[The effect of immune suppression on the take and development of the human neocortex transplanted into the spinal cord of the adult rat]. The reaction of rejection takes place in most cases of xeno-transplantations. It can be suppressed by hydrocortisone which inhibits processes of cell immunity. As a result the take of transplants is observed in 100% of cases. Processes of proliferation and differentiation of their cell elements are delayed. Little differentiated cells capable of mitotic division were noted to group into rosettes which might result from trauma of embryonic nervous tissues during taking the material or a reaction to the action of the environment. The injury of the spinal cord is followed by the formation of a scar deforming the surrounding structures which is formed not only by the glial but also by the connective tissue cells of spinal membranes. Against the background of immunosuppression a small soft scar is formed between the transplant and the host spinal cord consisting mainly of fibrous astrocytes.


[The effect of an altered hormonal background on the mother-fetus system on the development of the neuroglia]. The method of electron microscopy was used in studying the antero-parietal area of neonatal rats born from mothers treated by desoxycorticosterone-acetate (DOCA) during the last 7 days of gestation (II group) or last 14 days (III group). The animals of the III group were given greater doses of DOCA. The neocortex of experimental newborn rats had accelerated differentiation of glial elements: differentiating glioblasts and astroblasts were noted more frequently, while the III group of animals had in addition single cells looking like oligodendrogliocytes. Processes of differentiation of glioblasts were more pronounced in the III group of rats whose mothers were given greater doses of DOCA and during a longer period of time while processes of proliferation were more pronounced in the neocortex of newborn rats of the II group (mitosis figures most often).


[Changes in the skin and sciatic nerve after soft-tissue damage to the extremity by a high-speed small-caliber bullet]. The character of contusive changes has been determined in the skin and sciatic nerve after lesion of soft tissues of the extremity with a high-speed small-bore bullet. A high-speed filming, tensiometry have been used. They allow to observe and measure processes of formation of the temporal pulsating cavity appearing at the moment of injury in the block of 20% gelatin and its influence on the imitator of the vascular-neural bundle. In the investigation performed on test-animals by means of neuromorphological, histological and histochemical techniques certain contusive changes are stated in the skin and sciatic nerve at various distances from the edge of the entrance and axis of the wound canal. The investigation of the material in 1, 3, 5 days after the lesion makes it possible to differentiate initial changes connected mainly with the effect of contusion from the secondary ones.


[The structure of the endothelialized and nonendothelialized areas of myointimal thickening of the rabbit aorta]. De-endothelialization of the abdominal aorta of the rabbit was performed with a balloon catheter. As a result, a partially endothelialized myointimal thickening was formed consisting of smooth myocytes and macrophages. As compared with the zone devoid of the endothelium the endothelialized zone was characterized by less thickness and by the presence of an additional elastic membrane. Great amount of leukocytes and solitary thrombocytes were adhesed just in the place of contact. In the center of nonendothelialized zone no adhesion was observed. In the zone covered by the endothelium smooth myocytes of the synthetic and contractile phenotype were seen with similar frequency. The nonendothelialized zone was presented mainly by smooth myocytes of the synthetic phenotype and macrophages. The myointimal thickening of the rabbit aorta might be considered as an informative model for analysis of myoendothelial interactions.


[Anthropological approaches in human anatomy]. Principles of anthropological methodology used by human anatomy have been formulated as the elucidation of forms and factors of variability of structures and their correlation in the integral organism. Under consideration was the use of different morphological signs for their integral estimation of the condition of the human body. The realization of these principles in research represents an anthropological trend in human anatomy. Its advantages in 1980s were preceded by the preliminary development of certain problems of anatomical anthropology by our national and foreign scientists. A review of researches on anthropological trends of human anatomy is given which were considered as a basis for the further development of medical and sports anthropology.


[The status of the lymphoid organs in the maternal organism as a reflection of the efficacy of correcting venous congestion during pregnancy in rats]. Under study was the influence of polyphenolic complexes of great burnet and venoruton upon the thymus, spleen, iliac lymph nodes of the uterus area in experimental phlebo-occlusion syndrome of pregnant rats. The data obtained show the changes of the drainage function of the lymphatic system under the influence of the drugs under study, certain reaction of T- and B- dependent zones of the central (thymus) and peripheral lymphoid organs. The structural-functional shifts had positive effects upon the fetus state. The action of polyphenols of great burnet is more effective as compared with venoruton.


[The effect of an experimental autoimmune process on the structural-functional changes in the spleen of progeny]. During early postnatal ontogenesis structural-functional changes of the spleen have been studied in the offspring of the females, having an experimental chronic autoimmune process with a predominant liver lesion. An increase of the spleen index, amount of IgM-producing cells and karyocytes in the spleen has been noted in the offspring of the given group of animals during all periods of the investigation, while in B-zones certain changes have been revealed demonstrating an enhancement of proliferative and differentiation processes. As a whole, these results are signs of the humoral immunogenesis strain. Simultaneously, in the spleen of the animals a decrease in the number of cells, forming rosellas with sheep erythrocytes and inhibition of their temperature resistivity have been noted. Besides, in the periarterial zones of their spleen, changes demonstrating certain inhibition of proliferation have been revealed; this can be considered as a depression of reactions of the cellular immunity.


[Quantitative changes in the lymphoid cell populations of the skin and regional lymph node after exposure to whole-body deep hypothermia]. The effect of general deep hypothermia on quantitative changes in populations of lymphoid cells in the skin and regional lymph node (LN) was studied in experiments in 20 male albino rats. The narcotized animals were cooled up to 18 degrees C of rectal temperature, kept at this temperature during 2h and then warmed up to 37 degrees C. Early terms of the posthypothermia period were characterized by less density of the population of intraepidermal lymphocytes and a simultaneous increase of their amount in the papillary and reticular layers of the derm without any changes in the hypodermis. Subsequently the lymphocyte population density in the derm was decreased, a little later their amount in the hypodermis was decreased. A simultaneous increase of the amount of lymphocytes took place in the area of postcapillary venules of the paracortical zone of LN. At the late post-hypothermal period the quantity of lymphocytes in the skin was restored. In the B-zones of LN less sizes of lymphoid nodules were noted as well as decreased population density (PD) of mitotically dividing cells, blasts and lymphocytes with pyknotized nuclei. A simultaneous increase of PD of plasmocytes took place in cerebral cords and elevated activity of alkaline phosphomonoesterase was noted in these cells. At the late posthypothermia period the area occupied by cerebral cords on the section was increased and correspondingly the area occupied by the cortical substance was decreased. A conclusion is made that resistant properties of the skin are activated after hypothermia procedures.


[The anatomy and topography of lymphoid clusters in the walls of the human pharynx in postnatal ontogeny]. A macro-microscopic investigation was performed on preparations of the pharynx from 110 corpses of people practically healthy in their life-time. Lymphoid accumulations (prenodules) by the rhinopharynx are disposed mainly in the area of salpingo-pharyngeal folds and between them, in the oral part of the organ--near salpingo-pharyngeal folds and in the posterior wall. In children the lymphoid accumulations by laryngopharynx are found near the middle line of the posterior wall, while in adult people they are concentrated in the area of piriform recesses. In the rhinopharynx walls the lymphoid accumulations are adjacent immediately to the basal layer of the epithelium, by the oral and laryngeal parts of the organ they are disposed closer to the muscular layer. The maximum quantity of the lymphoid accumulations was observed in early childhood, it was twice lower in senile people. The greatest sizes of them were noted in juvenile age.


[The development of the interfollicular epidermis in rats following autotransplantation]. Under study were changes to the structure of the rat epidermis detached with the help of incomplete vacuum after its autotransplantation onto the surface of the subcutaneous fat. The epidermis was transferred from the donor area onto the receptive bed protected by a preserving chamber with the help of the glue partly soluble backing. The transplanted epidermis, despite certain traumatization during the detachment, preserves its vital capacity and is actively developing under new conditions during the whole period of the investigation (28 days). Necrotic areas are eliminated within 3 days. As long as up to the 10th day the transplanted epidermis becomes considerably thicker due to the increased amount of layers of nucleus-containing cells. On the 5-14th days there occur single ingrowths of the epidermis into the thickness of the formed granulation tissue. During the following weeks stabilization of the transplant structures takes place. However, even on the 28th day the transplanted epidermis has no morphological distinctions from the intact epidermis.


[The morphofunctional characteristics of the healing of a skin wound in rats by exposure to low-intensity laser radiation]. A specific course of the reparative process in the skin under the influence of low-energy laser radiation was studied in albino rats by a complex of methods. High phagocytic activity of macrophages was observed as early as 6 h after trauma. It resulted in rapid debridement of the wound and prepared conditions for the proliferation phase. At later terms (5 and 10 days) the reaction to laser irradiation manifested itself as a powerful vascularization of the wound and increased amount of secreting fibroblasts. Favorable conditions for the reparative process resulting from the laser action were responsible for its optimum result as well. Cicatrization of the wound in animals given laser therapy was accompanied by the formation of hair follicles and the structure of the scar approximated to the structure of the intact skin.


[The lysosomal system of the hepatocytes during the development of extrahepatic cholestasis (a quantitative analysis)]. Electron microscopic and morphometric studies of the lysosomal system of hepatocytes with quantitative, informative and dispersion analysis of electron micrographs in healthy rats and rats with extrahepatic cholestasis have revealed the stage-like character of changes of the reaction of the liver subcellular structures in the processes of development of the pathologic process. At the first stage (12h-3 days) in parallel with the symptoms of injury (dilation of the lumen of bile canals with dystrophic alterations of epitheliocytes microvilli, depletion of the cytoplasm by glycogen, appearance of lipid inclusions, accumulation of the bile pigments) the initiation of urgent reactions of compensation was observed (using part of primary lysosomes in heterophagic processes, activation of autophagocytosis) as well as the beginning of the formation of long-term reactions with a somewhat increased amount of primary lysosomes and greater amount of small primary forms. There occur normalization of the ratio of primary and secondary forms. The 2nd stage (the 2nd half of the 1st week--the 2nd week) is characterized by the prevalence of compensatory adaptation reactions, underlaid by the formation of long-term reactions of compensation (considerable increase of the amount of primary lysosomes at the expense of intensification of their synthesis, active resorption of bile and lipid metabolites with the transformation of the latter in glycogen). The 3rd stage (the 3rd week) is characterized by depletion of reserves of the lysosomal system: sharp drop of the ability for self-renewal of the structures, change of the population composition of organelles expressed as prevalence of autophagosomes and residual bodies, transformation of the lysosomes in residual bodies.


