Methotrexate decreases thymidine kinase activity.

MTX cytotoxicity is not fully explained by its well-known inhibition of dihydrofolate reductase activity which leads to a decrease in the dTMP synthase reaction, since TdR kinase which converts TdR to dTMP could readily circumvent MTX action through this salvage activity. TdR kinase is of particular significance, since in various types of carcinoma cells its activity is orders of magnitude higher than that of dTMP synthase. To throw light on this problem, we tested the hypothesis that the impact of MTX treatment might in fact involve an inhibition or decrease in TdR kinase activity. Injection in rat of MTX (i.p.) decreased TdR kinase activity in a time- and dose-dependent fashion in liver (t1/2 = 46 h; IC50 = 95 mg/kg), bone marrow (t1/2 = 10 h; IC50 = 5 mg/kg) and rapidly growing transplantable hepatoma 3924A (t1/2 = 56 h; IC50 = 5 mg/kg). Injection in rat of cycloheximide (15 mg/kg, i.p.), an inhibitor of protein biosynthesis, rapidly decreased TdR kinase activity in the hepatoma (t1/2 = 3.6 h); activities of other purine and pyrimidine synthetic enzymes, dTMP synthase, IMP dehydrogenase, GMP reductase and GMP synthase, declined at a markedly slower rate (t1/2 = 11, 11.6, 12 and 22 h, respectively). MTX, by curtailing purine and pyrimidine biosynthesis, limits product of TdR kinase which is more sensitive to unopposed protein degradation than other enzymes of nucleic acid biosynthesis. TdR kinase is a newly discovered target of MTX treatment.


Augmentation of transient low-threshold Ca2+ current induced by GTP-binding protein signal transduction system in GH3 pituitary cells.

We characterized the effects of thyrotropin-releasing hormone (TRH; 500 nM) and guanosine 5'-0-3-thiotriphosphate (GTP gamma S; 50 microM) on two types of Ca2+ currents in pituitary-hormone-secretory GH3 cells and were surprised to find marked increases in transient, low-threshold Ca2+ currents (T currents) induced by extracellularly applied TRH or intracellularly applied GTP gamma S. The effect of TRH was blocked by intracellularly applied guanosine 5'-0-2-thiodiphosphate (GDP beta S; 100 microM). The increase in the T current was found to be accompanied by a decrease in long-lasting, high-threshold Ca2+ current (L-current), in response to both TRH or GTP gamma S. These indicate that the enhancement of Ca2+ influx by TRH (500 nM) is largely conferred by T currents in GH3 cells. A reduced concentration of TRH (5 nM) still markedly increased the T current, but failed to decrease the L current. These data suggest that the augmentation of the T currents as well as depression of the L currents by TRH (500 nM), through the activation of a GTP-binding protein, may constitute an important regulatory mechanism of sustained pituitary hormone secretion in GH3 cells.


Expression, purification and biochemical comparison of natural and recombinant human non-pancreatic phospholipase A2.

The gene coding for human non-pancreatic phospholipase A2 (npPLA2) was cloned in a eukaryotic expression vector and transfected into chinese hamster ovary (CHO) cells. A number of cell lines stably expressing npPLA2 were obtained. Northern analysis of these cell lines showed an abundant transcript of expected size 1200 nt. The recombinant enzyme was efficiently secreted in quantities up to 400 micrograms npPLA2 per liter culture medium in the most productive cell lines. npPLA2 was purified to homogeneity from conditioned medium as previously described (1). The recombinant npPLA2 migrated by SDS--PAGE as a single band with an apparent mass of 14,000. The recombinant enzyme displayed the pH-optimum, calcium dependence and substrate preference that were characteristic of the human platelet and synovial fluid enzymes.


Vascular smooth muscle cells exhibit increased growth in response to elevated glucose.

Diabetes mellitus is associated with an increased risk of cardiovascular disease. In order to elucidate the association between hyperglycemia and vascular complications, the growth patterns of vascular smooth muscle cells were studied under high glucose conditions. We examined the effect of culturing porcine aortic smooth muscle cells (PVSMC) in high glucose (25 mM, HG) on total cell protein, cell volume, DNA synthesis and cell number. We observed that cells cultured in HG had higher total cell protein content which was associated with increased cell volume as compared to the cells cultured under normoglycemic conditions (5.5 mM glucose, NG). PVSMC cultured in HG also had 1.4 fold increased growth rate and a greater fetal calf serum-induced DNA synthesis rate compared to cells cultured in NG. These observations suggest for the first time that elevated glucose could lead to both hypertrophic and hyperplastic effects in PVSMC. We also examined protein kinase C (PKC) activities as well as the cellular levels of the 12-lipoxygenase product, 12-hydroxyeicosatetraenoic acid (12-HETE) in NG and HG as possible mechanisms for the enhanced growth effects in HG. The results show that PVSMC cultured in HG have increased PKC activity as well as increased levels of 12-HETE. Therefore hyperglycemia may be linked to accelerated vascular disease by increasing smooth muscle cell growth and proliferation.


The primary structure of rat ribosomal protein L3.

The amino acid sequence of the rat 60S ribosomal subunit protein L3 was deduced from the sequence of nucleotides in a recombinant cDNA. Ribosomal protein L3 has 403 amino acids and has a molecular weight of 46,106. Hybridization of the cDNA to digests of nuclear DNA suggests that there are 7 to 9 copies of the L3 gene. The mRNA for the protein is about 1,400 nucleotides in length. Rat L3 is homologous to ribosomal proteins from other eukaryotes and to proteins from eubacterial, archaebacterial, and chloroplast ribosomes.


The effect of physician and patient gender on preventive medicine practices in patients older than fifty.

This study examined whether the sex of physicians and patients affected the preventive care of middle-aged and older patients of family physicians. The charts of 61 male and 75 female patients older than 50 years, whose primary physicians were third-year family practice residents, were reviewed to determine whether tests to screen for colorectal, breast, and cervical cancer had been offered to them in the previous 18 months by their primary physicians. Male residents had offered rectal examinations significantly more frequently than female residents to male patients older than 70. Female residents had offered mammograms, pelvic exams, and Pap smears significantly more frequently to women older than 50 than had male residents. Female residents had significantly higher rates of offering pelvic exams and Pap smears to women between the ages of 50 and 70, but this difference was not significant for women over 70. There were no significant differences in the number of refusals by male or female patients to male or female residents. Results suggest that the sex and age of the patient and the sex of the physician may play a role in differential rates of cancer screening.


Obesity in a high school football candidate: a case presentation.

A 14-yr-old male presented for medical clearance to play fall football for his high school team. He had stayed out of the prior spring football practice sessions after a shoulder injury on the first day of practice, but indicated no other positive responses to the standard medical questionnaire. He was severely overweight with height of 180 cm, weight 133.4 kg, and his estimated body fat was 36%. His examination was otherwise not revealing. He demonstrated poor aerobic fitness, exercise-induced bronchospasm, residual left shoulder weakness, and a dyslipoproteinemia on further medical evaluation. He was disqualified on an empirical basis, the attending physician making the clinical decision that it would be of greater harm than good for this adolescent to participate. However, there is little data and no established guidelines for this type of situation. The overweight football athlete is a challenge to the sports medicine team, both in managing the condition and in determining athletic eligibility.


A hyperventilation interpretation of the termination of panic attacks: a reply to van den Hout, de Jong, Zandbergen and Merckelbach.

This paper summarizes the brief publication history of how a hyperventilatory positive-feed-back-loop theory of panic attacks explains the termination of panic attacks. A cautionary note is suggested when interpreting generalizations pertaining to panic attacks in panic-disorder sufferers in the everyday world made from laboratory findings based on healthy asymptomatic subjects.


Molecular and prospective phenotypic characterization of a pedigree with familial Alzheimer's disease and a missense mutation in codon 717 of the beta-amyloid precursor protein gene.

We present prospective clinical and neuropathologic details of a pedigree segregating familial Alzheimer's disease (FAD) associated with a mutation (G----A substitution) at nucleotide 2149 in exon 17 of the amyloid precursor protein (APP) gene. This mutation, which is predicted to cause the missense substitution of isoleucine for valine at codon 717 of APP, cosegregated perfectly with the FAD trait (lod score = 3.49 at theta = 0.00). The earliest clinical manifestations of the disease relate to deficits in memory function, cognitive processing speed, and attention to complex cognitive sets. These changes occurred in the absence of changes in nonmemory language and visuospatial functions. The neuropathologic features of FAD associated with the APP717 mutation in this family include severe neuronal loss, abundant neurofibrillary tangles, amyloid plaques, and amyloid angiopathy. These results provide independent confirmation that mutations in the APP gene are linked to the FAD trait in some families.


APP-collagen interaction is mediated by a heparin bridge mechanism.

The amyloid precursor protein (APP) is a glycoprotein consisting of at least four isoforms derived from a single gene by a process of alternative splicing. The membrane-bound forms of APP have been suggested to have adhesive properties and to mediate neural cell adhesion. Previous studies have demonstrated the ability of Fab' fragments of antibodies to extracellular domains of APP to inhibit neural cell binding to a collagen substrate, suggesting a physiological role for the collagen-binding properties of APP. The binding of APP has been demonstrated to be specific for type IV collagen, and no binding to other extracellular matrix components, including fibronectin and laminin, was detected. The APP-collagen binding appeared to be mediated by a heparin-bridge mechanism, since the binding was abolished by the addition of excess heparan or heparinase. These results were observed by both a homogenate-collagen binding assay and a cell-surface adhesion assay, thus providing further evidence for the adhesion role of APP. They also pose the question of the possible role of the heparin-binding properties of APP in the genesis of the neuritic plaques characteristic of Alzheimer's disease.


Effects of aluminum speciation on murine neuroblastoma cells.

