Hemicrania continua: a possible symptomatic case, due to mesenchymal tumor.

The case of a 28-year old woman with headache resembling hemicrania continua (HC) is described. Since her childhood she had a history of right-sided, side-locked, painful headache attacks, with increasing attack frequency during the last two years, each attack lasting around 24 hours. There were only a few "migrainous" symptoms and signs, thus no photo- and phono-phobia and no vomiting. Only occasionally did she have slight nausea. The clinical picture as well as the complete indomethacin effect suggested a case of HC. However, the indomethacin effect faded away after > 2 months. At that time, a CT scan revealed a tumor in the right sphenoidal bone involving the clinoid process and the base of the skull. A biopsy of the tumor during craniectomy showed a mesenchymal tumor, and the patient was considered inoperable (April, 1989). After cytostatic treatment, she is back in full time work; the headache disappeared and it still has not recurred after approximately 2 years of observation. Neuroradiological investigation should, therefore, be included in the work-up of patients with HC. At the present stage of knowledge, neuroradiological investigations should probably also be included when faced with a typical clinical picture.


Influences of female partner preference on potential reproductive outcome in Japanese macaques.

The immediate effects of female partner preference on male mating behaviors and its potential influence on male reproductive success and conception in the Japanese macaque (Macaca fuscata) were analyzed. Although male dominance interactions probably led to low-ranking males having more single-day consortships and high-ranking males more multi-day consortships, dominant males were unable to prevent females from mating with preferred subordinate males. Ultimately, there was no marked difference in the number of estimated offspring sired. Females chose not to mate with certain males and actively mated with others, suggesting that female partner preferences do affect conception. Evidence for this was found in paternity estimates, which reflected observed preferences for particular middle-ranking young adult males.


Capturing wild long-tailed macaques (Macaca fascicularis).

Long-tailed macaques (Macaca fascicularis Raffles, 1821) were captured at various locations in the north of Sumatra as part of a study on social behaviour and genetic relationships. We used individual cage traps, a group trap, a blowpipe and an air-pressure rifle. Provided that the monkeys were willing to take bait, individual cage traps proved most successful; they gave a high capture rate with minimal disturbance of the group. Success with young juveniles and peripheral animals could be improved by placing elevated traps in the centre and in clusters at the periphery of the trapping site. Trapping had no clear lasting effect on the natural behaviour of the animals.


Amazing grace: religion and identity among elderly black individuals.

A sample of forty-three "life stories" collected from elderly African-Americans residing in Southwestern Virginia is analyzed from the perspective of Continuity Theory. The focus is on the "theme" which religion plays as a bulwark of continuity in the lives of the respondents. The data reveal that religion serves at least seven significant and positive functions in the normal aging process of Black-Americans. As is customary, all names of respondents have been changed to protect their anonymity.


Older motorist yielding to pedestrians: are older drivers inattentive and unwilling to stop?

A field experiment investigated factors expected to influence yielding by motorists to a pedestrian waiting to cross a city street. One-hundred and sixty motorists passing through a marked crosswalk were participants. In addition, data were gathered on 120 baseline motorists who passed through the test intersection when a pedestrian was not present. A comparison of the age composition of the experimental sample with the baseline sample showed that the youngest group of drivers, i.e., under twenty-six years, was significantly more represented in the experimental sample and was more likely to stop for the experimental pedestrian than were motorists in other age groups. Contrary to a prediction that older motorists over age sixty-five would be less attentive to a pedestrian and, therefore, less likely to stop, this oldest group of drivers was not underrepresented in the experimental sample; i.e., their likelihood of yielding matched their likelihood of driving through the intersection. Further analysis, however, revealed that motorists over sixty-five years of age were significantly more likely than younger motorists to stop for a pedestrian who was conspicuously dressed (bright, highly visible clothing) and who was moving to cross the street rather than patiently waiting. Implications of these findings are discussed in terms of difficulties that older drivers have in judging the speed of moving objects in a traffic environment.


The accuracy of older and younger Australians' understanding of mental health and aging.

