Discrepancies between clinical assessments of sensory function and electrical perceptual thresholds after incomplete chronic cervical spinal cord injury.

STUDY DESIGN: Prospective experimental. OBJECTIVES: To compare sensory function as revealed by light touch and pin prick tests of the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI) and the electrical perceptual threshold (EPT) exams in individuals with chronic incomplete cervical spinal cord injury (SCI). SETTING: Pittsburgh, United States. METHODS: EPT was tested using cutaneous electrical stimulation (0.5 ms pulse width, 3 Hz) in 32 healthy controls and in 17 participants with SCI over key points on dermatomes C2 to T4 on each side of the body. Light touch and pin prick ISNCSCI scores were tested at the same key dermatomes in SCI participants. RESULTS: In controls, EPT values were higher in older males (1.26±0.2 mA, mean±s.d.) compared with younger males (1.0±0.2 mA) and older females (0.9±0.2 mA), regardless of the dermatome and side tested. Fifteen out of the seventeen SCI participants showed that the level of sensory impairment detected by the EPT was below the level detected by the ISNCSCI (mean=4.5±2.4, range 1-9). The frequency distribution of EPTs was similar to older male controls in dermatomes above but not below the ISNCSCI sensory level. The difference between EPT and ISNCSCI sensory level was negatively correlated with the time post injury. CONCLUSIONS: The results show that, in the chronic stage of cervical SCI, the EPT reveals spared sensory function at lower (~5) spinal segments compared with the ISNCSCI sensory exam. It is hence found that the EPT is a sensitive tool to assess recovery of sensory function after chronic SCI.

Improvement in survival and quality of life with new therapeutic agents in metastatic castration-resistant prostate cancer: comparison among the results.

Androgen deprivation therapy is the mainstay of treatment for men affected by metastatic prostate cancer (PC). Unfortunately, nearly all patient will become resistant to the initial hormonal approach, developing a metastatic castration-resistant prostate cancer (mCRPC). For many years, chemotherapy with docetaxel has been the only established standard of care for men with mCRPC. Recent developments in the knowledge of the disease biology have shown that during the progression to the castrate status PC remains dependent on androgens and androgen receptor (AR) pathway. As a consequence, new agents like abiraterone acetate and enzalutamide have been rapidly developed and approved for clinical use. Other drugs with different mechanisms of action, such as sipuleucel-T, cabazitaxel, and radium-223 have shown to improve overall survival, symptom control and quality of life of mCRPC patients. However, the optimal sequencing and combination of these treatments are not defined yet. Studies on biomarkers for treatment selection, such as AR splice variants, are promising, but the initial data still need prospective validation on large patient series.

Choroidal neovascularisation as an unusual ophthalmic manifestation of cat-scratch disease in an 8-year-old girl.

To report the first case of choroidal neovascularisation (CNV) that appeared during the primary Bartonella henselae infection in an 8-year-old girl. An 8-year-old girl was referred to our clinic complaining of a central scotoma in the right eye. Fundus examination revealed a bilateral disc oedema and in the right eye neuroretinitis with macular star and CNV, which was confirmed by fluorescein angiography. The optical coherence tomography revealed the presence of macular serous retinal detachment. Laboratory analysis showed rising IgM and IgG titres for B. henselae. Cat-scratch disease was diagnosed, and an 8-week treatment with azithromycin was initiated. In addition, an intravitreal injection of ranibizumab was performed in the right eye to treat the CNV. A month later, we decided to administer a systemic antibiotic again for an additional 5 months, due to the persistence of papillitis. Cat-scratch disease should be considered among the different causes of inflammatory CNV secondary to infectious uveitis. Our case was the first described in the literature in which a CNV appeared during the primary infection and not as a later complication. The combination of systemic antibiotic treatment with intravitreal anti-VEGF therapy was a successful choice because it allowed us to obtain the complete resolution of neuroretinitis, associated with the scarring of the choroidal neovascular membrane, with a final visual acuity of 20/20 in both eyes.

Interaction of cortical networks mediating object motion detection by moving observers.