Murine neuroblastoma cells behave differently in the presence of Al(acac)3 [acac = 2,4-pentanedionate; acetylacetonate] or Al(malt)3 [malt = 3-hydroxy, 2-methyl, 4-pyronate; maltolate] with respect to Al(lac)3 [lac = 2-hydroxypropionate; lactate]. Thus, a remarkable cytotoxic effect was observed in the first case; on the contrary, an evident cytostatic and neuritogenic effect was produced by aqueous Al(lac)3. The hydrolytically stable complexes Al(acac)3 and Al(malt)3 were both toxic in the concentration range of 0.10-0.30 and 0.10-0.50 mM, respectively, over 24 h. In contrast with this behavior Al(lac)3 displayed a potent cytostatic activity with induction of neurites at 0.2-10 mM. Al(OH)3 manifested biological effects comparable to those exhibited by Al(lac)3. AlPO4 was also cytostatic and led to a morphological differentiation of the neuroblastoma cells, qualitatively different from that elicited by Al(lac)3. The morphological effects induced by Al(lac)3, Al(OH)3, and AlPO4 were irreversible.


A fetal type of Minamata disease. An autopsy case report with special reference to the nervous system.

Our knowledge concerning the pathology of fetal cases of human Minamata disease (methylmercury poisoning) is relatively limited. We report here a case with description of the distribution of mercury in the systemic organs, and the ultrastructural changes of the nervous system after a survival of 29 yr. The patient was a female born in 1957, with a body wt of 3000 g, who died in 1987. She carried a diagnosis of cerebral palsy, and had a convulsion at age 3 yr. Mercury levels in her mother's hair were 101 micrograms/g at the time of examination in 1959. At autopsy, the body measured 43 cm and weighed 23 kg. The brain weighed 920 g and showed marked cerebral atrophy, mild neuronal loss in the calcarine, postcentral and precentral cortices, cerebellar atrophy, and segmental demyelination of peripheral nerves. Mercury granules were present in the brain, kidney, and liver. Ultrastructural examination of the calcarine, post- and precentral cortices, and cerebellar cortices, showed severe atrophy of nerve cells, with a decrease in rough ER and an increase in nuclear chromatin and preservation of mitochondria. Autophagosomes were increased in number. In addition, high electron density, globular and dense bodies, measuring 0.3-1.8 microns in diameter, were found, surrounded by limited membrane, within both cerebral and cerebellar neurons. In the cellebellum, synapses were well-preserved.


The role of lipid peroxidation in the possible involvement of membrane-bound monoamine oxidases in gamma-aminobutyric acid and glucosamine deamination in rat brain. Focus on chemical pathogenesis of experimental audiogenic epilepsy.

Incubation of rat brain synaptosomes and mitochondria with LPO inducers (Fe2+ and ascorbate) was accompanied by a decrease of deamination of serotonin (substrate of MAO-A) in mitochondria, but not in synaptosomes, with simultaneous stimulation of GABA and GLCA deamination, apparently owing to modification of catalytic properties of brain membrane-bound MAO. Oxidation of PEA (substrate of MAO-B) was insignificantly altered in both fractions. Reactions of deamination of serotonin, GABA, and GLCA (but not PEA), were highly sensitive to a selective inhibitor of MAO-A pyrazidol (pyrlindole). Isoniazid and hydrazides of quinoline carbonic acids (inhibitors of both modified MAO and copper-containing amine oxidases) strongly inhibited deamination of GABA and GLCA. During epileptiformic seizures in rats, genetically selected for high incidence of audiogenic epilepsia, stimulation in brain synaptosomes and mitochondria of LPO was observed. This was accompanied by a marked decrease in serotonin and PEA deamination, with a simultaneous increase in GABA and GLCA deamination in both fractions. The data obtained suggest that appearance of GABA-deaminating activity owing to modification of catalytic properties of MAO, might be an essential pathogenetic component in the development of epileptic seizures.


Platelet MAO-B activity and vitamin B12 in old age dementias.

Platelet MAO-B activity, serum vitamin B12 levels, and plasma folate were measured in patients suffering from presenile (AD) and senile (SDAT) dementia of Alzheimer-type, and vascular dementia (VD). MAO-B was higher in the SDAT group than in AD and controls. An inverse relationship between MAO-B activity and vit. B12 levels was documented in the whole group and in each category studied; furthermore, MAO-B was positively related to age. All the patients were then divided into two groups, according to vit. B12 levels (Group I: less than 200 pg/mL; Group II: greater than or equal to 200 pg/mL); Group I showed a significantly higher MAO-B activity with respect to Group II. The results indicate the existence of a negative association between platelet MAO-B activity and serum levels of vitamin B12 and confirm the existence of biological differences between presenile and senile dementia of Alzheimer type.


Impact of the USMLE step 1 on teaching and learning of the basic biomedical sciences. United States Medical Licensing Examination.

Medical licensure in the United States is in transition. In June 1991, the National Board of Medical Examiners (NBME) made major modifications in the content, format, pass/fail standards, and score reports of the NBME Part I examination. This year, Part I became Step 1, the first of three components of the United States Medical Licensing Examination (USMLE), which will shortly be the sole examination pathway to initial licensure for allopathic physicians. This essay describes Step 1, reviews the phase-in plans for the USMLE, and discusses the potential impact of both on medical schools' teaching and students' learning of the basic biomedical sciences. The authors recommend that medical schools (1) abandon the use of Step 1 as a sole criterion for student promotion to the third year and (2) carefully review other examination-related requirements for promotion and graduation.


Primary cultures of astrocytes from rat as a model for biotin deficiency in nervous tissue.

The activities and biotin-dependence of the three mitochondrial biotin-dependent carboxylases: pyruvate carboxylase, propionyl CoA carboxylase, and beta-methylcrotonyl CoA carboxylase of primary culture of astrocytes have been examined. An increase of the three mitochondrial carboxylase activities was observed during cell growth, as was the case for developing rat brain. Mitochondrial carboxylase activities from 3-wk-old primary cultures of astrocytes were higher than those in the neonatal rat brain. When astrocytes were grown in a 10% serum-enriched medium supplemented with avidin to bind biotin, the mitochondrial carboxylase activities were reduced to 15% of control value. Consistent with these results, after 3 wk in culture, the 3-hydroxyisovaleric acid concentration in the growth medium was tenfold higher than the controls. In this culture condition, cellular growth and the nonbiotin-dependent enzyme, glutamine synthetase, were not modified with respect to control. Primary cultures from newborn rat brain hemispheres are suggested as an experimental approach to the study of biotin deficiency in nervous tissue.


The psychological basis of problem-based learning: a review of the evidence.

Several potential advantages for students' learning are claimed for problem-based learning (PBL). Students in PBL curricula may be more highly motivated; they may be better problem solvers and self-directed learners; they may be better able to learn and recall information; and they may be better able to integrate basic science knowledge into the solutions of clinical problems. Although some of these claims find theoretical support from the literature on the psychology of learning, to date there has been no review of the experimental evidence supporting the possible differences in students' learning that can be attributed to PBL. In this review article, the authors examine each claim critically in light of that evidence. They conclude that (1) there is no evidence that PBL curricula result in any improvement in general, content-free problem-solving skills; (2) learning in a PBL format may initially reduce levels of learning but may foster, over periods up to several years, increased retention of knowledge; (3) some preliminary evidence suggests that PBL curricula may enhance both transfer of concepts to new problems and integration of basic science concepts into clinical problems; (4) PBL enhances intrinsic interest in the subject matter; and (5) PBL appears to enhance self-directed learning skills, and this enhancement may be maintained.


Potential role of viruses in neurodegeneration.

Viruses have the capacity to induce alterations and degenerations of neurons by different direct and indirect mechanisms. In the review, we have focused on some examples that may provide new avenues for treatment or altering the course of infections, i.e., antibodies to fusogenic virus membrane proteins, drugs that interfere with lipid metabolism, calcium channel blockers, immunoregulatory molecules, and, and inhibitors of excitotoxic amino acids. Owing to their selectivity in attack on regions of nervous tissue, governed by viral factors and by routes of invasion, viral receptors or metabolic machineries of infected cells, certain viral infections show similarities in distribution of their resulting lesions in the nervous system to that of the common human neurodegenerative diseases (namely, motor neurons disease, Parkinson's disease, and Alzheimer's disease). However, it should be emphasized that no infectious agent has as yet provided a complete animal model for any of these diseases, nor has any infectious agent been linked to them from observations on clinical or postmortem materials.


Protein kinase C activity in permanent focal cerebral ischemia.

Protein kinase C (PKC) activity was investigated in a model of focal stroke in the rat. Following 6 h of left middle cerebral artery occlusion, rat brains were frozen in situ. In the peripheral ischemic zone, total PKC activity declined by close to two-thirds (1.07 +/- 0.35 vs 2.77 +/- 0.12 nmol/min/mg protein; p less than 0.05, n = 4), and the proportion of total activity associated with the particulate fraction decreased from 33.3 +/- 1.5% to 16.2 +/- 1.4% (p less than 0.01, n = 4). Thus, overall particulate PKC activity in the ischemic zone was less than 20% of control. The cerebral energy metabolite profile of tissue from the ipsilateral hemisphere, corresponding to the region where samples were obtained for PKC activity assay, suggests that this tissue may have been part of the ischemic penumbra before further deterioration.


Comparing the characteristics of schools that produce high percentages and low percentages of primary care physicians.

To examine whether the medical school environment is important in influencing students to choose careers in primary care, the authors in 1991 compared certain characteristics of the environments of schools that produced high percentages of primary care physicians with those of schools that produced low percentages over a five-year period. The authors used the American Medical Association Physician Masterfile to identify the percentage of graduates of each of 121 medical schools for the period 1981-1985 who entered primary care specialties. They then compared the 25 schools that produced low percentages (22-29%) with the 25 schools that produced high percentages (39-56%). The results demonstrate important differences between the two groups of schools in their commitments to primary care education, their research programs, and their clinical environments supporting required clerkships. The authors conclude that a school's educational environment is an important factor in influencing some students to pursue careers in primary care medicine.


Screening test length for sequential testing with a standardized-patient examination: a receiver operating characteristic (ROC) analysis.

The feasibility of using sequential testing (i.e., using a screening test) to reduce the length and expense of a performance-based examination with standardized-patient cases was demonstrated previously. In the present study, quantitative criteria rather than practical considerations were used to determine optimal values for the length of the screening test (i.e., number of cases) and the location of the screening pass-fail cutoff (i.e., its relation to the mean of the pass levels for the different cases). Data were derived from five classes of senior students at the Southern Illinois University School of Medicine, 1987-1991. Specifically, receiver operating characteristic (ROC) curves were plotted for screening tests of varying lengths, with the points on each ROC curve corresponding to different pass-fail cutoffs on the screening test. The results showed that good accuracy can be attained with a screening test that is only one-third the length of the full examination and that the cutoff for this screen should be set slightly above the mean of the case pass levels to maximize sensitivity and specificity. The authors conclude that their study demonstrates the value of an ROC analysis in evaluating the psychometric properties of a screening test in sequential testing.