[The morphofunctional characteristics of the enterochromaffin cells of the major duodenal papilla in the dog during experimental fasting]. A luminescent-histochemical method was used in investigation of the enterochromaffin cells (EC-cells) of the ampulla in the major duodenal papilla of 3 control dogs and 6 dogs under experimental fasting. In the ampulla wall a large number of EC-cells containing serotonin and catecholamine were detected. The degree and shining colour of these endocrine cells depend upon their interrelationship. During fasting changes of secretory activity and fluorescence index of EC-cells in major duodenal papilla of dogs take place.


[A quantitative analysis of the architectonics of the brain cortical fields during aging]. Under study was the cytoarchitectonics of motor cortical fields 4 and 6 and speech cortical fields 44 and 45 in man. Special attention was given to changes of neuron density in layers III and IV, change of the square area of the profile field of neurons and their nuclei, variability of the cellular composition. The investigation has revealed the decreased neuron density, less square area of the profile neuron field and their layers and rearrangement of the neuronal composition of cytoarchitectonic layers. Individual specific features of the process of aging of the brain in different individuals are noted.


[The effect of early partial postnatal deafferentation of the visual cortex on synapse formation]. A quantitative analysis of the synaptic population of the upper layers of the visual cortex of mice Acomys cahirinus has shown that the process of postnatal synaptogenesis proceeds during all the period of observations (1-13 days), the intensity of morphological differentiation of various types of synapses being higher during the first 5 days of life. Partial deafferentation of the visual cortex (dissection of the corpus callosum) in 3-, 5- and 13-day-old Acomyses results in changes of synapses of the II-III layers of the visual cortex of adult animals--with age of the operated animals the number of types of synapses, where quantitative morphological changes are observed, decreases. Thus, there exists a correlation between the maturity of synaptic population at the moment of damaging and the character of ultrastructural changes in response to this damage.


[The neuronal characteristics of the subnuclei of the paraventricular hypothalamic nucleus in rats (based on the data from morphometric and informational analyses)]. Subnuclei of the paraventricular nucleus (PVN) of the hypothalamus were studied in chronic experiments in 60 male Wistar rats (3 groups of animals) under normal conditions and under the influence of intensive and moderate regiments of hypoxic trainings. The division of macro- and micro-cellular populations of neurons of PVN is justified not only due to the peculiarity of the topographo-anatomical arrangement of them in the nucleus and the neuroanatomical relations but also due to a difference of their morphometrical (volumes of the cells, their nuclei, cytoplasm, nucleo-cytoplasmic coefficient) and informative characteristics (relative entropy and informative excess). The use of this approach in the assessment of the functional state of neurosecretory cells when compared with the change of organism resistance allows more complete assessment of the level of morphofunctional activity of neurons of subnuclei ot PVN and of their adaptation reserve which is important from the viewpoint of prognosis of the possibility of ther participation in protective-adaptational and compensatory reactions.


[The ultrastructural changes in the hemato-encephalic barrier in the neocortex of rat progeny with prenatal exposures to desoxycorticosterone acetate]. Electron microscopic methods were used to study the antero-parietal area of the cortex of newborn rats from intact mothers (I group) and rats born after intramuscular injection of desoxycorticosterone acetate (DOCA) to pregnant rats during the III trimester (II group) in dose 10 mkg/100 g of the body mass or during the II-III trimester of gestation (III group) in dose of 2 mkg/100 g. By the moment of delivery the hormone dose in the both experimental groups was gradually decreased up to 0.8 mkg/100 g of the body mass. Prenatal treatment by DOCA resulted in the following changes in the structure of hematoencephalic barrier: ultrastructural changes of endotheliocytes and pericytes showing accelerated synthetic and metabolic processes; lengthening of interendotheliocytic dense junctions, increase of the amount of astroblast peduncles; accelerated development of the basement membrane (lengthening and thickening) and differentiation of astroblasts. Signs of accelerated differentiation of glioblasts and vascular wall were much more pronounced in the neocortex of the III group of animals. However, part of the vessels were surrounded by edema. The perivascular edema was accompanied by loosening of the basement membrane, flattening of endotheliocytes, pericytes and increase of their electron density.


[The ultrastructure of human intracardiac neuroganglia]. Light and electron microscopic studies of nervous ganglia of the sinoauricular area of the heart were performed in 7 people dead at the age from 23 to 58 years (44 +/- 6) from not cardiac causes. The ganglia were disposed under the epicardium and had from 1 to 17 neurons as well as bundles of myelinated (MNF) and nonmyelinated nerve fibers (NNF). The ganglia most often had light neurons with a rounded nucleus and a compact nucleolus, with invariable cisterns of the granular endoplasmic reticulum microfilaments, electron-dense bodies, lipofuscin granules and edematous mitochondria. More rare were dark neurons with osmiophilic cytoplasm and nucleus of an irregular shape. Most NNF and MNF in the ganglia had normal ultrastructure. In part of NNF and MNF there were edemas of axis cylinders, fragmentation of neurofilaments and microtubules, sometimes MNF with transverse and longitudinal cleavage of myelin were seen. The significance of influences of the age, intravital pathology and postmortem alterations on the ultrastructure of intracardiac nervous ganglia of man is discussed.


[The correlations of somatotypes and the total ridge count in Russian men of the White Sea area]. Under investigation there were 158 Russian men of the city of Arkhangelsk and Arkhangelsk Province aged from 18 to 30 years. The total ridge count (TRC) and indices of the body constitution (according to V. M. Shevkunenko--A. M. Geselevich) were studied: relative length of the trunk (RLT), relative length of lower extremities, relative width of the shoulders and relative width of the pelvis. The hypothesis of normal distribution of these indices was confirmed by the chi-square criterion. The division into groups of dolicho- (DS), meso- and brachymorphic somatotypes (BS) was performed according to each sign and with special reference to limits X+/-S. Comparison of people of BS and DS groups has revealed significant differences only for RLT. The correlation coefficient proved to be valuable exceptionally for RLT. The method of succession analysis has shown that the least amount of observations for the determination of significant differences according to TRC is required in somatotyping according to RLT. Further investigations with other parameters of somatotyping require considerable amount of observations. The correlation analysis has determined the significant correlation coefficient for RLT only. A conclusion is made of the correlation of finger patterns and TRC with the rate of growing processes of organism.


[The cellular composition of the iliac lymph nodes and thymus in mice under local x-ray irradiation of the gonads at high and low doses]. The cellular composition of iliac lymph nodes and thymus of 150 male white mice was studied 4 weeks after local irradiation of the gonads by doses 7.34 and 360 cGr by histological and electron microscopic methods. Intact animals and corresponding groups of false irradiation were used as control. Changes of the cellular composition of B-dependent zones of the lymph nodes were shown both after irradiation by high (360 cGr) and low (7 cGr) doses. The effect of irradiation by the dose 34 cGr on the content of certain cell forms was less while the ultrastructural transformations were more pronounced than those caused by weak X-ray irradiation. Certain similarity was established in the dynamics of cell reactions in false irradiation of the animals (imitation control) and irradiation by low doses. A supposition is put forward concerning the influence of non-irradiation factors accompanying the irradiation on the value and character of the response to radiation loads of low intensity.


[The diameters of the central canals of the osteons in tubular bones (based on data from scanning electron microscopy and centrifugal porosimetry)]. The centrifugal poremetry is based on preliminary filling the pores of prepared samples with the working fluid and the following removal of it from the pores at different fixed velocities of rotation. Measurement of the quantity of the remaining fluid after each rotation allows obtaining the distribution of the pore volume depending on their radius. Since the samples are not destroyed they can be used for measuring the pores diameter in electron micrograph. Comparison has been made of the distribution of the pores quantity by their diameters obtained by morphometry with the distribution of the pores volume by their diameters obtained by differentiation of poremetry curves. Besides greater detailization of the prevailing diameters of the pores, the method of poremetry allows the information to be obtained concerning the distribution of not only sizes of central canals of osteons but also smaller pores characterizing the system of lacunae of osteocytes and canals connecting them.


[The structure of the lymph nodes sequentially located along the lymph flow]. Special features of the construction of more centrally disposed lumbar lymph nodes allow a greater velocity of lymph flow through them to be suggested. In lumbar nodes the states of immune reaction such as lymphocytic hyperplasia and proliferation of the reticular cells as well as degeneration of the connective tissue after the action of harmful factors are met more often than in the peripheral nodes since they have more vast basin of the lymph collection. Specificities of the cellular composition give grounds to suggest a greater strain of immune reactions in the peripheral nodes especially those draining the internal and somatic organs simultaneously.


[Modulation of the immune response of HSIAH strain rats with the preparations Nakom and L-dopa. Hereditary stress-induced arterial hypertension]. A morphometrical and cytological study of the iliac lymph nodes was carried out in 5-month-old rats of the NISAG strain (40 animals) given injections of distilled water and drugs L-dopa and Nakom increasing synthesis of catecholamines. Injections to rat-cubs of distilled water which was used for preparing suspensions of the drug resulted in lessening the mass of the lymph nodes in adult animals by 74% as compared with intact rats. The presence of L-dopa returned this index to the level characteristic of intact animals, and administration of Nakom gave its 62% elevation. In all the animals injected water the section area of the cortical substance was decreased while the relative square area of the medullary substance increased. The cortico-medullary index dropped by 53% which suggested a change of the lymph node type. Under the influence of L-dopa and Nakom an inclination to a one-direction reaction was noted: dilatation of marginal sinuses containing great amount of cells; change of the ratio of the medullary and cortical substance at the expense of growing paracortical zone; narrowing of the cortical plateau at the expense of newly formed secondary lymph nodules with a rather typical 2-3 raw arrangement of them. The changes were more pronounced after the administration of Nakom, greater amount of cells of the lymphoid and plasmacytic raw in all zones except the paracortical one where the portion of blasts, middle-size lymphocytes, macrophages, reticular and mitotically dividing cells became less.(ABSTRACT TRUNCATED AT 250 WORDS)


[The structural-functional changes in the thymus of the progeny of female rats with experimental chronic cholestasis]. Structural-functional changes to the thymus of progeny of female rats with chronic cholestatic lesions of the liver at different terms of early postnatal ontogeny were investigated. The progeny of this group of animals was found to have less, as compared with controls, mass of the thymus at all periods of the studies, less intensity of the immune reaction of higher sensitivity of the delayed type, less amount of thymocytes of E-RFC. The immunological shifts observed were in close correlation with the morphological alterations in the thymus. The results obtained might be taken as an evidence of the depression of cellular immunity in this group of animals.