The task of parceling perceived visual motion into self- and object motion components is critical to safe and accurate visually guided navigation. In this paper, we used functional magnetic resonance imaging to determine the cortical areas functionally active in this task and the pattern connectivity among them to investigate the cortical regions of interest and networks that allow subjects to detect object motion separately from induced self-motion. Subjects were presented with nine textured objects during simulated forward self-motion and were asked to identify the target object, which had an additional, independent motion component toward or away from the observer. Cortical activation was distributed among occipital, intra-parietal and fronto-parietal areas. We performed a network analysis of connectivity data derived from partial correlation and multivariate Granger causality analyses among functionally active areas. This revealed four coarsely separated network clusters: bilateral V1 and V2; visually responsive occipito-temporal areas, including bilateral LO, V3A, KO (V3B) and hMT; bilateral VIP, DIPSM and right precuneus; and a cluster of higher, primarily left hemispheric regions, including the central sulcus, post-, pre- and sub-central sulci, pre-central gyrus, and FEF. We suggest that the visually responsive networks are involved in forming the representation of the visual stimulus, while the higher, left hemisphere cluster is involved in mediating the interpretation of the stimulus for action. Our main focus was on the relationships of activations during our task among the visually responsive areas. To determine the properties of the mechanism corresponding to the visual processing networks, we compared subjects' psychophysical performance to a model of object motion detection based solely on relative motion among objects and found that it was inconsistent with observer performance. Our results support the use of scene context (e.g., eccentricity, depth) in the detection of object motion. We suggest that the cortical activation and visually responsive networks provide a potential substrate for this computation.

Validation of the Meet-URO score in patients with metastatic renal cell carcinoma receiving first-line nivolumab and ipilimumab in the Italian Expanded Access Program.

BACKGROUND: The Meet-URO score allowed a more accurate prognostication than the International Metastatic RCC Database Consortium (IMDC) for patients with pre-treated metastatic renal cell carcinoma (mRCC) by adding the pre-treatment neutrophil-to-lymphocyte ratio and presence of bone metastases. MATERIALS AND METHODS: A post hoc analysis was carried out to validate the Meet-URO score on the overall survival (OS) of patients with IMDC intermediate-poor-risk mRCC treated with first-line nivolumab plus ipilimumab within the prospective Italian Expanded Access Programme (EAP). We additionally considered progression-free survival (PFS) and disease response rates. Harrell's c-index was calculated to compare the accuracy of survival prediction. RESULTS: Overall the EAP included 306 patients, with a median follow-up of 12.2 months, median OS was not reached, 1-year OS was 66.8% and median PFS was 7.9 months. By univariable analysis, both the IMDC score and the two additional variables of the Meet-URO score were associated with either OS or PFS (P < 0.001 for all comparisons). The four Meet-URO risk groups (G) had 1-year OS of 92%, 72%, 50% and 21% for G2 (29.1% of patients), G3 (28.8%), G4 (33.0%) and G5 (9.1%), respectively. OS was significantly shorter in each consecutive G (P = 0.001 for G3, P < 0.001 for both G4 and G5 compared to G2). Similarly, Meet-URO Gs 2-5 showed decreasing median PFS and response rates. The Meet-URO score showed the highest c-index for both OS (0.73) and PFS (0.67). Limitations include the post hoc nature of this analysis and the lack of a comparative arm to assess predictive value. CONCLUSION: The Meet-URO score appeared to show better prognostic classification than the IMDC alone in patients with mRCC at IMDC intermediate-poor risk treated with first-line nivolumab and ipilimumab.

Acoustic facilitation of object movement detection during self-motion.

In humans, as well as most animal species, perception of object motion is critical to successful interaction with the surrounding environment. Yet, as the observer also moves, the retinal projections of the various motion components add to each other and extracting accurate object motion becomes computationally challenging. Recent psychophysical studies have demonstrated that observers use a flow-parsing mechanism to estimate and subtract self-motion from the optic flow field. We investigated whether concurrent acoustic cues for motion can facilitate visual flow parsing, thereby enhancing the detection of moving objects during simulated self-motion. Participants identified an object (the target) that moved either forward or backward within a visual scene containing nine identical textured objects simulating forward observer translation. We found that spatially co-localized, directionally congruent, moving auditory stimuli enhanced object motion detection. Interestingly, subjects who performed poorly on the visual-only task benefited more from the addition of moving auditory stimuli. When auditory stimuli were not co-localized to the visual target, improvements in detection rates were weak. Taken together, these results suggest that parsing object motion from self-motion-induced optic flow can operate on multisensory object representations.

SAUL, a single-arm study of atezolizumab for chemotherapy-pretreated locally advanced or metastatic carcinoma of the urinary tract: outcomes by key baseline factors, PD-L1 expression and prior platinum therapy.