Health education programs in U.S. medical schools.

To examine the status of teaching programs on health education in undergraduate medical education, the author in 1990-91 surveyed representatives of all 126 U.S. medical schools. Of the 97 institutions that responded, 63 (65%) offered instruction in patient education and 72 (74%) offered instruction in community health promotion. The responses indicated that a number of departments participated in instruction and that diverse methods of instruction and evaluation were used. Opinions of the representatives regarding the importance and adequacy of instruction in health education were quite favorable. The author concludes that more information is needed to determine the effectiveness of the instructional programs and their impact on the quality of medical care.


Teaching the process of obtaining informed consent to medical students.

This paper describes a unit on the informed consent process taught to 119 first-year students at the Michigan State University College of Osteopathic Medicine in 1988-89. The unit consisted of a pretest and a posttest, a lecture, readings, small-group discussions, a model videotaped interview, and the students' videotaped interviews with one of two simulated patients. In the interviews, the students were most successful in establishing rapport and engaging the patients in discussions of treatment alternatives, and were less successful in perceiving the patients as unique individuals and in dealing with situations that involved conflict or confrontation. The authors suggest that curricula can be enhanced by focusing on the importance of patients' participation in the informed consent process.


How the topic of homosexuality is taught at U.S. medical schools.

In 1991 the authors surveyed all U.S. medical schools to assess both the number of curriculum hours devoted to the topic of homosexuality and the instructional strategies employed in its academic treatment; responses were sought from faculty with responsibility for teaching the topic (mostly directors of medical student education in psychiatry). Of the 126 schools, 82 (65%) responded. The mean number of hours reported was 3 hours and 26 minutes, with significant differences based on geographic region. The most frequently cited strategy was lectures in human sexuality, followed distantly by panel presentations and meetings with gay men or lesbians (both health care providers and others). To enhance sensitivity and comfort with gay and lesbian issues and to counter stereotypic responses, the authors propose that the topic of homosexuality be wholly integrated throughout the curriculum.


Assessing personal occupational safety and health training for students at U.S. medical schools.

Medical students potentially are exposed to numerous occupational hazards. This study examined the training and preventive measures medical schools use to protect the health and safety of students. In late 1990, questionnaires were mailed to the 126 schools in the United States. One hundred (79%) responded, reporting numerous incidents of illness and injury. Of the 100 schools, 60 agreed with the statement that their students were adequately prepared to work safely; 11 disagreed, and 24 gave neutral responses (five did not respond to the statement). However, 36 indicated that they planned to revise health and safety training. The authors recommend that schools adopt policies, procedures, and a uniform curriculum regarding students' occupational safety and health.


Prematriculation program grades as predictors of black and other nontraditional students' first-year academic performances.

This study explored the relative strengths of select background variables, including grades in a summer prematriculation program (SPP), as predictors of students' first-year academic performances. During the years 1980-1989, 115 black and other nontraditional prematriculants at the Medical College of Georgia School of Medicine attended a four-week SPP featuring courses in biochemistry, anatomy, and immunology. Canonical correlation analysis revealed that the combination of undergraduate grade-point average (GPA) and SPP grades in biochemistry and anatomy was the best predictor of the students' academic performances based upon their first-year grades in biochemistry, anatomy, and microbiology, and upon their GPAs for all first-year basic science courses. The authors conclude that SPP grades can be used to identify the specific academic weaknesses of nontraditional students at highest risk of falling into academic jeopardy.


Comparing the transfusion medicine content of the NBME's examinations in 1984-1985 and 1989-1990.

Recognition of the seriousness of transfusion-transmitted diseases has been demonstrated by U.S. medical schools through the integration of transfusion medicine (TM) content into their curricula. To evaluate the degree to which these changes in curricula have been reflected in the National Board of Medical Examiners' (NBME) examinations, a study conducted in 1991 evaluated the proportions of TM-related items on Parts I and II of the NBME examinations for 1984-1985 versus 1989-1990. Both Part I (basic sciences) and Part II (clinical sciences) demonstrated significant gains in TM items between the comparison periods (p less than .001), with Part II having the higher gain. An analysis of students' knowledge revealed that students in 1989-1990 tended to perform better on TM items than on examination items generally. The increases in TM content and student performance on TM items on the 1989-1990 examinations suggest that the national effort to expand and improve teaching of TM in U.S. medical schools has been effective.


Attitudes of medical school faculty toward gifts from the pharmaceutical industry.

The American Medical Association (AMA) has recently published guidelines for the receipt of gifts from industry representatives. To examine faculty members' attitudes toward that AMA policy as it pertains to gifts from the pharmaceutical industry, the authors surveyed the faculty of the University of Kentucky College of Medicine in 1991. Of 462 faculty members, 248 (54%) completed the questionnaires. The faculty generally agreed with the AMA guidelines. A majority of the faculty believed that personal relationships had the potential to influence prescribing patterns but that gifts, in general, did not greatly influence prescribing behaviors. Compared with the 169 M.D. faculty, the 69 Ph.D. faculty significantly favored more restrictive policies (p less than .001). The authors discuss both the ethical considerations and the utility of guidelines for physician-industry interactions.


Multiday driving patterns and motor carrier accident risk: a disaggregate analysis.

A method has been developed to estimate the relative accident risk posed by different patterns of driving over a multiday period. The procedure explicitly considers whether a driver is on duty or off duty for each half hour of each day during the period of analysis. From a data set of over 1,000 drivers, nine distinct driving patterns are identified. Membership in the patterns is determined exclusively by the pattern of duty hours for seven consecutive days; for some drivers an accident occurred on the eighth day while others had no accident, therefore each pattern can be associated with a relative accident risk. Additional statistical modeling allowed the consideration, in addition to driving pattern, of driver age, experience with the firm, hours off duty prior to the last trip and hours driving on the last trip (either until the accident or successful completion of the trip). The finding of the modeling is that driving patterns over the previous seven days significantly affect accident risk on the eighth day. In general, driving during the early and late morning (e.g., midnight to 10 A.M.) has the highest accident risk while all seven other multiday patterns had indistinguishable risk. Consecutive hours driven also has a significant effect on accident risk: the first hour through the fourth hour having the lowest risk with a fluctuating increase in risk to a maximum beyond nine hours. Driver age and hours off duty immediately prior to a trip do not appear to affect accident risk significantly. These findings quantitatively assess the relative accident risk of multiday driving patterns using data from actual truck operations. Further research is recommended in the areas of refining model structures, adding explanatory variables (such as highway type), and testing more complex models.


Empirical Bayes approach to the estimation of "unsafety": the multivariate regression method.

There are two kinds of clues to the unsafety of an entity: its traits (such as traffic, geometry, age, or gender) and its historical accident record. The Empirical Bayes approach to unsafety estimation makes use of both kinds of clues. It requires information about the mean and the variance of the unsafety in a "reference population" of similar entities. The method now in use for this purpose suffers from several shortcomings. First, a very large reference population is required. Second, the choice of reference population is to some extent arbitrary. Third, entities in the reference population usually cannot match the traits of the entity the unsafety of which is estimated. To alleviate these shortcomings the multivariate regression method for estimating the mean and variance of unsafety in reference populations is offered. Its logical foundations are described and its soundness is demonstrated. The use of the multivariate method makes the Empirical Bayes approach to unsafety estimation applicable to a wider range of circumstances and yields better estimates of unsafety. The application of the method to the tasks of identifying deviant entities and of estimating the effect of interventions on unsafety are discussed and illustrated by numerical examples.


The effectiveness of motor carrier safety audits.

In 1986 the federal government expanded its program of company inspections for enforcement of motor carrier safety regulations. We find that many parts of these inspections are unrelated to the safety performance of firms. Never the less, reinspection of firms found to be unsatisfactory in a previous inspection does appear to bring about a substantial improvement in their safety performance. However, such firms represent a small fraction of the industry, and the probability of being inspected is very low. Thus, the program does not appear to have resulted in a detectable improvement in the accident rate of the industry.


Interactivity, information, and compliance cost in a consumer product warning scenario.

The effects of information content, physical interactivity, and cost of compliance on safe behavior of 356 subjects were examined using a common consumer product. The use of gloves for a "new formulation" consumer cleaning product was tested along with subject perceptions of the risk associated with the product's use. Results indicated that cost of compliance was the only variable that significantly affected the safe use of the product. Implications for consumer product safety and regulation are discussed.


Can road traffic law enforcement permanently reduce the number of accidents?

In this paper it is argued that conventional analyses of road user adaptation to traffic law enforcement, based on parametric rational-choice theory, are flawed. Such analyses only consider road-user actions as a response to enforcement level and penalty size and do not simultaneously consider enforcement as a response to road-user behaviour. If each party is considered a rational agent who adapts to the other's behaviour, the proper way to analyze the outcomes is by the way of game theory. A game-theoretic model is presented and the main implications are: (i) most attempts at enforcing road traffic legislation will not have any lasting effects, either on road-user behaviour or on accidents; (ii) imposing stricter penalties (in the form of higher fines or longer prison sentences) will not affect road-user behaviour; (iii) imposing stricter penalties will reduce the level of enforcement; (iv) implementing automatic traffic surveillance techniques and/or allocating enforcement resources according to a chance mechanism, and not according to police estimates of violation probability, can make enforcement effects last, but both alternatives are difficult to implement. Relevant empirical studies are reviewed, and they seem to support the conclusions arrived at by the game-theoretic model.


Introducing beer sales at a Canadian ball park: the effect on motor vehicle accidents.

The impact of introducing the legal sale of beer in a Toronto stadium on drinking-driving accidents is investigated. The results suggest that a greater proportion of accidents in the postgame time are alcohol-related when compared to pregame times and to control times. No significant effect was found, however, for the introduction of legal beer sales, suggesting that drinking was common before the public sales policy.


Falls in 84- to 85-year-old people living at home.

