Growth hormone and nutritional support: adverse metabolic effects.

The use of growth hormone in clinical nutritional support has received considerable attention over the past decade. The most encouraging results have been improved nitrogen retention and protein synthesis in the presence of hypocaloric nutritional support. Adverse effects, however, can limit the clinical usefulness of this technology. In the following case study, an obese 71-year-old man with a history of chronic obstructive pulmonary disease remained ventilator dependent 2 months following anterior cervical fusion and had severe depletion of visceral proteins despite nitrogen equilibrium. He was treated with 10 mg of recombinant human growth hormone (Genentech) subcutaneously every other day while also receiving nutritional support. We hypothesized that growth hormone administration could promote both protein synthesis and the development of muscle mass, particularly in the respiratory muscles, without increasing nutrient intake and, therefore, without increasing CO2 production. The patient, however, developed two potentially life-threatening adverse effects: hyperglycemia and fluid retention. The severity of these adverse effects led to discontinuation of this mode of therapy.


Limiting bacterial contamination of enteral nutrient solutions: 6-year history with reduction of contamination at two institutions.

Running enteral nutrient solution (ENS) bacterial contamination logs that were collected over a 6-year time frame are presented. At hospital A, reconstituted ENS were prepared by the pharmacy department in bulk and were frozen in the final container. These solutions were cultured and counted after 12 hours of storage at room temperature to stimulate this institution's hang time. Major reductions in ENS bacterial counts occurred after improvements in sanitation, a reduction in solution hang time, the conversion to the use of sterile water for dilution and reconstitution of ENS, and most dramatically, after the incorporation of a preservative (potassium sorbate) to reconstituted ENS. At hospital B, ENS usage consisted of canned feedings that were prepared by nursing personnel and were transferred to the feeding container at the bedside. Reductions in final counts of contamination of ENS occurred after procedural changes, which included container changes every 24 hours, use of sterile water for dilution, cleansing of can lids with alcohol swabs before use, rinsing and air drying of intermittent feeding containers between feedings, and limiting feeding container fills to 4-hour hang time quantities. At both institutions, the value of an ongoing three-class enteral quality control program with a defined acceptance/rejection criteria was demonstrated in that ENS contamination was reduced to acceptable levels comparable with federal standards for milk and dairy products.


Animal models in human nutrition research.

Animal models are used extensively in nutritional research. Studies with animal models may not provide a discussion of the applicability of the model to humans, and seldom do such studies discuss the limitations of the model. This article presents information that is targeted toward the nutrition support practitioner about the use of animal models in nutritional research. The rationale for using animal models and the applicability to humans, the limitations of applicability, and the unique opportunities related to animal models is presented.


Molecular biology in nutrition.

Recent progress in the field of molecular biology has had a considerable effect on both basic and applied clinical nutrition and offers even greater promise for the future. It is important for individuals working in clinical nutrition, as well as basic science investigators, to have an understanding of the fundamental concepts of molecular biology in order to be able to evaluate and apply new approaches to clinical problems as they become available. The purpose of this review is to provide those who are not molecular biologists with a brief overview of the fundamental concepts of molecular biology and then to describe a number of the recent applications of molecular biological methods and tools in the field of nutrition.


Antioxidant drug mechanisms: transition metal-binding and vasodilation.

In our work evaluating the antioxidant properties of a number of cardiovascular drugs, we have emphasized the importance of lipophilicity as a property contributing to antioxidant potency. Thus, the dihydropyridine calcium channel blockers and propranolol, one of the most lipophilic beta-blockers, were found to exhibit the greatest potency in membrane and cellular models. Both beta-blockers and calcium channel blockers are classified as antihypertensive agents. We found that the specific chemical moieties of various drugs may participate in the antioxidant mechanism of action. While reviewing relevant work from the past literature, it became apparent that some of the chemical moieties of antihypertensive and vasodilator drugs may bind transition metals. Thus, this present review focuses on common properties of transition metal-interaction that are shared, to a greater or lesser degree, by a number of vasoactive drugs and chemical agents. Although this observation has been pursued by other investigators in the past, we submit that the potential relevance to the newer pharmacological agents needs to be explored further. In addition, new information regarding the role of transition metals and free radicals involving vascular cells focuses greater importance on transition metal-interaction as a potential mechanism in vasodilation. This review does not intend to be inclusive of all chemical structures capable of binding transition metals; only those that are clinically relevant will be considered in some detail. Potential mechanisms of metal-chelating actions leading to vasodilation are also discussed.


Lipogenesis from n-butyrate in colonocytes. Action of reducing agent and 5-aminosalicylic acid with relevance to ulcerative colitis.

Cell membranes of colonic epithelial cells (CEC) in ulcerative colitis show structural abnormalities which are specific to the disease and which suggest impaired lipogenesis in CECs. Lipogenesis from [1-14C]-n-butyrate, the chief oxidative fuel of colonic epithelial cells, was measured in isolated CECs under control conditions, with or without glucose and in the presence of mercaptoacetate, a major reducing agent in the colonic lumen. Glucose significantly (p < 0.01) stimulated lipogenesis from [1-14C]-butyrate which was reversed by 5 mM mercaptoacetate. Mercaptoacetate significantly diminished CEC thiolase activity (EC 2.3.1.9). 5-Aminosalicylic acid reversed the adverse effects of mercaptoacetate in the saponifiable fraction of extracted lipids. Changes in lipogenesis due to colonic luminal reducing agents would affect the barrier function of CECs a feature relevant to the disease process of ulcerative colitis.


An AP-1-like motif in the first intron of human Pro alpha 1(I) collagen gene is a critical determinant of its transcriptional activity.

The first intron of the human Pro alpha 1(I) collagen gene contains an orientation-dependent enhancer composed of both positive and negative cis-acting elements involved in the transcriptional regulation of this gene. Deletion of a 360 bp Sau 3A intronic fragment spanning nucleotide +494 to +854 (S360) resulted in dramatic down-regulation of pCOL-KT (Thompson et al., J Biol Chem 266: 2549-2556, 1991). Using a DNaseI protection assay, we demonstrate a single footprint located at +590 to +615 in the S360 fragment; nuclear extracts prepared from mesenchymal and nonmesenchymal cells exhibited similar binding characteristics. A double stranded oligonucleotide representing a consensus Ap-1 binding sequence competed with S360 for binding. In contrast to what occurred in response to S360 deletion which was always accompanied by reduced expression, the deletion of the Ap-1 binding site (+598 to +off) caused either increased or decreased expression of the reporter gene depending on the target cell. Site-directed mutations in the Ap-1-like cis-element of Pro alpha 1(I) were also tested in transient expression assays. Consistent with the paradoxical results of Ap-1 deletion, we observed that the functional consequences of mutations in the Ap-1 site also varied in different cells. In A204 cells, one point mutation, which resulted in the loss of protein binding to S360, led to increased CAT activity while another point mutant, which retained binding of the Ap-1 like trans-acting factor(s), showed decreased CAT expression. The effects of these two mutations in the HFL-1 cells were exactly opposite of what was seen for A204 cells. Based on these observations, we postulate that the Ap-1 site plays a critical role in the transcriptional activity of the human Pro alpha 1(I) gene. The implications of an apparently dual mode of regulation through a single cis-regulatory element are discussed.


Morphological changes in Krebs II ascites tumour cells induced by insulin are associated with differences in protein composition and altered amounts of free, cytoskeletal-bound and membrane-bound polysomes.

A three-step sequential detergent/salt extraction procedure was used in order to isolate three distinct subcellular fractions containing free (FP), cytoskeletal-bound (CBP) and membrane-bound polysomes (MBP), respectively, from Krebs II ascites cells (Vedeler et al., Mol Cell Biochem 100: 183-193, 1991). The purpose was to study changes in the distribution of polysomes in these three fractions during long-term incubation with insulin under either stationary conditions or in roller suspension culture. Insulin caused a redistribution of polysomes between FP, CBP and MBP fractions. The hormone appeared to promote an entry of ribosomes into polysomes both in CBP and MBP populations. When cells were grown in stationary culture in the presence of insulin and thus promoted to attach to the substratum and undergo morphological changes, a diversion of ribosomes from CBP into MBP was observed. The level of protein synthesis was apparently very high in this latter fraction since more than 70% of ribosomes were in polysomes. Morphological changes observed following insulin treatment were accompanied by a shift of certain proteins among subcellular fractions (for example actin and p35). The fibronectin content was about 20% higher in attached compared to non-attached cells. The results suggest that morphological changes induced by stimulation with insulin are associated with an increased activity of MBP, presumably reflecting a requirement for an increased synthesis of membrane proteins.


Effects of alloxan and ninhydrin on mitochondrial Ca2+ transport.

Alloxan at millimolar concentrations slightly inhibited the velocity of Ca2+ uptake by isolated rat liver mitochondria irrespective of the free Ca2+ concentration between 1 and 10 microM and was an effective concentration-dependent stimulator of mitochondrial Ca2+ efflux. Ninhydrin also slightly inhibited the velocity of mitochondrial Ca2+ uptake but only at free Ca2+ concentrations above 5 microM. However, ninhydrin was a strong stimulator of mitochondrial Ca2+ efflux even at micromolar concentrations, 10-50 times more potent than alloxan. The mitochondrial membrane potential was reduced 10-20% at most by alloxan and ninhydrin. Alloxan and ninhydrin also stimulated Ca2+ efflux from isolated permeabilized liver cells. When isolated intact liver cells had been pre-incubated with alloxan or ninhydrin before permeabilization of the cells the ability of spermine to induce mitochondrial Ca2+ uptake was abolished. Glucose provided the typical protection against the effects of alloxan on mitochondrial Ca2+ transport only in experiments with intact cells but not in experiments with permeabilized cells or isolated mitochondria. Therefore glucose protection is apparently due to inhibition of alloxan uptake into the cell. Glucose provided no protection against effects of ninhydrin under any of the experimental conditions. Thus both alloxan and ninhydrin are potent stimulators of Ca2+ efflux by isolated mitochondria but very weak inhibitors of the velocity of mitochondrial Ca2+ uptake. The direct effects of ninhydrin on mitochondrial Ca2+ efflux may contribute to the cytotoxic action of this agent whereas the direct effects of alloxan on mitochondrial Ca2+ transport require concentrations which are too high to be of relevance for the induction of the typical pancreatic B-cell toxic effects of alloxan. However, the effects on mitochondrial Ca2+ transport during incubation of intact cells which may result from the generation of cytotoxic intermediates during alloxan xenobiotic metabolism may well contribute to the pancreatic B-cell toxic effect of alloxan.


