Preservation of probing attachment and alveolar bone levels in 2 random population samples. The present study is an attempt to elucidate the relation between ageing and loss of periodontal tissue support, by studying the occurrence of probing attachment and alveolar bone loss in two samples of randomly selected individuals. The 1st sample was recruited in Japan and comprised 319 subjects aged 20-79 years. The 2nd sample was recruited in Sweden and comprised 192 subjects aged 30-65 years. All individuals underwent a radiographic and a comprehensive clinical examination, including recordings of probing attachment level. Within the 2 samples, subsamples of individuals whose periodontal status indicated minimal experience of destructive periodontal disease were selected. In these particular subsamples, it was revealed that a substantial proportion of tooth surfaces, also in older subjects, remained with no attachment or alveolar bone loss. To a lesser extent, this could be also observed when the entire samples were analyzed, despite the presence of abundant plaque and gingival inflammation. The results indicated that intact supporting periodontal tissues can be retained in subjects of increased age and corroborate the suggestion that loss of clinical attachment and alveolar bone is not an obligatory consequence of ageing.


The effect of partial denture connectors on gingival health. The effect on the gingiva of a variety of relationships of a removable partial denture connector to the gingival margin was investigated in 10 subjects. Acrylic resin baseplates were designed incorporating a variety of relationships of the connector to the gingival margin. The appliances were worn for a 12 hour period daily, for 21 days. At baseline and at days 7, 21 and 49, plaque index, gingival index and probing pocket depth measurements were recorded, and subgingival plaque samples were examined using darkfield microscopy. No increase in plaque accumulation was detected in any area at any time interval. There was a significant increase in gingival index at day 21 in areas where the appliance covered the gingival margin. Small increases in probing pocket depth were recorded at day 21, there being no difference between any of the test areas. Baseline values were re-established by day 49. No significant differences were detected in the percentage of motile organisms or spirochaetes counted in the subgingival plaque samples collected from any area. It was concluded that deterioration in gingival health occurred rapidly following the insertion of a removable appliance, and that coverage of the gingival margin, irrespective of the degree of gingival relief, had a detrimental effect.


Clinical effects of simultaneous ultrasonic scaling and subgingival irrigation with chlorhexidine. Mediating influence of periodontal probing depth. The clinical and microbial effects of a single episode of simultaneous ultrasonic scaling and subgingival irrigation with chlorhexidine (CHX) were studied as a function of clinical probing depth in patients with adult periodontitis. 60 patients were randomly assigned to receive subgingival irrigation under cavitation with either sterile water or 0.12% CHX delivered through the tip of an ultrasonically activated scaler as part of initial periodontal therapy in a double-blind study design. 3 periodontal sites were randomly selected for examination from each patient on the basis of clinical probing depth, with 1 site being selected within each of the following ranges: 1-3 mm, 4-6 mm, and 7-9 mm. Pretreatment and post-treatment (days 14 and 28) clinical assessments included a plaque index (PI), gingival index (GI), and clinical probing depth (CPD). Subgingival specimens also were collected from 1-3 mm and 4-6 mm sites on a random subset of patients (15 per group). Plaque counts of spirochetes and motile organisms were made by darkfield microscopy. Significant reductions in PI, GI, and CPD were observed among all sites within both treatment groups at 14 and 28 days post-treatment. CHX irrigation resulted in a significantly greater reduction in CPD than did water among sites initially probing 4-6 mm at both 14 and 28 days post-treatment (25% versus 13% and 31% versus 18%, respectively). Spirochete counts were modestly but nonsignificantly reduced at 14 days post-treatment among sites 4-6 mm within both treatment groups. These results suggest that subgingival irrigation with CHX during ultrasonic scaling provides differential clinical benefits that are site-dependent.


A sensitive method for the detection of immune complexes in human gingival crevicular fluid. An assay for immune complexes [ICs] in gingival crevicular fluid [GCF] could be potentially useful to ascertain the risk of periodontal disease activity at specific oral sites. This paper describes and ELISA-based method sufficiently sensitive to measure ICs in GCF samples at levels below 1 microgram/ml. Static GCF samples taken from 5 adults showed IC levels ranging from 5 to 166 micrograms/ml. Additional tests of 10 GCF samples from 1 adult were conducted with complement components and indicated that either C1q or rabbit anti-human C3d was suitable as a capture agent in the assay procedure. Further application of this assay may help to assess the usefulness of IC levels in GCF samples as possible diagnostic indicators of periodontal disease activity.


Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease. This paper describes the development of a stable, controlled-release formulation of metronidazole for use in the treatment of periodontal disease. It is formulated as a suspension, which undergoes transformation to a release-controlling, semi-solid on contact with gingival fluid. The system is based on the ability of mixtures of monoglycerides and triglycerides to form liquid crystals, i.e., reversed hexagonals, in contact with water. The reversed hexagonal form was found to have the most favourable sustained release properties, compared with those from the cubic form. The source of metronidazole is the prodrug, metronidazole benzoate, which further helps to slow down the release rate. Product characteristics are assessed by differential scanning calorimetry and viscometry. The release data derive from the results of in vitro dissolution tests. X-ray diffraction, phase diagrams, and polarized light microscopy were used to elucidate the structure of the liquid crystalline phases.


Systemic absorption of metronidazole after application of a metronidazole 25% dental gel. Systemic absorption of metronidazole was studied after one application of a metronidazole 25% dental gel into inflamed periodontal pockets. 14 patients with periodontal disease participated. Metronidazole gel was applied into the pockets of all teeth with probing depth > or = 5 mm, minimum 10 teeth/patient. Excess gel was carefully collected in order to calculate the amount of metronidazole applied into the pockets. Blood samples for analysis of metronidazole in plasma were taken before and up to 72 h after application. To determine the bioavailability of metronidazole administered as gel, the patients were later given an i.v. dose of 100 mg metronidazole. Metronidazole was quantified by HPLC. The mean actual dose of metronidazole in gel was 55 mg (SD: 24 mg, range: 29-103 mg). Allowing for the fact that excess gel corresponding to about 60% of the applied amount of metronidazole under normal clinical conditions may be swallowed, the systemic load after one application of metronidazole 25% dental gel will still be less than after one metronidazole 250 mg tablet. Peak plasma concentrations varied between 223 and 1303 ng/ml (mean: 581 ng/mk, SD: 320 ng/ml) and were reached within 2 to 8 h (mean: 4.4 h). The mean bioavailability of metronidazole dental gel was 71%.


Concentration of metronidazole in periodontal pockets after application of a metronidazole 25% dental gel. The metronidazole concentration was monitored in gingival crevicular fluid (GCF) of inflamed periodontal pockets after 1 application of a 25% gel. 12 patients with periodontal disease were included in the study. Metronidazole gel was applied with a syringe into the pockets of 10 teeth with probing depths > or = 5 mm. Samples of GCF were taken with Periopaper before application and 4, 8, 12, 24 and 36 h after application. At each time, samples from 2 teeth were pooled in order to obtain a sufficient amount of fluid for analysis. By means of a calibrated Periotron, the collected volume of GCF was measured. High-performance liquid chromatography was used to determine the amount of metronidazole. MIC50 for anaerobic periopathogens susceptible to metronidazole is below 1 microgram/ml. In this study, the concentration obtained was higher than 1 microgram/ml in all samples after 4 and 8 h, in 92% after 12 h, in 50% after 24 h and in 8% after 36 h. Thus, metronidazole concentrations in the pockets were generally above MIC50 for susceptible periopathogens 24 h after 1 application of a 25% metronidazole gel.


The effect of topical metronidazole therapy on experimentally-induced periodontitis in the beagle dog. The present study was performed to assess the effect of topical metronidazole therapy on ligature-induced periodontitis in beagle dogs. 6 beagle dogs with experimentally-induced periodontitis on the mandibular 2nd, 3rd and 4th premolars were treated with metronidazole 10% dental paste 2 x daily for 4 weeks in an open placebo-controlled study using a split-mouth design. Recordings of probing pocket depth, bleeding on probing and gingival index were performed before commencement of treatment and repeated weekly during the 4-weeks treatment period. Concurrently, samples for microbiological analysis were collected from 2 of the dogs. The results demonstrated that probing pocket depth, bleeding on probing and gingival index had improved significantly in the metronidazole-treated side compared with the placebo-treated side. Black pigmented Bacteroides spp. and Spirochetes, present in all samples before treatment, were eliminated from the metronidazole-treated side after the 1st week of treatment and throughout the treatment period, whereas they were present in all samples from the placebo-treated side. The result of the present study demonstrates that topical application of metronidazole in a dental paste, improves the clinical features of the experimentally-induced periodontitis and eliminates some of the micro-organisms associated with the disease.


3 regimens of topical metronidazole compared with subgingival scaling on periodontal pathology in adults. This report presents the findings from an open randomized multicentre clinical trial designed to compare the clinical efficacy of scaling with application of 3 different preparations/dose frequencies of topical metronidazole in the treatment of adult periodontitis. The 4 treatments were: (A) metronidazole 25% dental gel administered 1 x a week for 2 weeks; (B) metronidazole 15% dental gel applied 1 x a week for 2 weeks; (C) metronidazole 15% dental gel applied 2 x a week for 2 weeks; (D) subgingival scaling, performed 1 x only. A split mouth design was used. Patients were included in the study if they had at least 1 tooth in each quadrant with a pocket depth > or = 5 mm in at least 1 of 4 sites. A total of 61 patients from 4 centres were entered into the study. The efficacy parameters were probing pocket depth and bleeding on probing. Follow-up visits for recording of clinical efficacy were made at 2, 4, 6 and 12 weeks after the end of metronidazole treatment. All 3 antibiotic treatments (A, B, C) reduced the symptoms of periodontal pathology and yielded results comparable to those seen after subgingival scaling (D). When using a topical drug therapy, it seems important to use a preparation that requires as few applications as possible. The best candidate for drug therapy would therefore be treatment (A) metronidazole 25% applied 1 x a week for 2 weeks.


