Multi-Slice MRI of Rat Brain Perfusion During Amphetamine Stimulation Using Arterial Spin Labeling

When a single coil is used to measure perfusion by arterial spin labeling, saturation of macromolecular protons occurs during the labeling period. Induced magnetization transfer contrast (MTC) effects decrease tissue water signal intensity, reducing the sensitivity of the technique. In addition, MTC effects must be properly accounted for in acquiring a control image. This forces the image to a single slice centered between the labeling plane and the control plane. In this work, a two-coil system is presented as a way to avoid saturation of macromolecular spins during arterial spin labeling. The system consists of one small surface coil for labeling the arterial water spins, and a head coil for MRI, actively decoupled from the labeling coil by using PIN diodes. It is shown that no signal loss occurs due to MTC effects when the two-coil system is used for MRI of rat brain perfusion, enabling three-dimensional perfusion imaging. Using the two-coil system, a multi-slice MRI sequence was used to study the regional effects of amphetamine on brain perfusion. Amphetamine causes significant increases in perfusion in many areas of the brain including the cortex, cingulate, and caudate putamen, in agreement with previous results using deoxyglucose uptake to monitor brain activation.     

Stapled hemorrhoidectomy: Initial experience of a Latin American group

The purpose of the present study was to determine the value of circular emorrhoidectomy (procedure for prolapse and hemorrhoids [PPH]) on the basis of data collected prospectively during the initial experience of a group of Latin American surgeons. Between 2000 and 2001, PPH was performed using a circular stapler in 177 patients who had third- and fourth-degree hemorrhoidal disease. The average age of the patients was 47.7 years (range 26 to 85 years). Anal bleeding was the most common preoperative complaint (93.2%) followed by anal pain (60.2 %), anal itching (43%), and constipation (41 %). Hemorrhoids were classified as third degree in 132 patients (74%) and fourth degree in 45 patients (25.4%). Skin tags were detected in 86 patients (48.8%) and rectocele in 14 patients (7.9%). Data collected included patient demographics, type of anesthesia, and specific details of the surgery such as duration of the operation, distance from the staple line to the dentate line, need for complementary hemostasis, and any unexpected occurrences. Postoperative data collected included the degree of pain, which was evaluated on the basis of the type and dosage of analgesics required, laxative consumption, and the presence of bleeding, fever, urinary retention, or hematomas. Each patient completed a written questionnaire addressing these events. Patients returned for follow-up visits on days 7, 15, 30, and 90. Responses to pain, bleeding, fever, anal continence, recurrence of hemorrhoids, and level of satisfaction were compiled. The duration of the procedure ranged from 6 minutes to 2 hours (average 2 3 minutes), and most operations lasted no more than 20 minutes, with the exception of one that lasted 2 hours because of intraoperative bleeding. Intraoperative problems were minor. An additional one or a few sutures were required in 58.7% of patients to achieve perfect hemostasis. In 128 patients (72.3%) the hospital stay was less than 24 hours. Same-day surgery was chosen for 37 patients (20.9%). Pain was controlled with analgesia only using one to six doses of oral dipirona in 126 patients. Five patients were readmitted to the hospital: four for control of bleeding and one for conventional hemorrhoidectomy due to an acute episode of external hemorrhoidal thrombosis. At day 30, patients rated the efficacy of the procedure in alleviating preoperative symptoms as follows: 77.5% excellent; 16% good; 5.3% average, and 1.2% poor. At 3 months postoperatively no patient had had a recurrence of hemorrhoidal prolapse, and there were no instances of stenosis or anal incontinence. Surgeons also rated the efficacy of the procedure as excellent in 75%, good in 19.8%, average in 4.7%, and poor in 0.6%. With proper selection of patients and adequate stapling technique, stapled hemorrhoidectomy may be considered safe; it is easily learned, has a satisfactory degree of pain, and is well accepted by both patients and surgeons. Supported in part by Johnson & Johnson.     

Estimation of water extraction fractions in rat brain using magnetic resonance measurement of perfusion with arterial spin labeling

The model used for calculating perfusion by MRI techniques that use endogenous water as a tracer assumes that arterial water is a freely diffusible tracer. Evidence shows that this assumption is not valid in the brain at high blood flow rates, at which movement of water into and out of the microvasculature becomes limited by diffusion across the blood-brain barrier. In this work, the arterial spin-labeling technique is used to show that fraction of arterial water that is dependent on blood flow rate remains in the vasculature and does not exchange with brain tissue water. By using perfusion measurements without and with magnetization transfer (MT) effects, one can distinguish arterial label that exchanges into tissue because blood has much smaller MT than brain tissue. Using this technique, the extraction fraction for water is measured in the rat brain at various cerebral blood flow rates. At high flow rates (-5 ml/g/min), the extraction fraction for water is found to be about 45% in rat brain. Disruption of the blood-brain barrier with D-mannitol caused an increase in the extraction fraction for water. It was possible to form an image related to the extraction fraction for water. The ability to estimate the amount of vascular water exchanging with tissue water by MRI may represent a noninvasive approach to detect the integrity of the blood-brain barrier.     