Effect of n-3 and n-6 fatty acids on hepatic microsomal lipid metabolism: a time course study.

The present study examines the time dependent effects of n-6 and n-3 polyunsaturated fatty acids on liver microsomal lipid metabolism in FVB mice fed a diet supplemented with a mixture of free fatty acids (mainly 18:3n-6 and 20:5n-3) at 25 mg/g diet. Significant changes in the fatty acid composition of total liver and microsomal lipids were observed after 7 days on the diets. Thereafter, some animals remained on the same diet while others were fed a diet supplemented with hydrogenated coconut oil (HCO). With the exception of 20:5n-3 which showed a slower recovery, establishment of the HCO pattern was rapid indicating that the diet-induced changes could be easily reversed. The unsaturation index, the cholesterol/phospholipid ratio and the microviscosity of the microsomal membranes were not affected by these dietary manipulations. Unsaturated fatty acid supplementation reduced the activity of delta 9 desaturase by 50%. Feeding the HCO diet to mice previously fed the EPA/GLA diet led to a progressive increase in delta 9 desaturase activity, reaching 80% of the day zero values after 14 days. The monoene content of hepatic total lipids reflected, in most cases, the changes in enzyme activity. This study shows that a low dose of a n-3 and n-6 free fatty acid mixture increases the quantities of members of the n-3 family, without loss of n-6 fatty acids in microsomal membranes and modifies the activity of delta 9 desaturase without altering the microsome physicochemical parameters.


Cardiac dilatation associated with collagen alterations.

There is a complex collagen network in the heart. Various components have been identified and generally on the basis of form and position some functions have been ascribed to one or another of these components. Since the various components all appear to be connected in a hierarchial network of some type assigning function is not difficult but demonstrating a given function is somewhat hazardous. We have demonstrated that two I.V. infusions of disulfide reagents one week apart activates a collagenolytic system that results in near complete loss of the collagen struts that interconnect myocytes, the collagen struts that connect capillaries to all adjacent myocytes and the weave complex that surrounds groups of myocytes. Increases in pre load or afterload result in responses indicating that the disulfide treated animals generate pressure equal to or greater than the control hearts, thus, the treatment has no affect on either myocyte contractility or force delivery to the ventricle. However, static pressure volume measurements in the disulfide treated animals are shifted far to the right indicating marked dilatation of the ventricle and increase in distensibility. This indicates that the weave complex contributes to the initial rectilinear portion of the pressure volume curve.


Menadione-resistant Chinese hamster cell variants are cross-resistant to hydrogen peroxide and exhibit stable chromosomal and biochemical alterations.

We have investigated the antioxidant properties of V79 Chinese hamster cells rendered resistant to menadione by chronic exposure to increasing concentrations of this quinone. MD1, a clone of resistant cells, was compared to the parental M8 cells; the former showed increased activity of catalase (3 fold), glutathione peroxidase (1.6 fold) and DT-diaphorase (2.6 fold), as well as an increase in glutathione (3.2 fold). Although one of the products of menadione metabolism is superoxide anion, no changes in total superoxide dismutase activity was observed in MD1 cells. MD1 menadione resistant cells were also resistant to killing by hydrogen peroxide and contained tandem duplication of chromosome 6. A similar duplication of chromosome 6 was seen in several independently derived menadione resistant clones and therefore seems closed linked to the establishment of the resistance. Upon removal of menadione from the medium, some of these properties of MD1 cells, viz., resistance to menadione, elevated glutathione levels, and glutathione peroxidase activity, were lost and the cells resembled M8 cells. However, resistance to H2O2, elevated catalase activity and the duplicated chromosome remained stable for more than 40 cell passages in the absence of menadione. The increase in catalase activity was correlated with an increase in catalase mRNA content and a 50% amplification of catalase gene, as determined, respectively, by Northern and Southern blot analysis. The role of the chromosome 6 duplication in resistance to oxidative stress remains to be established. It is not responsible directly for elevated catalase levels since the catalase gene is on chromosome 3.


Public policy analysis for registered nurses in a baccalaureate curriculum.

As nurses become more involved in the macro-decision-making arena, they need policy analysis skills in order to make effective recommendations on policy alternatives. Dunn's policy analysis framework, useful for examining and understanding policy issues, is relevant to nursing education and practice and provides guidance for effective action. This framework guided an educational experience for registered nurse (RN) students in a baccalaureate nursing program. The students participated in community-based policy analysis, examining public policies affecting the health of individuals, families, groups, and populations. Dunn's framework and this policy experience can be incorporated into formal education courses or continuing education programs.


People's Community Clinic: collaboration in the Third World.

A West African government undertook to improve primary health care (PHC) training of mid-level health workers. In partnership with a neighboring squatter settlement, the premiere local training institution created a community-sponsored clinic, providing low-cost, PHC services, and a birthing center, as well as student experiences. Their collaboration in mobilization, research, planning and operations are described. Their success should encourage other educational and training institutions to consider a similar approach.


Improving home health care for the Navajo.

Home health care clients on the Navajo reservation present complex nursing problems that require interventions that are culturally sensitive. A collaborative project was developed that used the skills of researchers, clinicians, and members of the Navajo culture to develop culturally appropriate nursing care. Traditional life themes, values, and beliefs of the Navajo related to health and illness are described with examples of how the project facilitated home health care for Navajo clients.


Involving the target population and their providers in evaluation of substance abuse videos.

Substance abuse prevention and case finding are serious challenges to nurses who care for pregnant women and their infants. Audiovisual media can be useful in helping these nurses and their patients. This article discusses the insights of pregnant, low-income, minority women and their health care providers regarding selected substance abuse prevention videos. Focus group sessions were used to elicit valuable information, not only about reactions to substance abuse media but on their use in facilitating communication between patients and providers. Through this process, collaborative relationships were fostered among pregnant inner-city women, nurse clinicians, and nursing faculty, all of whom share a concern about substance abuse and an interest in working together to combat the problem.


A collaborative process and framework for nursing research.

Currently, there is a need for outcome research in nursing practice. To facilitate practice-based research, collaboration between education and service is essential. Although a few studies have been reported in the literature on partnerships between education and service, there is a need to describe the nature of a successful collaborative research process between a university college of nursing and a medical center. Nursing leaders from a university college of nursing and a medical center developed a collaborative framework and process by which to obtain funding for research. The following elements were crucial to the framework and facilitated the research process: commitment from leaders and individuals; concentration on positive outcomes and communication between institutions and within groups; matching of individuals; consensus on issues; and adherence to deadlines. The major benefits to this partnership are the enhancement of and opportunity for intradisciplinary research. The process provides a study site for the research and prepared faculty to develop it. All of the above elements factors contribute to a collaborative working arrangement and ensure successful outcomes for future projects.


Retrospective study of optometric referrals.

We undertook a retrospective study of the referral patterns of optometrists. During the study period 13,107 patients had been seen, of whom 2.86% had been referred. Of the referred patients, 66.67% were referred to an ophthalmologist via the general practitioner, 25.87% to their general practitioner alone, and 7.47% directly to an ophthalmologist. The conditions for which patients were referred are given along with information on any supplementary tests used. The effect of practitioner age and seasonal variations on referrals was also determined. The role of the optometrist in screening for ocular disease is discussed.


Screening for glaucoma: age and sex of referrals and confirmed cases in England and Wales.

This paper is based on a prospective survey covering 275,600 sight tests by optometrists in England and Wales. It analyses the age and sex distribution of 1402 referrals for suspected glaucoma and 456 confirmed cases of the disease. The proportion of sight tests which led to a confirmed case increased with age, for both sexes, to a maximum at approximately 70 years, and then tended to decline. Cases of glaucoma in people aged 36-51 years accounted for about a tenth of the total, which is more than is generally recognized. Wider adoption of routine tonometry for middle aged people would help to ensure that these cases are detected at an early stage. Confirmed cases of glaucoma in which raised intraocular pressure had not been given as a reason for referral, i.e. probable low tension glaucomas, increased from 5% of patients < 51 years old to 13% of patients > 75 years old. Glaucoma was found to be much more common in men.


Evaluation of two infrared autorefractors in pseudophakia.

We investigated the viability of using an objective infrared autorefractor to identify high corneal astigmatism (> 3.00 D) in a pseudophakic population. The eyes of 91 patients, who had recently undergone cataract extraction and intraocular lens implanation, were refracted manually and using two infrared autorefractors, a Canon RK-1 and a Nikon NR-2000. Autorefractor measurements were repeated to provide estimates of reliability for each instrument. LogMAR visual acuities were also recorded with both the manual and autorefractor corrections. Approximately 75% of repeat autorefractor measurements were within 0.50 D of the initial readings, and about 75% of measurements were within 1.00 D of the manual refractions. Visual acuities with manual corrections were, on average, one line better than with autorefractor corrections. By validating the autorefractors against manual refraction, the efficiency of the autorefractors for detecting astigmatism > 3.00 D was calculated. Setting the cut-off criterion to ensure high sensitivity (95%), so that almost all patients with > 3.00 D were detected, resulted in both instruments having a poor specificity of about 40%.


