Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2 micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC).     

Safety considerations for operating room personnel during hyperthermic intraoperative intraperitoneal chemotherapy perfusion.

The new treatment strategy for Peritoneal Surface Malignancy combines a cytoreductive surgery and perioperative intraperitoneal chemotherapy. Cytoreduction removes all macroscopic tumor. Intraperitoneal chemotherapy avoids implantation of microscopic residual tumor cells on intra-abdominal surfaces when it is administered intraoperatively and/or early in the postoperative period. Delivering cytotoxic drugs directly into the peritoneal cavity maximizes dose intensity and minimizes systemic toxicity. Hyperthermia is selectively cytotoxic for malignant cells and potentiates the effect of chemotherapy. Implementation of this procedure makes the perioperative personnel to face a risk of exposure to cytotoxic agents. Furthermore, peritonectomies and electro-evaporation of tumor nodules are performed with high voltage electrocautery, generating a large amount of surgical smoke during several hours. Inhalation of these fumes may be also a risk for healthcare workers. In this article, we analyse in depth these new risks of the operating room personnel, we review the literature, and we give guidelines for secure performance of cytoreductive surgery and hyperthermic intraoperative intraperitoneal chemotherapy, as well as for early postoperative intraperitoneal chemotherapy administration. These new procedures are safe techniques for patients and healthcare workers provided adequate policies are adopted to avoid occupational exposure.     

Altered functional status of the hypothalamic dopaminergic tone in patients with chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: a pilot study.

We compared the functional status of the hypothalamic dopaminergic tone in patients given an allogeneic hematopoietic stem cell transplantation (allo-HSCT) with chronic graft-versus-host disease (GVHD) with that observed in patients with allo-HSCT without chronic GVHD and in healthy controls. The effect of acute dopaminergic blockade with intravenous metoclopramide on serum prolactin (PRL) concentrations was evaluated. Twenty volunteers, 20 to 52 years of age, seronegative for both hepatitis C virus and the human immunodeficiency virus, were studied: (1) 10 clinically healthy men (group 1), and (2) 9 patients with leukemia, and 1 patient with refractory aplastic anemia who underwent allo-HSCT, 5 of whom (3 men and 2 women) developed chronic GVHD (group 2), and 5 (3 men and 2 women) who did not develop chronic GVHD (group 3). Serum PRL concentrations were measured both fasting and after intravenous administration of metoclopramide (10-mg bolus). The area under the PRL curve was calculated. Patients in group 2 were older than those in groups 1 and 3 (P<.018), but their body mass index was similar. Fasting serum PRL concentrations were similar among the 3 groups; however, group 2 had higher PRL concentrations throughout the test (P<.001) and a greater area under the PRL curve than groups 1 and 3 (P<.001), without differences between the last 2 groups. The differences remained significant after adjustment for age (P<.01). Our results in a small group of patients with chronic GVHD after allo-HSCT suggest the existence of an increased functional level of their hypothalamic dopamine tone, which would favor a tendency toward a diminished endogenous production, release of pituitary PRL, or both. This could represent an adaptive mechanism aiming to maintain circulating PRL concentrations within a physiological range.     

Diagnosis of serous neuroretinal detachments of the macula in severe preeclamptic patients with optical coherence tomography.

OBJECTIVE: Visual symptoms are common in patients with preeclampsia, and are caused by various underlying pathological changes in the retina. Blurred vision may be one of these symptoms. We describe three cases in which the underlying retinal pathology of blurred vision was clarified using optical coherence tomography (OCT), a novel, non-invasive ophthalmic imaging technique that provides micrometer-scale resolution images of the human retina. METHODS: Three patients with preeclampsia complained of blurred vision postpartum. In all cases, ophthalmoscopy was performed at the bedside, followed by the assessment of best corrected visual acuity, slit-lamp biomicroscopy, fluorescein angiography (FLA), and OCT. In all cases, the presence of central visual defects was examined by an Amsler-grid. RESULTS: In one case, the symptoms were bilateral. In all affected eyes, the patients complained of a relative central scotoma. Ophthalmoscopy showed edema in the affected maculae, while OCT examination clarified a serous neurosensory detachment of the macula. In one case, a neurosensory detachment was also detected in the papillomacular region of a fellow eye with no symptoms. In two cases, FLA was performed, but only in one case could we detect late leakage and subretinal exudates. The serous detachments observed showed total resolution in all cases within 5 to 10 weeks, with restoration of visual acuity. CONCLUSION: In patients with preeclampsia, OCT may provide a useful method for the precise assessment of retinal changes, distinguishing retinal edema from serous neurosensory detachments. This finding may help to clarify the pathophysiological circulatory changes seen in preeclampsia.     

Left pulmonary artery evaluation through transesophageal echocardiography.

INTRODUCTION: Transesophageal echocardiography (TEE) has become increasingly useful in the study of patients with suspected pulmonary thromboembolism. OBJECTIVE: The aim of this study was to prospectively evaluate the usefulness of TEE in the study of the distal part of the left pulmonary artery (LPA) as well as the influence of this procedure on total echocardiographic exam duration. METHODOLOGY: A prospective study in two groups of consecutive patients referred for TEE with a one- year interval between evaluation of Group A: 33 patients, 17 male, mean age 54 +/- 24 years, and Group B: 42 patients, 20 male, mean age 48 +/- 27 years (p = NS). The procedure was considered long when it took more than 3 min to evaluate the distal part of the LPA. RESULTS: In group A we were able to visualize the distal part of the LPA in 24 patients (73%) without significant prolongation of total exam duration in 16 patients (48% of group A). In one of the patients with suspected pulmonary thromboembolism thrombi were only observed in the distal part of the LPA. In group B we were able to visualize the distal part of the LPA in 36 patients (86%) without significant prolongation of total exam duration in 26 patients (61% of group B). CONCLUSIONS: 1. Visualization of the distal part of the LPA was possible in more patients, and with TEE time prolongation in less patients, in group B. These differences can be accounted for by the training of the operator in this technique. 2. The importance of visualization of this part of the LPA in guiding treatment in the subset of patients with pulmonary thromboembolism confirms the usefulness of this specific procedure.     