Inadequacies in contemporary mental health care for elderly individuals may come about partly through ignorance of both positive aspects of mental health in old age (e.g., the responsiveness of older clients to psychotherapy) and the negative aspects (e.g., elderly men's unusually high suicide risk). A quiz measuring knowledge of both kinds was administered to a total of 250 Australian men and women aged seventeen to eighty-one years who were either retired, employed, housewives, or university students. As hypothesized, the retired group scored lowest on the quiz, with no significant differences among younger students versus non-students. Age was found to be a more important mediator of the retired group's low scores than gender, living with an older person, or self-definition as retired versus employed or a housewife. A previous finding of higher scores by Australians than by U.S. undergraduates in an aging course was also replicated and extended to older nonstudent groups. Implications of these findings for mental health services for elderly individuals and for educational interventions to improve understanding of mental health in older age groups were considered.


Associations among healthy habits, age, gender, and education in a sample of retirees.

In this exploratory and descriptive study, data are drawn from a sample of 1,864 Bank of America retirees collected in 1987 to investigate correlations among healthy habits, age, gender, and education. Findings include: 1) Health habits are strongly and positively associated with each other and negatively associated with unhealthy habits. 2) Age is statistically significant and positively associated with fiber, fat consumption, and lack of exercise, but negatively associated with cigarette use. 3) Women are more likely than men to smoke, use seat belts, and eat foods high in fiber. Men are more likely than women to exercise and drink excessively. 4) Education is statistically significant and positively associated only with fiber in the diet and no other habit. 5) Fiber consumption emerges as the healthy habit most consistently associated with all other habits.


Personality and politics among older Americans: a rural case study.

This study examines personality factors as predictors of political attitudes and behavior among a sample of rural older Americans. Results indicate that trait variables (extraversion, openness, and neuroticism) and measures of self-concept (locus of control) affect political attitudes and behavior in predictable ways. Suggestions for future research are outlined.


Clinical pharmacokinetics of teicoplanin and aminophylline during cotreatment with both medicaments.

The influence of teicoplanin and aminophylline (theophylline ethylenediamine) on their mutual steady-state pharmacokinetics was studied in two parts, namely experimental and clinical studies. The concentrations of teicoplanin and aminophylline (theophylline) were evaluated at several times after intravenous administration of teicoplanin (3 and 15 mg/kg) and aminophylline (5 mg/kg) in 12 rabbits. Ten COPD patients were treated for 5 consecutive days with a short-term intravenous infusion of 240 mg aminophylline twice daily; ten more patients received for 5 days a short-term intravenous infusion of 200 mg teicoplanin twice daily. On the last day, blood samples were taken for teicoplanin and theophylline determination by means of the HPLC method. Subsequently, while aminophylline and teicoplanin were continued at the same dosage, the first ten patients received in addition a short-term intravenous infusion of 200 mg teicoplanin twice daily, and the second ten patients a short-term intravenous infusion of 240 mg aminophylline twice daily. After 5 days the serial assays of serum teicoplanin and theophylline were repeated. Our results demonstrated, in both experimental and clinical studies, no influence of theophylline on the steady-state pharmacokinetics of teicoplanin. Likewise teicoplanin had no significant effect on the steady-state pharmacokinetics of intravenous administration of theophylline in the form of aminophylline.


A return to infancy: old age and the second childhood in history.

Throughout Western history scholars and writers have characterized old age as a period of a second childhood and childish behavior. The second childhood stereotype has endured and finds expression in numerous works of literature, in a variety of historical contexts including ancient through contemporary times. Explanations for this stereotype were linked to the humoral theory of aging, the perceived and actual dependency of older people for care, dementia, and other ties between childhood and old age. The second childhood was also interpreted as a stage of life where the lifecycle returned to its beginning. The stereotype, while predominantly viewed as negative, may also be viewed in a positive light and underscores the duality and ambiguity that characterized the way older people have been viewed in Western history. The stereotype, while enduring, may have been more prevalent during certain periods, such as those periods when older people were devalued. Cultural representations and more importantly interpretations have also varied within historical context.


Tolerance of ofloxacin in the treatment of pulmonary tuberculosis in presence of hepatic dysfunction.