Variability of fixation disparity and accommodation when viewing a CRT visual display unit.

Fixation disparity and accommodation were measured while subjects viewed a target on a cathode ray tube at a 50 cm viewing distance. The psychophysical method of sequential testing was used. For measuring fixation disparity a series of brief dichoptic nonius targets was presented and the direction of perceived misalignment was reported by the subject. From these responses the psychometric function of fixation disparity can be derived which gives not only the mean fixation disparity but also the range of fluctuation during the period of measurement. During a 5 min period, this range was +/- 1.5 min arc averaged over subjects, when expressed as the range in which instantaneous fixation disparity fell with a probability of 68%. Repeated measurements on 5 days within 2 weeks gave a larger range of +/- 2 min arc. However, individual results can differ considerably from these average values. Repeated measurements and the analysis of the psychometric function can provide a more complete description of individual binocular status than is obtained with a single adjustment of continuously visible nonius targets. Laser optometry revealed that, compared to the stimulus distance of 50 cm, accommodation lagged behind in the range 1-2 D. The two display modes of bright characters on dark background and vice versa gave very similar results.


Rapid- and slow-velocity vergence eye movements.

Previously we have measured rapid-velocity vergence responses to targets at different distances that provided no disparity or accommodative stimulation. To evaluate the possibility that this rapid-velocity vergence occurs during saccades, the latencies of eye movement between two long dim luminous rods were compared under two conditions. Rapid-velocity vergence with an average latency of approximately 300 ms was elicited when subjects alternately viewed horizontal rods at distances of 38 and 78 cm, and with a vertical separation of 5.2 degrees. Horizontal saccades with a comparable latency were measured when the rods were equidistant and oriented vertically. The correlation between the mean latencies of vergence and saccadic movements was 0.97, suggesting that the two movements occurred together. In a second experiment vergence responses were measured when the subject looked between a bright vertical line on a screen at 76 cm and a second pair of lines (vertically displaced between 0.15 degrees and 3 degrees) with crossed disparity to simulate a target at 38 cm. Slow-velocity vergence often occurred alone when the vertical separation between targets was small; rapid-velocity vergence intruded when the separation between the targets was larger. The results can be accounted for if proximity and disparity stimulation act through a single vergence controller, the output of which produces slow- or rapid-velocity vergence depending upon whether the saccadic system is concurrently active.


Method for identifying amblyopes whose reduced line acuity is caused by defective selection and/or control of gaze.

Three visual tests were administered to a group of 15 amblyopic children, 15 adult amblyopes and two age-matched control groups, each of 20 subjects. Test results comprised visual acuity for recognizing high contrast letters presented in line (i.e. Snellen) format, isolated-letter format and repeat-letter format. The classical Snellen format confounds the effects of gaze control defects with the effects of adjacent contours on a patient's ability to recognize a foveated letter. We designed a repeat-letter format intended to unconfound these effects. The repeat letter format is much less sensitive to gaze control defects, and somewhat more sensitive to adjacent contour interactions than is the Snellen format. We report that amblyopic eyes can be subdivided empirically into three repeat-letter categories: repeat-letter acuity significantly better than Snellen acuity; repeat letter acuity not significantly different from Snellen acuity; and repeat letter acuity significantly worse than Snellen acuity. We report that this subdivision cuts across the clinical subclassification of amblyopia and also across the crowding/no crowding subclassification. We suggest that, rather than abnormal lateral interactions, defective selection and/or control of gaze is an important factor in depressed visual acuity in amblyopic eyes of the first repeat-letter category but not for the third type, in which abnormal lateral interactions may be important. To test the hypothesis that the response to patching and refractive therapy may be less satisfactory in our first category of amblyopic eyes, we are carrying out a prospective study.(ABSTRACT TRUNCATED AT 250 WORDS)


Contribution of accommodation and disparity-vergence to transient nearwork-induced myopic shifts.

Many investigations have attempted to demonstrate a relationship between sustained near-vision and the aetiology of environmentally-induced myopia, but it remains unclear whether myopic development relates to the actions of either accommodation or vergence. The present study investigated the effect of varying the disparity-vergence demand during a near-vision task while maintaining the accommodative stimulus constant. We required 20 young subjects to perform a near task (viewing distance = 20 cm) for 20 min through base-in, zero power and base-out prisms. The magnitude of the prisms for each individual corresponded to one-third their near vergence range. Pre- and post-task measurements of refractive state were determined objectively using an infrared optometer, with post-task readings being recorded over the initial 50 s following task completion. The results indicated no significant difference between the transient far-point shift for the three disparity-vergence conditions. However, combining data across conditions, a significant, mean shift in the myopic direction of 0.14 D was observed during the 10-20 s period immediately following task completion which dissipated within 20-50 s post-task. These findings suggest that the transient post-task myopic shift was not related to the output of disparity-vergence.


Effect of attention on the VEP in binocular and monocular conditions.

To study the effect of voluntary concentration on the visual evoked potential (VEP) with monocular and binocular rivalry stimulation, pattern reversal VEPs were recorded using 5.5 min arc and 50 min arc check sizes. Subjects viewed the VEP stimulus with the left eye and a light emitting diode (LED) with the right eye. They were asked to concentrate on either the VEP stimulus or the LED. The two targets were arranged so that the left eye remained accurately focused on, and directed to, the centre of the VEP stimulus throughout the recordings. The binocular VEP wave became attenuated when the subject concentrated on the LED. The wave was reduced to around two-thirds of the amplitude present when concentrating on the VEP stimulus. This reduction in the VEP amplitude is considered to be due to a binocular interaction because there was a lack of amplitude attenuation when the experiment was repeated with monocular conditions. The results also suggest that the wave is smaller when the non-dominant eye receives the VEP stimulus compared with that when the dominant eye is stimulated by the VEP target.


Relationship between axial length and chromatic refraction of the eye.

A new mathematical expression is derived to provide an estimate, alpha x, of the axial length of the human schematic eye. Approximations in the expression are made after considering effects in the Gullstrand-Emsley schematic eye. Parameters required to solve the expression are, for two wavelengths, the refractive indices of the humours, the focal power of the cornea and refractive errors in two states of accommodation. Unlike recognized optical methods, additional intraocular parameters are not required. For emmetropic variants of the Gullstrand-Emsley schematic eye with axial lengths between 19 and 27 mm, alpha x is within 0.06 to 0.26 mm of the actual value. Furthermore, alpha x is essentially independent of variations in the refractive indices of the crystalline lens. However, the estimate of alpha x is critically dependent on the accuracy of values assigned to the parameters. For that reason, the model is considered impractical for clinical application.


Refractive plasticity of the developing chick eye.

We have developed a lightweight plastic goggle with rigid contact lens inserts that can be applied to the eyes of newly hatched chicks to explore the range and accuracy of the developmental mechanism that responds to retinal defocus. Convex and concave lenses of 5, 10, 15, 20 and +30 D were applied to one eye on the day of hatching. The chick eye responds accurately to defocus between -10 and +15 D, although hyperopia develops more rapidly than myopia. Beyond this range there is first a levelling off of the response and then a decrease. The resulting refractive errors are caused mainly by increases and decreases in axial length, although high levels of hyperopia are associated with corneal flattening. If +/- 10 D defocusing lenses are applied nine days after hatching the resulting myopia and hyperopia are equal to about 80% of the inducing power. After one week of inducing myopia and hyperopia with +/- 10 D lenses, the inducing lenses were reversed. In this case, the refractive error did not reach the power of the second lens after another week of wear. Instead, astigmatism in varying amounts (0-12 D) was produced, being greater when reversal was from plus to minus. Finally, astigmatism can also be produced by applying 9 D toric inducing lenses on the day of hatching. The astigmatism produced varies from 2 to 6 D, and the most myopic meridian coincides with the power meridian of the inducing lens. This astigmatism appears to be primarily due to corneal toricity.(ABSTRACT TRUNCATED AT 250 WORDS)


Twice-daily use of a chlorobutanol-preserved artificial tear on rabbit corneal epithelium assessed by scanning electron microscopy.

Female pigmented rabbits received two drops of a chlorobutanol 0.5%-preserved, polyvinyl alcohol-based artificial tear at 21.00 h and 09.00 h for 1, 2, 3, 6 or 12 consecutive days. The animals were killed at 15.00, 6 h after the last treatment. Scanning electron microscopy of the corneal epithelial surface at x 200 magnification revealed only occasional cell exfoliation averaging < 8% of the surface analysed at central, mid-peripheral and peripheral sites, showing minimal cytotoxic effects. The level of exfoliation was maximal after 2 to 3 days treatment and then returned to close to zero, so the eye adapts to repeated use of the artificial tears. Evaluation of the surface microplicae of the cells at x 15,000 indicated subtle, but distinct, changes in what might be the mucus material associated with the cell surface, especially after 2 and 3 days treatment.


Meridional profiles of variance-covariance of dioptric power. Part 1. The basic theory.

It has recently become possible to calculate and represent variation or spread of dioptric power in a meaningful way. This is important for the proper analysis and interpretation of data on dioptric power in a number of areas of the vision sciences. The representation takes the form of a symmetric matrix of six (usually) variances and covariances. Although the matrix is satisfactory for several formal statistical purposes, such as the testing of hypotheses, it does not give an intuitively satisfactory picture of the extent and nature of the variation, nor is it easy to interpret in a way that could be useful to the researcher or clinician. A useful graphical representation of variation can be constructed from the variance-covariance matrix. It consists of curves that show the meridional dependence of the variation. These meridional profiles of variation give a complete and intuitively satisfactory picture of the nature and extent of the variation of power and are potentially of general use to researcher and clinician. A complete theoretical basis is provided for the construction of meridional profiles of variation of dioptric power. An accompanying paper employs the theory to construct profiles for a number of representative samples of dioptric power.


