Modulation of thiopental-induced vascular relaxation and contraction by perivascular adipose tissue and endothelium.

BACKGROUND: Thiopental induces relaxation of vascular smooth muscle cells through its direct and/or indirect vasodilator effects. The perivascular adipose tissue (PVAT) and the endothelium are known to attenuate vascular contraction, and we have recently reported that PVAT potentiates the relaxation effect of propofol through endothelium-dependent and -independent mechanisms. Here, we studied the mechanisms of thiopental-induced vascular responses in relation to the involvement of PVAT and endothelium. METHODS: Thoracic aortic rings from male Wistar rats were prepared with or without PVAT (PVAT+ and PVAT-) and with an intact endothelium (E+) or with the endothelium removed (E-) for functional studies. The contraction and relaxation responses of these vessels to thiopental in the presence of agonists and various receptor antagonists and channel blockers were studied. RESULTS: In vessels pre-contracted with phenylephrine or KCl, thiopental-induced relaxation was highest in vessels denuded of both PVAT and the endothelium. PVAT attenuated the relaxation response to thiopental, and this attenuation effect was reduced by both angiotensin II (Ang II) type 1 receptor antagonists CV-11974 (2-n-butyl-4-choloro-5-hydroxymethyl-1-[2'-(1H-tetrazol-5-yl)biphenyl-methyl]-imidazole) or losartan and the angiotensin-converting enzyme inhibitor enalaprilat. Thiopental at high concentration (3 × 10(-3) M) caused a contraction through an endothelin-dependent mechanism. CONCLUSIONS: Thiopental induced relaxation in rat aorta through an endothelium-independent pathway and the presence of PVAT, endothelium, or both attenuated this relaxation response through Ang II-dependent and endothelin-dependent mechanisms, respectively.

Decreased apoptosis despite severe CD4 depletion in the thymus of a human immunodeficiency virus-1 infected child.

Thymic epithelial space (TES), where thymopoiesis is located, and thymic perivascular space (PVS), where T lymphocytes are pooled, appear differentially involved in human immunodeficiency virus 1 (HIV-1)-infected children. The decline of CD4+ T cells during HIV-1 infection is probably due to a relative predominance of CD4+ T cell destruction on cell proliferation. Antiretroviral therapy (ART) typically increases circulating CD4+ T cell counts, but it is debated whether ART reduces the destruction of existing CD4+ T cells or enhances the production of new cells. We report on postmortem flow-cytometry, immunohistochemistry, and terminal deoxynucleotide transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) studies performed on thymus of an 11-year-old vertically HIV-1 infected child receiving ART. Thymus tissue sections showed that CD4+ and CD8+ cells were more numerous in PVS than in TES (p=0.0334 for CD4+ cells, p<0.0001 for CD8+ cells). Thymus cell suspension showed that CD4+ CD8+ cells (immature thymocytes) were 15.4% (age-related control: 80.5%). Very few apoptotic CD4+ cells were seen in TES. Very low to absent proliferation activity was demonstrated in both TES and PVS. We suggest that 1) lymphocyte depletion in HIV-1 infection is more pronounced in TES than in PVS, 2) immature thymocytes are not enhanced, and 3) an anti-apoptotic effect in the thymus seems to be a potential ART mechanism to explain the CD4+ pool increase.

High-dose chemotherapy and autologous stem cell transplantation for primary central nervous system lymphoma: a multi-centre retrospective analysis from the United Kingdom.

The prognosis of patients with primary central nervous system lymphoma (PCNSL) has improved in recent years. This has partly been achieved by remission induction protocols incorporating high-dose methotrexate (HD-MTX) and rituximab. Given the high rates of relapse, consolidation therapy is usually considered in first response. Whole brain radiotherapy may prolong PFS but appears to confer no long-term survival advantage and is associated with significant neurocognitive dysfunction. Attempts to improve efficacy and reduce neurotoxicity of consolidation therapy have included thiotepa-based high-dose chemotherapy and autologous stem cell transplant (HDC-ASCT). This multi-centre, retrospective study reports the outcome of 70 patients undergoing HDC-ASCT for PCNSL in the United Kingdom. The median age at diagnosis was 56 years and all patients received HD-MTX-containing induction regimens. All patients underwent HDC-ASCT in first response. The rate of complete response increased from 50% before HDC-ASCT to 77% following HDC-ASCT. Treatment-related mortality was 6%. At a median follow-up of 12 months from HDC-ASCT, the estimated 1- and 2-year PFS rates were 71.5% and overall survival 86.4% and 83.3%, respectively. These data are comparable to published studies of HDC-ASCT for PCNSL, supporting its feasibility and efficacy.