Clinical responses to subgingival application of a metronidazole 25% gel compared to the effect of subgingival scaling in adult periodontitis. A newly developed metronidazole 25% dental gel was compared with subgingival scaling in the treatment of adult periodontitis. 206 patients in 9 centres participated in the study. Probing pocket depth (PPD) and bleeding on probing (BOP) were recorded before treatment and 2, 6, 12, 18, and 24 weeks after the treatment. All patients had at least 1 tooth in each quadrant with a PPD of 5 mm or more. The treatments consisted of 2 applications of dental gel (days 0 and 7) in 2 randomly selected quadrants (split mouth design) and 2 sessions of subgingival scaling (1 quadrant on day 0, and 1 quadrant on day 7). Instruction in oral hygiene was given 2 weeks after completed treatment. The average PPD and the average frequency of BOP were calculated over all sites with initial PPD of 5 mm or more. PPD and BOP were thus, at each examination, calculated from the same sites. The mean PPD was 5.9 mm before gel application and 5.8 mm before scaling (p = 0.31). BOP was 88% in both treatment groups. 24 weeks after the treatment, PPD and BOP were significantly reduced in both groups and for both parameters (p < 0.01). PPD was reduced by 1.3 mm after gel application and 1.5 mm after scaling; BOP was reduced by 32% and 39%, respectively. The difference between the treatments was statistically significantly, but considered as clinically unimportant.


Retinoids in cancer treatment.

Retinoids in cancer treatment. Since initial studies identifying the important role of vitamin A and its derivatives (retinoids) in maintaining the integrity of epithelial tissues, these compounds have served as paradigms for experimental studies exploring the pharmacologic modification of carcinogenesis. Retinoids have clearly been shown to inhibit chemically induced mammary and urothelial carcinogenesis in experimental animals. Prohibitive toxicity of the parent compound, vitamin A, led to a systematic search for synthetic derivatives with an improved therapeutic index. More than 1500 such compounds have been synthesized, many retaining chemopreventive potential, but with less toxicity. Although several anecdotal reports confirming therapeutic benefits of cis-retinoic acid in patients with acute promyelocytic leukemia and myelodysplastic syndromes appeared in the late 1970s and early 1980s, the remarkable studies of Huang and his colleagues in China in 1988 reporting complete remissions in patients with this uncommon variety of acute myelogenous leukemia with the transisomer of retinoic acid (all-trans-retinoic acid) led to a resurgence of interest in the retinoids as differentiating agents for the prevention and therapy of cancer. Furthermore, molecular studies showing DNA rearrangements of the alpha nuclear receptor for retinoic acid located on chromosome 17 in patients with acute promyelocytic leukemia, a disease invariably associated with a translocation between chromosomes 15 and 17, provided a direct connection between an altered nuclear receptor and the development of a human malignancy. The retinoids also may have important beneficial effects in prevention of recurrent malignancies once the primary tumor has been treated, such as in squamous cell carcinoma of the head and neck. Because retinoids appear to be less effective in inducing differentiation in nonpromyelocytic leukemia cells, investigators have conducted a number of studies to exploit potential synergism between retinoids and other differentiating agents or biologic effectors. Differentiation therapy and chemoprevention are attractive alternative approaches to intensive cytotoxic chemotherapy. It is now clear that retinoids represent one class of compounds with which it may be possible to reverse the progression of malignant disease and prevent carcinogenesis.


A comparison of regulatory approval times for new chemical entities in Australia, Canada, Sweden, the United Kingdom, and the United States. Regulatory approval times of new chemical entities (NCEs) in Australia, Canada, Sweden, the United Kingdom (UK), and the United States (US) were compared. The approval times of a set of common 25 NCEs and a larger set of unmatched NCEs were very similar in Australia, Canada, Sweden and the US, with median approval times from 23 to 29 months. The median approval time in the UK was approximately 11 months. Analysis of the data showed that the approval times in Australia, Sweden, and the UK were not significantly affected by the therapeutic classification of the drug, the amount of additional data requested and received, or the submission date. In Canada, the date the drug submission was received and the frequency of additional data requests significantly affected the approval times. In the US, the date the drug submission was received and the frequency of additional data received significantly affected the approval times. The therapeutic classification of the drug did not significantly affect the approval time in Canada or the US.


Advances in the diagnosis of adverse drug reactions. The clinician plays a key role in the detection and diagnosis of adverse drug reactions (ADRs). The diagnosis of ADRs, however, is a complex task. In the past, there were no systematically applied diagnostic criteria for ADRs, no formal methods of case analysis, no standardized epidemiologic approaches, and a limited knowledge of mechanisms. This resulted in the overdiagnosis of ADRs, which has negative consequences such as limiting treatment options. Recently, there have been various improvements in the diagnosis of ADRs, such as the development of standardized decision aids and of in vitro diagnostic tests. This article briefly reviews some of this knowledge, discusses the role of in vivo and in vitro rechallenge, and summarizes a probabilistic approach for collecting relevant information and diagnosing ADRs. The intention is to increase awareness of the different approaches for diagnosing ADRs as well as to stimulate researchers to continue to collect pharmacoepidemiologic information, study the pharmacologic, immunologic, and genetic factors involved in the pathogenesis of drug reactions, and develop and test new diagnostic instruments under various clinical conditions.


N-acetylation polymorphism and diabetes mellitus among Saudi Arabians. The acetylator phenotypes of 200 Saudi diabetics and an equal number of control subjects of the same origin were determined by measuring the peak height ratio of two urinary caffeine metabolites, 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1-methylxanthine (1MX), using a simplified high-performance liquid chromatographic method. Urine samples were collected from the diabetics and the control subjects who regularly drink coffee, tea, or caffeinated beverages as part of their normal daily diet. The patients were classified as either type 1 (insulin-dependent) (28 patients) or type 2 (insulin-independent) diabetics (172 patients) according to standard criteria. The reproducibility of acetylator phenotype was established by examining the peak height ratio of AFMU/1MX in 18 diabetics and 6 control subjects on different days. Significant differences in the proportion of rapid acetylators were observed between type 1 (53.6%) and type 2 (33.7%) diabetics (P < or = .0436), and between the control group (26%) and the overall diabetics (36.5%) (P < or = .024) or those with type 1 disease (P < or = .0028). Also, there was a significant (P < or = .0436) association between rapid acetylator status and type 1 diabetes mellitus.


Arithmetic versus harmonic mean values for cyclosporin-A pharmacokinetic parameters. The harmonic and arithmetic mean values for volume of distribution at steady state, half-life, and clearance of intravenous cyclosporin-A were calculated using an index set of 22 renal transplant candidates to determine if harmonic mean values provide a less biased estimate of central tendency than arithmetic mean values. Cyclosporin-A was measured using a nonspecific radioimmune assay method. The arithmetic mean value for volume of distribution was 16% larger than calculations by the harmonic mean method. Similarly, the arithmetic mean half-life and clearance values were larger than harmonic mean values by 10% and 15%, respectively. However, 95% confidence intervals for these pharmacokinetic parameters overlapped. When these mean pharmacokinetic parameter values were used to predict actual values in a test group of 22 renal transplant candidates receiving cyclosporin-A, similar levels of precision were demonstrated by either method. Both methods produced positively biased predictions for volume of distribution and clearance. However, these differences were not significant. These findings suggest there is little practical value for the use of harmonic mean calculations to describe the central tendency of pharmacokinetic parameters of cyclosporin-A under the conditions studied. The value of harmonic mean values for pharmacokinetic parameters in other patient populations or with other assay methods for cyclosporin remain to be studied.


Mirror images: the analysis of pharmaceutical enantiomers. Pharmaceutical enantiomers often exhibit different pharmacodynamic and pharmacokinetic properties. Stereospecific chromatographic assays are available to separate these stereoisomers. Therapeutic agents often contain chemical functional groups (e.g. amino, hydroxyl, carbonyl, and carboxylic acid). These can be reacted with enantiomerically pure reagents to give diastereoisomers suitable for analysis on achiral gas chromatographic (GC) and high performance liquid chromatographic (HPLC) columns. Alternatively, derivatized or underivatized drugs may be resolved on chiral chromatographic phases. A wide variety of GC (e.g. amino acid, cyclodextrin, and metal-complex) and HPLC (mobile phase additive, crown ether, pi-pi interaction and related phases, protein, cyclodextrin, polysaccharide, methacrylate and amide polymer, and ligand exchange) columns are commercially available. This article reviews the chromatographic separation of enantiomers.


The importance of stereochemistry in drug action and disposition. Many biologically active synthetic drugs contain chiral centers, although they are used as racemic mixtures. Enantiomers are hard to distinguish in the chemical laboratory but are readily discriminated in the body and differ in their biological activities and disposition. The pharmacokinetic profiles of enantiomers can be variable, especially for drugs with a first-pass effect and enantioselective pharmacokinetic monitoring should be carried out. Ultimately, whether to exploit a racemate or a single enantiomer in therapy is a multi-faceted decision to which drug disposition data have important contributions to make.


Stereochemistry and bioequivalence.

Stereochemistry and bioequivalence. Despite the fact that many important drugs are chiral, for a variety of reasons they are marketed as racemates (i.e., an equal proportion of two enantiomers). Although enantiomers of racemic drugs often differ from one another in their pharmacodynamic and pharmacokinetic properties, bioequivalence assessments are made using nonstereospecific assays. Such an approach may provide a poor assessment of therapeutic equality. This can be true particularly for drugs with complicated pharmacokinetics and those that exhibit extensive stereoselectivity in their disposition kinetics. Accordingly, examples of bioequivalence studies based on stereospecific assays have started to appear in the literature. Fortunately, facile stereospecific assays have become available in the last several years for many drugs. Consequently, regulatory agencies have started to take the issue of stereochemistry into consideration in the assessment of bioequivalence, particularly from the standpoint of generic substitution.


