The addition of deep hyperthermia to gemcitabine-based chemoradiation may achieve enhanced survival in unresectable locally advanced adenocarcinoma of the pancreas.

INTRODUCTION: Driven by the current unsatisfactory outcomes for patients with locally advanced pancreatic cancer (LAPC), a biologically intensified clinical protocol was developed to explore the feasibility and efficacy of FOLFORINOX chemotherapy followed by deep hyperthermia concomitant with chemoradiation and subsequent FOLFORINOX chemotherapy in patients with LAPC. METHODS: Nine patients with LAPC were treated according to the HEATPAC Phase II trial protocol which consists of 4 cycles of FOLFORINOX chemotherapy followed by gemcitabine-based chemoradiation to 56 Gy combined with weekly deep hyperthermia and then a further 8 cycles of FOLFORINOX chemotherapy. RESULTS: One grade three related toxicity was reported and two tumours became resectable. The median overall survival was 24 months and 1 year overall survival was 100%. CONCLUSIONS: Intensification of chemoradiation with deep hyperthermia was feasible in nine consecutive patients with LAPC.

Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

Local hyperthermia combined with radiotherapy and-/or chemotherapy: recent advances and promises for the future.

Hyperthermia, one of the oldest forms of cancer treatment involves selective heating of tumor tissues to temperatures ranging between 39 and 45°C. Recent developments based on the thermoradiobiological rationale of hyperthermia indicate it to be a potent radio- and chemosensitizer. This has been further corroborated through positive clinical outcomes in various tumor sites using thermoradiotherapy or thermoradiochemotherapy approaches. Moreover, being devoid of any additional significant toxicity, hyperthermia has been safely used with low or moderate doses of reirradiation for retreatment of previously treated and recurrent tumors, resulting in significant tumor regression. Recent in vitro and in vivo studies also indicate a unique immunomodulating prospect of hyperthermia, especially when combined with radiotherapy. In addition, the technological advances over the last decade both in hardware and software have led to potent and even safer loco-regional hyperthermia treatment delivery, thermal treatment planning, thermal dose monitoring through noninvasive thermometry and online adaptive temperature modulation. The review summarizes the outcomes from various clinical studies (both randomized and nonrandomized) where hyperthermia is used as a thermal sensitizer of radiotherapy and-/or chemotherapy in various solid tumors and presents an overview of the progresses in loco-regional hyperthermia. These recent developments, supported by positive clinical outcomes should merit hyperthermia to be incorporated in the therapeutic armamentarium as a safe and an effective addendum to the existing oncological treatment modalities.

Occupational hazards of municipal solid waste workers.

The removal of municipal solid waste is a job associated with a variety of physical, chemical, and biological hazards. Municipal solid waste workers (MSWWs) have a risk of fatal occupational injuries that is much higher than for the general workforce. Among this group of workers, non-fatal injuries are mainly musculoskeletal. Other common injuries are fractures, ocular trauma, and bites, and diseases include skin and gastrointestinal disorders. Workers at municipal solid waste incinerators are exposed to a variety of concerning substances, such as heavy metals, respirable quartz dust, dioxins, furans, and mutagens. Workers can be protected by using safety procedures on and around garbage trucks and with personal protective equipment. The burden of morbidity due to occupational exposure to bioaerosols and carcinogens among MSWWs is unknown.

Verbal learning and memory in schizotypal personality disorder.

The investigation of cognitive deficits in patients with schizotypal personality disorder (SPD) is important both to establish commonalities between SPD and schizophrenia and to clarify the significance of these cognitive deficits for schizophrenic disorders. The purpose of this study was to examine verbal learning and memory with the California Verbal Learning Test (CVLT) in a group of patients with SPD (n=24) and a group of patients with personality disorders other than SPD (OPD; n=25). The results indicated that SPD patients learned significantly fewer words with practice on the CVLT than OPD patients (F=4.32, df=1,47, p < 0.05), and their rate of learning was reduced relative to normative standards. These findings suggest that SPD patients have a deficit in verbal learning that is similar to, although not as severe as, the impairments seen in schizophrenia.

Meperidine and alfentanil do not reduce the gain or maximum intensity of shivering.

