Antibody-mediated thyroid dysfunction during T-cell checkpoint blockade in patients with non-small-cell lung cancer.

Background: Programmed cell death protein-1 (PD-1) blockade therapies have demonstrated durable responses and prolonged survival in a variety of malignancies. Treatment is generally well tolerated although immune-related adverse events (irAEs) can occur. Autoimmune thyroid dysfunction is among the most common irAE, but an assessment of the clinical, mechanistic, and immunologic features has not been previously described. Patient and methods: Patients with advanced non-small-cell lung cancer (NSCLC) treated with pembrolizumab at Memorial Sloan Kettering Cancer Center (n = 51) as part of KEYNOTE-001 (NCT01295827) were included. Thyroid function test and anti-thyroid antibodies were assessed prospectively at each study visit, beginning before the first treatment. Frequency of development of thyroid dysfunction, association with anti-thyroid antibodies, clinical course, and relationship with progression-free survival and overall survival to treatment with pembrolizumab was evaluated. Results: Of 51 patients treated, 3 were hypothyroid and 48 were not at baseline. Ten of 48 [21%, 95% confidence interval (CI) 10% to 35%] patients developed thyroid dysfunction requiring thyroid replacement. Anti-thyroid antibodies were present in 8 of 10 patients who developed thyroid dysfunction, compared with 3 of 38 who did not (80% versus 8%, P < 0.0001). Thyroid dysfunction occurred early (median, 42 days) in the pembrolizumab course, and a majority (6 of 10 patients) experienced brief, transient hyperthyroidism preceding the onset of hypothyroidism; no persistent hyperthyroidism occurred. Both hyperthyroidism and hypothyroidism were largely asymptomatic. Overall survival with pembrolizumab was significantly longer in subjects who developed thyroid dysfunction (hazard ratio, 0.29; 95% CI 0.09-0.94; P = 0.04). Conclusions: Thyroid dysfunction during pembrolizumab treatment of NSCLC is common and is characterized by early-onset, frequently preceded by transient hyperthyroidism, closely associated with anti-thyroid antibodies, and may be associated with improved outcomes. The presence of antibody-mediated toxicity in T-cell-directed therapy suggests an under-recognized impact of PD-1 biology in modulating humoral immunity.

Necrotizing Enteritis and Hyperammonemic Encephalopathy Associated With Equine Coronavirus Infection in Equids.

Equine coronavirus (ECoV) is a Betacoronavirus recently associated clinically and epidemiologically with emerging outbreaks of pyrogenic, enteric, and/or neurologic disease in horses in the United States, Japan, and Europe. We describe the pathologic, immunohistochemical, ultrastructural, and molecular findings in 2 horses and 1 donkey that succumbed to natural infection with ECoV. One horse and the donkey (case Nos. 1, 3) had severe diffuse necrotizing enteritis with marked villous attenuation, epithelial cell necrosis at the tips of the villi, neutrophilic and fibrinous extravasation into the small intestinal lumen (pseudomembrane formation), as well as crypt necrosis, microthrombosis, and hemorrhage. The other horse (case No. 2) had hyperammonemic encephalopathy with Alzheimer type II astrocytosis throughout the cerebral cortex. ECoV was detected by quantitative polymerase chain reaction in small intestinal tissue, contents, and/or feces, and coronavirus antigen was detected by immunohistochemistry in the small intestine in all cases. Coronavirus-like particles characterized by spherical, moderately electron lucent, enveloped virions with distinct peplomer-like structures projecting from the surface were detected by negatively stained transmission electron microscopy in small intestine in case No. 1, and transmission electron microscopy of fixed small intestinal tissue from the same case revealed similar 85- to 100-nm intracytoplasmic particles located in vacuoles and free in the cytoplasm of unidentified (presumably epithelial) cells. Sequence comparison showed 97.9% to 99.0% sequence identity with the ECoV-NC99 and Tokachi09 strains. All together, these results indicate that ECoV is associated with necrotizing enteritis and hyperammonemic encephalopathy in equids.