Bioequivalence of racemic drugs.

Bioequivalence of racemic drugs. Although pharmacokinetic and pharmacodynamic differences between the enantiomers of a chiral drug have been known or suspected for many years, racemate drugs have frequently been developed and approved without clinical pharmacologic consideration of their chiral components. In the late 1970s, the technology to isolate, manufacture, and detect pure enantiomers of racemate drugs became generally available. This availability has created new demands on both pharmaceutical firms and regulatory agencies. To prepare for this new technology, the Center for Drug Evaluation and Research at the Food and Drug Administration is formulating a policy statement to guide evaluation of new chiral drugs. At this time, it appears that whatever new policies are developed will not necessarily be applied retroactively to previously approved racemate drugs. Additional policies to guide the development and approval of generic and OTC chiral drugs may be required. In the Office of Generic Drugs in the Center, abbreviated new drug or antibiotic applications are approved on the basis of adequate chemistry, manufacturing, and control procedures and comparative pharmacokinetics (bioequivalence). The generic drug must be a racemate or single enantiomer if the corresponding innovator drug is a racemate or single enantiomer respectively. Whether a generic firm will be required to provide bioequivalence information on enantiomers of a racemate is determined on a case-by-case basis. Although it might be claimed that a generic drug product should be required only to undergo the same general kind of pharmaceutical evaluation as did the innovator, there may be instances when the approval of a generic drug or antibiotic will require measurement of specific enantiomers of a chiral drug.


Pure enantiomers of 2-arylpropionic acids: tools in pain research and improved drugs in rheumatology. The mode of action of aspirinlike drugs in pain is widely referred to as inhibition of prostaglandin synthesis. Salicylic acid, however, at low doses, is an analgesic but not a potent anti-inflammatory agent. This "enigma" may be resolved by recent findings employing 2-arylpropionic acids. Pure enantiomers of these chiral drugs show a different pharmacodynamic and pharmacokinetic profile. Using pure enantiomers of flurbiprofen, ibuprofen, and ketoprofen, we could show that (1) R-enantiomers of these drugs are inverted to S-enantiomers to a different degree in different species, including humans, (2) the pharmacokinetic parameters of both pure enantiomers differ in a drug- and a species-specific manner, and (3) both enantiomers exert differential analgesic effects. It appears particularly interesting that R-flurbiprofen, for instance, which is not or only to a small extent inverted in humans and rats, is practically devoid of prostaglandin synthesis inhibition in vitro. Consequently, in line with current thinking, R-flurbiprofen is not toxic to the gastrointestinal tract and shows no anti-inflammatory effects. In contrast to current concepts, however, this enantiomer does exert analgesic activity in different models of pain and nociception. It is concluded that R-flurbiprofen and, possibly, other R-enantiomers of 2-arylpropionic acids may exert novel analgesic effects independently of peripheral prostaglandin synthesis inhibition in inflamed tissue.


Unique topographic separation of two spectral classes of cones in the mouse retina. We have found two immunologically distinguishable cone types in the retina of the mouse, each localized to two opposite halves of the eye. One cone type was labelled by the monoclonal antibody COS-1 specific to the middle-to-long wave sensitive visual pigment of the mammals, while the other type was stained by the shortwave-specific monoclonal antibody (OS-2). These results were confirmed with other antibodies directed against specific sequences of the visual pigments. As a result of the uneven distribution of the two cone types the mouse retina is divided into two fields separated by an oblique meridional line. The middlewave sensitive cones were present exclusively in the dorsal half of the mouse retina (M-field). The overwhelming majority of the shortwave sensitive cones occupied the ventral half (S-field), and only a small number was scattered among the middlewave sensitive cones in the dorsal retina. The ratio of the two cone types in the M-field corresponds to what has been found in the retina of other mammals, including rodents such as the gerbil and the rat. The S-field represents an entirely unique area with the unusually great number of shortwave sensitive cones and with the complete lack of the middlewave sensitive ones. The present study provides the structural basis for dichromacy in a rodent species considered for a long time to be monochromat. In addition, it shows that the ventral retina, containing exclusively S-cones in a relatively high density, is a unique retinal field not present in other mammalian species studied so far.


Central projections and motor nuclei of the facial, glossopharyngeal, and vagus nerves in the mormyrid fish Gnathonemus petersii. Most of the information about the anatomy of the fish's cranial nerves was collected in the first two decades of this century. Experimental analysis of the VIIth, IXth, and Xth cranial nerves by modern tract tracing techniques started about 20 years ago. Several species have been investigated to date, including one species of Agnatha (Myxinoidea), two species of elasmobranchs, and species of some orders of Teleostei like Cyprinidae, Siluriformes, Perciformes, and Gadidae. The sensory and motor nuclei of the VIIth, IXth, and Xth cranial nerves of Gnathonemus petersii were studied by anterograde and retrograde axoplasmatic transport of horseradish peroxidase and cobaltous lysine complex. The sensory nuclei form a continuous column of cells in the brain stem extending caudal to the obex. The rostral one-fourth of this column is occupied by the overlapping terminals of the VIIth and IXth nerves. The vagus nerve has 5 roots. The first 4 of these innervate the gills and the fifth supplies viscera. Afferents from the gills terminate ipsilaterally rostral to the obex in topographic order and their terminal fields overlap. Viscerosensory fibers terminate ipsilaterally in the obex region and bilaterally in the commissural nucleus of Cajal. The facial motor nucleus is located rostral to the sensory nucleus. Facial motoneurons have pear-shaped and multipolar perikarya. Their axons form a rostrally directed knee before leaving the brain. The motoneurons of the IXth and Xth nerves have a common cell column. The vagal motoneurons form a periventricular, a medial, and an intermediate cell group rostral to the obex. In the obex region and also caudal to it, a lateral and a caudal group can be distinguished. Vagal motoneurons show a topographic arrangement that is similar to that of the sensory vagal projections. The majority of motoneurons have pear-shaped perikary and ventrolaterally oriented dendrites. In the caudal nucleus the dendrites extend dorsally and overlap the terminals of sensory fibers. The axons form a dorsolaterally directed arch before joining the sensory roots. Since G. petersii uses its electrosensory system primarily for detection of food, its gustatory system is less developed than in other fishes, which possess a large number of taste buds.


Cytoarchitectonic organization and morphology of cells of the field L complex in male zebra finches (Taenopygia guttata). The organization of the field L complex, a thalamorecipient auditory region in the telencephalon of birds, was examined in Nissl and Golgi preparations of male zebra finches (Taenopygia guttata). The field L complex comprises five cytoarchitectonic subdivisions: L1, L2a, L2b, L3, and L, although the border between L and L2b is not distinct. L2a is a plate extending dorsocaudally from the dorsal medullary lamina in the caudal neostriatum. L1 lies on the anterodorsal border and L3 lies on the posteroventral border of L2a. L, the area designated "field L" by Rose (J. Psychol. Neurol., 1914, 2:278-352), forms the medial and posterior borders of the field L complex. L2b is a thick band that forms the dorsal and dorsolateral boundary of the field L complex and is continuous with L medially. Nucleus interface (NIf) is a nucleus that lies between L2a and L1 near the lateral edge of the complex. The four types of Golgi stained neurons that occur in the zebra finch field L complex correspond to those described for the European starling (Sturnus vulgaris). Additionally, type 3 neurons are subdivided into "unoriented" neurons with spherical dendritic fields and "oriented" neurons with bipolar dendritic fields. NIf contains a distinct class of neurons that have large somata with both thick and thin spiny dendrites. The distribution of Golgi cell types between the subdivisions of the field L complex corresponds to the morphology of cells seen in Nissl material. Type 3 oriented cells are found almost exclusively within L2a. L3 has significantly greater numbers of the largest cells (type 1) and significantly smaller numbers of the smallest cells (type 4) than does L1. There are no significant differences in the distribution of Golgi stained cells between L2b and L.


Design and control of the head retractor muscle in a turtle, Pseudemys (Trachemys) scripta: I. Architecture and histochemistry of single muscle fibers. We are using the head retractor muscle (RCCQ) of a turtle, Pseudemys scripta, to analyze the neuromuscular mechanisms by which organisms vary the force and timing of muscle contraction. Previously we demonstrated that RCCQ comprises three histochemically defined fiber types: fast glycolytic (Fg), fast oxidative glycolytic (FOG), and slow oxidative (SO). In the present paper we report the 1) architectural features of single muscle fibers in RCCQ, including their lengths, diameters, and taper characteristics, 2) histochemical profiles of single muscle fibers, and 3) quantitative relations between our architectural and histochemical variables. Single fibers in RCCQ exhibit an order of magnitude variation in length (4-60 mm). Approximately 40% span the full muscle. The remaining fibers generally attach to bone or tendon at one end, and the other end tapers intramuscularly; rarely a fiber may taper at both ends. The maximum (untapering) diameters of single fibers are bimodally distributed, forming two diameter classes. Fibers also vary in the percentage of their total length that tapers and in the shape of the tapering region. Large diameter muscle fibers generally are longer and have shorter, more blunted tapers than small diameter fibers. The large diameter fibers are almost all Fg types; these fibers have a median diameter of 59.3 microns, and they account for approximately 60% of total fibers in RCCQ. FOG and SO fibers generally have small diameters (median: 32.5 microns and 35.8 microns), and they typically account for 30% and 10% of total fibers. We use these relations to draw inferences about the attachments and architecture of glycolytic (Fg) and oxidative (FOG, SO) fiber types. Taken together, our data suggest that single muscle fibers in RCCQ may be architecturally as well as histochemically specialized to perform different roles in head retraction. In the accompanying paper we report the efferent innervation of these fibers and consider some of the neural control problems posed by these diverse fiber types.


