Principal component analysis and exploratory factor analysis. In this paper we compare and contrast the objectives of principal component analysis and exploratory factor analysis. This is done through consideration of nine examples. Basic theory is presented in appendices. As well as covering the standard material, we also describe a number of recent developments. As an alternative to factor analysis, it is pointed out that in some cases it may be useful to rotate certain principal components if and when that is appropriate.


Correspondence analysis in medical research. Various applications of correspondence analysis to biomedical data are presented. The basic concepts of profile, mass and chi-squared distance are introduced in an initial simple example using data on the relationship between headache types and age. The main result of the correspondence analysis is a geometric map of this relationship showing how the relative frequencies of headache types change with age. A second example maps the association between personality types and various medical diagnostic groups, while a third example deals with categorical rating scales such as an efficacy scale for a medication or a scale of pain. A final example illustrates the more complex situation when several categorical variables are involved using test data on a collection of bacterial isolates, with the object of comparing bacterial types and understanding the inter-relationships of the different tests.


Design and analysis of reliability studies. This review covers the design and analysis of essentially two types of reliability study: method comparison studies and generalizability (including inter-rater reliability) experiments. Likelihood-based methods of inference (confirmatory factor analysis and REML estimation of variance components, for example) are advocated, partly because of their ease of use but, primarily as a stimulus to the use of more ambitious designs for the investigation of the quality of measurements. The more sophisticated approaches are not intended to replace the simpler traditional methods, however, but are expected to be used to supplement them.


Structural equation models in medical research. Structural equation modelling (SEM) is a modern statistical method that allows one to evaluate causal hypotheses on a set of intercorrelated nonexperimental data. The sample variances and covariances, and possibly the means, are compared to those predicted by a theory-based hypothetical model after optimal estimation of the parameters of the model. The goodness-of-fit of the empirical data to the hypothesized model is evaluated statistically. This review describes the underlying statistical theory and rationale of SEM. Both confirmatory factor analysis and latent variable path models are discussed. The applicability of SEM to assessment of reliability and validity is noted. A detailed example is provided, and several examples from the medical literature are briefly reviewed. Cautions regarding the possible misuse or misinterpretation of the technique are also mentioned. Possible future directions for the use of SEM in medical research are suggested. Two appendices provide more technical details.


Measurement of reliability for categorical data in medical research. The problem of measuring reliability of categorical measurements, particularly diagnostic categorizations, is addressed. The approach is based on classical measurement theory and requires interpretability of the reliability coefficients in terms of loss of precision in estimation or power in statistical tests. A general model is proposed, leading to definition of reliability indices. Design and estimation approaches are discussed. Issues and approaches found in the research literature that either lead to confusing or misleading results are presented. The signs and symptoms of unreliable diagnoses are identified, and strategies for improving the reliability of such diagnoses are discussed.


Modelling patterns of agreement and disagreement. This article presents a survey of ways of statistically modelling patterns of observer agreement and disagreement. Main emphasis is placed on modelling inter-observer agreement for categorical responses, both for nominal and ordinal response scales. Models discussed include (1) simple cell-probability models based on Cohen's kappa that focus on beyond-chance agreement, (2) loglinear models for square tables, such as quasi-independence and quasi-symmetry models, (3) latent class models that express the joint distribution between ratings as a mixture of clusters for homogeneous subjects, each cluster having the same 'true' rating, and 4) Rasch models, which decompose subject-by-observer rating distributions using observer and subject main effects. Models can address two distinct components of agreement--strength of association between ratings, and similarity of marginal distributions of the ratings.


Longitudinal studies with continuous responses. The analysis of serial measurements obtained in longitudinal studies plays an increasingly prominent role in applied research. The last few years have seen the development of many new techniques for carrying out analyses, including computer software. These methods can be used in a variety of standard problems, including repeated measures and cross-over designs, as well as growth curve analyses. We review these new methods, their application, and available computer packages. Data from a longitudinal study of lung function is used to illustrate the methods.


Statistical methods for longitudinal and clustered designs with binary responses. Dependent binary response data arise frequently in practice due to repeated measurements in longitudinal studies or to subsampling primary sampling units as in fields such as teratology and ophthalmology. Several classes of approaches have recently been proposed to analyse such repeated binary outcome data. The different classes of approaches measure different effects of covariates on binary responses and address different statistical questions. This article compares the different classes of approaches in terms of parameter interpretation and magnitude, standard errors of model parameters and Wald tests for covariate effects. The results help to clarify the substantive questions which data analysts can address with each approach, as well as why the covariate effects measured by different approaches may be different. Finally, I will provide guidelines to the advantages and disadvantages of alternative approaches for analysing dependent binary responses. Simulations and example data illustrate these findings.


Incomplete data in repeated measures analysis. Complete (or balanced) repeated measures data arise when all subjects in a study are measured at the same set of time points. Data are often incomplete, because measurements are missed, or the design of the study results in subjects being measured at different sets of time points. This article reviews methods of analysis for incomplete repeated-measures data of this form, from an applied statistician's perspective. Limitations of approaches that (a) ignore between-subject variation, or (b) impute for missing values are discussed. Two methods are advocated that are relatively easy to implement using existing software, namely between-subject analysis of within-subject summary measures, and maximum likelihood based on a model for the data. Methods are applied and compared on four real-data examples with varied analytical objectives.


Repeated assessment of risk factors in survival analysis. Regression models for survival data with time-dependent covariates are considered. We review estimation in the Cox regression model and discuss problems in connection with data requirements for the analysis, with interpretation of results and with prediction based on such a model. In particular, we discuss how the latter problems may be approached within an extended (Markov process) model. A clinical trial in liver cirrhosis is used for illustration.


Analysing the temporal effects of age, period and cohort. Longitudinal trends can be analysed in terms of the effect of age, birth cohort or year of diagnosis. All three temporal effects are thought to be useful by epidemiologists, but they are not identifiable when assessed simultaneously. Partitioning the effects in terms of linear and curvature components is one approach to understanding the problem and finding a reasonable summary of trends. Other solutions can be expressed in terms of these components, and they can also be used to understand both subgroup and temporal interactions. One approach that may offer a way of understanding the effect of risk factor trends on population based rates is to use models that incorporate an effect due to the risk factors. These methods are discussed using lung cancer incidence and mortality to illustrate the underlying concepts.


[The economic evaluation of the early diagnosis of breast carcinoma: a review of the literature]. This paper reviews the economic aspects of screening for breast cancer: from a bibliographic search we identified studies on complete economic evaluation of screening programs in different parts of the world. At the methodological level, it goes as far as proposing a reference model for economic evaluation. An examination of the results obtained from various studies indicates that the introduction of screening program involves a cost per life-year saved of between 3,800 and 88,000 dollars. Allowing for quality of life, the range is 4,050 to 91,650 dollars. A discussion of some examples of sensitivity analysis shows how, and how much, the results change as a consequence of different assumptions regarding crucial variables: discount rate, reference period of the analysis, frequency of screening, age of the target population, volume of activity of each screening unit, compliance, sensitivity and specificity of the test.


Methodologic issues in using epidemiologic studies of occupational cohorts for cancer risk assessment. This paper focuses on presenting a review and discussion of the major methodologic issues involved in using epidemiologic studies of occupational groups for assessing human cancer risks. Although animal studies have been most often used for quantitative risk assessment, it is generally recognized that well conducted epidemiologic studies would provide the best basis for estimating human risk. However, there are several features related to the design and analysis of epidemiologic studies which frequently limit their usefulness for quantitating risks. The lack of accurate information on exposure in epidemiologic studies is perhaps the most frequently cited limitation of these studies for risk assessment. However, other features of epidemiologic study design such as statistical power, length of follow-up, selection bias, confounding and effect modification may also limit the inferences that can be drawn from these studies. Furthermore even when the aforementioned limitations are overcome, substantial uncertainty exists concerning the choice of an appropriate statistical (or biologic) model for extrapolation beyond the range of exposures observed in a particular study. An empirical example is provided in which estimates of risk varied by nearly 3 orders of magnitude depending on which functional form of the model was chosen. Modeling of epidemiologic data for QRA should be based upon internal comparisons rather than on modeling Standardized Mortality Ratios (SMRs) when possible. Because of the limitations discussed in this paper, epidemiologic data should not be viewed as a panacea for the problems inherent in using animal bioassay data for QRA.(ABSTRACT TRUNCATED AT 250 WORDS)


[Factors associated with alcohol consumption in the youth of the province of Brescia]. We investigated factors related to adolescent alcohol consumption by administering an anonymous questionnaire to 2737 9th and 13th grade high-school students in the province of Brescia. A total of 1364 students coming from an urban area (the town of Brescia with about 200,000 inhabitants) and 1373 students from a mountainous area (Breno, Local Health Unit N. 37 in the Lombardy Region with 83,000 inhabitants) were interviewed. The associations between alcohol drinking and some demographic, socio-economic, behavioural and environmental variables were assessed by computing the correspective odds ratios (OR) by fitting logistic regression models for ordinal response variables ("cumulative odds" models). The results showed that the following variables were positively associated with alcohol consumption: 1) residence in a mountainous area, especially as regards spirits consumption; 2) experimental and regular smoking; 3) peer alcohol drinking (best friend and partner). Parents' daily alcohol consumption was associated with wine drinking, but not with either spirits consumption or frequency of drunkenness among students. A slight inverse relationship was also found between students' alcohol intake and their knowledge of the health hazards of alcohol, but it was not significant for all groups of students.


[Surveillance in public health: the methodological problems in identifying risk factors]. Identification of clusters of health events as well as more general problems in public-health surveillance are being increasingly debated. The authors discuss the differences between the systematic (epidemiologic surveillance) and non-systematic (episodic identification of clusters and/or sentinel events) observations. In this regard the role played by statistical methods appears to be specially worthy of consideration, so as to define the capabilities of a given surveillance system in identifying increasing risks. To take into account the relationship between size of the risk to be evidenced and probability (= power) that the implemented test may be significant, specific tables have been developed displaying the relationship between 1st and 2nd type error, sample size and minimum detectable risk, under different exposure levels.


