Conversion from cyclosporine to tacrolimus is preferred by pediatric renal transplant recipients: a focus on opinions and outcomes.
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Biomedical subjects
Publications and source records attributed to L D Smith.
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BACKGROUND: Traditional resuscitation regimens have been recently challenged. This study evaluates hypotensive resuscitation with a hemoglobin-based oxygen-carrying (HBOC) solution after severe hemorrhage in a porcine model. We hypothesized that HBOC-201 restores tissue perfusion at a lower mean arterial pressure than standard resuscitation fluids. METHODS: Yorkshire swine (55-65 kg, n = 30), were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and randomized into groups. Group I was resuscitated with an HBOC solution to a MAP of 60 mm Hg. Groups II and III were resuscitated to a MAP of 80 mm Hg with lactated Ringer's solution (LR) alone or LR (40 mL/kg) followed by shed blood, respectively. Group IV was resuscitated with shed blood alone to a MAP of 60 mm Hg. Group V received an HBOC solution to a MAP of 50 mm Hg. Hemodynamic variables, Swan-Ganz parameters, blood gas samples, and lactate levels were followed for 5 hours. Data were analyzed by analysis of variance/Duncan multiple range test. RESULTS: There were no significant differences in mortality between any groups. Groups I, IV, and V had lower (p < 0.05) cardiac output, pulmonary artery wedge pressure, and MAP than either group II or group III. Svo2 was significantly lower in the HBOC groups. There were no significant differences in arterial pH or lactate between groups I, III, and IV. Lactate levels, base excess, and arterial pH were significantly worse in the LR-alone and HBOC-50 groups. CONCLUSION: Hypotensive resuscitation with HBOC-201 at a MAP of 60 mm Hg after a controlled hemorrhage in swine provides sufficient tissue perfusion and oxygen delivery to reverse anaerobic metabolism on the basis of global physiologic markers despite continued hypotension, hypovolemia, and low cardiac output.
Right sided endocarditis usually involves the tricuspid valve, predominantly in intravenous drug users. It is also occasionally acquired in hospital as a result of contaminated intravascular devices. Isolated infection of the pulmonary valve is rarely seen. A case of community acquired Staphylococcus aureus pulmonary valve endocarditis that caused diagnostic confusion is reported. This infection occurred in a patient with no history of intravenous drug abuse and a previously structurally normal heart.
The expression of defensive morphologies in prey often is correlated with predator abundance or diversity over a range of temporal and spatial scales. These patterns are assumed to reflect natural selection via differential predation on genetically determined, fixed phenotypes. Phenotypic variation, however, also can reflect within-generation developmental responses to environmental cues (phenotypic plasticity). For example, water-borne effluents from predators can induce the production of defensive morphologies in many prey taxa. This phenomenon, however, has been examined only on narrow scales. Here, we demonstrate adaptive phenotypic plasticity in prey from geographically separated populations that were reared in the presence of an introduced predator. Marine snails exposed to predatory crab effluent in the field increased shell thickness rapidly compared with controls. Induced changes were comparable to (i) historical transitions in thickness previously attributed to selection by the invading predator and (ii) present-day clinal variation predicted from water temperature differences. Thus, predator-induced phenotypic plasticity may explain broad-scale geographic and temporal phenotypic variation. If inducible defenses are heritable, then selection on the reaction norm may influence coevolution between predator and prey. Trade-offs may explain why inducible rather than constitutive defenses have evolved in several gastropod species.
Although the fledgling psychology of 100 years ago was assertively empirical, there were no inferential statistics to guide psychologists' data analyses. However, 19th-century developments had left psychology with a rich array of techniques for analyzing and presenting data, some of which remain underutilized today. These include comparisons across replications, within-subject designs, reanalysis of data, analyses of factorial designs, and especially the use of tables and graphs. As the merits of hypothesis-testing statistics are debated at the turn of the 21st century, the history of data-handling practices can remind psychologists that there are many ways to overcome the current uniformity of statistical practice.
OBJECTIVE: To assess complications of diagnostic cardiac catheterisation in a non-surgical centre by review of the first three years' experience and audit of 2804 diagnostic left heart procedures. DESIGN: Analysis of a prospective database of cardiac catheter procedures. SETTING: District general hospital without available on site cardiac surgery. RESULTS: The rate of major complications of cardiac catheterisation was 0.07%. Mortality was 0. 07%, and the rate of arterial complications (requiring surgical repair) was 0.24% for brachial arteries and 0.17% for femoral. These results are comparable to those reported from national and international surgical centres. CONCLUSION: A diagnostic cardiac catheterisation service can be offered in non-surgical hospitals without an increased risk to patients. It highlights the relevance of training in angioplasty and questions the appropriateness of starting preliminary invasive cardiology training of specialist registrars in district general hospitals.