Parent-child agreement on children's behaviours reported by the Child Behaviour Checklist (CBCL). The authors examined agreement between parent and child ratings on the Child Behaviour Checklist in a sample of 1299 referred adolescents over a period of three years. Correlations ranged between 0.72 and 0.08 (mean = 0.28), while agreement using kappa was similar but slightly lower (mean = 0.24; range 0.71-0.07). Agreement on externalizing was higher than on internalizing items, and concordance increased with age for boys, while there were no differences in parent-child agreement between boys and girls. Agreement was higher for dimensions of behaviour, e.g. depression (r = 0.40).


Erotomania in an adolescent: clinical and theoretical considerations. Erotomania is a relatively rare delusional syndrome, typically seen in heterosexual women of middle-age or beyond. This is the first reported occurrence in an adolescent, and one of very few involving homosexual orientation. A detailed case report is discussed in the context of adolescent developmental phenomena, including "crushes", identity formation, and the resolution of sexual orientation. The presentation of erotomania as alleged sexual abuse, and a possible etiologic role for childhood sexual trauma, are considered.


Preference for outdoor play during early adolescence. The present study examined the extent to which boys' and girls' preference for outdoor, vigorous activity changed as they became socialized to middle school. A sample of 133 boys and girls were studied for one year: those just beginning middle school (sixth graders) and those with one year experience (seventh grade). Measures of children's preference for the playground, the duration of their stay outdoors, and behaviors while outdoors were obtained through direct observational methods. Additionally, teachers' rated children's level of achievement, physical attractiveness, and facility in games. Children also rated each other in terms of dominance status. Results indicated that boys', compared to girls', preference to play outdoors existed only in sixth grade. Factor analyses indicated that three factors described these children: Teachers' Choice, Active Female Oriented, and Outdoor Male Oriented. All three factors varied as children progressed through middle school. Results are discussed in terms of life course developmental theory.


Adolescents' perceptions of significant individuals in their lives. 180 adolescents, aged 11-12 years, and 180, aged 15-16 years, from one Scottish secondary school participated in this study. The purposes of the investigation were: to determine the most significant family member and unrelated person in young peoples' lives; and to identify which characteristics rendered these persons important. 'Mother' and '(same sex) friend' emerged as the outstanding choices. Family members (except siblings) were associated with positive characteristics, whilst amongst unrelated adults, youth group leaders were viewed positively. By contrast, school teachers were primarily seen as occupying a challenging role. Where age and sex differences were found, it was invariably those in early adolescence and females who were more likely to attribute positive characteristics. These results are discussed in relation to the concept of 'mentoring' and the role of mentors in adolescents' lives.


Ethnic identity and self-esteem: an exploratory longitudinal study. Recent models of ethnic identity formation in minority youth suggest a progression over time from an unexamined or diffuse stage to an achieved ethnic identity. To examine changes with age in ethnic identity and self-esteem, eighteen adolescents from three ethnic groups (Asian American, Black, and Hispanic) were assessed at age 16 and three years later. Results of this exploratory study showed a significant change to higher stages of ethnic identity over the three-year period. Self-esteem and ethnic identity were significantly related to each other at each time period and across the three-year time span.


Moratorium-achievement (MAMA) cycles in lifespan identity development: value orientations and reasoning system correlates. Three important questions emerging in identity research are: Why do only some persons with Foreclosed identities move on to Identity Achievement? Why do some Identity Achievement persons move "back" to Foreclosure? How can life-span identity re-formulation be accounted for? This study proposes that individual's positions on two variables, "instrumental vs. experiential orientation" and formistic vs. dialectrical thinking, may be important in answering these questions. Among 60 university students, 23 males and 37 females, those in an identity status characterized by formation and maintenance of structure (Foreclosure) were instrumentally-oriented while those characterized by openness to change and revision (Moratorium) were experientially-oriented. Similarly, more Moratoriums than other statuses were high in dialectic thinking. These results are discussed in terms of their theoretical implications for life-span identity development.


Interpersonal needs in middle adolescents: companionship, leadership and intimacy. Recent research suggests that, along with identity, intimacy is an important developmental construct during adolescence. Are there gender differences in current society regarding intimacy development? Two hundred and seven middle adolescents (70 males and 137 females) were measured using Schutz's (1958) Fundamental Interpersonal Relationship Inventory (FIRO). The FIRO is a self-report survey which assesses the subject's perceived expressions and perceived desires in three categories of interpersonal relationships: Inclusion (companionship), control (leadership), and affection (intimacy). Results indicated that there were differences in expression of inclusion, control, and affection, and desire for inclusion and affection. A second analysis addressed the perceived ranking in importance of the three interpersonal categories measured. Males ranked control expressed highest and affection desired lowest; females ranked affection desired as highest and control expressed lowest. Both groups ranked inclusion desired and expressed as moderate. The current research suggests that gender differences in the development of intimacy may occur as early as middle adolescence.


Perceived parental rearing, personality and mental status in Japanese adolescents. As a part of a prospective study on the psychological adjustment of Japanese teenagers enrolled in a foreign exchange student program, the Parental Bonding Instrument (PBI), the Maudsley Personality Inventory and the General Health Questionnaire (GHQ) were administered to 130 females and 47 males aged 17 through 19 before departure. Parental practices were found to influence personality features, which in turn contribute to the mental health status, but no direct significant relationship was found between the PBI and GHQ measures. The last finding is in contradistinction to the previous reports which report low care and high overprotection in unipolar depressives and anxiety disorder patients but in accordance with a recent finding which failed to replicate them in general population. It is possible that the earlier findings in clinical populations were a case of Berkson bias.


[Synthetic bioantioxidants--inhibitors of acetylcholinesterase activity]. The inhibitory effects of synthetic antioxidants (3-oxypyridine, pyrimidine and hindered phenols) on the enzymic activity of membrane-bound acetylcholinesterase (AChE) was studied. In terms of estimated kinetic characteristics of AChE-reaction (KM, Vmax, KI), the pattern of enzyme inhibition by the hindered phenol compounds was found to be of non-competitive or mixed type depending on the inhibitor structure or on the substrate acetylcholine or acetylthiocholine used. The comparative study of the inhibitory action of water-soluble derivatives of hindered phenols and fatty-soluble ionol made it possible to reveal possible contributions to the inhibition of both direct and mediated (by the membrane microsurroundings) effects on the membrane-bound AChE by the studied synthetic bioantioxidants.


[The factors influencing the sound activity of forest voles]. The article is devoted to the effect of context on the acoustic activity of bank voles of 4 species (Clethrionomys glareolus, C. centralis, C. rutilus, and C. rufocanus) living in experimental groups. In addition to species differences and social state of a specimen in the group, the acoustic activities of vole is affected by such factors as locomotor activity of the vole itself and its partners (especially dominant ones) and aggression of surrounding voles.


[The development of the pouch-like structures at the angles of the mouth in the ontogeny of the hamster Phodopus campbelli]. The development of mouth angle sacciform structure was studied in the ontogenesis of hamster Phodopus campbelli. It was found that the true sacciform structure with all components characteristic for adult animals was formed by the 20th day of postnatal development. Histological data have shown than the sacciform structure is formed in ontogenesis as a result of a complex epidermal transformation involving muscular and connective tissues which comprise the external coat. The structure studied is not formed on the basis of sebaceous glands and cannot be assigned to the class of gland as considered before.


Completed suicide and recent lithium treatment. Of 1397 completed suicides in Finland in one year, all victims (N = 20) that had used lithium in prophylaxis and treatment of a mood disorder during the three final months were carefully examined. Eight victims (40%) fulfilled the criteria of recent adequate lithium prophylaxis. Continuous or intermittent noncompliance with psychopharmacological treatment during the last two years was reported in the majority (85%) of the victims. Only two cases used lithium as a suicide method. The study suggests that problems especially in compliance but also in quality of treatment are likely to limit the usefulness of lithium treatment in suicide prevention.


Characteristics of the Edinburgh Post Natal Depression Scale in The Netherlands. The Edinburgh Post Natal Depression Scale (EPDS), a 10-item self-rating depression scale, was translated into Dutch and compared in 293 postpartum women with other self-rating scales commonly in use in The Netherlands. In addition the structure of EPDS was analyzed by various factor analyses to reveal some of its dimensional aspects. The Dutch version of EPDS was found to be a self-rating scale with good psychometric characteristics which measures what it claims to measure: the strength of depressive symptoms. With LISREL a 2-factor model could be distinguished which contained subscales reflecting depressive symptoms and cognitive anxiety.


[Adaptation to chemical mutagens].

[Adaptation to chemical mutagens]. Pre-adaptation of normal and tumor cells to the action of methylnitrosourea was studied. To attain these ends, a single low dose (10 mg/kg) was administered to animals two hours prior to the administration of main therapeutic dose (100 mg/kg) and the number of chromosomal rearrangements was determined. A significant decrease in translocation incidence was observed in metaphases of Ehrlich-ICP ascitic strain. Similar results were obtained on cells of murine bone marrow. The mechanisms of pre-adaptation to the action is discussed.


Unipolar depression: diagnostic inconsistency and its implications. Major depressive disorder using Feighner et al. (Arch. Gen. Psychiatry 26, 57-63, 1972) and DSM-III or DSM-III-R criteria has proven to be a heterogeneous diagnosis. It apparently includes a wide variety of clinical conditions. This report, based upon the results of a multi-year blind follow-up of 500 randomly selected psychiatric outpatients focuses on certain problems associated with the diagnosis of primary unipolar affective disorders. At index, 141 patients received diagnoses of primary unipolar depression. At follow-up, only 62 (44%) of these received the same diagnosis, with an additional 14 (10%) receiving a diagnosis of undiagnosed: questionable primary unipolar depression, and 5 (4%) a diagnosis of bipolar disorder. Thus, about 43% received other diagnoses at follow-up: 35 (25%) diagnoses of secondary depression and 25 (18%) other diagnoses without indication of an affective component. Bipolar patients' stability was significantly better for those who were manic at intake.