The present study is a part of the Swedish longitudinal population study "70-year-old people in Gothenburg". The aim of the present study was to analyse retrospectively incidence, circumstances, and consequences of falls during one year among 741 home-living people aged 84-85. A comparison of social and medical characteristics of fallers and non-fallers aged 85 was performed. Information was collected by interviews and clinical examinations. In 1986/1987, 732 home-living people (244 men and 488 women), aged 85 gave information about falls during the last year. Three hundred and one (41%), 97 men and 204 women, had fallen at least once during the last year, mainly indoors. No sex difference was found in incidence. The most dominant triggering causes of falls were stumbling, dizziness, and feebleness. In 80% of the falls an injury occurred, of which every fourth was a fracture. A multivariate regression procedure showed that dizziness, vertigo and unsteadiness, transient ischemic attacks, antidepressant drugs, and poor subjectively experienced health characterized the fallers. Mortality rate of those between 85 and 88 years of age showed no association with falls.


Some biases in the alcohol investigative process in traffic fatalities.

This study compares data regarding alcohol involvement from police records and from chemical analyses of body fluids taken prior to or after death of 121 traffic fatalities in Washtenaw County, Michigan. Differences regarding the choice of who will or will not be screened for alcohol were found. The police and emergency room personnel were more likely to focus on males and drivers, while medical examiners were less biased. The police documented whether or not drinking took place in only 36% of the cases and suspected drinking in only half of these cases. Males and at-fault drivers were most likely to be investigated. Blood alcohol level was measured before death in 11 of 29 emergency room treated victims, with 10 (91%) positive samples. All but two of those tested before death were drivers, and all but one were males. After death, blood alcohol was measured in 47% of the 121 cases, with a higher proportion of males and motor-vehicle occupants tested, compared to females and pedestrians. Alcohol was detected in 63% of the samples. A lower mean blood alcohol concentration was found in victims who received intravenous treatment, and a higher proportion of positive samples was found in victims who died immediately in the crash. Thus, the frequency of alcohol-related traffic fatalities varied between the different data sources. The police records revealed 51%, the emergency records 91%, and the medical examiner records 63% with alcohol involvement. This wide discrepancy has the potential of leading to erroneous results here and possibly in studies done elsewhere.(ABSTRACT TRUNCATED AT 250 WORDS)


Traffic volume and collisions involving transit and nontransit vehicles.

This study reports an analysis of collisions occurring between public transit vehicles operated by the San Francisco Municipal Railway System (Muni), the public transit agency for the City of San Francisco, and nontransit vehicles. The analysis, focusing on weekday collisions during 1987, demonstrated a strong association between hourly transit collisions rates and hourly traffic volume. The collision rate varied from 0.01 per 1,000 Muni vehicle-hours of operation during the interval 5 A.M. to 6 A.M., a time of very low traffic volume, to 0.93 (approximately 1 collision per 1,000 Muni vehicle-hours of operation) during the interval 5 P.M. to 6 P.M., a time of very high traffic volume. Using a power function to predict either the total number of collisions, or the rate of collisions per 1,000 Muni vehicle-hours, almost 90% of total variation was accounted for by traffic volume. A very similar pattern was found for collisions judged either avoidable or unavoidable. A peak in the collision rate between 2 A.M. and 3 A.M. could not be accounted for by traffic volume alone. That peak occurred in the one-hour interval following the 2 A.M. closing of bars in San Francisco, and was composed entirely of a sharp increase in unavoidable collisions. Increasing traffic volume appeared to operate through two mechanisms: (i) an increase in the number of opportunities for a collision, defined as a quantity proportional to the product of the number of Muni and non-Muni vehicles; (ii) an increase in the probability of a collision occurring between any given pair of vehicles.


In vitro loss of alcohol from tissue conditioners.

The rate of alcohol loss from two tissue conditioners was investigated by applying them to complete denture record bases and immersing them in water in a sealed container. Samples were taken regularly and analysed by gas chromatography. The alcohol was found to leach out much more quickly than expected with the greatest loss occurring in the first 12 hours and peaking at approximately 60 hours.


Color changes of porcelain surface colorants resulting from firing.

Differential loss of chrome from surface colorants during firing can make the prediction of final porcelain color difficult. This investigation was undertaken to assess the color change of nine extrinsic colorants during firing. Colorants were applied to metal-ceramic substrates, and color was measured both before and after firing using a colorimeter. CIE LAB color coordinates were obtained as a measure of the direction and quantity of color change. Color change for yellow (delta E*ab = 4.00) was significantly greater than that for the other groups (delta E*ab = 0.41-1.25). Changes in L*a*b* values for yellow samples were toward those of the controls.


The influence of the retromylohyoid extension on mandibular complete denture stability.

It has been a clinical impression that the retromylohyoid extension in complete mandibular dentures contributes to stability. This hypothesis was tested in six individuals by means of cineradiography and placement of a metal marker in the mandible and dentures during chewing exercises, with and without the relevant denture extension. Analysis of tracings of the movements of the markers revealed that statistically significant differences existed between first and second chewing experiences. Movement in a horizontal plane around a vertical axis, however, was common to all dentures during all chewing. It is concluded that the retromylohyoid extension has a stabilizing effect on complete mandibular dentures.


Wear of I-bar clasps and porcelain laminate restorations.

Partial-coverage porcelain laminate restorations, placed to provide undercut areas for I-bar direct retainers of removable partial dentures, were evaluated over simulated 2- and 5-year periods of placement and removal movements. SEM photomicrographs and computer imaging were used to quantify wear of the I-bar tips and the contacting laminate surfaces. These data were statistically compared to previously collected data of I-bar clasp tip wear against human enamel under the same experimental conditions. None of the laminate restorations debonded during this investigation. I-bars contacting laminates exhibited significantly more wear than I-bars contacting human enamel; however, the combined laminate-I-bar wear compared to the combined enamel-I-bar wear produced no significant difference.


Efficacy of various spray disinfectants on irreversible hydrocolloid impressions.

This study evaluated the effectiveness of eight disinfectant sprays on irreversible hydrocolloid impressions contaminated with three microorganisms (Staphylococcus aureus, Mycobacterium phlei, or Bacillus subtilis) or mixed oral flora. Alcide LD, OMC II, Biocide, and Professional Lysol Spray were relatively ineffective under the test conditions. Sporicidin and 0.525% sodium hypochlorite were able to effect a 4-log10 (99.99%) reduction against S aureus only. A 4-log10 reduction in bacterial counts was achieved by 5.25% sodium hypochlorite and Impresept in all tests except against B subtilis. Full-strength sodium hypochlorite (5.25%) was the most effective disinfectant overall and required the shortest contact time.


Bond strength of three nonaqueous elastomeric impression materials to a light-activated resin tray.

The bonding of nonaqueous elastomeric impression materials to the impression tray is critical for an accurate impression; mechanical locks and adhesive materials are commonly used to enhance bonding. This study evaluated the bonding of three elastomeric materials to a light-polymerized resin tray. Roughening the tray surface prior to the application of an adhesive enhanced the bond.


Relationship of removable partial denture use to root caries in an older population.

The pattern and severity of root caries in a selected older population, living in the community and attending a general dental practice in Bexhill, East Sussex, England, is reported. A total of 146 patients were examined to determine the relationship among removable partial dentures, their design, and root caries. Of those patients, 57% wore removable dentures and had a higher prevalence of exposed root surfaces and root caries, particularly on abutment teeth. In addition, root caries lesions on abutment surfaces were found to be larger and more active than those on nonabutment surfaces.


Tensile strength of three resin cements following two alloy surface treatments.

Retainers for composite retained prostheses ("Maryland bridges") have traditionally relied upon an etched base metal alloy for micromechanical retention. This study compared the tensile bond strength of three resin cements using two alloy surface treatments. Rexillium III and Olympia disks were cast, oxidized, and given simulated porcelain firings. Paired specimens were cemented with Comspan, Panavia EX, or C & B Metabond after air abrasion with aluminum oxide or silicoating. Air-abraded Olympia disks were tin plated prior to luting with Panavia EX. Electrolytically etched Rexillium III specimens luted with Comspan served as controls. Specimens were thermocycled and tested in tension. Highest tensile bond strengths were achieved with: (1) Olympia specimens, where the bonding surface was air abraded but tin plated before cementation with Panavia EX, and (2) Rexillium III specimens, where the bonding surface was air abraded or silicoated and the disks were cemented with C & B Metabond.


Measurements of dimensional accuracy using linear and scanning profile techniques.

Various measurement methods have been described for the determination of dimensional accuracy and stability of denture base materials. This investigation introduces a computerised coordinate measuring machine (CCMM) and compares it with two methods routinely used for assessment of the accuracy of fit of denture base materials. The results demonstrate that the three methods (digital calipers, optical comparator, and CCMM) are acceptable for linear measurement. The CCMM was also used in its scanning mode to define and to quantify the contour changes of the resin bases. The advantages of the CCMM become apparent when two-dimensional changes require assessment.


An analysis of edentulous maxillary arch width and palatal height.

This study involving 500 edentulous patients (250 males, 250 females) was undertaken to introduce a dimensionless factor termed the "palatal height ratio," defined as the ratio of the width of the edentulous maxillary arch to the height of the palate. The authors categorized the height, width, and anteroposterior dimensions of the edentulous maxillae. Measurements were made on diagnostic casts at five defined points. The difference between males and females was statistically analyzed and the variables were categorized. The results of this study may be helpful for a better standardization of the same variables in future studies.


A comparison of two methods for removing zinc oxide-eugenol provisional cement.

Two methods of removing zinc oxide-eugenol (ZOE) luting cement from amalgam were compared by determining their effect on the tensile bond strength of amalgam cylinders luted together using a 4-META resin cement. The samples were examined using scanning electron microscopy and energy dispersive x-ray analysis. Results showed that mechanical cleansing with pumice leaves ZOE residue mixed with pumice, which inhibits bonding, while the bond strength of samples cleansed with a dental degreasing agent was similar to that of an uncontaminated control group.


Heat-pressed ceramics: technology and strength.

The flexural strength of a new heat-pressed ceramic material (IPS-Empress) was measured before and after pressing and/or simulated firing treatments (eg, veneering, surface coloring, glazing). Heat pressing the material significantly improved its flexure strength whereas heat treating the material alone did not. Additional firings (heat treatments) after heat pressing further increased material strength. The final strength values ranged between 160 and 180 MPa and were comparable to some other all-ceramic systems. No clinical implications were drawn from these data.