OBJECTIVE: To describe a case of pseudotumor cerebri associated with the administration of intermediate-dose cytarabine. CASE SUMMARY: An 11-year-old Hispanic boy with acute myeloblastic leukemia developed symptoms of pseudotumor cerebri (headache, diplopia, photophobia, nausea, vomiting) after receiving chemotherapy including cytarabine. The patient improved after a lumbar puncture and treatment with prednisone and acetazolamide, and is now asymptomatic. DISCUSSION: Pseudotumor cerebri is a condition usually associated with obese women of child-bearing age. Case reports in pediatric patients are unusual. Several medications have been implicated in causing pseudotumor cerebri, including antimicrobials (tetracycline, naladixic acid), amiodarone, lithium carbonate, vitamin A and its derivatives, growth hormone, and corticosteroids. Chemotherapy agents reported to cause pseudotumor cerebri include busulfan with cyclophosphamide, and the combination of vinblastine, cisplatin, and bleomycin. Most of the information on medication-induced pseudotumor cerebri is in the form of case reports. Different mechanisms for causing this condition have been offered for individual medications. Most of these explanations involve fluid imbalance or interference with the Na+/K+ adenosine triphosphatase pump. Controlled studies are difficult because this condition is an unpredictable and rare occurrence. Cytarabine has frequently been associated with neurologic toxicities, but few reports of pseudotumor cerebri can be found. CONCLUSIONS: The exact cause of pseudotumor cerebri in this patient is unknown, but cytarabine seems a likely cause. The mechanism by which cytarabine could cause this reaction is unclear.
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In one experiment, White South African boys drew pictures in response to four musical intervals. In the second, the subjects were of both sexes and drawn from White, urban Black, and rural Black populations. Six intervals were used. Drawing content was similar cross-culturally. Consonances were perceived as generally positive; dissonances, generally negative. There was also an activity dimension. Children in a lower grade drew more concrete pictures than did those in a higher grade, regardless of age. Even young listeners were fairly consistent in their responses. This suggests that perception of musical meaning is a universal rather than culturally based phenomenon.
BACKGROUND: In vitro and in vivo evidence suggests that atrial natriuretic peptide can enhance fluid flux from intravascular to extravascular compartments. The relevance of this to human pathophysiology remains unclear. OBJECTIVES: To determine whether a central haemodynamic change associated with increased plasma concentrations of atrial natriuretic peptide produces detectable change in the capillary filtration coefficient in a peripheral microvascular bed. PATIENTS: 12 patients with programmable dual chamber permanent pacemakers. METHODS: Calf capillary filtration coefficient (using a modified plethysmographic technique) and plasma atrial natriuretic peptide concentrations were measured during atrioventricular synchronous and ventricular pacing. RESULTS: Atrioventricular asynchrony was associated with higher mean (SD) concentrations of atrial natriuretic peptide (231.9 (123.1) v 53.5 (38.8) pg/ml) and an increased mean (SD) calf capillary filtration coefficient (4.2 (1.1) v 3.6 (1.1) ml/min.mm Hg.100 ml x 10(-3)), but there was no correlation between the magnitude of the change in these variables in individual patients. CONCLUSIONS: The peripheral capillary filtration coefficient may change in response to altered central haemodynamics. Atrial natriuretic peptide remains one potential candidate mechanism, but other factors are also likely to be involved.
Bacterio-opsin is made as a precursor in Halobacterium halobium, which has 13 additional residues at the amino terminus. The codons for these residues have been proposed to form a hairpin structure in the mRNA and play a role in ribosome binding; the leader peptide sequence also has been proposed to have a role in membrane insertion of bacteriorhodopsin (BR). We have made mutations in the bop gene region coding for the leader sequence and expressed the mutant genes in an H. halobium mutant lacking wild-type BR. The leader sequence coding region was found to be important for the stability of the mRNA and for its efficient translation. Single base substitutions in this region that did not affect the amino acid sequence caused significant reductions in protein expression. Deletion of the leader region resulted in unstable mRNA and almost no BR production. Introduction of a new ribosome-binding sequence within the coding region of the mature protein restored mRNA stability and some protein expression. Protein made without the leader peptide was properly assembled in the membrane.