[The effect of therapy with cytostatics and immunomodulators on mitotic pathology in Lewis tumor cells in mice]. The effect of cytostatics (methylnitrosourea and methotrexate), immunomodulators (thymalin and reaferon) and their combinations on the mitotic pathology of mice Lewis tumour cells was studied. It was revealed that chemotherapy with these agents changed the interrelation between mitotic phases and somewhat enhanced the incidence of pathologic mitoses mainly connected with the damage of mitotic apparatus. Immunomodulators differently affected the cytostatic activity of antitumour agents that may be associated with their mechanisms of action.


The validity of major depression with atypical features based on a community study. This article reports on evidence for the validity of major depression (MDD) with atypical features (defined as overeating and oversleeping) as a distinct subtype based on cross-sectional and 1-year prospective data from the Epidemiologic Catchment Area study. MDD with atypical features, when compared to MDD without atypical features, was associated with a younger age of onset, more psychomotor slowing, and more comorbid panic disorder, drug abuse or dependence, and somatization disorder. These differences could not be explained by differences in demographic characteristics or by symptom severity. This study, based on a community sample, found that major depression with atypical features may constitute a distinct subtype.


[Changes in the intensity of protein synthesis in the gastric mucosa following the laser irradiation of a duodenal ulcer]. The intensity of protein synthesis (incorporation/pool) is usually low in normal stomach mucosa and enhanced in exacerbation of peptic ulcer; following the effective laser therapy it decreases only in one third of cases. Therefore the scarring of ulcer not always coincides with the normalization of protein synthesis. The results characterize also the community of reactions in stomach and duodenal mucose membranes. The changes in protein synthesis intensity following the laser irradiation depended neither on the initial size of ulcer nor on the age of patient and the total duration of disease.


Proposed subtypes of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with hyperthymic temperament. In an attempt to improve the classification of Bipolar II disorders, we have examined a consecutive series of 687 primary major depressives: 5.1% gave a past history of mania (Bipolar I), 13.7% met our operational criteria for hypomania (Bipolar II), and the remaining 81.2% were provisionally categorized as 'unipolar.' Although Bipolar II was in some respects intermediate between Bipolar I and Unipolar, gender, familial bipolar history, age at onset and course characteristics generally supported its closer kinship to bipolar illness. Seventy one of the unipolars (10.3% of the total series) further met our operational criteria for hyperthymic temperament (U-HT), leaving behind a purer unipolar group of 487 major depressives. With respect to the proportion having male gender and bipolar family history, U-HT was similar to Bipolar I and II, and all three differed significantly from pure unipolar; as for age at onset, number of episodes and related indices of course, BI and BII were similar, and U-HT was closer to pure unipolar. These findings suggest that major depressive episodes arising from a hyperthymic temperament (constituting 12.4% of the 'unipolar' universe by conventional definition) are 'genotypically' closer to Bipolar II defined by hypomania, and course-wise similar to other unipolars.


Prodromal symptoms in panic disorder with agoraphobia: a replication study. The majority of 20 patients suffering from panic disorder with agoraphobia reported experiencing agoraphobic avoidance, generalized anxiety, and/or hypochondriacal fears and beliefs before the first panic attack. The results replicated those of a previous investigation and are in accordance with an increasing number of studies concerned with prodromal symptoms, epidemiologic surveys, and analysis of mechanisms of change upon treatment.


The Galway Study of Panic Disorder. II: Changes in some peripheral markers of noradrenergic and serotonergic function in DSM III-R panic disorder. Sixty six patients with panic disorders, fulfilling the DSM III criteria for panic attack, together with a group of age and sex matched controls, were studied for changes in their peripheral noradrenergic and serotonergic status before treatment and during six months treatment with either clomipramine or lofepramine. The results of this study suggest that, despite clinical improvement, the peripheral markers of both adrenergic (platelet aggregation to noradrenaline, platelet alpha 2 receptor density and lymphocyte beta receptor density) and serotonergic (platelet aggregation to serotonin, 3H-ketanserin binding to platelet 5HT2 receptors and 3H-5HT uptake into platelets) function largely remained abnormal. It is concluded that such abnormalities are trait markers of biogenic amine function in patients with panic attack. Further studies are needed to determine whether or not these parameters eventually normalize in those patients showing prolonged remission of symptoms.


High prevalence of cobalamin deficiency in elderly outpatients. To measure the prevalence of cobalamin (vitamin B12) deficiency in geriatric outpatients as documented by both low serum cobalamin levels and elevations of serum methylmalonic acid and homocysteine and to determine the response to cobalamin treatment. Prospective study screening elderly subjects for cobalamin deficiency using radiodilution cobalamin assays as well as stable isotope dilution gas chromatography-mass spectrometry methylmalonic acid and homocysteine assays. In patients with serum cobalamin levels < or = 300 pg/mL, the response to cobalamin treatment in the group with levels of methylmalonic acid and/or homocysteine > 3 standard deviations (SD) above the mean for normals was compared with that of those without such elevations. Outpatient geriatric clinics at the VA Medical Center and University Health Sciences Center, Denver, CO. One-hundred and fifty-two consecutive outpatients, ages 65 to 99, were screened. Twenty-nine subjects with serum cobalamin levels < or = 300 pg/mL were prospectively evaluated and treated with cobalamin. Cobalamin, methylmalonic acid, homocysteine, complete blood counts, neurologic examination, and neuropsychological testing. The prevalence of cobalamin deficiency as defined by a serum cobalamin level < or = 300 pg/mL and levels of serum methylmalonic acid and/or homocysteine elevated to > 3 SD was 14.5% of the screened outpatients. A similar proportion of patients with low normal serum cobalamin levels (between 201 and 300 pg/mL) demonstrated elevated metabolites > 3 SD (56%) compared with patients with low serum cobalamin levels (< or = 200 pg/mL) (62%). Cobalamin therapy caused a marked fall or complete correction of the elevated methylmalonic acid and homocysteine levels in each patient who was treated prospectively. Results for complete blood count, lactate dehydrogenase, bilirubin, baseline neurologic score, and baseline neuropsychologic scores did not differ in the group of patients with elevated metabolites compared with those with normal metabolites. The mean red cell volume fell significantly in the patients with elevated metabolites after 6 months of cobalamin treatment. One patient with elevated metabolites had marked improvement in his neurologic abnormalities after 6 months of cobalamin treatment. There was a high (14.5%) prevalence of cobalamin deficiency as demonstrated by elevations in serum methylmalonic acid and homocysteine in addition to low or low normal serum cobalamin levels in elderly outpatients. The serum cobalamin level was insensitive for screening since similar numbers of patients with low normal serum cobalamin levels of 201-300 pg/mL compared with patients with low cobalamin levels (< or = 200 pg/mL) had markedly elevated metabolites which fell with cobalamin treatment. Additional studies will be required to define the full clinical benefit from treatment with Cbl in elderly subjects.


Attitudes toward discussing life-sustaining treatments in extended care facility patients. To determine nursing home residents' attitudes toward discussing life-sustaining treatment plans with their physicians and the factors associated with these attitudes. Random-sample, interviewer-administered survey. Forty-one nursing homes in which some residents were cared for by house-staff physicians of the Hennepin County (Minnesota) Medical Center Extended Care Department. Random sample of 150 nursing home residents receiving primary care from Extended Care Department physicians, 131 (87%) of whom completed the interview. Older individuals were less likely to have spoken with physicians and family members about treatment plans (p < 0.05), and to have felt that they had more say than necessary in their treatment (P < 0.05). Only 19 (14.5%) residents had formal treatment plan discussions about limiting life-sustaining treatment. Although perceived current health status did not differ between residents with and without treatment plans, those residents who had discussions about advance directives were more likely to report health improvement over the past 6 months (P < 0.05). Residents with formal advance directives were, on average, 8.4 years younger than those without them (P < 0.05). Younger patients are more likely to have had discussions about life-sustaining treatment and are also more frequently involved in plan development. Preferences for level of involvement should be considered during advance directive planning, and it should be recognized that these preferences may vary with age. Future research should evaluate whether this age relationship is a true age or a cohort effect.


Prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly. To study prevalence and characteristics of symptomatic gastroesophageal reflux disease in the elderly. Survey by questionnaire of stratified random sample. City of Turku, Finland. Population-based random sample consisting of non-institutionalized subjects aged 65 years or over. A questionnaire was sent to 559 subjects. The response rate was 92%. Twenty-nine incompletely filled forms were rejected. Thus, the questionnaires from 487 subjects, representing 87% of the original number, constitute the basis for the study. The questionnaire inquired about the following symptoms: heartburn, regurgitation, chest pain, dysphagia, dyspepsia, respiratory symptoms, vomiting, and belching. The age-adjusted prevalence of daily symptoms suggestive of gastroesophageal reflux disease was 8% in men and 15% in women (P < 0.05). Fifty-four percent of men and 66% of women reported that they had symptoms at least once a month (P < 0.05). The prevalence of symptoms was roughly the same across age groups. The occurrence of chest pain, dyspepsia, vomiting, belching, dysphagia, chronic cough, hoarseness, and wheezing were associated with symptoms suggestive of gastroesophageal reflux disease. Symptoms suggestive of gastroesophageal reflux disease are common in elderly subjects. Women suffer from these symptoms more frequently than men. Typical reflux symptoms are often associated with atypical complaints, such as abdominal symptoms, chest pain, or respiratory symptoms.


