Thalamohippocampal atrophy in focal epilepsy of unknown cause at the time of diagnosis.

BACKGROUND AND PURPOSE: Patients with chronic focal epilepsy may have atrophy of brain structures important for the generation and maintenance of seizures. However, little research has been conducted in patients with newly diagnosed focal epilepsy (NDfE), despite it being a crucial point in time for understanding the underlying biology of the disorder. We aimed to determine whether patients with NDfE show evidence of volumetric abnormalities of subcortical structures. METHODS: Eighty-two patients with NDfE and 40 healthy controls underwent magnetic resonance imaging scanning using a standard clinical protocol. Volume estimation of the left and right hippocampus, thalamus, caudate nucleus, putamen and cerebral hemisphere was performed for all participants and normalised to whole brain volume. Volumes lower than two standard deviations below the control mean were considered abnormal. Volumes were analysed with respect to patient clinical characteristics, including treatment outcome 12 months after diagnosis. RESULTS: Volume of the left hippocampus (p(FDR-corr)  = 0.04) and left (p(FDR-corr)  = 0.002) and right (p(FDR-corr)  = 0.04) thalamus was significantly smaller in patients relative to controls. Relative to the normal volume limits in controls, 11% patients had left hippocampal atrophy, 17% had left thalamic atrophy and 9% had right thalamic atrophy. We did not find evidence of a relationship between volumes and future seizure control or with other clinical characteristics of epilepsy. CONCLUSIONS: Volumetric abnormalities of structures known to be important for the generation and maintenance of focal seizures are established at the time of epilepsy diagnosis and are not necessarily a result of the chronicity of the disorder.

Encapsulated benzoic acid supplementation in broiler diets influences gut bacterial composition and activity.

1. The present study investigated the effects of encapsulated benzoic acid (BA) supplementation in broiler feed on performance and gastrointestinal microbiota. 2. Eighty broilers were randomly divided into two groups. Birds in the control group were fed on maize-soybean-based diets. Birds in the treatment group were provided the same diet supplemented with 2 g/kg BA encapsulated in a vegetable oil matrix. 3. At the end of the trial (d 35), pH, bacterial composition and metabolites were determined in the crop, jejunum, ileum and caecum. 4. Growth performance variables and pH were not significantly different. 5. BA concentration decreased rapidly in the proximal gut. However, the treatment diet showed higher BA in the crop, jejunum, ileum and caecum. 6. Total lactate in the crop and D-lactate in the jejunum was higher in the BA treated group. Caecal total and branched chain fatty acids were decreased due to the treatment. 7. Lactobacilli populations were significantly altered by BA supplementation. A trend for increased lactobacilli was observed in the crop, while it became significant in the jejunum and ileum. Lactobacillus species responded differently to the treatment. Four of 5 measured Lactobacillus species, particularly in the ileum, followed the course observed for total lactobacilli; only Lactobacillus salivarius was not modified. 8. Correlation analysis showed that BA modified the intestinal microbiota. Lactobacilli correlated negatively to all studied clostridial clusters and enterobacteria. Clostridial clusters IV and XIVa were significantly increased in the jejunum, whereas only clostridial cluster XIVa was increased in the caecum. 9. Encapsulated BA modified the intestinal microbiota which can lead to the conclusion, that the main beneficial mode of action of BA in the gut appears to be the enhancement of lactic acid bacteria, which in turn may act as a vanguard against pathogens.

Outbreak of pyrazinamide-monoresistant tuberculosis identified using genotype cluster and social media analysis.

