ARTISTRY-7: phase III trial of nemvaleukin alfa plus pembrolizumab vs chemotherapy for platinum-resistant ovarian cancer.

Standard single-agent nonplatinum chemotherapy provides only modest benefit in a small proportion of patients with platinum-resistant/-refractory ovarian cancer, with objective response rates of 6-20% and progression-free survival of ≈3-4 months. Nemvaleukin alfa (nemvaleukin, ALKS 4230) is a novel cytokine designed to capture and expand the therapeutic potential of high-dose interleukin-2 (IL-2) while mitigating its associated toxicity issues. Nemvaleukin preferentially activates cytotoxic CD8+ T cells and natural killer cells with minimal, non-dose-dependent effects on CD4+ regulatory T cells. The global, randomized, open-label, phase III ARTISTRY-7 trial will compare efficacy and safety of nemvaleukin plus pembrolizumab with chemotherapy in patients with platinum-resistant ovarian cancer. The primary end point is investigator-assessed progression-free survival. Clinical Trial Registration: GOG-3063; ENGOT-OV68; NCT05092360 (ClinicalTrials.gov).

In many patients with ovarian cancer who are treated with platinum-based chemotherapy, the tumor comes back after a few months and fails to respond to repeated treatment. This type of disease is called platinum-resistant ovarian cancer (PROC). Researchers are searching for new medicines to help more patients with PROC. One treatment approach that has shown promise in different cancers is called immunotherapy. These medicines work by helping the body's immune system attack cancer cells. One of the immunotherapies being studied is called nemvaleukin. It is designed to trigger specific immune responses that may result in the immune system attacking cancer cells while potentially avoiding other immune responses that can block the attack or cause certain unwanted side effects. Nemvaleukin is being studied in a variety of cancer types. In a worldwide clinical trial called ARTISTRY-7, researchers are investigating how nemvaleukin works in patients with PROC when given with another immunotherapy called pembrolizumab. Patients who participate in this trial will be randomly assigned to one of four treatment groups: the combination of nemvaleukin and pembrolizumab, nemvaleukin by itself, pembrolizumab by itself, or a type of chemotherapy selected by the treating physician. The main purpose of ARTISTRY-7 is to understand whether the combination of nemvaleukin and pembrolizumab helps patients with PROC live longer without their cancer getting worse. At the time of this writing, ARTISTRY-7 is open for new patients to join.

A meta-epidemiological study of bias in randomized clinical trials of open and laparoscopic surgery.

BACKGROUND: Blinding, random sequence generation, and allocation concealment are established strategies to minimize bias in RCTs. Meta-epidemiological studies of drug trials have demonstrated exaggerated treatment effects in RCTs where such methods were not employed. As blinding is more difficult in surgical trials it is important to determine whether this applies to them. The study aimed to investigate this using systematic meta-epidemiological methods. METHOD: The Cochrane Database of Systematic Reviews was searched for systematic reviews of RCTs that compared laparoscopic and open abdominal surgical procedures. Each review was then scrutinized to determine whether at least one of the included trials was blinded. Eligible reviews were updated and individual RCTs retrieved. Extracted data included the primary outcomes of interest (length of stay and complications), secondary outcomes and a risk of bias assessment. A multistep meta-regression analysis was then performed to obtain an overall difference in the reported outcome differences between trials that employed each bias-minimization strategy, and those that did not. RESULTS: Some 316 RCTs were included, reporting on eight different procedures. Patient-blinded RCTs reported a smaller difference in length of stay between laparoscopic and open groups (difference of standardized mean differences -0·36 (95 per cent c.i. -0·73 to 0·00)) and complications (ratio of odds ratios 0·76 (95 per cent c.i. 0·61 to 0·93)). Blinding of postoperative carers and outcome assessors had similar effects. CONCLUSION: Lack of blinding significantly altered the treatment effect estimates of RCTs comparing laparoscopic and open surgery. Blinding should be implemented in surgical RCTs where possible to avoid systematic bias.

