-dose heparin calcium compared with enoxaparin sodium, a low-molecular-weight heparin, for thromboembolism prophylaxis after colorectal surgery. METHODS: We used decision analysis, with an economic perspective of a third-party payer. Efficacy data were obtained from the Canadian Multicentre Colorectal Deep Vein Thrombosis Prophylaxis Trial and a literature review. Canadian costs for diagnosis and treatment of deep vein thrombosis (DVT), pulmonary embolism (PE), and major bleeding were obtained from chart review and a national hospital database of colorectal surgery; American costs were obtained from published literature. The main outcomes were incremental benefits (symptomatic DVTs, symptomatic PEs, and major bleeding events avoided) and incremental costs for every 1000 patients treated. RESULTS: In the Canadian Colorectal Trial, the relative risk of DVT and PE for enoxaparin compared with low-dose heparin was 1.0 (95% confidence interval, 0.7-1.5), and the relative risk of major bleeding was 1.8 (95% confidence interval, 0.8-3.9). With the use of these data in the baseline analysis, a strategy of enoxaparin prophylaxis was associated with equal numbers of symptomatic DVTs and PEs, and an excess of 12 major bleeding episodes for every 1000 patients treated, with an additional cost of $86 050 (Canadian data) or $145 667 (US data). In a sensitivity analysis using optimal assumptions for efficacy and safety of enoxaparin (relative risk of DVT, 0.8; relative risk of PE, 0.4; relative risk of major bleeding, 1.0), a strategy of enoxaparin prophylaxis was associated with 0.8 fewer symptomatic DVT, 3 fewer symptomatic PEs, and equal numbers of major bleeding episodes for every 1000 patients treated, with an additional cost of $15 217 (Canadian data) or $107 614 (US data). CONCLUSION: Although heparin and enoxaparin are equally effective, low-dose heparin is a more economically attractive choice for thromboembolism prophylaxis after colorectal surgery.
Anticoagulants↗
Management of the submerged deciduous tooth: I. Aetiology, diagnosis and potential consequences.
The management of submerged deciduous teeth can present a dilemma for general practitioner and specialist alike. These teeth are often extracted to avoid potential problems. The recent literature, mainly publications in specialist journals of paediatric dentistry and orthodontics, suggests that a conservative approach is often preferable, particularly when the permanent successor is present. The purpose of this article is to review the aetiology, diagnosis and potential consequences of submerging deciduous molars; a second paper will discuss the treatment options available.
Child, Preschool↗
Management of the submerged deciduous tooth: 2. Treatment.
The previous article in this series dealt with the aetiology, diagnosis and potential consequences of submerging deciduous teeth. This paper will discuss the appropriate treatment options. The management is highly dependent on whether the permanent successor is present or absent. The degree of submergence and the age of the patient are also important factors for consideration.
Adult↗
Pharmacokinetics and pharmacodynamics of milrinone lactate in pediatric patients with septic shock.