SETTING: Monoresistance to pyrazinamide (PZA) has infrequently been associated with Mycobacterium tuberculosis. OBJECTIVE: To report an outbreak of PZA-monoresistant M. tuberculosis in Virginia involving two genotype clusters from December 2004 to August 2010. RESULTS: Thirty cases were identified involving a predominantly young, US-born population with histories of substance use and incarceration and a large proportion of children aged <15 years (n= 6, 20%); of these, 23 cases (77%) were culture-confirmed as M. tuberculosis complex. DNA fingerprinting and molecular analysis of the PZA resistance gene, pncA, demonstrated a clonal strain that was not M. bovis. Genotypic data provided the initial link between seemingly unrelated cases, and helped reveal a historic genotype cluster of cases from 2004. Further genotype cluster and contact investigation procedures, including the novel use of the social networking website Facebook.com, revealed additional links between the 2004 and 2009 genotype clusters and described an ongoing, extensive outbreak necessitating an enhanced screening and treatment protocol for contacts. CONCLUSIONS: This outbreak demonstrates how tuberculosis can spread through a young, vulnerable population. The use of genotypic data and the novel incorporation of social media investigations were critical to understanding the settings and context of infectivity.

Nerve fiber impairment of anterior thalamocortical circuitry in juvenile myoclonic epilepsy.

BACKGROUND: Juvenile myoclonic epilepsy (JME) is a syndrome of idiopathic generalized epilepsy (IGE) without structural brain abnormalities detectable by MRI or CT. OBJECTIVE: In the present study, we addressed the question of whether diffusion tensor MRI (DTI) can detect disease-specific white matter (WM) abnormalities in patients with JME. METHODS: We performed whole head DTI at 3 T in 10 patients with JME, 8 age-matched patients with cryptogenic partial epilepsy (CPE), and 67 age-matched healthy volunteers. Nerve fiber integrity was compared between the groups on the basis of optimized voxel-by-voxel statistics of fractional anisotropy (FA) maps obtained by DTI (analysis of covariance, categorical factor "group," covariate "age"). RESULTS: FA was reduced in a WM region associated with the anterior thalamus and prefrontal cortex in patients with JME compared to both control subjects and patients with CPE (p < 0.001). The patients with CPE showed normal values in this particular WM region. The FA reductions in the patients with JME correlated with the frequency of generalized tonic-clonic seizures (Spearman R = 0.54, p = 0.05). No significant correlations were found in the JME sample between FA reduction and the duration of antiepileptic medication. CONCLUSIONS: The results support the hypothesis that juvenile myoclonic epilepsy is associated with abnormalities of the thalamocortical network that can be detected by diffusion tensor MRI.

Effects of suburban land use on phosphorus fractions and speciation in the Upper Peruque Creek, Eastern Missouri.

This field study was conducted to explore the spatial and seasonal changes in total phosphorus and fraction distribution in relation to land uses. Water samples were collected biweekly at four sampling locations, which represented different potential phosphorus sources along the Upper Peruque Creek in Eastern Missouri. Total phosphorus concentrations of > 0.8 mg/L appeared sporadically at site 2, downstream of a small community, with an average of 0.82 +/- 0.14 mg/L in fall. Particulate phosphorus accounted for approximately 80% of total phosphorus at all sampling sites, except for site 2, where approximately 50 to 75% of dissolved phosphorus was often observed. Approximately 71 and 85% of total phosphorus in the sediment was in the form of iron (III) phosphate at the headwaters and downstream sites, respectively; 29 and 15% was in the form of phytic acid at the two sites. Land uses affect the total phosphorus concentration and alternate phosphorus fraction and speciation in the creek.

Outcomes of a 2-year investigation on enhanced biological nutrients removal and trace organics elimination in membrane bioreactor (MBR).