The complex multi-sectoral impacts of drought: Evidence from a mountainous basin in the Central Spanish Pyrenees.

We analyzed the impacts of drought severity on a variety of sectors in a topographically complex basin (the upper Aragón basin 2181 km2) in the Central Spanish Pyrenees. Using diverse data sources including meteorological and hydrological observations, remote sensing and tree rings, we analyze the possible hydrological implications of drought occurrence and severity on water availability in various sectors, including downstream impacts on irrigation water supply for crop production. Results suggest varying responses in forest activity, secondary growth, plant phenology, and crop yield to drought impacts. Specifically, meteorological droughts have distinct impacts downstream, mainly due to water partitioning between streamflow and irrigation channels that transport water to crop producing areas. This implies that drought severity can extend beyond the physical boundaries of the basin, with impacts on crop productivity. This complex response to drought impacts makes it difficult to develop objective basin-scale operational definitions for monitoring drought severity. Moreover, given the high spatial variability in responses to drought across sectors, it is difficult to establish reliable drought thresholds from indices that are relevant across all socio-economic sectors. The anthropogenic impacts (e.g. water regulation projects, ecosystem services, land cover and land use changes) pose further challenges to assessing the response of different systems to drought severity. This study stresses the need to consider the seasonality of drought impacts and appropriate drought time scales to adequately assess and understand their complexity.

Axial length measurement using optical versus immersion ultrasound: Impact on predicted refractive outcome following cataract surgery

Objective: To evaluate optical vs immersion ultrasound biometry to measure ocular axial length (the distance between the anterior surface of the cornea and the fovea). Design and Methodology: The axial length of the eye is usually measured by A-scan ultrasonography or optical coherence biometry. Optical biometry is the gold standard, but cannot be used for patients with dense cataracts, when immersion ultrasound biometry is utilized. Both optical and immersion ultrasound biometry were performed on patients scheduled to undergo cataract surgery between November 2017 and November 2018. Statistical difference was determined using a two tailed t-test. Results: There was no statistical difference between mean axial length measured using optical biometry (23.83 mm ± 1.34) vs immersion ultrasound biometry (23.80 mm ± 1.30); t(46)= -0.05, p=0.96. Conclusion: Accurate axial length measurement is essential for reliable intraocular lens power calculation, minimizing refractive error following cataract surgery. The cost of optical coherence biometry equipment is prohibitive and this technology is not readily available in the public hospital eye clinics. There was no statistical difference in axial length measured using optical biometry and immersion ultrasound. This suggests that in low resource settings, immersion biometry can be utilized without compromising surgical outcome.

Prognostic factors for stage III epithelial ovarian cancer treated with intraperitoneal chemotherapy: a Gynecologic Oncology Group study.

OBJECTIVES: To determine prognostic factors for survival in ovarian cancer patients treated with intraperitoneal (IP) chemotherapy using ancillary data from cooperative group clinical trials. METHODS: Data were collected from 428 patients with stage III ovarian cancer who underwent optimal surgical cytoreduction (<1 cm) followed by IP paclitaxel/platinum chemotherapy. Primary endpoints were progression free survival (PFS) and overall survival (OS). Potential prognostic variables were included in Cox proportional hazard regression models. Multivariate analysis was conducted to identify independent prognostic factors. RESULTS: Median PFS was 24.9 months (95% CI, 23.0-29.2) and median OS was 61.8 months (95% CI, 55.5-69.8). Predictors for PFS were histology, surgical stage and residual disease. Age, histology, and residual disease were prognostic for OS. There were no differences in the hazard ratio for death or progression between patients with positive, negative, or unknown lymph node status. For patients receiving IP chemotherapy (n=428), 36% of patients had no residual disease with median PFS of 43.2 months (95% CI 32.5-60.4) and median OS of 110 months (95% CI, 60.0-161.3). CONCLUSIONS: Age, histology, and extent of residual disease were predictors of OS in stage III patients treated with IP chemotherapy following optimal cytoreduction. Patients with no residual disease following primary surgery that are treated with adjuvant platinum based IP chemotherapy have survival measures that exceed any rates previously seen in this population.