Effects of ion exchange on hardness and fracture toughness of dental ceramics.

Dental ceramics generally fail because of the growth of microscopic surface flaws that form during processing or finishing or that result from surface impact during service. The ion-exchange process has been shown to be effective in improving the flexural strength of most dental porcelains through the development of a compressive surface layer. The Vickers hardness and crack resistance of several commercial dental ceramics were determined by indentation techniques. The results of this investigation indicate that ion-exchange reinforcement can significantly improve the resistance of the ceramic surface to crack propagation with little effect on apparent surface hardness.


Investigation of the effect of magnetic retention systems used in prostheses on buccal mucosal blood flow.

The purpose of this study was to investigate the probable effects of the magnetic field produced by dental magnets on neighboring capillary circulation. Ten subjects were used. Transparent acrylic resin devices were prepared to receive the dental magnets and were used continually by subjects except during sleep. The maxillary buccal mucosal blood flow was measured on both sides (control and experimental) in the same subjects before the use of dental magnets and after 3, 7, 15, 30, and 45 days by the 133Xe clearance technique. Upon analysis it was found that the difference in blood flow between the control and experimental sides was insignificant (P greater than .05). The decrease in blood flow as time progressed was attributed to the pressure exerted by the oral devices rather than by the effect of the magnetic field.


Movement between centric relation contact position and the intercuspal position.

Casts of 42 patients free from temporomandibular joint problems were mounted on an articulator in centric relation contact position. The movement of the horizontal axis of rotation was measured when the casts were moved from centric relation contact position to the intercuspal position. Measurements of the vertical and horizontal movements of the incisal pin were also made during this movement. There was a highly significant correlation between the movement of the horizontal axis in the horizontal plane and the ratio of vertical to horizontal movement as measured at the incisal pin. The greater this ratio was, the smaller the horizontal movement of the axis was; the smaller the ratio (the larger the horizontal component) was, the larger was the horizontal movement of the axis. The clinical implications are discussed.


Mechanical properties of new denture resins polymerized by visible light, heat, and microwave energy.

Properties of seven newer resins polymerized using a water bath, microwave energy, or by visible light were measured. Generally, the new resins were harder and less flexible but had lower impact strength than did the heat-polymerized, rubber-modified resin (Lucitone). The light-activated urethane dimethacrylate resin (Triad) was the least flexible. Microwave polymerization improved the modulus of elasticity of two resins, decreased the impact strength of one, and had little effect on the properties of two other resins.


Tensile stress in glass-ceramic crowns: effect of flaws and cement voids.

The objective of this study was to analyze the relative effect of loading site, occlusal thickness, ceramic flaws, elastic modulus of the cement, and voids in the cement layer on tensile stress that develops in molar glass-ceramic crowns under applied loads. Finite-element stress analyses were performed. Resin cement with a thickness of 0.05 mm was used. A central conical flaw (0.05 mm [diameter] x 0.05 mm) and a circular grooved flaw located under the cusp tips were included in all flaw cases. A void space confined within the occlusal region of the cement layer was also included in selected cases. For a ceramic thickness of 0.5 mm and a vertical distributed load applied at a distance of 1.3 mm from the vertical axis, the maximum tensile stresses were 100 MPa for a crown with flaws and a void, 87 MPa for a crown with no flaws and a void, and 75 MPa for a crown with flaws and no void. For a 1.5-mm-thick crown with flaws and a void, the tensile stress decreased to 22 MPa. When the load of 600 N was concentrated at the central point of the occlusal region, the peak tensile stress in a crown with flaws and no void was increased to 325 MPa. For the conditions analyzed in this study a large void in a flawed occlusal region of a thin molar crown (0.5 mm) is proposed as a mechanism of crown failure.


Use of image analysis in determining masticatory efficiency in patients presenting for immediate dentures.

Image analysis was used to determine masticatory efficiency and performance before and after placement of immediate dentures. Sections of cored carrot were used as the test food and the particle size of chewed expectorated food was measured using image analysis. Measurements were shown to be accurate and reproducible. Masticatory function of immediate-denture patients was also compared with a similar number of dentate individuals and experienced complete-denture wearers. Dentate subjects were significantly (P less than .01) more efficient at masticating the test food than were the complete- or immediate-denture wearers. The new method of measurement removes the necessity for the unpleasant and unhygienic sieving process previously used in this type of study.


Direct measurement of dimensional accuracy with three denture-processing techniques.

The Michigan Computer-Graphics Coordinate Measurement System (MCGCMS) was used to determine the dimensional accuracy of dentures processed by three different techniques: conventional heat compression, microwave, and visible-light activation. Standardized dentures were fabricated from casts made in an RTV silicone mold. All casts were duplicated with hydrocolloid and 42 dentures were made (ie, 14 dentures for each technique). The MCGCMS measured 22 points on two frontal planes to compare master casts to dentures. The results showed no significant difference in overall dimensional accuracy. At specific sites, however, the visible-light-activated technique produced significantly more flange distortion than did either the conventional or microwave techniques.


In vitro bond strength of silica-coated metal posts in roots of teeth.

This study determined the in-vitro bond strength of abrasive-sprayed and silica-coated Ni-Cr-Be posts to roots of extracted teeth using three resin cements (Panavia EX [P], Super-Bond C&B [SB], Prisma Universal Bond 2-Dicor [PUB-D]) and zinc phosphate cement (ZP). There were no significant differences among bond strengths of resin cements (8.8 to 10.8 MPa) bonded to abrasive-sprayed posts, but the bonds were stronger than those obtained using zinc phosphate cement (4.4 MPa). With the silica-coated posts, Super-Bond C&B produced the highest bond strength (14.5 MPa), followed by PUB-D (10.9 MPa), P (7.5 MPa), and ZP (5.4 MPa).


The effect of clasp form on permanent deformation.

This study was conducted to discover whether a relationship exists between clasp width-thickness ratios and wear or deformation. Five different forms of circumferential clasps were studied. The clasps were fabricated with a 160 degree curvature around an 8-mm (diameter) cylinder and cast in Ticonium alloy. The clasps were subjected to 1500 cycles of 0.01 inch flexure. The degree of permanent deformation was not related to clasp form or width-thickness ratio. Of the five forms, only one exhibited no permanent deformation. According to Duncan's Multiple Range Test, significant differences in wear against a steel tooth model were observed among the five clasp forms evaluated (alpha = 0.05).


Survival, function, morphology and serological aspects of rat renal allografts. Effect of short-term treatment with cyclosporine A, anti-CD4 and anti-interleukin-2 receptor monoclonal antibodies.

The aim of this study was to investigate the effect of short-term treatment with cyclosporine A (CyA) combined with anti-CD4 (OX-38) and anti-interleukin-2 receptor (OX-39) monoclonal antibodies (MAbs) on graft survival, graft function, morphology, and anti-donor antibody levels in a BN-to-LEW rat kidney transplantation model. Spontaneous rejection occurred at 9.3 days (range 9-10 d). Administration of CyA (12.5 mg/kg/d) for 14 days prolonged graft survival to 33 days (range 23-40 d, P less than 0.02). Supplementing with OX-38 and OX-39 100 micrograms/kg/d, given i.p. from days 0 to 7, further prolonged graft survival to 70 days (range 38- greater than 100 d, P less than 0.02 vs controls and CyA group). One of seven recipients had good graft function for more than 100 days. A three-fold increase of the MAb dosage did not improve mean graft survival (53.5 d), but three of eight recipients had well functioning grafts for greater than 100 days. Kidney function was characterized by reduced creatinine clearance, also in the recipients with long-term graft survival, and a defect in concentrating urine creatinine with subsequent pronounced increase in urinary output. Graft histology showed a complex pattern of interstitial alterations including mononuclear cell infiltration, fibrosis, tubular atrophy and vascular damage with intimal/endothelial cell hyperplasia and perivascular inflammation. In nine of 10 MAb-treated recipients with graft survival greater than 60 days, granular deposits of immunoglobulins and C3 were found by immunofluorescence microscopy (IFM). The deposits were localized in the glomerular capillaries and mesangium. IFM in MAb-treated control animals could not demonstrate any deposits. Flow cytometric evaluation of posttransplant serum samples against donor target cells showed increasing amounts of anti-donor antibodies until the time of rejection, while recipients with long-term graft function had moderately positive cross-matches up to two months after transplantation. Hereafter antibody titres decreased and cross-matches at the time of sacrifice were again negative. The morphological findings and the flow cytometric cross-match results seem to indicate a postponed antibody-mediated type of rejection. The reason why some kidney recipients showed decreasing antibody titres and stable long-term graft function is unclear.


Increased expression of adhesion proteins (MAC-1) and altered metabolic response in human leukocytes exposed to surfactant in vitro.

In this study the modulatory effects of a well-defined surfactant preparation on blood leukocytes were investigated. The expression of the cell surface receptor MAC-1 was analyzed by flow cytofluorometry, and the metabolic response was measured by a chemiluminescence technique. An increase (p less than 0.05) in the MAC-1 receptor expression was observed in the granulocytes but not in the monocytes. There was a decrease in the metabolic response of the leukocytes after stimulation with phorbol myristate acetate (PMA) and a delay (p less than 0.01 for both) in the peak activity. Formyl-methionyl-leucyl-phenylalanine (fMLP) caused an increased peak (p less than 0.01). Thus, the surfactant preparation had a modulatory effect on blood leukocytes with regard to the expression of the cell surface receptor MAC-1 and the metabolic response.


Peripolar cells and other granulated epithelial cells in renal biopsies.

The peripolar cell is a recently described glomerular epithelial cell which is situated within Bowman's capsule at the vascular pole. It contains cytoplasmic granules which contain plasma proteins, although it may also have a secretory function. The relationship between peripolar cells, other granulated glomerular epithelial cells and tubular epithelial cells is unclear. We have studied 242 biopsies from 19 types of renal disease for peripolar cells, other granulated epithelial cells and granulated tubular epithelial cells. Peripolar cells were most numerous in mesangioproliferative glomerulonephritis, IgA nephropathy, focal segmental glomerulosclerosis, membranous glomerulonephritis and lupus nephropathy. Other granulated glomerular epithelial cells were most prominent in diffuse lupus nephropathy, focal glomerulonephritis, acute vascular transplant rejection, crescentic glomerulonephritis and mesangioproliferative glomerulonephritis. Granulation of the tubular epithelium was most prominent in minimal change nephrotic syndrome and amyloidosis. It is likely that the granules in tubular epithelial cells represent lysosomes containing plasma proteins which have been absorbed from the tubular fluid. However, granulation of glomerular cells may represent a more specific response to glomerular damage. In addition, peripolar cells are prominent in only certain diseases, suggesting a specialized function.