HIV prevalence and risk factors in a Brazilian penitentiary

HIV infection among prison inmates shows one of the highest prevalence rates for specific population subgroups, reaching as high as 17% in Brazil and elsewhere in the world. The present study aimed to estimate HIV antibody prevalence and risk factors for infection in male inmates at the Ribeir?o Preto Penitentiary, S?o Paulo State, Brazil, from May to August 2003. Using simple random sampling, 333 participants were selected, answered a standardized questionnaire, and had blood samples collected. Enzyme-linked immunosorbent assay (ELISA) and indirect immunofluorescence were used for HIV serological diagnosis. Overall HIV prevalence among inmates was 5.7% (95%CI: 3.2-8.2). All variables associated with HIV antibodies in the univariate analysis were submitted to unconditional multivariate logistic regression. Independent predictors of HIV infection were: total prison sentence less than five years and sharing needles and syringes.     

Growth factors and stromal support generate very efficient retroviral transduction of peripheral blood CD34+ cells from Gaucher patients

We have achieved high-efficiency gene transfer into nonmobilized peripheral blood (PB) CD34+ cells from patients with Gaucher's disease using a clinically acceptable retroviral supernatant transduction protocol. In our studies, bone marrow (BM) and PB CD34+ cells were transduced using a high titer (10(8) particles/mL) retroviral supernatant once a day for 4 consecutive days in the presence of interleukin-3 (IL-3), IL-6, and stem cell factor (SCF), with or without an irradiated allogeneic BM stromal layer. The growth factors alone resulted in 29% +/- 10% gene transfer of PB CD34+ clonogenic cells in contrast with 71% +/- 17% gene transfer efficiency using stroma with the growth factors; a 2.5-fold increase. The increase in gene transfer efficiency was less prominent when BM CD34+ cells were used (40% +/- 16% without and 57% +/- 8% with stroma, a 1.5-fold increase). The overall transduction efficiency of both PB and BM CD34+ cells was lower when the cells were transduced over a stromal cell layer without added growth factors. The combination of IL-3, IL-6, and SCF with stroma transduced 75% of primitive long-term culture initiating cells (PB LTC- ICs) in comparison with 34% of LTC-ICs when IL-3, IL-6, and SCF were used without stromal support. Using this clinically acceptable supernatant/cytokines/stroma transduction protocol, correction of the glucocerebrosidase (GC) deficiency in the progeny cells of PBLTC-ICs from Gaucher's-disease patients has been accomplished. Efficient transduction of the PB CD34+ cells using this transduction protocol may allow repeated delivery of "GC-corrected" hematopoietic stem and progenitor cells to Gaucher's-disease patients.     

Surveillance of cytomegalovirus infection in haematopoietic stem cell transplantation patients

OBJECTIVES: The aim of this study was to describe our experience in the control of active CMV infection following HSCT using two strategies of CMV infection treatment: ganciclovir universal prophylaxis at low doses and pre-emptive therapy with ganciclovir. METHODS: The surveillance was based on the monitoring of antigenaemia (AGM) and on a nested polymerase chain reaction (N-PCR) for the detection of CMV in both strategies. Forty-five recipients with malignant diseases and with a risk for CMV disease received universal prophylaxis (Group A). The non-treated group consisted of 24 patients, most of them with non-malignant diseases who did not receive universal prophylaxis (Group B). RESULTS: In Group A, the incidence of positive AGM was 51%, with a positive PCR of 68.9%. In Group B, the AGM positivity was 66.7% and that of N-PCR was 66.7%. CMV disease occurred in 6/55 patients (10.9%), with 2/36 (5.5%) from Group A and 4/19 (21%) from Group B. Two of these six patients (33.3%) died of CMV disease. CONCLUSIONS: Our result suggests that AGM and N-PCR can be used as markers for assessing the monitoring and the introduction pre-emptive therapy. This approach could prove to be more cost-effective than ganciclovir universal prophylaxis for treating CMV infection.     

Direct demonstration that autologous bone marrow transplantation for solid tumors can return a multiplicity of tumorigenic cells

Patients with solid tumors are increasingly being treated by autologous bone marrow transplantation (BMT). Although response rates appear to be increased, disease recurrence is the commonest cause of treatment failure. Whether relapse is entirely due to residual disease in the patient or arises also from infiltrating malignant cells contained in the autologous marrow transplant has not been resolved. If the latter explanation is correct, then purging would be required as part of the transplantation procedure. We used retrovirally mediated transfer of the neomycin-resistance gene to mark BM harvested from eight patients with neuroblastoma in clinical remission. The marked marrow cells were subsequently reinfused as part of an autologous BMT. At relapse, we sought the marker gene in malignant cell populations. Three patients have relapsed, and in each the marker gene was detected by phenotypic and genetic analyses of resurgent malignant cells at medullary and extramedullary sites. Analysis of neuroblast DNA for discrete marker gene integration sites suggested that at least 200 malignant cells, each capable of tumor formation, were introduced with the autologous marrow transplant and contributed to relapse. Thus, autologous BMTs administered to patients with this solid tumor may contain a multiplicity of malignant cells that subsequently contribute to relapse. The marker-gene technique we describe should permit evaluation of the mechanisms of relapse and the efficacy of purging in patients receiving autologous marrow transplantation for other solid tumors that infiltrate the marrow.     

Psychological criteria for contraindication in lung transplant candidates: a five-year study

Lung transplantation presents a wide range of challenges for multidisciplinary teams that manage the care of the recipients. Transplant teams should perform a thorough evaluation of transplant candidates, in order to ensure the best possible post-transplant outcomes. That is especially true for the psychologist, because psychological issues can arise at any point during the perioperative period. The objective of our study was to evaluate the psychological causes of contraindication to waiting list inclusion in a referral program for lung transplantation. We retrospectively analyzed data on psychological issues presented by lung transplant candidates, in order to understand these matters in our population and to reflect upon ways to improve the selection process.