Twenty-nine patients with extensive pulmonary tuberculosis and drug-induced hepatitis were treated with ofloxacin along with other relatively non-hepatotoxic drugs, either during the interim phase to await recovery of liver function in some, or as definitive therapy as required by the compromised hepatic status of others. No adverse drug reactions were noted and no treatment failures were observed. This preliminary experience indicates the exceedingly good tolerance of ofloxacin when utilized in treatment of extensive pulmonary tuberculosis in the face of deranged liver function tests. Due to the small number of patients and numerous variables, no definite conclusion can be drawn on the specific efficacy of ofloxacin against Mycobacterium tuberculosis. However, it is concluded that acquisition of further clinical experience is warranted for similar patients.


A new theory about the ages of man.

Genetic psychologists who have long been studying the periods of growth in the ages of Man, endeavoring to determine their average durations, set the limits separating these periods empirically, and do not pursue their study beyond childhood and adolescence. In my book published in Paris (1986) I propound a new, radically different approach which takes into account Man's whole lifespan, without separating the various ages, and without separating old age from those that precede it. According to my theory, the Ages of Man, nine in number, all follow the same mathematical law, which determines their respective durations on the basis of a geometrical progression, ratio two. Their durations would be of three and six months for gestation, one, two, four, and eight years for childhood and early adolescence, sixteen for youth, thirty-two for adult maturity, sixty-four for old age. This amounts to a theoretical potential lifespan of 127 years.


Bioavailability of a new controlled-release oral naproxen formulation given with and without food.

The influence of concomitant food intake on the plasma concentration of naproxen given as a new controlled-release (CR) formulation (750-mg tablet) was investigated in a crossover study design. Twelve healthy volunteers received a single tablet of naproxen on two occasions separated by a 3-week washout period:- after an overnight fast and immediately after a standard meal. Plasma naproxen levels were measured through HPLC at intervals suitable for obtaining concentration-time curves of both regimens in the range 1--48 hours. It was found that average plasma AUC values were 1978.7 mcg.hr/ml in fasting participants and 1778.6 mcg.hr/ml in postprandial participants. The confidence interval computed by Westlake's method indicated equivalence of values. Food decreased the peak plasma concentration of CR naproxen by about 14%, but the confidence interval (+/- 22%) barely exceeded equivalence limits. There were no significant differences between fasting versus postprandial values for the mean absorption time, or plasma absorption and disposition half-lifes. It is concluded that the bioavailability of CR naproxen is not substantially altered by the ingestion of food.


T-cell alterations in immunoglobulin A nephropathy.

In the present paper are reported alterations of the cellular immunity found in 24 patients with immunoglobulin A nephropathy (IgAN). CD4+ and CD25+ cells were increased in patients in comparison with controls. The mean of interleukin-2 (IL-2) and interleukin-4 (IL-4) levels in sera were similar in patients and controls, but the levels of IL-2 in supernatants of stimulated peripheral blood mononuclear cells from patients were higher than those of controls. There were no correlations between renal function, serum IgA levels, urinary findings, cellular subsets, and IL-2 or IL-4 sera levels. These immunological data were also unrelated to the mode of clinical presentation. The results suggest a pivotal role of IL-2 in cellular immune response with regard to T-cell activation in patients with IgAN.


Central analgesic activity of ibuprofen. A neurophysiological study in humans.

Ibuprofen is a widely used non-steroidal anti-inflammatory drug (NSAID). Inhibition of prostaglandin biosynthesis is considered to be the main mechanism of action of this substance. Recently, a central analgesic activity was described in an experimental study. In order to explore the possibility that ibuprofen induces analgesia at central level in humans, we investigated, in a double-blind design, the effects of orally-given 600 mg granular ibuprofen or placebo on nociceptive flexion reflex in normal volunteers. Ibuprofen produced a significant increase, as compared to placebo, in the threshold of the nociceptive reflex. The ratio between subjective pain threshold (Tp) and reflex threshold (Tr) was unchanged after either ibuprofen or placebo administration, indicating that Tp strictly paralleled Tr. These results indicate that ibuprofen displays a central antalgic activity in humans. Different supraspinal structures are probably involved, but the exact mechanisms are still to be clarified.