Is the retrojugular approach safer than the conventional approach for carotid endarterectomy?

BACKGROUND: The retrojugular approach is promoted as an alternative to traditional antejugular carotid endarterectomy. Absence of named posterior venous branches and ease of distal internal carotid dissection reduce time for carotid exposure together with improved distal exposure. However, a higher incidence of local nerve injury and persistent hoarse voice has been reported. We compare the incidence of these and other complications for the antejugular and retrojugular approaches. DESIGN: This is a nonrandomised retrospective review of prospectively collected data on consecutive patients undergoing carotid endarterectomy. RESULTS: Our 178 patients formed two groups who were homogeneous in terms of sex and age. Mean operative times, patch usage, and general/local anaesthesia did not differ significantly for the two groups. Postoperative complications including transient ischemic attack (TIA), major stroke, or death; hypertension; miosis; and hypoglossal injury were similar for the two groups. However, there was a significantly increased incidence of persistent hoarse voice (p < 0.05) in the retrojugular group. CONCLUSIONS: Reports of increased incidence of persistent hoarse voice associated with the retrojugular approach to carotid endarterectomy are supported by our findings, which point to a learning curve effect. A randomized controlled trial would be necessary before any strong recommendation could be made for or against the retrojugular approach.

Vulvar cancer in young women: demographic features and outcome evaluation.

OBJECTIVE: The objective of the study was to identify prognostic and environmental factors associated with vulvar carcinoma in young women. STUDY DESIGN: This study was a review of patients younger than 45 years who were diagnosed with vulvar squamous cell carcinoma between 1994 and 2006. RESULTS: Fifty-six patients were identified. Median age was 38 years and median follow-up was 25.3 months. Fifty-eight percent of patients presented with stage I disease; 77% smoked tobacco. Of patients with advanced disease, 53.3% were smokers, 40% had human papillomavirus (HPV) exposure, 46.7% had a history of vulvar intraepithelial neoplasia (VIN), and 6.7% were immunocompromised. Symptoms were present for more than 12 months in 47%, but symptom duration did not correlate with stage (P = .42) or positive lymph nodes (P = .28). Disease recurred in 10.7% and 5.4% died of disease. CONCLUSION: Young women with vulvar cancer tend to have early-stage disease, smoke, have a history of HPV, and have VIN. Many of the factors that place these patients at continuous risk are modifiable.

Stage IVB endometrial cancer: does applying an ovarian cancer treatment paradigm result in similar outcomes? A case-control analysis.