The equivalency of infrared tympanic membrane thermometry with standard thermometry in nursing home residents. To compare the equivalence of infrared tympanic membrane (TM) measure of body temperature with standard electronic oral (PO) and rectal (R) measures in a nursing home population. Randomized repeated-measurement design. For the study, 82 randomly selected residents (mean age 79 +/- 10 years) of the Nursing Home Care Unit of the VAMC West Los Angeles had PO, R, and TM temperatures measured before arising (6-8 am). An otoscopic exam and the age, sex, presence of neurologic disease, and compliance with thermometry was noted. Also, repeated measures of PO and TM temperatures were performed three times to assess variability. The Pearson's correlation coefficient was determined for PO versus R and for TM versus R temperatures. Stepwise regression analysis was performed with the dependent variable of R temperature and the independent variables of the mean TM temperature, age, sex, presence of neurologic disease, position of the resident, and extent of ear canal occlusion. The correlation of TM versus R (r = .39, P = .004) was better, though not significantly, than of PO versus R (r = .28, P = .04). TM had less variability than PO (pooled standard deviation .38 vs .45 degrees F, respectively) and TM was implemented successfully more often than PO or R (96% vs 81% vs 81%). Therefore, TM was at least equivalent or better than PO measures of temperature in this population. The efficacy of fever detection and the use and durability of long-term use by nursing staff needs to be studied.


Nocturia: a risk factor for falls in the elderly. To determine if nocturia is a risk factor for reported falls and bone fractures in older persons. Cross-sectional study comparing falls in men and women with and without nocturia. Longitudinal health screening program of ambulatory elderly participants. Participants included 988 (65.5%) women and 520 (34.5%) men who had completed their tenth annual visit to the program. Reported falls in the past year and reported bone fractures in the past 5 years. Participants who reported nocturia at least twice during the night were at significantly greater risk to report falls (Odds Ratio = 1.84; 95% CI = 1.05-3.22), and the risk increased in subjects reporting more than three nocturia events (Odds Ratio = 2.15; 95% CI = 1.04-4.44). The significant increase in falls reported by nocturia participants did not result in an increase in reported bone fractures in the past 5 years (P < 0.4360). Nocturia is an important risk factor for falls in ambulatory elderly persons. Preventive measures should be taken to decrease nocturia events and to decrease the risk of falling during these nocturia events.


Bedside assessment of executive cognitive impairment: the executive interview. This study is a pilot validation of the Executive Interview (EXIT), a novel instrument designed to assess executive cognitive function (ECF) at the bedside. Inter-rater reliability testing and validation using inter-group comparisons across levels of care and measures of cognition and behavior. Forty elderly subjects randomly selected across four levels of care. Settings ranged from independent living apartments to designated Alzheimer's Special Care units in a single 537-bed retirement community. The EXIT: a 10-minute, 25-item interview scored from 0-50 (higher scores = greater executive dyscontrol) was administered by a physician. Subjects were also administered the Mini-Mental State Exam (MMSE) and traditional tests of "frontal" executive function by a neuropsychologist, and the Nursing Home Behavior Problem Scale (NHBPS) by Licensed Vocational Nurses. Interrater reliability was high (r = .90). EXIT scores correlated well with other measures of ECF. The interview discriminated among residents at each level of care. In contrast, the MMSE did not discriminate apartment-dwelling from residential care residents, or residential care from nursing home residents. The EXIT was highly correlated with disruptive behaviors as measured by the NHBPS (r = .79). These preliminary findings suggest that the EXIT is a valid and reliable instrument for the assessment of executive impairment at the bedside. It correlates well with level of care and problem behavior. It discriminates residents at earlier stages of cognitive impairment than the MMSE.


A prospective evaluation of the Geriatric Depression Scale in an outpatient geriatric assessment center. To prospectively evaluate the Geriatric Depression Scale (GDS) in cognitively intact and impaired patients undergoing outpatient geriatric assessment. One hundred ninety-four geriatric patients evaluated in a 1-year period. The outpatient Geriatric Assessment Center of the University of Nebraska Medical Center. The 30-item GDS was completed by all patients. The patients were then evaluated by one of three geriatric psychiatrists who were blind to the GDS results. The prospective clinical diagnosis of major depression was compared to the GDS results. Patients were categorized as cognitively impaired or intact on the basis of the Mini-Mental State Examination. Data were analyzed using ROC curves. An optimal cutoff was identified which was the total score on the GDS with the highest combined sensitivity and specificity. ROC curve analyses showed good agreement between the clinical diagnosis and the GDS in both cognitively intact and impaired subjects. Cognitively intact, euthymic patients reported a mean of 8.4 symptoms, while cognitively impaired, euthymic patients, reported a mean of 8.7. Cognitively intact, depressed patients reported a mean of 14.7 symptoms, while cognitively impaired, depressed patients reported a mean of 15.0. This study provides further evidence that the GDS is as accurate a screening test for depression in cognitively impaired as in intact patients.


Predictors of two-year post-hospitalization mortality among elderly veterans in a study evaluating a geriatric consultation team. To determine predictors of 2-year post-hospitalization mortality in a cohort of elderly hospitalized patients originally assembled to assess the impact of a Geriatric Consultation Team (GCT). Two-year follow-up of an inception cohort. University-affiliated tertiary care VA Medical Center. One hundred sixty-seven veterans age 75 or older discharged following hospitalization on medical, surgical, or psychiatry services but not intensive care units. None specifically studied here though cohort was previously part of randomized control trial of a Geriatric Consultation Team. Mortality during 2 years of post-hospitalization follow-up. Two-year post-hospitalization mortality was 28 percent with no difference between the original GCT and control groups. For the entire sample, age, mental status, admission or discharge ADLs (but not change in ADL status), number of admission problems, number of discharge diagnoses, and discharge site were significant predictors of mortality in univariate analysis. Only discharge ADLs and discharge site remained significant in multivariate analysis. Measures of ADLs during hospitalization are stronger predictors of mortality following hospitalization than disease diagnoses. Impaired ADLs and placement other than at home are significant predictors of mortality, suggesting that the decision for nursing home placement contains other independently predictive information within it and/or that the subsequent nursing home period produces excess mortality. As had been indicated in short-term follow-up, there was no survival advantage for the Geriatric Consultation Group.


Alcohol abuse in elderly emergency department patients. To determine the prevalence of alcohol abuse in elderly emergency department (ED) patients; to determine the prevalence of alcohol abuse for various categories of illness and injury among these patients; and to determine the frequency of detection of elderly alcohol abusers by ED physicians. Cross-sectional prevalence study. The emergency department of a 625-bed university hospital that serves a mixed urban and rural population. 205 patients aged 65 and over who came to the ED during an 8-week period. A structured interview, which included the CAGE questionnaire and other questions regarding alcohol use, was administered. Emergency department records and past medical records were reviewed. The prevalence of lifetime alcohol abuse (CAGE positive or self-reported drinking problem) was 24%. The prevalence of current alcohol abuse (CAGE positive or self-reported drinking problem and alcohol use within the last year) was 14%. There was a particularly high prevalence (22%) among those presenting with gastrointestinal problems and a surprisingly low prevalence (7%) among those who presented with falls or other trauma. Physicians detected only 21% of the current alcohol abusers. Alcohol abuse is a prevalent and important problem among elderly ED patients. It is not well detected by physicians in this setting. Alcohol abuse appears to be less common among elderly trauma patients than their younger counterparts, but is very common among patients with gastrointestinal problems.


Reported home health agency referrals by internists and family physicians. To evaluate the frequency of home health agency referrals (HHRs) by internists and family physicians. Telephone survey of a randomly selected, nationally representative, stratified physician sample. One thousand one hundred sixty-one interviews with 576 family physicians and 585 internists selected from the American Medical Association Physician Masterfile. Most respondents (88%) reported making HHRs (mean for those making HHRs = 43/year). Physicians with > or = 48 annual HHRs (n = 315) reported a mean of 2.6 hours/week in home care telephone management and 2.1 hours/week on related paperwork. Rural internists and family physicians (n = 230) reported less availability of several types of non-physician home health services than non-rural respondents (n = 931), yet rural physicians were more likely to refer patients to home health agencies. Using multivariate linear regression, the reported frequency of HHRs was significantly related to rural practice location, number of home-bound patients, proportion of geriatric patients, number of house calls, graduation from a U.S. or Canadian medical school, physician knowledge of community resources, and physician experience either as a medical director, a member of the board of directors, or a consultant for a home health agency. Internists and family physicians who work at least 10 hours per week in ambulatory care report making approximately three home health agency referrals per month and spending substantial amounts of time coordinating home health agency care. Despite reporting less availability of many home health agency services, rural physicians report greater involvement than non-rural physicians in the delivery of home care.


A comparison of patient risk for pressure ulcer development with nursing use of preventive interventions. (1) Determine if the Braden scale or Norton scale predicted the same patients to be at risk for pressure ulcer development as were receiving preventive nursing interventions. (2) Identify the items on the Braden and Norton risk assessment scales that the nurses used intuitively to determine a patient's need for a preventive intervention. Cross-sectional study. Six hundred-bed, state-supported, long-term care facility. War veterans who were 82% male and 97% caucasian, mean age 73. (1) Patients were categorized as at-risk or not-at-risk by the Norton and Braden scales. (2) The presence of a preventive nursing intervention was noted. Agreement in assignment of at-risk status among the two assessments and presence of a preventive intervention was analyzed using Cohen's Kappa. (3) The staff nurses' use of preventive interventions was modeled using stepwise logistic regression. The items from the Braden and Norton risk assessment scales were used as independent variables with staff nurse implementation of a preventive intervention as the dependent variable. Nurse preventive interventions were found on 45% of patients. The Norton scale identified 38% and the Braden scale identified 27% of patients as at-risk. Agreement among the three methods was 0.53. Agreement between the Braden and Norton scales was 0.73. Agreement between use of a preventive intervention and a classification as at-risk by the Braden or Norton scale was 0.41 and 0.43, respectively. Stepwise logistic regression revealed that low Braden mobility scores (Odds Ratio: 2.74) and low Braden friction/shear scores (Odds Ratio: 3.29) were associated with an increased likelihood of a patient receiving a preventive nursing intervention. The overall level of agreement among the two scales predicting risk and the presence of a preventive intervention was not high. Agreement, however, between the two risk assessment scales was close. The staff nurses apparently relied on a patients' mobility, their exposure to friction/shear, and additional unidentified factors to guide implementation of a preventive intervention. Further study is needed to define the cost, efficacy, and related cost effectiveness of routine pressure ulcer risk assessment.


