Electroimmuno- and immunonephelometric assays of apolipoprotein A-I by using a mixture of monoclonal antibodies

The use of mixtures of well-defined monoclonal antibodies may represent a step forward in the standardization of immunochemical assays. We developed and optimized working conditions for using such a mixture to determine apolipoprotein A-I in human sera by two independent techniques (electroimmuno- and immunonephelometric-assays). Six monoclonal antibodies, each addressed to distinct epitopes located at the surface of apolipoprotein A-I, were used in combination to permit a reproducible measurement of the protein, without prior delipidation of samples. Parallel standard curves for a high-density lipoprotein subfraction (HDL3, the primary standard) and a reference serum (the secondary standard) were obtained. Within- and between-run coefficients of variation were acceptable for both methods. Apolipoprotein A-I concentrations, as measured in 60 subjects selected to present a large range of apolipoprotein content by electroimmunoassay (y1) and immunonephelometric assay (y2) with monoclonal antibodies, compared well with those measured by the same techniques but with polyclonal antibodies (x): r1 = 0.96, r2 = 0.99; y1 = 1.19x - 0.11 g/L, y2 = 0.98x. Comparison of results obtained by electroimmunoassay and immunonephelometric assay performed with monoclonal antibodies was also good: r = 0.96; y2 = 1.08y1 + 0.13 g/L.     

End-tidal Carbon Dioxide Monitoring during Procedural Sedation

OBJECTIVE: To prospectively determine whether end-tidal carbon dioxide (ETCO2) monitors can detect respiratory depression (RD) and the level of sedation in emergency department (ED) patients undergoing procedural sedation (PS). METHODS: This was a prospective observational study conducted in an urban county hospital of adult patients undergoing PS. Patients were monitored for vital signs, depth of sedation per the physician by the Observer's Assessment of Alertness/Sedation scale (OAA/S), pulse oximetry, and nasal-sample ETCO2 during PS. Respiratory depression was defined as an oxygen saturation <90%, an ETCO2 >50 mm Hg, or an absent ETCO2 waveform at any time during the procedure. The physician also determined whether protective airway reflexes were lost during the procedure and assisted ventilation was required, or whether there were any other complications. Rates of RD were compared with the physician assessment of airway loss and between agents using chi-square statistics. Spearman's rho analysis was used to determine whether there was a correlation between ETCO2 and the OAA/S score. RESULTS: Seventy-four patients were enrolled in the study. Forty (54.1%) received methohexital, 21 (28.4%) received propofol, ten (13.5%) received fentanyl and midazolam, and three (4.1%) received etomidate. Respiratory depression was seen in 33 (44.6%) patients, including 47.5% of patients receiving methohexital, 19% receiving propofol (p = 0.008), 80% receiving fentanyl and midazolam, and 66.6% receiving etomidate. No correlation between OAA/S and ETCO2 was detected. Eleven (14.9%) patients required assisted ventilation at some point during the procedure, all of whom met the criteria for RD. Pulse oximetry detected 11 of the 33 patients with RD. Post-hoc analysis revealed that all patients with RD had an ETCO2 >50 mm Hg, an absent waveform, or an absolute change from baseline in ETCO2 >10 mm Hg. CONCLUSIONS: There was no correlation between ETCO2 and the OAA/S score. Using the criteria of an ETCO2 >50 mm Hg, an absolute change >10 mm Hg, or an absent waveform may detect subclinical RD not detected by pulse oximetry alone. The ETCO2 may add to the safety of PS by quickly detecting hypoventilation during PS in the ED.     

Estimation of the bronchodilatory effect of deep inhalation after a free run in children.

The bronchomotor effects of a deep inhalation (DI) may provide relevant information about the mechanisms of exercise-induced airway obstruction in children and may be assessed by respiratory conductance (Grs) measured using the forced oscillation technique. The aims of the present study were to assess the effect of DI on Grs after exercise in relationship to the lung function response to exercise. Grs at 12 Hz using a head generator and spirometric data were measured in 62 children suspected of asthma before and 5 min after a 6-min free run. After exercise, Grs was significantly increased by DI in 38 subjects, who also showed larger Grs and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) responses to exercise than the 24 nonresponders. Stepwise regression indicated significant correlation between the response of Grs to DI and both Grs and FEV1/FVC responses to exercise. The data are consistent with exercise-induced bronchoconstriction being reversed by deep inhalation.     

International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson's disease: the NMSQuest study.