We cloned the Xenopus laevis form of Gq alpha subunit to study its effects on oocyte maturation. Injection of Xenopus Gq alpha mRNA into stage 6 oocytes activated the phospholipase C/phosphatidylinositol pathway. The oocyte membrane became permeable to calcium ions and was able to generate transient inward currents (T(in)), due to the opening of Ca(2+)-dependent Cl- channels. The T(in) amplitude developed over several hours and disappeared by 24 hr. Diacylglycerol levels were found to parallel the appearance and disappearance of the T(in). The concurrent decline of T(in) values and diacylglycerol was not due to a failure in the synthesis of Gq alpha protein, which was produced continuously for > 24 hr. After Xenopus Gq alpha mRNA injection, germinal vesicle breakdown (GVBD) was variable (0-100%) in stage 6 oocytes, whereas none of the stage 4 oocytes underwent GVBD. In contrast, stage 6 oocytes injected with mRNA encoding the Go alpha G protein consistently underwent GVBD but did not acquire T(in). Our results show that activation of phospholipase C is not an absolute requisite for the induction of maturation, although in oocytes of some frogs phospholipase C activation can trigger a pathway to GVBD.
It has been shown that about two thirds of Xenopus oocyte or sea urchin egg cytoplasmic poly(A)+ RNA contains interspersed repetitive sequences. The functional significance of this interspersed RNA has remained unknown. Here the function of a subfamily of interspersed RNA (XR family; McGrew and Richter, 1989: Dev Biol 134:267-270) in Xenopus oocytes was studied. We found that the elimination of T7 XR (one of the two complementary strands of the XR repeat) interspersed RNA by complementary oligodeoxynucleotides significantly inhibited protein synthesis. On the other hand, the injection of in vitro synthesized T7 XR RNA stimulated translation. Moreover, the insertion of the T7 XR RNA sequence into globin mRNA repressed the translation of the globin mRNA. In order to explain these results, we analyzed interactions between the XR interspersed RNA and oocyte proteins. We found that the major XR RNA binding proteins were p56 and p60, which could be the known mRNA "masking" proteins that bind mRNA and inhibit translation. Further, a 42 kD protein has been identified that appears to bind T7 XR RNA relatively specifically, although it interacts with mRNA with a lower affinity. Based on all of these data, we have proposed that interspersed RNA may be involved in regulating translation by competing with mRNA to interact with certain proteins that can regulate translation.
Angiography is the definitive procedure for characterising the extent and course of coronary artery disease. We describe the methodology required to measure, with optimal resolving power, angiographic changes in coronary artery disease. We utilised recent technological developments in image digitization, storage and analysis. The measures of change quantified both diffuse and focal atherosclerosis. Frames from angiographic cine films were digitized at high resolution (1024 x 1024 pixels, 8 bit grey scale) and archived on optical disk. Four radiographic projections were stored to ensure good visualization of as many as possible of a set of ten major arterial segments. Edges of segments and catheter were automatically delineated by computer using a dynamic programming algorithm involving a cost function which contained terms based on edge strength and on continuity. For every digitized radiographic projection, delineation was repeated in three adjacent frames, to improve precision. Edge points for each coronary segment were stored on disk. From these we computed the mean width along the segment (pixels). Scaling to obtain the Mean Absolute Width of the Segment (MAWS, mm) was achieved using catheter dimensions known from micrometry, systematic error due to imaging system line-spread function being corrected using data from computer simulations and phantom studies. Correction for geometric image intensifier distortion was also applied. We used the methodology in a randomized, controlled trial of the effect of lipid-lowering therapy, the St Thomas' Atherosclerosis Regression Study. The fundamental measure of change of disease in each segment was the change in MAWS (delta MAWS). Using in-vitro and in-vivo studies we established that the overall resolving power for one segment delta MAWS was 0.10 mm at 2 mm width and 0.14 mm at 4 mm width. Subsidiary end-points were the change (delta) in minimum absolute width of segment (MinAWS), edge irregularity index (EII) and percent diameter stenosis (%DS). Delta%DS (the conventional angiographic measure of coronary disease) was significantly correlated with change in all indices, closest correlation being seen with delta EII (r = 0.94, p < 0.001).