OBJECTIVES: The objectives of this study were to determine the pharmacokinetics of milrinone lactate in pediatric patients with septic shock and to determine whether a relationship exists between steady-state plasma milrinone concentrations and changes in hemodynamic variables. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, interventional study. In study phase 1 patients were randomized and underwent loading and infusion with milrinone lactate (50 microg/kg, then 0.5 microg/kg/min), and invasive hemodynamic values were determined. Steady-state was determined by obtaining plasma samples at 30, 15, and 0 minutes before the end of the milrinone infusion. Study phase 2 started when milrinone was discontinued by the patient care team. Steady-state was reaffirmed and plasma samples were obtained at 0.5, 1, 2, 4, 6, and 8 hours after the end of the infusion. RESULTS: The average plasma concentration at steady-state (Css avg) and total body clearance for phase 1 were 81.3+/-38.6 ng/ml (mean +/- SD) and 0.0106+/-0.0053 L/kg/min, respectively (n = 9). All but two patients underwent reloading with milrinone. In phase 2 Css avg and total body clearance were 65.8+/-42.1 ng/ml and 0.0110+/-0.0096 L/kg/min, respectively (n = 11). The average time of infusion was 51+/-21 hours. Eight patients were evaluated for phase 2 elimination. The mean elimination rate constant was 0.0091+/-0.0061 min(-1) (n = 8). The median half-life was 1.47 hours (range, 0.62 to 10.85 hours). All patients had creatinine clearances greater than 61 ml/min/1.73 m2. The volume of distribution at steady-state was 1.47+/-1.03 L/kg. No correlation existed between age and the elimination rate constant or the volume of distribution at steady-state. All patients achieved at least a 20% change in cardiac index and systemic vascular resistance index while maintaining a Css avg of 35 to 160 ng/ml. No adverse effects were noted. All patients achieved primary hemodynamic end points (cardiac index and systemic vascular resistance index) during the milrinone infusion. CONCLUSIONS: Loading doses of 75 microg/kg milrinone lactate and starting infusion rates of 0.75 to 1.0 microg/kg/min for patients with normal renal function should be used; the infusion rate should then be titrated to effect. We recommend that for every increase of 0.25 microg/kg/min, a 25 microg/kg bolus dose be given. Because the median half-life is 1.47 hours, immediate hemodynamic effects may not be seen unless appropriate loading doses and infusion adjustments are made.
Adolescent↗
Epithelial-myoepithelial carcinoma of the bronchus.
An extremely rare case of epithelial-myoepithelial carcinoma (EMC) of a lobar bronchus in a 47-year-old female is reported. Grossly, the tumor formed a polypoid mass obstructing the bronchial lumen. Microscopically, it was composed of two cellular types--epithelial cells with eosinophilic cytoplasm and clear myoepithelial cells. Numerous tubules formed by an inner epithelial and outer myoepithelial layer were found. Focally, the tumor showed solid growth of clear cells. Prominent hyalinization of the stroma was found. The nature of the cells was confirmed by positive expression of cytokeratins and epithelial membrane antigen in epithelial cells and vimentin and smooth muscle actin in myoepithelial cells. Differential diagnosis of EMC includes a broad spectrum of salivary gland-type tumors. Furthermore, metastases of clear cell carcinoma of the kidney or thyroid, clear cell ("sugar") tumor of the lung, glandular form of carcinoid, bronchioalveolar adenocarcinoma with myoepithelial cells and pulmonary adenosquamous carcinoma with amyloid-like stroma must be distinguished from EMC. The tumor has neither recurred nor metastasised, a fact supporting the current opinion, that EMC is a tumor of low grade malignancy.
Actins↗
The effect of ionic strength on liposome-buffer and 1-octanol-buffer distribution coefficients.
The distribution of salmeterol and proxicromil between unilamellar vesicles of dioleoylphosphatidylcholine (DOPC) and aqueous buffer at pH 7.4 has been studied, using an ultrafiltration method, as a function of compound concentration, DOPC concentration, and buffer ionic strength. The binding of these ionized lipophilic compounds to neutral DOPC vesicles induces a surface charge, which causes the observed membrane distribution coefficient D(mem)obs to vary significantly with bound compound to DOPC ratio and with ionic strength. This variability is shown to be well-described with use of the Gouy-Chapman theory of the ionic double layer and is contrasted with the ideal behavior shown by the neutral compound clofibrate. Increasing ionic strength is also shown to increase the observed 1-octanol-buffer distribution coefficients D(o/w)obs of proxicromil but through a very different mechanism involving the extraction of ion pairs. This study highlights the experimental difficulty in determining concentration-independent liposome distribution coefficients of ionized lipophilic compounds and describes when deviations will be significant and how observed values may be corrected for such effects. The general effect of ionic strength on membrane-buffer distribution and 1-octanol-buffer distribution is discussed with particular reference to the very different propensity for ion pair formation shown by the two systems, and the most suitable experimental conditions that should be used with each system.
1-Butanol↗
Preliminary evaluation of recombinant amino-terminal fragment of human bactericidal/permeability-increasing protein in children with severe meningococcal sepsis.