BACKGROUND: The impact of pretreatment factors on immune checkpoint inhibition in platinum-refractory advanced urothelial cancer (aUC) deserves further evaluation. The aim was to study the association of Bellmunt risk factors, time from last chemotherapy (TFLC), previous therapy and PD-L1 expression with atezolizumab efficacy in platinum-refractory aUC. PATIENTS AND METHODS: This was a post-hoc analysis of patients who had received prior cisplatin or carboplatin in the prospective, single-arm, phase IIIb SAUL study (NCT02928406). Patients were treated with 3-weekly atezolizumab 1200 mg intravenously. The primary outcome was overall survival (OS). Relationships were analysed using Cox regression and long-rank test. RESULTS: Of 997 patients in SAUL, 969 were eligible for this analysis. The number of Bellmunt risk factors was associated with OS (P < 0.001); median OS (mOS) for 0, 1 and 2-3 risk factors was 17.9, 8.9 and 3.3 months, respectively. Significant associations were also observed between OS and TFLC (P < 0.001), programmed death-ligand 1 (PD-L1) expression (P = 0.002), and prior perioperative chemotherapy (P = 0.013); mOS was 6.97 versus 11.63 months for TFLC ≤6 versus >6 months, 7.75 versus 11.6 months for PD-L1 expression on <1% of tumour-infiltrating immune cells (ICs) (IC0)/expression on 1% to <5% of tumour-infiltrating ICs (IC1) versus expression on ≥5% of tumour-infiltrating ICs (IC2/3) and 10.2 versus 7.8 months for prior versus no prior perioperative chemotherapy, respectively. The type of platinum compound and number of previous treatment lines were not associated with outcomes. CONCLUSIONS: Post-platinum atezolizumab is active in aUC, irrespective of previous platinum compound and lines of therapy. Bellmunt risk stratification, PD-L1 expression, TFLC and perioperative chemotherapy were identified as prognostic factors for OS with second-line atezolizumab, indicating the need for novel prognostic signatures for immunotherapy-treated patients with aUC.

Immune-inflammatory biomarkers as prognostic factors for immunotherapy in pretreated advanced urinary tract cancer patients: an analysis of the Italian SAUL cohort.

BACKGROUND: Reliable and affordable prognostic and predictive biomarkers for urothelial carcinoma treated with immunotherapy may allow patients' outcome stratification and drive therapeutic options. The SAUL trial investigated the safety and efficacy of atezolizumab in a real-world setting on 1004 patients with locally advanced or metastatic urothelial carcinoma who progressed to one to three prior systemic therapies. PATIENTS AND METHODS: Using the SAUL Italian cohort of 267 patients, we investigated the prognostic role of neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII) and the best performing one of these in combination with programmed death-ligand 1 (PD-L1) with or without lactate dehydrogenase (LDH). Previously reported cut-offs (NLR >3 and NLR >5; SII >1375) in addition to study-defined ones derived from receiver operating characteristic (ROC) analysis were used. RESULTS: The cut-off values for NLR and SII by the ROC analysis were 3.65 (sensitivity 60.4; specificity 63.0) and 884 (sensitivity 64.4; specificity 67.5), respectively. The median overall survival (OS) was 14.7 months for NLR <3.65 [95% confidence interval (CI) 9.9-not reached (NR)] versus 6.0 months for NLR ≥3.65 (95% CI 3.9-9.4); 14.7 months for SII <884 (95% CI 10.6-NR) versus 6.0 months for SII ≥884 (95% CI 3.7-8.6). The combination of SII, PD-L1, and LDH stratified OS better than SII plus PD-L1 through better identification of patients with intermediate prognosis (77% versus 48%, respectively). Multivariate analyses confirmed significant correlations with OS and progression-free survival for both the SII + PD-L1 + LDH and SII + PD-L1 combinations. CONCLUSION: The combination of immune-inflammatory biomarkers based on SII, PD-L1, with or without LDH is a potentially useful and easy-to-assess prognostic tool deserving validation to identify patients who may benefit from immunotherapy alone or alternative therapies.

Baseline brain function in the preadolescents of the ABCD Study.