The relation of hand preference to hand performance in left-handers: importance of the left brain. The associations among hand preference, hand skill (peg moving time, PMT) and hand performance (dot filling/20 s) were analyzed in left-handed subjects. In the total sample, the degree of left-hand preference linearly decreased from -100 to zero (Geschwind scores, GSs) as the number of dots placed by the right hand increased (direct correlation); the left hand did not show any significant relation to GSs. The right-hand PMT linearly decreased as the GSs decreased (negative linear correlation); the left hand skill did not exhibit any significant correlation with GSs. There was a negative linear correlation between right-hand PMT and dot-filling with right hand; the left-hand PMT was not related to dot-filling with left hand. In males, the right-hand PMT showed a negative linear correlation with GSs; no significant correlation between PMT and GSs was found for the left hand. There was a negative linear correlation between right minus left (R - L) PMT and GSs. Dot-filling with right hand was found to be positively linearly correlated with GSs (no correlation for the left hand). The L - R dot-filling showed a negative linear correlation with GSs. PMT for the right hand exhibited a significant negative linear relation to dot-filling only with right hand. Sex and familial sinistrality caused minor changes in these relationships. It was concluded that the left brain would constitute the main factor determining the degree of left-handedness.


Motor stability in visuomotor control of repetitive hand movements and its differential cerebral control in right-handed subjects. The stability of asymmetric motor control was studied in right-handed subjects. Hand skill was assessed by a peg moving task in ten trials. The mean peg moving time (PMT) and its standard deviation (SD) were calculated for each hand. Standard deviation was taken as an index of the stability of visuomotor control. The mean rate of a repetitive movement (mean PMT) did not always show an association with its stability (SDs). This depended upon familial sinistrality, sex, and cerebral lateralization such as eye and foot preferences of the subjects. The left-right differences in movement stabilities also showed different contributions of the right and left brains of the subjects depending upon these factors. It was suggested that these factors should be taken into consideration in studies concerning the hemispheric control of especially corrective components of skilled movements of hands.


Contributions of the right and left brains to manual asymmetry in hand skill in right-handed normal subjects. The relation of intermanual difference in hand skill to cerebral lateralization was studied in right-handed male and female subjects. Hand preference was assessed by the Edinburgh Handedness Inventory. Hand skill was measured by the peg moving task. In subjects with familial sinistrality (FS+), the mean right hand peg moving times (PMTs) were found to be significantly and negatively linearly correlated with the mean left minus right (L - R) hand PMTs in females (no correlation in males). Contrarily, there was a direct relationship between the mean L - R hand PMTs and the mean left hand PMTs in FS+ males (no correlation in FS+ females). Similar results were obtained with the FS- subjects. The correlations were modified by eye and foot preferences. The overall results suggested that generally the right brain in males and the left brain in females are of importance in determining the intermanual difference in hand skill; an insufficient right brain (a slower left hand) in males and a sufficient left brain (a faster right hand) in females would create a more asymmetrical organization in skill between hands.


Comparison of the antinociceptive effects induced by electroacupuncture and transcutaneous electrical nerve stimulation in the rat. The analgesic effects induced by two different kinds of peripheral conditioning stimulations, electroacupuncture (EA) and transcutaneous electrical nerve stimulation (TENS), were compared in the rat using the latency of radiant heat-evoked tail flick reflex as nociceptive index. The parallel elevations of withdrawal latency of tail flick were produced by EA and TENS administrations at the acupoints of S36 and Sp6 with low intensity (1-2-3 mA) and one of three different frequencies (2, 15 and 100 Hz). Analgesic effects of EA or TENS were characterized by slow-on and slow-off nature, and a significant linear correlation was found between both at any one of three frequencies. Systemic naloxone hydrochloride (2 mg/kg) almost completely and partially antagonized 2 and 15 Hz EA- or TENS-induced analgesia, respectively, but failed to affect those induced by 100 Hz EA or TENS. Tolerance to EA stimulation with one of three frequencies reduced the corresponding frequency TENS-induced analgesia and vice versa. These data indicate that: (a) there is no significant difference in producing antinociception for two different peripheral conditioning stimulations when applied at the same sites and (b) the common neural mechanisms most likely process the analgesic effects of EA and TENS. The involvement of (an) endogenous opiate mechanism in the management of different frequency EA and TENS analgesia is discussed in detail.


Influence of sex on the blood brain barrier permeability during bicuculline-induced seizures. Sex related differences of the blood brain barrier permeability was investigated during bicuculline-induced seizures in Wistar rats. The rats were anesthetized with diethyl-ether. Evans-blue, which was used as a blood brain barrier tracer, was injected into femoral vein 5 minutes before administering bicuculline to induced grand mal seizures. Evans-blue albumin extravasation was determined as a macroscopical finding; and a quantitative estimation with spectrophotometer using homogenized brain to release the dye was also performed to evaluate the macroscopic findings. During convulsions the mean arterial blood pressure increased in both female and male rats, but the difference was in the extravasation of Evans-blue being more pronounced in the females. Blood brain barrier lesions were present in 85% of female rats and 61% of male rats. Mean value for Evans-blue dye in the whole brain was found to be 1.197 +/- .402 mg % in the group consisting of all the female rats, and .755 +/- .247 mg % in the group of all male rats during bicuculline-induced seizure. This difference between female and male rats was found to be statistically significant (p < .001). Severe protein leakage was seen in the thalamus, hypothalamus, hippocampus, globus pallidus, nucleus caudatus, periaqueductal gray and mesencephalon bilaterally in female rats. However, in male rats, Evans-blue leakage was similar to that of female rats except that the frequency and intensity of blood brain barrier breakdown was less after convulsions. Our results showed that the extravasation of Evans-blue albumin was most pronounced in the brains of female rats compared to male rats after bicuculline induced seizure.


Correlation of neuronal cell body size in motor cortex and hippocampus with body height, body weight, and axonal length. This study examined the comparative effects of body height and body weight on the neuronal cell size in humans and investigated their possible mechanisms. A total of 21 cases between the ages of 20 and 40 years were studied. Data on body height, body weight, and neuropathology were obtained from autopsy records. Mean cross sectional areas of cell bodies for 30 normal neurons were determined for the motor cortex projecting to lumbar spinal cord segments (L) 1-4 (Betz cells) as well as various regions of the hippocampus. Approximate axonal length of the motor neuron studied was measured from motor cortex to L2. We found that only motor cortex neuronal cell body size was significantly proportional to body height and the respective axonal length (p < .05). The findings indicate that: 1) body height has a greater effect than body weight on the motor neuron cell size, probably because of its association with axonal length; 2) the effect is regional (motor cortex) rather than general.


Calcification of the pineal gland: relationship to laterality of the epileptic foci in patients with complex partial seizures. The right and left temporal lobes differ from each other with respect to the rate of intrauterine growth, the timing of maturation, rate of aging, anatomical organization, neurochemistry, metabolic rate, electroencephalographic measures, and function. These functional differences between the temporal lobes underlies the different patterns of psychopathology and endocrine reproductive disturbances noted in patients with temporolimbic epilepsy. The right hemisphere has greater limbic and reticular connections than the left. Since the pineal gland receives direct innervation from the limbic system and the secretion of melatonin is influenced by an input from the reticular system, I propose that lesions in the right temporal lobe have a greater impact on pineal melatonin functions as opposed to those in the left dominant temporal lobe. Consequently, since calcification of the pineal gland is thought to reflect past secretory activity of the gland, I predicted a higher prevalence of pineal calcification (PC) in epileptic patients with right temporal lobe as opposed to those with left temporal lobe foci. To investigate this hypothesis, the prevalence of PC on CT scan was studied in a sample of 70 patients (43 men, 27 women, mean age: 29.2 years, range 9-58; SD = 10.1) with complex partial seizures, of whom 49 (70.0%) had a right temporal lobe focus. PC was present in 51 patients (72.8%) and was unrelated to any of the historical and demographic data surveyed. In the patients with a focus in the right temporal lobe, PC was present in 46 cases (93.8%) as compared to 5 of 21 patients (23.8%) with left temporal lobe foci.(ABSTRACT TRUNCATED AT 250 WORDS)


Taurine induces bicuculline/strychnine-insensitive dose-dependent inhibition of cortical visual evoked responses. Modulatory influences of taurine on cortical visual evoked responses and their susceptibility to GABAergic and glycinergic antagonists were studied in adult rats. Taurine topically administered to the visual cortex produced dose-dependent inhibition of the positive-negative fast component of the cortical visual evoked responses. Neither bicuculline nor strychnine antagonized the taurine effect, as revealed by absence of a shift to right, a change in slope or in the taurine IC50 value in the dose-response curve. Results suggest that taurine-induced depression of cortical responses evoked in the visual cortex are mediated by receptors other than the GABAA and glycine receptors.


Amelioration of experimental parkinsonism by intrahypothalamic administration of haloperidol. Accumulation of amines in the degenerating axons of ascending catecholamine-containing neurons in the hypothalamus has been proposed as a site of function neurotransmitter release and may thereby participate in the development of motor impairment seen after central dopamine-depleting lesions. To test this hypothesis further the dopamine receptor antagonist haloperidol (1 microL of a 14 nmol solution) was injected directly into the lateral hypothalamus (LH) in 6 different injection regimes to determine whether amphetamine-induced turning could be attenuated with this treatment. The injection of haloperidol at 1 and 24 h (group 1), 24 h (group 2) or 6+ 7 d (group 3) after 6-hydroxydopamine (6-OHDA) did not modify amphetamine-induced turning. However, the injection of haloperidol at 1 h, 24 h, 7 d, and 8 d (group 4), days 1-7 (group 5), or gradual infusion (14 nmol/microliters/h) for 7 days (group 6) all reduced the 6-OHDA-induced turning to a level similar to that of controls. These results add further support to the contention that amines are released from the axons of degenerating neurones in the hypothalamus and that this phenomenon participates in the elicitation of behavioral impairment attributed solely to the loss of functional neurotransmitters from terminal fields. Furthermore, the data emphasize the importance of hypothalamic pathology in the development of Parkinsonism and suggest that intrahypothalamic administration of dopamine blocking agents might be useful in the treatment of Parkinsonism.