BACKGROUND: Meningococcal sepsis remains an important cause of morbidity and mortality. We hypothesised that children with severe meningococcaemia might benefit from inhibition of the inflammatory processes thought responsible for fulminant disease. rBPI21 is a recombinant, N-terminal fragment of human bactericidal/permeability-increasing protein, which kills meningococci and binds to and clears bacterial endotoxin, these being the primary inducers of the systemic inflammation. The aim of this study was to determine the safety and kinetics of rBPI21 in children with severe meningococcaemia and to make a preliminary assessment of clinical outcome. METHODS: In this open-label, dose-escalation, phase I/II trial in severe meningococcaemia (Glasgow meningococcal prognostic septicaemia score [GMSPS] > or = 8), 26 patients aged 1-18 years, who had received their first dose of antibiotics no more than 8 hours earlier were given rBPI21 by infusion at total doses of 1.0, 2.0, and 4.0 mg/kg. FINDINGS: The patients had significantly raised plasma concentrations of bacterial endotoxin and cytokines. Peak and steady state BPI concentrations were comparable with pharmacokinetic data in healthy adults. All complications were compatible with the expected pattern for severe meningococcal sepsis. Only one patient died. This outcome was found to compare favourably with a predicted mortality of > or = 30% by GMSPS, > or = 15% by plasma endotoxin values, > or = 28% by plasma interleukin-6 concentrations, 29-49% by severity of coagulopathy, and 20% (11/54) by comparison with recent historical patients consecutively treated in participating centres before this study. INTERPRETATION: This, the first clinical trial or rBPI21, shows that rBPI21 can be safely administered to children with severe meningococcaemia and that the pharmacokinetics are consistent with patterns seen in healthy adults. Predicted mortality, on the basis of GMSPS, laboratory indices of inflammation and coagulopathy, and historical controls, was for between four and eight deaths. These findings have prompted a phase III randomised trial.
Adult↗
Drug-phospholipid interactions. 2. Predicting the sites of drug distribution using n-octanol/water and membrane/water distribution coefficients.
The in vivo tissue distribution of seventeen drugs has been modeled by using estimated n-octanol/water and membrane/water distribution coefficients. In this study, the membrane affinities are estimated using the new technique of immobilized artificial membrane (IAM) column chromatography. delta (log D(n-octanol/water-membrane/water)), which measures a hypothetical equilibrium of the drug between of n-octanol and membrane phase, is a better model of in vivo tissue distribution, as measured by Adipose Tissue Storage Index (ASI), than either n-octanol/ water or membrane/water distribution coefficients alone. This demonstrates the importance of membrane distribution coefficients as a complementary descriptor of lipophilicity to n-octanol/water distribution coefficients, in modeling in vivo distribution of drugs. This rapid method for predicting in vivo distribution of drugs, based on n-octanol and membrane/water distribution coefficients, may be a useful tool to aid the selection of drugs with beneficial pharmacokinetic profiles.
Adipose Tissue↗
Mammographically detected breast cancer. Benefits of stereotactic core versus wire localization biopsy.
OBJECTIVE: The authors evaluated the differences between stereotactic core needle biopsy (SCNBx) and needle localization surgical biopsy (NLBx) in cost and treatment course for patients with mammographically detected breast cancer. SUMMARY BACKGROUND DATA: Stereotactic core needle breast biopsy is a reproducible and reliable alternative to surgical biopsy for histologic diagnosis of mammographic lesions. METHODS: Records from 52 consecutive patients with invasive breast cancer diagnosed by SCNBx (n = 21) or NLBx (n = 31) over 2 years were reviewed. Episode-of-care costs were extracted from the Barnes Hospital billing system database. RESULTS: At the time of excision, surgical margins were statistically more frequently positive in patients treated with NLBx (55%) than patients treated with SCNBx (0%, p < 0.0001). Furthermore, patients in the NLBx group undergoing breast conservation surgery required re-excision more frequently (74%) than those in the SCNBx group (0%, p = 0.001). There were no complications in either group after the diagnostic procedure. All SCNBx results were correct in the diagnosis of invasive breast cancer. The median cost of SCNBx was approximately $1000 less than the median cost of NLBx. This cost difference was carried through the definitive procedure, whether it was breast conservation or mastectomy. CONCLUSIONS: This study shows the advantage of SCNBx to diagnose breast cancer and definitive operative care at a single procedure. The preoperative diagnosis of breast cancer eliminated positive operative margins and procedures to re-excise breast tissue. The use of SCNBx also saved approximately $1000 per patient compared with the use of NLBx. Our data suggest that SCNBx is the diagnostic procedure of choice for mammographically detected cancers.