The Adolescent Brain Cognitive Development (ABCD) Study® is a 10-year longitudinal study of children recruited at ages 9 and 10. A battery of neuroimaging tasks are administered biennially to track neurodevelopment and identify individual differences in brain function. This study reports activation patterns from functional MRI (fMRI) tasks completed at baseline, which were designed to measure cognitive impulse control with a stop signal task (SST; N = 5,547), reward anticipation and receipt with a monetary incentive delay (MID) task (N = 6,657) and working memory and emotion reactivity with an emotional N-back (EN-back) task (N = 6,009). Further, we report the spatial reproducibility of activation patterns by assessing between-group vertex/voxelwise correlations of blood oxygen level-dependent (BOLD) activation. Analyses reveal robust brain activations that are consistent with the published literature, vary across fMRI tasks/contrasts and slightly correlate with individual behavioral performance on the tasks. These results establish the preadolescent brain function baseline, guide interpretation of cross-sectional analyses and will enable the investigation of longitudinal changes during adolescent development.

Neural activity underlying the detection of an object movement by an observer during forward self-motion: Dynamic decoding and temporal evolution of directional cortical connectivity.

Relatively little is known about how the human brain identifies movement of objects while the observer is also moving in the environment. This is, ecologically, one of the most fundamental motion processing problems, critical for survival. To study this problem, we used a task which involved nine textured spheres moving in depth, eight simulating the observer's forward motion while the ninth, the target, moved independently with a different speed towards or away from the observer. Capitalizing on the high temporal resolution of magnetoencephalography (MEG) we trained a Support Vector Classifier (SVC) using the sensor-level data to identify correct and incorrect responses. Using the same MEG data, we addressed the dynamics of cortical processes involved in the detection of the independently moving object and investigated whether we could obtain confirmatory evidence for the brain activity patterns used by the classifier. Our findings indicate that response correctness could be reliably predicted by the SVC, with the highest accuracy during the blank period after motion and preceding the response. The spatial distribution of the areas critical for the correct prediction was similar but not exclusive to areas underlying the evoked activity. Importantly, SVC identified frontal areas otherwise not detected with evoked activity that seem to be important for the successful performance in the task. Dynamic connectivity further supported the involvement of frontal and occipital-temporal areas during the task periods. This is the first study to dynamically map cortical areas using a fully data-driven approach in order to investigate the neural mechanisms involved in the detection of moving objects during observer's self-motion.

Docetaxel plus oblimersen sodium (Bcl-2 antisense oligonucleotide): an EORTC multicenter, randomized phase II study in patients with castration-resistant prostate cancer.

BACKGROUND: This randomized, phase II study assessed the activity of oblimersen sodium, a Bcl-2 antisense oligonucleotide, administered before docetaxel (Taxotere) to patients with castration-resistant prostate cancer. PATIENTS AND METHODS: Chemotherapy-naive patients with prostate-specific antigen (PSA) progression and testosterone < or = 0.5 ng/ml received docetaxel 75 mg/m2 on day 1 or oblimersen 7 mg/kg/day continuous i.v. infusion on days 1-7 with docetaxel 75 mg/m2 on day 5 every 3 weeks for < or = 12 cycles. Primary end points were confirmed PSA response (Bubley criteria) and major toxic events. RESULTS: Confirmed PSA response was observed in 46% and 37% of 57 and 54 patients treated with docetaxel and docetaxel-oblimersen, respectively. Partial response (RECIST) was achieved in 18% and 24%, respectively. Oblimersen added to docetaxel was associated with an increase in the incidence of grade > or = 3 fatigue, mucositis, and thrombocytopenia. Major toxic events were reported in 22.8% and 40.7% of patients with docetaxel and docetaxel-oblimersen, respectively. CONCLUSIONS: The primary end points of the study were not met: a rate of confirmed PSA response >30% and a major toxic event rate <45% were not observed with docetaxel-oblimersen.

Cross-Modal Cue Effects in Motion Processing.

The everyday environment brings to our sensory systems competing inputs from different modalities. The ability to filter these multisensory inputs in order to identify and efficiently utilize useful spatial cues is necessary to detect and process the relevant information. In the present study, we investigate how feature-based attention affects the detection of motion across sensory modalities. We were interested to determine how subjects use intramodal, cross-modal auditory, and combined audiovisual motion cues to attend to specific visual motion signals. The results showed that in most cases, both the visual and the auditory cues enhance feature-based orienting to a transparent visual motion pattern presented among distractor motion patterns. Whereas previous studies have shown cross-modal effects of spatial attention, our results demonstrate a spread of cross-modal feature-based attention cues, which have been matched for the detection threshold of the visual target. These effects were very robust in comparisons of the effects of valid vs. invalid cues, as well as in comparisons between cued and uncued valid trials. The effect of intramodal visual, cross-modal auditory, and bimodal cues also increased as a function of motion-cue salience. Our results suggest that orienting to visual motion patterns among distracters can be facilitated not only by intramodal priors, but also by feature-based cross-modal information from the auditory system.