Intrathecally injected antibody can diffuse into spinal cord. Antibody microinjection has been widely used to investigate the function of neuropeptides, but the capability of antibody to diffuse in the brain tissue has not been well characterized. The present study was conducted with an immunohistochemical method to determine if the anti-enkephalin serum injected intrathecally could diffuse into the spinal cord. Enkephalin immunoreactivity was observed in laminae I and II in slight amounts after 10 min, in moderate amounts after 30 minutes and very clearly after 60 min of the intrathecal injection of enkephalin antiserum. In addition, marked nonspecific staining was observed in the dorsal part but not in the ventral part of the white matter. These results indicate that antibodies injected intrathecally are capable of diffusing into the spinal cord within a time period of 10-60 min.


Event-related potentials in a guessing task: the gleam in the eye effect. Event-related potentials (ERPs) were recorded from a single subject performing a forced-choice guessing task. On each trial, ERPs were elicited by four, sequential, graphic images; 2 1/2 seconds after the last stimulus was delivered, the subject guessed which of the four images was experimentally (randomly) designated as the target. P200 had greater amplitude over the posterior scalp for stimuli which were guessed by the subject to be targets than for not-guessed stimuli. The amplitude of the P100, N100, and P300 components was unrelated to the subject's guess. A positive displacement evident in the waveforms from about 150-500 ms post-stimulus onset suggested that Slow Wave may have been partially responsible for the observed differences. These results suggest that ERPs may contain predictive information about a subject's subsequent responses in forced-choice guessing tasks. We termed this the "gleam in the eye" effect.


Postnatal cerebral maturation in Down's syndrome children: a developmental EEG coherence study. Eyes-closed EEG was recorded from 19 scalp locations in thirty Down's Syndrome children and young adults, aged 9 months to 26 years. These subjects were age-matched to normal children and normal young adults. EEG coherence was computed for five groups of electrode pairings: 1--anterior-to-posterior, 2--posterior-to-anterior, 3--posterior temporal, 4--anterior temporal and 5--interhemispheric. The results showed that EEG coherence strongly and consistently discriminated between the two groups. Developmental trajectories in the Down's group were weakly linear and often with negative slopes. In contrast, normal children showed strong linear and nonlinear developmental trajectories with only positive slopes. The greatest differences between groups was in the left hemisphere and in posterior cortical regions as compared to frontal regions. The normal children exhibited growth spurts in EEG coherence at particular postnatal ages, whereas the Down's Syndrome children failed to exhibit strong growth spurts in EEG development.


Dependence of intermanual difference in hand skill on right or left cerebral motor control in right-handed male and female subjects. The relations of the mean differences in right and left hand skills (L-R) to the mean right and left hand skills were studied in right-handed male and female subjects with and without familial sinistrality (FS+, FS-). Hand skill was measured by the peg moving task. In FS+ males, there was a significant negative linear correlation between L-R and right hand peg moving times (PMTs). In FS+ females, there was a significant positive linear correlation between L-R and left hand PMTs. There were no significant correlations between L-R and left hand PMTs in FS+ males, and right hand PMTs in FS+ females. FS- subjects could be described as follows. In males and females with right eye and right foot preference, L-R PMTs were found to be positively linearly correlated with left hand PMTs (no correlation between L-R and right hand PMTs). In subjects with left eye and right foot preference, the correlations were found to be similar to those for FS+ subjects. In subjects with mixed eye and right foot preference, there was a negative linear correlation between L-R and right hand PMTs in females; a positive linear correlation between L-R and left hand PMTs in males. There were no significant correlations between L-R and right hand PMTs in males, and left hand PMTs in females. These results indicated that left brain in FS+ males, and right brain in FS+ females would produce the L-R difference between hands in PMTs.(ABSTRACT TRUNCATED AT 250 WORDS)


Somatosensory event-related potentials following different stimulus conditions. We studied somatosensory event-related potentials (ERPs) in response to rare target, frequent nontarget and rare nontarget stimuli in 12 healthy subjects. Compared with the corresponding peaks following frequent stimuli, the responses elicited by rare target stimuli showed higher amplitudes for N70, P100 and N140 components and those evoked by rare nontarget stimuli showed higher amplitudes for N70 and N140 components. The P300 component following rare nontarget stimuli was shorter in latency and lower in amplitude than that elicited by target stimuli. ERP waveforms evoked by rare nontarget stimuli also showed obvious N240 and P300 components, which differed from those following frequent nontarget stimuli. These findings suggest that there are differences in signal processing in response to target, frequent nontarget and rare nontarget stimuli. The P300 component was distributed symmetrically and there was no significant hemispheric predominance with regard to any ERP component in response to either right or left side stimulation.


Sensitivity of dopamine receptors in the lateral hypothalamus is altered in 6-hydroxydopamine treated rats. Amine accumulation is observed in the lateral hypothalamus (LH) after nigrostriatal neurons degenerate. It has been proposed that this accumulation is a source of amines which are released into the hypothalamus thereby affecting the function of adjacent aminergic receptors. To approximate this condition of continuous exposure of LH receptors to endogenous amines, dopamine (DA) was injected into the LH of rats once daily for 5 consecutive days. A control group received 4 daily injections of tartaric acid vehicle and then DA on day 5. Rats pretreated with DA showed severe impairment of open field performance and motor reflex control on day 5 when they were compared to control animals which received vehicle pretreatment. In a second study, the DA receptor antagonist haloperidol was injected into the area of amine accumulation in the LH to determine whether this might block amine release from areas of accumulation thereby to attenuate lesion-induced rotation. Haloperidol administered once daily for 4 out of 7 days, once daily for 7 days or via a continuous infusion for 7 days, all reduced d,l-amphetamine-induced turning to control levels. These results suggest that prolonged exposure of hypothalamic DA receptors alters their sensitivity to subsequent doses of DA and that amine released from areas of accumulation may be blocked by haloperidol to enhance behavioral recovery from DA depleting lesions. Moreover, these findings indicate that the hypothalamus participates in the behavioral effects induced by DA depleting lesions and highlight the importance of hypothalamic pathology in Parkinson's disease.


Strain variation in immune response and behavior following the death of cage cohorts. Strain differences in both immune function and behavior were observed following exposure of mice to the death of cage-cohorts. AKR/J, BALB/cN, and C3H/HeJ mice were exposed to a dead cohort for two hours at 48 hour intervals for 30 days. During this two hour period, AKR/J mice displayed intense fighting and mounting behavior. In addition, these mice attacked, cannibalized, and buried carcasses. Neither C3H/HeJ nor BALB/cN mice exhibited the complete repertoire of behaviors directed at either carcasses or cage-cohorts observed in AKR/J mice. After 15 exposures to the death of cage-cohorts, allogeneic cytotoxic T-lymphocyte (CTL) response was suppressed in AKR/J mice, but was enhanced or unchanged in C3H/HeJ and BALB/cN mice, respectively. Other immune parameters including natural killer (NK) cell activity, and lipopolysaccharide-stimulated B cell proliferation were unchanged in AKR/J mice but increased in BALB/cN mice exposed to the death of cage-cohorts for thirty days. These results suggest: 1) that both suppression of the CTL response and behaviors indicative of defensive burying in AKR/J mice may specifically be due to the loss of cage-cohorts, since they were not observed following exposure of these mice to the death of contraspecific animals; and 2) that both the behavioral repertoire and immune responses following exposure to the death of cage-cohorts may be strain dependent. This strain dependence may reflect differences in the ability to cope with the intermittent presentation of a stressor, and may explain, at least in part, variability in stress-induced changes in immune functions.


Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation. Levels of circulating thyroid stimulating hormone (TSH), tetraiodothyronine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5' triiodothyronine (reversal T3 or rT3) were measured in 25 children with trisomy of chromosome 21, also known as Down's syndrome (DS), and in 14 normal children. In subjects with DS TSH levels were increased, while plasmic levels of rT3 were decreased. No alteration in T3 and T4 levels was observed. Before zinc supplementation, plasmic levels of zinc and thymulin, a zinc dependent thymic hormone, were significantly decreased in DS children. After four months of dietary supplementation with zinc sulphate, a normalization of plasmic zinc, thymulin and TSH levels was observed. Plasmic levels of rT3 significantly increased, and after zinc treatment no difference was detectable between DS children and normal children. Clinical evaluation of the health status of DS children showed that zinc supplementation decreased the incidence of infectious diseases and improved school attendance. Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland.


Biochemical study of different conditions of type 2C muscle fiber in rat. Type 2C muscle fibers were histochemically and biochemically examined under three different conditions in rats: in the neonatal stage, after neonatal denervation and on regenerating process after bupivacaine-induced injury. On histochemical examination, soleus was found to contain up to 90% of type 2C fiber in every condition, whereas both gastrocnemius and extensor digitorum longus contained 40-70%. On biochemical analysis, triglyceride was the smallest and glycogen was the largest in amounts in neonatal muscles, triglyceride was the largest and glycogen was lowest in amount in neonatal denervated muscles, while both triglyceride and glycogen were low in amounts in bupivacaine-treated muscles. These results suggested that although histochemical characteristics are the same, significant differences in biochemical properties exist between type 2C fibers in these three different conditions.


Testosterone, estradiol, ACTH and musical, spatial and verbal performance. Testosterone, estradiol, and ACTH were determined in blood serum of 26 healthy males aged 19.16 and of 25 healthy females aged 18.77 years on average, and results were correlated with test scores of three spatial tests, a verbal fluency measure, and a test measuring general musical ability. In addition, hemispheric lateralization for verbal material and handedness was assessed. While testosterone and estradiol alone were not significantly related to any of the cognitive or musical tests, testosterone/estradiol ratio was significantly negatively correlated with spatial tests, and ACTH was significantly positively correlated with spatial and musical tests. Correlations were stronger in females than in males. The laterality index was significantly negatively correlated with testosterone in males indicating that right hemisphere involvement in verbal processing was associated with high testosterone levels.