[The mitotic activity of the follicular and parafollicular (C) cells in the thyroid of rats with hypercalcemia]. Slices of the thyroid gland were impregnated with silver nitrate and stained with hematoxylin. Separate calculation of the index of calchicin mitosis of the follicular and parafollicular (C-) cells was made. The material of 37 mature albino rats was analyzed. Calcium-rich diet was given to 22 animals during 10 days. Different levels of hypercalcemia were achieved by different doses of vitamin D2 (from 1 to 10 thousand MU daily, 11 experimental groups). The mitotic index of C-cells was found to grow but under mild hypercalcemia (10% of the control level). Further elevation of the calcium concentration in blood was followed by a decrease of the amount of the dividing parafollicular cells down to control values. In rats fed by the diet optimal for the stimulation of C-cells division (11 rats, 2000 MU as a daily dosage of vitamin D2) within the interval from 1 to 10 days increased mitotic activity of the follicular cells was found from the 3rd day, while that of C-cells only as late as the 9th-10th day. In all the experimental rats the mitotic index of the follicular thyrocytes was 3.5-4 times as high as the mitotic index of C-cells. Relatively not high proliferative activity of parafollicular cells might be due to their pronounced polyfunctional character and their participation in complex paracrine interactions with other cell elements of the thyroid gland.


Hypertension and endothelial function--aspects of atheroma protection. Old concepts of an "inert" vascular endothelium have been entirely discredited. It is now known that the vascular endothelium and media form a "functional unit", communicating via both electric and humoral signals. Normal endothelium maintains vascular dilation through release of various dilatory substances, the main one being endothelial relaxing factor (EDRF), which is nitric oxide (NO). EDRF is, for example, released in response to increased shear stress that accompanies high flow rates, and acts by engaging the cyclic GMP system of smooth muscle cells. Even potential vasoconstrictors such as vasopressin, catecholamines and serotonin release EDRF. Endothelial release of prostacyclin supplements the EDRF action. EDRF (and prostacyclin) also inhibit platelet aggregation. In the presence of hypertension and/or atherosclerosis, endothelial function is often impaired and pressor/thrombogenic factors such as endothelin, thromboxane, vasopressin, catecholamines, and serotonin become more dominant. Antihypertensive therapy should, ideally, seek to restore endothelial function to normal.


Hemodynamics of elevated blood pressure. In young hypertensives (less than 30 years) there are signs of increased sympathetic drive with higher than normal heart rates and cardiac output. Over the years, established hypertension is associated with an elevated total peripheral resistance, an abnormally low cardiac output (particularly during exercise), and reduced coronary reserve.


Hemodynamic profiles of antihypertensive agents. Alpha-blockers tend to normalize central hemodynamics and only modestly reduce the systolic blood pressure-heart rate (SBP x HR) product. Similarly, dihydropyridine calcium antagonists normalize central hemodynamics, but at the expense of an increased heart rate (which tends to normalize chronic treatment). Non-dihydropyridine calcium antagonists tend to reduce resting heart rate. Angiotensin converting enzyme (ACE) inhibitors normalize central hemodynamics with no change in heart rate. Classic beta-blockers, particularly the non-selective agents, lower heart rate and cardiac output at rest and during exercise, with a reflex increase in total peripheral resistance (TPR), which lessens with chronic therapy. With dual-acting beta-blockers like carvedilol, the fall in blood pressure is accompanied by a fall in TPR and only a modest drop in cardiac output; the increase in AVO2 difference is less marked with carvedilol compared to a classic beta-blocker, suggesting that the body's reserve mechanisms may be less reduced.


Hypertension--interaction with other coronary heart disease risk factors. Hypertension can no longer be regarded as a single entity; it frequently coexists with other powerful coronary risk factors such as left ventricular hypertrophy (LVH), lipid and clotting disorders, obesity, and insulin resistance/impaired glucose tolerance.


Hypertensive therapy--effect on coronary risk factors. Antihypertensive agents, particularly diuretics and beta-blockers, can "worsen" certain coronary risk factors, e.g. plasma lipids, which could theoretically offset the benefit of lowering blood pressure. However, the use of such surrogate markers may be inappropriate; propranolol has been shown to significantly decrease the frequency of myocardial infarction (MI) as evidenced by the appearance of Q-waves on ECG, and diuretics have significantly reduced the frequency of clinical MI in the elderly patient with isolated systolic hypertension.


Left ventricular hypertrophy as a coronary risk factor. Left ventricular hypertrophy (LVH) is one of the most powerful risk factors known for cardiovascular disease. It is associated with impaired left ventricular filling, ventricular ectopy, impaired left ventricular contractility, and myocardial ischemia. Myocardial ischemia has a multifactorial pathogenesis and results from an increased oxygen demand (due to increased hemodynamic burden and increased muscle mass) and a decreased oxygen supply secondary to microvascular disease and coronary artery disease.


Reversibility of left ventricular hypertrophy. Left ventricular hypertrophy (LVH) is a powerful independent risk factor for coronary artery disease. This overview of 104 studies examines the ability of various types of antihypertensive therapies to reverse LVH as assessed by echocardiography. Combination therapy, angiotensin converting enzyme (ACE) inhibitors, and methyldopa were the most effective in reversing LV mass; vasodilators such as minoxidil and hydralazine had no effect on LVH. These differences were independent of the degree of fall in blood pressure and duration of therapy. beta-blockers were as effective as ACE inhibitors in decreasing LV wall thickness. Possible reasons for drug differences in reversing LVH are discussed. Preliminary evidence suggests that reversing LVH by antihypertensive drug therapy is associated with a reduction in cardiovascular complications.


Effect of antihypertensive therapy on left ventricular hypertrophy and on its pathophysiologic sequelae. Recent evidence has shown that a decrease in left ventricular hypertrophy (LVH) by antihypertensive agents suppresses ventricular ectopy, improves ventricular filling, and maintains or even enhances LV function. However, not all antihypertensive drugs reverse LVH or reduce ectopy in spite of their ability to lower blood pressure. Preliminary data suggest that the reversal of LVH is linked to a decrease in cardiovascular morbidity and mortality.


Twenty-four hour blood pressure monitoring and end-organ damage. Ambulatory blood pressure monitoring (ABPM) over 24 hours has become quite common. Evidence suggests that the mean 24-hour measurement is more closely associated with end organ damage, including end-points such as left ventricular hypertrophy (LVH), than is a single blood pressure measurement taken in the doctor's office. Clinicians disagree about the particular significance of blood pressure measurements obtained during exercise, blood pressure variability, and blood pressure load (a measurement above 140/90 over 24 hours). However, the morning peak in blood pressure appears to be associated with the highest incidence of coronary events, and end organ damage may be greater in subjects in whom nocturnal blood pressure falls only slightly from a diurnal baseline (non-dippers). From now, ABPM serves mainly as a research tool. Longitudinal controlled studies are needed to compare the value of ABPM to office blood pressure readings in terms of how these measurements can predict cardiovascular end-points or, more realistically, surrogate end-points, such as the development or regression of LVH.


Twenty-four-hour blood pressure and antihypertensive treatment. Normal values for 24-hour blood pressure (BP) have not been well characterized. However, it is believed that the maintenance of normal blood pressure control is a desirable feature of an antihypertensive agent. This is particularly important with respect to the drug's ability to (1) maintain circadian variation, albeit from a lower baseline, (2) lower BP throughout the 24 hours, (3) avoid the development of postural hypotension, (4) avoid decreases in BP sufficient to precipitate an ischemic event, (5) and to reduce BP variability toward the normal BP limits.


Acute effect of manidipine on renal blood flow measured by pulsed-Doppler flowmeter in normal subjects. The purpose of this study was to examine the effect of manidipine hydrochloride, a new calcium antagonist, on renal blood flow in healthy subjects, using the newly developed pulsed-Doppler flowmeter with colored flow imager and digital computer analyzer. Results in previous studies differed because the para-aminohippurate clearance method measures the average not real-time value. Sixteen healthy volunteers (n = 7, manidipine 20 mg; n = 9, placebo control) participated in the study. Before and 1 h after drug administration, pulsed-Doppler measurements were carried out by transabdominal approach with patients in the supine position. Manidipine hydrochloride increased renal blood flow significantly compared with placebo (13.8 +/- 4.7% vs. 6.1 +/- 5.6%; p < 0.05). There was a significant (p < 0.005) between group difference in the reduction in systolic blood pressure (-14.8 +/- 1.6 mmHg manidipine; -3.0 +/- 2.1 mmHg placebo). These data suggest that manidipine hydrochloride has a vasodilating effect on renal arterioles and a beneficial effect on the kidneys of hypertensive patients. Further, the pulsed-Doppler flowmeter may become a very useful tool for noninvasive measurement of renal blood flow.