Two configurations of membrane bioreactors were identified to achieve enhanced biological phosphorus and nitrogen removal, and assessed over more than two years with two parallel pilot plants of 2m3 each. Both configurations included an anaerobic zone ahead of the biological reactor, and differed by the position of the anoxic zone: standard pre-denitrification, or post-denitrification without dosing of carbon source. Both configurations achieved improved phosphorus removal. The goal of 50 microgP/L in the effluent could be consistently achieved with two types of municipal wastewater, the second site requiring a low dose of ferric salt ferric salt < 3 mgFe/L. The full potential of biological phosphorus removal could be demonstrated during phosphate spiking trials, where up to 1 mg of phosphorus was biologically eliminated for 10 mg BOD5 in the influent. The post-denitrification configuration enabled a very good elimination of nitrogen. Daily nitrate concentration as low as 1 mgN/L could be monitored in the effluent in some periods. The denitrification rates, greater than those expected for endogenous denitrification, could be accounted for by the use of the glycogene pool, internally stored by the denitrifying microorganisms in the anaerobic zone. Pharmaceuticals residues and steroids were regularly monitored on the two parallel MBR pilot plants during the length of the trials, and compared with the performance of the Berlin-Ruhleben WWTP. Although some compounds such as carbamazepine were persistent through all the systems, most of the compounds could be better removed by the MBR plants. The influence of temperature, sludge age and compound concentration could be shown, as well as the significance of biological mechanisms in the removal of trace organic compounds.

[Analysis of direct costs in therapy of Parkinson disease]. / Analyse der direkten Kosten in der Parkinson-Therapie.

The increasing prevalence of Parkinson syndrome and its cost-intensive modern therapies make for a growing economic burden. Studies on cost to date have limited validity owing to the various methods employed (retrospective, focus on partial expenses, minimal case numbers, etc.). The present study collected data pertaining to direct costs. Seventy-seven patients were followed for 10 months. They had been outpatients when enrolled in the study. Hospitalization or comparable changes during the course of observation were registered accordingly. The most significant result revealed by the study is that expenses for medication by far take up the biggest share of the direct costs. In the early stage of the disease (H and Y I), the monthly costs of drug treatment amount to 397.67 Euros. With advancing ailment, costs rose to 561.56 Euros in H and Y 2, 588.30 Euros in H and Y 3, 604.86 Euros in H and Y 4, and 645.77 Euros in H and Y 5. (Average costs for disease remedies amount to 25.46 Euros.) Inpatient costs were 13.47 Euros (with DBS, 19.04 Euros). Adjuvants aggregated to 3.50 Euros per month, medical technical diagnostic workup to 18.74 Euros (47.60 Euros including DBS), and medical services to 15.73 Euros.

Adenovirus-activated PKA and p38/MAPK pathways boost microtubule-mediated nuclear targeting of virus.

Nuclear targeting of adenovirus is mediated by the microtubule-dependent, minus-end-directed motor complex dynein/dynactin, in competition with plus- end-directed motility. We demonstrate that adenovirus transiently activates two distinct signaling pathways to enhance nuclear targeting. The first pathway activates integrins and cAMP-dependent protein kinase A (PKA). The second pathway activates the p38/MAP kinase and the downstream MAPKAP kinase 2 (MK2), dependent on the p38/MAPK kinase MKK6, but independent of integrins and PKA. Motility measurements in PKA-inhibited, p38-inhibited or MK2-lacking (MK2(-/-)) cells indicate that PKA and p38 stimulated both the frequency and velocity of minus-end-directed viral motility without affecting the perinuclear localization of transferrin-containing endosomal vesicles. p38 also suppressed lateral viral motilities and MK2 boosted the frequency of minus-end-directed virus transport. Nuclear targeting of adenovirus was rescued in MK2(-/-) cells by overexpression of hsp27, an MK2 target that enhances actin metabolism. Our results demonstrate that complementary activities of PKA, p38 and MK2 tip the transport balance of adenovirus towards the nucleus and thus enhance infection.

Personal pollen exposure compared to stationary measurements.