Sequential left pneumonectomy and right upper lobectomy for hemoptysis in post-tuberculosis destroyed lung and aspergilloma.

The case of a 30-years-old man from Angola who was referred with a history of previous tuberculosis at the age of 14, recurrent hemoptysis and a radiological picture of destroyed left lung and shrunken right upper lobe containing a fungus ball is presented. After careful functional evaluation the patient underwent sequential left pneumonectomy and right upper lobectomy due to the fear of massive and possibly fatal hemoptysis. Both operation were well tolerated and had an uneventful postoperative course. There was no significant difference between his postoperative and his preoperative functional status. The patient is now living an active life with only seven lung segments.

The use of flexible spiral drains after non-cardiac thoracic surgery. A clinical study.

OBJECTIVE: After an observational study on 50 patients determined the efficacy and safety of a small calibre (19F), flexible, fluted spiral drains with round cross-section after non-cardiac thoracic surgery we undertook a prospective study to compare these drains to standard chest drains also in terms of pain using a Visual Analog Score. METHODS: One hundred consecutive patients who had to undergo non-cardiac chest surgery either by thoracotomy or by VATS were randomly assigned to receive small calibre drains with round cross-section (group A) or the standard chest drains (group B) to drain the pleural space. Drains were connected to a unitized chest drainage system. Pain was assessed using a Visual Analog Scale (VAS) 0-100. RESULTS: The amount of fluid evacuated daily in patients who received the spiral drains was as much as 1150 ml, that of patients who received standard drains was as much as 950 ml. In no case did spiral drains have to be replaced with standard tubes. In group A first drain was removed after a mean of 3.4 days and the second after a mean of 5.9 days; in group B after a mean of 4.1 and 6.1 days, respectively. Patients were discharged after a mean of 8.5 days in group A (SD 4.04) and 8.1 days in group B (SD 4.76). There were no drains-related complications in both groups. The drains-related pain for the patient was significantly less for patients with spiral drains compared to standard drains at rest, during cough induced by respiratory therapists and at the time of removal. CONCLUSIONS: Spiral drains proved to be at least as safe and effective as conventional tubes after lung surgery; they allowed for evacuation of large amounts of blood/fluid as well as air, and were associated with minimal discomfort.

Visual acuity and macular sensitivity in myopic eyes before and after laser in situ keratomileusis.

PURPOSE: To evaluate the changes in visual acuity (VA) and in macular sensitivity in myopic eyes subjected to laser in situ keratomileusis (LASIK) refractive surgery. METHODS: In 38 myopic eyes, VA by Snellen's table and macular sensitivity by scanning laser ophthalmoscope (SLO) microperimetry were assessed before and after 24 weeks after LASIK surgery. The myopic eyes were divided into three age-matched groups: Group A = from -5 diopters (D) to -7 D and normal SLO-macular sensitivity (15 eyes); Group B = from -8 D to -16 D and normal SLO-macular sensitivity (9 eyes); and Group C = from -8 D to -16 D and abnormal SLO-macular sensitivity. RESULTS: Group A and B eyes, at the first week after LASIK surgery, we observed a significant analysis of variance, p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values, while after 12 and 24 weeks no differences (p>0.01) were found when compared to baseline. In Group C patients, at 1 and 4 weeks after surgical treatment, we observed a significant (p<0.01) reduction in VA and SLO-macular sensitivity with respect to baseline values. At 12 and 24 weeks the values of VA were reduced, but not significantly (p>0.01), while values of SLO-macular sensitivity were still significantly (p<0.01) reduced. CONCLUSIONS: LASIK could induce a reduction in VA and SLO-macular sensitivity in all myopic eyes during the 4 weeks following the surgery. This reduction is still present after 24 weeks only in eyes with the highest preoperative degree of myopia combined with the greatest reduction in macular sensitivity.

Influence of pyridostigmine on growth hormone (GH) response to GH-releasing hormone pre- and postprandially in normal and obese subjects.