Clinical outcomes in elderly patients with advanced non-small cell lung cancer: results from ARIES, a bevacizumab observational cohort study.

AIMS: Retrospective analyses from first-line clinical studies in advanced non-small cell lung cancer (NSCLC) have reported conflicting results on progression-free survival (PFS) and overall survival benefits with the addition of bevacizumab to chemotherapy in elderly patients. Here we report effectiveness and safety outcomes by age subgroup for patients with NSCLC in the ARIES observational cohort study. MATERIALS AND METHODS: ARIES enrolled patients with advanced non-squamous NSCLC who received first-line bevacizumab-containing treatment per physician's choice. Kaplan-Meier estimates were used to calculate medians and 95% confidence intervals for PFS and overall survival for patients aged <65, ≥65, <75 and ≥75 years. RESULTS: In total, 1967 patients receiving first-line treatment with bevacizumab and chemotherapy were enrolled. The median PFS and overall survival values were 6.4 (95% confidence interval = 6.0-6.8) and 14.2 (95% confidence interval = 12.7-15.2) months for patients aged <65 years, respectively, and 6.8 (95% confidence interval = 6.3-7.0) and 12.1 (95% confidence interval = 11.4-13.1) months for patients ≥65 years, respectively. For patients <75 years, the median PFS and overall survival values were 6.6 (95% confidence interval = 6.3-6.9) and 13.5 (95% confidence interval = 12.6-14.5) months, respectively, and 6.6 (95% confidence interval = 5.9-7.1) and 11.6 (95% confidence interval = 10.0-12.5) months, respectively, for patients ≥75 years. Incidence proportions of bevacizumab-associated adverse events were generally similar across all age groups. CONCLUSIONS: Data from the ARIES study suggest that treatment with bevacizumab in combination with chemotherapy is a viable first-line treatment option for elderly bevacizumab-eligible patients with advanced non-squamous NSCLC.

Identification of a novel papillomavirus in a Northern Fulmar (Fulmarus glacialis) with viral production in cartilage.

We report the identification of a novel papillomavirus, Fulmarus glacialis papillomavirus 1 (FgPV1), present within an interdigital foot mass of a Northern Fulmar (Fulmarus glacialis). The mass of interest was composed of normal stratified and keratinized epithelium and dense mesenchymal cells with central cartilaginous islands. Within the nuclei of many chondrocytes were loose aggregates or paracrystalline arrays of virions approximately 50 nm in size. Degenerate polymerase chain reaction was used to identify the virus as a putative papillomavirus, and the entire viral genome of 8132 base pairs was subsequently amplified and sequenced. Analysis revealed canonical papillomavirus architecture, including the early open reading frames E6, E7, E1, and E2 and the 2 late proteins L1 and L2. FgPV1 is most closely related to a cluster of avian and reptilian papillomaviruses as visualized by phylogenetic trees. This observation suggests that papillomavirus virion production can occur in mesenchymal cells.

Safety and effectiveness of bevacizumab treatment for metastatic colorectal cancer: final results from the Avastin(®) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study.