Interspersed RNA is an abundant class of cytoplasmic poly(A)+ RNA which contains repetitive elements within mostly heterogeneous single copy sequences. In spite of its quantitative importance in oocytes or eggs (two-thirds of the total poly(A)+ RNA), very little is known about its synthesis, its interaction with other molecules, and its functional significance. Here, we analysed a prevalent family of interspersed RNA (XR family) during Xenopus oogenesis. We found that XR interspersed RNA, unlike extracted interspersed RNA, did not form RNA duplexes in vivo. In small oocytes (stage III), XR RNA interacted with proteins forming rapidly sedimenting ribonucleoprotein particles (RNPs) with a median sedimentation constant of 80S. However, towards the end of oogenesis (stage VI), these XR RNPs changed into smaller particles with a median sedimentation constant of 40S. By analysing the proteins associated with XR RNA sequence, we have identified a 42 kilodalton protein in small oocytes, which was replaced by a 45 kilodalton protein at stage V of oogenesis.
Interspersed RNA makes up two-thirds of cytoplasmic polyadenylated RNA in Xenopus and sea urchin eggs. Although it has no known function, previous work has suggested that at least one family of interspersed RNA, XR, binds Xenopus oocyte proteins, and can influence the rate of translation. We have used two Xenopus repeat families, Ocr and XR, to explore their protein binding abilities. Ocr RNA binds the same pattern of highly abundant oocyte proteins that XR RNA binds, which are believed to be messenger ribonucleoprotein (mRNP) particle proteins. In addition, we show that Ocr RNA binds the Oct-60 protein, a member of the POU-domain family of transcription factors found in Xenopus oocytes. Using a 32 base pair sequence from the XR repeat in a DNA affinity column two proteins were isolated, 66 kDa and 92 kDa, that together form a complex with XR DNA. One of these proteins (92 kDa) also binds XR RNA. We suggest that the role of at least a subset of interspersed RNAs in development may be to bind, and sequester in the cytoplasm, DNA-binding proteins until the end of oogenesis.
OBJECTIVES: Previous studies of peripheral microvascular function in human heart failure have concentrated on changes in flow, and there is little information concerning the impact of heart failure on the principal determinants of transcapillary fluid exchange. This study investigated whether alterations in capillary pressure and microvascular fluid permeability can be detected in subjects with idiopathic dilated cardiomyopathy. METHODS: Finger nailfold capillary pressure and calf capillary filtration coefficient (CFC) were measured in parallel studies of two overlapping groups of 12 non-oedematous subjects with idiopathic dilated cardiomyopathy and mild to moderate heart failure and in age- and sex-matched healthy controls. Capillary pressure was measured by direct cannulation using an electronic resistance feedback servonulling technique, and CFC by mercury-in-silastic strain gauge plethysmography using a modification of the technique which avoids assumptions concerning isovolumetric venous pressure. RESULTS: Following correction for differences in skin temperature, capillary pressure was lower in the subjects with heart failure (P = 0.02). Both CFC and isovolumetric venous pressure were greater in the subjects with heart failure than in controls (3.4 +/- 0.9 vs. 2.6 +/- 0.7 ml.min-1.mmHg-1.100 ml-1, P = 0.03; 27.1 +/- 8.4 vs. 17.2 +/- 7.2 mmHg, P = 0.01). CONCLUSIONS: These data suggest that factors other than changes in arterial inflow and venous outflow pressures are likely to play an important role in the disruption of microvascular homeostasis which occurs in heart failure. Changes in capillary hydraulic conductance may contribute to the pathogenesis of oedema.
Xenopus oocyte cytoplasmic poly(A)+ RNA has been shown to include two major complex classes: mRNA and interspersed RNA. The former is defined by its translatability, while the latter consists of non-translatable repeat-containing transcripts with unknown functions. In this study we compared the accumulation patterns of total mRNA and a subfamily of interspersed RNA, the XR family (McGrew & Richter, 1989, Dev. Biol. 134, 267-70). The results showed that the XR interspersed RNA level continued to increase throughout oogenesis, while the total mRNA level reached a peak at late stage II and then decreased as much as 40% between stage II and stage VI of oogenesis. In addition we have found that, like mRNA, only about half of the non-translatable XR interspersed RNA underwent deadenylation at oocyte maturation. This result suggested that about half of the interspersed RNA, like certain mRNAs, also contains the U-rich element to protect it from the automatic deadenylation, implying the poly(A) tail of interspersed RNA may play a role during early development.