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.     

Application of breast cancer risk prediction models in clinical practice.

Breast cancer risk assessment provides an estimation of disease risk that can be used to guide management for women at all levels of risk. In addition, the likelihood that breast cancer risk is due to specific genetic susceptibility (such as BRCA1 or BRCA2 mutations) can be determined. Recent developments have reinforced the clinical importance of breast cancer risk assessment. Tamoxifen chemoprevention as well as prevention studies such as the Study of Tamoxifen and Raloxifene are available to women at increased risk of developing breast cancer. In addition, specific management strategies are now defined for BRCA1 and BRCA2 mutation carriers. Risk may be assessed as the likelihood of developing breast cancer (using risk assessment models) or as the likelihood of detecting a BRCA1 or BRCA2 mutation (using prior probability models). Each of the models has advantages and disadvantages, and all need to be interpreted in context. We review available risk assessment tools and discuss their application. As illustrated by clinical examples, optimal counseling may require the use of several models, as well as clinical judgment, to provide the most accurate and useful information to women and their families.     

The European Menopause Survey 2005: women's perceptions on the menopause and postmenopausal hormone therapy.

OBJECTIVES: To identify and describe current women's thoughts about the menopause, hormone treatment (HT) and perceptions about breast cancer. METHODS: Between December 2004 and January 2005, 4201 postmenopausal women in seven European countries were interviewed via a standardized computer-aided telephone interview protocol. RESULTS: Almost all women reported to have experienced climacteric symptoms, and 63% of the women rated them as being severe. Only 52% of women were aware of the benefits of HT for relief of climacteric symptoms. Although 84% felt that severe symptoms should be treated, only 40% had used HT at some point in time. Thirty-four percent of the women preferring treatment with natural products did so because of the risk of breast cancer associated with HT. HT was recognized by 59% of the women as one of the most important contributors to an increased breast cancer risk. Most women received their information about HT and breast cancer risk from the media. CONCLUSIONS: This European survey reveals that the majority of women experience climacteric symptoms but that their decision whether or not to use HT is highly dependent on their concern about breast cancer risk. An increase in knowledge of the benefits and risks of HT is required for women to make appropriate decisions about hormone use.     

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.     

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.     

Experiments on the nature of the signal that induces spinal neuroplastic changes following a peripheral lesion.

This study aimed at identifying the signal(s) that elicit myositis-induced neuroplastic changes in background activity and responsiveness of spinal neurones. It is based on previous data suggesting that in dorsal horn neurones, responsiveness to peripheral input on one hand and background activity on the other are probably controlled by different mechanisms. In anaesthetized rats, myositis was induced in the gastrocnemius-soleus muscle and the activity of single dorsal horn neurones was recorded in segment L3. Impulse traffic and axoplasmatic transport in dorsal roots L4 and L5 were selectively blocked by lignocaine or vinblastine for various time periods relative to the induction of the myositis. The results show that the main triggering signal for the myositis-induced changes in both responsiveness and background activity is the altered impulse activity in primary afferent fibres. In contrast, 'no axonally transported chemical signal controlling the discharge behaviour of dorsal horn neurones was found. However, the time course of the electrical signals that cause the myositis-induced changes in background activity and responsiveness is different. For changes in responsiveness, a rather narrow time window of 2 h directly after induction of the myositis existed, during which the impulses from the inflamed muscle must reach the spinal cord. Accordingly, to prevent the increase in responsiveness, the electrical input had to be blocked during the first 2 h; a block of the same duration at another time had no effect. The change in background activity seems to be due to a continuous input from the inflamed muscle which adds up over the hours. Therefore, with regard to background activity, blocking the electrical signals is effective at any time, but only a block of long duration has a significant effect.