Quick-freezing of cultured cardiac cells in situ with special attention to the mitochondrial ultrastructure. A new method has been developed which allows quick-freezing in situ of primary, cardiac cell cultures grown to confluence on gas-permeable membranes (Petriperm dishes). Small pieces of the growth substratum, with rhythmically beating myocardial cells, were slam-frozen, without cryoprotectants, against the surface of a helium-cooled copper block at approximately 16 K. The quality of the cellular cryopreservation, as judged by ultrastructural criteria, was studied in freeze-substituted specimens processed for transmission electron microscopy. The ultrastructure of cryofixed cardiac cells was compared with that of unfrozen, chemically fixed samples. The severity of cryodistortions increased progressively with increasing distance from the point of first impact. Of particular interest were the dramatic alterations of the mitochondrial ultrastructure. The concept that the reticular and the outer mitochondrial membranes are intimately and strongly associated was clearly demonstrated. Optimally frozen material revealed cryopreserved ultrastructure of high quality. The method described appears to offer an ideal model system for correlating the information gained by phase-contrast microscopy of living cell cultures with the ultrastructure of the same samples fixed in situ by chemical or physical techniques. Cryofixation would be particularly useful for studying dynamic cellular processes associated with physiological and pathophysiological conditions, e.g. metabolic inhibition, anoxia and substrate deprivation.


Fibrodysplasia ossificans progressiva in the cat. A case report. Clinical, radiographic, electromyographic, and pathologic findings in a cat with fibrodysplasia ossificans progressiva are described. The features of five previously reported cases of this feline disorder are also presented. This disorder affects young adult to middle-aged cats of both sexes. Characteristic clinical features include progressive stiffness of gait, with enlargement of proximal limb musculature. Radiography reveals multiple mineralized densities within the affected musculature. The clinical course is rapid, with development of severe disability within 2 weeks to several months. Electromyographic and pathologic findings suggest that this is a disorder of connective tissue, affecting primarily the epimysium, tendons, and fasciae, and results in marked proliferation of fibrovascular connective tissue, with associated chondroid and osseous metaplasia.


Fibromyalgia: a time-series analysis of the stressor-physical symptom association. The purpose of this study was to investigate the association among daily stressors, cognitive rumination, and fibromyalgia symptoms using time-series methodology and to determine whether autocorrelation was present in the self-report data. Twelve female fibromyalgia subjects monitored their daily level of stressors, cognitive rumination, and fibromyalgia symptoms for 30-35 days. Time-series regression analyses indicated that there was a positive association between previous-day stressors and fibromyalgia symptoms for one subject and between previous-day cognitive rumination and fibromyalgia symptoms for four subjects. For 7 out of 12 subjects autocorrelation was present, and generalized least-squares methods were used with these subjects. These results indicate that ordinary least-squares methods may often not be appropriate for within-subject designs with self-report data. These results also question the often reported stressor-physical symptom association. This study illustrates a useful methodology and analysis to investigate psychosocial-physical symptom associations.


Neospora caninum infection in English Springer Spaniel littermates. Diagnostic evaluation and organism isolation. Progressive paraparesis developed in four male English Springer Spaniel pups from a litter of five during the first 10 weeks of life. Two of the pups, which had the earliest onset of neurologic signs, were euthanatized without further workup. However, a detailed investigation was completed on the remaining two littermates at 12 weeks of age. Both pups had progressive paraparesis for 3 to 4 weeks before presentation, with one dog developing subsequent asymmetric pelvic limb extensor rigidity. Based on results from neurologic examination, cerebrospinal fluid (CSF) analysis, electrophysiology, and muscle/nerve biopsy, a presumptive diagnosis of protozoal polyradiculitis and polymyositis was made. Necropsy of the most severely affected pup confirmed the clinical diagnosis of inflammatory nerve root and muscle disease but no organisms were found. To increase the potential yield of organisms, the second pup was placed on immunosuppressive doses of corticosteroids and euthanatized 2 weeks later. Numerous organisms were found in lesions in muscle and the central nervous system. Organisms grew in tissue culture and were isolated from the peritoneal fluid of gerbils inoculated with infected tissue. Organisms were not isolated from inoculated mice, guinea pigs, rabbits, and hamsters. No parasites were seen in feces or tissues of three cats fed infected dog tissues. Serologic testing demonstrated a strong positive titer to Neospora caninum in both pups, and electron microscopy showed the characteristic morphology of this parasite.


Smoking rate, carboxyhemoglobin, and body mass in the Second National Health and Nutrition Examination Survey (NHANES II). The relationship of body mass and triceps skinfold thickness to both reported number of cigarettes smoked per day and carboxyhemoglobin levels was examined in healthy cigarette smokers in the NHANES II. Among both men and women, higher carboxyhemoglobin levels were related to lower body mass and thinner skinfolds, whereas higher levels of reported daily cigarette smoking were related to increased body mass and thicker skinfolds among men only. These relationships were independent of age, education, caloric intake, physical activity, and exercise. The opposite effects of number of cigarettes smoked per day and a biological index of cigarette smoke exposure on body mass suggest that increased cigarette smoking may covary with factors that would favor increased body weight among men, whereas decreases in body weight with increases in carboxyhemoglobin may reflect the effects of nicotine exposure on energy expenditure in both men and women.


Social and behavioral factors associated with episodes of inhibitory breathing. Previous research has shown that episodes of inhibitory breathing, characterized by low-frequency breathing, occur both in laboratory animals during intervals preceding avoidance tasks and in humans in the natural environment. The present study investigated social and behavioral factors accompanying episodes of inhibitory breathing that occur in the natural environment. Breathing frequency and tidal volume of ambulatory subjects were monitored via inductive plethysmography. Information concerning location, social environment, behavior, and mood was self-recorded in a computerized diary. The percentage of episodes of inhibitory breathing was found to be significantly greater in social situations than when subjects were alone. Additional analyses eliminated talking as an explanation for these effects. Inhibitory breathing was more frequent when subjects were sedentary rather than active, and inhibitory breathing was not associated with changes in mood or appraisal. Additional research is needed to determine the nature of the social interactions that elicit inhibitory breathing, its physiological concomitants, and its long-term health implications.


Effects of cognitive style and maintenance strategies on breast self-examination (BSE) practice by African American women. A convenience sample of 159 African American women, 18-45 years old, was trained to perform breast self-examination (BSE) and was categorized according to the participants' cognitive style (monitors/blunters). Participants were then randomly assigned to one of four groups differing in BSE maintenance strategy (self-management, positive reinforcement, both, or neither). Self-reported monthly compliance with BSE was subsequently assessed during a 9-month period. A significant interaction between maintenance strategies and cognitive style was found. For blunters, the highest compliance rates and the highest competency scores occurred in the group with no maintenance strategy, whereas for monitors, the highest compliance rates and competency scores were found in the groups receiving positive reinforcement and/or self-management strategies. Additional results indicate that high levels of BSE competency were achieved across conditions and that competency improved over time.


Matching pain coping strategies to the individual: a prospective validation of the cognitive coping strategy inventory. The validity of the Cognitive Coping Strategy Inventory (CCSI; Butler et al., 1989) was tested in a prospective fashion. Subjects were randomly assigned to one of three conditions. Some were "matched" to a strategy for which they received a high CCSI score, some were "mismatched" to a strategy for which they received a low CCSI score, and some were given a choice of strategies. Those subjects using a matched strategy obtained better threshold and tolerance times on the cold pressor than subjects who used a mismatched strategy. Despite clear differences in exposure to the cold pressor these conditions did not differ from each other in self-reported levels of pain. It was concluded that the CCSI appears to be a valid and useful tool for selecting a coping strategy to help particular individuals manage acute pain. Though the CCSI is relatively easy to administer and score, the comparative costs and benefits of using it must be weighed against the somewhat more efficient approach of simply offering the subject a choice of treatments. Subjects given a choice of strategies performed as well as subjects matched to a strategy on the basis of CCSI scores.


Measuring life event stress in the lives of college students: the Undergraduate Stress Questionnaire (USQ). We describe the development of the Undergraduate Stress Questionnaire (USQ), a life events checklist designed to measure stress among undergraduates. Several studies demonstrate the USQ's validity. The USQ correlates positively with physical symptoms and negatively with mood. Students rated the USQ as the most complete and accurate of four different life events questionnaires. In a panel study, the USQ closely tracked subjective reports of stress, both during the term and finals week. The USQ predicted symptoms more reliably than three other stress measures, controlling for negative affect. Students waiting in the college infirmary score higher on the USQ than students socializing on campus. Finally, we compare the checklist format to subjective scaling, and show the superiority of the checklist version. We discuss the usefulness of the USQ in terms of validity, representativeness, adaptability, brevity, and low confounding with negative affect.


The role of microtubule-associated protein 2 (MAP-2) in neuronal growth, plasticity, and degeneration. Microtubule associated protein 2 (MAP-2) historically has been perceived primarily as a static, structural protein, necessary along with other cytoskeletal proteins to maintain neuroarchitecture but somewhat removed from the "mainstream" of neuronal response mechanisms. Quite to the contrary, MAP-2 is exquisitely sensitive to many inputs and recent investigations have revealed dynamic functions for MAP-2 in the growth, differentiation, and plasticity of neurons, with key roles in neuronal responses to growth factors, neurotransmitters, synaptic activity, and neurotoxins. These discoveries indicate that modification and rearrangement of MAP-2 is an early obligatory step in many processes which modify neuronal function.


Expression of the T-lymphocyte activation gene, F5, by mature neurons. F5 was first identified as an mRNA expressed by activated but not resting T-lymphocytes. Subsequent studies suggested that it also is selectively expressed by mature neurons. Although the F5 protein coding sequence is highly conserved, the function of the F5-encoded protein is unknown. The present studies were undertaken to define the anatomic distribution, cellular specificity, and developmental pattern of F5 mRNA expression in the mouse nervous system, addressing specifically the question of whether the expression pattern of F5 corresponds to that of known ligand-receptor or signal-transduction systems. The use of a nonradioactive in situ hybridization method and paraffin-embedded sections provided excellent morphological preservation and a high degree of cellular resolution. F5 mRNA was detected in the central nervous system, peripheral nervous system, and retina in cells having the location and morphological features of neurons. Combined in situ hybridization histochemistry for F5 mRNA and immunofluorescence staining for cell-specific markers confirmed that neurons expressed F5 mRNA but astrocytes did not. The neuronal expression of F5 mRNA had two interesting features. First, the level of expression appeared to correlate directly with the size of the neuronal perikarya, the length of the axonal projection, or the extent of dendritic arborization. Second, F5 mRNA appeared late in post-natal development. These observations are of interest because of preliminary data suggesting that F5 may function as a substrate for protein kinase C, which demonstrates a similar expression pattern in the nervous system.