The prevalence of selective IgA deficiency in type 1 diabetes mellitus.

A significant increase in the prevalence of selective IgA deficiency has been observed in patients with autoimmune disorders such as systemic lupus erythematosus and rheumatoid arthritis. Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease and susceptibility to both IDDM and IgA deficiency is associated with HLA DQB1 alleles encoding non-Asp amino acids at position 57. In order to assess whether the prevalence of selective IgA deficiency is increased in IDDM, we have screened a homogeneous series of adult patients with IDDM for selective IgA deficiency. One patient (1:261) was found to have a selective IgA deficiency. The prevalence of selective IgA deficiency among adult French blood donors is 1:1400. Thus, although IDDM and selective IgA deficiency are both associated with the presence of non-Asp amino acids at position 57 of the HLA DQ beta chain, the frequency of this immunodeficiency in adult IDDM patients is not significantly increased.


Expression of the epidermal growth factor receptor gene in human brain metastases.

Biopsy specimens of human brain metastases were examined for amplification and expression of the proto-oncogene c-erbB1 (located on chromosome 7) encoding the epidermal growth factor receptor (EGFR). Moreover, the tumour DNA was also examined for amplification of other cancer-related genes on this chromosome: the proto-oncogene c-met, the gene for platelet-derived growth factor A-chain, and the gene for plasminogen activator inhibitory type 1. All 18 brain metastases demonstrated positive binding of biotinylated EGF on cryosections. Three out of 18 metastases had amplification of the EGFR gene; the other chromosome-7 genes tested were not amplified. Thus, an increased EGFR gene expression seems to be a general finding in a wide range of carcinomas metastatic to the brain, whereas we found only occasional selective EGFR gene amplifications in single cases.


Neonatal Proteus meningoencephalitis. Case report.

Proteus is an uncommon pathogen in neonatal meningitis and has, to our knowledge, not previously been described from Scandinavia. Our case illustrates the typical course of the disease when onset is within the first two weeks of life. The typical patient is a previously healthy, sometimes slightly preterm infant, who develops multiple brain abscesses and has a very poor prognosis. In cases with a later onset, factors predisposing for infection are common and the outcome is less severe. Our patient was a girl born at a gestational age of 36 full weeks, who was a little less alert than normal during the first three days and then became dramatically sick with convulsions and apnoeas. She died at the age of six days with severe brain damage.


IgG subclass antibodies against Helicobacter pylori heat-stable antigens in normal persons and in dyspeptic patients.

Measurement of serum IgG antibodies against Helicobacter pylori seems to be useful in the diagnosis of H. pylori infections. IgG subclass antibodies against H. pylori have, however, not been investigated thoroughly. In this study IgG1, IgG2, IgG3 and IgG4 antibody levels against H. pylori were measured using an ELISA technique in 187 normal adult persons and in 174 patients with dyspeptic symptoms, of whom 99 patients were H. pylori positive. None of the IgG subclass antibody levels were better than the total IgG level for the diagnosis of H. pylori infection. The discrimination between H. pylori-positive and H. pylori-negative patients was better with IgG1, IgG2 and IgG4 antibody levels than with IgG3 antibody level. IgG2 was the IgG subclass antibody that mainly contributed to the age-dependent increase in the IgG antibody level. This sustains the suspicion that cross-reactions between lipopolysaccharide (LPS) from H. pylori and LPS from other Gram-negative bacteria may occur.


Experimentally induced ileal ulcers in rats. Formula diet is a preventive factor.

We recently described an experimental model in the rat to create recurring chronic ileal inflammation including ulceration. This model is dependent on an "in vivo culture" of normal intestinal contents. In the present experimental study we examined the effect of a polymeric and a hydrolyzed formula diet on the formation of ulcerating lesions using our rat model. Two groups of rats (twenty in each group) were fed either one of these formula diets eight weeks prior to the experimental procedure and this diet was continued until sacrifice eight weeks later. Twenty control rats also underwent the experimental procedure but were fed standard rat pellets for the same time periods. At sacrifice 60% of the control rats had developed ileal ulcers. None of the rats fed the formula diets developed macroscopic ileal inflammation or ulceration. The effectiveness of formula diets in inducing remission in Crohn's disease in humans may be linked to alterations in the intestinal microflora. We hypothesize that the formula diets in this experiment exerted a protective effect against ileal ulceration by altering the ileal microflora. Preliminary studies support this hypothesis but need to be expanded.


Synthetic surfactant (Exosurf) inhibits endotoxin-stimulated cytokine secretion by human alveolar macrophages.

Tumor necrosis factor-alpha (TNF), interleukin-1 beta (IL-1), interleukin-6 (IL-6), and interleukin-8 (IL-8) are inflammatory cytokines produced by alveolar macrophages (AMs) and implicated in sepsis-related adult respiratory distress syndrome (ARDS). Preliminary findings from clinical trials suggest that aerosolized delivery of the synthetic surfactant Exosurf (Burroughs Wellcome Co.) reduces mortality in patients with sepsis-induced ARDS. The purpose of the present study was to examine the effect of Exosurf on inflammatory cytokine secretion from AMs in vitro. AMs were obtained from normal nonsmoking adult volunteers. Secreted TNF, IL-1, IL-6, and IL-8 were measured by enzyme-linked immunoassays in 24 h culture fluids of AMs. Exosurf inhibited LPS-stimulated TNF, IL-1, and IL-6 secretion in a dose-dependent fashion. IL-8 secretion was not affected by Exosurf under these conditions. However, if AMs were preincubated for 24 h in media and then LPS-stimulated, IL-8 secretion was inhibited by Exosurf. Regulation of IL-8 production may differ from TNF, IL-1, and IL-6. Unstimulated cytokine secretion was not affected by any of the tested concentrations of Exosurf. The inhibitory effect of Exosurf on endotoxin-induced cytokine secretion by human AMs suggests that Exosurf may modulate inflammatory cytokine production in the lung.


Polyamine transport and ornithine decarboxylase activity in hypoxic pulmonary artery smooth muscle cells.

Hypoxia causes remodeling of the pulmonary circulation that is dependent on increases in lungs polyamine contents. Mechanisms by which polyamines are regulated in hypoxic lung cells are unknown, but ornithine decarboxylase (ODC) activity, the initial enzyme in de novo biosynthesis, is depressed and polyamine transport is augmented in lungs from hypoxic rats (R.-T. Shiao et al. 1990. Am. J. Physiol. 259:L351-L358). To determine if hypoxia directly influences polyamine regulatory mechanisms in pulmonary vascular cells, we examined [14C]spermidine (SPD) transport and ODC activity in bovine main pulmonary artery smooth muscle cells (PASMCs) cultured under standard (culture medium Po2: greater than 100 mm Hg), "normoxic" (culture medium Po2: 50 to 70 mm Hg), or "hypoxic" (culture medium Po2: 18 to 30 mm Hg) conditions. Uptake of [14C]SPD in cells cultured under standard conditions was temperature- and concentration-dependent, exhibited saturation kinetics, and was abolished by metabolic inhibition. Modeling of transport according to Michaelis-Menten kinetics revealed that [14C]SPD uptake in cells cultured under standard conditions was characterized by Km and Vmax values of 0.78 microM and 4.5 pmol/min/10(6) cells, respectively. In comparison to cells cultured under standard conditions, Km was unaffected by culture under normoxic or hypoxic conditions while Vmax was increased to 18 pmol/min/10(6) cells in normoxic cells and to 33 pmol/min/10(6) cells in preparations cultured under hypoxic conditions. Inhibition of ODC with alpha-difluoromethylornithine (DFMO) also induced SPD transport, as evidenced by an increase in the Vmax to 65 pmol/min/10(6) cells. Both hypoxia- and DFMO-induced increases in [14C]SPD transport were suppressed by cycloheximide and actinomycin D, thus highlighting the importance of protein and RNA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)


Elevation of glutathione levels in bovine pulmonary artery endothelial cells by N-acetylcysteine.

N-Acetylcysteine (NAC), a cysteine derivative with chemoprotective and radioprotective effects, was found to elevate bovine pulmonary artery endothelial cell (EC) glutathione after in vitro incubation. The elevation in glutathione was associated with enhanced uptake of radioactivity of cystine from the medium. Because cystine in medium was converted rapidly to cysteine and cysteinyl-NAC in the presence of NAC and given that cysteine has a higher affinity for uptake by EC than cystine, we conclude that the enhanced uptake of radioactivity was in the form of cysteine and at least part of the stimulatory effect of NAC on EC glutathione was due to a formation of cysteine by a mixed disulfide reaction of NAC with cystine similar to that previously reported for Chinese hamster ovarian cells (R. D. Issels et al. 1988. Biochem. Pharmacol. 37:881-888). However, NAC was more effective than cysteine in elevating cellular glutathione at equimolar concentrations, and at higher concentrations of NAC an elevation of EC glutathione occurred even in the absence of cystine in the medium through a currently unknown mechanism. Thus, at least two mechanisms are operative in the elevation of endothelial cellular glutathione by NAC. NAC may be a useful compound for elevating glutathione of the pulmonary vasculature for protection against oxidant stress.


Hydrogen peroxide increases the availability of arachidonic acid for oxidative metabolism by inhibiting acylation into phospholipids in the alveolar macrophage.