The aim of this study was to examine to what extent stationary outdoor pollen measurements are representative for estimating personal exposure to pollen. Ten subjects were studied during a total of 36 days in spring and summer Pollen was sampled using personal SKC total dust samplers and stationary Burkard pollen traps. The personal activity pattern was recorded quarter-hourly as well as the time spent outdoors. As a reference, SKC and Burkard samplers were run stationary and in parallel. Stationary comparison of the samplers showed good correlation (r = 0.981, p <0.001). However, the SKC sampler collected systematically about four times less pollen than the Burkard sampler. Taking into account the systematic difference between the sampling devices, the personal exposure data were about 30% of the stationary pollen concentrations with significant correlation (log-transformed data, r = 0.719, p <0.0001). Considering the average time the subjects spent outdoors (14% of sampling time), the indoor-outdoor ratio for pollen was 0.2. In conclusion, pollen reports are reliable for estimating personal exposure over a limited time period although personal pollen exposure is much lower.

Inhibition of glucose trimming with castanospermine reduces calnexin association and promotes proteasome degradation of the alpha-subunit of the nicotinic acetylcholine receptor.

To identify factors involved in the expression of ligand-gated ion channels, we expressed nicotinic acetylcholine receptors in HEK cells to characterize roles for oligosaccharide trimming, calnexin association, and targeting to the proteasome. The homologous subunits of the acetylcholine receptor traverse the membrane four times, contain at least one oligosaccharide, and are retained in the endoplasmic reticulum until completely assembled into the circular arrangement of subunits of delta-alpha-gamma-alpha-beta to enclose the ion channel. We previously demonstrated that calnexin is associated with unassembled subunits of the receptor, but appears to dissociate when subunits are assembled in various combinations. We used the glucosidase inhibitor castanospermine to block oligosaccharide processing, and thereby inhibit calnexin's interaction with the oligosaccharides in the receptor subunits. Castanospermine treatment reduces the association of calnexin with the alpha-subunit of the receptor, and diminishes the intracellular accumulation of unassembled receptor subunit protein. However, treatment with castanospermine does not appear to alter subunit folding or assembly. In contrast, co-treatment with proteasome inhibitors and castanospermine enhances the accumulation of polyubiquitin-conjugated alpha-subunits, and generally reverses the castanospermine induced loss of alpha-subunit protein. Co-transfection of cDNAs encoding the alpha- and delta-subunits, which leads to the expression of assembled alpha- and delta- subunits, also inhibits the loss of alpha-subunits expressed in the presence of castanospermine. Taken together, these observations indicate that calnexin association reduces the degradation of unassembled receptor subunits in the ubiquitin-proteasome pathway.

Recent benzodiazepine use in depressed patients: a confound of psychoimmunologic studies?

UNLABELLED: Several studies have indicated that benzodiazepines influence immunity in both animals and humans. As these medications are commonly utilized by and for psychiatric patients, investigation of psycho-immunologic relationships in human psychiatric disorders may be confounded by use of these medications. METHOD: We undertook an investigation for possible effects of recent benzodiazepine use on depression-immune relationships by comparing 43 patients with current major depressive disorder (MDD) who used benzodiazepines in the week prior to study to 27 patients with current MDD but no use of benzodiazepines in the past month. Both functional and ennumerative measures were investigated. RESULTS: We found no differences in absolute numbers of lymphocytes or the lymphocyte and NK functional measures. We did find differences between these two groups in the percentage of lymphocytes and of NK cells. Upon further analysis, controlling for symptom severity, these differences were shown to not be independently predicted by benzodiazepine use. CONCLUSION: Immune measures in subjects with current MDD and recent benzodiazepine use did not differ from those without such recent use. Therefore, such recent use is unlikely to confound PNI results.

Psychosocial and immune effects of self-hypnosis training for stress management throughout the first semester of medical school.