The neural cell adhesion molecule (NCAM) heparin binding domain binds to cell surface heparan sulfate proteoglycans. The neural cell adhesion molecule (NCAM) has been strongly implicated in several aspects of neural development. NCAM mediated adhesion has been proposed to involve a homophilic interaction between NCAMs on adjacent cells. The heparin binding domain (HBD) is an amino acid sequence within NCAM and has been shown to be involved in NCAM mediated adhesion but the relationship of this domain to NCAM segments mediating homophilic adhesion has not been defined. In the present study, a synthetic peptide corresponding to the HBD has been used as a substrate to determine its role in NCAM mediated adhesion. A neural cell line expressing NCAM (B35) and its derived clone which does not express NCAM (B35 clone 3) adhered similarly to plates coated with HBD peptide. A polyclonal antiserum to NCAM inhibited B35 cell-HBD peptide adhesion by only 10%, a value not statistically different from inhibition caused by preimmune serum. Both these experiments suggested no direct NCAM-HBD interactions. To test whether the HBD peptide bound to cell surface heparan sulfate proteoglycans (HSPG), HSPG synthesis was inhibited using beta-D-xyloside. After treatment, B35 cell adhesion to the HBD peptide, but not to control substrates, was significantly decreased. B35 cell adhesion to the HBD peptide could be inhibited by 10(-7) M heparin but not chondroitin sulfate. Preincubation of the substrate (HBD peptide) with heparin caused dramatic reduction of B35 cell-HBD peptide adhesion whereas preincubation of B35 cells with heparin caused only modest reductions in cell-HBD adhesion. Furthermore, inhibition of HSPG sulfation with sodium chlorate also decreased the adhesion of B35 cells to the HBD peptide. These results strongly suggest that, within the assay system, the NCAM HBD does not participate in homophilic interactions but binds to cell surface heparan sulfate proteoglycan. This interaction potentially represents an important mechanism of NCAM adhesion and further supports the view that NCAM has multiple structurally independent binding sites.


MHC class II-positive microglia in human brain: association with Alzheimer lesions. Cells of the mononuclear phagocytic system (MPS) present foreign antigen on their cell surfaces bound to major histocompatibility complex (MHC) class II molecules. Previous studies of normal human brain samples reported MHC class II expression primarily by perivascular MPS cells and white matter microglial cells. Marked increases in MHC class II-expressing microglia have been shown in many neuropathologic disorders, including Alzheimer's disease (AD). A close morphologic association between these cells and Alzheimer senile plaque beta-amyloid has been demonstrated. The present study used a mixed aldehyde fixative to enhance the localization of MHC class II-expressing MPS cells in non-AD and AD brain. Two antibodies against MHC class II (HLA-DR; LN3), as well as the lectin Ricinus communis agglutinin (which recognizes both ramified and activated microglia) were used for light and electron microscopic analyses. We now report that MHC class II-expressing ramified microglia are distributed in a uniform reticular array throughout the grey, as well as the white matter in non-AD cases. In AD cases, immunolabelled cells had the morphology of activated microglia, with darkly stained plump somata and short, thick processes. Microglia clustered around senile plaque amyloid and neurofibrillary tangles (NFT), rather than forming the uniform array characteristic of control tissue. Finally, we report that perivascular MPS cells are found in a morphologic relationship with vascular amyloid identical to that seen between microglial cells and senile plaque beta-amyloid. These data suggest that MHC class II-expressing cells may be involved in the degradation of NFT-laden neurons and the posttranslational modification of extracellular-NFT epitopes. In addition, both parenchymal and perivascular MPS cells are ideally situated to uptake and process the beta-amyloid protein precursor and deposit beta-amyloid on senile plaques, NFT, and the cerebrovasculature.


Developmental expression of neuronal calmodulin mRNA species in the rat brain analyzed by in situ hybridization. The temporal and spatial distribution of calmodulin mRNAs which are preferentially expressed in neurons was determined during postnatal development of rat central nervous system. Expression of these mRNAs was strongly detected in the developing neocortex, hippocampus, and cerebellum. Differences in the pattern of expression of a 1.8 and 4.0 kb neuronal calmodulin mRNA species were identified in the developing cerebellum. Expression of the smaller mRNA appeared to correlate with proliferating and developing cerebellar granule neurons while the larger mRNA was present in the mature granule neuron population. A transient elevation in the neuronal calmodulin mRNA species was observed in the superior and inferior colliculus and in the thalamus at postnatal days 5 and 10.


Interaction of AChE with Lens culinaris agglutinin reveals differences in glycosylation of molecular forms in sarcoplasmic reticulum membrane subfractions. Fractionation of muscle microsomes rich in sarcoplasmic reticulum (SR) by isopicnic centrifugation yielded three types of membranes. Heavy (HM), intermediate (IM), and light membranes (LM), with isopicnic points of 38, 33, and 25% w/w sucrose, were rich in terminal cisternae/triads, longitudinal SR, and T-tubules, respectively. All membrane subfractions displayed acetylcholinesterase (AChE) activity. About 60, 80, and 50% of total AChE in HM, IM, and LM was extracted with a Tris-saline-Triton buffer. AChE molecular forms of 4.5 S (G1), 10.5 S (G4), and 16 S (A12) were found in all membranes but their relative proportion varied among the several membranes. Asymmetric and tetrameric forms were partly sedimented with Lens culinaris agglutinin (LCA), but most of the monomeric AChE failed to interact with the lectin. However, some of the monomers, exclusively found in LM, reacted with LCA. The data suggest that monomeric AChE is classified in rough endoplasmic reticulum. A subset is destined to SR, a second one converted into oligomeric forms, and a third one is associated to external membrane after passing through the Golgi system.


In search of the central respiratory neurons: I. Dissociated cell cultures of respiratory areas from the upper medulla. Dissociated cells from the areas of the nucleus ambiguus and the nucleus tractus solitarius obtained by tissue punch or block dissection from coronal slices of the medulla at the level of the obex were cultured from fetal rats at 18 to 21 days gestation. The dissociated neurons were plated either directly in vitrogen-coated 35 mm tissue culture dishes or in such dishes which had been seeded with subcultures of cortex- or medulla-derived astrocytes. After the astrocytes reached confluency and were treated with an antimitotic agent, dissociated nucleus ambiguus or nucleus tractus solitarius was plated at 0.5-1.0 x 10(6) cells per dish. Neurons grew well on monolayers of medullary or cortical astrocytes, but survived poorly on vitrogen-coated dishes without a cellular substrate. Rat medulla was preferred as the source of astrocytes. Tissue dissociation with papain rather than trypsin produced less cellular debris, and the neuronal yield from the tissue was higher. The neuronal population was heterogenous in morphology including small and large bipolar, pyramidal, and multipolar cells. Neurons sensitive to CO2 and/or low pH (Rigatto et al., J Neurosci Res 33:590-597, 1992) did not appear to have any definitive morphologic characteristics, but most were multipolar. These neurons stained well with antibodies to neuron-specific enolase and Fragment C of tetanus toxin, but not to choline acetyltransferase (ChAT). These findings suggest that neurons possibly responsible for the central regulation of respiration can be maintained for several weeks in dissociated cell culture, providing a system for neurotransmitter, electrophysiological, and morphological studies.


In search of the central respiratory neurons: II. Electrophysiologic studies of medullary fetal cells inherently sensitive to CO2 and low pH. Although extensively pursued, the central respiratory neurons have remained elusive. We departed from the more conventional physiologic and morphologic methods of system and tissue examination and cultured dissociated fetal rat cells (Fitzgerald et al., J Neurosci Res 33:579-589, 1992) from the area of the nucleus ambiguus and the nucleus tractus solitarius located within the 2 mm rostral to the obex. Pacemaker-like cells, with a regular single or bursting activity, studied at 3-5 weeks of age, responded to very small pulses of CO2 (50 ms) and low pH with an increase in spike frequency and a decrease in spike amplitude. Other irregularly beating or silent cells did not respond or else required very large pulses (> 200 ms) to do so. The pacemaker cells also responded to hypoxia induced by administration of sodium hydrosulfite with an increase in spike frequency and amplitude; high oxygen (> 600 torr) and adenosine produced a decrease in electrical activity. Most of these cells were multipolar after staining with antibodies to neuron-specific enolase (NSE) and Fragment C of tetanus toxin. They did not stain for choline acetyltransferase (ChAT). The results suggest that these cultured cells, expressing a phenotype inherently responsive to CO2 and low pH, have the characteristics of central respiratory chemoreceptors, and may be involved in the generation of the respiratory rhythm.


Elevation of extracellular potassium facilitates the induction of hippocampal long-term potentiation. Hippocampal long-term potentiation (LTP) is widely believed to be a cellular substrate for learning and memory. A likely physiological stimulus for initiating LTP is repetitive neuronal activity, which also results in K+ accumulation extracellularly. Therefore, the involvement of elevated extracellular K+ concentrations in the induction of LTP of the stratum radiatum-CA1 neuronal synapse was investigated in the hippocampal slice preparation. Increasing the K+ content in extracellular perfusing medium from 3.1 to 15 mM resulted in facilitation of LTP induction in weak excitatory postsynaptic potentials (EPSPs). Since changes that occur to generate LTP are thought to be localized to synaptic regions, it would be relevant to selectively increase synaptic K+ levels. To this end, the following experiments were conducted: i) baclofen, a GABAB receptor agonist which, in addition to having a disinhibitory presynaptic action, activates a K+ conductance in CA1 neuronal dendrites, was applied to the slice; ii) K+ was directly applied by iontophoresis. At a concentration of 5 microM baclofen, as well as with K+ iontophoresis (200-300 nA), LTP of weak EPSPs was facilitated. The present data suggest that an increase in synaptic K+ levels can fulfill the condition of cooperativity for LTP induction, raising the possibility that an elevation of this monovalent ion plays a physiological role in triggering LTP.