BACKGROUND: Thermoregulatory shivering can be characterized by its threshold (triggering core temperature), gain (incremental intensity increase with further core temperature deviation), and maximum intensity. Meperidine (a combined mu- and kappa-agonist) treats shivering better than equianalgesic doses of pure mu-opioid agonists. Meperidine's special antishivering action is mediated, at least in part, by a disproportionate decrease in the shivering threshold. That is, meperidine decreases the shivering threshold twice as much as the vasoconstriction threshold, whereas alfentanil (a pure mu-agonist) decreases the vasoconstriction and shivering thresholds comparably. However, reductions in the gain or maximum shivering intensity might also contribute to the clinical efficacy of meperidine. Accordingly, we tested the hypothesis that meperidine reduces the gain and maximum intensity of shivering much more than alfentanil does. METHODS: Ten volunteers were each studied on three separate days: (1) control (no drug); (2) a target total plasma meperidine concentration of 1.2 microg/ml; and (3) a target plasma alfentanil concentration of 0.2 microg/ml. Skin temperatures were maintained near 31 degrees C, and core temperatures were decreased by central-venous infusion of cold lactated Ringer's solution until maximum shivering intensity was observed. Shivering was evaluated using oxygen consumption and electromyography. A sustained increase in oxygen consumption identified the shivering threshold. The gain of shivering was calculated as the slope of the oxygen consumption versus core temperature regression, and as the slope of electromyographic intensity versus core temperature regression. RESULTS: Meperidine and alfentanil administration significantly decreased the shivering thresholds. However, neither meperidine nor alfentanil reduced the gain of shivering, as determined by either oxygen consumption or electromyography. Opioid administration also failed to significantly decrease the maximum intensity of shivering. CONCLUSIONS: The authors could not confirm the hypothesis that meperidine reduces the gain or maximum intensity of shivering more than alfentanil does. These results suggest that meperidine's special antishivering effect is primarily mediated by a disproportionate reduction in the shivering threshold.

Prediction of relapse within eight weeks after an acute asthma exacerbation in adults.

Associations between historical, presenting, and treatment-related characteristics and relapse within 8 weeks after a moderate to severe asthma exacerbation were studied in a cohort of 284 adult asthmatics. Data were collected prospectively, and a multivariate model was developed and internally validated. Within 10 days, only 8% had relapsed, increasing to 45% by 8 weeks. Three variables that could be identified at the time of discharge were independently associated with relapse. These included: having made three or more visits to an emergency department in the prior 6 months (hazard ratio (HR) = 2.3, 95% CI = 1.6-3.4); difficulty performing work or activities as a result of physical health in the 4 weeks prior (HR = 2.7, 95% CI = 1.6-4.3); discontinuing hospital-based treatment for the exacerbation within 24 hours without having achieved a peak expiratory flow rate of at least 50% of predicted (HR = 2.6, 95% CI = 1.6-4.1). These risk factors may help to identify patients with poorly controlled asthma in need of more intensive and comprehensive management.

Circadian changes in the sweating-to-vasoconstriction interthreshold range.

Thermoregulatory defenses are characterized by thresholds, the core temperatures triggering each response. Core body temperature is normally maintained within the interthreshold range, temperatures between the sweating and vasoconstriction thresholds that do not trigger autonomic defenses. This range usually spans only some 0.2 degrees C, but it remains unknown whether similar precision is maintained during the circadian core temperature cycle of about 0.8 degrees C. Accordingly, we evaluated the interthreshold range at four times of the day. We studied ten male volunteers, each at 3 a.m., 8 a.m., 3 p.m., and 8 p.m. At least 12 h elapsed between tests, and the order was randomly assigned. At each study time, volunteers were warmed peripherally until sweating was observed. Skin temperature was subsequently kept constant while core temperature was decreased by central-venous infusion of ice-cold fluid until peripheral vasoconstriction was detected. The volunteers were not permitted to sleep during threshold determinations, although sleep was not otherwise controlled. The core temperature triggering an evaporative water loss of 40 g.m-2.h-1 identified the sweating threshold. Similarly, the vasoconstriction threshold was defined by the core temperature triggering the initial decreases in plethysmographic finger tip blood flow. The interthreshold range at 3 a.m. was twice that observed at the other study times (P<0.05). Our data suggest that autonomic control of body temperature is reduced at 3 a.m., even when sleep is denied. This result contradicts the general perception that circadian variation alters the thermoregulatory target temperature, but not precision of body temperature control.

Efficacy of intraoperative cooling methods.