Meridional profiles of variance-covariance of dioptric power. Part 2. Profiles representing variation in one or more of sphere, cylinder and axis.

Meridional profiles of variation of dioptric power are constructed. Using the basic theory developed in an accompanying paper, samples are selected in a systematic way to illustrate variation only in sphere, only in cylinder and only in axis, and in all possible combinations of sphere, cylinder and axis. For each of the seven samples, scatter plots are constructed together with ellipsoids that represent the estimated distribution of powers in the population from which the sample was taken. The surfaces of the ellipsoids are surfaces of constant probability density within which 95% of the population is calculated to lie. The scatter plots and distribution ellipsoids are plotted in a three-dimensional space called h-space. Meridional profiles of variation are constructed for each of the samples. Properties of the profiles are discussed. Meridional profiles are also presented for eyes before and after radial keratotomy. Among other things, the profiles show meridians of greatest and least variation and are intuitively satisfying. They are potentially useful for the researcher and clinician including the surgeon. They may help to improve surgical and therapeutic techniques. Certain patterns may prove to be characteristic of physiological or pathological conditions, in which case meridional profiles may have use as a diagnostic tool.


Analysis of refractive status of Hong Kong Chinese infants.

Recently developed methods of quantifying changing dioptric power are applied to the refractive status of Hong Kong Chinese infants from about 10 to about 40 weeks of age. The analysis confirms that hyperopia decreases during the period and that with-the-rule astigmatism predominates. Change, however, is not constant over the period. The rate of decrease of hyperopia slows down and the refractive status becomes more spherical. The mean refractive status is calculated at 10, 20, 30 and 40 weeks. The spread of refractive status is represented by variance-covariance matrices calculated for each group and 95% confidence ellipsoids on the mean are constructed. The variance-covariance exhibits little change over the period. The right and left eyes show similar behaviour.


Strategy for the design of multifocal surfaces.

A method is proposed which may prove useful as an aid in the design of non-spherical surfaces with desired multifocal properties. More specifically, if an axially symmetrical surface is described by a polynomial then the coefficients of this polynomial can be found such that optical path lengths between given object and image points are nearly constant over desired portions of the surface. Three examples are given. One of the examples, a 'trifocal' surface, is compared to an aberration-free two-segment concentric bifocal contact lens.


Construction of a model eye and its applications.

Construction details are given of a model eye, based on the Bennett and Rabbetts schematic eye. It incorporates a cornea, lens, and spherical fundus. Distilled water filled the anterior and vitreous chambers. By means of a micrometer screw, the vitreous chamber depth can be precisely varied to produce axial ametropia from +11 to -17 D. Readings taken over the greater part of this range with a Topcon Autorefractor RM-A6500 were found to be repeatable and reproducible within +/- 0.25 D. The model eye was used to investigate the relationship between the actual size of a fundus feature and its photographic image in two different fundus cameras. With a Zeiss Oberkochen camera of telecentric design the magnification was found to remain constant whatever the degree of axial ametropia, whereas with a Carl Zeiss Jena camera the magnification varied linearly with ametropia. A technique developed by Littmann for determining the actual size of a retinal feature when using a fundus camera of telecentric design is discussed briefly.


Effects of different ocular fixation conditions on A-scan ultrasound biometry measurements.

A-scan readings must be taken along the visual axis for accurate axial length measurement. Various fixation targets, which ideally should not induce accommodation, are used to limit eye movements. In this study results using the Humphrey biometer under different fixation conditions were compared to establish the most suitable target. We also investigated corneal applanation effects by comparing optical and ultrasonic measurements of anterior chamber depth. We examined 12 randomly selected normal eyes of 12 young subjects. Three A-scans were recorded for each of five fixation conditions: spotlight at 6 m; Snellen letter at 6 m; solid probe's built-in green fixation target; Snellen letter at 6 m viewed through a -4.00 DS lens; spotlight at 6 m under cycloplegia (the comparison condition). Variability 'within' each fixation condition, estimated by the standard deviation for each subject, was equal throughout the 12 subjects for each fixation condition. Also variation was independent of size of the ocular dimension. The good agreement between the comparison condition and optical anterior chamber depth measurements indicated that the solid probe produced little applanation. Differences 'between' fixation conditions were investigated. It was concluded that a spotlight or letter at 6 m provides a suitable fixation target for biometry. Built-in fixation targets can produce significant errors.


Capillary filtration in venous hypertension. Comparison between the vacuum suction chamber (VSC) device and straingauge phlethysmography.

To evaluate capillary filtration a group of normal subjects and two groups of subjects with venous incompetence (50 with deep and 50 with superficial incompetence) were studied with the vacuum suction chamber (VSC) device applied onto the internal perimalleolar region. This method was compared with straingauge plethysmography rate of ankle swelling (RAS). By the VSC the time taken for the weal to disappear (VSC time) was considered indicative of capillary filtration. The values obtained with the two methods were well related (r < 0.742) and there was a good separation between patients and normals. The separation between the two groups of patients was significantly better (p < 0.05) with the VSC time. In conclusion VSC time is a good indication of capillary filtration in comparison with straingauge plethysmography RAS. It may be used to assess variations in capillary filtration in venous hypertension and possibly to follow up the effects of treatments.


Cholesterol in normal and pathological seminal plasma.

One hundred and twenty eight samples (seminal plasma) were studied for cholesterol. They included normozoospermia (44), oligozoospermia (22), oligoasthenozoospermia (34) and azoospermia (28). The cholesterol level in normal group was 61.48 mg/dl (32.5-97.5 mg/dl). Among the groups no difference was seen in cholesterol level. Correlation (r = 10.35) was existing between total spermatozoa count and the level of cholesterol in normozoospermia. A reverse pattern was seen in oligozoospermia (r = -4.04). There was no correlation present between cholesterol and spermatozoa motility in any groups studied.


Relations between subcellular events in the degenerating notochord and histopathological features of the spinal chordomas.

The authors focused their attention on the cytology of the degenerating notochord at the level of the vertebral anlagen and compared it with data of the literature on the histopathology of the spinal chordomas. The purpose of the research was to investigate the notochordal histological features justifying the fact that the remnants of a structure destined to atrophy during prenatal life, maintain a proliferative potential in postnatal life. Therefore, from the earliest stages (24th incubation hour) to the terms of development, the notochord was studied by electron microscope in chick embryo. The data obtained show that, in most notochordal cells, signs of metabolic damage and progressive degeneration coexist with signs of secretory and mitotic activity, from which the proliferative potential of these cells seems to derive. Vacuolar degeneration is also likely due to the progressive metabolic segregation of the notochord, owing to the absence of blood-vessels and the appearance of perichordal sheath.


Experimental investigation on histocompatibility of bovine collagen in rat tongue.

Authors injected a 1.5-2 cc Gax-Collagen into the tongue of 13 rats in order to examine the reactivity of the tissues around the graft and its attitude and duration. The research had practical purposes as the material is mainly used in E.N.T. for reconstructing the vocal cords. The animals have been sacrificed from 1 day to 9 months and the tongue subjected to the ordinary histologic methods. Our conclusions are as follows: a) a moderate inflammatory reaction following the introduction of the foreign body, then it attenuates and disappears at the third month; b) the implant is well tolerated, does not cause structural alterations in the surrounding tissues, in particular in the musculature where it is placed; c) a neovascularization appears, it lessens over the time, keeping itself only at the edge of the graft; d) in the formed fissures, fibroblasts, traces of collagen and neocollagen are present. All these conditions allow for taking root and the persistence of the implant. It is remarkable that the spherical form of the Gax-Collagen does not modify even if it has been implanted into a muscular organ and therefore subjected to severe and continuous mechanical stress.


Usefulness of the determination of carcinoembryonic antigen (CEA) in the serum of patients with colorectal cancer in Albania.

In our work we have studied the value of the determination of serum CEA in patients with colorectal cancer. We have studied 56 patients with colorectal cancer aged 40 +/- 16 years of both sexes, 26 of whom have metastasis and 30 not. The positivity of serum CEA in the patients with colorectal cancer was 66% (37/56) in the patients without metastasis 53% (16/30) and in the patients with metastasis 80.7%. (21/26). The referent values of serum CEA were significantly lower than the values of serum CEA in the patients with colorectal cancer with and without metastasis (p1 < 0.001). Also we noticed that the values of serum CEA of the patients with colorectal cancer with metastasis were considerably higher than those without metastasis (p2 < 0.001). Analysing the values of serum CEA in the patients with colorectal cancer we noticed that all the patients of our work that had serum CEA value 20 ng/ml had metastasis. Relying on our data we conclude that the determination of serum CEA in the patients with colorectal cancer is very useful for the diagnosis and the prognosis of these patients.


Effect of immunostimulating therapy on the immunocompetent system in breast carcinoma.

The authors studied 68 patients suffering from breast cancer, with or without lymph node metastasis, who underwent surgery and antitumour therapy (CMF). Twenty-three patients were treated using CMF and 1.5 mg/kg of thymostimulin, 24 with CMF and 1 mg/kg of thymostimulin and lastly, 21 subjects received anti-tumour therapy with CMF alone. Thymostimulin was administered every day for a week prior to surgery; subsequently, it was administered on alternate days for a week and then twice a week for 3 months. The blastogenesis of immunocompetent cells was evaluated. During thymostimulin treatment a higher rate of 3HTdR captation (p < 0.005) by cells stimulated with ConA + IL-2 was observed; these levels tended to increase after 3 weeks and reached statistically significant levels after 3 months of treatment; no significant changes were observed in those patients treated with CMF alone. In addition, the cytotoxic activity of monocytes and NK cells against K-562 cells and against short-lasting cell lines derived from breast carcinoma was also studied. It was observed that this activity increased significantly (p < 0.002) following thymostimulin treatment; this increase was greater in subjects treated with 1.5 mg/kg compared to those treated with 1 mg/kg, but the difference was not statistically significant. The study also evaluated the presence of IL-2 receptors (Tac): thymostimulin treatment for 3 months led to the appearance of receptors, although in restricted numbers, on non-stimulated cells. After IL-2 stimulation, the percentage of cells with Tac receptors increased significantly (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)


Surgical approach to combined abdominal aortic aneurysm and renal artery stenosis.