Modification of receptive fields of posteriomedial barrel subfield neocortical single units by known concentrations of iontophoresed noradrenaline in the rat. Using quantitative electromechanical stimulation of vibrissae poststimulus time histograms were used to map the receptive fields of single units from laminae II/III (12 units), IV (24 units) and V (12 units) of the posteriomedial barrel subfield in urethane anaesthetized rats prior to, and during the iontophoresis of known concentrations of Noradrenaline. All units had multivibrissae receptive fields prior to noradrenaline iontophoresis with laminae II/III units having the smallest size of center and surround receptive field and laminae V the largest. Lamina IV showed the strongest center receptive field response probability magnitude (spikes/stimulus) and the shortest modal latency of evoked responses. Noradrenaline iontophoresis diminished the size of surround receptive fields in each lamina and additionally decreased the size of center receptive fields in laminae IV and V. In Lamina IV, in contrast to laminae II/III and V, response probability magnitude from center receptive field vibrissae was not significantly depressed whilst modal latency of the evoked response was significantly reduced.


The relationship between leftward turning bias and visuospatial ability in humans. A significant relationship was found between a bias to make complete counter-clockwise (leftward) turns and performance levels on tests of visuospatial function. Subjects who turned preferentially to the left over a four-day period performed above average on visuospatial tests with those having the greatest turning bias performing the best. Subjects who tended to turn to the right performed below average on tests of visuospatial function. There was no relationship between rotational bias and verbosequential skills, but there was a significant relationship between turning bias and a cognitive profile defined as the difference between visuospatial ability and verbosequential ability. The cognitive profile effectively partialed out overall ability suggesting that the turning bias is related to the bias for better visuospatial processing rather than the level of visuospatial performance per se. Asymmetric turning has been shown to be related to asymmetries of dopamine activity in rats. Therefore, the present results are discussed in relation to the possibility that the dopamine neurotransmitter system may underlie both rotational behavior and visuospatial cognitive function in humans.


Immunohistochemical localization of type IV collagen and laminin in the gingival capillary basement membrane of the diabetic rat. Distribution of type IV collagen and laminin in the gingival capillary basement membrane from streptozotocin-induced diabetic rats was investigated using immunoelectron microscopy. Both type IV collagen and laminin were found throughout the basement membrane. Quantitative analysis revealed that the immunoreactive area for laminin did not change with age, and the width of laminin deposition remained constant, even when diabetes was induced in the animals. However, the immunoreactive area for type IV collagen thickened with age. Further, the width of type IV collagen in the basement membrane increased markedly 36 weeks after diabetes was induced. It was concluded that the thickening of the gingival capillary basement membrane in experimentally induced diabetic rats was due an increase of type IV collagen deposition.


Melatonin and petit-mal epilepsy: an hypothesis. Intraventricular administration of the opioid peptide leucine-enkephalin has been reported to induce petit-mal-like seizures in rats. These seizures have been found to be an age-dependent phenomenon. In rats, the full manifestation of these seizures develops after 4 weeks of age during which time ethosuximide was effective in aborting these seizures, while phenytoin and phenobarbital were ineffective. The period associated with the development of enkephalin-induced seizures in rats coincides with an important milestone in pineal chronobiology. In rats, melatonin plasma levels peak at 3 weeks of age, a period which also corresponds with the emergence of melatonin circadian rhythms. It is proposed that melatonin mediates the anticonvulsant action of drugs effective for petit-mal (absence) epilepsy and that the pineal gland is implicated in the pathogenesis of this form of childhood epilepsy.


The effects of immobilization stress on electrodermal activity and brain catecholamine levels in rats. The effects of immobilization stress on electrodermal activity (EDA); skin conductance response magnitude and rate, skin conductance level and habituation number, and brain catecholamine levels; norepinephrine (NE) and dopamine (DA) were investigated in rats. Electrodermal activity was recorded using constant current method. Brain catecholamine levels were determined by a spectrophotophlorometric method. Electrodermal activity parameters (except skin conductance level) increased during immobilization. It was observed that, during immobilization stress, the alteration of norepinephrine and dopamine levels in rat brain was related to cerebral region and the duration of immobilization stress. It was concluded that these electrodermal activity alterations can be attributed to the changes in central norepinephrine metabolism induced by immobilization.


Glycosaminoglycans in the lamina propria and submucosal layer of the monkey palatal mucosa. Glycosaminoglycans (GAGs) in monkey palatal lamina propria plus both fatty and glandular zones of palatal submucosa were compared. Chemical analysis revealed that GAG contents of the lamina propria and glandular zone were higher than that of the fatty zone. The four GAGs identified by electrophoretic analysis were hyaluronic acid, dermatan sulfate, chondroitin sulfate and heparan sulfate. Each mucosal layer contained all four GAG components. The predominant GAG in both the lamina propria and glandular zone was dermatan sulfate followed by hyaluronic acid. The reverse situation (predominant hyaluronic acid, less prominent dermatan sulfate) was noted in the fatty zone of the submucosa. The three tissue regions showed different molar ratios of unsaturated chondroitin sulfate disaccharides. The ratio of delta Di-4S to delta Di-6S was lower in the lamina propria than in either the fatty or glandular submucosal zones.


Magnetic fields mimic the behavioral effects of REM sleep deprivation in humans. The discovery of rapid eye movement (REM) sleep by Aserinsky and Kleitman in 1953 initiated the impetus for sleep research and specifically the investigations of the effects of REM sleep deprivation (RSD) on animal and human behavior. The behavioral effects of RSD include the enhancement of motivational and "drive"-related behaviors. In laboratory animals, RSD has been reported to increase appetite, sexual behavior, aggressiveness, and locomotor activity. Moreover, RSD reportedly improves mood in patients with endogenous depression and heightens appetite and sexual interest in normal subjects. Since "drive"-related behaviors are thought to involve activation of limbic dopaminergic reward sites, RSD may enhance motivational behaviors through an action on limbic dopaminergic functions. In the present communication, we present two patients (one with multiple sclerosis and the other with Parkinson's disease) in whom treatment with magnetic fields produced behavioral effects which paralleled those observed in REM-sleep-deprived animals and humans. We propose, therefore, that the behavioral and mental effects of treatment with magnetic fields may be mediated via RSD and, by inference, involve activation of limbic dopaminergic reward sites.


The prescription of transdermal nicotine patches for tobacco-using dental patients: current status in Indiana. As Indiana dentists become involved in office-based smoking cessation efforts, they can prescribe the recently-developed Federal Drug Administration (FDA)-approved nicotine transdermal patch delivery systems for their smoking patients who wish to overcome nicotine addiction. This article reviews the evolutionary and scientific development of transdermal nicotine patch systems within an oral health setting. It discusses dental office-based cessation programs which have been designed by faculty members at the Indiana University School of Dentistry and by dentists who work with the National Cancer Institute. Finally, it presents the rationale for patch usage and specific techniques which are utilized in prescribing and monitoring this medication.


Tumor cell kinetics and expression of type IV collagen and E-cadherin in a human gingival carcinoma xenograft line in nude mice. In order to elucidate the relationship of tumor invasion with the expression of E-cadherin and type IV collagen, I carried out immunohistochemical studies on a human gingival carcinoma xenograft line, GK-1, in nude mice. The transplanted tumors were divided into four stages of progression for examination at 5, 7, 10 and 15 weeks after transplantation based on the value of the labeling index for BrdU. The labeling index for BrdU showed its greatest value at seven weeks after transplantation. There was a marked decrease of E-cadherin expression in the tumors at seven weeks after transplantation, and the amount of expression negatively correlated with the labeling index. In addition, the expression of type IV collagen decreased, having a positive correlation with the expression of E-cadherin, and it became discontinuous and unstable. From the above findings, both the decreased expression of E-cadherin and the discontinuous expression of type IV collagen suggest that the tumor cells maintain high invasiveness.


The effect of finishing techniques on marginal adaption and surface morphology of three glass ionomer cements. Three formulations of glass ionomer filling materials were finished with discs lubricated with either water or petroleum jelly. No changes in surface micromorphology or marginal adaptation were found which would indicate that petroleum jelly should be used as a lubricant during finishing instead of water.


Clinical observations on the development of third molars. In order to investigate the developmental conditions of third molars in Japanese, we studied the panoramic radiographs taken during dental treatment at the Pediatric Outpatient Section of Osaka Dental University Hospital of 9,111 children (4,646 boys and 4,465 girls) between the ages of 7 years 0 months and 16 years 11 months, in addition to 2,769 panoramic radiographs of students of this university (2,312 men 457 women) kept by the Department of Oral Radiology. The following results were obtained. 1. Calcification of the third molars in both boys and girls began as early as 7 years 6 months in the maxilla and 7 years 0 months in the mandible. The average age for initiation of calcification in the maxilla was 9 years 4 months for boys, and 9 years 2 months for girls, while the ages in the mandible were 9 years 1 month and 8 years 9 months, respectively. 2. The average age for completion of the third molar crowns in the maxilla was 11 years 8 months for boys and 11 years 5 months for girls, while in the mandible it was 12 years 4 months and 12 years 3 months, respectively. 3. At greater than 13 years of age, the tooth germ could be found in boys about 70% of the time in the maxilla and 75% of the time in the mandible, while these figures for girls were 65 and 80%, respectively. 4. All four third molars were present in 52.3% of the males and 45.5% of the females, while 9.5% of the males and 12.0% of the females had no third molars at all. 5. The direction of eruption was classified as either vertical, mesial, horizontal, distal, or buccal/lingual type. The rate for the vertical type in males was 70% in the maxilla and 45% in the mandible, while these figures for females were 50 and 40%, respectively. 6. Microdontia of the third molars appeared only in the maxilla. 7. Congenital absence of the third molars was more common in females than males, and occurred more frequently in the maxilla than in the mandible. The results of this study allow a better understanding of the third molars of Japanese and provide an aid to planning in such areas of clinical pediatric practice as guiding occlusal development.


Surgical treatment using porous hydroxylapatite blocks for severe habitual dislocation of the bilateral temporomandibular joint in a patient with epilepsy. A patient with severe habitual dislocation of the bilateral temporomandibular joint involving epilepsy was operated using porous hydroxylapatite blocks as intervention material. The patient was followed up for 4 years. He has been well without recurrence of dislocation or any complication. In this paper, we report the procedure and the relevant literature is discussed.