The influence of treatment descriptions on advance medical directive decisions. To determine whether the wording of the descriptions of life-sustaining interventions would affect the choices elderly patients make when completing advance directives. Survey. General community in Omaha, Nebraska. Two hundred one community-dwelling elderly were selected from a population-based sample. Subjects were asked whether they would accept or reject three life-sustaining interventions: cardiopulmonary resuscitation, mechanical ventilation, or tube feeding in three separate hypothetical case scenarios. The three life-sustaining interventions were each described positively, negatively, and exactly as they are worded in a widely used advance directive. Subjects reviewed each scenario three times with three different descriptions of the three interventions. For the three interventions presented in three scenarios, subjects opted for the intervention 12 percent of the time when it was presented negatively, 18 percent of the time when it was phrased as in an advance directive already in use and 30 percent of the time it was phrased positively. One hundred fifty-five of the 201 subjects (77 percent) changed their minds at least once when given the same scenario but a different description of the intervention. Of these 155, 33 percent changed decisions one to three times, 33 percent changed decisions four to seven times, and another 34 percent changed decisions eight to seventeen times based solely on the description of the intervention. The decisions patients make about whether to accept or reject life-sustaining treatments are affected by the descriptions of the treatments. These findings emphasize the critical importance of doctor-patient consultation when patients execute advance directives.


Historical perspective: the neurotrophic theory of skin ulceration. Though nearly forgotten, the neurotrophic theory was very much a part of mainstream medical thinking during the mid-nineteenth century. This theory stated that all bodily organs are maintained by special nutritional factors secreted by the central nervous system. Development of skin ulceration in the face of neurologic injury became a model for the theory, and controversy involved two great neurologists of the time, Jean Martin Charcot and Edouard Brown-Séquard. As the neurotrophic theory fell into disfavor, interest in decubitus ulcers waned as well. Today, pressure sores remain a major epidemiologic problem for the growing population of frail elderly persons in both acute and long-term care settings. Because of the increased mortality, morbidity, and cost associated with these lesions, attention needs to be refocused on research and education concerning the decubitus ulcer.


What will the scope of optometric practice be in the year 2000? For the past 100 years, the scope of optometric practice has been constantly expanding. As the body of knowledge about visual function has increased, new treatment options have been developed. Optometry must accept the professional responsibility for treatment of all conditions of the eye and visual system. By the year 2000, optometry must be prepared with expanded curricula and accountable for the treatment of all visual conditions in order to maintain its place as a primary provider within the health care system.


Should optometry evolve as a vertically integrated discipline that includes all components of ophthalmology? Change in the optometric profession is inevitable. Persuasive economic factors will play a great role in shaping the future of optometry and ophthalmology. Optometry is in a position now and into the future to leverage its great strengths to benefit the public in a cost conscious manner.


What are the appropriate skills and knowledge required for the entry-level practice of optometry? All health professions have developed a national program of competence assessment to address the specific issue of "entry-level practice." This is also true in optometry through the 3-Part examinations of the National Board of Examiners in Optometry. These examinations test the cognitive (knowledge) skills necessary to be fit to practice and the communication, affective and psychomotor skills that are required to apply the underlying knowledge in the solution of patient problems. The scope of the National Board examinations and how they change to keep pace with the expansion and the scope of practice, demonstrates that entry-level is a dynamic concept.


Time for educational reform.

Time for educational reform. As the profession of optometry evolves, complementary changes in the educational process must occur if graduates are to be fully prepared to practice primary eye care. A national conference to address these educational priorities including curriculum design, faculty manpower and financial resources has recently been held. The need for educational reform facing the profession is outlined.


The expanding scope of optometry and the impact on the curriculum of schools and colleges. The expansion of the profession of optometry has placed pressures on the schools and colleges of optometry to reduce traditional curricular elements, add new ones, obtain faculty trained for the new scope of the profession, and provide additional patient experiences for hands-on learning. While the schools have adapted to these pressures and are leading the profession into new areas, the traditional 4-year optometry curriculum is critically filled. Further expansion will require difficult decisions.


The expanding scope of practice and the optometric curriculum. The expansion of the scope of optometric practice has put tremendous pressures on the curricula of the optometric teaching institutions. The pressures and the solutions that have been proposed in the optometric literature are outlined. The possibility of eliminating portions of the curriculum that have traditionally been regarded as the educational foundation of the practice of optometry and what effect this would have on the very definition of the term "optometry" is discussed.


An appropriate patient base for clinical optometric education. The reasons for the need of an expanded patient base for adequate clinical instruction in the 4-year professional program are discussed. Optometric education must establish the "reasonable set" standard for patient size and diversity particularly in view of its expanded scope of professional responsibility.


What are the pros and cons of requiring postgraduate residency training as an entry level practice requirement? The technological and knowledge explosion that has occurred in this century has created a curriculum crunch within all health professional schools. The various optometric institutions are dealing with this crunch and important decisions need to be made in order to provide the best entry-level practitioners possible. This paper provides some of the pros and cons of requiring a year of postgraduate training as a requirement for entry level optometry practice.


What role will residency education take in the profession by the year 2000? Residency education has enjoyed relatively slow but steady growth since its inception in the mid-1970s. A certain segment of recent graduates consider graduation from optometry school as entry level and perceive the need for additional clinical education. The creation of new residency programs and the expansion of existing ones may occur in a variety of settings. For residency education to realize its full potential, optometry must seek federal support for post-graduate clinical education. This would be consistent with federal support provided to other professions for the support of post-graduate clinical education.


What role will residency education take in the profession by the year 2000? There is a need to expand the number of optometric residencies to meet the current increased demand from graduates seeking to fill the expanding number of residency positions, as well as the projected needs of the profession for the 21st century. Supportive rationales and recommendations for potential development of residencies are discussed.


The need to incorporate professional principles, attitudes and ethics in optometric education. This paper reviews the development of ethical principles for the profession of optometry over the past 90 years, and how these principles have been modified and expanded in conjunction with the scope of practice during that period. The author discusses the mandated principles of licensing boards as well as Medicare and Medicaid requirements. In addition, areas of "non-mandated" ethical principles are reviewed such as the aging and AIDS patient, over testing, continuing education, corporate employment, patient records and referrals. The author suggests that ethical issues should be incorporated into all optometric courses in the curriculum and not just in a specific ethics course in order that many role models offer their input to students in the development of an ethical model for their professional lives.


The need to incorporate professional principles, attitudes and ethics in optometric education. It is vital to the continued independence of optometry for its practitioners to exude professionalism. Professional principals, attitudes and ethics must be incorporated into the curriculum of optometric education at the earliest possible time and be reinforced by lesson and example throughout the educational experience.


How can the optometric profession expand the pool of qualified applicants? The American Optometric Association and the Association of Schools and Colleges of Optometry need an aggressive public awareness campaign to encourage an increase in the pool of qualified applicants for a career in optometry. One of the most significant ways an individual AOA member can impact this process is to serve as role model for potential applicants.


How can the optometric profession expand the pool of qualified applicants? The health professions, including optometry, are facing a declining applicant pool. The American Optometric Association has taken steps to address the challenge of increasing the pool of qualified applicants to the schools and colleges of optometry. However, the most significant factor in the process will be the efforts of individual AOA members.


How can optometry become more effective in recruiting and retaining appropriate numbers of underrepresented and disadvantaged students. The proportion of minority students in optometry schools remains very small compared to that in the general population. The numbers in the general population are rising and the gap could widen if serious recruitment programs are not implemented. The most effective methods of expanding the applicant pool and recruiting students involve personal contact with people in the profession. Admissions processes must be carefully analyzed to eliminate systematic bias. Retention programs should be in place and can also be used to benefit all students. Financial aid programs must be expanded to accommodate a higher proportion of students from lower socio-economic backgrounds.


Why should optometric research be designated as a priority for the profession? Research is the discovery of new information, ideas or theories that increases our knowledge and understanding of ourselves and our environment. Optometric research focuses on the health, functioning and performance of people with emphasis on their eyes and vision. The goal of optometric research is to enable optometrists to provide high quality eye and vision care for their patients.


What should be the proper size and number of optometric schools? The Health Professions Educational Assistance Act brought infusion of millions of dollars into optometric education at a time when the profession was ill prepared with inadequate space standards and cost studies. The profession presently faces the need to make major curricular changes at a time of severely constricted resources. Optometry, in a dynamic mode, needs to establish acceptable standards consistent with the profession's demands and goals for the 21st century.


Student indebtedness and practice mode choice. Student indebtedness upon graduation from optometry school has long been cited as the major factor influencing practice mode choice. A review of the literature, practice trends for optometry, medicine and dentistry, and forces affecting the health care industry reveal other factors as well.


The recruitment and retention of disadvantaged and underrepresented groups in optometry. The recruitment and retention of disadvantaged students represents a formidable challenge to optometric educators. Referrals by optometrists and counsellors, visits to minority campuses, and information through the news media can help the recruitment process. Academic achievement and retention rates can be enhanced by tutorial programs, development of learning centers, learning modules, self-paced materials, and computer software. The most important element is the sensitivity of faculty and administrators to the educational needs of the students and the health care needs of disenfranchised populations.