Remission induction with carboplatin-epirubicin-prednimustine followed by consolidation radiotherapy in advanced ovarian cancer.

Adjuvant chemoradiotherapy was administered to 26 patients with stage Ic-IV ovarian cancer after radical cytoreductive surgery. All patients received six cycles of carboplatin, epirubicin, and prednimustine and had no clinical evidence of disease after completion of chemotherapy. They received whole-abdominal radiation and radiation to the retroperitoneal lymph nodes. This protocol was discontinued for five (23%) patients because of myelosuppression, progressive disease, or withdrawal. One patient had a small bowel obstruction due to intraperitoneal adhesions. The survival of ten stage-III ovarian cancer patients, who received chemoradiotherapy and were evaluable for assessment of treatment efficacy, was retrospectively compared with the survival of 11 stage-III patients who received chemotherapy only. At 36 months, a slight advantage of the chemoradiotherapy versus the chemotherapy-only group was observed (p = 0.11). These preliminary results suggest that adjuvant chemoradiotherapy may prolong the "no evidence of disease" interval of radically operated ovarian cancer patients. Toxicity is acceptable when second-look surgery is avoided and when subsequent radiotherapy is limited to patients with no evidence of disease.


The TATA-binding protein is a general transcription factor for RNA polymerase III.

The TATA-binding protein (TBP) is a principal component of the general factor TFIID and is required for specific transcription by RNA polymerase II. We have shown that TBP is also a general factor for RNA polymerase III.


Multiple effects on liver-specific gene expression in albino lethal mice caused by deficiency of an enzyme in tyrosine metabolism.

alf/hsdr-1 is a locus in the mouse defined by albino deletions to be essential for neonatal viability. Homozygous deletion of alf/hsdr-1 leads to a pleiotropic phenotype in liver and kidney, including impaired perinatal activation of hormone-dependent genes, and the induction of detoxifying enzymes and early-response genes. To elucidate the molecular basis of this complex phenotype, we have identified the gene mapping at alf/hsdr-1 by positional cloning, using overlapping albino locus deletions to define the location of alf/hsdr-1. The gene encodes fumarylacetoacetate hydrolase, FAH, an enzyme of tyrosine metabolism. Genetically determined FAH deficiency in man leads to a severe liver failure in infants. In mice, we find that the normal sites of expression of FAH correlate tightly with cell-types which display abnormalities in albino lethal mice. The identification of the Fah gene as a candidate for alf/hsdr-1 offers a novel explanation for the complex phenotype, one into which all aspects can be accommodated. The phenotype can now be understood as a sequence of responses to toxic electrophilic metabolites.


The role of the transcriptional activator protein DBP in circadian liver gene expression.

DBP, a liver-enriched transcriptional activator protein of the leucine zipper protein family, accumulates according to a very strong circadian rhythm (amplitude approx. 1000-fold). In rat parenchymal hepatocytes, the protein is barely detectable during the morning hours. At about 2 p.m., DBP levels begin to rise, reach maximal levels at 8 p.m. and decline sharply during the night. This rhythm is free-running: it persists with regard to both its amplitude and phase in the absence of external time cues, such as daily dark/light switches. Also, fasting of rats for several days influences neither the amplitude nor the phase of circadian DBP expression. Since the levels of DBP mRNA and nascent transcripts also oscillate with a strong amplitude, circadian DBP expression is transcriptionally controlled. While DBP mRNA fluctuates with a similar phase and amplitude in most tissues examined, DBP protein accumulates to high concentrations only in liver nuclei. Hence, at least in nonhepatic tissues, cyclic DBP transcription is unlikely to be controlled by a positive and/or negative feedback mechanism involving DBP itself. More likely, the circadian DBP expression is governed by hormones whose peripheral concentrations also oscillate during the day. Several lines of evidence suggest a pivotal role of glucocorticoid hormones in establishing the DBP cycle. Two genes whose mRNAs and protein products accumulate according to a strong circadian rhythm with a phase compatible with regulation by DBP encode enzymes with key functions in cholesterol metabolism: HMG-coA reductase is the rate-limiting enzyme in cholesterol synthesis; cholesterol 7-alpha hydroxylase performs the rate-limiting step in the conversion of cholesterol to bile acid.(ABSTRACT TRUNCATED AT 250 WORDS)


Developmental regulation of globin gene expression.