AIMS: The Avastin(®) Registry - Investigation of Effectiveness and Safety (ARIES) observational cohort study (OCS) was designed to prospectively examine outcomes associated with bevacizumab-containing treatment for metastatic colorectal cancer (mCRC) in a community-based setting, where patient populations are less restricted than those in randomised trials. MATERIALS AND METHODS: Patients with mCRC who were eligible for bevacizumab in combination with chemotherapy in first- or second-line treatment were enrolled from November 2006 to September 2008. There were no protocol-specified treatment regimens; the dose and schedule of bevacizumab and chemotherapy were at the treating physician's discretion. The objectives in the ARIES OCS included analyses of progression-free survival (PFS), overall survival, treatment patterns and safety in each of the first- and second-line treatment cohorts. RESULTS: ARIES enrolled 1550 patients with mCRC receiving first-line therapy with bevacizumab. The median follow-up time was 20.6 months. The median PFS in this cohort was 10.2 months (95% confidence interval 9.8-10.6) and the median overall survival was 23.2 months (95% confidence interval 21.2-24.8). In a separate cohort of 482 patients with second-line mCRC, the median follow-up time was 16.9 months, the median PFS and overall survival from the start of second-line treatment to the end of follow-up was 7.9 months (95% confidence interval 7.2-8.3) and 17.8 months (95% confidence interval 16.5-20.7), respectively. Incidences of known bevacizumab-associated adverse events in ARIES were generally consistent with those previously reported in OCSs and randomised trials. CONCLUSION: Results from the prospective ARIES OCS add further evidence to support the effectiveness and safety of bevacizumab when added to first- and second-line treatment regimens for patients with mCRC in community treatment settings.

Ulcerative umbrellar lesions in captive moon jelly (Aurelia aurita) medusae.

Over a period of 6 months, dozens of moon jelly (Aurelia aurita) medusae from a single-species exhibit at the California Science Center (CSC) developed exumbrellar ulcers. Ulcers were progressive, causing umbrellar creases that expanded radially to the bell rim and occasional adoral erosions that extended into gastrovascular cavities. Husbandry interventions, including addition of ultraviolet light sterilizers, repopulation with fresh cultures, and enclosure disinfection, did not arrest the recurrence of lesions. Biopsies or whole specimens representing 17 medusae (15 affected and 2 grossly unaffected) from CSC and 2 control medusae from Aquarium of the Pacific were submitted to a private diagnostic laboratory and processed for light and electron microscopy. Microscopic lesions were present in all CSC medusae and were not observed or negligible in control medusae. Lesions included ulceration, necrosis, and hyperplasia in all umbrellar layers, with most severe lesions in the exumbrella and amoebocyte infiltration in the underlying mesoglea. Special stains, electron microscopy, and fungal culture did not associate microorganisms with the lesions. Bacterial cultures from the CSC population consistently grew Shewanella and Vibrio spp, both of which were considered commensal. Trauma and environmental stress are proposed as possible causes for the ulcers.

Suspicious cervical lymph nodes detected after thyroidectomy for papillary thyroid cancer usually remain stable over years in properly selected patients.

CONTEXT: The risk of loco-regional recurrence in papillary thyroid cancer (PTC) patients ranges from 15-30%. However, the clinical significance of small-volume loco-regional recurrence detected by highly sensitive ultrasonography is unclear. OBJECTIVE: Our objective was to describe the natural history of abnormal cervical lymph nodes (LN) diagnosed after initial treatment. DESIGN: We conducted a retrospective cohort study. PATIENTS: 166 PTC with patients who had at least one abnormal LN outside the thyroid be on ultrasound and selected for active surveillance were included. MAIN OUTCOME MEASURE: LN growth during a period of active surveillance was the primary outcome. RESULTS: Most patients had classical PTC (85%) and an intermediate risk of recurrence (77%). The median LN size at the start of the observation period was 1.3 cm (range, 0.5-2.7 cm) in largest diameter, with all nodes having at least one abnormal sonographic characteristic (70% of patients had LN with at least two abnormal features). In almost all patients, the LN were in the lateral neck, primarily in levels 3 (43%) and 4 (58%). After a median follow-up of 3.5 yr, only 20% (33 of 166) grew at least 3 mm, 9% (15 of 166) grew at least 5 mm, and 14% (23 of 166) resolved. None of the clinical or sonographic features were predictive of LN growth (positive predictive value range = 0.21-0.57). There were no local complications (nerve damage or local invasion) related to the abnormal nodes and no disease-related mortality. CONCLUSIONS: Suspicious cervical LN in the lateral neck usually remain stable for long periods of time in properly selected PTC patients and can be safely followed with serial ultrasounds.