Clinical application of a newly developed surveying system for designing and fabricating removable partial dentures. In this paper, some problems in commercially available surveying systems were discussed, and a clinical technique for designing and fabricating clasps by using an improved 'Digital Surveyor' and a computer system were presented. This system has the advantages as follows: (1) morphological factors on abutment teeth could be measured and evaluated using the improved 'Digital Surveyor' and its accessories set, (2) clasps providing with proper mechanical properties according to various conditions in the mouth could be designed and fabricated precisely and easily. It became clear that conventional surveying methods involved empirical rules should be re-examined and replaced by the more rational surveying method like this system.


Histological study on bone response to resin-hydroxyapatite. Resin-Hydroxyapatite has been developed to take the advantages of bioactivity of hydroxyapatite (HAP) and plasticity of resin (Bis-GMA). It was composed of 75% HAP, 15% Bis-GMA and 10% quartz reinforced filler. Tested pellets of Resin-HAP as well as its constituents were implanted into subcutaneous connective tissue of femurs of adult dogs. Histological observation at 12 weeks postoperatively showed that each pellet was surrounded by the fibrous connective tissue almost free of the inflammatory cells. The thickness of the fibrous layer around HAP was relatively thin, while those around Bis-GMA and Resin-HAP showed some variance. Taking our previous data into consideration, it was suggested that Resin-HAP had bio-compatibility both in soft tissue and bone, although its long-term stability as well as its stability under function should further be examined.


Orthodontic crown lengthening.

Orthodontic crown lengthening. As comprehensive dentistry becomes more complex, procedures must be developed to save teeth once considered unsuitable for crown restoration due to inaccessible finishing lines. Orthodontic crown lengthening is less invasive than a flap procedure and does not result in crestal bone reduction. The crown lengthening procedure is a simple and time-saving remedy for a difficult restorative problem.


Intramuscular hemangioma in the digastric muscle. Intramuscular hemangioma is a distinctly rare neoplasm originating within normal muscle. In the head and neck region, it occurs most frequently in the masseter muscle. Diagnosis of intramuscular hemangioma is extremely difficult because it is not encountered frequently and is often confused with salivary gland stone, parotid neoplasm or other tumors. In this report, a second case of intramuscular hemangioma of the digastric muscle and the diagnosis of this type of tumor in the early stage and the importance of its treatment are described.


Adhesive strength between teeth and resin cements for porcelain laminate veneer. We performed an experiment on adhesive strength between teeth and resin cements for porcelain laminate veneer. A compression shear test was performed using three types of resin cement in extracted human anterior teeth. In dentin, the effects of various surface treatment methods were also evaluated. All three types of resin cement showed high adhesive strengths to enamel, but low adhesive strengths to dentin that were less than 1/2 of those to enamel. Treatment of the dentin surface with both a surface treatment agent and primer significantly increased adhesive strength.


Activation of cathepsin B involved in enkephalin production by bradykinin and its cleavage products in cultured fibroblasts of the rat dental pulp. Mechanisms of cathepsin B activation involved in methionine-enkephalin (ME) production induced by bradykinin (BK), des-Arg9-BK or L-arginine (L-Arg) were studied using cultured fibroblasts of the rat dental pulp, especially from a viewpoint of intracellular signal transduction. BK, des-Arg9-BK, L-Arg or cysteine enhanced the release of ME-like peptides from the cells, and the release of ME-like peptides induced by des-Arg9-BK was inhibited by des-Arg9-[Leu8]-BK (BK B1-receptor antagonist) and E-64 (a specific inhibitor of cysteine proteinases). The activation of cathepsin B by BK or des-Arg9-BK was inhibited by des-Arg9-[Leu8]-BK or islet-activating protein (IAP), and the activation of cathepsin B by L-Arg was inhibited by Leu-Arg (kyotorphin-receptor antagonist) or Botulinum C3-enzyme. The activation of cathepsin B by those stimulants was dependent on calcium ion. These results suggest that the ME production by BK or des-Arg9-BK may be mediated by Ca(2+)-dependent cathepsin B activation through B1-receptors and IAP-sensitive G-proteins, whereas the production by L-Arg may be mediated by Ca(2+)-dependent cathepsin B activation through kyotorphin-receptor and Botulinum C3-enzyme-sensitive G-proteins. On the other hand, the activation of cathepsin B was inhibited by neomycin B (phospholipase C inhibitor) and various serine/threonine kinase inhibitors. These results indicate that phospholipase C and serine/threonine kinases are involved in the activation of cathepsin B by BK, des-Arg9-BK or L-Arg. Genistein inhibited the activation of cathepsin B by des-Arg9-BK or L-Arg in a different fashion, suggesting that tyrosine kinase(s) is also involved in the activation. Cathepsin B activation by BK or L-Arg but not des-Arg9-BK was inhibited by L-NMMA (inhibitor of NO synthesis), and the activation by L-Arg was enhanced by beta-glycerophosphate (beta-GP: inhibitor of phosphatases), while the activation by BK or des-Arg9-BK was inhibited by beta-GP. These results suggest that BK-induced cathepsin B activation in the fibroblasts may be due to a combined effect of des-Arg9-BK and L-Arg.


Development of a mandibular tracking device with six degrees of freedom using optoelectronic system. The purpose of this study was to develop a prototype handy mandibular tracking device with six degrees of freedom using the optoelectronic kinematic data acquisition system and to evaluate its accuracy. The system consisted of the light-weight sensor part mounted on the mandibular incisor portion and two 2-D PSD cameras positioned in front of the patient. On the sensor part, three light emitting diodes (LEDs) were attached in triangular form. Displacements of the sensor part were detected by two cameras, transformed into electric signals, and sampled by A/D converter in a desktop computer. Since the overall accuracy of this system was about 0.03 mm in the displacement and 0.06 degrees in the rotation angles, this system was proven to be capable for the wide range of clinical application.


Differential effects of 1 alpha, 25-dihydroxycholecalciferol and 24R,25-dihydroxycholecalciferol on the proliferation and the differentiated phenotype of rabbit craniofacial chondrocytes in primary culture. The response of chondrocytes from the craniofacial complex to vitamin D3 has been investigated in vitro. Chondrocytes were isolated from nasal septal cartilage (NSC), sphenooccipital synchondrosis (SOS) and mandibular condylar cartilage (MCC) of New Zealand rabbits weighing from 250-350 g. Treatment of NSC-chondrocytes with 1,25-(OH)2D3 or 24,25-(OH)2D3 for 6 days from days 4 to 10 in medium containing charcoal-treated FBS increased DNA synthesis dose-dependently at the concentrations of 10(-9) M to 10(-8) M, or 10(-11) M to 10(-9) M, respectively. 1,25-(OH)2D3 inhibited GAG synthesis dose dependently at the concentrations of 10(-11) M to 10(-8) M. 24,25-(OH)2D3 had no effect on GAG synthesis in NSC-chondrocytes. 1,25-(OH)2D3 increased DNA synthesis in SOS-chondrocytes at a concentration of 10(-10) M and inhibited GAG synthesis. 24,25-(OH)2D3 had no significant effect on DNA and GAG syntheses of SOS-chondrocytes. 1,25-(OH)2D3 slightly increased GAG synthesis at a concentration of 10(-10) M in MCC-chondrocytes but had no effect on DNA synthesis. 24,25-(OH)2D3 had no effect on DNA and GAG synthesis in MCC-chondrocytes at concentrations of 10(-11) M to 10(-9) M. These finding suggest that vitamin D3 metabolites, 1,25-(OH)2D3 and 24,25-(OH)2D3 play an important role in the growth of craniofacial cartilage by differently stimulating proliferation and expression of the differentiated phenotype of chondrocytes from NSC, SOS and MCC.


Biomechanical responses of tooth to orthodontic forces applied at the lingual bracket positions. The present study was designed to investigate biomechanical responses of tooth to orthodontic forces applied at the lingual bracket positions. A three-dimensional finite element model of the upper central incisor was developed to analyze tooth displacements and stress distributions in the periodontal ligament. Lingual horizontal and apical vertical forces of 100 gf were applied at a point on the labial surface of the crown and at three different points on the lingual surface of the crown. Tooth displacements and stress distributions from the forces applied at the lingual points were compared with those from the labial force loading. The following results were obtained. 1. Lingual horizontal force produced almost similar patterns of tooth displacements and stress distributions, irrespective of labial and lingual application points of the orthodontic forces. 2. Apical vertical force applied at the lingual points produced more uniform tooth displacements and stress distributions than labial application of the force, although the force applied at the lingual point close to the cervix generated different patterns from those with the remaining lingual force loadings. The present results suggest an important role of the positional relation of force application points to the center of resistance. It is shown that lingual force application may produce more optimal tooth movement in terms of more uniform patterns of tooth displacements and subsequent stress distributions in the PDL.


Stimulation of alkaline phosphatase activity by ascorbic acid and suppression by 1,25-dihydroxycholecalciferol in rabbit craniofacial chondrocytes in culture. To clarify the role of vitamins D and C in chondrocyte hypertrophy of craniofacial cartilage, we have studied cultured chondrocytes from rabbit mandibular condylar cartilage (MCC), sphenooccipital synchondrosis (SOS) and nasal septal cartilage (NSC) under conditions in which these cells mature into hypertrophic chondrocytes. In cultures of MCC- and SOS-chondrocytes, alkaline phosphatase (ALPase) activity started to increase on day 9 at confluence and the cessation of cell division, and reached a maximum on day 18. The degree of the increase of ALPase activity on day 18 was higher in MCC-chondrocytes than in SOS-chondrocytes. ALPase activity was very low level in NSC- and CGC-chondrocytes. Ascorbic acid induced a marked increase in ALPase activity in MCC-, SOS-, NSC- and CGC-chondrocytes. The ALPase activities in MCC- and SOS-chondrocytes with 50 micrograms/ml ascorbic acid were 2.5-times those in its absence. Those in NSC- and CGC-chondrocytes were 10 times and 20 times, respectively. When chondrocytes were cultured with 10% charcoal-treated serum, ALPase activity decreased less than that in cultures with 10% normal serum in MCC-, SOS-, NSC- and CGC-chondrocytes. Treatment of 1,25-(OH)2D3 for 9 days from days 4 to 13 in MCC-chondrocytes and for 14 days from days 4 to 18 in SOS-, NSC- and CGC-chondrocytes inhibited ALPase activity dose-dependently at the concentrations of 10(-12) M to 10(-8) M in MCC- chondrocytes, 10(-10) M to 10(-8) M in SOS- and CGC-chondrocytes, 10(-11) M to 10(-9) M in NSC-chondrocytes. These findings suggest that 1,25-(OH)2D3 and ascorbic acid may be involved in the control of cartilage growth and terminal differentiation.