Haloperidol prevents induction of the hsp70 heat shock gene in neurons injured by phencyclidine (PCP), MK801, and ketamine. The non-competitive NMDA receptor antagonists, PCP (phencyclidine), MK801, and ketamine produce psychosis in humans and abnormal vacuoles in posterior cingulate and retrosplenial rat cortical neurons. We show that PCP (> or = 5 mg/kg), MK801 (> or = 0.1 mg/kg), and ketamine (> 20 mg/kg) induce hsp70 mRNA and HSP70 heat shock protein in these vacuolated, injured neurons, and PCP also induces hsp70 in injured neocortical, piriform, and amygdala neurons. The PCP, MK801, and ketamine drug induced injury occurs in 30 day and older rats, but not in 0-20 day old rats, and is prevented by prior administration of the antipsychotic drugs haloperidol and rimcazole. Since haloperidol and rimcazole block dopamine and sigma receptors, and since M1 muscarinic cholinergic receptor antagonists also prevent the injury produced by PCP, MK801, and ketamine, future studies will be needed to determine whether dopamine, sigma, M1, or other receptors mediate the injury.


Ethanol administration during early embryogenesis affects neuronal phenotypes at a time when neuroblasts are pluripotential. Our previous studies have reported that ethanol administration during a critical period of development profoundly affects the expression of neuronal phenotypes in whole brains of chick embryos. The present study examines a) the long-lasting effects of early ethanol treatment on neurotransmitter phenotypic expression and b) its differential effects on anatomically discrete regions of the developing chick CNS. Ethanol (10 mg/50 microliters) was administered to embryos via the air sac from E1 to E3. Embryos were sacrificed on days 4, 8, 10, or 15 of embryonic development (E4, E8, E10, E15) and assayed in specific regions of the CNS for glutamate decarboxylase (GAD) or choline acetyltransferase (ChAT) as markers for GABAergic or cholinergic neurons, respectively. The magnitude of the developmental profile for ChAT was highest in spinal cord (SC), with similar profiles observed for cerebral hemispheres (CH) and optic lobes (OL). In contrast, the developmental profile for GAD was highest in OL and lowest in SC. Thus, neuronal phenotypes inhabit specific CNS areas from early primordial stages of development. Furthermore, cholinergic neuronal populations in discrete CNS areas reached mature levels by E10, whereas GABAergic populations continued to increase throughout the experimental period. We suggest that GABAergic precursor neuroblasts may differentiate at a later embryonic age and that specific regional factors may play a role in neuronal distribution and the rate of maturation. As reported previously, primordial CNS areas exposed to ethanol (E1-E3) exhibited a differential sensitivity. Cholinergic neuronal expression in CH remained retarded throughout the experimental period examined, whereas the early decline observed at E4 in SC cholinergic expression was reversed by E15.(ABSTRACT TRUNCATED AT 250 WORDS)


Biphasic changes in NCAM level after an NMDA lesion to the hippocampal formation: a quantitative dot-immunobinding assay. With a quantitative dot-immunobinding assay, the time course changes of neuronal cell adhesion molecule (NCAM) concentrations and total tissue content were monitored in the rat hippocampus after a 40 nmol NMDA injection. A biphasic alteration was observed; a decrease occurred at day 3, an increase at day 30. The time course of changes differed from that of the glial fibrillary acidic protein (GFAP), a marker for reactive astroglial cell, but was similar to that for the markers of sprouting neurites, i.e., low (L) and high (H) molecular weight subunits of the neurofilament polypeptides. It is suggested that NCAM is implicated in the onset of neurite sprouting in the hippocampus after an excitotoxic trauma.


Recovery of pulmonary diffusing capacity after maximal exercise. Pulmonary diffusing capacity (DICO), together with spirometric variables, arterial oxygen tension (paO2) and cardiac output were determined before and at intervals after maximal arm cranking, treadmill running and ergometer rowing. Independent of the type of exercise, D1CO increased immediately post-exercise from a median 13.6 (range 7.3-16.3) to 15.1 (9.3-19.6) mmol min-1 kPa-1 (P < 0.01). However, it decreased to 11.6 (6.9-15.5) mmol min-1 kPa-1 (P < 0.01) after 24 h with cardiac output and paO2 at resting values, and D1CO normalized after 20 h. Thoracic electrical impedance at 2.5 and 100 kHz increased slightly post-exercise, indicating a decrease in thoracic fluid balance, and there were no echocardiographic signs of left ventricular failure at the time of the decrease in D1CO. Also, active muscle (limb) circumference and volume, and an increase in haematocrit from 43.8 (38.0-47.0) to 47.1 (42.7-49.8) (P < 0.01), had normalized at the time of the decrease in D1CO. Vital capacity, forced vital capacity, forced expiratory volume in 1 s, peak and peak mid-expiratory flows did not change. However, total lung capacity increased from 6.8 (5.0-7.6) to 7.0 (5.1-7.8) litres (P < 0.05) immediately after exercise and remained elevated at 6.9 (5.1-8.7) litres (P < 0.05) when a decrease in D1CO was noted. The results demonstrate that independent of the type of maximal exercise, an approximate 15% reduction in D1CO takes place 2-3 h post-exercise, which normalizes during the following day of recovery.


A model of the elastic take-off energy in the long jump. A theoretical analysis of the long jump take-off is presented, with the conclusion that elastic effects are important. Measured data from the literature for groups of top athletes and average performers in the long jump confirm this conclusion and lead to an estimate of elastic energy conversion efficiency, which is very low (between 0.2 and 0.3), in contrast with much higher conversion efficiencies for the running stride.


Pre-season physiological characteristics of English first and second division soccer players. This investigation was undertaken in an effort to establish physiological characteristics of soccer players and to relate them to positional roles. A total of 135 footballers (age 24.4 +/- 4.6 years) were assessed for body mass, % body fat, haemoglobin, maximal oxygen uptake (VO2 max), leg power, anaerobic capacity and speed prior to an English league season. The sample included 13 goalkeepers, 22 full-backs, 24 centre-backs, 35 midfield players and 41 forwards. The goalkeepers were significantly heavier (86.1 +/- 5.5 kg; P < 0.01) than all groups except the centre-backs, had significantly higher estimated body fat percentages than centre-backs, forwards, midfield players (P < 0.01) or full-backs (P < 0.05), significantly lower estimated VO2 max values (56.4 +/- 3.9 ml kg-1 min-1; P < 0.01) and were slowest over 60 m (12.71 +/- 0.42 s). The midfield players had the highest predicted VO2 max values (61.4 +/- 3.4 ml kg-1 min-1), this being significantly greater (P < 0.05) than for the centre-backs. The forwards were the fastest group over 60 m (12.19 +/- 0.30 s), being significantly quicker than goalkeepers or centre-backs (P < 0.01) and full-backs (P < 0.05). Anaerobic power, as well as knee extensor torques (corrected for body mass) and extensor-flexor ratios, were similar between groups. No difference in estimated body fat percentage was observed between any of the outfield players, and haemoglobin concentrations were similar among players of all positions.(ABSTRACT TRUNCATED AT 250 WORDS)


[Newly developed MRSA medium].

[Newly developed MRSA medium]. We have developed a new selective medium, tentatively named MR(SA)2, for rapid identification of methicillin-resistant Staphylococcus aureus (MRSA) from clinical specimens. MR(SA)2 medium contained modified Müller-Hinton agar supplemented with 75 g of NaCl, 10 g of mannit, 20 mg of bromcresol purple, 20 g of egg-yolk, 4 mg of oxacillin, and 12.5 mg of ceftisoxime per 1,000 ml. There were no differences between the growth of MRSA strains on this medium at 30 C and that of 37 C. This medium can detect the egg-yolk reaction instead of the coagulase reaction. By single streaking of a test material on the surfaces of MR(SA)2 agar, MRSAs can easily be distinguished from methicillin-resistant coagulase-negative staphylococci (MR-CNS), other bacteria and fungi from their colony morphologies in a quantitative manner. A few MRSA strains would not form colonies on this medium because of their susceptibilities to ceftisoxime, but this may not inpede its use, since most MRSA strains isolated from clinical materials showed resistance to ceftisoxime. From the above results, the MR(SA)2 medium may be suitable for rapid detection of MRSA and MR-CNS.


[Proposal for the nosocomial infection control of methicillin-resistant Staphylococcus aureus (MRSA)]. To determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in hospital environments, quantitative isolation of MRSA from environmental and human specimens was performed. It was found that as many as 6 x 10(4) colony forming units (CFU)/100cm2 of MRSA and also methicillin-resistant coagulase-negative Staphylococcus (MRCNS) were isolated from 1) 25-100% of the bed-mattresses tested in 10 out of 11 (90%) hospitals, and also 2) bed sheets for patients, floors of patient wards, laundry, bath-room, toilet and laundry storage-room. And seven and eight palms of 20 patients were contaminated with MRCNS and MRSA, respectively, and MRCNS contamination was revealed in six of medical staffs. These results indicate that hospital environments, especially the mattresses and hospital floors are highly contaminated with MRCNS and MRSA, and sanitation and cleanliness of mattresses and floors are necessary to prevent the dissemination of both MRCNS and MRSA in hospital.


[Chemical and serological study of lipopolysaccharide isolated from Shigella flexneri 88-893 possessing a new type-antigen]. The O-specific polysaccharide chain which represents a new type-antigen in lipopolysaccharide (LPS) of Shigella flexneri 88-893 was investigated. The O-polysaccharide chain was found to be composed of repeating units comprising rhamnose, N-acetylglucosamine and glucose (3:1:2). In the passive hemolysis test, group-6 antiserum of S. flexneri exhibited a high hemolytic titer (50% hemolysis titer: 7,900) against sheep red blood cells (SRBC) sensitized with intact 893 LPS, but virtually no hemolytic activity against SRBC sensitized with alkali-treated 893 LPS. None of the type-specific antisera (I-VI), showed any significant hemolytic titer against SRBC sensitized with either intact or alkali-treated 893 LPS. Thus, 893 LPS contained both the group-6 antigen and a new type-antigen which is distinct from any known type-antigen of S. flexneri.