OBJECTIVE: The pattern of metastasis for Stage IV endometrial carcinoma (EC) is similar to that for ovarian carcinoma (OC), hence the goal of surgical management for both diseases is optimal cytoreduction (CRS) followed by adjuvant chemotherapy. The objective of this study is to evaluate overall survival (OS) and progression-free survival (PFS) in patients with advanced EC compared to a cohort of patients with OC matched for age and residual disease. METHODS: Patients with Stage IVB EC treated with curative intent between the years of 1990-2006 were identified and data abstracted regarding demographics, surgical procedures, pathologic factors, and follow-up. Two patients with Stage IIIC OC were matched for each Stage IVB EC based on age and residual disease. Stage IVB EC patients with distant metastasis were excluded. All OC patients underwent primary CRS and received combination platinum based chemotherapy. PFS and OS were evaluated using Kaplan-Meier curves and log-rank analysis. RESULTS: 55 patients with Stage IVB EC underwent primary CRS and adjuvant therapy with curative intent. Optimal CRS (<1 cm residual disease) was achieved in 87% (n=48). The most common histologic subtypes were serous (53%, n=29), endometrioid (44%, n=24) and clear cell (3%, n=2). Adjuvant therapy with curative intent included platinum based combination chemotherapy (60%, n=33), platinum based chemotherapy with radiation (25%, n=14), and radiation alone (15%, n=8) depending on the time period of treatment. Seven patients had residual disease >1 cm following CRS, 6 of whom received chemotherapy alone. Two-year OS for the entire cohort was 52 vs. 76% for patients with EC compared to OC (p=0.008). For suboptimal EC vs. OC patients was 33% vs. 66% for OC patients (p=NS). EC patients with optimal CRS had OS of 57% at 2 years compared to 82% for OC patients (p=0.02). Median PFS was 13 months vs. 20 months for all EC and OC patients, respectively (p=0.01). Using a Cox proportional hazards model, optimal CRS was associated with a survival advantage over suboptimal for EC patients with a hazard ratio of 2.4. CONCLUSIONS: The treatment paradigm for advanced EC has undergone a drastic evolution from palliation to CRS and combination chemotherapy. Despite similarities in disease distribution and histology, OS for EC patients with intraperitoneal metastasis does not approach that of patients with advanced OC. Further research to identify the molecular characteristics of EC may identify important differences from OC and provide insight for the development of novel primary and salvage treatment strategies for patients with advanced EC.

Cervical dysplasia among women over 35 years of age.

OBJECTIVE: The objective of the study was to review the cytologic and histopathologic features among women 35 years of age or older with cervical dysplasia. STUDY DESIGN: Patients presenting between 2001 and 2005 were included. Patients were labeled as pre- (PRE) or postmenopausal (POST) based on age younger than or 50 years old or older. Statistics were performed using SAS 8.0. RESULTS: Three hundred fifty-nine patients were identified: 270 PRE and 89 POST. PRE and POST patients had similar referral cytology with atypical cells of undetermined significance (ASC)/low-grade squamous intraepithelial lesion (LSIL) in 60% and 65% and high-grade squamous intraepithelial lesion (HSIL) in 35% and 27%, respectively. Among patients with ASC/LSIL, POST had significantly more cervical intraepithelial neoplasia (CIN) 3 (41% vs 29%; P = .027) as well as more malignancies (17 vs 0%; P = .002). Among patients referred for loop electrical excisional procedure secondary to HSIL cytology not explained by colposcopy, CIN 2 or greater was identified more often in POST (71 vs 32%; P = .03). CONCLUSION: Our data demonstrate a high proportion of severe cervical dysplasia in age groups traditionally thought to have less risk than younger patients.

Human tumor antigens Tn and sialyl Tn arise from mutations in Cosmc.

Neoplastic lesions typically express specific carbohydrate antigens on glycolipids, mucins, and other glycoproteins. Such antigens are often under epigenetic control and are subject to reversion and loss upon therapeutic selective pressure. We report here that two of the most common tumor-associated carbohydrate antigens, Tn and sialyl Tn (STn), result from somatic mutations in the gene Cosmc that encodes a molecular chaperone required for formation of the active T-synthase. Diverse neoplastic lesions, including colon cancer and melanoma-derived cells lines, expressed both Tn and STn antigen due to loss-of-function mutations in Cosmc. In addition, two human cervical cancer specimens that showed expression of the Tn/STn antigens were also found to have mutations in Cosmc and loss of heterozygosity for the cross-linked Cosmc locus. This is the first example of somatic mutations in multiple types of cancers that cause global alterations in cell surface carbohydrate antigen expression.

Pathologic findings and outcomes for octogenarians presenting with uterine malignancy.