Thirty-four cases of combined abdominal aortic aneurysm (AAA) and renal artery stenosis (RAS) are reported. Hypertension was found at admission in 32 subjects, the other two being well responsive to drug therapy. Angiography and selective renal vein renin assay were always performed: renal artery stenosis was unilateral in 21 (61.7%) subjects and bilateral in 13 (38.3%). In 9 cases renal artery stenosis was not correlated to the hypertensive state. Mild chronic renal insufficiency was demonstrated preoperatively in 20 patients (58.8%). Simultaneous surgical treatment was carried out in 25 cases (73.5%). Mortality was 4% (one subject), severe renal insufficiency 8% (two subjects) and permanent renal failure 4% (one subject) All complications occurred among the group with bilateral RAS. While surgical repair of AAA is always mandatory, simultaneous surgical treatment of AAA and RAS should be carried out in carefully selected cases, due to elevated mortality rates reported in the literature, in order to cure renovascular hypertension, when it is demonstrated as related to RAS, or to preserve renal functionality, when RAS is contralateral to a functionally excluded or hypotrophic kidney or it exceeds 80% of the diameter of the artery.


Therapeutic effects of pulsed magnetic fields on joint diseases.

The present paper describes the effects of pulsed magnetic fields (MF) on diseases of different joints, in chronic as well as acute conditions where the presence of a phlogistic process is the rule. Optimal parameters for MF applications were sought at the beginning of the study and then applied for 11 years; a technical modification in the MF generator was introduced 5 years ago to satisfy the requirement of a hypothesis advanced to understand the mechanism of MF treatment. 3,014 patients were treated by means of MF at extremely low frequencies and intensities. Patient follow-up was pursued as constantly as possible. Pain removal, recovery of joint mobility and maintenance of the improved conditions represented the parameters for judging the results as good or poor. The chi-square test was applied in order to evaluate the probability that the results are not casual. A general average value of 78.8% of good results and 21.2% of poor results was obtained. Higher (82%) percentages of good results were observed when single joint diseases were considered with respect to multiple joint diseases (polyarthrosis); in the latter, the percentage of good results was definitely lower (66%). The high percentage of good results obtained and the absolute absence of both negative results and undesired side-effects, together with the therapeutic advantage due to a technical modification in the MF generator, led to the conclusion that magnetic field treatment is an excellent physical therapy in cases of joint diseases. A hypothesis is advanced that external magnetic fields influence transmembrane ionic activity.


Persistent pain and personality evaluation. A report of seven multi-operated patients for chronic pain complaints of non malignant origin.

The MMPI scores, the PPI and the MPQ of seven multi-operated patients for chronic pain complaints of non malignant origin were studied. The results of the analysis performed in this group of surgically treated patients point out that there is a strong evidence of relationship between personality traits and the persistence of pain.


Emotional characteristics of chronic and acute incestuous daughters.

Incest can have a devastating effect on the emotional stability of the victim both in childhood and in adulthood. The present research was conducted to determine: (1) emotional variables associated with chronic and acute incestuous daughters, and (2) a comparison of the similarities and/or differences of each. Results suggested ten different variables of importance in father-daughter incest, however, there were significant differences regarding which of these tended to be associated more with either the chronic or acute incestuous daughters.


Combined adrenal adenoma and myelolipoma in a patient with Conn syndrome. Case report.

Adrenal myelolipoma is an uncommon benign tumor usually discovered by chance in patients with hypertension, obesity, arteriosclerosis or cancer. The association with adrenocortical endocrine dysfunctions is rare. We report herein an unusual case, the second in the literature to the best of our knowledge, of combined adrenal adenoma and myelolipoma in a patient with Conn syndrome.


[Prevalence of HIV antigens in cerebrospinal fluid and in serum of patients with both asymptomatic and symptomatic HIV infection].

Prevalence of HIV-Ag in both serum and CSF has been determined in 19 HIV infected patients, including 7 patients without any symptoms or only generalized lymphadenopathy, 5 patients with ARC and 7 patients with AIDS. The results have been correlated with clinically evident neurological disorders. HIV-Ag have been detected in 9 out of 12 patients with ARC (AIDS Related Complex) and AIDS. In 8 of them neurological disorders have been present. Out of the remaining 7 patients in only one HIV-Ag has been detected in CSF (p < 025). No correlation between the presence of HIV antigen in CSF and serum has been noted.


[Quantitative assay of CD8+ (cytotoxic and suppressor) lymphocytes in patients with both asymptomatic and symptomatic HIV infection].

Lymphocytes CD8+ have been assayed prospectively in 245 individuals infected with HIV. Percentage and number of CD8+ have been nearly two-fold higher in asymptomatic patients or patients with lymphadenopathy than those in the control group. The number of CD8+ lymphocytes has been rapidly decreasing parallel to the progression of HIV (ARC and AIDS), while their percentage has increased--however insignificantly. There has been a positive correlation between the number of CD4+ and CD8+ cells and all clinical stages of HIV infection.


[Tuberculosis of the lymphatic nodes and coexisting invasion with Toxoplasma gondii].

Six cases of the peripheral lymphatic nodes tuberculosis with positive serologic reactions to Toxoplasma gondii antigen are presented. It was shown, that independently of a complex of clinical examinations histologic examination is decisive for the diagnosis of lymphatic nodes tuberculosis with coexisting toxoplasmosis. A positive serologic reaction with T. gondii antigen in patients with lymphatic nodes tuberculosis may reflect inactive infection with T. gondii. Use of anti-toxoplasmosis drugs may be not necessary in such cases.


[Incubation period of varicella in children with neoplastic diseases].

Duration of varicella incubation period has been analysed in 21 pediatric patients with neoplastic diseases and in 59 children without immunological deficiency. In has been found, that incubation period has been significantly longer in children with neoplastic diseases (mean 19.58 days), than that in children without immunologic disorders (15.45 days). The difference was statistically significant (p < 0.001).


[Effect of ethylenediaminetetraacetic acid disodium salt and doxycycline on drug resistant bacteria].

Effect of Na2EDTA and doxycycline applied alone and in combination in the treatment of experimentally induced dermatitis in rabbits with Staphylococcus aureus resistant to tetracyclines was studied. The rabbits were divided into three groups. The animals of group I were treated locally with the ointment containing 1% doxycycline or 1% Na2EDTA. In group II topical treatment was applied by means of injections of Na2EDTA solution in doses of 12.5 and 6.25 mg Na2EDTA per 1 kg/body weight. Group III was also treated locally with Na2EDTA solution like in group II, but additionally doxycycline in a dose of 50 micrograms per 1 kg/body weight was given i.v. Favourable therapeutic results were observed in the case of local, simultaneous application of Na2EDTA and doxycycline, or local application of Na2EDTA, and intravenous administration of doxycycline. However, the best therapeutic effect was seen in the case of local, simultaneous application of the ointment containing Na2EDTA and doxycycline.


[Sarcoidosis in coexistence with Toxoplasma gondii invasion].

Two cases of sarcoidosis with peripheral lymphatic nodes involvement and coexisting toxoplasmosis are presented. Both cases illustrate diagnostic and differentiating problems in patients with chronic lymphatic nodes enlargement and positive serological reaction to T. gondii antigen. An emphasis is on the importance of the histological examination of the lymphatic nodes for the sarcoidosis diagnosis and contribution of T. gondii to the disease. Positive serological reaction to T. gondii antigen in patients with sarcoidosis may reflect inactive toxoplasmosis; however, periodical serological tests are necessary monitoring the due immunosuppressive treatment used in patients with sarcoidosis.


[Late episodes of apnea in a premature infant infected with E. coli O111K58].

Typical episodes of apnoea with paleness and cyanosis have been noted noted in premature baby born on the 28th week of pregnancy with body weight 1,010 g as a result of infection with enteropathogenic strain of E. coli O111K58 on the 21st day of life (3rd day of the infection). Effective treatment with antibiotics produced recovery.


[A new case of cutaneous myiasis from South America via the larva Dermatobia hominis (L. Jr.)].

A case of cutaneous myiasis produced by D. hominis in a 26-year Polish missionary, who spent 3 months in Peru in 1990 is presented. Practical indications helpful in the diagnosis of this parasitosis are given together with data concerning occurrence and biology of D. hominis.


[Aspergillosis of the lymphatic nodes].

The authors emphasize fungal lesions to the lymphatic nodes confirmed by the presence of Aspergillus flavus in blood and throat smear cultures (on Sabouraud's medium) and presence of A. flavus in cytological examination of biopsy from the lymphatic node, increased number of eosinophils in peripheral blood, and infiltration of eosinophils in bone marrow and lymphatic nodes. Aspergillosis coexisted with the infection with Candida albicans and S. aureus. The treatment of recurrent tonsillitis with antibiotics and also lowered granulocyte myeloperoxidase activity with increased production of O2 peroxide ion might predispose to such fungal infection.


[Antibodies labelled with dyes their application in diagnosis].

Antibodies labelled with some disperse dyes, colored polymers, fluoro- and chemiluminescence, formazan, colloidal gold and selenium are reviewed. An application of the labelled antibodies in commercially available diagnostic home tests is presented.