[Structure and function of the experimental polycystic kidney induced by diphenylthiazole with special reference to renal micropuncture study]. Autosomal dominant polycystic kidney disease (ADPKD) is one of the major causative diseases leading to renal failure and dialysis treatment. Although the genetic study on the disease has been progressed so far, the initial trigger for cyst formation and several factors enhancing the progression of ADPKD remain to be clarified. Using an animal model of ADPKD, induced by 2-amino-4,5-diphenylthiazole hydrochloride (DPT), we examined the early events in cytogenesis. Especially the role of tubular obstruction in the model in triggering off tubular dilatation was investigated by means of renal micropuncture and tubular microperfusion techniques. Light and electron microscopic studies demonstrated epithelial hyperplasia along collecting ducts after 2 weeks of DPT feeding. In addition, some collecting ducts revealed partial obstruction with hyperplastic cells. Cystic change became prominent over 8 weeks of the treatment. Then micropuncture and microperfusion experiments were performed to measure intratubular pressure in the rats fed DPT for 2-5 weeks (PKD rats) and pair-fed control Sprague-Dawley rats (control rats). Free flow pressure in proximal segments of PKD rats (21.5 +/- 1.0mmHg) was not significantly elevated, as compared with that in control rats (21.3 +/- 1.0mmHg). During the stepwise increments in proximal tubular flow rate, proximal tubular pressure in PKD rats significantly increased especially at higher flow rate, 41.0 +/- 3.6 mmHg in PKD rats and 19.4 +/- 3.1mmHg in control rats (P < 0.01) at 40nl/min. On the other hand, the transit time of loop of Henle was longer in PKD rats (38.9 +/- 2.4 sec) than in control rats (24.9 +/- 0.6 sec, P < 0.01). These results suggest that cyst formation in PKD rats could be preceded by the elevation of tubular resistance, which might be explained by the partial obstruction of collecting ducts. Moreover, these tubular obstruction in the distal segments might be the trigger for the cyst formation in this model.


[Effects of glucose on proliferation and collagen synthesis in cultured rat mesangial cells]. The influence of glucose concentration on proliferation and collagen production was studied in rat cultured mesangial cells. The cells at passage 6-8 were cultured in 10% FCS/DMEM with different glucose concentration (5, 15 or 25 mM). (3H) thymidine uptake was significantly suppressed in 25 mM glucose condition in the presence or absence of FCS. Immunocytochemistry revealed a dramatic increase in intracellular staining for collagen I, III and IV in 25 mM glucose condition. Analysis of soluble extracellular matrix production using ELISA also showed increased concentration of collagen I, III and IV in the supernatant of mesangial cells grown in 25 mM glucose. The message for collagen I, III and IV increased and decreased rapidly within 24 h after refeeding, making a first peak of message level. After 24 h mRNA for collagen I, III and IV increased again in 25 mM glucose media, whereas the message remained depressed in 5 mM glucose media. These results obtained from in vitro studies suggest that high blood glucose per se may play an important role in increased extracellular matrix in diabetic glomerulosclerosis.


[Studies on the mechanism of action of angiotensin converting enzyme inhibitors on the dog kidney]. The effects of angiotensin-converting enzyme (ACE) inhibitors, rampipril, captopril and enalapril, on the renal circulation and function were examined in normotensive dogs, in relation to the renin-angiotensin-aldosterone (R-A-A) and kallikrein-kinin (K-K) systems and prostaglandins (PGs). These inhibitors markedly decreased renal vascular resistance (RVR) in parallel with a reduction in systemic blood pressure, and increased renal blood flow (RBF). Captopril exerted its effects rapidly, but its disappearance was also rapid. The onset of ramipril's effects was slightly delayed, but its antihypertensive and RVR-decreasing effects were fairly prolonged. Ramipril showed more potent and longer-lasting RBF-increasing effect and induced marked Na diuresis. Enalapril had no diuretic effect, and captopril's effect was only temporary. Plasma renin activity was increased similarly by the three inhibitors, but only ramipril significantly decreased plasma aldosterone concentration. This aldosterone secretion inhibition by ramipril may be partly involved in the diuretic effect. Involvement of the K-K system and PGs in ramipril's effects on the dog kidney was examined. When systemic PG biosynthesis was inhibited by indomethacin pretreatment, ramipril-induced increases in RBF and urine volume were inhibited about 50%. Inhibition of the K-K system by aprotinin pretreatment resulted in marked inhibition of urine volume increase, but scarcely affected RBF increase. These results indicate that ramipril produces the most potent effect on the renal circulation and function of the dog among the three ACE inhibitors and that its diuretic action is mostly due to kinins and kinin-induced PGs in the kidney and the RBF increase, due to the R-A-A system and PGs.


[A study of the measurement of p-aminohippurate in diabetic subjects]. Glomerular filtration rate has been found to be elevated in the early stage of insulin-dependent diabetes mellitus and has been proposed to play a pathogenetic role in the development of diabetic nephropathy. However, the reports about the change in renal plasma flow (RPF) among diabetic subjects were inconsistent, suggesting that the presence of hyperglycemia may in some way interfere the procedures of RPF measurement. Recently, it has been reported that the glucose in the urine may react with p-aminohippurate (PAH), a widely used marker for RPF measurement, and influence the chemical measurement of PAH, misleading the result of RPF value. In fact, we obtained the decrease of PAH value in urine samples obtained from diabetic subjects during the storage for one week in frozen condition. In order to clarify the factors which may influence the glucose-PAH reaction, we have conducted various in vitro studies. The decrease of PAH values was dose-dependent to urine glucose. The pH of the test solution or urine was also found to greatly influence the result of PAH measurement when glucose was present. The analysis of glucose-PAH reactants by HPLC suggested that the amino residue of PAH might be reacted with glucose, producing the glycation product (Schiff base). The rate of glycation of PAH was time- and pH-dependent. However, when the reaction time was prolonged at the last step of PAH measurement after the addition of the acid solution, the decrease of PAH value was gradually corrected reaching to the theoretical value in 7 hours.(ABSTRACT TRUNCATED AT 250 WORDS)


[Percutaneous nephrostomy versus the placement of double pigtail ureteral stent for the treatment of postrenal failure secondary to malignancies]. From August 1989 through September 1991 we performed percutaneous nephrostomy under ultrasonic guidance in 26 kidneys of 25 patients. We also indwelled double pigtail ureteral stents by endoscopy in 14 kidneys of 13 patients. No patients died because of renal failure. The survival was dependent on progression of primary disease and performance status. Neither significant nor life-threatening complications were encountered. The difference in the improvement of renal function between nephrostomy group and stent group was not statistically significant. Although the indwelling ureteral stent method requires no external drainage bag, this method has certain drawback such as occasional obstruction of stent. Especially in poor risk patients, percutaneous nephrostomy technique seems to be better than placement of double pigtail ureteral stent in the treatment of postrenal failure secondary to malignancies.


[Studies on the sodium concentration of dialysate solution for continuous ambulatory peritoneal dialysis]. Overloaded sodium(Na) induces the expansion of extracellular volume in case with severe renal insufficiency. Accordingly, in patients undergoing CAPD, the Na balance via trans-peritoneum is the critical determinant of fluid state. This study was performed to clarify the trans-peritoneal Na kinetics in patients using standard dialysate (Na: 132mEq/1,2-1), and to explore the clinical effects of lower Na concentration solution. Peritoneal dialysis effluent obtained from 87 patients was analysed [1.5% dextrose dialysate (D): 33 bags, 2.5%D: 54 bags]. In terms of net-Na removal, no significant relation was found with serum Na level. Whereas, a significant positive relation was found with ultrafiltration (UF) volume (p < 0.01). Net-Na removal was 10.0 +/- 3.3mEq in 1.5%D and 30.2 +/- 1.8 mEq in 2.5%D (mean +/- SEM). On the other hand, ultra low sodium concentration dialysate (ULNaD, Na level: 98mEq/1, Osm:340mOsm/1, 2l) was effectively used for the purpose of increasing Na removal. Net-Na removal was 78.1 +/- 5. 6mEq after 4-hr dwelling (n = 18). ULNaD was applied to ten patients who showed signs of overhydration, using once a day consecutively instead of standard one. After 9 days (mean) in this regimen, signs of overhydration were disappeared. Significant reductions in their body weight and fall in blood pressure were found compared to the periods before commencement of ULNaD, showing remarkable increase in Na removal (p < 0.01, respectively). No significant changes were found in serum Na level or UF volume.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effect of angiotensin II(AII) on peritoneal transport during peritoneal dialysis in rat]. Ultrafiltration volume (UFV) in peritoneal dialysis is expressed as the difference between net transcapillary ultrafiltration (TCUF) and lymphatic absorption (LA) in peritoneal cavity. An increase in LA results in a decrease in UFV. Endogenous hormones may modulate peritoneal membrane permeability and LA. This study was conducted to assess the effect of angiotensin II(AII) on peritoneal permeability and LA in rat. Rats (BW, approximately 300g) with normal renal function were dialyzed for 4 hours using 30ml of hypertonic dialysate (dextrose concentration: 3.86%). AII was added in dialysate at the concentration of 10(-9)-10(-2) mol/30ml. Peritoneal membrane permeability and UFV were studied by clearance of urea N and inorganic phosphate, albumin excretion, glucose absorption and LA. LA was calculated by the concentration change of dextran 70 in dialysate. AII decreased UFV from 15.7 +/- 2.8ml/4hr(control) to 5.7 +/- 1.5(AII 10(-4) mol/dwell). LA was increased in a dose dependent fashion (ED50:0.25 x 10(-6)mol) with no change in TCUF and clearances of urea N and inorganic phosphate. Ten types of AII analogue were used to investigate the site of action for LA in 8 amino acids of AII. [beta-Asp1], [Val5], [Ile3, Val5] and [Sar1] AII showed agonistic action against LA. [Sar1, Thr8], [Sar1, Ile8], [Sar1, Leu8], [Sar1, Ala8], [Sar1, Val5, Ala8] and [Sar1, Gly8] AII had no effect on LA, which found the importance of the 8th amino acid of AII for LA. These actions of AII analogue against LA were similar to those for vascular smooth muscle.(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of superimposed renal lesions of IgA and membranous nephropathy with diabetic nephropathy]. A 64-yr-old man presented with diabetes mellitus, proteinuria, hypertension and moderate renal dysfunction. Renal biopsy revealed diabetic glomerulosclerosis (diffuse lesion), IgA nephropathy and membranous nephropathy (stage 2). Both mesangial IgA and subepithelial IgG deposits were demonstrated by immunofluorescence and immunoelectron microscopy. Electron microscopic studies by immunogold method showed localization of IgA (diameter 15nm gold particles) within mesangial dense deposits and IgG (diameter 15nm gold particles) within subepithelial dense deposits. Overlapping IgA and membranous nephropathy was revealed in the same diabetic glomeruli with functional and biochemical alternations.