The effect of manidipine on renal hemodynamics in essential hypertensive patients: responses to acute stress. The effects of the calcium antagonist manidipine 20 mg/day on changes in blood pressure and renal hemodynamics in response to acute stress by the mental arithmetic test (MAT) and the cold pressor test (CPT) were investigated in 14 patients with essential hypertension (median age: 50 +/- 2, WHO stage I-II). During the drug-free period, acute stress by both MAT and CPT caused an increase in the renal vascular resistance index (RVRI) [% change in RVRI, 17% for MAT (p < 0.05) and 26% for CPT (p < 0.01)] and an increase in blood pressure [% change in mean blood pressure (MBP): 17% for MAT (p < 0.001) and 16% for CPT (p < 0.001)]. CPT stress resulted in a reduction in RAFV (% change in RAFV: -12%, p < 0.05). Oral administration of manidipine resulted in hypotensive effects at rest [MBP: from 116 to 99 mmHg, p < 0.001], no change in RAFV (31.3 to 32.9 cm/sec, p = ns), and reduced RVRI (from 3.9 to 3.2 mmHg.sec/cm, p < 0.02). Manidipine inhibited the hypertensive response to acute stress by both MAT and CPT [% change in MBP: from 17% to 11% for MAT (p < 0.02) and from 16% to 11% for CPT (p < 0.01)] and also inhibited the increase in RVRI [% change in RVRI: from 17% to -1% for MAT (p < 0.05) and from 26% to 8% for CPT (p < 0.01)]. Manidipine has beneficial effects on blood pressure and renal hemodynamics at rest in patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of manidipine, a new calcium antagonist, on intrarenal hemodynamics in essential hypertension. The effect of manidipine, a new Ca2+ antagonist, on intrarenal hemodynamics was assessed in essential hypertension and compared with nicardipine, a previously studied Ca2+ antagonist. Identical 2-week studies were repeated before and during the administration of manidipine (10 mg once daily, 2 weeks) in 3 patients with essential hypertension who were given regular- and sodium-restricted diets for 1 week each. The renal function curve (pressure-natriuresis relationship) was drawn by plotting the urinary sodium excretion rate on the y-axis as a function of the systemic mean arterial pressure (MAP) on the x-axis. Assuming that the difference between MAP and the extrapolated x-intercept of the renal function curve represents the effective filtration pressure across the glomerular capillary walls, the intrarenal hemodynamics were calculated (e.g., afferent arteriolar resistance (RA), efferent arteriolar resistance (RE), and glomerular pressure (PG)). During the regular sodium diet, MAP was lowered from 100 +/- 7 to 93 +/- 5 mmHg (p < 0.04) and the effective filtration pressure was lowered from 20 +/- 2 to 10 +/- 3 mmHg (p < 0.05); the renal plasma flow rate (pre: 560 +/- 74 vs. post: 627 +/- 108 mL/min) and glomerular filtration rate (82 +/- 10 vs. 78 +/- 5 mL/min) were not altered. RA remained unchanged (3,800 +/- 700 vs. 3,400 +/- 300 dyn.sec.cm-5; % reduction: 4 +/- 16%) whereas RE was reduced from 4,300 +/- 700 to 3,300 +/- 800 dyn.sec.cm-5 (19 +/- 15%). Thus, PG was lowered from 58 +/- 2 to 50 +/- 2 mmHg (13 +/- 3%), which parallels with the reduction in MAP.(ABSTRACT TRUNCATED AT 250 WORDS)


Clinical evaluation of the efficacy and safety of manidipine in hypertensive patients with renal disorders. Hypertension is an important factor that accelerates deterioration in renal function. This study evaluated the antihypertensive effectiveness, tolerability, and safety of manidipine hydrochloride, a new dihydropyridine calcium channel antagonist. Sixteen patients (10 men and 6 women) with hypertension and renal disorders received 10 or 20 mg of manidipine once daily for 12 weeks. After 4 weeks of therapy, manidipine treatment produced significant reductions in both systolic and diastolic blood pressures to 146.9 +/- 3.2/87.1 +/- 2.1 mmHg from a baseline value of 174.4 +/- 3.0/98.4 +/- 3.0 mmHg. The antihypertensive effect was well tolerated and sustained during drug administration. Biochemical variables including serum creatinine were essentially unchanged during therapy despite the marked reduction in blood pressure. In addition, renal function did not deteriorate during manidipine therapy as assessed by urinary excretion of phenolsulfonphthalein (22.6 +/- 4.0% vs. 27.9 +/- 6.0%, control). No severe adverse effects were encountered during therapy. We conclude that manidipine is a safe and useful antihypertensive agent for the management of hypertensive patients with renal disorders.


Regulation of the gene expression of type-1 angiotensin II receptor in spontaneously hypertensive rats. Regulation of the gene expression of type-1 angiotensin II receptor (AT1) by treatment with manidipine, a calcium channel blocker, or delapril, an angiotensin converting enzyme inhibitor, for one week was assessed in the adrenal gland, heart, kidney, and brain from spontaneously hypertensive rats (SHR). Tissue AT1 receptor messenger RNA (mRNA) content was measured by reverse transcriptase-polymerase chain reaction. Treatment with manidipine (3 mg/kg/day) or delapril (30 mg/kg/day) lowered systolic blood pressure (SBP) significantly (p < 0.01) (delta SBP; -73 mmHg or -67 mmHg, respectively). Although delapril markedly increased plasma renin activity (PRA), manidipine did not alter PRA. AT1 receptor mRNA content in the adrenal gland was significantly (p < 0.01) decreased by treatment with manidipine or delapril. In contrast, cardiac AT1 receptor mRNA content was significantly (p < 0.01) increased by treatment with either agent. There was no significant change in renal and brain AT1 receptor mRNA contents. These findings suggest that although the expression of AT1 receptor gene depends on the circulating renin-angiotensin system (RAS), it is regulated independently in a tissue-specific manner via the local RAS in each tissue of SHR.


Effects of a new calcium antagonist, manidipine, on the renal hemodynamics and the vasoactive humoral factors in patients with diabetes mellitus. The effects of manidipine (10 mg/day for 7 days) on the renal hemodynamics and vasoactive humoral factors were examined in 6 adults with diabetes mellitus (DM). Mean duration of DM was 9 +/- 2 years; serum creatinine concentration was 0.9 +/- 0.04 mg/dL. Plasma endothelin-1 (ET-1) concentration was 5.4 +/- 0.7 pg/mL before manidipine, compared with 1.9 +/- 0.2 pg/mL in 14 controls (p = 0.03%). Systolic and mean blood pressure decreased significantly during treatment without changes in glomerular filtration rate, renal plasma flow, or filtration fraction. Renal vascular resistance tended to decrease and fractional excretion of sodium significantly increased from 1.35 +/- 0.27% to 2.06 +/- 0.47 (p = 2.96%). ET-1 significantly decreased from 5.4 +/- 0.7 pg/mL to 3.5 +/- 0.6 (p = 2.95%), while plasma angiotensin II, atrial natriuretic factor, urinary excretion rate of ET-1, and albumin excretion rate did not change. Manidipine lowers blood pressure without adversely affecting renal function in diabetic patients. Manidipine, which lowers ET-1, may protect from progressive renal injury in diabetics.


Effects of manidipine and delapril on glucose and lipid metabolism in hypertensive patients with non-insulin-dependent diabetes mellitus. Effects of manidipine, a new calcium antagonist, and delapril, an angiotensin converting enzyme inhibitor, on glucose and lipid metabolism were investigated in mild to moderate hypertensive patients with non-insulin-dependent diabetes mellitus (NIDDM). The patients were treated with either manidipine 10 mg/day (n = 12, mean age 63 +/- 2 years) or delapril 30 mg/day (n = 8, 62 +/- 3 years) for 12 weeks. Glucose and insulin (IRI) responses to 75 g oral glucose load, glycosylated hemoglobin A1c (Hb A1c), serum levels of total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride and apolipoproteins, and 24 h urinary excretion of C-peptide were measured before and at the end of treatment. Both manidipine and delapril showed adequate hypotensive effects. Neither manidipine nor delapril affected blood glucose and IRI responses to glucose load. Manidipine showed no effect on lipids whereas delapril increased HDL cholesterol (47 +/- 5 mg/dL to 61 +/- 7, p < 0.05), although total cholesterol and triglyceride were not altered. The ratio of TC-HDL cholesterol/HDL cholesterol was decreased by delapril (3.44 +/- 0.30 to 2.61 +/- 0.45, p < 0.05). There were no significant changes in apolipoproteins. Both manidipine and delapril have adequate antihypertensive actions without unfavorable effects on glucose and lipid metabolism in hypertensive patients with NIDDM. Delapril seems to have a beneficial effect on lipid metabolism.


Effect of manidipine, a novel calcium channel blocker, on quality of life in hypertensive patients. A multicenter open study was performed to evaluate manidipine monotherapy for 6 months on quality of life in hypertensive patients. One hundred and sixty-six patients with essential hypertension were enrolled. Of these, 2 were excluded because of violation of entry criteria, 4 withdrew from treatment because of side effects, and 12 for personal reasons. Manidipine treatment observed at a daily dose of 10 to 20 mg produced effective reduction in blood pressure during the course of the study. Adverse reactions such as palpitation or headache were experienced by 5 of 166 (3%) patients. Quality of life (QOL), assessed grossly by attending physicians, was rated as improved in 62% and unchanged in 36% of patients. Significant improvements in mean QOL scores were noted in general symptoms, physical symptoms and general well-being, work performance and satisfaction, sleep scale, emotional state, cognitive function, sexual function, and self-control. Elderly patients, age 60 years and older, achieved significant improvement in the same QOL items as in all cases; there was no difference between younger and older age groups. In conclusion, manidipine monotherapy is useful for treating patients, including the elderly, with essential hypertension, and this therapy improves their quality of life.


Mesangial cell growth in genetically hypertensive rats and effect of calcium antagonists upon this growth. Mesangial cells play an important role in physiological and pathophysiological regulation of glomerular functions. To explore the involvement of deranged mesangial cell functions in the pathogenesis of hypertension, the growth activity of mesangial cells was compared in stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY). Upon exposure to fetal calf serum, the growth rate was significantly higher in mesangial cells cultured from glomeruli of 4-week old SHRSP than in those of age-matched WKY. This abnormally high growth of SHRSP mesangial cells was significantly inhibited by dihydropyridine calcium antagonists. Of the three antagonists tested, manidipine was the most potent inhibitor. Significant growth inhibition occurred at a concentration as low as 10(-12) M; inhibition as high as 65% was found at 10(-6) M. Calcium antagonists, particularly manidipine, may prevent or delay the development of hypertension not only through vasodilation but also through inhibition of mesangial cell growth. By slowing mesangial cell proliferation, calcium antagonists also may slow the progression of hypertension-induced glomerular sclerosis.