Adenocarcinoma↗
Hemodynamic effects of i.v. milrinone lactate in pediatric patients with septic shock. A prospective, double-blinded, randomized, placebo-controlled, interventional study.
STUDY OBJECTIVE: To determine the hemodynamic effects of i.v. milrinone lactate in pediatric patients with nonhyperdynamic septic shock. Specifically we tested the hypothesis that i.v. milrinone would increase cardiac index by 20% and decrease systemic vascular resistance index by 20% during a 2-h study period. DESIGN: Prospective, double-blinded, randomized, placebo-controlled, descriptive, interventional study. SETTING: Twenty-six-bed pediatric ICU at Children's Medical Center of Dallas and a 10-bed pediatric trauma ICU at Parkland Memorial Hospital. PATIENTS/PARTICIPANTS: Twelve patients (age range, 9 months to 15 years) with nonhyperdynamic septic shock despite administration of catecholamines (cardiac index [CI] normal [3.5 to 5.5 L/min/m2] or low [< or =3.5 L/min/m2]; systemic vascular resistance index [SVRI] normal [800 to 1,600 dyne.s.cm5/m2] or high [> or =1,600 dyne.s.cm5/m2]; and pulmonary capillary wedge pressure [PCWP] normal [8 to 12 mm Hg] or higher) with clinical signs of poor perfusion were enrolled, randomized, and treated in a blinded fashion with i.v. milrinone and placebo. INTERVENTIONS: Patients were randomized into two groups. Group A received a loading dose of 50 micrograms/kg i.v. of milrinone followed by a continuous i.v. infusion of 0.5 microgram/kg/min while group B received an equal volume loading dose and continuous infusion of placebo. After 2 h, group A received an equal-volume loading dose followed by a continuous infusion of placebo while the milrinone infusion continued, while group B received a 50 micrograms/kg loading dose of milrinone followed by a continuous infusion of 0.5 microgram/kg/min while the placebo infusion remained. Outcome variable were measured at baseline, 0.5, 1.0, 2.0, 2.5, 3.0, and 4.0 h. Echocardiographic measurements were taken at baseline, hour 2, and hour 4 in all subjects. No changes in other inotropic or mechanical ventilatory support were allowed during the study period. MEASUREMENTS AND MAIN RESULTS: Milrinone significantly increased CI, stroke volume index (SVI), right and left ventricular stroke work index, and oxygen delivery (Do2) at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05) while significantly decreasing SVRI, pulmonary vascular resistance index, and mean pulmonary arterial pressure at 0.5, 1.0, and 2.0 h postloading dose (p < 0.05). No clinically or statistically significant changes in heart rate, systolic and diastolic BP, mean systemic arterial pressure, or PCWP were observed during milrinone treatment compared to placebo. CONCLUSIONS: CI, SVI, and Do2 significantly increased while SVRI significantly decreased when compared to placebo after i.v. administration of milrinone to pediatric patients with nonhyperdynamic septic shock. No adverse effects were observed. In a volume-resuscitated pediatric patient with septic shock, when administered in addition to catecholamines, milrinone will improve cardiovascular function.
Adolescent↗
A skeletal muscle-specific enhancer regulated by factors binding to E and CArG boxes is present in the promoter of the mouse myosin light-chain 1A gene.