Nonmotor symptoms (NMS) of Parkinson's disease (PD) are not well recognized in clinical practice, either in primary or in secondary care, and are frequently missed during routine consultations. There is no single instrument (questionnaire or scale) that enables a comprehensive assessment of the range of NMS in PD both for the identification of problems and for the measurement of outcome. Against this background, a multidisciplinary group of experts, including patient group representatives, has developed an NMS screening questionnaire comprising 30 items. This instrument does not provide an overall score of disability and is not a graded or rating instrument. Instead, it is a screening tool designed to draw attention to the presence of NMS and initiate further investigation. In this article, we present the results from an international pilot study assessing feasibility, validity, and acceptability of a nonmotor questionnaire (NMSQuest). Data from 123 PD patients and 96 controls were analyzed. NMS were highly significantly more prevalent in PD compared to controls (PD NMS, median = 9.0, mean = 9.5 vs. control NMS, median = 5.5, mean = 4.0; Mann-Whitney, Kruskal-Wallis, and t test, P < 0.0001), with PD patients reporting at least 10 different NMS on average per patient. In PD, NMS were highly significantly more prevalent across all disease stages and the number of symptoms correlated significantly with advancing disease and duration of disease. Furthermore, frequently, problems such as diplopia, dribbling, apathy, blues, taste and smell problems were never previously disclosed to the health professionals.     

Importance of Dietary Fiber in Childhood

Dietary fiber has important health benefits in childhood, especially in promoting normal laxation. Currently, children consume amounts of dietary fiber that appear to be inadequate for optimal health promotion and disease prevention. It is prudent to recommend that children older than 2 years of age increase dietary fiber intake to an amount equal to or greater than their age + 5 g/day. According to the “age + 5” rule dietary fiber intake would increase from 8 g/day at age 3 years to 25 g/day by age 20 years. After age 20, dietary fiber levels of 25 to 35 g/day are recommended. Dietary fiber intake should be increased gradually in childhood by increasing consumption of a variety of fruits, vegetables, legumes, cereals, and other whole-grain products. Although very high fiber intake in childhood could have adverse effects, the potential health benefits of a moderate increase in dietary fiber substantially outweigh the possible risks, especially in highly industrialized countries such as the United States. A safe range of dietary fiber intake for children may be between age + 5 and age + 10 g/day. This range is considered safe even for children and adolescents with marginal intakes of some vitamins and minerals; should provide enough dietary fiber for normal laxation; and may provide enough added dietary fiber to help prevent chronic diseases.J Am Diet Assoc. 1995; 1140-1146, 1149.     

A New Method for Estimating Dermal Absorption from Chemical Exposure. 3. Compared with Steady-State Methods for Prediction and Data Analysis

Purpose. This paper compares unsteady-state and steady-state methods for estimating dermal absorption or analyzing dermal absorption data. The unsteady-state method accounts for the larger absorption rates during short exposure times as well as the hydrophilic barrier which the viable epidermis presents to lipophilic chemicals. Methods. Example calculations for dermal absorption from aqueous solutions are presented for five environmentally relevant chemicals with molecular weights between 50 and 410 and log₁₀K_ow between 0.91 and 6.8: chloromethane, chloroform, chlordane, 2,3,7,8-TCDD, and dibenz(a,h)anthracene. Also, the new method is used to evaluate experimental procedures and data analyses of in vivo and in vitro permeation measurements. Results. In the five example cases, we show that the steady-state approach significantly underestimated the dermal absorption. Also, calculating permeability values from cumulative absorption data measured for exposure periods less than 18 times the stratum corneum lag time will overestimate the actual permeability. Conclusions. In general, steady-state predictions of dermal absorption will underestimate dermal absorption predictions which consider unsteady-state conditions. Permeability values calculated from data sets which include unsteady-state data will be incorrect. Strategies for analyzing in vitro diffusion cell experiments and confirming steady state are described.     