Initial therapy with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation is associated with very low rates of structural disease recurrence in properly selected patients with differentiated thyroid cancer.

OBJECTIVE: To describe the risk of structural disease recurrence in a cohort of patients with differentiated thyroid cancer selected for treatment with either thyroid lobectomy or total thyroidectomy without radioactive iodine remnant ablation (RRA). DESIGN: Retrospective review. PATIENTS: A total of 289 patients were selected for either thyroid lobectomy (n = 72) or total thyroidectomy (n = 217) without RRA and followed with modern disease detection tools in a tertiary referral centre. Most patients had papillary thyroid cancer (89%) without clinically evident lymph node metastases (91%). However, 55% (156/289) of patients had primary tumours that were >1 cm and 10% (28/289) had minor extrathyroidal extension. MEASUREMENTS: The primary endpoint was detection of recurrent/persistent structural disease. RESULTS: After a 5-year median follow-up, structural disease recurrence was detected in 2·3% (5/217) of patients treated with total thyroidectomy without RRA, and in 4·2% (3/72) of patients treated with thyroid lobectomy. Size of the primary tumour, the presence of cervical lymph node metastases and American Thyroid Association risk category were all statistically significant predictors of recurrence. Changes in serum thyroglobulin were not helpful in identifying the presence of persistent/recurrent structural disease. Importantly, 88% (7/8) of the patients that had recurrent disease were rendered clinically disease free with additional therapies. CONCLUSIONS: Initial risk stratification is able to identify a cohort of patients with differentiated thyroid cancer with a very low risk of structural disease recurrence following treatment with either thyroid lobectomy or total thyroidectomy without RRA. Our data strongly support a selective approach to the initial management of thyroid cancer.

Comparison of efficacy of 2220 MBq versus 3700 MBq I-131 for ablation of thyroid remnant in patients with differentiated thyroid cancer.

AIM: We evaluated the efficacy of two doses of I-131 (2220 MBq versus 3700 MBq) after thyroid hormone withdrawal for thyroid remnant ablation postoperatively in patients with differentiated thyroid cancer (DTC). METHODS: A total of 133 patients with DTC were studied retrospectively. Group 1 (N.=48) included patients with a primary tumor less than 4 cm in mean diameter and confined to the thyroid gland that received an average ablation dose of 2220 MBq. Group 2 (N.=81) included patients with a primary tumor equal to or greater than 4 cm in mean diameter and/or with vascular invasion and/or intrathyroidal lymphovascular invasion and/or microscopic extrathyroidal extension that received an average ablation dose of 3700 MBq. There was no significant difference between the two groups in terms of demographic characteristics or the radioiodine uptake in the neck (2.86+2.31% versus 2.84+1.21%, P=0.97). The success of the remnant ablation was judged by the standard institutional protocol: I-123 whole body scan (WBS) and serum Thyroglobulin (Tg) level after thyroid hormone withdrawal or preparation with recombinant human TSH (rhTSH) 6-12 months after ablation. RESULTS: Overall, remnant ablation was successful in 121/133 (91%) patients. There was no statistically significant difference in the success of ablation between Group 1 and Group 2 (87.5% versus 93%, P=0.273). CONCLUSION: Therefore, for thyroid remnant ablation after thyroid hormone withdrawal, an administered I-131 dose of 2220 MBq is just as effective as 3700 MBq and has the potential for fewer longterm side effects.

Participation of women in clinical trials of drug therapies: a context for the controversies.