The mouse myosin light-chain 1A (MLC1A) gene, expressed in the atria of the adult heart, is one of the first muscle genes to be activated when skeletal as well as cardiac muscles form in the embryo. It is also transcribed in skeletal muscle cell lines at the onset of differentiation. Transient transfection assays of mouse skeletal muscle cell lines with DNA constructs containing MLC1A promoter fragments fused to the chloramphenicol acetyltransferase (CAT) gene show that the first 630 bp of the promoter is sufficient to direct expression of the reporter gene during myotube formation. Two E boxes located at bp -76 and -519 are necessary for this regulation. MyoD and myogenin proteins bind to them as heterodimers with E12 protein and, moreover, transactivate them in cotransfection experiments with the MLC1A promoter in nonmuscle cells. Interestingly, the effect of mutating each E box is less striking in primary cultures than in the C2 or Sol8 muscle cell line. A DNA fragment from bp -36 to -597 confers tissue- and stage-specific activity to the herpes simplex virus thymidine kinase promoter in both orientations, showing that the skeletal muscle-specific regulation of the MLC1A gene is under the control of a muscle-specific enhancer which extends into the proximal promoter region. At bp -89 is a diverged CArG box, CC(A/T)6AG, which binds the serum response factor (SRF) in myotube nuclear extracts, as does the wild-type sequence, CC(A/T)6GG. Both types of CArG box also bind a novel myotube-enriched complex which has contact points with the AT-rich part of the CArG box and adjacent 3' nucleotides. Mutations within the CArG box distinguish between the binding of this complex and binding of SRF; only SRF binding is directly involved in the specific regulation of the MLC1A gene in skeletal muscle cell lines.
Animals↗
Biliary sludge after liver transplantation: 2. Treatment with interventional techniques versus surgery and/or oral chemolysis.
OBJECTIVE: Interventional treatment of biliary sludge in liver transplant recipients includes transhepatic biliary drainage and saline irrigation, catheter chemolysis and/or basket extraction, and endoscopic intervention. The purpose of this study was to compare these interventional procedures with oral chemolysis and with surgical treatment of biliary sludge in order to evaluate the effectiveness of interventional procedures as an alternative to surgery in the treatment of this complication. MATERIALS AND METHODS: We retrospectively evaluated the outcome of several forms of treatment for biliary sludge occurring after liver transplantation in 49 cases. Treatments included oral chemolysis with chenodeoxycholic acid (n = 35), percutaneous transhepatic biliary drainage (n = 13) followed by irrigation with heparinized saline solution (n = 4), intraluminal chemolysis with glycero-octanoate-carnosine and bile salts-EDTA (n = 3) and/or basket extraction (n = 5), and endoscopic intervention (n = 2) or surgery (n = 26). Oral chemolysis was attempted in all cases of biliary sludge if no other complications were present. If this conservative treatment failed and the sludge was limited to the main bile ducts, interventional procedures were attempted. Surgical removal of the sludge (n = 15) or retransplantation (n = 5) without any attempt at prior nonsurgical treatment was performed if concomitant complications were present (n = 14) or if the extent of the sludge was considered too time-consuming for an interventional attempt (n = 6). The six patients in whom nonsurgical treatment failed underwent surgery. Treatment was considered successful if cholangiograms obtained after therapy showed no more evidence of sludge. Treatment was considered a failure if biliary sludge was shown after therapy by means of cholangiography, surgery, or autopsy. RESULTS: Complete disappearance of biliary sludge as a result of oral chemolysis was achieved in 14 (40%) of 35 cases. Interventional procedures were performed in 15 of the patients in whom oral treatment failed. After percutaneous transhepatic biliary drainage, the sludge was successfully removed by chemolysis with glycero-octanoate-carnosine in three cases, by basket extraction in one case, and by a combination of chemolysis and basket extraction in three cases. In two other cases, underlying recurrent tumor was treated palliatively with percutaneous transhepatic biliary drainage or endoscopic stenting. Irrigation with heparinized saline solution failed in four cases, and percutaneous or endoscopic basket extraction failed in one case each. Surgical treatment was successful in 18 (86%) of 21 cases, and retransplantation was successfully done in five patients. In all, interventional techniques were used in 43% of the patients with biliary sludge who could not be treated successfully with oral chemolysis, and the overall success rate was 60%. CONCLUSION: Interventional techniques are effective therapeutic alternatives for treating biliary sludge occurring after liver transplantation and should be considered before surgical procedures. An indication for interventional procedures in biliary sludge is lack of success of oral chemolysis and an absence of other complications that require surgery or retransplantation.