[Glomerulopathy associated with glomerular microtubular deposits: a report of a case]. A male aged 58 was admitted to our hospital because of proteinuria, hematuria and bilateral pretibial edema. Laboratory tests showed normocytic, normochromic anemia and moderately impaired renal function. Antinuclear antibodies were negative. Neither M-protein nor Bence-Jones protein were detected. Light microscopic study on the biopsied renal specimen indicated a moderate mesangial proliferation accompanying with the deposition of PAS-positive and Congo red-negative materials in the subendothelial area. C3 accumulated segmentally along the capillary walls, which was clarified by immunofluorescence microscopy. Staining for IgG, IgA, IgM and light chains were negative. Electron microscopy demonstrated the deposition of microtubules in the mesangial, subepithelial and subendothelial areas. The diameter of these microtubules ranged from 40 to 80 nm. Such type of the microtubules have been reported to exist in the glomeruli in the patients with systemic diseases such as amyloidosis, systemic lupus erythematosus, cryoglobulinemia and light chain disease. In our patient, however, any clinical or serological findings suggestive of these systemic diseases were not obtained. On the other hand previous report pointed out that microtubules deposited in the glomeruli in the patients with immunotactoid glomerulopathy or other glomerulopathies. Our patient had the clinical features consistent with these glomerulopathies. However, no depositions of immunoglobulins were observed. This case is an atypical glomerulopathy accompanying with the glomerular microtubular deposits.


[A case of rheumatoid arthritis with immunotactoid glomerulopathy]. The patient was a 64-year-old female who had been treated by a local doctor for rheumatoid arthritis and hypertension for 10 years. Malaise and edema developed since July, 1990, and as proteinuria and renal dysfunction were noted, the patient was admitted to our hospital on November 2. On admission, BUN was 33mg/dl, creatinine was 2.5mg/dl, and proteinuria was about 3g/day. Renal biopsy was performed after admission. Light microscopy revealed nodular lobulation of glomeruli and occlusion of loops. Dylon staining was negative. Immunofluorescent study showed granular deposition of IgG, IgM, C3, C4, Clq in the glomerular basement membrane and mesangial area. Electron microscopy showed a large amount of electron dense deposits in the subendothelium and mesangial area and dense aggregation of tubular structure in the deposit, part of which exhibited a profile of fingerprint deposit. The tubular structures were classified into three major types, which were 120, 100, and 50nm in diameter. From these findings, a diagnosis of immunotactoid glomerulopathy was made. After renal biopsy, plasmapheresis and prednisolone were administered, and the patient has been managed conservatively to date.


[A case of extra-adrenal pheochromocytoma with frostbite in extremities]. We describe a patient who presented frostbite in extremities in addition to characteristic symptoms, such as severe hypertension, sweating attacks, palpitations and headache. The patient was eventually diagnosed as having single extra-adrenal pheochromocytoma. The frostbite in extremities rapidly resolved after the removal of the tumor as well as other characteristic clinical symptoms. It is speculated that this frostbite might have been induced by severe continuous constriction of peripheral artery and loss of heat by frequent sweating attacks. Regarding cutaneous symptoms in this disease, pallor, acrocyanosis and cold extremities are commonly found. However, it seems that typical frostbite associated with pheochromocytoma has not been reported so far.


[A case of sarcoidosis with hypercalcemia, urolithiasis, nephrocalcinosis and renal insufficiency]. A sixty nine-year-old woman was admitted to the hospital because of further examination of hypercalcemia. On July 1990, she complained of general fatigue and loss of appetite. She was pointed out to have hypercalcemia (15.1mg/dl), urolithiasis, and renal insufficiency. CT films of the chest showed swelling of the mediastinal lymphnodes and CT of the abdomen nephrocalcinosis. Ga-scintigraphy demonstrated an abnormal accumulation of gallium in the mediastinum. Levels of the parathyroid hormone was normal. Levels of the serum calcium (13.7mg/dl), angiotensin converting enzyme (30.4IU/L) and 1.25 (OH)2D (87PG/ml) were elevated. Giant cells were found in the biopsy specimen of the lung. A significant relationship between the serum calcium and creatinine were observed (r = 0.76, p < 0.02). Proximal fractional reabsorption of sodium showed to be suppressed (47.7%), and distal fractional reabsorption of sodium showed to be normal (88.4%). From these findings hypercalcemia and urolithiasis was suggested to result from sarcoidosis. The hypercalcemia and renal insufficiency improved with corticosteroid therapy.


[The prevalence and the clinical characteristics of silent myocardial ischemia detected by stress thallium scintigraphy]. The prevalence of silent myocardial ischemia was retrospectively assessed in a group of 100 consecutive patients with angiographically proved coronary artery disease, and diagnostic ECG, by symptom-limited exercise thallium-201 scintigraphy. Twenty-four patients had no evidence of ischemia despite adequate exercise level. So among 76 patients with exercise induced ischemia, only 33 patients (43%) stopped exercise due to anginal pain (symptomatic ischemia: Group 3). And 43 patients with asymptomatic ischemia composed of 23 patients (30%) with ECG change (Group 2B) and 20 patients (26%) without ECG change (Group 2A). Patients background including the history of old myocardial infarction and diabetes mellitus, were similar among Group 2A, 2B, and Group 3. And our major observation was that the extent and severity of quantified SPECT perfusion defects was nearly identical between 3 groups Thus in this study group, there was a rather high prevalence rate of silent ischemia (57%) by exercise thallium-201 criteria. Patients with silent ischemia, associated with positive and negative exercise ECG findings, and those with exercise angina had similar background and comparable amount of jeopardized myocardium.


[Relation between serum PAP (prostate acid phosphatase) and bone scintigraphy in prostatic cancer]. Seventy-seven patients with prostatic cancer were treated at our department in the last 5 years. Of these patients 30 cases were followed by bone scintigraphy and serum PAP. In 27 follow-up scintigraphy procedures changes of bone scintigraphy corresponded to changes in serum PAP levels Changes of PAP levels did not always correspond to changes of scintigraphy, but almost all cases in which the level of PAP increased in a short period showed progression of bone metastasis. A 3-month interval between bone scintigraphy procedure in stage D2 prostatic cancer patients is generally recommended. However, we think that in prostatic cancer patients follow-up bone scintigraphy at regular short intervals is unnecessary if there is no change in serum PAP levels, symptoms or physical condition. Bone scintigraphy should be performed when the tumor marker changes rapidly or when any physical symptom appears.


[Influence of increased 201Tl lung uptake on the myocardial viability of the patients with dilated cardiomyopathy under congestive heart failure]. Influence of increased 201Tl lung uptake on the myocardial viability was studied in 15 patients with dilated cardiomyopathy under congestive heart failure. Rest and 4 hours delayed 201Tl SPECT were obtained. At the same time anterior planar images were collected. In 10 patients of 15 patients 201Tl lung heart ratio in SPECT (LHR) was larger than that in planar images. Maximal 201Tl lung uptake was noted at the lower left lung adjacent to the heart. In the delayed images 201Tl lung uptake diminished. In 10 patients the value of LHR in the delayed images was less than 0.5. By comparing initial images with delayed images it was proved to be difficult to determine the myocardial margin adjacent to the increased 201Tl lung uptake. In 2 patients lateral defects were concealed by the increased 201Tl lung uptake. In the remaining patients lateral wall was similar to the hypertrophic myocardium. The effect of scatter due to the increased 201Tl lung uptake was noted in the neighboring myocardium. In most cases %201Tl uptake in the septum was relatively depressed by increased %201Tl uptake in the lateral wall. In the delayed images pseudo-redistribution was noted in the septum. Mean value of differences in %201Tl uptake between initial and delayed images was 8 (2-15)%. It was concluded that in case of increased 201Tl lung uptake SPECT could not accurately estimate myocardial viability by initial images and delayed images were necessary for precise estimation.


[Influence of hypertensive left ventricular hypertrophy on detection of ischemic area with exercise thallium-201 myocardial scintigraphy]. Sixty-four patients with single left anterior descending artery disease having effort angina (group A: 40 patients without hypertension, group B: 10 patients with hypertrophic hypertension, group C: 14 patients with non-hypertrophic hypertension) were assessed the influence of hypertensive left ventricular (LV) hypertrophy on detection of ischemic area. The criterion of hypertrophy by two-dimensional echocardiography was > 12 mm in the wall thickness of interventricular septal or posterior wall. Population in Group B might show low detectability in ischemic area by 201Tl myocardial scintigraphy (positive thallium rate 60%, defect score 2.7 +/- 3.6), and high lung thallium uptake and high frequence of ECG positive among three groups. In semiquantitative analysis, the washout rate of the posterolateral wall and %RD (delayed %uptake-initial %uptake) of the septal wall in patients with Group B were lowest among three groups. However, the washout rate in the septal wall against the posterior wall, and the initial %uptake and the delayed %uptake of the septal wall were not significantly different among three groups. We could conclude that the decreased washout rate in nonischemic area with hypertensive LV hypertrophy might make the ischemic area masked.


[Calculation algorithm of three-dimensional absorbed dose distribution due to in vivo administration of nuclides for radiotherapy]. In the in vivo administration of radionuclides for radiotherapy including radioimmunotherapy, an algorithm is proposed for the purpose of calculating three-dimensional absorbed dose distributions of tumors and adjacent tissues, and neighboring organs. The absorbed dose distribution due to the algorithm is given by convolution of the three-dimensional dose matrix for a unit cubic voxel containing unit cumulated activity, with the three-dimensional matrix of the cumulated activity distribution given by the same voxel size above. The dose calculation algorithm does not depend upon the source size, the source shape, and the nonuniform and irregular activity distribution. In addition, it can exceedingly decrease computation time compared to other calculation algorithms. Computer simulations were performed using the MIRD thyroid phantom for 32P, 90Y, 131I, 186Re, and 188Re that appear promising for radioimmunotherapy, and their results verified the validity of the proposed calculation algorithm and high accuracy of the calculations.


[Time course of regional myocardial glucose metabolism after transient ischemia assessed by positron emission tomography]. The purpose of this study was to examine the significance of glucose metabolism in ischemic canine myocardium after reperfusion. Transient ischemia was induced by 90 or 180 minutes occlusion of the left anterior descending coronary artery. Twelve hours and 4 weeks after reperfusion, myocardial blood flow (MBF) and glucose metabolism were assessed (with H2(15)O and 18F-FDG, respectively) by positron emission tomography (PET) under the fasting state, and the metabolic findings were compared with the histologic examination. Glucose metabolism in ischemic regions was inversely related to the amount of tissue necrosis 12 hours and 4 weeks after reperfusion (r = -0.89 and r = -0.82, respectively). The perfusion-metabolism mismatch pattern was seen in the area with less than 10 percent necrosis 12 hours after reperfusion, but this pattern disappeared after 4 weeks. The area with 10 to 50 percent necrosis showed the mismatch pattern until 4 weeks after reperfusion, and in the area with more than 50 percent necrosis, perfusion-metabolism concordantly decreased. Thus, metabolic index assessed early after reperfusion by PET identified myocardial viability, and the perfusion-metabolism mismatch pattern sustained in relation to the degree of ischemic injury. Since some regions estimated to be irreversible by PET were viable by the histologic examination, PET study might underestimate the myocardial viability.