Reactive oxygen species stimulate metabolism of arachidonic acid (AA) to eicosanoids in a variety of cells and tissues, yet the pathway(s) by which oxidants increase the availability of AA for oxidative metabolism are not known. Thus, we explored the effects of hydrogen peroxide (H2O2) on deacylation and reacylation of AA to determine the enzymatic mechanism(s) by which this oxidant increases levels of free, unesterified AA, and thereby its oxidative metabolism to eicosanoids, in the rat alveolar macrophage (AM). Over the range from 0.1 to 0.5 mM, H2O2 caused marked time- and dose-dependent inhibition of incorporation of [3H]AA into macrophage phospholipids, whereas calcium ionophore A23187 and zymosan particles did not cause such inhibition. Within this concentration range, there was an almost exact reciprocal correlation between inhibition of [3H]AA acylation and H2O2-stimulated accumulation of free [3H]AA in prelabeled AM cultures. Thimerosal, which blocks AA reacylation but spares deacylation via phospholipase A2 (PLA2), did not affect accumulation of free [3H]AA in prelabeled cells stimulated with H2O2, while markedly augmenting [3H]AA release in response to A23187 and to zymosan. Despite its ability to block AA acylation almost completely, H2O2 did not directly inhibit arachidonoyl CoA synthetase or arachidonoyl CoA:lysophosphatide acyltransferase, which catalyze AA incorporation into phospholipids. However, H2O2 (0.1 to 0.5 mM) markedly depleted AMs of ATP, required for synthesis of the acylation intermediate arachidonoyl CoA, suggesting that this was the means by which H2O2 inhibited acylation. Notably, H2O2 (0.03 to 3 mM) failed to stimulate macrophage PLA2 activity. We conclude that H2O2, in contrast to A23187 and zymosan, inhibits incorporation of AA into phospholipids, and that this represents the major mechanism by which the oxidant increases the availability of free AA for oxidative metabolism in the AM. This may be an important basis for release of eicosanoids in oxidant-induced inflammation and injury of the lung.


Localization of surfactant-associated proteins SP-A and SP-B mRNA in rabbit fetal lung tissue by in situ hybridization.

Pulmonary surfactant is a lipoprotein substance, comprised of approximately 80% phospholipid and approximately 10% protein, that lowers surface tension at the air-alveolar aqueous interface. Surfactant is synthesized and secreted by alveolar type II epithelial cells where it is stored intracellularly in lamellar bodies. In the present study, we used the technique of in situ hybridization to localize the mRNA for two surfactant-associated proteins, SP-A and SP-B, in developing rabbit fetal lung tissue. We found that SP-A mRNA was first localized in rabbit fetal lung alveolar type II cells on day 26 of gestation, the time at which lamellar bodies are first observed within fetal lung type II cells. On day 28 of gestation, a very small amount of SP-A mRNA was also detectable in the epithelial cells of some bronchioles. In neonatal and adult rabbit lung tissue, SP-A mRNA was primarily restricted to alveolar type II cells; however, the epithelial cells of some bronchioles contained small amounts of SP-A mRNA. SP-B mRNA was first detected in cuboidal epithelial cells in the prealveolar region of the rabbit fetal lung tissue on day 24 of gestation, i.e., at least 2 days before the appearance of SP-A mRNA and lamellar bodies within differentiated alveolar type II cells. SP-B mRNA was detected in most bronchiolar epithelial cells of the rabbit fetal lung tissue at day 28 of gestation.(ABSTRACT TRUNCATED AT 250 WORDS)


Localization of muscarinic receptor subtype mRNAs in human lung.

m2 mRNA in airway smooth muscle; m3 mRNA in airway epithelium, airway smooth muscle, and submucosal glands. No detection of m4 and m5 mRNAs was observed in any cellular structures. The presence of various muscarinic receptor subtype mRNAs was confirmed by Northern blot analysis. Only human lung mRNA hybridized to the m1 probe giving a single 3.2 kb transcript. mRNA from the human cultured airway smooth muscle cells gave m2 and m3 hybridization bands of about 6.0 kb and 4.5 kb, respectively, while mRNA from the cultured airway epithelial cells gave only m3 hybridization band of 4.5 kb. With the exception of the airway epithelium, there was a good correlation between the distribution of mRNAs by in situ hybridization and the distribution of receptor subtypes by autoradiographic mapping. These results may have an important clinical implication, and also give rise to further investigation of gene regulation of pulmonary muscarinic receptor subtypes in health and disease.


[Primary effect of carotid body stimulation on left ventricular inotropism in swine].

The cardiovascular response to carotid body stimulation has been a interesting and simultaneously controversial subject. In fact, several authors described different responses depending on the animal species used (cat, dog, rabbit, monkey), time of stimulation (short-term v. long-term) and experimental conditions and procedures. According to our experience, the response to carotid body stimulation with cyanide, in normal breathing dogs, consists in hyperpnoea, bradycardia with arterial blood pressure fall (by means of longer diastolic periods), followed by a marked rise in arterial blood pressure and heart rate, after curarization. Concerning the inotropic response to carotid chemoreceptors stimulation, there exists some controversial and even antagonic opinions. In fact, some authors describe a positive inotropic effect, others a negative inotropic effect, and others still defend no inotropic response at all. In the present work, the authors try to contribute to the solution of this problem, studying a group of animals (pig) anaesthetised with chloralose, in which the major modulators of the inotropic response to carotid body stimulation (ventilation; heart rate; and ventricular load conditions) were controlled. To the evaluation of cardiac contractile state, indexes derived from the systolic isovolumic phase were used (maximum left ventricular pressure, dP/dtmax; dP/dtmin) in all the animals. In some animals, other indexes were also used (Vmax, Vpm, (dP/dt)/DP40, Tau and PB). The authors concluded that, in the present experimental conditions, the primary response to carotid body stimulation, in the pig, includes a positive inotropic effect.


[Value of transesophageal echocardiography in the diagnosis of acute aortic dissection].

We describe our experience of six patients with clinical suspicion of acute aortic dissection (AAD) who were studied consecutively by transesophageal echocardiography (TEE) from April to July of 1991. All of them were previously submitted to transthoracic echocardiogram. The diagnosis was correctly established by TEE in five cases, confirmed by aortography and/or surgery (four cases), or by autopsy (one case). In one patient the diagnosis of AAD was excluded by TEE, and posteriorly by nuclear magnetic resonance. Four patients had a Stanford type A, and one patient a type B dissection. The site of entry was identified in three cases; the intimal entry tear of the type B dissection, not observed by TEE, was localized in the aortic arch by aortography. In three of the four type A dissection cases, a thrombus in the false lumen and an aortic regurgitation were found. No other noninvasive methods were used after the diagnosis of AAD by TEE. The surgical repair was successful in three cases, one of which, without previous necessity of aortography. In our experience, TEE increased extraordinarily the diagnosis efficacy of AAD, making possible an earlier therapeutic approach, and probably contributing to the improvement of the prognosis of this pathology.


[Influence of the use of Swan-Ganz catheter on the mortality from acute myocardial infarction].

to evaluate the statistical significance of the haemodynamic examination making use of the Swan-Ganz catheter (S-G) on the hospitalary mortality of patients (pts) with acute myocardial infarction (AMI). CONCEPTION: Not randomized, not controlled and retrospective study. Intensive coronary care unit (CCU). 2562 pts with AMI sequentially admitted to a CCU were studied. The 2562 pts were divided in two groups: Group A--involving 2117 pts not submitted to haemodynamic examination; Group B-constituted by 445 pts (17% of all pts) submitted to haemodynamic examination. All pts admitted to the study were distributed according to the four classes of Killip. The pts included in each Killip class were distributed by the groups A (not catheterized) and B (catheterized). Hospitalary mortalities of the pts included in the global A and B groups, and the mortalities of the patients included in the particular A and B groups in each Killip class were determined. To evaluate the statistical significance of the differences in distributions of the number of pts who survived and who died in each set of A and B groups square chi test was used. Values of p less than 0.05 were considered as statistical significant. The distributions of the pts who died and who survived during the stay in the hospital by the A and B groups, be it in the total group of patients be it in each Killip class, were not significant different (p greater than 0.05). The mortalities of pts with AMI submitted or not to haemodynamic examination with S-G catheter did not significantly differ even in each Killip class, which means that it was not demonstrated a benefit with the S-G catheter use in the pts with AMI. In the presence of this conclusion and considering that retrospective studies must be interpreted with circumspection, it seems necessary to accomplish a prospective randomized and controlled study for evaluation the risk/benefit relation of the haemodynamic examination with the S-G catheter in pts with AMI.


[Specifying for the general physician. Digitalis therapy in elderly patients].

The experimental and clinical evidence on the decreased efficacy of digitalis on old age are reviewed. The trials on the efficacy of digitalis on elderly in heart failure and sinus rythm, are analysed and we try to characterize the sub-group of responders. So we try to explain the criteria to choose the therapeutic dose, to avoid intoxication and to interpret the seric concentrations. We describe the pharmacocynetics of digitalis on old people on heart failure which can explain the susceptibility to intoxication. We reviewed the incidence of digitalis intoxication on old age and the difficulties on its recognition.


[Anomalous origin of the left coronary from the pulmonary artery in adults: diagnosis with bidimensional, pulsed and color Doppler echocardiography].

Anomalous origin of the left coronary artery (LCA) from the pulmonary trunk (PT) is an uncommon but frequently lethal congenital lesion of infancy. Clinically it may be difficult to distinguish from congestive cardiomyopathy, and the diagnosis is usually made by angiography. We describe the case of a 38 years old woman, in whom identification of this anomaly was achieved by 2D-Echo, pulsed Doppler and color flow mapping. She complained of fatigue, effort dyspnea and atypical chest pain. A II/VI systolic murmur at left sternal border was heard. There was cardiac enlargement on chest X-ray and ECG was suggestive of an old anterolateral myocardial infarction. The 2D-Echo study showed a dilated, poorly contracting left ventricle. A prominent right coronary ostium was recorded, but the LCA ostium could not be visualized. There was retrograde diastolic and systolic flow in proximal PT, where an anomalous vessel was seen in continuity with it by color flow mapping. Cardiac catheterization confirmed the diagnosis. The patient underwent successful reimplantation of the anomalous LCA, from the PT to the aorta. This case demonstrates usefulness of Echocardiography in the assessment of coronary artery anomalies.


[Ventilation in intensive care units].

In this article the author intends to make a review of the most important indications and aims of mechanical ventilation, and the repercussion of artificial ventilation over the different systems of the body. The main kinds of ventilators used for the management of the critically ill patient, connected to a ventilator are reviewed.


Cardiac function and Fourier phase data from simulated Wolff-Parkinson-White syndrome in a baboon model.