OBJECTIVE: We evaluated prognostic, demographic and outcome data for patients>80 years old with uterine cancer (UC). METHODS: A retrospective review of clinical records was performed. Categorical data were compared using Fisher's exact test and Kaplan-Meier for survival data. RESULTS: Sixty-five patients were identified with a mean age of 84 and BMI 27. Sixty-five percent of patients had medical co-morbidities. Forty-two (65%) were Stage I; 10 (15%) were Stage II; 8 (12%) were Stage III; and 5 (8%) were Stage IV. Stage I patients included those identified via hysterectomy with lymph nodes (LND) (30) or clinical impression (12). Comparing clinically Stage I UC to those with LND, the clinical group was older (86 vs. 83; p=0.01) and tended to have more medical co-morbidity (89% vs. 63%; p=0.14). Two-year overall survival (OS) among unstaged vs. staged patients was 62% vs. 77%; p=0.11. Among staged patients with Stage I UC, 21 (70%) met high intermediate risk (HIR) criteria per GOG 99 and 90% received no adjuvant therapy. Three patients (16%) recurred with 1 (5%) locoregional recurrence. Two-year OS is 77%. CONCLUSION: Elderly patients with UC have features associated with extrauterine spread. Both clinically and surgically staged Stage I patients had excellent OS at 2 years despite no adjuvant therapy. Prevalent medical co-morbidities may impact survival more than recurrence risk. The 23% recurrence rate among HIR patients in GOG 99 was not observed in our data, suggesting that observation for elderly Stage I patients is acceptable.

A LEEP cervical conization is rarely indicated for a two-step discrepancy.

OBJECTIVES: The current indications for conization of the cervix include a 2-step discrepancy between cervical cytological and histological findings. We sought to determine the utility of a loop electrocautery excision procedure (LEEP) cone for a 2-step discrepancy. METHODS: A retrospective institutional review board-approved chart review was performed on all women recommended to undergo a LEEP secondary to a discrepancy between a referral high-grade squamous intraepithelial lesion cytological finding and a subsequent colposcopic biopsy result revealing either normal or cervical intraepithelial neoplasia (CIN) 1 histological finding; CIN 2 was excluded from the study. Statistical analysis was performed using SAS 9 (SAS Institute, Inc, Cary, NC). The results were considered significant if a p value less than or equal to.05 was demonstrated. RESULTS: Fifty-nine patients received a LEEP for a 2-step discrepancy between cytological and histological findings. Twenty-seven patients had a second pass or LEEP cone. Among the patients with a normal cervical biopsy result and a high-grade cytological finding, 10 (29%) of 34 had normal histological findings, as revealed by LEEP, and 14 (41%) of 34 had CIN 3; 16 (64%) of 25 patients with high-grade cytological finding and CIN 1 biopsy finding had CIN 3, as revealed by LEEP. Compared with patients with an initial normal cervical biopsy result, those with CIN 1 on initial biopsy were more likely to have CIN 3 on their LEEP findings (p =.08). Twenty-seven of 59 patients underwent a LEEP cone surgery; 1 of 27 had CIN 3 finding in the second-pass portion. This was associated with a CIN 3 identified on the first pass and associated with positive margins. The second pass of the LEEP cone failed to demonstrate CIN 96% of the time (p < .0001). Patients with a normal or a CIN 1 finding on the first pass had a normal finding on the second pass in 100% of cases. CONCLUSIONS: A LEEP cone is rarely indicated for the evaluation of a 2-step discrepancy. A randomized trial of this finding is warranted.

Gynecologic Oncology Group risk groups for vulvar carcinoma: improvement in survival in the modern era.