Women's participation in clinical trials, particularly those involving drugs, has been said to be both overrepresented and underrepresented. How can this be? Studies of participation are compared and contrasted to elucidate some reasons for this contradiction. The history of women's participation in clinical trials is chronicled through policies and regulations filled with restrictions. Since 1993, however, the National Institutes of Health has mandated, and the Food and Drug Administration has emphasized, inclusion of women in clinical trials, only to be thwarted by other regulations excluding many women. Gender-specific analyses are required to detect gender differences in effects of pharmaceutical and nonpharmaceutical interventions, but they are seldom performed. The exclusion of women from clinical trials means that women's healthcare is compromised by lack of sex-specific information about dosing of drugs and unique uses of drugs. A database, although currently quite limited, tracks the participation of women in clinical trials funded by federal agencies, industries, and nonprofit groups. Federal regulations have recently changed. Additional changes in access to all phases of clinical trials and enhanced monitoring of clinical trials are recommended.

Presbyopia, accommodation, and the mature catenary.

OBJECTIVE: To demonstrate a plausible explanation of aging changes and to reduce the controversy relative to accommodation by using a mechanical model of the catenary theory of lens change. MECHANICAL MODELING: A mechanical model was used to simulate a human lens in both the accommodated and unaccommodated state to demonstrate changes in the mechanism of accommodation with age. METHODS: Fluid-filled latex balloons were supported by a plastic wrap hammock to form a catenary that models the human lens. Increasing volumes were used to simulate that of the aging lens, and variations in curvature were measured. MAIN OUTCOME MEASURES: The degree of curvature of a simulated anterior lens surface was measured and compared with mathematical modeling of its optical surface based on the catenary hydraulic suspension theory. RESULTS: The measurements showed that accommodative loss and other features such as mass displacement, reproducible lens surfaces, and zonule support are consistent with the catenary theory of accommodation and an increasing lens volume with age. CONCLUSIONS: The catenary theory of accommodation provides a basis for evaluating age changes of the human lens. Variable results with surgical procedures for presbyopia are also predictable with the model. These results can be used to provide a basis for intraocular lens design.

Droperidol vs. prochlorperazine for benign headaches in the emergency department.

OBJECTIVE: To compare the efficacy of droperidol with that of prochlorperazine for the treatment of benign headaches in emergency department (ED) patients. METHODS: Prospective, randomized clinical trial in an urban ED. Patients were given either droperidol, 5 mg intramuscular (IM) or 2.5 mg intravenous (IV), or prochlorperazine, 10 mg IM or 10 mg IV. Measurements included side effects and the patient's pain perception as measured on a 100-mm visual analog scale (VAS) at baseline, 30, and 60 minutes after the medication was given. Data were analyzed using chi-square, two-tailed t-tests, and two-way analysis of variance (ANOVA) when appropriate. RESULTS: During an eight-month period, 168 patients were enrolled. Eighty-two (48.8%) of the patients received droperidol; 86 (51.2%) received prochlorperazine. In the droperidol group, 49 (59.6%) received IM administration and 33 (40.4%) IV. In the prochlorperazine group, 57 (66.3%) received IM administration and 29 (33.7%) IV. Sixty minutes after the medication, the mean decrease in the VAS scores was 81.4% for droperidol and 66.9% for prochlorperazine (p = 0.001). At 30 minutes, 60.9% of the patients receiving droperidol and 44.2% of the patients receiving prochlorperazine had obtained at least a 50% reduction in their VAS scores (p = 0.09). At 60 minutes, 90.2% of the patients receiving droperidol and 68.6% of the patients receiving prochlorperazine had at least a 50% reduction in their VAS scores (p = 0.017). No difference between IM dosing and IV dosing was detected. Side effects, including dystonia, akathisia, and decreased level of consciousness, were seen in 15.2% of the patients receiving droperidol and 9.61% of the patients receiving prochlorperazine. No significant or persisting morbidity was detected. CONCLUSIONS: Droperidol was more effective than prochlorperazine in relieving pain associated with benign headaches.

Human parathyroid hormone 1-34 reverses bone loss in ovariectomized mice.