Effects of manidipine hydrochloride on proliferation and glycosaminoglycan synthesis of cultured vascular smooth muscle cells. The effects of manidipine hydrochloride, a calcium channel blocker, on the proliferation and the synthesis of glycosaminoglycans (GAG) in cultured rat aortic vascular smooth muscle cells (VSMC) were studied. Mandipine hydrochloride suppressed the DNA synthesis of VSMC dose dependently at concentrations of more than 10(-8) M. Mandipine hydrochloride 10(-6) M suppressed proliferation of VSMC to 50% of the control value. Manidipine hydrochloride stimulated the synthesis of GAG at concentrations above 10(-11) M. Manidipine hydrochloride 10(-8) M stimulated synthesis of GAG to 450% of control. Our findings suggest that because mandipine hydrochloride suppresses proliferation and stimulates GAG synthesis of VSMC, it may be an anti-arteriosclerotic agent.


Effects of manidipine on DNA and protein syntheses in cultured vascular smooth muscle and endothelial cells and on proto-oncogene expression. To elucidate the importance of Ca2+ influx via voltage-dependent Ca2+ channels in the mechanism of vascular remodeling, we investigated effects of a new Ca2+ channel blocker manidipine on DNA and protein syntheses stimulated by several mitogens in cultured rat vascular smooth muscle cells (VSMC) and bovine endothelial cells (EC), and growth-related immediate early proto-oncogenes expression in VSMC. Endothelin-1 (ET-1) induced receptor-mediated phosphoinositide breakdown and increased cytosolic free Ca2+ levels in rat VSMC, with concomitant increases in proto-oncogenes (c-fos c-myc) mRNA levels as well as DNA and protein syntheses. Manidipine dose-dependently (10(-9) M to 10(-6) M) inhibited DNA, and protein syntheses stimulated by 10(-7) M ET-1 in rat VSMC; manidipine was a more potent inhibitor for protein synthesis (IC50: 10(-8) M) than for DNA synthesis (IC50: 10(-7) M). Manidipine also inhibited DNA synthesis stimulated by 10 ng/mL bFGF and 2.5% FCS in rat VSMC and bovine EC; manidipine was more potent in inhibiting DNA synthesis stimulated by bFGF than that by FCS in both cells. The expression of ET-1-induced c-fos and c-myc mRNAs levels was unaffected by manidipine. These results suggest that manidipine has potent inhibitory effects on the ET-1-induced hyperplasia and/or hypertrophy of VSMC, as well as on the bFGF-induced hyperplasias of VSMC and EC, thus implicating its potential usefulness for preventing abnormal VSMC proliferation and angiogenesis associated with hypertension and atherosclerosis.


Manidipine inhibits the progression of hypertension and atherosclerosis in endothelium-injured and cholesterol-fed Goldblatt 2K1C rats. In the present study, arteriosclerotic change of the aorta was induced in rats. The effects of manidipine hydrochloride on the resulting hypertension and arteriosclerotic change were studied. In endothelium-injured cholesterol-fed Goldblatt 2K1C rats, moderate elevation of blood pressure was noted at 3, 4, and 5 weeks. Laboratory studies performed at the end of 6 weeks also showed hypercholesterolemia, accompanied by a reduction of triglycerides and HDL cholesterol. Regular doses of manidipine (200 or 500 mg/kg) resulted in a dose dependent inhibition of the blood pressure elevation and a reduction of HDL cholesterol, but had no effect on cholesterol or triglyceride levels. Morphological studies in endothelium-injured rats afflicted with hypercholesterolemia and hypertension, showed medial thickening and intimal hyperplasia. Hyperplasia of the intima was a result of excessive proliferation of the smooth muscle cells. These cells showed an unusually large number of fat droplets and were considered indicative of atheromatous plaque formation. In rats treated with manidipine, hyperplasia of the media was completely suppressed while hyperplasia of the intima was reduced by a minimum of 50%. This study demonstrated that hypercholesterolemia and hypertension produced arteriosclerotic change in endothelium-injured rats, which was inhibited by manidipine. It is not known whether antiarteriosclerotic action was involved in the antihypertensive effect of manidipine.


Regression of hypertension-induced vascular hypertrophy by an ACE inhibitor and calcium antagonist in the spontaneously hypertensive rat. This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.


Effect of manidipine on cardiac hypertrophy and coronary circulation in DOCA/salt hypertensive rats. The effect of manidipine on cardiac hypertrophy, coronary circulation, left ventricular weight and maximal coronary flow in hypertension was measured in DOCA/salt treated systolic hypertensive rats with and without manidipine treatment. Normotensive rats were used as controls. After feeding with 0.05% manidipine-containing food, blood pressure was reduced only in DOCA/salt hypertensive rats, but not in control rats. After 3 weeks of treatment, sodium excretion was significantly increased in DOCA/salt-treated rats with or without manidipine treatment. Hearts were removed and perfused with modified Krebs-Henseleit solution with adenosine (5 x 10(-5) M) in a Langendorff apparatus. Maximal coronary flow (MCF) was significantly decreased only in DOCA/salt hypertensive rats without treatment, while manidipine treatment restored MCF. Left ventricular weight/body weight was also markedly greater in DOCA/salt-treated rats not given manidipine. Left ventricular weight in DOCA/salt-treated rats given manidipine was significantly reduced compared with DOCA/salt hypertensive rats without treatment, although it was heavier than in the control animals. Morphological examination showed that the increased wall/lumen ratio in DOCA/salt hypertensive rats was reduced by manidipine treatment. These findings suggest that treatment with manidipine in DOCA/salt hypertensive rats lowered high blood pressure and improved impaired coronary circulation with a reduction in left ventricular and vascular hypertrophy.


Acute effects of manidipine on renal blood flow and sympathetic nerve activity in conscious, spontaneously hypertensive rats. To examine acute effects of manidipine hydrochloride, a new calcium antagonist, on renal blood flow (RBF) in spontaneously hypertensive rats, we recorded changes in RBF as the Doppler shift and a neurogram of renal sympathetic nerve activity (RSNA) simultaneously in a conscious and unrestrained state. An intravenous infusion of manidipine did not decrease RBF until mean arterial pressure (MAP) fell by 20 +/- 1 mmHg and RSNA increased by 98 +/- 18%. At the nadir of RBF (-25 +/- 2%, MAP: -31 +/- 2 mmHg, RSNA: +154 +/- 25%), percent increase in RSNA significantly correlated with percent decrease in RBF (r = -0.802, p < 0.02). On the other hand, the infusion of sodium nitroprusside did not decrease RBF significantly even at a nadir of MAP (-35 +/- 2 mmHg). Air jet stress increased both MAP and RSNA associated with a decrease in RBF. Responses of MAP and RBF were blunted after manidipine infusion while the stress evoked a similar degree of enhancement of RSNA to that of the control trial. Although manidipine may be less effective than nitroprusside in maintaining RBF during abrupt reductions of MAP, the results of this study suggest that antihypertensive treatment with manidipine may be clinically beneficial in maintaining RBF both at rest and during psychologically stressful conditions.


Renal and extra-renal renin gene expression in spontaneously hypertensive rats. To study the effect of antihypertensive therapy on the regulation of renin gene expression, the levels of tissue renin messenger RNA (mRNA) were measured after treatment with a calcium channel blocker (manidipine hydrochloride 3 mg/kg/day) or an angiotensin-converting enzyme inhibitor (delapril hydrochloride 30 mg/kg/day), administered orally for 1 week, in spontaneously hypertensive rats (SHR). Male SHR, aged 15 weeks old, were used in this study (n = 5 per group). Control rats were administered the vehicle alone. Tissue total RNA was isolated from kidney, adrenal gland, heart, and brain tissue, and tissue RNA was reverse-transcribed to complementary DNA (cDNA), which was specifically amplified by polymerase chain reaction with labeled-primers for the rat renin gene. The radioactivity of the cDNA products was measured directly. Although delapril increased plasma renin activity (PRA) about 5-fold compared with the control group, manidipine did not change PRA. The kidney renin mRNA content was increased about 6-fold by treatment with delapril. Manidipine and delapril significantly decreased the renin mRNA content in the heart (p < 0.01 and p < 0.05, respectively). The level of renin mRNA in the adrenal gland and brain tissues was not significantly changed by treatment with either drug. These results suggest that tissue renin gene expression in SHR is regulated by a tissue-specific process independent of the circulating renin-angiotensin system.


Renal vascular responses in spontaneously hypertensive rats chronically treated with manidipine. An enhanced renal vasoconstrictive response to emotional stress may be related to the pathogenesis of essential hypertension. We examined the effects of chronic manidipine treatment on renal blood flow (RBF) responses to air jet stress, angiotensin II (ANG II), and endothelin-3 (ET-3) in the conscious unrestrained spontaneously hypertensive rat (SHR). Male SHRs were placed on a control diet or one containing 0.05% of manidipine for 4 weeks. Age-matched Wistar-Kyoto (WKY) rats placed on a control diet served as normotensive controls. In comparison with control SHRs, manidipine reduced blood pressure (p < 0.01), increased urinary sodium excretion (p < 0.01), and reduced body weight (p < 0.01). Air jet stress elevated arterial pressure and increased RBF. The pressor response was enhanced more in the control SHRs than in the WKY rats (p < 0.01) and was not altered by manidipine. The percent fall in RBF in the manidipine-treated SHRs (-16%) was less than that in the control SHRs (-30%, p < 0.05) and similar to that in the WKY rats (-18%). In contrast, the pressor effect and the percent fall in RBF caused by ANG II (0.1 nmol/kg/min) were similar in the three groups. Intravenous ET-3 (1 nmol/kg) caused a transient fall, followed by a sustained increase in systemic blood pressure, both of which were associated with a decrease in RBF. The RBF response to ET-3 was blunted in SHRs compared to WKYs and was not altered by manidipine treatment. These results suggest that antihypertensive therapy with manidipine may be beneficial in maintaining RBF during emotional stress.


Effects of the calcium antagonist manidipine on renal hemodynamics and function in dogs: comparison with nifedipine. The renal effects of manidipine, a new dihydropyridine calcium antagonist, were compared with those of nifedipine in anesthetized dogs. Intrarenal administration of manidipine 1 and 5 micrograms/kg resulted in prolonged (120 min) increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (UF), and urinary excretion of electrolytes. In contrast, the renal effects of nifedipine disappeared within 5 to 10 min after administration. These results demonstrate that manidipine is a long-acting calcium antagonist. Manidipine proportionally increased RBF and GFR. As a result, filtration fraction was kept constant. The changes in afferent and efferent arteriolar resistance suggested that manidipine increases GFR via dilation of afferent arterioles with subsequent elevation of filtration pressure in the glomeruli. Manidipine also proportionally increased Tc H2O and Cosm; Tc H2O/Cosm did not change throughout the experiments. In addition, manidipine increased the fractional excretion of sodium from the distal tubule which was calculated from the lithium and sodium clearance. The mode of diuretic action of manidipine most likely involves inhibition of sodium reabsorption in the proximal and distal tubules, except the medullary portion of the ascending limb of Henle. The renal vascular site of action of manidipine might be the afferent arteriole.