[Aerobic actinomycetes and their significance in human and animal pathology. I. Actinomycetales infections--characteristics, etiology, epidemiology and pathogenesis].

Aerobic actinomycetes causing nocardiosis, GRT-(Gordona, Rhodococcus, Tsukamurella) infections, actinomycetomas, dermatophilosis and extrinsic allergic alveolitis, including etiology, epidemiology and pathogenesis of the diseases are described. The name "actinomycetosis" for all these diseases has been proposed. Many clinical important and potential pathogens, as well as an increasing number of opportunistic, immunosuppressed and immunocompromised cases are discussed. A review of the abundant literature up to date, concerning the problem, is presented.


[Regulation of immunoglobulin class E synthesis].

IgE production by B cell is T cell dependent. Induction of human IgE synthesis requires IL-4 and T/B cell physical interactions. The pivotal role of cytokines and of Fc epsilon R2 and its soluble fragments in regulation of IgE synthesis are presented.


[Dna adducts--characterization and role in chemical carcinogenesis].

A review of the metabolic pathways and interaction with DNA of benzo[a]pyrene and some other carcinogens is presented. Consideration is given to the formation and persistence of adducts in relation to carcinogenic process.


[Role of blood platelets in pathogenesis of ischemic cerebral infarction].

The author considers the role of platelet reaction as adhesion, release, and aggregation in the development of ischaemic stroke. The special attention is paid to the problem of platelet behaviour in stroke victims and the role of platelet activity in brain infarction in the young.


[Mechanism and kinetics of micronuclei formation in mouse bone marrow].

The paper presents a review of results concerning mechanism and kinetics of micronuclei formation. Special attention has been paid to differences in the induction of micronuclei by clastogenic compounds and spindle poisons as well as modifying factors which play important role in micronuclei formation.


[The role of iron in immunologic processes].

Iron, apart a for long time well-known function connected with: transportation (hemoglobin), storage (myoglobin), and utilize (cytochromes, cytochrome oxidase) oxygen for respiration, has a critical role in host-pathogen interactions. Iron is essential for microbial growth, but also for immune function. The role of iron in infection, thermoregulation, acute lymphocytic leukemia, neoplasia, rheumatoid arthritis, stimulation of free radical reactions, and studies with iron chelation therapy are discussed.


[Alcohol dehydrogenase--polymorphism, properties and role in ethanol metabolism].

The paper presents the molecular and kinetics aspects of alcohol dehydrogenase polymorphism. The role of this enzyme in ethanol metabolism are too discussed.


[Interaction of acetaldehyde and proteins].

A review of literature dealing with acetaldehyde-proteins reactions in vitro and in vivo was done. The changes in proteins structure and functions resulting from acetaldehyde binding were discussed.


[Acute poisoning with trichloroethylene, toluene and xylene--toxicokinetic mathematical models and clinical experiments].

The paper presents a review of toxic activity of three solvents and mathematical models of their metabolism and different routes of elimination. Special attention was paid to clinical difficulties and complications which may occur during acute poisonings, especially the immunological disorders and coagulation disturbances.


[Effect of atropine therapy on sudden infant death. A multicenter survey of 7851 children at risk].

The results of a multicentre inquiry started in 1988 in reference centres of sudden infant death are presented. This study concerns the sudden and unexplained mortality of infants under 1 year of age who were treated with atropinics for an alleged risk of sudden death. The 7,851 infants involved were divided into 2,605 siblings, 1,067 premature babies and 4,179 infants who experienced malaises. Only one of the 2,034 infants treated with atropinics (385 siblings, 435 prematures, 1,214 with malaise) died, as opposed to 27 deaths among the 5,817 infants who where not treated (10 deaths among 2,220 siblings, 6 among 632 premature and 11 among 2,965 infants with malaise); P = 0.005. These results are encouraging, but they suffer from the limitations and biases inherent in all large inquiries. They certainly do not allow us to conclude without reservation that vagal hyperreflectivity is the mechanism responsible for sudden infant death and that atropinics must be systematically given to all infants at risk. Wide and randomized prospective studies are highly desirable in this particular field.


[Hepatobiliary manifestations in AIDS in adults. Place of cholecystectomy].

In AIDS patients an acalculous cholecystitis may be responsible for abdominal pain subsiding after cholecystectomy. But the indications for cholecystectomy are not clear: cholecystitis is usually associated with diffuse cholangitis and this might cause the symptoms. Since 1985, 8 AIDS patients have undergone cholecystectomy for acute cholecystitis. Ultrasonography revealed a 5 to 12 mm thickening of the gallbladder wall in all of them and gallbladder stones in two; four patients had cholangitis. The decision to operate was based on persistent pain associated with fever, poor general condition and muscular rigidity at palpation. Four patients had septic shock at the time of surgery; one died in the immediate postoperative period. In all other patients pain and septic syndrome subsided. Two patients died of AIDS complications 20 days after surgery; the remaining five died of AIDS 6, 9, 10, 12 and 14 months respectively after surgery; in two of them cholestasis had reappeared due to cholangitis. To summarize, in the 8 AIDS patients studied cholecystectomy was performed for clinical deterioration. Gallbladder pathology was responsible for the abdominal pain and the febrile general condition which was relieved by cholecystectomy.


[Neuroendocrine tumor of the trachea of the intermediate type. Value of its individualization].

Tracheobronchial neuroendocrine tumours can be divided into 4 main groups: typical carcinoid; well-differentiated neuroendocrine carcinoma (atypical carcinoid); neuroendocrine carcinoma of the intermediate type, and small-cell carcinoma. Typical and atypical carcinoids are differentiated tumours, whereas intermediate neuroendocrine tumours and small cell carcinomas are little or not differentiated. Morphological or architectural criteria usually suffice to distinguish between carcinoid tumours and small cell carcinomas. In some cases, however, the neuroendocrine nature of poorly differentiated and non-small cell carcinomas is suggested by morphological criteria, but it can be confirmed only by immunohistochemistry and electron microscopy. Tracheobronchial neuroendocrine tumours of the intermediate type have been studied from a first, well-documented clinical case which demonstrated two important points: the prognosis of these tumours seems to be worse than that of carcinoid tumours, and they favourably respond to chemotherapy. In view of the therapeutic consequences, it is necessary to investigate, by the appropriate techniques, the neuroendocrine nature of these poorly differentiated carcinomas.


[Fetal toxicity of non-steroidal anti-inflammatory agents].

All non-steroidal anti-inflammatory drugs (NSAIDs) are prostaglandin inhibitors, which explains their foetal toxicity. So far, no epidemiological study of their cardiopulmonary and renal effects has been carried out, but case-reports have been published. The cardiopulmonary effects of NSAIDs include closure of the ductus arteriosus, pulmonary hypertension cardiopathy and tricuspid valve insufficiency. They were responsible for 31 neonatal accidents, 8 of which were fatal (for 22 pregnant women, 7 bearing twins, 1 bearing triplets). The renal effects of NSAIDs consisted of acute renal failure with oedema, oliguria, hyponatraemia and marked hyperkalaemia. They affected 23 neonates, 8 of whom died (for 17 pregnant women, 4 bearing twins, 1 bearing triplets). A few epidemiological studies have reported foetal haemorrhages when aspirin was used by the mother as anti-inflammatory agent. In comparative trials of indomethacin as short treatment of premature labour and polyhydramnios the drug proved to be effective. In obstetrical tocolysis NSAIDs can be given in the absence of alternative therapy with beta-adrenergic agents, and their risk can be minimized by ultrasonographic examination and monitoring of foetal cardiac function and diuresis. In the field of rheumatology, corticosteroids would be a good alternative to NSAIDs for rheumatic diseases, but using NSAIDs for low back pain, sciatica, haemorrhoids, toothaches, sinusitis, etc., would not be justified in pregnant women. Self medication must be discouraged.


[Reactions of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with amines].

The reaction of the title compounds with amines gave in dependence of the reaction conditions and the structure of the title compounds and the amine 3-acylamino-thieno[2,3-b]pyridine-2-carbonamides (B), 4-oxo-4 H-pyrido[3',2':4,5]thieno[3,2-d]pyrimidines (D),N-(2-carboxy-thieno[2,3-b]pyridine-3-yl)amidines (C) and N-(thieno[2,3-b]pyridin-3-yl)amidines (E). Substances of structure C and E seem to be of biological interest, especially for their antianaphylactic reactions.


MAOI activity of some novel series of substituted thiazol-2-yl-hydrazines.

Three series of 2-thiazolylhydrazines were synthetized and evaluated for their MAO inhibitory (MAOI) activity, both by in vivo tests, to assay their influence on several MAOI activity-related parameters (the variation on blood pressure induced by tyramine and clonidine and L-amfetamine-induced hypermotility) and in vitro tests, to assay their effect on rat brain mitochondria by a kinuramine fluorimetric assay. In vivo, all the tested compounds significatively influenced the evaluative parameters used. As regards in vitro test, all compounds displayed MAOI activity at a concentration of 1.10(-4) mol.l-1, which was significant in several cases. In the discussion of the results, the influence of the structure on the biological activity of the prepared compounds was delineated.


[Antiarrhythmic active amidinohydrazones of substituted benzophenones. 3. The isomerization of (E)-2-amino-5-chlorobenzophenone amidinohydrazones].

The isomerization of the title compound in a preparative scale can be realized by acetylation/deacetylation or by influence of protons in dimethylformamide. The title compound is obtained als main product of the condensation of 2-amino-5-chlorbenzophenone and aminoguanidine if the reaction is carried out in the presence of formaldehyde.


[Synthesis of N-(2-carboxy-thieno(2,3-b)pyridin-3-yl)amidines by means of reaction of 4-oxo-4H-pyrido(3',2':4,5)thieno(3,2-d)-1,3-oxazines with primary aliphatic amines].