Barriers to Colorectal Cancer Screening in Pakistan.

Background The prevalence of colorectal cancer (CRC) is growing in Pakistan; however, there are no national screening programs or guidelines in place to curb its development. This study was conducted with the aim of ascertaining public awareness and attitudes regarding CRC and current screening practices. Furthermore, the study assessed perceived barriers which could impact future screening processes. Methods A cross-sectional, questionnaire-based study was conducted among urban dwellers of Karachi, Pakistan. We excluded any individuals belonging to the medical profession, those diagnosed previously with CRC or having any significant co-morbidity. The validated and pre-tested questionnaire was administered among the study participants to record demographic information, awareness of CRC risk factors, symptoms and screening tests. Attitudes towards screening and perceived barriers to screening were also assessed. Data were analyzed using Statistical Package for Social Sciences (SPSS version 20.0) (IBM Corp., Armonk, NY). A knowledge score, out of a total of 14 points was calculated to reflect a participant's overall knowledge regarding CRC risk factors and signs/symptoms. Results The prevalence of CRC screening in eligible individuals (50 years or older) was 2.6% in our study population. Positive attitudes towards CRC management and screening were observed, with 75.1% (n = 296) acknowledging the preventive role of screening tests. Despite this only 14.9% (n = 58) of study participants expressed a future desire to undergo screening. Major barriers to screening were reported to be "a lack of knowledge regarding the screening procedure", a "lack of screening facilities" and that the "screening procedure is too expensive". A majority (n = 285, 72.3%) of the participants expressed a greater willingness to undergo screening if their doctor recommended it. Conclusion A national CRC screening and awareness program should be launched to promote awareness and facilitate screening in risk groups. General practitioners are needed to play a key role in counseling patients and endorsing healthy screening practices.

Pregnancy outcomes in women with or without placental malaria infection.

OBJECTIVE: To assess delivery outcomes in women with placental malaria who presented at public hospitals in Kisumu, a holoendemic region in western Kenya. METHODS: A cross-sectional study using both histology and molecular biology was conducted with 90 consecutive pregnant women who presented at 3 hospitals during a 2-week period. Data collectors completed standardized questionnaires using each patient's hospital record and physical examination results, and registered birth indices such as weight, head circumference, and weight-head ratio. Malaria infection of the placenta was assessed using a molecular biology approach (for genomic differences among parasite species) as well as histology techniques. Of the 5 histologic classes of placental infection, class 1 corresponds to active infection and class 4 to past infection; class 2 and 3 to active chronic infection; and class 5 to uninfected individuals. Plasmodium species typing was determined by polymerase chain reaction amplification of the parasite's genome. RESULTS: In newborns at term, low birth weight was directly associated with classes 2 and 4 of placental infection (P = 0.053 and P = 0.003, respectively), and differences in birth weight remained significant between the 5 classes (P < 0.001) even after adjusting for parity and mother's age. Plasmodium falciparum was the only detected parasite. CONCLUSIONS: In Kisumu, infection with P. falciparum is an important cause of low birth weight and morbidity when it is associated with histologic classes 2 and 4 of placental infection. Moreover, polymerase chain reaction assays should be supported by ministries of health as an ancillary method of collecting data for malaria control during pregnancy and providing a baseline for future interventions.

Benign intracranial hypertension in pregnancy: current diagnostic and therapeutic approach.

Four cases of benign intracranial hypertension (BIH) in pregnancy are presented. Literature regarding this rare entity is reviewed. Various diagnostic and therapeutic approaches in the management of BIH are described, with special emphasis on the newer neurodiagnostic and neurosurgical approaches. Guidelines have been suggested in diagnosing and managing this syndrome in pregnancy.

Comparing angiographic coronary revascularization strategies: a 'natural' experiment.