OBJECTIVE: Patients with vulvar cancer were stratified into risk groups for survival based on surgicopathologic findings from a prospective study conducted by the Gynecologic Oncology Group from 1977-1984. The purpose of this study is to reassess these risk groups in patients treated in an era of contemporary management. METHODS: Patients with vulvar carcinoma were identified from 1990-2005 for retrospective analysis. Charts were abstracted for clinical, histopathologic and surgical data, and patients stratified into four risk groups for survival based on the clinical size of tumor and extent of lymph node metastasis. Univariate and multivariate characteristics were evaluated and 5-year survival determined by Kaplan-Meier method. RESULTS: 175 patients were identified that underwent surgical management with a median age at diagnosis of 59.9 years. Stage distribution included: I (n=89, 51%), II (n=53, 30%), III (n=29, 17%), and IV (n=4, 2%). Stratification into risk groups included: minimal (n=89, 51%), low (n=69, 40%), intermediate (n=11, 6%), and high (n=6; 3%). The survival rate was 100%, 97%, 82% and 100%, respectively, at median follow-up of 54.5 months. Comparatively, the survival rates for historic groups were 97.9%, 87.4%, 74.8% and 29.0%. Using multivariate analysis, age (p=0.04) and lymph node metastasis (p=0.009) were predictive of survival. CONCLUSIONS: Survival among the minimal and low risk groups is preserved in spite of less radical surgery. 5-year survival rate for intermediate and high risk patients also appears to be improved. This is likely a result of advancement in adjuvant chemo-radiation and a younger patient population that presents with less advanced disease.

Third stage of labor.

All staff involved in obstetric care should be competent in performing active management of the third stage of labor. Active management has been shown to be clearly superior to physiologic or expectant management. Comparison of the various uterotonic agents has pointed to misoprostol as a potential first-line agent in treating obstetric hemorrhage. Its cost, routes of delivery, and efficacy make it an appealing drug in urban and rural settings. By being facile with the active management of labor and the prompt recognition and treatment of postpartum hemorrhage, the morbidity from significant blood loss and subsequent surgery can be reduced significantly.

Well-differentiated papillary mesothelioma of the uterine serosa identified at cesarean section: a case report.

BACKGROUND: Peritoneal mesotheliomas encompass a variety of benign and malignant neoplasms. Well-differentiated papillary mesothelioma (WDPM) is uncommon, is thought to be of low malignant potential and is often discovered incidentally during abdominal or pelvic surgery. We describe a highly unusual case in which WDPM arising from the uterine serosa was identified at the time of cesarean delivery. CASE: A 21-year-old primigravida underwent cesarean delivery at term for arrest of the active phase of labor. A 2-cm, polypoid lesion was excised from the posterior uterine fundus; final pathology showed well-differentiated papillary mesothelioma. Subsequent examination and computed tomography were negative. A follow-up laparoscopic examination with abdominal washing for cytology and peritoneal biopsies revealed no residual disease. CONCLUSION: Survey of the pelvic cavity during cesarean section is important. Knowledge of the variable disease spectrum of mesothelioma is important in patient counseling and management. Differentiating between WDPM and malignant mesothelioma, other peritoneal tumors and implants from primary sites is necessary to avoid overtreatment.

Dye-determined amniotic fluid volume and intrapartum/neonatal outcome.

OBJECTIVE: To ascertain if a dye-determined amniotic fluid volume was predictive of intrapartum and perinatal outcome. MATERIALS AND METHODS: The low and normal amniotic fluid volumes (< 5th percentile and > or =5th percentile for gestational age) and the raw dye-determined amniotic fluid distributions were correlated with 10 clinical outcome measures in 74 pregnancies. RESULTS: In this observational study, median gestational age at delivery was 36 weeks (range 26 to 41) and 16 deliveries were for fetal distress (14 Cesarean and two forceps). There were no differences between the outcomes of pregnancies with low and normal amniotic fluid volumes for any of the clinical outcomes (variable decelerations influencing delivery, p=0.381; late decelerations, p=0.875; Cesarean births for fetal intolerance of labor, p=0.259; intrauterine growth restriction, p=0.998; or umbilical cord arterial pH< 7.2, p=0.259). Analogous results were obtained when the gestational age-adjusted amniotic fluid volumes were compared directly between the pregnancies with normal and abnormal outcomes. There was no difference between the mean amniotic fluid volumes in those pregnancies with variable decelerations influencing delivery (p=0.287), late decelerations (p=0.555), Cesarean births for fetal intolerance of labor (p=0.310), intrauterine growth restriction (p=0.267) or umbilical cord arterial pH< 7.2, and the pregnancies without these intrapartum events. Reduced variability was more commonly observed in pregnancies with higher amniotic fluid volumes (p=0.038, 771 ml, 95% CI 468 to 1269, compared to those without normal variability 444 ml, 95% CI 374 to 526). CONCLUSIONS: Dye-determined amniotic fluid volume does not appear to be predictive of adverse intrapartum and neonatal outcome.