The title compounds were synthesized by the reaction of tricyclic compounds of structure B with primary aliphatic amines under different conditions and useful isolation methods in good yields. These compounds showed an acceptable antianaphylactic activity.


[Antiarrhythmic active amidinohydrazones of substituted benzophenones. 4. The photoisomerization of (Z)- and (E)-2-amino-5-chlorobenzophenone amidinohydrazones and the corresponding (E)-N-phenylamidinohydrazone].

The title compounds undergo a photoisomerization by irradiation. If the E-isomers are irradiated by light of a wavelength of an absorption maximum typical for them, they can be converted quantitatively to the corresponding Z-isomers. In case that the synthesis of analogs of the title compounds give only one configurational isomer, sometimes the missing one can be obtained by photoisomerization.


Development of medicated aerosol dressings of chlorhexidine acetate with hemostatics.

Aerosol formulations to act as medicated aerosol dressings have been prepared with an aim of forming a protective film over the wound after spraying combining the properties of antiseptics and hemostatics. Chlorhexidine acetate along with three hemostatics namely zinc acetate, methyl cellulose and Calendula tincture were used for the formulations. The formulations were found to be satisfactory in their performance and purpose.


[The effect of cholesterol on membrane potentials, proliferation and migration of cultivated endothelial cells].

The influence of cholesterol added as cholesterol containing liposomes [sphingomyelin/cholesterol (1: 1; mol/mol)] or as cholesterol suspensions on cultured bovine aortic endothelial cells was investigated. 10(-6) mol/l cholesterol enhanced membrane potential, 10(-5) mol/l caused depolarisation. The proliferation of the cells was dependent on the concentration influenced in opposite directions too. The proliferation was stimulated by 10(-6) mol/l cholesterol and inhibited by 10(-5) mol/l. The migratory rate of the cells was increased by 10(-6) mol/l and 10(-5) mol/l cholesterol. Our results suggest that exogenous cholesterol is integrated in membranes of the endothelial cells and causes in this way changes of membrane potential, proliferation rate and migratory activity.


[The development of pharmaceutical analysis at German universities in the 19th and 20th century].

The aim of this paper is to trace some features of the historical development of drug analysis as an academic discipline in its relation to the emergence of pharmaceutical science. In the first half of the nineteenth century pharmacists identified and characterized minerals, plants and drugs. K.F. Mohr played a decisive part in the founding of the new discipline drug analysis. The development described here, which began in Marburg, Breslau and Königsberg and was extended to other places, led to the evolution of drug analysis. The establishing of independent departments, for instance in the former G.D.R., played a decisive role in developing the discipline drug analysis.


The reproductive revolution: new survey findings.

A reproductive revolution is spreading across much of the developing world. Use of effective contraception has risen rapidly, and fertility has been falling. But there is still a long way to go. More than one woman in every five wants to avoid pregnancy but is not using contraception.


Is stupor by itself a catatonic symptom?

Many patients present with stupor or substupor without classical catatonic signs as described by Kahlbaum. The phenomenological literature is not clear as to whether stupor, when it presents alone, constitutes a separate syndrome or is a forme fruste of catatonia. All patients who presented with stupor, (a) partial or total mutism or (b) absent or decreased motor responses (n = 22), were compared with patients who also had classical catatonic signs such as negativism or waxy flexibility (n = 43) over a one-year period (1988), on sociodemographic and clinical variables. There were very few significant differences between the two groups (age, sex, diagnosis, duration of illness, number of ECTs required). The stupor group had a slight excess of patients with manic-depressive psychosis, depression and more frequently positive family histories of mental illness. The current study provides a tentative support to the hypothesis that stupor is a catatonic sign, and even when present alone can be considered to constitute a catatonic syndrome.


A polydiagnostic approach to self-perceived cognitive disorders in schizophrenia.

The relationship between the self-perceived cognitive disorders (SPCD) assessed using the Frankfurt Complaint Questionnaire (FCQ) and 21 definitions of schizophrenia was studied in a sample of 118 consecutively admitted patients. The FCQ total score was significantly associated (p < 0.05) with the presence of Schneider's, Yusin's and Present State Examination criteria of schizophrenia. A significant association, in this case negative, was also found between the FCQ total score and the presence of the DSM-III-R criteria of schizophrenia. The results suggest that the SPCDs are more associated with Schneider-related criteria than with chronic or deficit models of schizophrenia. It was also found that the female sex as well as the presence of insight were significantly associated with a greater number of SPCDs.


On the distinctions between diagnosis, description and measurement of schizophrenia.

The distinctions between diagnostic classification of schizophrenia, the description of the characteristics and course of schizophrenia, and measurement of its severity are discussed. There is confusion among these three categories by both researchers and clinicians. The causes for this confusion are discussed, and it is noted that there are few appropriate measures of cognitive function in schizophrenics. It is proposed that the research design used in most schizophrenia research does not lend itself to the development of more informative interval scales. It is proposed that rather than using performance as a dependent measure with a task of fixed level of difficulty, a 'threshold design' should be used, where the environmental factors are varied to produce a given performance level.


Exploration of obsessive compulsive phenomena: a preliminary investigation.

Different dimensions of obsessions and compulsions were explored in 103 obsessions and 60 compulsions recorded from 32 subjects who received a primary diagnosis of obsessive compulsive disorder. Intrusiveness and repetitiveness formed relatively discrete dimensions, while resistance, distress, irrationality, interference and ease of dismissal tended to be associated within themselves. An anxiety-provoking effect was an additional dimension observed among compulsions.


Suicide in the Nordic countries.

There are great differences in the suicide rates in the closely related Nordic countries. The suicide rates are higher in Finland, especially in males, and Denmark, especially in females, and lower in Norway and Iceland, with Sweden in a middle position. The statistics are found to be comparable. In this article the development from 1880 to the present day is described, and special emphasis is laid on the development from 1960 onwards. Denmark and Finland still keep the top position, while the rise in suicide rates, especially in the age group 15-29 years, has been most marked in Norway. Within the Nordic region Greenland has an extremely high suicide rate, especially in youngsters, while the Faroe islands have a very low rate. Tentative explanations are given for the development of suicide rates in the Nordic countries.


Music psychopathology. V. Objective features of instrumental performance and psychopathology.

Mental disease systematically impairs musical expression according to nosologic classification. This was demonstrated with a polarity profile of the instrumental performances of 60 inpatients and 14 controls matched for musical aptitude. Objective performance characteristics such as irregularities and playing faults were analyzed too. No meaningful correlation between these features and psychopathology resulted. This indicates that even in severe psychopathologic alterations performance features, which depend mainly on education and actual training, are not altered in a systematic manner, in contrast to expressive qualities.


Music psychopathology. VI. The course objective instrumental performance characteristics with psychiatric inpatients.

The impairment of musical expression due to mental disease is reversible with growing remission. This finding resulted from follow-up examinations of instrumental playings assessed by means of a polarity profile with 60 psychiatric inpatients and 14 controls. A follow-up comparison of objective performance characteristics as defined by careful analysis of the recordings did not reveal a meaningful variation. This is taken as a strong indication that even in severe psychopathologic alterations, learned motor patterns of music performance are fairly stable. A simple reduction in playing irregularities cannot explain the systematic influence of psychopathology on musical expression.


Checkers and washers: valid subtypes of obsessive compulsive disorder.

The current study aimed to examine sociodemographic and clinical variables between washer and checker subgroups of obsessive compulsive disorder. Of 412 subjects seen during 1975-1984, there were 123 washers, 70 checkers and 89 washers and checkers (mixed group). Checkers were more likely to be single and male and have an earlier age of onset and consultation; if married the illness was more likely to have started prior to marriage. The mixed group appeared to be a female-dominated pathoplastic variant of the checkers group. The current study suggests that other variables should also be explored in differentiating these disorders.


Trichotillomania. Two case reports from a similar cultural background.

Case reports of 2 female patients from the Makrani culture are presented. They were both around 30 years of age, clinically depressed and responded favorably to antidepressants. One of these patients was infertile, and the other one had started pulling her hair when deprived of her jewelry. Fertility and possession of jewelry represent femininity in the Makrani culture. A brief review of the literature on trichotillomania and its psychopathology is also included.


Differentiation of DSM-III-R anxiety disorders by severity of illness and symptom onset sequences.

187 patients were investigated by a structured interview for DSM-III-R and various clinicians' and patients' ratings. A high frequency of comorbidity between different anxiety disorders and between anxiety and depression was found. According to sociodemographic data, various anxiety disorders showed more similarities than differences. Patients with a generalized anxiety disorder showed an earlier age at onset compared to patients with panic disorder as well as a greater severity of illness and comorbidity. Avoidance behavior occurred before, simultaneous with, as well as after the onset of panic disorder.


Obsessive-compulsive disorder in adolescence. Differential diagnostic considerations in relation to schizophrenia and manic-depressive disorder: a comparison of phenomenology and sociodemographic characteristics.

Some borderline cases of obsessive-compulsive disorder (OCD), schizophrenia, and manic-depressive disorder in whom the diagnosis had been difficult to assess in adolescence are presented. The records of 27 OCD patients with admission both in adolescence and adulthood were compared to a group of manic-depressive and schizophrenic patients with an admission in adolescence where the OCD diagnosis had been given. Some differential diagnostic considerations and difficulties in the borderline area between OCD, manic-depressive psychosis and schizophrenia at the time of the first manifestation in adolescence are described. The symptomatology in the three groups of patients as it was presented in adolescence only showed a few differences, and the patients offered differential diagnostic difficulties to the clinicians.


A typology of alcoholism in Taiwan aborigines: a study on evolving process of community cases.