Effects of manidipine on blood pressure and renal function in salt-loaded, spontaneously hypertensive rats. The purpose of this study was to investigate the effects of 4-week oral administration of manidipine (40 mg daily), a newly developed calcium channel blocker, on blood pressure and renal function in salt-loaded (8% NaCl) spontaneously hypertensive rats. Systolic blood pressure of spontaneously hypertensive rats increased from 167 +/- 4 to 221 +/- 7 mmHg with salt loading for 4 weeks; manidipine completely prevented this elevation in blood pressure. Urinary excretion of sodium in salt-loaded spontaneously hypertensive rats was twelve-fold compared with those receiving a normal diet (0.38% NaCl). The pressure-natriuresis relationship was obtained during week 4 of the metabolic study. At similar renal perfusion pressures, sodium excretion was significantly higher in salt-loaded rats than in rats fed a normal diet. Glomerular filtration rate and renal plasma flow were similar between the two groups. In salt-loaded spontaneously hypertensive rats, treatment with manidipine improved the pressure-natriuresis relationship toward lower pressures. Further, manidipine attenuated the autoregulation of glomerular filtration rate and renal plasma flow. These results indicate that manidipine normalizes the relation between sodium excretion and renal perfusion pressure in salt-loaded spontaneously hypertensive rats by resetting pressure natriuresis.


Manidipine attenuates a progressive renal injury in remnant kidneys of rats. The effects of a calcium antagonist, manidipine, on the outcome of the remnant kidney model of chronic renal failure in rats were studied. After 5/6 nephrectomy (5/6 Nx), rats were assigned to one of the following groups, and fed: Nx without manidipine, group 1; diet with 0.01% manidipine, group 2. A sham 5/6 Nx group was also included as the control. Each diet contained the same calories (3.44 kcal/g) and protein (25% casein). Increased systolic blood pressure seen after 8 weeks postablation was less with manidipine in group 2. Group 2 also had significantly less proteinuria. By 12 weeks postablation, group 1 showed severe parenchymal damage, characteristic of end-stage renal pathology. These changes were prevented by manidipine. The percentage of glomeruli with severe structural damage including sclerosis and/or hyalinosis, arbitrarily defined as glomerular sclerosis index (GSI) was significantly less in group 2 (41 +/- 11%) compared with group 1 (58 +/- 10%). Tubulointerstitial injury (TII) was also less in group 2 (29.1 +/- 9.1%) compared with group 1 (45.1 +/- 10.3%). Sham-Nx control group without manidipine showed normal renal morphology (GSI, 0.2 +/- 0.6, TII, 3.8 +/- 1.0). These results indicate that manidipine attenuates the development of end-stage renal pathology in the remnant kidney model of chronic renal failure in rats. The mechanism(s) remains to be elucidated.


Preventive effect of manidipine on severe hypertension and proteinuria induced by the inhibition of endothelial-derived relaxation factor formation in stroke-prone spontaneously hypertensive rats. The effect of a calcium antagonist, manidipine, on blood pressure and proteinuria induced by the inhibition of endothelial-derived relaxation factor (EDRF) formation was examined. Manidipine attenuated the increase in blood pressure and prevented proteinuria caused by renal damage associated with the inhibition of EDRF formation in stroke-prone spontaneously hypertensive rat (SHRSP) and Wistar Kyoto (WKY) rats.


A study of the effects of manidipine on the diurnal variation of arterial pressure and hemodynamics in patients with essential hypertension. In order to investigate the effects of manidipine, a newly developed long-acting calcium antagonist, on the diurnal variation of arterial pressure and systemic hemodynamics in patients with essential hypertension, we examined 24-h arterial pressure using a direct arterial pressure monitoring method and cardiac output using the cuvette method before and during manidipine treatment. Once-a-day administration of manidipine at daily doses of 10 to 40 mg decreased systolic and diastolic arterial pressures at almost all measurement points. The arterial pressure reductions were not significantly different between daytime and nighttime. Arterial pressure variability expressed in terms of the standard deviation of values was not affected by manidipine treatment. Thus, it appears that patients treated with manidipine can avoid the excessive decrease in arterial pressure during nighttime that may occur with the use of some other calcium antagonists. Heart rate and its variability were unaffected by manidipine treatment. A hemodynamic study revealed that manidipine did not change cardiac output, but significantly decreased total peripheral vascular resistance at rest. It is concluded that once-a-day administration of manidipine at daily doses of 10 to 40 mg brings about a safe and stable antihypertensive effect over a 24-h period, without affecting the diurnal variation of arterial pressure and heart rate. Dilation of the resistance vessels underlies the antihypertensive effect of the agent.


Efficacy of manidipine on circadian blood pressure in essential hypertension. The 24-h blood pressure (BP) response to once-daily manidipine monotherapy was examined in an open, nonrandomized study of 17 patients with untreated essential hypertension. Manidipine (10-30 mg) was administered once daily for a minimum of 2 weeks. BP and heart rate (HR) were monitored every 30 min for 48 h by an ambulatory BP monitoring device (ABPM-630, Nippon Colin) before and after therapy. Manidipine significantly (p < 0.005) decreased mean systolic and diastolic BP during the entire 24 h, day-active and night-resting periods. The reduction in both systolic and diastolic BP was consistent throughout the whole day. Manidipine also significantly reduced the fractionated pressure-time indices of both systolic and diastolic BP consistently throughout the 24-h period. The circadian amplitude of BP in hypertensive patients, which was higher than that in normal reference subjects, was reduced by manidipine into the reference range. The acrophase of BP in hypertensive patients, which was similar to the reference value, was not altered by manidipine treatment. Manidipine did not change the mean HR during 24-h, day-active or night-resting periods. Therefore, once-daily manidipine monotherapy showed a consistent antihypertensive effect over 24 h and optimized the circadian amplitude of BP without an increase in HR.


Glove wearing in Northern Ireland and an assessment of the loss of tactile perception. The increased awareness of the need for cross-infection control in dentistry has led to recommendations that operating gloves be worn routinely by dental surgeons. A survey conducted amongst general dental practitioners in Northern Ireland showed a drop in glove wearing from 100% in the newly qualified to 47% in those who had qualified between 15 to 35 years ago. A frequently stated reason for the non wearing of gloves in this group is the diminution of tactile sense. To test this, a blind tutor was engaged to read a random standard length Braille passage whilst wearing selected gloves and the reading time recorded and compared with ungloved reading. The wearing of gloves increased reading time and, by implication, the loss of tactile perception, by between 14% and 37%, depending on the glove used. The thickness and stiffness of the gloves were also determined and the results suggest a relationship between these quantities and the loss of tactile perception.


The role of third molars in the cause of anterior arch crowding. The evidence against the third molar as a cause of dental crowding is contradictory. In particular, many orthodontic patients have their wisdoms removed in order to minimise the risk of anterior crowding.


The treatment received by children in the general dental service in Northern Ireland, 1977-1988. The reports of the Central Services Agency were analysed to investigate the treatment received by children in general dental practice in Northern Ireland. In recent years there was an increase in the number of children who attended for dental care which was paralleled by reductions in extractions and the restoration of permanent teeth. It was concluded that there had been marked changes in the pattern of dental treatment in children in Northern Ireland between 1977 and 1988.


Updates in dental materials--Part 1: Dental composites. Recent years have seen a number of innovations and developments with respect to dental materials and their applications in clinical dentistry. This series of short articles considers the more important aspects of these developments under the general term 'Updates in Dental Materials'. Dental composite systems and bonding to tooth material are discussed in Part 1. Resin cements are treated in Part 2. Part 3 presents dental amalgams and Part 4 advances in ceramic materials.


The role of natural killer cells and lymphokine activated killer cells in the pathogenesis of hepatic injury in hepatitis A [corrected]. In order to clarify the mechanism of liver damage in hepatitis A, we studied the role of Natural Killer (NK) cells and Lymphokine Activated Killer (LAK) cells in non-specific immunological reactions using hepatitis A (HAV) infected cells (JTC-12.P3 cell) using the 51Cr release assay. No significant difference in specific cytotoxicity was observed between uninfected cells (JTC) and HAV-infected cells (JTC-HAV) to fresh and Poly I:Cor rIL-2 pretreated peripheral blood mononuclear cells (PBMC) from healthy donors or patients with acute hepatitis A. But in an experiment employing fresh and rIL-2 pretreated PBMC from cynomolgus monkey as effectors, a significant difference in NK and LAK sensitivity between JTC and JTC-HAV was noticed. Cytotoxicity assay was then carried out using as effectors fresh or rIL-2 pretreated cells of B, NK and T cell fractions obtained after separation of PBMC from monkey by the E-rosette formation method. Both fresh and rIL-2 pretreated B/NK cells showed significantly higher cytotoxicity for JTC-HAV than JTC, but neither fresh or rIL-2 pretreated T cells showed cytotoxicity for JTC-HAV or JTC. These results imply that both NK and LAK cells may play a part in the mechanism of hepatocellular injury.


The mechanism of action of serum immunosuppressive factor in Crohn's disease: it blocks the growth of mitogen-stimulated lymphocytes in early G1 phase through an inhibition of transferrin receptor expression. The presence of serum immunosuppressive factor has recently been reported in patients with Crohn's disease. We investigated the mechanism of action of this immunosuppressive factor in vitro. The factor in serum fraction from patients with Crohn's disease had an inhibitory activity on the proliferation of phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (PBMCs) from healthy volunteers. The growth of tumor cell lines, however, was not inhibited by the factor. While the factor did not influence the production of interleukin 2 (IL2) or the expression of IL2 receptor of PHA-stimulated PBMCs, it inhibited the expression of transferrin receptor. The effect of the factor on cell cycle of PHA-stimulated PBMCs was examined by flow cytometry analysis. The factor kept the cells in quiescent G0/G1 phase and decreased the number of cells in S phase. Prostaglandin E2, an immunosuppressive substance, may not participate in the inhibitory action of the factor, since indomethacin did not affect the inhibitory activity of the factor. These results suggest that the immunosuppressive factor in serum from patients with Crohn's disease is unique in the mechanism of inhibitory action and further clarification of this factor might contribute to the development of a new diagnostic assay for Crohn's disease and the elucidation of the pathogenesis of this disease.