ASIC or PIC? Implantable stimulators based on semi-custom CMOS technology or low-power microcontroller architecture.

To gain a better understanding of the effects of chronic stimulation on mammalian muscles we needed to generate patterns of greater variety and complexity than simple constant-frequency or burst patterns. We describe here two approaches to the design of implantable neuromuscular stimulators that can satisfy these requirements. Devices of both types were developed and used in long-term experiments. The first device was based on a semi-custom Application Specific Integrated Circuit (ASIC). This approach has the advantage that the circuit can be completely tested at every stage of development and production, assuring a high degree of reliability. It has the drawback of inflexibility: the patterns are produced by state machines implemented in silicon, so each new set of patterns requires a fresh production run, which is costly and time-consuming. The second device was based on a commercial microcontroller (Microchip PIC16C84). The functionality of this type of circuit is specified in software rather than in silicon hardware, allowing a single device to be programmed for different functions. With the use of features designed to improve fault-tolerance we found this approach to be as reliable as that based on ASICs. The encapsulated devices can easily be accommodated subcutaneously on the flank of a rabbit and a recent version is small enough to implant into the peritoneal cavity of rats. The current devices are programmed with a predetermined set of 12 patterns before assembly; the desired pattern is selected after implantation with an electronic flash gun. The operating current drain is less than 40 microA.

Prevalence of dyspepsia: the epidemiology of overlapping symptoms.

Studies of the epidemiology of dyspepsia have been complicated by the use of different symptom definitions, subject populations and time frames of investigation. Published figures for the prevalence of dyspepsia vary from 20% to 40%, of which perhaps only a quarter can be attributed to peptic ulcer disease. General practitioners see only a fraction of the dyspepsia within the community, the majority of which is either ignored or treated by self-medication. However, dyspepsia still accounts for about 3-4% of all general practice consultations and for about 14% of all patients attending. In about half of all cases, even extensive investigation reveals no underlying organic lesion. There has been much recent interest in the clinical value of grouping dyspeptic symptoms into particular subtypes. These have been called ulcer-like, dysmotility-like and reflux-like. Although these patterns have descriptive value, there is no evidence that they result from discrete pathophysiological processes. Indeed, studies both in general practice and in the community show a large degree of overlap between them.

Bone lead content assessed by L-line x-ray fluorescence in lead-exposed and non-lead-exposed suburban populations in the United States.

Measurements of lead (Pb) in bone reflect cumulative Pb exposure, whereas blood Pb levels are indices of absorption during the previous 21-30 days. This study was undertaken to estimate bone Pb concentrations by L-line x-ray fluorescence (LXRF) in a United States suburban population which was exposed to unusually high levels of Pb in emissions from an adjacent factory during 1963-1981, compared with concentrations similarly estimated in a matched suburban community without unusual Pb exposure. The mean bone Pb value in 269 residents of the highly exposed suburb (15 ppm) was 3-fold greater than that of the reference suburb (5 ppm). LXRF estimates of bone Pb identified those individuals at risk for adverse effects of Pb, whereas blood Pb levels were uninformative. Average LXRF-estimated bone Pb concentrations in residents of the unusually exposed suburb approximated estimated values in workers at Pb-processing factories.