[The usefulness of dipyridamole stress myocardial scintigram as a preoperative test for detecting ischemic heart disease before vascular surgery]. We evaluated the usefulness of dipyridamole 201Tl myocardial scintigraphy (DS) for detecting myocardial ischemia in 18 candidate for vascular surgery. DS indicated significant thallium redistribution in 6 patients. Coronary angiography was performed in 5 of these 6 patients and revealed significant coronary artery disease in all patients. As a result, operation was cancelled in 4 patients with severe coronary artery disease. One of these cases died of acute myocardial infarction after being discharged from hospital. One other patient was operated after percutaneous transluminal coronary angioplasty. Another patient was operated knowing that he had significant but mild coronary artery disease. Subsequently, operations were performed in 14 patients. No serious cardiac event occurred in these 14 patients except one case with T wave inversion without myocardial enzyme elevation. Thus, we concluded that DS was a useful method for detecting ischemic heart disease and prevent cardiac event associated with vascular surgery.


[Correlation of the perfusion scintigram with pulmonary functions in chronic obstructive pulmonary disease]. We carried out ventilation-perfusion scintigraphy and pulmonary function tests in 21 patients with chronic obstructive pulmonary disease. We used 99mTc-macroaggregate for perfusion scintigram and 133Xe gas for ventilation scintigram. We added the radioactivities of rebreathing phase and made lung volume image using computer. Regions of interest (ROIs) were derived from radioactivities in each image. ROIs on lung volume image included each whole lung and those on perfusion image included the areas which had relatively high radioactivity. We counted the area of ROIs on lung volume (L) and perfusion (P) images. Then we used the ratio of perfusion to lung volume (P/L) as a parameter of pulmonary perfusion. P/L had the significant correlations with the vital capacity, the actual FEV1.0, arterial oxygen partial pressure, diffusing capacity, RV/TLC and peak flow rate. These results suggested that P/L was a useful parameter of pulmonary perfusion in chronic obstructive pulmonary disease.


[Usefulness and limitations of ECG-gated myocardial single-photon emission computed tomography with 99mTc-methoxy-isobutyl-isonitrile (MIBI) in patients with prior myocardial infarction]. To evaluate the relationship between regional wall motion and 99mTc-methoxy-isobutyl-isonitrile (MIBI) uptake, ECG-gated single-photon emission computed tomography (SPECT) with 99mTc-MIBI was performed in 20 patients with prior myocardial infarction. The left ventricular images at end-diastole (ED) and end-systole (ES) were divided into 39 segments, respectively. Based on circumferential profile analysis, relative uptake (%EDc, %ESc), percent count increase (% delta C), and normalized percent count increase (% delta Cn) were analyzed in each segment and compared with regional wall motion indices assessed by echocardiography and left ventriculography. ECG-gated SPECT with 99mTc-MIBI provided high contrast tomograms of the left ventricular myocardium. %EDc and %ESc showed good correlations with regional wall motion indices. % delta C and % delta Cn, however, showed lower correlations compared with %EDc and %ESc. In conclusion, high-quality left ventricular images were obtained with 99mTc-MIBI ECG-gated SPECT, but quantitative analysis based on only percent count increase (% delta C) have limitations for evaluation of regional wall motion.


[Usefulness of 18F-fluorodeoxyglucose positron emission tomography for evaluating myocardial viability in old myocardial infarction]. The purpose of this study is to compare the characteristics of images obtained by positron emission tomography (PET) using 18F-fluorodeoxyglucose (FDG) in the fasted state (> 6 hours) and in the glucose-loaded state (oral 50 g glucose load). In the both condition FDG-PET were performed in 18 cases with old myocardial infarction. PET images in the fasted state were divided into 2 groups (Group A; 12 cases and Group B; 6 cases). FDG uptake of normal region was visually absent (grade 0) in group A, whereas it was visually apparent (grade 1-3) in group B. Serum free fatty acid in group B was significantly lower than that in group A. In the 7 cases, the relation between myocardial FDG uptake of the infarcted regions and reversibility after coronary intervention was studied. Both in the fasted and in the glucose-loaded state, postoperative improvement was observed in the segments, in which myocardial uptake of FDG were visually apparent (glucose-loaded state, 11/13 segments; fasted state, 6/8 segments). Therefore FDG-PET images appeared to be useful for evaluating myocardial viability.


[Thallium-201 and gallium-67 scintigraphies in the diagnosis of pneumoconiosis combined with lung cancer]. Thallium-201 (201Tl) and Gallium-67 (67Ga) scintigraphies were performed on 62-year-old male with silicosis combined with lung cancer (squamous cell carcinoma). In 67Ga and early 201Tl images, radiotracer uptakes were observed in both sites of cancer and silicosis, and thus, it was impossible to differentiate cancer mass from the large opacity of pneumoconiosis. On the other hand, in the 201Tl delayed images, 201Tl was localized only in cancer mass, while it was washed out from the large opacity. Our findings indicated that 201Tl early and delayed scintigraphy findings were very useful to differentiate lung cancer from silicosis.


[A comparison of community-acquired lung infection and nosocomial infection--review of autopsy cases in Hisayama town]. All people in Hisayama town who died either at home or in hospital are autopsied in Kyushu University Hospital. We examined the incidence and the pathogen of community-acquired lung infection and nosocomial infection from the records of 463 autopsy cases from 1977 to 1988. Of these cases, 243 died at home. Among them, pulmonary infections were present in 122 cases (50.2%), and pulmonary infection was the cause of death in 87 cases (35.8%). Of 220 cases that died in hospital, pulmonary infections were present in 133 cases (60.5%) and were the cause of death in 83 cases (37.7%). In the cases that died at home, the incidence of pulmonary infections during the first 6-year period of the study was almost the same as that during the last 6 years. In the case that died in hospital, the incidence of pulmonary infections during the last 6-year period was higher than that during the first 6-year period. Regarding the pathogenic organisms of the fungal infections, only Candida was detected in case that died at home, while Candida, Aspergillus and Cryptococcus were detected in the case that died in hospital.


[Pulmonary blood flow measurement by acetylene rebreathing method in subjects without respiratory function disturbance]. Simultaneous measurement of pulmonary blood flow by the acetylene rebreathing method and cardiac output by the thermodilution method was performed in subjects without respiratory function disturbance during right heart catheterization. After the measurement of cardiac output, the subjects rebreathing a gas mixture containing acetylene and argon from the end tidal level. The inspiratory and expiratory gases were measured by a mass-spectrometer. Results were analyzed by a lung model consisting of two compartments (rebreathing bag compartment and lung compartment), while taking into account the volume reduction due to O2 and CO2 exchange and the fluctuation of end tidal gas concentration until equilibrium between the bag and the lung. The correlation coefficient between these two methods was 0.944, which was statistically significant. The regression line was near the line of identity. The measurement of pulmonary blood flow by the acetylene rebreathing method was applicable in cases without lung function disturbance.


[Pulmonary function and pulmonary hemodynamics in obstructive sleep apnea syndrome]. The prevalence and mechanisms of daytime pulmonary hypertension were examined in 24 cases of obstructive sleep apnea syndrome (OSAS). All patients were free from chronic lung disease. They underwent pulmonary function tests and blood gas analysis in the sitting and supine position, hypercapnic ventilatory response test, exercise test and right heart catheterization. Elevation of mean pulmonary arterial pressure (m-PAP) above 20 mmHg was observed in 5 out of 24 cases (20.8%). The group with pulmonary hypertension (PG+: m-PAP = 22.2 +/- 2.7 mmHg) showed marked obesity (p < 0.001), significant decrease of supine FRC/TLC (p < 0.05), increase of supine CC/FRC (p < 0.01), decrease of supine PaO2 (p < 0.02) and desaturation during exercise (p < 0.05) in comparison with the group without pulmonary hypertension (PH-: 13.9 +/- 3.1 mmHg). m-PAP was positively correlated with %IBW and desaturation during exercise (p < 0.01, p < 0.02) and negatively correlated with supine PaO2 (p < 0.01). Various changes in pulmonary function and pulmonary hemodynamics due to obesity seem to lead to daytime pulmonary hypertension of OSAS.


[Clinical study of bronchial inhalation challenge in summer-type hypersensitivity pneumonitis induced by Trichosporon cutaneum]. To evaluate the methods and criteria of judgement for the bronchial antigen inhalation challenge test, the test was performed with culture filtrate antigen of serotype I and II of Trichosporon cutaneum in 18 patients with summer-type hypersensitivity pneumonitis from 15 families. The quantity of 15 mg of culture filtrate antigen was adequate, and had no side effects. In the tests, 17 of 18 patients showed a positive reaction to both or either, serotype of antigen. In 36 performances of inhalation, there were 21 positive reactions and 15 negative reactions. According to the criteria of judgment for inhalation challenge test, the positive response rates of observation items were 75% for symptoms and signs, and 51% for laboratory data. Items with a high positive rate were cough, crepitant rales, and decrease of PaO2. On the other hand, low positive rates were observed for decrease of DLco, VC and positive CRP. Items with both high sensitivity and high specificity were cough, crepitant rales and decrease of PaO2. The low positive rate of decreased DLco was due to insufficient improvement before inhalation challenge. It was concluded that our methods and criteria of judgment for bronchial inhalation challenge test are useful.


[Generation of effector cells from primary lung cancer patients by stimulation with anti-CD3 monoclonal antibody followed by culture with recombinant interleukin-2]. Peripheral blood mononuclear cells obtained from 24 primary lung cancer patients were stimulated with anti-CD3 monoclonal antibody (alpha CD3MoAb) followed by culture with recombinant interleukin-2. The optimal concentration of alpha CD3MoAb for stimulation was 50 ng/ml in the liquid phase, and the sensitization culture was commenced at a cellular concentration of 1 x 10(6)/ml. Patients entered into this study were 14 cases of adenoca rcinoma, 7 of squamous cell carcinoma, and 3 of small cell carcinoma. After 4-6 days of stimulation with alpha CD3MoAb followed by culture with RIL-2 for 5-7 days, the cellular expansion was 3.7 folds (mean). Surface marker analysis of the cells revealed significant increments of CD3+, CD8+, HLA-DR+, and IL-2R+ cells after sensitization culture. In 2 cases, fresh autologous tumor cells could be obtained from surgical specimens. Effector cells generated in those 2 cases did not show significant cytotoxic activity against autologous tumor cells in 4 hr 51Cr release assay. In 5 cases, cytotoxicity against established lung cancer cell lines, STC-1 and L0301, were analyzed. In all cases, effector cells showed significant cytolytic activity against both targets. The sensitization culture utilizing alpha CD3MoAb was easy to perform and feasible for the majority of patients, and it is considered that utilization of this culture system would be worth while for adoptive immunotherapy in primary lung cancer patients.