Serum IgG subclass concentrations before and after administration of intravenous immunoglobulin in common variable immunodeficiency. IgG subclass levels were measured before and after administration of intravenous immunoglobulins (IVIGs) in patients with common variable immunodeficiency (CVI). Six patients were treated with IVIG at the dose of 100-150mg/kg to maintain a trough level of 200mg/dl every 4 or 5 weeks, except for patient 5 who was given IVIG only 3 or 4 times per year. Three kinds of IVIGs, polyethylene-glycol (PEG)-treated IVIG, alkylated IVIG and sulfonated IVIG were used for replacement therapy. Although serum IgGl levels were low before administration of IVIGs, they increased to the normal levels after each administration of IVIGs in four patients. IgG2 preserved normal levels before and after administration of IVIGs in all patients. IgG3 was present at low normal concentration in patient 1, low concentration in patients 2, 3 and 6, and undetectable in patients 4 and 5 before infusion. Although increases in IgG3 levels were shown after infusion of PEG-treated IVIG, there were no increases after infusion of sulfonated or alkylated IVIG. However, there have been several reports that IgG3 is detected in sulfonated or alkylated IVIG preparations by another method. IgG4 levels were somewhat low before administration, but four patients achieved normal serum levels with treatment. In light of the above results of replacement therapy with IVIGs, we should consider the IgG subclass levels for patients such as CVI or selective IgG subclass deficiency.


Immunoglobulin-complexed aspartate aminotransferase with a possible association with ulcerative colitis and its activity. We demonstrate immunoglobulin-complexed aspartate aminotransferase (macro-AST) in a 14-year-old boy with rectitis-type ulcerative colitis by using both gel filtration and electrophoresis methods. The immunoglobulin complexed with AST in this case was identified as an IgG kappa both by electrosyneresis and immunoprecipitation reactions. The present case was noted to have a concomitant elevation of macro-AST associated with deterioration of ulcerative colitis. However, macro-AST has continued to exist when the activity of ulcerative colitis subsided, and the serum level of AST became normal. Thus, macro-AST might be related to an immunological component of ulcerative colitis as well as to the activity of the disease.


The complement system and primary biliary cirrhosis. Primary biliary cirrhosis (PBC) is a chronic liver disease of unknown etiology. Several immunological abnormalities found in PBC support the hypothesis that autoimmune mechanisms are involved in its pathogenesis. The complement system being an important constituent of the immune system had not been extensively studied regarding its relationship with PBC. However, some workers reported abnormally high serum levels of some complement components with the exception of C4 that was found to be low. Here we review the literature and analyze the possible roles played by the complement system in PBC.


Selective detection of human hepatitis B virus surface and core antigens in some peripheral blood mononuclear cell subsets by flow cytometry. The presence of HBs and HBc antigens was investigated, by flow cytometry, on the surface of peripheral mononuclear cells (PBMC) from the following phenotype: CD3 (T lymphocytes), CD4 (T helper/inducer), CD8 (T cytotoxic/suppressor), CD19 (B lymphocytes) and CD56 (NK cells) among 8 patients suffering from chronic hepatitis B and 5 healthy HBV-negative subjects. This study demonstrated the presence of HBsAg and HBcAg on the lymphocyte surface for most of the patients. The mean percentage of labelled cells was 17% for HBsAg and 15% for HBcAg. Among the different lymphocyte subsets only B lymphocytes and the NK cells expressed HBsAg for 57% and 26% of cells, respectively. Similarly HBcAg was also detected among CD19 and CD56 cells only. PCR was used to search for the presence of HBV DNA and RNA in PBMC, using primers located in the S gene. HBV DNA was detected with variable intensity in the CD3, CD4, CD19 and CD56 subsets following their separation with a cell sorter. For HBV RNA the signal obtained after PCR and Southern blotting was higher for CD56 and CD19 cells than for CD3 cells and undetectable for CD4 cells. This study demonstrates that replication and transcription can occur in CD19 and CD56 cells. Positive signals in CD3 cells may possibly be due to contamination of this subpopulation by NK cells.


Effects of the streptococcal preparation OK-432 on in vitro cytokine production of peripheral blood mononuclear cells in patients with chronic viral hepatitis. We obtained peripheral blood mononuclear cells from 12 chronic hepatitis Type B patients, 12 Type C patients, and 15 healthy volunteers, and investigated the effects of OK-432, a streptococcal preparation, on in vitro production of 3 types of cytokines. Mononuclear cells in a concentration of 1 x 10(6) cell/ml were prepared in the culture medium. OK-432 (Chugai Pharmaceutical Co., Ltd., Tokyo) was added to this preparation and incubated for one to 4 days. Thereafter interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6) and interferon-gamma (IFN-gamma) levels in the culture supernatant were measured using enzyme-linked immunoassay kits. Cytokine production levels in cultures with OK-432 were significantly increased in the mononuclear cells of both patients and healthy volunteers. The largest increase was observed with IFN-gamma (p < 0.01), and then with IL-1 beta (p < 0.05). Responses of the cells from chronic hepatitis Type C patients to OK-432 were relatively good. When interferon (alpha and beta) treatment was first introduced, there were high hopes for a high efficacy. However, we now know 50-70% of patients with chronic hepatitis Type C do not respond satisfactorily to interferon. Some physicians suggest the necessity of using biological response modifier (BRM) as an adjuvant treatment for these patients. From our findings, OK-432 could be a useful BRM in patients with chronic hepatitis Type C.


Evaluation of different effects of sera of breast cancer patients on the activity of natural killer cells. In this study NK cell activity of 88 breast cancer patients in various stages of disease was investigated and a significantly lower activity in clinical stages I-III and especially in stage IV was found. Short term culture of peripheral blood lymphocytes (PBL) of these patients in medium RPMI 1640 with fetal calf serum (FCS) alone, gave a significant enhancement of NK cell activity and even more significantly if rhIL 2 was added to this medium. Considering the finding of diminished native NK cell activity in breast cancer patients and its augmentation by the above stated in vitro treatment, it was of interest to investigate the effect of sera of these patients, which represent the natural in vivo environment of NK cells, in order to see if the sera modulate the antitumor cytotoxic activity of these cells. In this sense, the in vitro treatment was performed on PBL of patients and controls with sera of patients with stages I-III (CaSa), stage IIIb (CaSb), stage IV (CaSm) and healthy control sera (HS). The results obtained for patients and controls show that compared to FCS all sera act in an inhibitory manner, but in contrast to HS, CaSa has a stimulative effect, while CaSb and CaSm give the greatest degree of NK cell inhibition of both controls and patients. Pooled metastatic sera (CaSp) and these sera after removal of molecules up to 8-10 kD by dyalisis (CaSd) show a similar degree of inhibition of NK cell activity of healthy controls and interfere in a reversible manner with NK cell activation by recombinant human interleukin 2 (rhIL 2). Analysis of soluble IL 2 receptor (s IL 2R) concentration, as a potential inhibitory factor in metastatic sera, rarely showed an increase. In conclusion, an impaired NK cell activity was found in patients with breast cancer. The impairment of NK cell activity progressed with the advancement of the disease. Along with this, the finding of a marked inhibitory effect of sera of breast cancer patients in advanced stage with metastases on the activity of NK cells and their activation by interleukin 2 may pose a problem for adjuvant immunotherapy with LAK cells and IL 2 and may indicate a need for prior plasmapheresis.


Oral polyvalent vaccine (Buccalin Berna) administration activates selected T-cell subsets and regulates the expression of polymorphonuclear leukocyte membrane molecules. Acute respiratory tract infections (ARIS) still represent a major clinical problem during influenza outbreaks. The virus-induced impairment of the immune system favors the entry of opportunistic microorganisms into respiratory tract mucosa. A useful strategy to reduce ARIS is to provide at risk subjects an orally administrable polyvalent vaccine (OPV) comprised of bacteria strains recognised as the major ones responsible for ARIS. For the present study, the main circulating leukocyte populations of a group of healthy subjects receiving OPV were monitored as a marker of immune response. Subjects were investigated immediately before taking OPV (day 0) and 10,20, and 30 days later. Data show that T lymphocytes were induced to enhance the expression of class II MHC molecules, whilst a consistent number of CD4+ lymphocytes lost L-selectin, both phenomena indicating an activation status. OPV administration also modulated important molecules on the membrane of polymorphonuclear leukocytes, namely CD11b and CD16, strongly suggesting an activation of these cells and an enhancement of their defensive capacities. Finally, OPV was found to be able to increase the titer of serum antibodies specific for bacteria strains contained in the vaccine preparation in a portion of individuals. We conclude that OPV is able to consistently influence important immune functions and suggest that this property may be of relevance in preventing ARIS. Also, the present data may help to further our understanding of the mechanisms of OPV activity.