OBJECTIVE: To study the impact of intracoronary stents on clinical restenosis in the 'real world'. DESIGN: Retrospective comparison of the rates of clinical restenosis between two cohorts exposed to different strategies for percutaneous transcatheter intervention. The endpoint was the first of death, myocardial infarction, coronary artery bypass grafting, repeat percutaneous transluminal coronary angioplasty (PTCA) or repeat coronary angiography within nine months. SETTING: Tertiary care cardiac referral centre serving a large, metropolitan population. PATIENTS: Patients undergoing angiographic revascularization from January 1 to February 28, 1996 (the 'restricted' group [R], n=147) were compared with a before and after cohort (the 'usual' group [U], n=232, divided into those who underwent revascularization between November 1 and November 30, 1995, and those who underwent revascularization between April 1 and May 31, 1996). INTERVENTIONS: The R group was revascularized during a period of economic constraint, which imposed a shortage on stent availability. The U cohort underwent revascularization before and after the shortage (an 'unrestricted' environment for stent usage). MAIN RESULTS: There was no difference in clinical restenosis rates between the R (34.7%) and U (37.9%) groups (P=0.524, OR R/U=0.915, 95% CI 0.694 to 1.206). Also, the rate of clinical restenosis was the same among patients who underwent PTCA without stent insertion (34.8%) and those who received a stent (39.4%) (P=0.368, OR=1.13, 95% CI 0.87 to 1.44). CONCLUSIONS: At the authors' institution, a restricted stenting policy did not result in a higher clinical restenosis rate than that of usual practice.

Predictors of same-admission cardiac catheterization in patients with acute ischemic syndromes.

BACKGROUND: Various strategies exist for the use of cardiac catheterization in unstable angina or non-Q wave myocardial infarction. At the authors' institution, the overall volume of cardiac catheterization has increased in recent years. OBJECTIVE: To investigate whether this increased volume of cardiac catheterization was due to adoption of a more invasive approach to the management of patients with acute ischemic syndromes. DESIGN: A retrospective cohort study was conducted using detailed chart review of coronary care unit admissions during 1990/91 and 1993/94. SETTING: A university-affiliated tertiary care referral centre with facilities for cardiac catheterization. PATIENTS: One hundred patients randomly selected from among those with unstable angina, non-Q wave myocardial infarction or chest pain not yet diagnosed in each of the study years. Detailed follow-up was complete for all patients. OUTCOME MEASURE: The use of cardiac catheterization during the index admission was documented. MAIN RESULTS: There was a trend towards more frequent use of same admission cardiac catheterization in the later period (21% [CI 14% to 31%] versus 12% [CI 7% to 20%], P = 0.09). However, after controlling for baseline characteristics and in-hospital events, the year of admission did not independently predict the use of catheterization (P = 0.60). By multivariate logistic regression, recurrence of chest pain and evidence of myocardial necrosis were most closely associated with same-admission cardiac catheterization. CONCLUSIONS: Although clinical factors partially explain the increased use of catheterization over time, there may have also been shift towards a more aggressive practice style at the authors' institution. Further study is needed to address this possibility.

Synthetic aperture pulse-echo imaging with rectangular boundary arrays [acoustic imaging].

The effectiveness of a square boundary array in finite-range, pulse-echo imaging is investigated. The images produced by such an array are quite poor when no additional signal processing is used. It is demonstrated through simulations that a synthetic-aperture signal processing technique called image addition can be used to reduce the sidelobes associated with the square boundary array, thereby improving the image quality. Image addition was originally proposed for narrowband imaging of far-field scenes, but it is also useful for finite-range, pulse-echo imaging. The conclusions are expected to apply to other, nonsquare boundary array geometries.

A structure for adaptive order statistics filtering.

In applications such as smoothing and enhancement of images, adaptive filtering techniques offer the flexibility needed for good performance with non-stationary observations. Many adaptive schemes can be based on the idea of determining the local statistics of the signal through appropriate tests on the data, to aid in the selection of a filtering procedure that is suited to the data. In the paper, the authors consider decision-directed or data-dependent adaptive filtering schemes that are based on order statistics. A general formulation for such a class of adaptive order statistics filters is presented. Approximate statistical performance analysis, especially in the presence of edges, may be carried out for this entire class of filters. The authors give examples of some existing filters that fit into this framework. The formulation also accommodates filters that employ multiple windows in their operation. To illustrate the potential of this class of multiple window (MW) filters, they construct and analyze simple filters, like the triple window median (TW-MED) and the triple window median of means (TW-MOM) filters, that are shown to yield useful performance. The class of mean-median hybrid (MMH) filters is also presented as a simple example which may be extended to give interesting performance.