The experimental work characterizing the anabolic effect of parathyroid hormone (PTH) in bone has been performed in nonmurine ovariectomized (OVX) animals, mainly rats. A major drawback of these animal models is their inaccessibility to genetic manipulations such as gene knockout and overexpression. Therefore, this study on PTH anabolic activity was carried out in OVX mice that can be manipulated genetically in future studies. Adult Swiss-Webster mice were OVX, and after the fifth postoperative week were treated intermittently with human PTH(1-34) [hPTH(1-34)] or vehicle for 4 weeks. Femoral bones were evaluated by microcomputed tomography (microCT) followed by histomorphometry. A tight correlation was observed between trabecular density (BV/TV) determinations made by both methods. The BV/TV showed >60% loss in the distal metaphysis in 5-week and 9-week post-OVX, non-PTH-treated animals. PTH induced a approximately 35% recovery of this loss and a approximately 40% reversal of the associated decreases in trabecular number (Tb.N) and connectivity. PTH also caused a shift from single to double calcein-labeled trabecular surfaces, a significant enhancement in the mineralizing perimeter and a respective 2- and 3-fold stimulation of the mineral appositional rate (MAR) and bone formation rate (BFR). Diaphyseal endosteal cortical MAR and thickness also were increased with a high correlation between these parameters. These data show that OVX osteoporotic mice respond to PTH by increased osteoblast activity and the consequent restoration of trabecular network. The Swiss-Webster mouse model will be useful in future studies investigating molecular mechanisms involved in the pathogenesis and treatment of osteoporosis, including the mechanisms of action of known and future bone antiresorptive and anabolic agents.

The tylosin-biosynthetic genes of Streptomyces fradiae.

The tylosin-biosynthetic (tyl) gene cluster occupies about 1% of the genome of Streptomycesfradiae and includes at least 43 open reading frames. In addition to structural genes required for tylosin production, the tyl cluster contains three resistance determinants and several regulatory genes. Tylosin production is evidently controlled by pathway-specific and pleiotropic regulators with the likely involvement of y-butyrolactone signalling factors. Accumulation of the polyketide aglycone is controlled by glycosylated macrolides and optimal performance of the complex polyketide synthase enzyme requires the activity of an editing thioesterase.

Skin-sparing mastectomy with immediate breast reconstruction: a critical analysis of local recurrence.

PURPOSE: The purpose of this study was to provide follow-up data regarding the incidence of local breast cancer recurrence in patients undergoing skin-sparing mastectomy versus conventional non-skin-sparing mastectomy methods. PATIENTS AND METHODS: A retrospective follow-up study and analysis were performed of patients who underwent mastectomies for invasive breast cancer at The New York Presbyterian Hospital, Cornell University Medical College and Strang-Cornell Breast Center between 1990 and 1998. RESULTS: A total of 198 patients were identified in this study, and the mean follow-up was 49 months. This group included 71 patients who underwent skin-sparing mastectomy and 127 who underwent non-skin-sparing mastectomy procedures. No statistical differences in local recurrence rates were demonstrated between patients treated with skin-sparing mastectomy and those who underwent non-skin-sparing mastectomy. Local recurrence was present in four of 71 (5.6%) patients undergoing skin-sparing mastectomy and in five of 127 (3.9%) of those undergoing non-skin-sparing mastectomy. CONCLUSIONS: The use of skin-sparing mastectomy does not lead to an increase in local recurrence rates when compared with conventional non-sparing mastectomies and provides for improved aesthetic results after immediate reconstruction.

Acute cardiac ischemia in patients with cocaine-associated complaints: results of a multicenter trial.