BACKGROUND: Patients may require perioperative cooling for a variety of reasons including treatment of a malignant hyperthermia crisis and induction of therapeutic hypothermia for neurosurgery. The authors compared heat transfer and core cooling rates with five cooling methods. METHODS: Six healthy volunteers were anesthetized with desflurane and nitrous oxide. The cooling methods were 1) circulating water (5 degrees C, full-length mattress and cover), 2) forced air (10 degrees C, full-length cover), 3) gastric lavage (500 ml iced water every 10 min), 4) bladder lavage (300 ml iced Ringer's solution every 10 min), and 5) ice-water immersion. Each method was applied for 40 min or until the volunteers' core temperatures approached 34 degrees C. The volunteers were rewarmed to normothermia between treatments. Core cooling rates were evaluated using linear regression. RESULTS: The first volunteer developed abdominal cramping and diarrhea after gastric lavage. Consequently, the technique was not again attempted. Bladder lavage increased heat loss approximately 10 W and decreased core temperature 0.8 +/- 0.3 degrees C/h (r2 = 0.99 +/- 0.002; means +/- SD). Forced-air and circulating-water cooling comparably increased heat flux, approximately 170 W. Consequently, core cooling rates were similar during the two treatments at 1.7 +/- 0.5 degrees C/h (r2 = 0.99 +/- 0.001) and 1.6 +/- 1.1 degrees C/h (r2 = 0.98 +/- 0.02), respectively. Immersion in an ice water slurry increased heat loss approximately 600-800 W and decreased core temperature 9.7 +/- 4.4 degrees C/h (r2 = 0.98 +/- 0.01). Immersion cooling was associated with an afterdrop of approximately 2 degrees C. CONCLUSIONS: Bladder lavage provided only trivial cooling and gastric lavage provoked complications. Forced-air and circulating-water cooling transferred relatively little heat but are noninvasive and easy to implement. Forced-air or circulating-water cooling, perhaps combined with intravenous administration of refrigerated fluids, may be sufficient in some patients. When noninvasive methods prove insufficient for rapid cooling, ice-water immersion or peritoneal lavage probably should be the next lines of defense.

A comparison between emergency diagnostic and treatment unit and inpatient care in the management of acute asthma.

BACKGROUND: Emergency diagnostic and treatment units (EDTUs) may provide an alternative to hospitalization for patients with reversible diseases, such as asthma, who fail to adequately respond to emergency department therapy. OBJECTIVE: To evaluate the medical and cost-effectiveness, patient satisfaction, and quality of life of patients receiving EDTU care for acute asthma compared with inpatient care. METHODS: A prospective, randomized clinical trial performed at 2 urban public hospitals enrolled patients with acute asthma (age range, 18-55 years) not meeting discharge criteria after 3 hours of emergency department therapy. Patients were treated with inhaled adrenergic agonists and steroids in an EDTU for up to 9 hours after randomization or with routine therapy in a hospital ward. Patients were followed up for 8 weeks. MAIN OUTCOME MEASURES: Discharge rate from the EDTU, length of stay, relapse rates, days missed from work or school, days incapacitated during waking hours, symptom-free days and nights, nocturnal awakenings, direct medical costs, patients satisfaction, and patient quality of life. RESULTS: The study consisted of 222 patients with asthma. Sixty-five patients (59%) treated in an EDTU were discharged home; the remainder were admitted to the hospital. There were no differences during the follow-up period in relapse rates (P = .74) or in any other morbidities between the EDTU and inpatient groups. There were significant differences in the length of stay, patient satisfaction, and quality of life favoring EDTU care. The mean (+/-SD) cost per patient in the EDTU group was $1202.79 +/- $1343.96, compared with $2247.32 +/- $1110.18 for the control group (P < .001). CONCLUSIONS: Treatment of selected patients with asthma in an EDTU results in the safe discharge of most such patients. This study suggests that quality gains and cost-effective measures can be achieved by the use of such units.

Thermoregulatory vasodilation increases the venous partial pressure of oxygen.