Modeling in Frequency Domain Used for Assessment of In Vivo Dissolution Profile

Purpose. To present a model-dependent approach for the assessment of the in vivo drug dissolution profile based on in vitrodata for the multiple unit dosage form, as an alternative to the numerical method proposed in the study by Hayashi et al, Pharm. Res. 12:1333–1337 (1995). Methods. The data for aspirin granules administered to healthy subjects obtained in the above mentioned study were re-evaluated. The subject dissolution system was considered to consist of two subsystems connected in series, i.e. the subsystem describing the gastric-emptying process and the subsystem describing the intestinal dissolution process. The frequency response method was used to model the subject dissolution system. Results. The model in vivodissolution profile of aspirin, assessed as the integral of the model weighting function of the subject dissolution system, was in agreement with the in vivo cumulative absorption profile calculated by the Wagner-Nelson method. Conclusions. Comparison of dynamic properties of the subject dissolution system with the subsystem describing the gastric-emptying process yielded quantitative confirmation of the decisive role of the gastric-emptying process in the in vivodrug dissolution after administration in the multi unit dosage form.     

Effects of erythromycin on the propulsive motility of upper gastrointestinal tract in rats

The differences between the postprandial mixing or propulsion and the interdigestive motility of the gastrointestinal (GI) tract are already known. Earlier studies showed dose-dependent differences in the effects of erythromycin on interdigestive motility. The various GI side-effects (vomiting, diarrhoea) also suggest that there are different effects of erythromycin on the GI motility. The aim of our study was to examine postprandially the propulsive effects of different doses of erythromycin on the movement of intraluminal contents in the upper GI tract of the rat. The animals were fasted for 24 h before the experiments but water was given freely. The rats received 1.5 ml 1.5% methylcellulose painted with 0.05% phenol-red intragastrically (test solution). Erythromycin(E. lactobionate) was given intravenously at doses of 0.05, 0.1, 0.25, 0.5, 1.0 and 5.0 mg/kg 15 min before the administration of a test solution. The animals were sacrificed 20,60 and 120 min after administration of methylcellulose, when the distance between the front of the painted intraluminal contents and the pylorus was measured and expressed as a percentage of the total length of small intestine. The phenol-red content in the stomach and small intestine was measured spectrophotometrically and the gastric emptying was calculated from the ratio of the measured total and intestinal phenol-red content. Our results showed that the small doses of erythromycin (0.1 and 0.25 mg/kg) accelerated gastric emptying after 20 min but did not change significantly the propulsive motility of upper small intestine; however, large doses of erythromycin (1.0 and 5.0 mg/kg) decreased gastric emptying and upper GI motility after 20 and 60 min. In summary, the prokinetic action of small doses of erythromycin was demonstrated, but its effecttime on GI motility is short and the ratio of the stimulating and inhibitory doses is 1:10. This paper was presented at the Section of IUPHAR GI Pharmacology Symposium on ’Biochemical pharmacology as an approach to gastrointestinal disorders (basic science to clinical perspectives)‘, October 12-14, 1995, Pécs, Hungary.     

Is colonic electrical activity a similar phenomena to small-bowel electrical activity?

PURPOSE: This study was designed to investigate colonic spike bursts regarding 1) their migration behavior, 2) their pressure correlates, and 3) comparing colonic short spike bursts with spike bursts from migrating myoelectric complex from the small bowel. METHODS: Rectosigmoid electromyography and manometry were recorded simultaneously in seven normal volunteers and electromyography alone in five others during two hours of fasting and for two hours after one 2,100-kJ meal. One patient with an ileostomy was also studied by the same method to record the migrating myoelectric complex from the terminal ileum during fasting. RESULTS: Three kinds of spike bursts were observed in the pelvic colon: rhythmic short spike bursts, migrating long spike bursts, and nonmigrating long spike bursts. The meal significantly increased the number of migrating and nonmigrating long spike bursts (from 25 to 38.7 percent of the recording time; P <0.01). These bursts of potentials showed a peak 15 minutes after the meal, which may be caused by the gastrocolic reflex. Migrating long spike bursts started anywhere along the rectosigmoid and migrated from there aborad 82 percent of the time and orad or in both directions in 10 or 7 percent of the time, respectively. They originated pressure waves 99 percent of the time. Short spike bursts were more frequent before the meal (15.1 percent before and 9.6 percent after the meal), but the difference was not significant; they neither propagated nor initiated pressure waves detected by the miniballoon. CONCLUSIONS: Migrating long spike bursts were the only potentials that migrated, sometimes for short distances. Short spike bursts are a different phenomenon from the small-bowel migrating myoelectric complex because they do not migrate; they can occur during the postprandial period and never originated intraluminal pressure waves.Supported by a grant from the Instituto Nacional de Investigação Científica, Proc. DBI-22086.Presented at the meeting of the Portuguese Congress of Gastrenterology, Vila Moura, Portugal, June 2 to 5, 1993.