We have used the globin family of genes in chicken to study developmental regulation of gene expression, both at the level of individual interaction of trans-acting factors with local promoters and enhancers, and at the level of chromatin structure. Regulation of all members of the alpha- and beta-globin clusters is affected by the erythroid regulatory factor GATA-1. Separate mechanisms exist for regulation of individual members of the family. As an example, we describe the control mechanisms that play a role in the expression of the rho-globin gene, which is expressed only in primitive lineage erythroid cells. In addressing the involvement of chromatin structure in gene activation, we have examined the role of locus control elements, and also considered the way in which RNA polymerase molecules might accommodate to the presence of nucleosomes on transcribed genes.


cis and trans regulation of tissue-specific transcription.

Analysis of both the cis-regulatory sequences which control globin gene switching as well as the trans-acting factors which bind to these sequences to elicit a differential, developmentally regulated response has lent insight into the general mechanisms responsible for tissue-specific gene regulation. We show here that the chicken adult beta-globin gene promoter sequences are intimately involved in competitive interaction with the beta/epsilon-globin enhancer to regulate differentially epsilon- versus beta-globin gene transcription. Secondly, we show that the family of GATA transcription factors directs gene regulation in a variety of discrete cell types, and describe potential cellular target genes for each member of the GATA factor family, as well as potential mechanisms whereby multiple GATA factors expressed in a single cell might be used to elicit differential transcriptional activities.


The bicoid and dorsal morphogens use a similar strategy to make stripes in the Drosophila embryo.

The anterior-posterior (A-P) and dorsal-ventral (D-V) axes of the early Drosophila embryo are established by two key maternal morphogens: bicoid (bcd) and dorsal (dl), respectively. The bcd protein is expressed in a broad concentration gradient along the A-P axis, with peak levels present at the anterior pole, while dl is expressed in a gradient along the D-V axis with peak levels along the ventral surface. The two morphogens are unrelated and their gradients are formed by distinct processes. Nonetheless, we have obtained evidence that they generate sharp on/off stripes of target gene expression through a similar mechanism. Both morphogens establish overlapping patterns of transcriptional activators and repressors in the early embryo. The activators and repressors bind to closely linked sites within short (300 to 500 bp) target promoter elements that have the properties of on/off switches. The activators act in concert with the morphogen to define a broad region where target genes can be initiated. Borders of target gene expression are established by the repressors, resulting in the formation of stripes.


Transcriptional control by Drosophila gap genes.

The segmented body pattern along the longitudinal axis of the Drosophila embryo is established by a cascade of specific transcription factor activities. This cascade is initiated by maternal gene products that are localized at the polar regions of the egg. The initial long-range positional information of the maternal factors, which are transcription factors (or are factors which activate or localize transcription factors), is transferred through the activity of the zygotic segmentation genes. The gap genes act at the top of this regulatory hierarchy. Expression of the gap genes occurs in discrete domains along the longitudinal axis of the preblastoderm and defines specific, overlapping sets of segment primordia. Their protein products, which are DNA-binding transcription factors mostly of the zinc finger type, form broad and overlapping concentration gradients which are controlled by maternal factors and by mutual interactions between the gap genes themselves. Once established, these overlapping gap protein gradients provide spatial cues which generate the repeated pattern of the subordinate pair-rule gene expression, thereby blue-printing the pattern of segmental units in the blastoderm embryo. Our results show different strategies by which maternal gene products, in combination with various gap gene proteins, provide position-dependent sets of transcriptional activator/repressor systems which regulate the spatial pattern of specific gap gene expression. Region-specific combinations of different transcription factors that derive from localized gap gene expression eventually generate the periodic pattern of pair-rule gene expression by the direct interaction with individual cis-acting "stripe elements" of particular pair-rule gene promoters. Thus, the developmental fate of blastoderm cells is programmed according to their position within the anterior-posterior axis of the embryo: maternal transcription factors regulate the region-specific expression of first zygotic transcription factors which, by their specific and unique combinations, control subordinate zygotic transcription factors, thereby subdividing the embryo into increasingly smaller units later seen in the larva.