This study was a 19-week prospective conducted to determine the effectiveness of a self-hypnosis/relaxation intervention to relieve symptoms of psychological distress and moderate immune system reactivity to examination stress in 35 first-year medical students. Twenty-one subjects were randomly selected for training in the use of self-hypnosis as a coping skill and were encouraged to practice regularly and to maintain daily diary records related to mood, sleep, physical symptoms, and frequency of relaxation practice. An additional 14 subjects received no explicit training in stress-reduction strategies, but completed similar daily diaries. Self-report psychosocial and symptom measures, as well as blood draws, were obtained at four time points: orientation, late semester, examination period, and postsemester recovery. It was found that significant increases in stress and fatigue occurred during the examination period, paralleled by increases in counts of B lymphocytes and activated T lymphocytes, PHA-induced and PWM-induced blastogenesis, and natural killer cell (NK) cytotoxicity. No immune decreases were observed. Subjects in the self-hypnosis condition reported significantly less distress and anxiety than their nonintervention counterparts, but the two groups did not differ with respect to immune function. Nevertheless, within the self-hypnosis group, the quality of the exercises (ie, relaxation ratings) predicted both the number of NK cells and NK activity. It was concluded that stress associated with academic demands affects immune function, but immune suppression is not inevitable. Practice of self-hypnosis reduces distress, without differential immune effects. However, individual responses to the self-hypnosis intervention appear to predict immune outcomes.

Cloning and characterization of a novel insulin-regulated membrane aminopeptidase from Glut4 vesicles.

The insulin-regulated glucose transporter isotype GlutT4 expressed only in muscle and adipose cells is sequestered in a specific secretory vesicle. These vesicles harbor another major protein, referred to as vp165 (for vesicle protein of 165 kDa), that like GluT4 redistributes to the plasma membrane in response to insulin. We describe here the cloning of vp165 and show that it is a novel member of the family of zinc-dependent membrane aminopeptidases, with the typical large extracellular catalytic domain and single transmembrane domain but with a unique extended cytoplasmic domain. The latter contains two dileucine motifs, which may be critical for the specific trafficking of vp165, since this has been shown to be the case for this motif in GluT4. However, the tissue distribution of vp165 is much wider than that of GluT4; consequently, vp165 may also function in processes unrelated to insulin action and may serve as a ubiquitous marker for a specialized regulated secretory vesicle.

Good reproductive health involves many services.

PIP: A survey of reproductive health activities in 50 countries shows that 25% of family planning programs provided all types of reproductive health services: family planning or safe regulation of fertility, maternal health and nutrition, protection from sexually transmitted diseases (STDs), and reproductive rights. Integrated reproductive health services reduce duplication and the number of workers and facilities needed. A program providing postpartum care and family planning services in Honduras and Peru increased contraceptive prevalence and saved money. Yet, combining new health services into a family planning program may strengthen one component while hurting the other. Health planners need to reflect on how to integrate reproductive health activities. Family planning providers can screen for STDs, distribute condoms, maintain hygienic facilities, and guarantee that contraceptive services or procedures do not spread or exacerbate genital tract infections. A simple way is needed to evaluate their clients' STD risk, such as interviewing clients about symptoms. At some family planning clinics in Brazil, a cartoon soap opera helps clients in small groups discuss STDs. Family planning clients tend to be married women who generally are not a high risk group. Providers should not recommend a contraceptive method without first determining the client's STD risk. Clients should not choose a method without first considering their STD risk. Family planning prevents maternal deaths. For example, a community project in rural Bangladesh increased contraceptive prevalence, which in turn contributed to a 33% decrease in maternal mortality. Family planning caregivers can tell women about prenatal care, pregnancy complications, and the benefits of breast feeding, as well as provide them with iodine and iron supplements, tetanus toxoid, and malaria prophylaxis. They can counsel postpartum mothers about birth spacing methods (e.g., lactational amenorrhea method).^ieng

Management of adenocarcinoma of the esophagus with chemoradiation alone or chemoradiation followed by esophagectomy: results of sequential nonrandomized phase II studies.