Aberrant hormone production from ovarian neoplasms: Strategies for diagnosis and therapy

Syndromes involving peptide or nonsex steroid hormone secretion due to aberrantly located tumors are rare. We report a collected series of 16 patients with ectopic hormone production from ovarian neoplasms, including 3 patients recently encountered at our institution as well as 13 additional cases identified in the recent literature. These tumors included 2 insulin-producing ovarian carcinoids, 1 ACTH-producing pituitary adenoma within a benign ovarian cystic teratoma, 2 cortisol-producing ovarian neoplasms, 8 gastrin-producing ovarian cystadenomata or cystadenocarcinomata, and 3 thyroxine-producing ovarian strumal carcinoids. All patients presented with syndromes of hormone excess. Only 62% of all tumors were localized preoperatively. Following ovarian resection, 87% of patients remained disease-free with a median follow-up period of 1.5 years. In addition to ovariectomy, 8 additional unnecessary ablative procedures were performed in 7 patients. These included distal pancreatectomy, pancreaticoduodenectomy, adrenalectomy, total gastrectomy, selective vagotomy, and subtotal thyroidectomy. Failure to localize the ovarian neoplasm preoperatively was associated with a significantly higher risk of subsequent unnecessary ablative procedures. Because of the potential for the ovary to act as a source of aberrant hormone secretion, we recommend complete preoperative evaluation of the pelvis in female patients presenting with nonlocalizable endocrine tumors.

---

Resumen Los síndromes relacionados con la secreción de péptidos o de hormonas esteroideas no sexuales por tumores de ubicación aberrante ocurren infrecuentemente. En este artículo reportamos una serie de 16 pacientes con producción hormonal ectópica por neoplasmas ováricos, la cual incluye 3 pacientes vistos recientemente en nuestra institución y 13 identificados en la literatura médica de los últimos años. El grupo incluye 2 carcinoides ováricos productores de insulina, 1 adenoma pituitario productor de ACTH, 2 neoplasmas ováricos productores de cortisol, 8 cistadenomas o cistadenocarcinomas ováricos productores de gastrina, y 3 carcinoides ováricos estrumales productores de tiroxina. Todas las pacientes se presentaron con síndromes de exceso hormonal. En sólo el 62% de los tumores se pudo establecer la ubicación anatómica en la fase preoperatoria. Después de realizada la resección del ovario, 87% de las pacientes permanecieron libres de enfermedad en el período de seguimiento, que fue de 1.5 años en promedio. Además de la resección ovárica, se practicaron otros 8 procedimientos adicionales innecesarios en 7 pacientes. Estos incluyeron pancreatectomía distal, pancreatoduodenectomía, adrenalectomía, gatrectomía total, vagotomía selectiva, y tiroidectomía subtotal. La falla en la localización preoperatoria del neoplasma ovárico apareció asociada con un riesgo aumentado de ulteriores procedimientos quirúrgicos innecesarios. En vista de la potencialidad del ovario de actuar como fuente de secreción hormonal aberrante, nosotros recomendamos una completa evaluación de la pelvis en las pacientes femeninas en quienes se diagnostiquen tumores endocrinos no localizables.

---

Résumé Les syndromes concernant la sécrétion d'hormones peptidique ou stéroïde nonsexuelle due à des tumeurs ectopiques sont rares. Nous rapportons une série de 16 patientes avec une production d'hormone ectopique provenant de néoplasmes ovariens, comprenant 3 patientes récemment soignées dans notre établissement ainsi que 13 cas supplémentaires relevés dans la littérature récente. Ces tumeurs comprennent 2 tumeurs carcinoïdes ovariennes productrices d'insuline, 1 adénome hypophysaire producteur d'ACTH à l'intérieur d'un tératome cystique ovarien bénin, 2 néoplasmes ovariens producteurs de cortisol, 8 cystadénomes ou cystadénocarcinomes ovariens producteurs de gastrine, et 3 carcinoïdes ovariens strumaux producteurs de thyroxine. Toutes les patientes avaient des syndromes d'hyperproduction hormonale. Soixante-deux pour cent seulement des tumeurs avaient été localisées en préopératoire. Après ovariectomie, 87% des patientes étaient apparamment sans récidive avec un suivi médian d'un an et demi. Cependent, outre l'ovariectomie, 8 interventions supplémentaires non nécessaires ont été accomplis chez 7 patientes. Celles-ci comprenaient: pancréatectomie distale, duodénopancréatectomie, surrénalectomie, gastrectomie totale, vagotomie sélective, et thyroïdectomie subtotale. L'impossibilité de localiser le néoplasme ovarien en période préopératoire était associée à un risque notoirement plus grand de faire une résection inutile. Compte tenu de la possibilité pour l'ovaire de se comporter en producteur de sécrétion ectopique d'hormone, nous recommandons un examen complet préopératoire du bassin chez les femmes se présentant avec des tumeurs endocrines non localisables.

---

---

Presented at the International Association of Endocrine Surgeons in Toronto, Ontario, Canada, September, 1989.