RBFN restoration of nonlinearly degraded images.

We investigate a technique for image restoration using nonlinear networks based on radial basis functions. The technique is also based on the concept of training or learning by examples. When trained properly, these networks are used as spatially invariant feedforward nonlinear filters that can perform restoration of images degraded by nonlinear degradation mechanisms. We examine a number of network structures including the Gaussian radial basis function network (RBFN) and some extensions of it, as well as a number of training algorithms including the stochastic gradient (SG) algorithm that we have proposed earlier. We also propose a modified structure based on the Gaussian-mixture model and a learning algorithm for the modified network. Experimental results indicate that the radial basis function network and its extensions can be very useful in restoring images degraded by nonlinear distortion and noise.

Array redundancy for active line arrays.

Active imaging arrays are used to image scenes composed of reflectors of transmitted radiation, and in many such applications, line arrays are employed. In this paper, we discuss scanned active line arrays for imaging based on image synthesis. We define the novel concept of array redundancy for active arrays, analogous to the well-known concept of redundancy applied to passive arrays, and we define and give examples of minimum redundancy and reduced redundancy line arrays composed of transmit/receive elements. Such arrays differ from their passive imaging counterparts both in geometry and in element count.

High resolution coherent source location using transmit/receive arrays.

A general approach to super resolution imaging of point sources using active arrays of transmit/receive elements is presented. The usual techniques of high resolution imaging using single transmitters and passive receive arrays fail in the presence of sets of coherent point sources, which often arise due to coherent multipath. However, data obtained from transmit/receive arrays may be arranged into matrices to which eigenspace direction of arrival estimation may be successfully applied, even int he presence of coherent sources. Each such matrix may be thought of as corresponding to a different transmit/receive array; this may be either the actual transmit/receive array or a virtual transmit/receive array whose effect is synthesized. This approach provides great flexibility, since a large number of different synthetic or virtual arrays may be available for a given transmit/receive array, and each can provide a different tradeoff between the total number of resolvable targets and the largest number of mutually coherent targets which can be resolved.

Coarray synthesis with circular and elliptical boundary arrays.

An elliptical boundary aperture is a collection of points lying on an ellipse from which energy is transmitted and/or received. An important special case is the circular boundary aperture. When these apertures are used with beamforming to produce a narrowband image of a far-field source, the corresponding point spread function (PSF) is characterized by high sidelobes. The concept of the coarray of an imaging system is used here to develop techniques which synthesize the effect of a more desirable PSF with an elliptical boundary aperture. Techniques are given for use in active imaging of spatially coherent sources, as well as passive imaging of spatially incoherent sources. Discrete arrays and continuous apertures are considered separately. The approach shows that the PSF synthesis problem can be solved in many more ways than previously recognized, and this fact is exploited to develop procedures which have a least-squares optimality property.

Diabetic halo. A reversible ultrasonic sign.

Two pregnant women with poorly controlled diabetes mellitus were noted to have "edematous" fetuses on ultrasonography. There was abdominal wall "edema" in one and scalp "edema" in both fetuses. In light of what is known about the fetal body composition in diabetic pregnancies, we propose that this sonographic appearance reflects increased fat deposition, rather than accumulation of edema fluid, in the fetal subcutaneous tissue; it has been called "diabetic halo." In a patient who had been treated for eight weeks but not in another, in whom treatment was only for 1.5 weeks, these sonographic features were reversed. This is probably in decreased fat deposition in the fetus. We suggest that this ultrasonographic sign be added to our means of diagnosing uncontrolled diabetic pregnancies and of monitoring the degree of control in diabetic pregnancies.

Ovarian hemorrhage in ovulating women receiving anticoagulant therapy. A report of two cases.

Women taking anticoagulants are at increased risk of ovarian hemorrhage when they ovulate. Management depends on the patient's clinical presentation and her medical, including obstetric, history. Bilateral oophorectomy should be considered for selected patients on chronic anticoagulation therapy and for those patients for whom reproduction is of no concern. Ovulatory suppression is warranted when conservative therapy is adopted.

Sickle-cell-induced hematuria in pregnancy. The current diagnostic and therapeutic approach.

Hematuria is a rather frequent complication in patients with sickling disorders. However, the occurrence, incidence and management of this complication during pregnancy have not been discussed in the medical literature. We treated three patients with sickle-cell-induced hematuria in pregnancy and developed an approach we find useful for such patients.