The effect of pyridostigmine (PYR), an inhibitor of acetylcholinesterase, on the GH response to GH-releasing hormone (GHRH) before and after a meal was studied in 14 normal subjects (8 females and 6 males) and 21 obese subjects (13 females and 8 males). In normal subjects tested in a fasting state, PYR was capable of stimulating GH secretion and increasing the GH response to GHRH. These effects were not apparent after food, suggesting a reduction in cholinergic hypothalamic activity. In obese subjects tested in a fasting state, PYR was ineffective when administered alone. On the contrary, it was able to increase the GH response to GHRH. After food, the augmenting effect of PYR on the GH response to GHRH was not observed, whereas a delayed inhibition of the GH response was found after PYR plus GHRH treatment. Our findings support the hypothesis that cholinergic hypothalamic activity plays a pivotal role in impaired GH regulation and the altered sensitivity of GH secretion to metabolic fuels in obese subjects.

Pre-operative chemoradiotherapy in non-small cell lung cancer stage III patients. Feasibility, toxicity and long-term results of a phase II study.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m2 for 1 day plus etoposide 120 mg/m2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IIIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70-90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia > or = grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia > or = grade 3 at nadir in seven cycles (9%), 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients (P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

Prognostic evaluation of patients submitted to surgery for malignant pleural mesothelioma.

The role of surgical resection remains controversial in malignant pleural mesothelioma. The assessment of its impact on prognosis is complicated by a poor understanding of the prognostic factors in the disease. We therefore evaluated, through univariate and multivariate analysis, the role on prognosis of 24 variables in 57 patients submitted to surgery from 1985 to 1993. Sixteen patients had only exploratory thoracotomy and 12 minimal residual disease after surgery (no nodules >1 cm in diameter). Thirty-four cases had epithelial histotype, 6 sarcomatous and 17 mixed. Median survival for the whole group was 15.7 months. Multivariate analysis showed a highly significant influence on survival for minimal residual disease after surgery (p=0.0006), followed by TNM stage (p=0.01). Median survival for patients with TNM stage I disease was 36.3 months and for patients with minimal residual disease 33 months. In conclusion, these data suggest that patients with limited disease have a longer survival after surgery than those with extensive disease. At the same time, our results indicate that the achievement of significant disease reduction with surgery has a critical impact on the prognosis of pleural mesothelioma.

GH response to GHRH before and after meals at different hours of the day in obese patients.

In normal subjects several factors are involved in the regulation of the GH response to GHRH, such as nutritional status, metabolic fuels and neurotransmitters. We previously have shown a paradoxical increase in the GH response to GHRH after meals in obese patients, in contrast to the blunted GH response observed after feeding in normal subjects. We have further investigated this phenomenon, studying the GH response to GHRH before and after meal at three different hours during the day in 10 obese patients, aged 18-35 yr, in comparison to that in eight normal women, aged 20-35 yr. GHRH was injected in a fasting state or 1 hr after a standard meal (800 KCal). In obese subjects, after food ingestion the peak GH response to GHRH was increased at 0900h and 1300h and was significant when the patients were tested after lunch (1300h). On the contrary, in the evening the GH response to GHRH remained unchanged, both before and after feeding. These data point to an altered sensitivity of GH secretion to metabolic signals in patients with obesity.

Influence of naloxone infusion on prolactin and growth hormone response to growth hormone-releasing hormone in anorexia nervosa.

Anorexia nervosa (AN) is frequently associated with anomalies of growth hormone (GH) and prolactin (PRL) secretion. We studied the GH and PRL responses to GHRH1-44 (50 micrograms IV) and the effect of a naloxone infusion (1.6 mg/hr), started 1 hr before GHRH administration, on this response in 12 female patients with AN, aged 15-30 yr, and in seven normal women, aged 19-27 yr, during the follicular phase as controls. In AN, GHRH induced an increase in GH levels similar to that observed in normal subjects. A significant inhibition of the GH response to GHRH was observed during naloxone infusion, similar to the inhibition in normal female subjects during the follicular phase. PRL levels showed a significant increment after GHRH alone and a slight, nonsignificant, PRL increment after GHRH during naloxone infusion in AN patients. In contrast a slight PRL decrease was observed after GHRH, both before and during naloxone infusion, in the normal subjects. Our study demonstrates that endogenous opioids play a role in influencing PRL secretion in patients with AN different from their role in normal subjects.