[Inhibitory effect of vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) on bronchoconstriction in guinea pigs]. The present studies were conducted to investigate whether or not VIP and PHI have a bronchodilator effect in vivo. VIP or PHI was administered intravenously in guinea pigs, and dynamic respiratory resistance was measured. Intravenous administration of VIP and PHI reduced dynamic respiratory resistance; however, the effect was significantly less than that of isoprenaline. VIP and PHI inhibited the increase in dynamic respiratory resistance by intravenous administration of histamine in a dose-dependent manner, suggesting that VIP and PHI may be involved in the pathogenesis of airway hyperresponsiveness through inhibiting the effect of mediators on the airway.


[Ultrastructural observation of eosinophils in bronchoalveolar lavage fluid in eosinophilic pneumonia]. To investigate the morphological changes of local eosinophils in the lungs, we observed the ultrastructure of eosinophils in bronchoalveolar lavage fluid (BALF) from patients with eosinophilic pneumonia. We also measured the BALF concentration of eosinophil cationic protein (ECP) as an index of the activation of eosinophils. The eosinophils in BALF from patients with eosinophilic pneumonia showed various ultrastructural changes compared to eosinophils in BALF of the control patient. Changes included degranulation or disintegration of specific granules, cytoplasmic vacuolation, increased lipid droplets and the appearance of Charcot-Leiden crystals. These changes of BALF eosinophils were more prominent than those of peripheral blood eosinophils. ECP concentration (mean +/- SD) in BALF from patients with eosinophilic pneumonia was 12.2 +/- 7.78 micrograms/l which was significantly higher than the concentrations in patients with bronchial asthma not during an attack (1.36 +/- 2.08 micrograms/l) and in healthy control subjects (2.14 +/- 4.62 micrograms/l). These results suggest that local eosinophils in the lungs are activated and degranulated by various stimuli and undergo structural degeneration in eosinophilic pneumonia.


[Expression of epidermal growth factor receptor in adult human airway epithelium--application of AMeX method]. To elucidate the role of epidermal growth factor (EGF) in the maintenance and repair of airway epithelial cells in adult humans, we investigated immunohistochemically whether EGF receptor (EGFR) is expressed in these cells. In the present study, we employed the AMeX method (Sato et al., 1986) for tissue preparation. We first examined the expression of EGFR in peripheral lung tissue and bronchial tissue obtained at surgery from thirteen adult patients with lung carcinoma. The results showed that there was no positive staining for EGFR in the bronchial surface epithelium, bronchial glandular cells, bronchiolar epithelium or alveolar lining cells. There was also no expression of EGFR in cells comprising areas of basal cell hyperplasia and epidermoid metaplasia in the bronchus, or alveolar cell hyperplasia and columnar cell metaplasia in fibrotic lung tissue. Second, we examined the expression of EGFR in regenerating distal airway epithelial cells, which were experimentally produced by xenotransplantation of human lung tissue into the subcutaneous tissue of nude mice. There was also no expression of EGFR at any stage of regeneration from one week through six weeks after the transplantation. It is concluded that EGFR is not expressed, at least at an immunohistochemically detectable level, by airway epithelial cells of adult humans, not only in the quiescent state but also under conditions in which epithelial cells are stimulated to replicate. Thus, it appears unlikely that the EGF/EGFR system plays an important role in either maintenance or repair of airway epithelial cells in adult humans.


[A case of round atelectasis associated with spontaneous pneumothorax]. A 59-year-old female was admitted for spontaneous pneumothorax. After evacuation, the chest X-ray film showed a round mass lesion at the left hilum. Following curettage and bronchoalveolar lavage of the left B3c, the mass became smaller, suggesting the diagnosis of round atelectasis. This is the first report of round atelectasis complicated by spontaneous pneumothorax. The mechanism of this case is suggested to resemble that of round atelectasis associated with pleural effusion.


[A case of Wegener's granulomatosis complicated by hypopituitarism]. A 71-year-old male complaining of chest pain was admitted to our hospital. A single cavitary mass shadow was observed on chest X-ray films. Urinalysis revealed microscopic hematuria. CT examination demonstrated a tumorous shadow in the maxillary sinus. The diagnosis of Wegener's granulomatosis was histologically established by biopsy specimens from the nasal mucosa which showed necrotizing vasculitis and granuloma with fibrinoid degeneration. He was treated with combination therapy of prednisolone and cyclophosphamide. The abnormal shadows on chest X-ray and in the maxillary sinus on CT improved rapidly, but the patient developed progressive weight loss and complained of cold intolerance, weakness and dysphagia. Serum T3, T4 and TSH were found to be reduced. Anterior pituitary function tests showed reduction of TSH, GH and ACTH responses, which was probably due to irreversible vasculitis.


[A case of secondary lung cancer of cystadenocarcinoma showing multiple thin-walled cavities]. A 74-year-old woman was admitted to our hospital with the complaint of general fatigue. Chest X-ray revealed multiple thin-walled cavities in both lung fields. Cystadenocarcinoma in the liver and secondary lung cancer were diagnosed on the basis of chest X-ray, abdominal CT, and lung biopsy. She died of respiratory failure, in spite of treatment with chemotherapy for 8 months. At autopsy, the liver mass was diagnosed as cystadenocarcinoma, which had developed from a benign cystadenoma with the capacity to produce mucinous material. Thin-walled cavities in the lungs showed the same histological findings. Therefore, the mechanism of cavity formation in this case was speculated to have been metastasis of mucin-producing cystadenocarcinoma, with entry of air secondary to communication with the terminal bronchiole.


[A case of squamous cell carcinoma of the lung associated with acanthosis nigricans and solitary bronchial papilloma]. A 58-year-old man diagnosed as having acanthosis nigricans symmetrically distributed on the face, neck, hands, navel and external genitals, was admitted to our department for further investigation of abnormal chest films. Bronchoscopy revealed squamous cell carcinoma of left S6 and solitary bronchial papilloma of left S3. After left pneumonectomy, facial hyperpigmentation improved slightly. About half of the reported cases of acanthosis nigricans are accompanied by various kinds of malignant neoplasms, mostly adenocarcinomas of the digestive system. The association with squamous cell carcinoma of the lung in our case appears to be unique. Only 16 cases of solitary bronchial papilloma, including our case which had the smallest diameter of 2 mm, have been reported in Japan. While it is suggested that malignant neoplasms contribute to abnormal epidermal growth such as acanthosis nigricans, a causal relationship between squamous cell carcinoma of the lung and bronchial papilloma cannot be established.


[Two cases of malignant mesothelioma controlled by pleurectomy]. Open biopsy and pleurectomy were performed in 2 cases of asbestos exposure with bloody pleural effusion. Pathological examination revealed marked proliferation of fibrous tissue containing tumor cells. The tumor was diagnosed as malignant pleural mesothelioma on the basis of histochemical staining and transmission electron microscopy. Almost complete excision of tumor tissue was performed, and malignant mesothelioma had not relapsed 10 and 12 months after the operation. We recommend open biopsy and pleurectomy for cases of exposure with bloody and intractable pleural effusion.


[A case of central nervous system sarcoidosis, presenting with psychomotor seizure]. A rare case of neurosarcoidosis presenting with psychomotor seizure is reported. A 35-year-old woman was admitted to our ward for further evaluation of syncopal attacks and suspected sarcoidosis. The patient had a history of syncopal attacks for about 15 years prior to admission; however, the pathogenesis was not clarified in spite of various examinations. Three months prior to admission, left peripheral facial nerve palsy, bilateral hypopion and bilateral hilar lymphadenopathy on plain chest film were noted at the departments of neurosurgery and ophthalmology of our hospital. She was referred and admitted to our ward. The diagnosis of sarcoidosis was made by scalene node biopsy. The syncopal attacks could not be controlled by several anticonvulsant agents. Although no significant findings were observed on brain CT and cerebral angiography, spike wave was revealed on electroencephalography (EEG) in the parieto-temporal lead. The syncopal attacks were diagnosed psychomotor seizures from both the clinical features and the EEG findings. We concluded that syncope was caused by neurosarcoidosis. The patient was prescribed steroid with much improvement of these symptoms.


[A case of obstructive ventilatory disturbance caused by bronchial wall granulation due to a fish bone]. A 62-year-old man was admitted to Kawasaki Medical School Kawasaki Hospital after suffering from wheezing for one year. His chest X-ray film showed no significant findings in the lung fields and mediastinum. A chest CT film showed a small protrusion at the posterior wall of the right main bronchus. Bronchofiberscopy disclosed a polypoid tumor with a smooth surface in the right main bronchus, confirming the finding of the chest CT, and a restiform eminence at the truncus intermedius. The restiform eminence was revealed to be a fish bone after removal from the bronchus using the forceps of a bronchofiberscope. Histological examination of a bronchoscopic biopsy specimen from the tumor of the right main bronchus showed inflammatory granulation tissue. We confirm subsequently questioned the patient who revealed that he had aspirated another fish bone two months earlier, and we presumed that the tumor of the right main bronchus might be granulation tissue secondary to the impaction of a fish bone. The patient was not aware that he had aspirated a foreign body, but it was presumed that he had aspirated the fish bone one year earlier, coinciding with the onset of wheezing. Immediately after removal, his wheezing disappeared. Comparison of the results of pulmonary function tests after removal with those before showed improvement of V25/predicted V25 ratio from 24% to 72%, and improvement of V50/V25 ratio from 3.7 to 2.4. This is considered to be a rare case of bronchial granulation due to a foreign body, which was recognized as a small polypoid tumor by chest CT.