Condylar atrophy in craniomandibular disorders. In order to investigate the clinical characteristics of patients with condylar atrophy, we examined 146 patients with craniomandibular disorders using tomography. No statistical difference in occurrence of the condylar atrophy between males and females was observed. Patients with condylar atrophy was younger than those without condylar atrophy. And, condylar atrophy was closely related to craniomandibular disorders, especially to internal derangement or osteoarthrosis of the temporomandibular joint.


Relationship between condylar atrophy and tooth loss in craniomandibular disorders. In order to investigate the relationship between condylar atrophy and tooth loss in craniomandibular disorders, we examined 37 patients with condylar atrophy (atrophy (+) group) and 109 patients without condylar atrophy (atrophy (-) group). No significant difference in the number of missing teeth between the atrophy (+) group and atrophy (-) group was observed. However, a significant relationship between condylar atrophy and loss of the lower first molars was found. And individuals in the atrophy (+) group had a tendency to lose one or both lower first molars and left them without any prosthetic restorations in the growth period of the TMJ components.


Three dimensional shape measurement system for residual ridges. It is very important for design and construction of complete dentures to evaluate the condition of residual ridges of edentulous patients objectively and precisely. The authors have been developing a shape measurement system for residual ridges. In this study, the outline of the system is described and the accuracy of the system is evaluated. The system consists of a high precision laser displacement meter, a working table and its controller, and a personal computer. The working table, on which a plaster model is placed, can move until the end of the moving range at a speed of 0.7 mm/sec. The height of the plaster model was measured intermittently with a frequency of 7 points/sec. To determine the accuracy of this system, experimental plaster models, which simulated the simplified shape of residual ridge, were measured and analyzed. The measurement error was 2.5%, which seemed to be highly accurate. The accuracy of the measurement decreased with the darkness of the color of the plaster model.


Serum soluble CD4, CD8 and IL-2R levels in adult acute myeloid leukemia in remission. We have measured the serum levels of soluble CD4, CD8 and IL-2R in 43 patients with AML in complete remission (AML-CR). The sCD8 levels of AML-CR patients (443.9 +/- 224.4 u/ml) were significantly high as compared to that of the normal controls (177.1 +/- 76.3 u/ml), p < 0.01. The sIL-2R levels of AML-CR patients were 715.0 +/- 646.3 u/ml, which significantly differed when compared to 322.1 +/- 65.7 u/ml for the normal controls, p < 0.01. However, the sCD4 levels of AML-CR patients were 9.6 +/- 4.7 u/ml, which did not differ from the 8.3 +/- 2.6 u/ml of the normal controls. The AML-CR patients showed significantly increased sCD8 and sIL-2R levels at all ranges during the remission from one to 188 months. The sCD8 levels and sIL-2R levels of the AML-CR patients showed a close correlation, p < 0.01. Further, the sCD8 levels and lymphokine activated killer cell cytotoxic activity showed a close correlation, p < 0.05. The presence of the activation of anti-tumor immunity may be related to the continuance of the remission in the AML-CR patients.


In vitro analysis of drug resistance in tumor cells from patients with acute myelocytic leukemia. A 72 hours fluorometric microculture cytotoxicity assay (FMCA) was used for the study of chemotherapeutic drug resistance in tumor cell suspensions from patients with acute myelocytic leukemia (AML). A marked heterogeneity with respect to sensitivity was observed for a panel of cytotoxic drugs tested in 76 samples from 60 patients with treated or untreated AML. Primary resistance to vincristine (Vcr) and prednisolone in untreated AML was observed as well as 'acquired' resistance to several other antileukemic drugs. Cross resistance patterns for AML active drugs revealed significant positive relationships between anthracyclines, VP16 and amsacrine (Amsa), whereas mitoxantrone (Mitox) was more weakly correlated. Sensitivity to cytosine arabinoside was unrelated to the anthracyclines, VP16, Amsa and Mitox but showed a significant relationship to 6-thioguanine. Several resistance modifying agents, including the novel non-immunosuppressive cyclosporin A analogue PSC 833, were able to potentiate the effects of doxorubicin and Vcr at concentrations achievable in the clinic. However, the pattern of activity was heterogenous and the frequency of responsive samples was higher in relapse compared to de novo cases. Individual in vitro/in vivo correlations based on quartile distributions of all accumulated drug sensitivity data from AML patients indicated a high specificity with respect to the identification of drug resistance. The results suggest that the FMCA may provide clinically valuable information on chemotherapeutic drug resistance in AML.


Epirubicin as a single agent therapy for the treatment of breast cancer--a pharmacokinetic and clinical study. Sixty women with breast cancer (mean age: 61 years; range 36-78 years) were treated with Epirubicin (4'epi-Doxorubicin), 60 mg m-2, as single drug therapy. The drug was administered as 2 hours' constant rate infusions. The pharmacokinetics of the drug during the first course of treatment was evaluated by measurements of the plasma concentration of Epirubicin at the end of the infusion period. There was a five-fold inter-individual variation of the dose-normalized maximum plasma concentration, which increased with increasing age of the patients. There was no correlation between this pharmacokinetic parameter and degree of obesity. An increase in maximum plasma concentration was associated with an increasing degree of alopecia (p = 0.025). Also the degree of nausea and vomiting showed a tendency to increase with increasing maximum plasma concentration (p = 0.07). Fifty four of the sixty patients entered in the present study were evaluable for clinical response. There was one CR (complete remission). Seventeen patients achieved PR (partial response), and twenty five patients had SD (stable disease). Eleven patients did not respond to treatment. The median maximum plasma concentrations were 322, 316, 336 and 288 ng ml-1 in patients with CR, PR, SD and PD, respectively. The results in the present study showed that 60 mg m-2 of Epirubicin given as a constant rate infusion over 2 hours is a useful alternative to more aggressive combination drug therapy for the treatment of breast cancer.


Control of cisplatin induced emesis--a multidisciplinary intervention strategy. A pharmacological, behavioural and nursing intervention strategy was evaluated for prevention of cisplatin (50 mg m-2) induced emesis in ovarian cancer patients. 46 patients received metoclopramide 2.5 mg kg-1 i.v., b.i.d., dexamethasone 20 mg i.v., lorazepam and biperiden as well as training in relaxation, nutritional advice and continuity in nursing care. Controls (n = 34) received standard treatment (metoclopramide 10-20 mg i.v. or dixyracin 20 mg i.v.). The intensity and duration of nausea and vomiting were significantly lower and measures of quality of life higher for patients on the experimental ward during the three cycles that were studied. No significant changes in emesis were observed between the cycles. There was no correlation between emesis and any of the parameters of quality of life measured. The reliability and validity of nausea ratings are discussed and we suggest that an underreporting of nausea and vomiting might be common.


Role of pineal melatonin and melatonin-induced-immuno-opioids in murine leukemogenesis. The relationship between the pineal gland, melatonin and melatonin-induced-immuno-opioids with the response of C57Bl/6 mice to A-RadLV induced T cell lymphomas was investigated. Mice were injected at day 0 with A-RadLV and from day 10 they were treated chronically with melatonin 4 mg/kg body weight, naltrexone 1 mg/kg or phosphate buffered saline, throughout the experiment. In another protocol, groups of mice were a) surgical pinealectomized at day-14, b) functional pinealectomized (24:24 hours light) from day -20 and c) sham pinealectomized. At day 0 each group was inoculated intrathymically with A-RadLV. The results show that melatonin accelerated (p < 0.005) leukemogenesis whereas the surgical pinealectomy and the functional pinealectomy delayed it (p < 0.005 and p < 0.01). Moreover, the action of melatonin was blocked by naltrexone (p < 0.005), indicating the involvement of melatonin-induced-immuno-opioids in the development of the lymphomas.


Clinical management of prolactinomas: a ten-year experience. A ten-year experience on 36 patients bearing macroprolactinomas (MP) and 86 others bearing microprolactinomas (mP) is reported in this study. Different therapeutical approaches were used: 1) trans-sphenoidal surgery in 24 patients with MP and in 25 with mP; 2) medical therapy with the oral form of bromocriptine (BRC) in all the 24 patients with MP previously subjected to surgery, in 48 patients with mP ab initio, and in 16 out of 25 patients with mP previously subjected to surgery; 3) medical therapy with the long-acting injectable forms of BRC in 12 MP- and 13 mP-bearing patients, and 4) conventional radiotherapy in 12 of the 24 patients with MP previously subjected to surgery. The follow-up, performed five years after surgery, showed that: a) all the 24 patients with MP but one had normal PRL levels during BRC administration, with a rebound of hyperprolactinemia in all cases after withdrawal; b) during the treatment BRC caused normalization of PRL in 15 of the 16 mP-bearing patients surgically treated and in all the 48 mP-bearing patients only treated with BRC; c) in 20 of the 25 patients the treatment with injectable retard BRC caused the normalization of plasma PRL and the shrinkage of the tumor mass in all the patients with MP but one, as revealed by seriate CT scans. In conclusion, the surgical treatment of prolactinomas was ineffective to normalize plasma PRL levels in most patients whereas BRC, in standard or in retard forms, was able to normalize plasma PRL levels, reduce the tumoral mass and preserve the pituitary residual tissue. BRC should be, therefore, used as first choice therapy both for MP and mP.