PURPOSE: The incidence of adenocarcinoma of the esophagus is increasing, but the optimal treatment for this disease is unknown. We evaluated the efficacy of chemoradiation and chemoradiation followed by esophagectomy as treatment for adenocarcinoma of the esophagus in sequential prospective nonrandomized phase II studies. METHODS AND MATERIALS: Between May 1981 and June 1992, all previously untreated patients (N = 35) with potentially resectable adenocarcinoma of the esophagus (clinical Stage I or II) were treated with curative intent in sequential prospective Phase II studies. From May 1981 to August 1987, 11 patients (median age 66) were treated with concurrent chemotherapy [mitomycin C, and 5-fluorouracil (5-FU)] and radiotherapy to a median dose of 60 Gy (CRT group). From September 1987 to June 1992, 24 patients (median age 65) were treated with the same regimen of chemoradiation followed by planned esophagectomy (CRT+PE group). Of these, 12 patients (median age 62) actually underwent esophagectomy (CRT+E subgroup). RESULTS: The median overall survival was 19 months for the CRT group and 15 months for the CRT+PE group. For the CRT+E subgroup, the median overall survival was 33 months. The 3-year actuarial overall survival for the CRT and the CRT+PE groups were 36 and 28% (p = 0.949). The subset of patients treated with chemoradiation followed by esophagectomy had a 3-year actuarial overall survival of 33% (p = 0.274). The 3-year actuarial freedom from local failure rates were similar: 62% in the CRT group vs. 58% in the CRT+PE group. Of the 12 patients who underwent esophagectomy (CRT+E group), 9 (75%) were free of local failure. Four of 12 (33%) patients had no pathologic evidence of malignancy in their surgical specimen. Six of 11 patients (55%) in the CRT group were free of local failure at the time of analysis. Two of five patients in this group who had local recurrence at 2 and 10 months underwent surgical salvage with subsequent survivals of 20 and 100 months, respectively. Treatment-related mortality was 0 out of 11 in the CRT group and 2 out of 24 in the CRT+PE group. Dysphagia relief was similar in the CRT group vs. the CRT+E subgroup; however, a greater percentage of patients treated with chemoradiation alone had normal long-term swallowing function when compared to those patients also undergoing esophagectomy (100% vs. 73%). CONCLUSION: High-dose chemoradiation alone appears to provide similar survival and relief of dysphagia compared with high-dose chemoradiation followed by esophagectomy for patients with potentially resectable esophageal adenocarcinoma. Local failure may be higher in patients undergoing chemoradiation compared to chemoradiation followed by esophagectomy, but surgical salvage is possible, thus providing similar overall local control. However, because of the small number of patients in each group, these treatment modalities need to be further evaluated in a prospective randomized Phase III study.

Chronic post thoracotomy pain.

Chronic post-thoracotomy pain (CPP) is a vexing clinical problem whose management has received scant attention. In order to identify the risk factors associated with CPP and determine the optimal treatment, the records of 238 consecutive patients who underwent thoracotomy were reviewed. CPP was defined as discomfort requiring the regular administration of analgesics that continued more than three months following surgery. CPP was present in 25 (11%) patients: 10/20 (50%) chest wall resections, 5/25 (20%) pleurectomies, 10/193 (5%) pulmonary resections. Among the 23 patients who required preoperative narcotics, 12 (52%) developed CPP. Improved pain control and decreased narcotic use was achieved via the administration of nonsteroidal anti-inflammatory medication and tricyclic anti-depressants. In addition, 10/25 patients required 11 pain procedures: trigger-point injection, intercostal blocks, injections of epidural steroids, stellate ganglion block. Recurrent pain occurred in 20 patients following initial control. All were found to have tumor regrowth. We conclude that CPP occurs more commonly following chest-wall resection and pleurectomy, and that preoperative narcotic use is a predictor of CPP. Worsening pain following initial relief should prompt a vigorous search for recurrent cancer.

Preoperative high-dose radiation and chemotherapy in adenocarcinoma of the esophagus and esophagogastric junction.