UNLABELLED: Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing relative venous stasis and hypoxia. Accordingly, we evaluated the effect of vasomotion on leg blood flow and venous oxygen tension. We studied five male volunteers, each of whom was warmed enough to trigger vasodilation and then cooled sufficiently to provoke thermoregulatory vasoconstriction. The process was then repeated during N2O/desflurane anesthesia. Venous oxygen tension and saturation (with a fraction of inspired oxygen of 1.0) were evaluated in blood samples taken from a catheter that was inserted into a saphenous vein at the ankle and advanced until the tip was proximal to the knee. Thermoregulatory vasodilation with or without general anesthesia significantly increased arteriovenous shunt flow by approximately 10-fold, and increased total leg flow approximately sixfold. However, vasodilated flows were similar with and without general anesthesia, as were vasoconstricted flows. Before induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 46 +/- 6 to 187 +/- 99 mm Hg and venous saturation from 79% +/- 6% to 99% +/- 2%. After induction of anesthesia, thermoregulatory vasodilation increased venous oxygen tension from 55 +/- 11 to 356 +/- 103 mm Hg and venous saturation from 84% +/- 8% to 100% +/- 0%. Our data thus indicate that thermoregulatory vasodilation markedly increases both leg flow and venous oxygenation; and that both factors may help prevent perioperative venous thrombosis. IMPLICATIONS: Thermoregulatory arteriovenous shunt vasoconstriction may facilitate deep-vein thrombosis by producing related venous stasis and hypoxia. In male volunteers, the authors found that when vasodilation induced by warming was produced, both blood flow and venous oxygenation increased, both of which may help prevent perioperative venous thrombosis.

Influence of thermoregulatory vasomotion and ambient temperature variation on the accuracy of core-temperature estimates by cutaneous liquid-crystal thermometers.

BACKGROUND: Recently, liquid crystal skin-surface thermometers have become popular for intraoperative temperature monitoring. Three situations during which cutaneous liquid-crystal thermometry may poorly estimate core temperature were monitored: (1) anesthetic induction with consequent core-to-peripheral redistribution of body heat, (2) thermoregulatory vasomotion associated with sweating (precapillary dilation) and shivering (minimal capillary flow), and (3) ambient temperature variation over the clinical range from 18-26 degrees C. METHODS: The core-to-forehead and core-to-neck temperature difference was measured using liquid-crystal thermometers having an approximately 2 degrees C offset. Differences exceeding 0.5 degree C (a 1 degree C) temperature range) were a priori deemed potentially clinically important. Seven volunteers participated in each protocol. First, core-to-peripheral redistribution of body heat was produced by inducing propofol/desflurane anesthesia; anesthesia was then maintained for 1 h with desflurane. Second, vasodilation was produced by warming unanesthetized volunteers sufficiently to produce sweating; intense vasoconstriction was similarly produced by cooling the volunteers sufficiently to produce shivering. Third, a canopy was positioned to enclose the head, neck, and upper chest of unanesthetized volunteers. Air within the canopy was randomly set to 18, 20, 22, 24, and 26 degrees C. RESULTS: Redistribution of body heat accompanying induction of anesthesia had little effect on the core-to-forehead skin temperature difference. However, the core-to-neck skin temperature gradient decreased approximately 0.6 degree C in the hour after induction of anesthesia. Vasomotion associated with shivering and mild sweating altered the core-to-skin temperature difference only a few tenths of a degree centigrade. The absolute value of the core-to-forehead temperature difference exceeded 0.5 degree C during approximately 35% of the measurements, but the difference rarely exceeded 1 degree C. The core-to-neck temperature difference typically exceeded 0.5 degree C and frequently exceeded 1 degree C. Each 1 degree C increase in ambient temperature decreased the core-to-fore-head and core-to-neck skin temperature differences by less than 0.2 degree C. CONCLUSIONS: Forehead skin temperatures were better than neck skin temperature at estimating core temperature. Core-to-neck temperature differences frequently exceeded 1 degree C (a 2 degrees C range), whereas two thirds of the core-to-forehead differences were within 0.5 degree C. The core-to-skin temperature differences were, however, only slightly altered by inducing anesthesia, vasomotor action, and typical intraoperative changes in ambient temperature.

The factor structure of schizotypal symptoms in a clinical population.

There is some support for the hypothesis that the factor structure of schizophrenia symptoms is similar to the factor structure of schizotypal symptoms in nonschizophrenia populations. However, no studies to date have examined schizotypal symptoms in patients with personality disorders. In this study, confirmatory factor analyses were conducted to test the relative fit of several models of the factorial structure of schizotypal symptoms in patients diagnosed with personality disorders. The EQS: Structural Equations Program was used to analyze DSM-III symptoms of schizotypal personality disorder (SPD) based on structured clinical interviews with 213 patients meeting a diagnosis for at least one personality disorder. A subgroup of the total sample was also evaluated for DSM-III-R criteria (n = 143) to test competing models of the DSM-III-R symptoms of SPD. A three-factor model consisting of a cognitive-perceptual, interpersonal, and paranoid factor yielded the best fit to the data relative to the other models tested. These results suggest that the three-factor model of schizophrenia symptoms may not entirely correspond to the factors underlying milder schizotypal symptoms expressed in a clinical population. It is suggested that future research focus on both the similarities and the differences between SPD and schizophrenia.