[Balters' appliance and its action on the neuromuscular system]. Bionator created by BALTERS comes directly from activator but is smaller allowing its use during day and night to achieve mainly: lip closure, tongue in contact with soft palate, make oral area bigger improving its functionality, get a better maxillary relationship making mandible longer and improve tongue position. The principle that a new neuromuscular pattern conducted by appliance drives to development of a new morphologic pattern. Its activity on neuromusculature is neither well documented nor studied. Actually it is admitted that craniomandibular muscles contraction depends on neural pattern of this muscles during movement. This pattern is modified by continuous sensorial feed-back coming from dentition, T.M.J., and muscular and tendinal length and strength receptors. Clinical studies on mandibular advancement, show that occlusion alteration in sagittal mandibular reposition drives to spontaneous activity changes in muscles and to changes in electromyographic rest of certain muscles like the temporal. In some cases it is founded an increase in molar bite due to anterior mandibular reposition force. Clinical studies on mandibular advancement show changes on mandibular muscles spontaneous activity and possibility of modifications of E.M.G. rest level of temporalis. In some cases an increasing of bite force on first molars is founded. Electromyographic changes appear in children early, and produce a new functional position that changes morphology. Feed-back information comes from periodontal and muscular receptors. Patients treated show lip closure without strength, better tongue positioning and swallowing, and lower tension on suprahyoid muscles.


[The suprahyoid muscles and functional appliances]. Once it is reviewed orthodontic literature about functional appliances ways of acting, there is exposed another factor that could influence mandibular growth, that is suprahyoidic muscles. Depending on their balance or unbalance they will increase or decrease growth. This is an hypothesis because experimental evidence is difficult. Physiology of the muscles is commented. There are also described their functions and their undoubtable relationship with the tongue. The conclusion is that from the therapeutic point of view this muscles can be adjusted with tongue re-education or using functional appliances with advanced jaw position in the constructive bite. Finally, three cases are exposed, studying what has happened to hyoidic bone once the treatment has been performed.


[Elastic activator appliances: Bimler's elastic appliance and Klammt's elastic activator]. The action of two elastic activators (Bimler and Klammt) is studied in twenty Class II/1 malocclusions, with a mean age of 10.2 years and a treatment time of 2.7 years. Intercanine and intermolar widths, and "anterior arch height" (Korkhaus) were measured on models at the beginning and at the end of treatment. On lateral X-Ray films following parameters (Ricketts) were measured: facial axis, facial depth, convexity, lower facial height, and corpus axis. Conclusions are: both appliances have a good transverse response, Bimler's Gebissformer increase vertical growth, and Klammt's elastic activator decrease convexity by a more anterior mandibular positioning.


[The potentiality of antero-posterior orthodontic extraoral traction: clinical and cephalometric results]. Heavy posterior orthopedic forces used for massive retropositioning of maxillary bone are among the orthopedic treatments preconised during mixed dentition. The clinical and cephalometric results of twelve cases treated by these means indicate that only dental movements can be obtained without the possibility of any orthopedic remodeling. These results corroborate those of other studies and it is possible to conclude that heavy orthopedic forces represent a very imprecise therapy which lead to side effects that are greater than the desired objectives.


[Pneumatization of the frontal sinus].

[Pneumatization of the frontal sinus]. Through phylogeny and ontogeny, we follow the evolution of the frontal sinus; embryology gives details about the development of it. Then, we proceed to the investigation of factors influencing pneumatization. Afterwards, we analyse the different anomalies regarding pneumatization. In the last part, we mention experiments in progress being a link between cephalometry and the study of the frontal sinus surface in the diagnosis of skeletal Classes III.


[Equilibrium and neuro-occlusal rehabilitation]. The author reminds you that in 1956 he had the honour of being Chairman in the Congress of the S.F.O.D.F. here in Madrid. He, at that time, had insisted already, the if we want that a corrected mouth does not recidivate, it should be balanced and in a dynamic balance with which the parodontal problem is prevented and that is our purpose.


[Extraction versus non-extraction. Does the pendulum swing too much?]. Therapeutic extractions in Orthodontics has decreased in the last few years. The idea of that early treatment, functional appliances, upper molar and bicuspids distal movements, upper sagittal suture opening and other proceedings, reduce extraction practice is widely extended. Unfavorable effects like facial profile worsening and TMJ problems has been related to extractions. In this study common arguments against extractions has been analysed and attacked. Some cases are presented to illustrate non-extraction reliability. Main conclusions are: there is not relationship between extraction and TMJ dysfunctions; profile changes depend on technique not on extractions "per se"; profile gets better in alveolar prognatisms; non-extraction tendency rely most on some viewpoints away from biologic facts than clinical evidences.


[Glossoplasty: hope and pre-orthodontic support?]. A sample of 30 children who were between 8 and 15 years old is used for this study. The first part, using a cephalometric study (with two analysis: Ricketts and Sassouni), of these children's facial type, try to explain what expected the orthodontist after a partial resection of the tongue before treatment. In a second part, dental and skeletal effects of this surgery are studied, during a short period (5 to 10 months) before the beginning of the orthodontic treatment. These results are discussed according to research works realized by different authors.


[The orthopedic effect of the Edgewise technic]. A statistical study of 30 cases treated in Edgewise technic shows the orthopedic effects of this technic upon adolescent patients who have a Class II, division 1 malocclusion. The Harvold's triangle and Mac Namara's analysis show the sagittal break of the maxillary growth, the significant acceleration of the horizontal growth of the mandible and the stabilization of the vertical growth of the face. The results are compared to the initial situation and to a prevision of growth without treatment.


[A histological and histomorphometric study of the mandibular condyle during prenatal growth of the human mandible]. There is still some controversy on condylar cartilage growth capacity, whether it is similar or not to long bones growth cartilage. Recently it has been set that human tibial proximal growth decreases gradually throughout the second half of pregnancy period. The aim of this study is to determine whether changes are produced within mandibular condylar cartilage during fetal period are similar or not those that take place in growth platform. Lateral X-rays from the right half of the mandible of 19 human foetus between 18 and 41 weeks had been obtained. Total mandibular length, corpus length, ramus length and gonial angle were measured. A hystological condylar study was made, recording its thickness from sagittal sections of the central condylar area. Total mandibular length as well as corpus and ramus length progressively increased during studied period, existing high correlation between those parameters and gestational age and weight. Gonial angle decreases in studied period. Changes in condylar thickness were correlated neither with pregnancy age nor with fetal weight or X-rays mandibular parameters. These outcomes show that changes in mandibular condyle are not similar to those produced in tibial growth proximal platform and suggest condylar modifications could be more related to local factors than with general body growth mechanisms.


[Lower anterior facial height excess at the end of orthodontic treatment: the value of genioplasty]. Despite successful orthodontic-orthopedic treatments, some patients present with lower face vertical excess, that causes labial incompetence. In order to treat that excess, and to restore normal balance between upper and lower face, the authors propose that functional genioplasty be carried out. Clinical and cephalometric criteria of vertical excess are describe, as well as the surgical technique and post-operative care. Several treated cases are presented.


[The use of orthodontic goniometry to study apical expansion, using Pr. Planas' method: neuro-occlusal rehabilitation]. In this work, the method of orthodontic goniometry is used, which is a simple technique and not expensive, that allows us to determine the apical expansion in the studied models. 42 patients are studied by means of the techniques of Neuro-Occlusal Rehabilitation. We reach by this method expansion to the level of the apex as far as 12 mm in the lower arch and 11 mm in the upper arch. A simple statistic analysis is made which shows an average of expansions of 7.76 mm at crown level of the upper arch and 8.11 mm at apex level; at the crown level of lower arch we get 6.43 mm and apex level 5.8 mm. We think these results are interesting and they should make us study in depth the Neuro-Occlusal Rehabilitation and its principles.


[The use of growth prediction and V.T.O.: special concepts]. Growth induces very important modifications of the skeletal positions of the maxilla and the mandible and the precise position of the teeth is not foreseeable before an attempt to evaluate the situation the bones will be in by the end of the treatment has been made. Predictability factors are examined and a specific construction of V.T.O. is suggested. Then a new superposition is proposed which allows to determine the direction and range of teeth displacements.


[Pharyngeal obstruction and the functional adaptation of the natural posture of the head and the hyoid bone in sleep apnea syndrome]. Variations in natural head posture (NHP) and hyoid bone (HB) positioning impart changes in the size and shape of the pharyngeal airways. In SAS, which was shown to be correlated with detrimental craniofacial anatomical conditions, control of pharyngeal permeability is lost during sleep. The aim of this study was determine if functional adaptation of NHP and HB position to these detrimental conditions could be observed, using Bonferonni probabilities, in a cephalometric comparison of 38 SAS adults in the wakeful state and a control group of 38 healthy adults. Since HB relationships with craniofacial anatomical structures vary with the positioning of the head, the cephalograms were taken according to the preliminarily tested NHP, thus making the method reproducible. In SAS craniovertical angulation was unchanged, but the head was maintained in a forward position (increased cervico-vertical angulation, P < 0.001). Maintenance of an acceptable pharyngeal permeability was associated with a more distant positioning of HB from the cervical column (P < 0.01) and from craniofacial references (P < 0.001). In spite of these facts lower pharynx opening was still reduced (P < 0.05). Soft palate and facial divergence were expectedly increased in the apneic group. All the individuals but one control could be correctly reclassified with the help of soft palate length, facial divergence, and two HB related variables. Prevention of pharyngeal collapsibility in SAS seems to be commonly associated with functional adaptation of NHP and HP position. The precise control mechanisms of this adaptation remains to be elucidated. Skeletal predispositions to SAS do probably develop already during infancy.


[Sex differences of segments and angles of the facial profile, as studied by discriminant analysis]. On cutaneous (6 linear and 5 angular parameters) and bony (5 linear and 4 angular parameters) facial profile of young adults, sexual differences were studied by discriminant analysis. They are important and boldly significant.