[Angioscopic findings of the peripheral pulmonary arteries in patients with chronic pulmonary diseases]. Angioscopic observation of the peripheral pulmonary arteries was performed in 14 patients with chronic lung diseases (male 9/female 5, age 70.8 +/- 8.3 years, pulmonary tuberculosis sequelae 6, chronic bronchitis 4, chronic pulmonary emphysema 3, pneumoconiosis 1). The blood flow was stopped by the inflated balloon of a 7F guiding catheter, and then the peripheral pulmonary arteries (inner diameter 1.0-4.5 mm) were observed with a fiberoptic catheter (outer diameter 0.7 mm). In 10 out of 14 patients abnormal findings were obtained, which included redness, erosion, ulceration of the vascular wall, thrombus, fibrous tissue, and occlusion of the lumen. The incidence of abnormal findings tended to be higher in chronic bronchitis and pulmonary tuberculosis sequelae than in chronic pulmonary emphysema. These results suggest that 1) various changes including "vasculitis" and thrombus exist in the peripheral pulmonary arteries of chronic lung diseases, and 2) that angioscopy may provide the detailed information about both the vascular wall and the lumen which cannot be obtained by pulmonary angiography.


Being a family. The experience of raising a child with a disability or chronic illness. This chapter examined the experiences of families of children with a variety of specialized needs, families who, as pioneers in family-centered, community-based care, are defining the future of services. It also looked at the services that are supposed to support the families in their efforts. On one hand, we have exposed the reader to the tension between traditional approaches to services for children with special needs and the expressed needs of families for coherence and empowerment. On the other hand, the data testify to the development of a new definition of the parent-professional relationship as individual professionals and select service systems around the country strive to work out what it means to support families. When the testimony of these families is carefully read, we are left with an impression of a schizophrenic system of public and private supports for home care for children with severe disabilities and specialized health care needs. The official rhetoric affirms the primacy of the family, and yet the experience of these families is otherwise. Again and again, the families told of benefits managers, case managers, discharge planners, social workers, program administrators, special educators, and the like who implied that parents were out to "milk the system." This attitude was conveyed even in dealing with entitlements and plans to which the parents had long contributed. Families were treated as beneficiaries of benevolent charity for which they should be grateful. Families, already struggling to come to terms with their child's impairment and the care demands associated with it, find themselves stigmatized, impoverished, and degraded. In a society of rugged individualists they are forced to ask for help. That in itself is more than some of the parents can deal with. It should be clear that these parents are not asking for charity. No one here is out to "milk the system." They are simply seeking support to meet some of the extraordinary demands associated with raising their children. As parents, they are not looking for the state to assume their responsibilities. Rather, they seek supports that will enable them to devote their energies to being parents. Their testimony suggests the need for states to recognize support for the family as an entitlement that affirms that the family. They base this call on the fact that support for families is the most cost effective service the state can provide.(ABSTRACT TRUNCATED AT 400 WORDS)


CAGE and the Brief MAST study of alcohol use and misuse by medical students in Papua New Guinea. This article reports a comparative study of alcohol use and misuse among Papua New Guinea medical students in their second, third, fourth and fifth years of undergraduate study using CAGE and the Brief MAST. The study instrument was divided into three parts, namely Part A for collecting demographic data, Part B comprising the four CAGE questions and Part C comprising the ten-item Brief MAST. The self-administered questionnaires were distributed to each year group separately by one of the two investigators (FYAJ or LI). Each year group took about ten minutes to complete the questionnaires. A total of 98 completed questionnaires were returned (41 out of 42 in the second year; 18 out of 22 in the third year; 21 out of 26 in the fourth year, and 18 out of 18 in the fifth year). This gives a total response rate of 98 out of 108 (90.7%). The collected data were evaluated by statistical analysis. The results are presented in Tables 1 to 6.


Drug abuse in America: medical and socio-legal dilemmas. This article's first section describes some medico-legal issues that have been most influential in shaping responses to drug abuse in America. The next section presents a number of approaches to combating substance abuse within the criminal justice and civil systems, and discusses their rationale, effectiveness and problems. The article concludes by raising socio-political dilemmas that face America regarding the control of drug use, and asks to what extent these dilemmas are the product of ill-conceived theory and practice.


Characteristics of ethics committees of Japanese medical schools. In Japan, almost all of the 80 medical colleges and medical faculties of universities have founded ethics committees voluntarily. To date, many of them have concentrated their deliberation on the general policy of advanced medical technologies which should be resolved at national level, while they have failed to become involved in ethical decisions in daily clinical cases.


Physician-assisted suicide: epistemological problems. In the debate over physician-assisted suicide, it is assumed that issues of who might appropriately be granted such extreme assistance or how such decisions might be made can be unambiguously decided. However, the validity of such judgments remains unknown. It is clear that some rate of error in diagnosis and clinical assessment is unavoidable, while there are presently no scientific grounds to believe that competency to request physician-assisted suicide can be reliably determined. At best, resolving the question of when or if to assist a patient in suicide would require a number of clinical judgments which are currently unsupported by any research. Moreover, these judgments are not clearly separable from the physician's feelings towards the procedure, the patient or the patient's family, thus potentially subverting the objectivity needed for such a decision. Even if physician-assisted suicide could be justified on purely ethical grounds, there is no reason to believe that it is possible for physicians accurately to determine whose requests should be granted according to any proposed standards of fitness.


Medical experimentation on humans: a moral point of view. This article deals with the medical ethical dilemma in performing experiments on humans. Its aim is to examine and offer solutions to the complex subject of medical experimentation in relation to the medical community, society, the patient, doctor and nurse, keeping in mind the importance of its benefits to the patient and to medical research. Doctors are obliged to follow the rules dictated by medical ethics, and are guided by them in times of decision-making and judgments regarding the performance of medical experimentation.


REMEDHOS: the development of a medical and hospital liability database in Quebec. Confronted in 1985 with the sudden rise of costs for liability protection, the health care sector in Canada took note of the fact that little or no reliable data were available and easily accessible to assess the actual scope and nature of the phenomenon of increasing medical liability suits in Canada. In order to correct this situation, a computerized database was created covering malpractice suits launched against Quebec health care professionals and establishments. This article presents the methodology that was used for the creation of the database; it describes the material that was used, the technical instruments that were developed and the software utilized. It also describes the structure and content of the database and presents its practical application with respect to the areas of risk management, health care evaluation, professional controls and tort reform.


Insanity: making law in the absence of evidence. The Insanity Defense Reform Act (IDRA) of 1984, passed by the United States Congress after two years of hearings, illustrates the dangers of making law in the absence of evidence. In attempting to produce fewer not guilty by reason of insanity (NGRI) verdicts, the lawmakers changed the test definition of insanity, banned ultimate opinion testimony by experts and altered the burden and standard of proof. Yet, when each of these changes was empirically tested, it failed to produce fewer NGRI verdicts. From an empirical vantage point, research now is exploring the common sense constructs of sane and insane that mock jurors consistently appear to use, and these turn out to be complex, relevant and powerfully determinative of verdict. Evidence for partial responsibility judgments, along with two types of culpability judgments--at the moment of the act for the act, and for earlier actions that may bring about the mental disability--have been found. Finally, a sequential schema for insanity, which assesses both types of culpability and their degree has been tested, and the results show the least variance and the greatest coherence with other judgments and ratings of responsibility.


Health care as a natural right.

Health care as a natural right. Health care is recognized as a right in the Universal Declaration of Human Rights and by the World Health Organization's Declaration on the Rights of Patients. This article demonstrates that this concept of a 'right' to health care draws strong support from leading modern works on natural law and justice and responds to the arguments, both theoretical and practical, put forward against this proposition. It concludes with two warnings: (a) Even in a system where health care is said to be a right, this can be meaningless if the system does not promote basic health, fails to set proper legal and ethical controls or ignores the important individual rights of patients. (b) Our primary commitment must be to those persons who are denied access to health care. To them, talk of patient's individual rights is superfluous. They cannot claim such rights if they are denied the more fundamental right to be a patient.


Where there's a will.

Where there's a will. Since the United States Supreme Court decision in the Cruzan case, there will be more use of living wills which authorize the discontinuance of medical treatment for the terminally ill. Nutrition and hydration have been included as medical treatment in some cases. The statutes which authorize these documents provide that they can be revoked. Medical personnel who may be in close contact with patients and their families, such as nurses and social workers, should be trained in the provisions of living wills and what can amount to their revocation.


The physician's physician: latent duties to protect third persons. It is apparent from a growing body of court decisions that physician-patient confidentiality has been limited in those circumstances where society has a need to know certain specific information. The treating physician's duty to breach confidentiality and to warn third parties of a patient's dangerousness because of violent intent, effects of medication or dangerous health condition encompasses a duty to report previously undisclosed impairment of a fellow physician who is in treatment. The alternative is to convince the impaired colleague to withdraw from practice until the impairment is remedied. Thus, a physician collegially providing care of a colleague shoulders a particular responsibility when the physician patient is found to manifest professional impairment. This article presents a development of this thesis based upon common law and legislation in the United States.


Dr Rogers' 'insanity detector' and the admissibility of novel scientific evidence. The R-CRAS (Rogers' Criminal Responsibility Assessment Scales) purports to be a systematic and empirically based approach to evaluations of criminal responsibility. This 'insanity detector' has been heralded as a reliable instrument in the resolution of the psycholegal controversies surrounding the plea of insanity. It is contended that, regardless of its possible scientific merit, most courts will find that the R-CRAS fails to satisfy the Frye test for admissibility of novel scientific evidence (that is, general acceptance by the relevant scientific community). Moreover, it is argued that the R-CRAS's potential for prejudice outweighs its probative value, in that it might unfairly bolster the testimony of the expert witness who relies upon it and might overwhelm the jury because of its 'aura of special reliability and trustworthiness'. Until such time as the R-CRAS does gain widespread acceptance and is shown to be sufficiently reliable to outweigh any potential prejudice (if ever), the author is of the opinion that forensic psychiatrists and psychologists may have to continue to conduct evaluations of criminal responsibility 'the old-fashioned way'. 'Truth does less good in the world than its appearances do harm' --La Rochefoucauld.


Psychosurgery in the modern era: therapeutic and ethical aspects. Brain operations for psychiatric illness were in the past the centre of public controversy. Fear of untoward side-effects and an exaggerated use of the procedure including treatment of societal aspects of the disease process caused a virtual cessation of psychosurgical operations. With the introduction of techniques that could accurately lesion specific areas in the brain, especially in the limbic system, psychosurgical procedures were revived. Psychiatric syndromes, such as obsessive-compulsive affective disorders, were shown to have benefited from such intervention, without giving rise to untoward side-effects. Given societal supervision it is appropriate to reconsider the use of psychosurgery in well-defined clinical entities of mental disease that do not respond to alternative therapy.