Physician delivery of smoking-cessation advice based on the stages-of-change model.

The purpose of this study is to assess whether a stage-based program of brief physician-delivered smoking-cessation advice changes smoking stages of readiness to quit smoking. First-year residents were trained to assess the stage of their continuity care patients who smoke, using Prochaska and DiClemente's methods, and to deliver brief messages and handouts based on the stages of precontemplation, contemplation, and action. Concurrent with the training, we administered a survey to 252 smokers, before their physician encounter. Eighty-nine smokers saw trained residents (intervention group), and 163 saw untrained residents (usual care group). A follow-up survey was administered six months later. Seventy-four percent of the subjects completed the follow-up survey. After we controlled for baseline stage, the percentage of precontemplators was lower in the intervention group (25%) than in the usual care group (36%) (P < .05, log-linear model). In the intervention group, 50% of the subjects had positive stage shifts versus 40% in the usual care group (P = .2). Subjects in the intervention group moved ahead a mean of 0.63 stage per subject, whereas subjects in the usual care group moved ahead 0.34 stage per subject (P < .05). The self-reported cessation rate was 15.5% and did not differ between the two groups. We conclude that our stage-specific brief advice program enhances short-term movement through the stages-of-change of smoking cessation. Measurement of this movement may be an important intermediary in evaluating small clinical trials of brief advice. Our findings indicate potential benefits of a staged approach for both clinicians and their patients.

Diuretic Doppler sonography in postnatal hydronephrosis.

Renal resistive indexes were measured by Doppler sonography in 12 children undergoing other standard diagnostic studies to evaluate hydronephrosis. Measurement of renal resistive indexes was modified by prior placement of a bladder catheter, oral hydration and administration of 1 mg./kg. furosemide after baseline measurement. Renal resistive indexes were again measured at 10 and 30 minutes after diuretic. While diuretic administration had no measurable influence on 10 nonobstructed kidneys, the elevated 10-minute post-diuretic renal resistive indexes recorded in 10 obstructed kidneys differed significantly from the indexes recorded in the nonobstructed group (p less than 0.001). The highest elevations in renal resistive indexes were recorded in nonpaired kidneys, which included 7 of the 10 kidneys in the obstructed group. In the 3 unilaterally obstructed kidneys the 10-minute post-diuretic renal resistive indexes did not differ significantly. However, renal resistive indexes in these kidneys increased at least 15% over baseline readings after diuretic administration. Diuretic Doppler sonography appears to be another useful method for differentiating functionally significant hydronephrosis from nonobstructive hydronephrosis in children.

Liver transplant rejection: value of the resistive index in Doppler US of hepatic arteries.

The authors prospectively evaluated the accuracy of the resistive index (RI) in Doppler ultrasound (US) for the detection of the increased vascular resistance that theoretically occurs with acute liver transplant rejection. RIs were calculated for the proximal hepatic artery and a more distal hepatic artery branch in 67 liver transplant recipients. Biopsies were performed within 24 hours of transplantation, with no intervening therapy. Examination of biopsy specimens by a single pathologist revealed findings of no, minimal, or moderate to severe rejection. RIs in hepatic arteries showed no significant differences among the three pathologic groups. No correlation was found between the RI and improved or worsened rejection in 11 patients who underwent biopsy and US more than once. RIs in hepatic arteries are of no value in the prediction of liver transplant rejection.

Mumps in the workplace. Further evidence of the changing epidemiology of a childhood vaccine-preventable disease.

The first documented mumps outbreak in the workplace took place between August and December of 1987, when 119 cases of mumps occurred among employees at three Chicago futures exchanges and their household contacts. Twenty-one patients developed 23 complications, and nine persons were hospitalized. Total direct and indirect economic costs associated with the outbreak were $120,738; the cost per case was $1473. Only three patients had written documentation of mumps immunization. The outbreak is consistent with the recent changing epidemiology of mumps and the increase in reported cases in the adolescent and young adult populations. Mumps vaccine was licensed in 1967, but its distribution was limited until 1977 when the Immunization Practices Advisory Committee of the US Public Health Service recommended it for universal use. As a result, a cohort of adolescents and young adults under-immunized against mumps and underexposed to disease is now entering the work force. Vaccination of susceptible employees could prevent the substantial health impact of mumps.