[Anomalies of the inclination of the occlusal plane: early treatment using indirect guide-planes--electromyographic response]. We discuss five cases of ANGLE's malocclusion Classes I, II or III that were rehabilitated basically by: restoration of masticatory function (previously pathological); the use of removable orthopaedic plates with indirect guideplanes. The patients (aged 6-15 years when treatment began) now have symmetrical balanced occlusion. Surface electromyography was used to study the function of the anterior temporal, surface masseter, deep masseter and anterior digastric muscles of 12 patients during rehabilitation of severe malocclusion. Electromyograms were obtained both with and without orthopaedic guideplanes installed. There were no significant differences as regards mean resting myoelectric activity. During maximum voluntary clenching in centric occlusion, the anterior temporal muscles were the most active, followed by the surface masseters. The activity of the anterior temporal muscles during clenching was significantly less (P < 0.01) with guideplanes than without. During lateral displacements, the non-working side anterior temporal muscle exhibited a significantly higher potential than the other muscles monitored, especially with guideplanes installed. The activity was lees with guideplanes during swallowing.


[Hypertrophy or hyperplasia of myocytes in heart hypertrophy?]. One of the most controversial problem in cardiac muscle pathology is the existence of myocyte hyperplasia. The term hypertrophy indicates an increase in size of the individual muscle cells without changing their total number, whereas in hyperplasia there occurs proliferation of the myocyte. This fundamental question of the character of cardiac growth remains unresolved in spite of the wide attention it has received. Contemporary views concerning the cardiac muscle hyperplasia are presented. From clinical point of view the problem is significant for two reasons. The loss of the ability of muscle cells to proliferate is responsible for the irreversible myocardial destruction after injury. From another point of view, if the increase of the heart muscle is maintained, although a complete remission of cardiac hypertrophy becomes impossible. In 103 hearts with various forms of cardiac muscle hypertrophy the following parameters were estimated: diameter, length, volume, density and number of myocytes, as well as the density of nuclei of myocytes. The values of all histometric parameters correlated well with the LV weight up to 350 g. In heavier hearts these parameters were approximately at the same magnitude. The number of myocytes was significantly higher in hearts with LV weight above 250 g than in hearts below 250 g: 5.53 x 10(9) vs 4.31 x 10(9), p < 0.001. The influence of coronary artery diameters, degree of atherosclerosis, weight and percent of fibrous tissue and age on LV weight were evaluated as well. From these parameters only coronary artery diameters significantly influenced on LV weight.(ABSTRACT TRUNCATED AT 250 WORDS)


[Foreign bodies in respiratory tracts of children treated at the Institute of Pediatrics in Krakow during the years 1987-1991]. Foreign bodies aspirated into respiratory tract may produce severe lung damage and threaten life. We have analysed retrospectively symptoms, physical findings, chest roentgenograms and bronchoscopy reports in 20 children with foreign body aspiration. Boys dominated in this group. Foreign body aspiration often accompanied by coughing, wheezing and vomiting. In chest X-ray examination it was revealed unilateral body trapping and obstructive emphysema. Foreign body aspiration should be considered in children with prolonged respiratory tract problems even when no adequate history is present and with negative chest roentgenograms.


[Mastoiditis--a forgotten disease?].

[Mastoiditis--a forgotten disease?]. The symptoms and clinical course of latent mastoiditis in 18. children treated in Polish-American Children's Hospital in Cracow were presented. The ultimate diagnosis of mastoiditis was based on typical findings on antrotomy and the presence of granulation on histology of the tissue obtained during the operation. The main symptoms of latent mastoiditis were: a lack of appetite, chronic or recurrent fever and failure to thrive. 11 children (61%) had experienced more than 3 episodes of acute otitis media before the diagnosis of mastoiditis was established. Bacteria most commonly isolated from the middle ear were those of Staphylococcus, Streptococcus and Proteus species. Radiograms of mastoid processes were negative in up to 45% of those children. The mean duration of antibiotic therapy was 10.7 weeks. After antrotomy complete dissolution of symptoms were observed in 14 patients (78%). It is concluded, that in the presence of symptoms suggesting latent mastoiditis, the possibility of antrotomy, which may shorten the period of ineffective antibiotic therapy, should be considered earlier.


[Paternity study in Chilean families using DNA fingerprints and erythrocyte blood markers]. In the last decade, the electromorphic phenotype corresponding to extremely polymorphic zones of DNA, that include variable number of tandem repeat loci (VNTR) of oligonucleotide sequences, have been added to classical markers to elucidate the problems of parenthood identification and ascription in human beings. Using VNTR of several loci, a band profile practically unique for each individual is obtained (DNA-fingerprints). Since the pattern of VNTR electrophoretic bands is inherited from parents in a proportion of 50% from each one, this system is extremely useful for paternity ascription or exclusion. Nine nuclear families were studied, randomly selected from a group of 170 families that were analyzed using 5 erythrocyte genetic markers and with VNTRs detected using the multi locus probe (CAC)5, aiming to explore the concordance of both methods. Results were similar for both methods; however for VNTR, there is no information available on population frequency of polymorphisms.


[Effect of casein on the temporo-spatial organization++ of the contractile activity of the small intestine in the dog]. Some observations in man and experimental animals have demonstrated that casein decreases intestinal transit speed. However, its effects on intestinal motility have not been studied previously in a systematic fashion. The aim of this work was to study the temporospatial distribution of small bowel motility before and after the administration of calcium caseinate. Studies were performed in fasting dogs using 6 catheters perfused with a pneumo-hydraulic system. After the administration of 300 ml of a 10% solution of calcium caseinate, a global decrease in motor activity was observed, specially of grouped propulsive contractions, they were reduced in 64.9 to 19.5%. On the contrary, a significative increase, in 1.4 to 22%, of individual wave, non propulsive motor activity was observed. These quantitative changes in contractions, specially in their organization and temporo-spatial distribution, may be responsible for the decrease in intestinal transit after the administration of casein.


[Phenytoin pharmacokinetics in young and older adults]. To study the effect of old age on phenytoin pharmacokinetics, twelve young and nine old adults aged 21.7 +/- 1.8 and 71.8 +/- 4.9 years respectively, were studied. No significant differences of phenytoin indicating the drug distribution and elimination does not change with aging. After oral administration, significant differences were observed between young and old adults for absorption, measured through oral residence half time (36.89 +/- 5.07 h in young and 29.25 +/- 8.64 h in old adults p < 0.05), absorption half time (6.91 +/- 3.6 vs 3.29 +/- 2.35 h) and maximal concentration (1.45 +/- 0.37 vs 2.0 +/- 0.79 micrograms/ml). However, absolute bioavailability of the drug was not different in both age groups (72.9 and 67.6% in young and old adults respectively). It is concluded that no modifications of phenytoin dosage are necessary in elderly people.


[Colon and rectum cancer complicated with obstruction: immediate results and long-term follow-up]. Colorectal cancer is the leading cause of large bowel obstruction in Chile. The aim of this work was to assess the immediate results and long term survival of the surgical treatment of this complication. The clinical features of 113 patients (48 male and 65 female) with a mean age of 65 years, operated in a period of 10 years, were reviewed. The follow up was made by clinic appointments or home visits. The tumor was localized in the right colon in 30 cases, transverse colon in 20, splenic angle in 14, left colon in 39 and rectum in 10. Operative mortality was 34% for tumors of the right colon and 14% form tumors of the left colon. The follow up of the 89 survivors was accomplished in 97% with a mean follow up of 54 months (range 6 months-10 years). The principal prognostic factor was the initial stage of the tumor; survival was 87% for Dukes-Turnbull stage A, 70% for stage B and 32% for stage C1. The maximal survival period for stages D was 28 months. Patients subjected to an initial resective surgical procedure fared better, although not significantly, than colostomized patients. Present tendency is to perform one surgical procedure, avoiding colostomies that worsen patients quality of life and require a second intervention that increases surgical morbidity.


[Current diagnosis of renal cancer: clinical experience with 71 cases]. The diagnosis of renal cell carcinoma was frequently delayed due to the anatomic location of kidneys. Recently, the development of echographic imaging techniques has drastically changed this situation. In this retrospective review of 71 patients with renal cell carcinoma, the diagnosis was made incidentally during a routine abdominal ultrasound examination in 49% of cases. These patients, has lower stage and smaller tumors than symptomatic patients. Among the latter, hematuria was the principal presenting symptom. The early diagnosis of renal cell carcinoma allows more conservative surgical procedures and has a favorable effect on long term survival.


[Prevalence of false seropositivity for syphilis in a population of pregnant women]. A retrospective chart review of 439 pregnant women with positive syphilis serology detected with VDRL was made. One hundred twenty two women (27.7%), aged 17 to 43 years and with a gestational age ranging from 8 to 38 weeks, had false positive VDRL tests. None of these patients had a titer over 1:4 and 65% had a weakly reactive VDRL. Forty percent of women were diagnosed as having an early latent syphilis and 20% as late latent syphilis. Due to the high frequency of these later diagnoses in women with VDRL titers below 1:2, with no risk factors and negative sexual partners, post partum follow up is essential to detect cases with false positive FTA-ABs tests.


[Characteristics of severe esophagitis in patients with collagen diseases]. Connective tissue disease may alter esophageal function generating symptoms due to gastroesophageal reflux and motor disturbances. Fifteen patients with connective tissue diseases and severe esophagitis defined by the presence of esophageal stenosis or ulcerations were studied. Diagnosis was made with radiologic, endoscopic and manometric studies. Dysphagia was present in 11 and gastroesophageal reflux in all. All patients has an hypotensive and shorter lower esophageal sphincter. Better therapeutic results were obtained with surgical treatment.


[Foramen ovale electrodes in the study of temporal lobe epilepsy]. Corticograms of the mesial structures of the temporal lobe may be obtained with the recently developed foramen ovale electrodes. Since their installation is easy and of low risk, they will probably displace other invasive techniques routinely used up to the moment for the localization and lateralization of epileptic foci originated in the temporal lobe. For the first time in our country, we have used this technique in 7 patients with medically intractable complex partial epilepsy. In all the patients, the study allowed to clear doubts about the laterality of the start of ictal activity and to define irritative foci not found with conventional continuous superficial electroencephalographic recordings. The procedure was uneventful and the implanted electrodes were optimally tolerated. Foramen ovale electrodes are an effective diagnostic method for temporal lobe epilepsies and their features are specially appropriate for our milieu.