Thirty-one habitual drinkers with a personal, familial, social complication were screened from a Taiwan aborigine community. Each was given an in-depth descriptive semistructured interview. The interview, recorded with audiotape, contained 4 aspects: (1) personal developmental history; (2) family structure and interaction; (3) developmental process and current state of drinking behavior, and (4) attitude toward drinking behavior. Based on the evolving process and current state of drinking behavior, three process patterns of alcoholism were defined: (1) social developmental type (67.7%); (2) deviant behavioral type (9.7%), and (3) special constitutional type (22.6%).


Assessment of saccadic eye movements as an instrument of differential diagnostic screening.

Fast conjugate (saccadic) eye movements tested for stimuli between 5 and 30 degrees to the left or the right are characterized by three parameters: latency, maximum velocity, and accuracy. The recordings of 152 patients, diagnosed by the psychiatrist for depressive and/or organic symptoms, demonstrate different sensitivity of saccadic parameters to instruction, medication, and psychopathology. The parameter maximal velocity appears to be a parameter of psychopathology, but above all also of medication, while the parameter latency appears to be primarily a parameter of psychopathology. Accuracy is the more 'psychological' or 'volitional' parameter.


Alexithymia and depression in families with alcoholics.

Alexithymia and depression in family members of alcoholics were examined among 48 families. Results were as follows: (1) The prevalence of alexithymia was 47.9% (23 cases), whereas that of depression was only 6.3% (3 cases); (2) no significant correlation between alexithymia and depression was noted; (3) expressiveness and conflict were significantly lower in families with alcoholics than in healthy families without alcoholics, although families with alcoholics do have strong conflicts. The results suggest the possibility that half of them forcefully suppress their conflicts, unconsciously deny the existence of alcoholics, and finally manifest secondary alexithymia.


Occupational epidemiological studies in risk assessment and their relation to animal experimental data.

The role of epidemiological and animal experimental studies in the process of qualitative and quantitative risk assessment is discussed. So far little agreement exists between animal experimental data and epidemiological outcomes in the procedure of qualitative risk assessment. Several reasons for these discrepancies are mentioned. The application of existing epidemiological study results in quantitative risk assessment is hampered by factors, such as the lack of exact exposure information (compound, level, duration), undefined other exposures in and outside the working environment, small sample sizes, the comparatively short duration of epidemiological studies and the absence of detailed information about the specific effects. All this resulted in a relatively small impact of epidemiological studies in risk assessment. Recommendations are made in order to improve the impact of epidemiology in risk assessment.


Environmental tobacco smoke.

In 1992, the U.S. Environmental Protection Agency (EPA) issued a "draft" assessment of ETS and lung cancer in adults and respiratory disorders in children. Relying on weak and inconclusive epidemiological data, the supposed similarity between ETS and MS, the presence of "known or suspected carcinogens" in MS and by extrapolation in ETS, and the "biological plausibility" of an adverse relationship between ETS and health, the EPA recommended that ETS be classified as a "Group A (known human) carcinogen." Fundamental physical and quantitative chemical differences among ETS, MS, and SS and human exposure to each smoke were disregarded: The three are not equivalent nor is ETS exposure a quantitative variant of cigarette smoking. A substantial difference in retention percentage overlays the huge dosimetric difference between exposures. As a result, the "dosage" of ETS retained is miniscule relative to MS. Also, conclusions reached by the EPA and the use of tenuous relationships as bases for Group A classification are unwarranted because of failure to consider the data upon which the "tumorigenicity" of the ETS components was based, questions on the presence and/or levels of these components in MS, and data indicating that a 25- to 30-fold decrease of a high-level dose of MS or MS condensate diminished the effects observed in bioassays from pronounced to zero, i.e., a threshold was demonstrated. Finally, EPA overlooked the more than 100 tobacco smoke components known to inhibit the tumorigenic action of many of the listed "tumorigens."


Macronutrient substitutes: safety evaluation.

Macronutrient substitutes, reduced-calorie substances used to replace organoleptic and/or functional properties of fats and sugars in the diet, may become a significant part of the diet as the trend toward lower fat and lower calorie diets continues. Procedures currently used to evaluate the safety of traditional food additives (microadditives) may be inadequate to properly assess the safety of macronutrient substitutes (macroadditives) because of the unique nature of these substances and the potentially large intakes. An evaluation procedure is proposed that recognizes the benefits to be derived from the test material, uses a structured approach to obtain animal and human nutritional and toxicological (including kinetic and dispositional) data that are critically evaluated and that provide a basis for further testing, encourages consultation with the regulatory agency (FDA), and recommends postmarketing surveillance of the macronutrient substitute. The proposed scheme differs from the traditional approach in many respects, such as using dispositional and kinetic data, assessing nutritional status, using human data collected under carefully controlled conditions early in the process, and consulting with the FDA. A case-by-case approach is recommended for safety evaluation of these macroadditives.


An assessment of the hazards of lead in food.

Exposure to lead (Pb) continues to be a source of concern for the U.S. Food and Drug Administration and other federal regulatory agencies. Blood lead levels as low as 10 micrograms Pb/dl have been associated with impaired neurobehavioral development in children and infants. Because of exposure to the fetus, blood lead levels of 10 micrograms Pb/dl are also of concern in pregnant women. Blood lead levels of 30 micrograms Pb/dl have been associated with elevated blood pressure and other adverse effects in adults. The dietary exposure that results in these blood levels of concern were estimated to be 60 micrograms Pb/day for children age 6 years or younger, 150 micrograms Pb/day for children age 7 years or older, 250 micrograms Pb/day for pregnant women, and 750 micrograms Pb/day for adults. A provisional tolerable total dietary intake was derived by applying a factor of 10 to obtain an exposure level that would include some margin of safety.


The Council for Health and Environmental Safety of Soils.

The Council for Health and Environmental Safety of Soils (CHESS) was organized in 1987 to develop a consensus soil risk assessment methodology to be used as a framework for establishing standards for soil contamination to protect the environment and public health. The wide range of contaminating substances of possible health concern in soil is affecting land use and development, causing excessive economic expenditures, and the regulatory approaches for control are disperse. The International Society of Regulatory Toxicology and Pharmacology agreed to sponsor the Council and through a Governing Board composed of experienced scientists from the federal government, state departments of public health and environmental protection, academia, and the private sector including industry and environmental organizations. The Board was created to support the goals of CHESS, its mode of operation, and to establish funding policies and directions. A technical council agreed to develop a peer-reviewed consensus methodology to assess public health risks from contaminated soil by technical committees composed of recognized experts in the area of soil contamination and other relevant disciplines. This methodology would then be made available to federal and state agencies, the private sector, and the scientific community at large. After extensive study, a final decision was made to develop a decision-tree framework to be used at the state and local levels for application to all types of soil contamination. Following extensive studies it was agreed the ubiquitous nature of petroleum contamination in soil has direct and immediate public health implications and CHESS therefore directed its first efforts to this area.(ABSTRACT TRUNCATED AT 250 WORDS)


Predicting blood lead concentrations from environmental concentrations.

A method is presented by which blood lead concentrations can be estimated from environmental concentrations using a multipathway analysis. For the ingestion and dermal uptake pathways the incremental increase in blood lead concentration is estimated as the product of the concentration in the relevant medium, a medium-specific contact rate, and an empirically determined ratio between intake and blood level. The inhalation pathway omits the contact rate and uses a ratio between the concentration in blood and the concentration in air. Model outputs corresponding to various input parameters are presented, and some of these are compared with outputs from the U.S. Environmental Protection Agency's Lead Biokinetic/Uptake model, Lead 5.


Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs).

The polycyclic aromatic hydrocarbons (PAHs; also referred to as the polynuclear aromatic hydrocarbons or PNAs) are commonly encountered at hazardous waste sites and are often the focus of site remediation activities. However, toxicity criteria are not available for all the PAHs. In the past, EPA has assessed risks posed by mixtures of PAHs by assuming that all carcinogenic PAHs are as potent as benzo[a]pyrene (B[a]P), one of the most potent PAHs. The available information on the toxicity of the PAHs suggests that most are considerably less potent than B[a]P and therefore, the EPA approach is likely to overestimate risks. Several approaches have been developed to allow the relative potency of the different PAHs to be considered in a site-specific risk assessment. This paper evaluates these approaches and presents a modified version that we feel more accurately reflects the state of knowledge on the relative potency of these compounds.


Reevaluating the carcinogenicity of ortho-toluidine: a new conclusion and its implications.

The aromatic amine ortho-toluidine has been recognized by IARC as an animal carcinogen for the past decade. Three recent epidemiological studies of worker populations have now implicated this chemical as a human bladder carcinogen. In a study by E. Ward, A. Carpenter, S. Markowitz, D. Roberts, and W. Halperin ((1991), J. Natl. Cancer Inst. 83, 501-506), workers definitely exposed to ortho-toluidine for at least 10 years experienced a Standardized Incidence Ratio (SIR) of 27.2 (90% CI = 11.8-53.7). The other major exposure was to aniline, which significant epidemiological studies have failed to confirm as a human carcinogen. In retrospect, studies by G. F. Rubino, G. Scansetti, G. Piolatto ((1982) Environ. Res. 27, 241-254) and M. J. Stasik ((1988) Int. Arch. Occup. Environ. Health 60, 21-24) also support the hypothesis that ortho-toluidine is a human bladder carcinogen. Animal studies of both ortho-toluidine and its possible confounders in these epidemiological investigations further confirm this hypothesis. When evaluated in a suitably comprehensive way, according to the traditional standards for assessing causality outlined by A. B. Hill ((1977) A Short Textbook of Medical Statistics, pp. 288-294, Lippincott, Philadelphia) the evidence that ortho-toluidine causes human bladder cancer has become much more conclusive. In this case, animal tests have proven a good predictor of human carcinogenicity.