BACKGROUND: Esophageal adenocarcinoma (EA) incidence is rising. Defining optimal management is essential because median survival after surgery alone is only approximately 12 months. High-dose radiation (> 5000 cGy) and chemotherapy (HDRCT) preoperatively for patients with EA has not been fully investigated. We evaluated tumor response, resectability, and survival following HDRCT in patients with localized EA. METHODS: Thirty patients with American Joint Committee on Cancer (AJCC) clinical stage I or II EA were prospectively treated with HDRCT. The treatment consisted of 60 Gy radiation at 2 Gy per fraction with concurrent infusional 5-fluorouracil (5-FU) and a bolus of mitomycin C followed by esophagogastrectomy. The range of follow-up was 7 to 69 months, with a median of 31 months. RESULTS: Twenty of 30 patients (67%) received full-course HDRCT. Severe esophagitis precluded full-dose radiation in 10 patients. Three patients developed neutropenia and fever requiring admission to a hospital. Two patients died preoperatively of treatment-related complications. Nine patients were not explored. Eighteen patients were resected with curative intent; the remaining three had metastatic disease at laparotomy. Seven of 18 resected patients (39%), or 7/30 (23%) of all patients treated, had a pathologic complete response. There was one operative death. Overall local control was seen in 25/30 patients (83%). Median overall survivals for resected and for all patients were 23 and 13 months, respectively. CONCLUSIONS: Preoperative HDRCT in patients with EA results in encouraging local tumor response and local control. Overall survival, however, may not be improved, and the treatment-related mortality of 10% is higher than reported with surgery alone or with preoperative chemotherapy.

Analysis of partial variance (APV) as a statistical approach to control day to day variation in immune assays.

The considerable day to day variability in some immunologic assays can obscure relationships among measures of interest and thereby complicate interpretation of findings when effect sizes are modest. Analysis of partial variance (APV) is a technique that utilizes data obtained from controls run in the laboratory on the day of each assay to control for day to day variance statistically. The application of this technique to permit detection of otherwise obscured effects for both larger and smaller samples is exemplified utilizing data from two studies in which subjects were assessed on multiple different dates. These included a study of the association of depression with in vitro immune measures in 296 adolescents and a longitudinal study of 20 spouses of patients admitted to a cardiac intensive care unit studied together with 20 matched controls. APV was most useful in analyses of mitogen-induced lymphocyte proliferation assays, which had considerable day to day variability. In general, multivariate studies with functional immune measures may benefit most from application of this technique.

Postoperative complications after combined neoadjuvant treatment of lung cancer.

Preoperative chemotherapy and radiation administered separately or in combination have been used in the treatment of locally advanced non-small cell lung cancer. To assess the postoperative morbidity and mortality associated with aggressive neoadjuvant therapy, we reviewed the records of 13 patients who underwent resection of locally advanced non-small cell lung cancer after two monthly cycles of infusional 5-fluorouracil, 640 to 800 mg/m2 (days 1 through 5); cisplatin, 20 mg/m2 (days 1 through 5); etoposide, 50 mg/m2 (days 1, 3, and 5); and concomitant radical thoracic irradiation (6,000 cGy) administered in 200-cGy daily fractions. Six patients underwent lobectomy with no mortality, whereas 7 pneumonectomies were associated with three deaths (43%). Culture-negative, diffuse pulmonary infiltrates developed 3 to 6 days after operation in 5 of 7 pneumonectomy patients and in 1 of 6 lobectomy patients. Two patients who had undergone pneumonectomy died of progressive adult respiratory distress syndrome. A third death resulted from a bronchopleural fistula that developed 30 days after pneumonectomy. Morbidity and mortality were not associated with preoperative pulmonary function test results, nutritional status, or intraoperative inspired oxygen fraction (p > 0.05 by chi 2 test). Only pneumonectomy correlated with increased morbidity and mortality (p < 0.05 by chi 2 test). We conclude that lobectomy may be performed safely after this combination of aggressive chemotherapy and high-dose radiation, but pneumonectomy is associated with unacceptable morbidity and mortality.