STUDY OBJECTIVE: To describe the characteristics of a large group of patients who presented to emergency departments with cocaine-associated symptoms consistent with acute cardiac ischemia (ACI) and to determine the incidence of confirmed ACI including acute myocardial infarction (AMI) in this population. METHODS: We performed a substudy on all patients in a multicenter prospective clinical trial (the Acute Cardiac Ischemia-Time Insensitive Predictive Instrument [ACI-TIPI] Clinical Trial) that enrolled ED patients with chest pain or other symptoms consistent with ACI including subjects with identified cocaine use. Demographic and clinical features, including initial and follow-up clinical data, ECGs, and tests to determine serum creatine kinase isoenzyme MB subunit concentrations, were analyzed. Diagnoses of AMI followed the World Health Organization criteria for AMI and of angina pectoris, the Canadian Cardiovascular Society Classification. RESULTS: Of the 10,689 patients enrolled in the trial, 293 (2.7%) had cocaine-associated complaints. Among the 10 participating hospitals, the incidence of patients with cocaine-associated symptoms varied from 0.3% to 8.4%. Only 6 patients (2.0%, 95% confidence interval [CI] 0.76% to 4.4%) had a diagnosis of ACI; 4 (1.4%, 95% CI 0.37% to 3.5%) had unstable angina, and 2 (0.7%, 95% CI 0.08% to 2.4%) had AMI. Although patients with cocaine-induced complaints were as likely to be admitted to the coronary care unit compared with all study patients without cocaine use (14% versus 18%, P =.14, difference not significant), these patients were much less likely to have confirmed unstable angina (1.4% versus 9.3%, P <.001) or AMI (0. 7% versus 8.6%, P <.001). Compared with patients younger than 45 years, patients with cocaine usage were more likely to be admitted to the ICU (14% versus 8.0%, P =.0018) but less likely to have confirmed AMI (0.7% versus 2.8%, P =.033). CONCLUSION: Patients presenting to EDs with cocaine-associated chest pain or related symptoms infrequently had ACI, and even less so, AMI. This suggests the need for selectivity in the hospitalization of patients with such cocaine-associated symptoms.

Clinical characteristics as predictors of recurrent alcohol-related seizures.

OBJECTIVE: To determine whether clinical data available in the emergency department can accurately predict a subset of patients at low risk of developing recurrent seizures following one or more initial alcohol-related seizures in the out-of-hospital arena. METHODS: This was a retrospective secondary analysis of data obtained from the placebo arms of two prospective, randomized trials of drug treatments for the prevention of recurrent alcohol-related seizures. Subjects with and without one or more recurrent alcohol-related seizures during the study period were compared according to the following characteristics: 1) age, 2) gender, 3) daily ethanol consumption, 4) years of ethanol abuse, 5) previous alcohol-related seizure, 6) previous seizure of other etiology, 7) temperature, 8) heart rate, 9) systolic blood pressure, 10) diastolic blood pressure, 11) respiratory rate, and 12) ethanol level. Data were analyzed with t-tests and chi-square where appropriate. RESULTS: One hundred five placebo-treated patients were analyzed and 31 (30%) developed recurrent alcohol-related seizures. None of the listed characteristics were statistically different between the two groups except for the initial ethanol level. Subjects with an ethanol level higher than 100 mg/dL were less likely (0%) to develop recurrent seizures than patients with a level equal to or below 100 mg/dL (36%) (p < 0.01). CONCLUSIONS: An initial ethanol level higher than 100 mg/dL was significantly associated with a low risk for recurrent alcohol-related seizures during the observation period. No other low-risk clinical characteristics could be identified.

Outcome of treatment for limb and limb girdle sarcomas at the Royal Marsden Hospital.

AIMS: In this study we aimed to determine local recurrence, mortality an d amputation rates in patients presenting with limb and limb girdle soft tissue sarcomas. METHOD: A review of all 439 patients presenting with p rimary or recurrent soft tissue sarcomas of limb and limb girdle to the Royal Marsden Hospital between 1989 and 1995 was carried out. RESULTS: The local recurrence rate was 15.5% and the mortality rate was 30%, with a median follow up of 3.2 years and an overall amputation rate of 4.8%. CONCLUSION: The outcome of limb and limb girdle sarcomas in this study i s comparable to those reported elsewhere.