The diagnostic value of Fourier phase analysis and planar scintigraphy in Wolff-Parkinson-White (WPW) syndrome has been suspect. This study investigates phase analytical data from planar radionuclide ventriculography of six baboons with simulated WPW syndrome by means of implanted electrodes. An electrode in the atrium controlled the heart rate and a subsequent stimulation was delivered by electrodes placed at different sites on the ventricles, delayed to cause the characteristic delta wave of the WPW syndrome. Sensitivity for accurately-localizing variously-situated first points of activation (FPAs) from the Fourier phase images was found highest for premature right ventricular (RV) activation, and for atrioventricular (AV) delays around 125 msec. Other sites were subject to artifacts. Changes in cardiac function, phase delay, and histogram parameters were not statistically meaningful.


[Development of sound lateralization].

Perceptual sound lateralization is determined from differences in time and loudness of signals arriving separately at bilateral ears, with the time difference being the more important one. The author examined the development of sound lateralization using a self-recording device developed by Sato T, which measures the sensitivity of sound lateralization on the basis of time and loudness differences separately. Subjects were 59 children aged 2 to 18 years and 12 adults who were audiologically and neurologically normal. Sound stimulus was 500 Hz continuous band noise. (1) The testable rate was increased in children older than the age of 4, and all children over 7 years of age could be tested. (2) Children over 4 years of age could lateralize sound on the basis of time difference. Sensitivity to time differences improved rapidly, showing a steep curve, in children from the ages of 4 to 6, and then increased slowly until adulthood. (3) Sensitivity to loudness differences increased and the normal range distribution decreased with age. There is a possibility that children aged 4 can discriminate loudness difference almost as well as adults.


Tumor and organ biochemical profiles determined in vivo following uptake of a combination of radiolabeled substrates: potential applications for PET.

This paper describes a method which generates an in vivo metabolic profile of tumors and organ tissues derived from the tissue uptake of a combination of radiotracers. Metabolic substrates labeled with carbon-11, a positron-emitting radionuclide (T1/2 = 20.4 min) have been used to probe tumor metabolism in vivo using positron emission tomography (PET). Carbon-11 labeled radiotracers which have been used include alpha-aminoisobutyric acid (AIB), 2-deoxy-D-glucose (2-DG), and thymidine (TdR). This paper reports data on the tissue distribution of carbon-14 labeled analogues of AIB, 2-DG, and TdR. Tissue distribution studies were carried out in normal male Copenhagen rats, in rats bearing Dunning R3327G or R3327H prostatic adenocarcinomas, and in tumor rats that have been treated with difluoromethylornithine and methylglyoxal-bisguanylhydrazone, or with diethylstilbestrol. A combination of the tissue distribution data of these radiolabeled agents is used to provide a metabolic description of the state of a tumor or tissue in vivo. This approach to defining a tissue's biochemical profile may be useful for the assessment and prediction of a therapeutic response, even at low tracer concentrations in a tumor, and may be useful in relating the biochemical characteristics of one tissue to that of another.


[Development of human cerebellar granular layer: a morphometric study].

Development of the cerebellar granular layer, the external granular layer (EGL) and the internal granular layer (IGL), was studied morphologically to make complete serial sections of the brain from human fetuses ranging 12 to 40 weeks' gestation (WG). To examine the chronological changes and the regional differences, we measured the thickness of the layer microscopically among five different parts of the cerebellum: anterior lobe/hemisphere (AH), anterior lobe/vermis (AV), posterior lobe/hemisphere (PH), posterior lobe/vermis (PV) and flocculus (FL). EGL was the most superficial layer composed of densely packed undifferentiated cells. Its thickness showed little changes during the fetal period of 12-40 WG for all parts except FL where EGL was thicker than those in other parts and made a gradual attenuation with development. We noticed at least three stages in the fetal development of IGL: 1) the primary or undifferentiated stage (before 18 WG) when IGL was hardly distinguishable from the layer of immature Purkinje cells (PCL); 2) the secondary or intermediate stage (18 to 30 or 35 WG) when it was clearly visible and almost stable in thickness for all parts; 3) the tertiary or developing stage (30 or 35 to 40 WG) when it showed a dramatic increase in thickness as the formation of cerebellar folia was proceeding. During the intermediate stage the Lamina dissecans was observed between PCL and IGL typically in PH. Regional differences were detected in a period of transition from the intermediate to the developing stage among each part: the developing stage appeared earliest in AV and FL and latest in PH.(ABSTRACT TRUNCATED AT 250 WORDS)


Detecting coronary artery disease using SPECT imaging: a comparison of thallium-201 and teboroxime.

Thirty subjects underwent single photon emission computed tomography (SPECT) imaging with technetium-99m teboroxime (TEBO). Of these, 26 underwent thallium SPECT imaging and 25 underwent quantitative coronary arteriography (QCA). Twenty-one of the subjects underwent all three studies. SPECT images were reviewed by two independent observers blinded to the clinical data. Stenoses were considered significant if there was a greater than or equal to 50% diameter narrowing as defined by QCA analysis of the coronary arteriograms. The overall sensitivity and specificity was 78% and 78%, respectively, for thallium-201. The overall sensitivity and specificity for teboroxime was 72% and 80%, respectively. The results obtained for these two tracers were not statistically different. Some of the false-positive results obtained from teboroxime imaging appear to have been due to the 10-min acquisition protocol and can be reduced with the use of new software programs using a continuous 3-min acquisition and dipyridamole. Teboroxime's rapid biologic half-life allows completion of SPECT imaging within 60-90 min, compared with the minimum of 4 h required for thallium SPECT imaging.


[Time-course changes of regional cerebral blood flow by SPECT with N-isopropyl-p-[123I]-iodoamphetamine in childhood partial seizures].

Single photon emission computed tomography (SPECT) with N-isopropyl-p-[123I]-iodoamphetamine was performed twice at different times in 18 children suffering from partial seizures to evaluate the time-course changes of the hemodynamics in the focal region. Comparison of the 2 SPECT images revealed that a decreased regional cerebral blood flow (CBF) in the first was normalized in 4 cases (22.2%) and contracted in 7 cases (38.9%). The region of decreased blood flow in the second was contralateral to that in the first in 1 case (5.6%) and unchanged in 6 cases (33.3%). Most of the normalized and contracted cases were those in which clinical seizures disappeared and the EEG findings were normalized. In these cases which responded to treatment, the decreased regional CBF was also found to be improved. Repeated SPECT appears to be useful for evaluating the therapeutic efficacy. On the other hand, most of the unchanged cases were those in which clinical seizures were frequent or uncontrolled, or which persistently showed the abnormalities in their EEG. SPECT was considered to reflect well the conditions of the epileptic foci. These results indicate that repeated SPECT for observing the time-course changes of the regional CBF represents a useful technique with can be applied in evaluating the therapeutic efficacy or deciding the time to discontinue treatment and for pathogenetic elucidation of the epileptic foci.


Dynamic human glycogen and glucose metabolism detection utilizing in vivo 13C NMR.

The dynamic detection studies of glucose-glycogen metabolism of the human liver were performed with normal volunteers. A single tuned surface coil of 20-cm diameter was used for 13C (at 16.04 MHz). Natural glucose 100 g was administered for the natural abundance 13C MR dynamic study and 13C enriched (99%) 1-13C-D-glucose 1 g mixed 75 g glucose was administered to study the 13C enrichment effect. The total scan time of this dynamic study was 1 hr and each single scan time was 20 min. We did not use proton decoupling for the human 13C MR study. Localized (PRIME) proton shimming was performed and the shim value was less than 20 Hz. Glucose and glycogen spectra were clearly visible at 120 to 80 ppm and about 3 hr later both peaks almost disappeared. These data demonstrate that dynamic hepatic glucose-glycogen metabolism should be possible to detect which should allow for the direct diagnosis of hepatic glucose-glycogen metabolic disorders.


[A biochemical study of an animal model with defective muscle glycolysis, induced by iodoacetate administration].

A rat model produced by intraaortic injection of sodium iodoacetate was analyzed biochemically. Hind leg muscles obtained from iodoacetate-injected site showed a selective inhibition of the glyceraldehyde-3-phosphate dehydrogenase (G3PD) activity less than 10% of control mean. No loss of mitochondrial enzyme activity was observed. Electrical stimulation at the sciatic nerve revealed muscle contractures and this muscle showed a mild degeneration in histochemically. This study indicates that this model will be useful to study the pathophysiology of human muscle glycogen storage diseases.


Application of Hilbert transform to radionuclide-gated cardiac studies: analysis of asynchronous emptying and filling in various heart diseases.

Fourier phase analysis has generally been used to investigate asynchronous emptying and filling in various heart diseases. A potential limitation of this form of analysis is curve fitting error, since a truncated Fourier series may not adequately describe the shape of a time-volume curve (TVC) and thus may produce errors in indices calculated from the fit. To overcome this problem, we developed a new method using Hilbert transform. Using Hilbert transform, the instantaneous phase (IP) curve was calculated directly from the TVC obtained from multigated cardiac blood pool images. Four parameters [time to maximum IP [T(max)], time to 0 in IP[T(0)], time to minimum IP[T(min)], and time from 0 to minimum IP [T(min-0)]] were extracted from the IP curves for each pixel, and functional images were constructed in 40 patients with ischemic heart disease (IHD), 16 with hypertrophic cardiomyopathy (HCM), 3 with dilated cardiomyopathy (DCM), and 7 normal controls (N). The standard deviations (SD) of these parameters were then calculated for the left ventricle. In IHD patients with a left ventricle ejection fraction (LVEF) of less than 50% and in DCM, the SDs of all parameters were significantly higher than in group N. In IHD patients with an LVEF of greater than 50%, the SDs of T(min), T(0), and T(min-0) were significantly higher than in group N, but there was no significant difference in the SD of T(max). In HCM patients, the SDs of T(min) and T(min-0) were significantly higher than in group N, suggesting the presence of asynchronous filling. In conclusion, this method appears to be promising for the quantitative analysis of asynchronous emptying and filling in various heart diseases.


[A case of cervical myelopathy due to atlanto-axial subluxation with athetoid cerebral palsy].

We reported cervical myelopathy due to atlanto-axial subluxation of athetoid quadriplegia of cerebral palsy. This lesion was present from upper cervix to lower medulla oblongata, and appeared on MRI. The changes of sSEP was useful to evaluate his spinal function. We think that pediatricians need to understand this pathophysiology, particularly for multihandicapped children.