Basis for body weight exponent (0.75) as a scaling factor in energy metabolism and risk assessment. The basis that led to the adoption of the exponent (0.75) as a scaling factor for the relationship between body weight and energy metabolism is presented. In the risk assessment formulation, it may be appropriate to use the 0.75 power of body weight as a scaling factor for carcinogenicity data obtained from animal studies.


One-year toxicity of orally administered acrolein to the beagle dog. Forty-eight dogs were separated into four groups of six males and six females. Acrolein (0.1% aqueous) was administered in gelatin capsules to three of these groups at dosing levels of 0.1, 0.5 and 1.5 mg kg-1 day-1 based on results of a range-finding study. After 4 weeks, the high dose was increased to 2 mg kg-1 day-1. The fourth group received deionized water in the same number of gelatin capsules as the high-dose group. Dosing was 7 days per week for 53 weeks. Blood and biochemical measurements were made pretest and at 3-month intervals thereafter. At termination, all dogs were subjected to full necropsy and histological examination. The major test effect noted was frequent vomiting after dosing. This was observed to be dose-dependent and the frequency decreased with time, indicating an adaptive effect. One mid-dose female died during the test and was diagnosed as having died of severe bronchial pneumonia, probably a result of vomitus aspiration. Serum albumin, calcium and total protein values were depressed in high-dose animals throughout the study. Some variability in red blood cell parameters and coagulation times were noted but the significance of these effects was not obvious.


Variable effects of chemical allergens on serum IgE concentration in mice. Preliminary evaluation of a novel approach to the identification of respiratory sensitizers. A wide variety of chemicals may induce allergic contact dermatitis (contact sensitivity). Some chemical allergens may, in addition, cause respiratory sensitization. Topical exposure of mice to contact and respiratory chemical sensitizers results in the initiation of divergent immune responses characteristic of preferential activation of different functional subpopulations of T helper (TH) cells. In the present study we have sought to make use of these differences, particularly differences in the ability of contact and respiratory allergens to provoke IgE responses, and to question whether opportunities exist for the identification of chemicals with the potential for respiratory sensitization. We have examined alterations in the serum concentration of IgE following topical exposure of mice to seven chemical allergens; trimellitic anhydride (TMA), phthalic anhydride, diphenylmethane-4,4'-diisocyanate (MDI), dicyclohexylmethane-4,4'-diisocyanate (HMDI), isophorone diisocyanate (IPDI), oxazolone and 2,4-dinitrochlorobenzene (DNCB). Three of these--TMA, phthalic anhydride and MDI--are known human respiratory sensitizers. The other four--HMDI, IPDI, oxazolone and DNCB--appear not to cause respiratory allergy, or at least have a very limited potential to do so. At the concentrations tested, exposure to all chemicals caused a lymphocyte proliferative response in lymph nodes draining the site of application. However, exposure only to TMA, phthalic anhydride and MDI resulted in a substantial increase in the concentration of serum IgE. Treatment with HMDI and IPDI failed to induce any change in serum IgE concentration. DNCB and oxazolone caused only small and transient elevations of IgE that were considerably less marked than those observed with respiratory sensitizers.(ABSTRACT TRUNCATED AT 250 WORDS)


Toxicity of 2-methyl-5,6-cyclopentapyrimidine (MCPP). 2-Methyl-5,6-cyclopentapyrimidine (MCPP, CAS No. 36274-29-0) is a white dusty solid with a powerful lingering odor and is formed as a by-product in the polymer synthesis of an experimental polymer. The acute toxicity following both oral and inhalation exposures and the effects of repeated inhalation exposures in rats were determined. Mutagenic activity was assessed using Salmonella as the indicator organism. The chemical is moderately toxic, with the lethal dose following a single oral administration being 90 mg kg-1. Doses greater than or equal to 130 mg kg-1 produced strong convulsions. Excessive salivation, hyperactivity and twitching were seen at 90 mg kg-1 and only mild initial weight loss was seen in surviving rats (less than or equal to 60 mg kg). Liver injury was produced at doses as low as 17 (but not at 12) mg kg-1. The material was highly toxic by inhalation, with the approximate lethal concentration in rats following single 4-h exposures being 9 ppm. Convulsive-like movements were seen at greater than or equal to 9 ppm (not at 2 ppm). Histological findings suggest that MCPP causes dilation of blood vessels with hyperemia of various organs apparent in rats exposed to 1 ppm and sacrificed 1 or 2 days post-exposure. No evidence of liver or central nervous system damage was seen. Repeated (nine daily 4-h exposures) inhalation of 2 ppm MCPP failed to produce any signs of a toxic response. No mutagenic activity was seen. The material needs to be considered as a potent acute toxin.


Calcium antagonists can be classified using in vitro toxicity and potency indices. The toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage-operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate an in vitro therapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that the in vitro therapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compounds.


Effect of single gallium arsenide exposure on some biochemical variables in porphyrin metabolism in rats. Gallium arsenide (GaAs) inhibited, dose dependently, delta-aminolevulinic acid dehydratase (ALAD) activity in blood (as observed on days 1, 7 and 15), liver and brain (on day 15) after a single oral treatment. Levels of blood zinc protoporphyrin (ZPP) and urinary delta-aminolevulinic acid (ALA) excretion were elevated on day 7 and day 15 following exposure to 2000 mg kg-1 GaAs. A dose-dependent increase in blood As contents was observed while blood Ga was detectable only at higher doses.


Alteration of brainstem auditory evoked potentials in diethylbenzene and diacetylbenzene-treated rats. Male Sprague-Dawley rats were treated either with 1,2-diethylbenzene (1,2-DEB) or its putative active metabolite, 1,2-diacetylbenzene (1,2-DAB). Experimental rats and appropriate controls were examined electrophysiologically for brainstem auditory evoked potentials (BAEP). Oral administration of 1,2-DEB (75 or 100 mg kg-1 once a day, 4 days a week, for 8 weeks) and intraperitoneal injection of 1,2-DAB (10 or 15 mg kg-1 once a day, 4 days a week, for 8 weeks) produced time- and dose-dependent increases in the peak latencies of all BAEP components as well as in interpeak (I-V) differences, and a decrease in the amplitudes of all the components. The absolute and interpeak latencies recovered partially during an 8-week (1,2-DEB) or a 10-week (1,2-DAB) recovery period, whereas there were long-lasting decreases in peak amplitudes.


The Ca(2+)-transport-ATPase of human erythrocytes as an in vitro toxicity test system--acute effects of some chlorinated compounds. Investigations to determine the inhibitory activity on the Ca(2+)-transport-ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4-chlorophenol, 2,4-dichlorophenol, 2,6-dichlorophenol, 3,4-dichlorophenol, 2,3,4-trichlorophenol, 2,3,4,5-tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)-camphene, toxaphene, dichlorodiphenyltrichloroethane (DDT), lindane, endrin, dieldrin, alpha-endosulfan, beta-endosulfan, paraquat, diallate, 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Some of the compounds investigated display an inhibitory effect on the Ca(2+)-transport-ATPase at very low concentrations. The in vitro results obtained in this enzyme assay can be correlated directly with the results of other in vitro assays and with the results of in vivo investigations in different species in which an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca(2+)-transport-ATPase indicates a toxic effect of these compounds to cell functions. Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the cellular toxicity of various compounds.


Haematological and hepatotoxic effects of silken styles of corn in albino rats. The alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maize Linn.) at 50, 100 and 150 mg kg-1 daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses. The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maize Linn.) are not significantly toxic at low and medium doses (50 and 100 mg kg-1).


Changes in lipid peroxidation levels and lipid composition in the lungs, livers, kidneys and brains of mice treated with paraquat. We examined lipid peroxide levels and the lipid composition of homogenates prepared from the lungs, livers, kidneys and brains of 48 male ICR mice treated with 30 mg kg-1 paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride). The mice were divided into eight groups, in which they were killed 0, 1.5, 3, 6, 12, 24, 48 and 120 h after the administration of paraquat. A significant increase in the lipid peroxide level was identified only in the liver. Change in lipid composition was identified in all the examined organs. However, the change was not a characteristic one in which there is a selective decrease of polyunsaturated fatty acids which become degraded in a lipid peroxidation reaction. It is possible that the mechanism of paraquat toxicity may differ in different organs.


ATP-MgCl2 increases cisplatin toxicity in the dog and rat. The purpose of this study was to examine if ATP-MgCl2, an agent that protects against acute cisplatin toxicity in vitro, protected against cisplatin toxicity in vivo. Baseline renal function measurements were obtained on dogs (n = 12) and rats (n = 20) on day -1. Dogs were given 90 mg m-2 cisplatin (n = 5), 90 mg m-2 cisplatin and 50 mumol kg-1 ATP-MgCl2 (n = 5), or 90 mg m-2 cisplatin and 150 mumol kg-1 ATP-MgCl2 (n = 2), in a slow bolus i.v. injection on day 0. Rats were given 4 mg kg-1 cisplatin i.p. (n = 6) and 25 mumol kg ATP-MgCl2 (n = 8) i.v. or 4 mg kg-1 cisplatin i.p. and 25 mumol kg-1 ATP-MgCl2 (n = 6) i.v. on day 0. Renal function was assessed on a routine basis for 14 days. All dogs had significantly decreased creatinine clearance following cisplatin administration. There were no significant differences in renal function tests between groups of dogs. One dog given 50 mumol kg-1 ATP-MgCl2 and both dogs given 150 mumol kg-1 ATP-MgCl2 in addition to cisplatin developed acute anuric renal failure and were euthanatized prior to completion of the study. Rats given 4 mg kg-1 cisplatin and 25 mumol kg-1 ATP-MgCl2 had significantly increased blood urea nitrogen and serum creatinine after drug administration, compared to rats given cisplatin alone. The results indicated that ATP-MgCl2 worsened in vivo cisplatin renal toxicity in the dog and rat.