Adolescent↗
Biliary sludge after liver transplantation: 1. Imaging findings and efficacy of various imaging procedures.
OBJECTIVE: Biliary sludge (inspissated, thickened bile or collective collagen tissue from destroyed [or necrotic] bile duct walls) can be found a few days to several years after liver transplantation, mainly in the common and main hepatic bile ducts. The purpose of this study was to review the imaging findings of biliary sludge occurring after liver transplantation and to determine the relative merits of various imaging procedures (cholangiography, CT, and sonography) for establishing the diagnosis. MATERIALS AND METHODS: Cholangiograms, sonograms, and CT scans obtained in 352 patients with 400 liver transplants were reviewed retrospectively for evidence of biliary sludge. In all patients, T-tube cholangiograms were routinely obtained 7 and 30 days and 3 months after transplantation. Thereafter, in the absence of findings, the T-tube was removed. In all patients, sonograms were obtained immediately, 2 and 7 days after transplantation. Additional cholangiograms were obtained when biliary complications were suspected (T-tube cholangiograms in 215 patients, percutaneous transhepatic cholangiograms in 79 patients, and endoscopic retrograde cholangiograms in five patients after T-tube removal). Additional sonograms were obtained in 289 patients and CT scans in 238 patients when complications were suspected. The findings of these various imaging studies were analyzed and compared with each other, with the clinical course of the patient, and with surgical and histologic findings to determine the relative merits of each imaging method for the diagnosis of biliary sludge. Criteria for the diagnosis of biliary sludge were filling defects or pluglike obstruction seen on cholangiograms or material filling the bile ducts seen on sonograms or CT scans. The radiologic diagnosis of biliary sludge was certified by gross specimens obtained at surgery (n = 21) or autopsy (n = 2) or by complete disappearance of the radiologic findings with specific oral or interventional treatment (n = 28). RESULTS: Biliary sludge was diagnosed on the basis of radiologic findings in 51 (13%) of 400 transplanted livers. Cholangiograms (T-tube in 34, percutaneous transhepatic cholangiography in seven, a combination of T-tube and percutaneous transhepatic cholangiography in eight, and a combination of endoscopic retrograde and percutaneous transhepatic cholangiography in two cases) showed biliary sludge in all 51 cases. Cholangiographic findings included filling defects in 34 (67%) and obstruction of the bile duct with pluglike appearance in 17 (33%) of the 51 cases. Dilatation of bile ducts was present in 32 (63%) of the 51 cases. The presence of biliary sludge was certified in 50 of these cases, with one case turning out to be a sutural granuloma at autopsy. On sonograms, biliary sludge was shown as echogenic material in the main bile ducts in only 16 (31%) of the 51 cases, with dilatation of bile ducts in 12 of them. In 10 others (20%), sonograms showed dilatation of the bile ducts but did not show the sludge itself. CT scans did not show the sludge in any of the 12 cases in which they were obtained. CONCLUSION: Our results show that cholangiography is the only accurate imaging method for diagnosing biliary sludge after liver transplantation. Sonography is limited and CT is of no value for this purpose. In the absence of a T-tube, endoscopic retrograde or percutaneous transhepatic cholangiography should be used. Otherwise, T-tube cholangiography is the method of choice. Filling defects and obstruction of the bile ducts with pluglike material are characteristic findings of biliary sludge seen on cholangiograms.
Adolescent↗
Secretion of biologically active human proapolipoprotein A-I in a baculovirus-insect cell system: protection from degradation by protease inhibitors.