Noise, noise sensitivity and psychiatric disorder: epidemiological and psychophysiological studies. Noise, a prototypical environmental stressor, has clear health effects in causing hearing loss but other health effects are less evident. Noise exposure may lead to minor emotional symptoms but the evidence of elevated levels of aircraft noise leading to psychiatric hospital admissions and psychiatric disorder in the community is contradictory. Despite this there are well documented associations between noise exposure and changes in performance, sleep disturbance and emotional reactions such as annoyance. Moreover, annoyance is associated with both environmental noise level and psychological and physical symptoms, psychiatric disorder and use of health services. It seems likely that existing psychiatric disorder contributes to high levels of annoyance. However, there is also the possibility that tendency to annoyance may be a risk factor for psychiatric morbidity. Although noise level explains a significant proportion of the variance in annoyance, the other major factor, confirmed in many studies, is subjective sensitivity to noise. Noise sensitivity is also related to psychiatric disorder. The evidence for noise sensitivity being a risk factor for psychiatric disorder would be greater if it were a stable personality characteristic, and preceded psychiatric morbidity. The stability of noise sensitivity and whether it is merely secondary to psychiatric disorder or is a risk factor for psychiatric disorder as well as annoyance is examined in two studies in this monograph: a six-year follow-up of a group of highly noise sensitive and low noise sensitive women; and a longitudinal study of depressed patients and matched control subjects examining changes in noise sensitivity with recovery from depression. A further dimension of noise effects concerns the impact of noise on the autonomic nervous system. Most physiological responses to noise habituate rapidly but in some people physiological responses persist. It is not clear whether this sub-sample is also subjectively sensitive to noise and whether failure to habituate to environmental noise may also represent a biological indicator of vulnerability to psychiatric disorder. In these studies noise sensitivity was found to be moderately stable and associated with current psychiatric disorder and a disposition to negative affectivity. Noise sensitivity levels did fall with recovery from depression but still remained high, suggesting an underlying high level of noise sensitivity. Noise sensitivity was related to higher tonic skin conductance and heart rate and greater defence/startle responses during noise exposure in the laboratory. Noise sensitive people attend more to noises, discriminate more between noises, find noises more threatening and out of their control, and react to, and adapt to noises more slowly than less noise sensitive people.(ABSTRACT TRUNCATED AT 400 WORDS)


Delay in breast cancer: a review of the literature. Delay in seeking medical attention for breast cancer symptoms, as well as delay in the diagnosing of and delivery of effective treatments for breast cancer may result in advanced states of disease, thereby contributing to breast cancer mortality. Our knowledge of the scope and characteristics of delay in breast cancer is limited. Delay can be divided into two components, patient and system delay. Patient delay is the time it takes for a women to seek help once she has discovered a breast symptom. System delay is the time it takes for a woman to be evaluated, diagnosed, and treated once she has sought help. Most of the studies have dealt with patient delay, with few studies being performed on system delay, especially in the United States. It is evident that patient and system delays of 2-3 months apiece do occur in a small percentage of cases. However, there is not a clear picture of the factors associated with these long delays. Studies have had conflicting results and have often been difficult to compare because of inconsistent definitions of delay. This review critically examines the available literature on delay in breast cancer. Given the lack of a complete understanding regarding the factors associated with long delay, and the fact that the earlier a breast cancer is diagnosed and treated, the greater the likelihood of long-term survival, it is especially important to do further work to determine the factors associated with long delay so that interventions can be designed to minimize delay and thus permit earlier diagnoses and treatments of breast cancers.


Major sources of stress among women managers, clerical workers, and working single mothers: demands vs. resources. The study of stress in general and occupational stress in particular has, until recently, usually included male samples, with findings erroneously extrapolated for women. This review outlines common occupational and domestic stressors, many of which are unique to women, especially to mothers in paid employment. Stress is viewed as resulting from the combination of high role demands and low coping resources (material, psychological, interpersonal, and organizational). Women in paid employment worldwide are still expected to assume primary responsibility for home and family and are subject to a double burden of work, especially when the children are young. Women are also subject to considerable conflict between marital/parental and occupational demands. They occupy different jobs than men, usually hierarchically inferior and entailing fewer benefits and opportunities for growth. In this conceptual framework, three groups of women in paid employment have been empirically identified as being at relatively high risk for stress as conceptualized above: clerical workers, managers, and single (mainly divorced) parents. Further research is needed to explore occupational stress in blue-collar working women, and to elucidate the role and variety of coping resources.


Are self-reported dates of mammograms accurate? This paper assesses the accuracy of self-reported dates of last mammograms from a postal survey compared to dates of mammograms in medical records. The subjects included women 50 years of age and older who were members of a local health maintenance organization, had reported ever having a mammogram, and had completed a postal questionnaire about breast cancer screening. The date of last mammogram from the postal surveys was compared to the date in medical records. Of 78 women who self-reported both the month and year of last mammogram in a postal survey, agreement within 1 month with the medical record data was 62.8% and agreement within 3 months was 75.6%. A total of 32.1% of the subjects underestimated the time since their last mammogram, while only 5.1% overestimated. Based on self-reported dates, 85.9% of the subjects had a mammogram within the last year compared to 76.9% based on medical records. Using medical records as the "gold standard", the sensitivity of self-reported mammogram within the last year versus more than 1 year ago was 98% and the specificity was 56%.


AIDS-related knowledge, attitudes, and behaviors among juvenile delinquents in Israel. Fifty-six Israeli adolescents under the care of probation officers were interviewed about their AIDS-related knowledge, attitudes, and behaviors. The results suggest that these adolescents put themselves at risk of HIV infection. A substantial proportion of the sample demonstrated a lack of knowledge on issues relevant for AIDS prevention. The majority held negative attitudes toward condoms but were also sexually active, and some had experienced unprotected sexual intercourse, anal sex, and drug use. Most of the respondents, moreover, showed a lack of competence in handling situations that pressure them to act unsafely. Implications for practice are discussed.


Contraceptive behavior of Jerusalem women seeking pregnancy counseling, 1980-1989. Inconsistencies between intent and action in the area of birth control are often attributed, in both theory and medical practice, to female ignorance and lack of contraceptive skills. In the light of prevailing theories, this survey examines the contraceptive behavior of 1,425 Jerusalem clients of the Pregnancy Counseling and Follow-up Service. The majority of clients were "in crisis" due to unplanned pregnancies and had turned to the counseling service for help in crisis resolution. The data are based on intake questionnaires and clinical records filled in by counselors. Recorded information included age, education, marital status, religious observance, previous pregnancies and abortions, contraceptives ever used and methods used prior to pregnancy, age of fetus, initial attitude, treatment process, and outcome. The results suggest that the women in the sample became pregnant not because they lacked the skills to avoid it, but because they failed to use those skills effectively. Younger, unmarried, and less educated women and those with many children were especially prone to risk-taking. They also waited longer than others before turning to counseling.


Measles during the Gulf War: a public health threat in Israel, the West Bank, and Gaza. A measles outbreak began in Ramallah District in the West Bank in the period just before the outbreak of the Gulf War in 1991. After a local control program, the outbreak was contained to a total of 236 reported cases, including one death, but sporadic cases appeared over the ensuing months. An epidemic of measles followed 2-3 weeks later in Beer Sheva district in Israel, initially among the Bedouin population just prior to the outbreak of the war, then spreading to the Jewish population. The epidemic reached its peak during the war in February, continuing into March. There were a total of over 433 reported cases, with 203 hospitalizations and 7 deaths. The epidemic was slowed by curtailment of school and other civilian activities, and a mass vaccination campaign reaching 60,000 children, but was spread by crowded conditions in hospital, and was spread to other parts of the country by internal population migration. An epidemic of a preventable disease occurring during a national emergency adds to the burdens of the health system. The public health system must be prepared to contain epidemics and other public health threats in wartime, employing standard control methods developed and practiced during peacetime. Routine immunization policies should take into account the possibility of a civilian epidemic during national emergencies, and the need to assure protection of both the civilian and military population in preparation for such contingencies.


Infectious disease and mortality surveillance in Israel in peace and war. The goals of infectious disease surveillance in war and in peace are the same: the detection of infectious diseases, outbreak identification and control, the assessment of vaccination programs, and the determination of the need for specific preventive measures. In the 1991 Gulf War, Israel's infectious disease surveillance system was utilized to follow the progress of a measles epidemic and to look for evidence of a concealed biological warfare attack. Stepped up mortality and morbidity surveillance, based on a prepared and smoothly functioning notification system, failed to uncover any suggestion that biological agents had been deployed.


["Revista Médica de Chile":120 years of continuous publication]. Revista Médica de Chile has been published monthly since its foundation in 1872. With the present issue, volume 120 is completed. It is the oldest medical journal in South America and the second in antiquity published in Spanish, after the Gaceta de México. It is ranked among the 28 older journals in the world, that were founded in the last century. The multiple aspects of Chilean medicine development are present in its pages. Revista Médica de Chile has been able to adapt to changes in medicine, improving its printing and design, adopting international regulations for periodic medical publications and, above all, making a strict selection of submitted papers using expert peer reviewers. The continuity in management and editorial policies has favored its progress and enhanced its educational role.


Rapid method for mapping morbidity and mortality during epidemics. A rapid method for mapping health information during epidemics is described. We divided maps of cities into coded squares and assigned a code to each street which corresponded to its location on the map. Thus, health data information could be easily transferred from the field by indicating the number of cases in each square and readily transferring this information onto a map. By applying density data of the civilian population in each neighborhood it was possible to calculate incidence and prevalence rates at any given time.


[Estimation of energy expenditure in clinical practice: applicability to individual multiple injury cases]. In 37 multiple trauma patients the estimated and measured energy expenditures were compared. Predicted energy expenditure overestimated it in 89% of patients. The correction factor for the different pathologies was the principal source of error, since the measured/predicted basal energy expenditure ratio was 1.19 +/- 0.17. This ratio had a wide range of values (0.84-1.61) which renders the prediction of individual energy expenditure highly unreliable. Since the overestimation of energy requirements in the critically ill patients may convey important complications, the direct measurement of such requirements is recommended.


The effects of the Gulf War in Israel--report from a rural family medical practice. Throughout the 1991 Gulf War a rural Family Medicine practice in central Israel, situated 20 km from the nearest Scud missile attack area, continued to operate normally. During this period a reduction of more than 50% in clinic visits was recorded. The volume of requests for emergency care remained unchanged but elective hospital admissions decreased. Surprisingly, few new patients were diagnosed with anxiety states and no marked increase was registered in anxiolytic drug prescribing. Many patients, however, expressed feelings of deviance for not conforming with nationally sanctioned and endorsed anxiety levels. The decline in clinic visits noted was probably mediated through a temporary drop in practice accessibility due to the altered population mobility patterns caused by the war. During the 1991 Gulf War the Israeli population suffered not only the general stresses and strains of being in an active war zone but also the real tensions and anxieties associated with night-time attacks on the country by Iraqi Scud missiles. This article describes some of the ways which one rural family medicine practice in central Israel was affected by the dramatic if short-lived events of this war.


Would provision of childcare for nurses with young children ensure response to a call-up during a wartime disaster? An Israeli hospital nursing survey. Researchers suspected that the role-conflict between nurse and mother would exacerbate during war and a survey confirmed that this problem was real. A solution in the form of shelters for children was found, and nurses were able to function during the Gulf War with the knowledge that their children were safe and near.