Studies of the structure and function of apolipoprotein A-I (apoA-I) often require its purification by delipidation of high density lipoprotein isolated from large quantities of human plasma and separation of apoA-I from other plasma apolipoproteins. To reduce the need for extensive purification procedures, we have developed an insect cell/baculovirus expression system for the production and secretion of human proapoA-I. The recombinant baculovirus containing full-length human apoA-I cDNA, when introduced into Spodoptera frugiperda, directs the synthesis of preproapoA-I, which is subsequently secreted into the growth medium as proapoA-I, indicating correct processing of the signal peptide during secretion. To prevent the extensive degradation of secreted proapoA-I, leupeptin and pepstatin A were added to the serum free cell culture medium. The protein was simply purified by filtration of the medium, which contained up to 80 mg/l proapoA-I, followed by chromatography on phenyl-sepharose CL-4B. The resultant proapoA-I was found to bind lipid and to activate lecithin:cholesterol acyltransferase as effectively as apoA-I from human plasma. The advantage of this expression system is the ease of purification of intact, biologically active apoA-I in high yield.
Animals↗
Expression of the SmN splicing protein is developmentally regulated in the rodent brain but not in the rodent heart.
The SmN protein is a tissue-specific splicing factor which is closely related to the ubiquitous SmB splicing protein but which is expressed only in the adult brain and heart. SmN is also detectable albeit at a low level in both the embryonic brain and heart. During heart development, SmN levels remain constant while during rodent brain development the levels of SmN rise such that SmN replaces SmB as the predominant protein in adult brain. This increase in SmN levels is dependent upon a corresponding increase in the SmN mRNA which is detectable by in situ hybridization within neurons in virtually all areas of the adult brain.
Animals↗
[Drain fistulography. Radiological sphincter identification in high anal fistulae].
To warrant permanent surgical cure of high anal fistulae, while avoiding at the same time faecal incontinence due to inadvertent division of the puborectalis muscle, distinction between a trans- and suprasphincteric fistula track is essential. This differentiation is often crucial, since digital rectal palpation and conventional fistulography tend to be unreliable. Therefore we developed a radiological technique of imaging the anorectal fistulous track, "drain fistulography". After silicon drainage of the fistula the contrast visualization of anal canal, rectum and fistula drain allows to assess the topographic relation between fistula and anal sphincters as well as the sphincteric functional component above the fistula. A trans-sphincteric fistula track was demonstrated in 7 of 8 patients (5 with recurrent fistulae) by means of "drain fistulography", permitting complete laying open of each fistula in a second operation. In one patient a suprasphincteric fistula track was found and a "mucosal flap repair" was carried out. After a mean observation time of 53 months all patients are perfectly continent and free of recurrence. The method of "drain fistulography" is a valuable diagnostic tool to select the appropriate definitive surgical procedure in the treatment of high anal fistulae.
Adult↗
Alterations in sarcoplasmic reticulum gene expression in human heart failure. A possible mechanism for alterations in systolic and diastolic properties of the failing myocardium.
Recent studies have shown that intracellular Ca2+ handling is abnormal in the myocardium of patients with end-stage heart failure. Muscles from the failing hearts showed a prolonged Ca2+ transient and a diminished capacity to restore a low resting Ca2+ level during diastole. Accordingly, we examined whether this defect in Ca2+ transport function is due to alterations in sarcoplasmic reticulum gene expression. We determined the messenger RNA (mRNA) levels of sarcoplasmic reticulum Ca2+ transport proteins in failing human hearts from 17 cardiac transplant recipients with a diagnosis of dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The expression levels of each mRNA were compared with each other and then correlated with that of atrial natriuretic factor (ANF) mRNA in the failing ventricle. The mRNA levels for the calcium release channel (ryanodine receptor, RYR2), Ca2+ uptake pump (Ca(2+)-ATPase, SERCA2 isoform), and phospholamban differed significantly between heart samples but showed an inverse relation with that of ventricular ANF mRNA. In contrast, calsequestrin mRNA levels remained unchanged in these failing hearts. In addition, beta-myosin and alpha-cardiac actin mRNA levels also showed an inverse relation with ANF mRNA levels. These changes were observed in both right and left ventricles of hearts with congestive heart failure due to dilated cardiomyopathy, primary pulmonary hypertension, or ischemic heart disease. The results are consistent with the hypothesis that abnormal calcium handling in the sarcoplasmic reticulum of failing hearts is due to the altered expression of the genes encoding sarcoplasmic reticulum proteins.
Adolescent↗