Cyclin A recruits p33cdk2 to the cellular transcription factor DRTF1.

Cyclins are regulatory molecules that undergo periodic accumulation and destruction during each cell cycle. By activating p34cdc2 and related kinase subunits they control important events required for normal cell cycle progression. Cyclin A, for example, regulates at least two distinct kinase subunits, the mitotic kinase subunit p34cdc2 and related subunit p33cdk2, and is widely believed to be necessary for progression through S phase. However, cyclin A also forms a stable complex with the cellular transcription factor DRTF1 and thus may perform other functions during S phase. DRTF1, in addition, associates with the tumour suppressor retinoblastoma (Rb) gene product and the Rb-related protein p107. We now show, using biologically active fusion proteins, that cyclin A can direct the binding of the cdc2-like kinase subunit, p33cdk2, to complexed DRTF1, containing either Rb or p107, as well as activate its histone H1 kinase activity. Cyclin A cannot, however, direct p34cdc2 to the DRTF1 complex and we present evidence suggesting that the stability of the cyclin A-p33cdk2 complex is influenced by DRTF1 or an associated protein. Cyclin A, therefore, serves as an activating and targeting subunit of p33cdk2. The ability of cyclin A to activate and recruit p33cdk2 to DRTF1 may play an important role in regulating cell cycle progression and moreover defines a mechanism for coupling cell-cycle events to transcriptional initiation.


SWI6 is a regulatory subunit of two different cell cycle START-dependent transcription factors in Saccharomyces cerevisiae.

Most genes involved in DNA replication in the yeast Saccharomyces cerevisiae are transcribed transiently during late G1 as cells undergo START. Their promoters all contain one or more versions of an 8-base pair motif (ACGCGTNA) called the MluI cell cycle box (MCB). MCBs have been shown to be both necessary and sufficient for the late G1-specific transcription of the TMP1 thymidylate synthase and POLI DNA polymerase genes. A different late G1-specific transcription element called the SCB (CACGAAAA) is bound by a factor containing the SWI4 and SWI6 proteins. We describe here the formation in vitro of complexes on TMP1 MCBs that contain the SWI6 protein and, we suggest, a 120 kDa protein that is distinct from SWI4. Transcription due to SCBs and MCBs occurs in the absence of SWI6 but it is no longer correctly cell cycle regulated. We suggest that SWI6 is an essential regulatory subunit of two different START-dependent transcription factors. One factor (SBF) contains SWI4 and binds to SCBs whereas the other (MBF) contains p120 and binds MCBs.


Transcriptional repression by methylation of CpG.

Methylated DNA in mammals is associated with transcriptional repression and nuclease resistant chromatin. In this review we discuss how these effects may be mediated by proteins that bind to methylated DNA.


Identification of Fos target genes by the use of selective induction systems.

c-Fos is a major component of the transcription factor AP-1 which has been implicated in the control of cell proliferation and differentiation as well as in transformation. In order to identify Fos target genes involved in these processes, we have taken advantage of the regulatory properties of the hormone-binding domain of the human estrogen receptor to develop transcriptional and post-translational induction systems, both of which allow selective elevation of Fos activity within a cell. Using this approach we have searched for Fos-responsive genes in rat fibroblasts and PC12 cells. Here we describe the identification and regulation of five Fos-responsive genes encoding a transcription factor (Fra-1), a secreted protein (Fit-1), a biosynthetic enzyme (ODC) and two membrane-associated proteins (annexin II and V), respectively. The post-translational induction system was also used to study the Fos-mediated block of neuronal differentiation of PC12 cells. These experiments demonstrate that Fos activity is dominant over NGF function and interferes with the expression of late NGF-inducible genes.


[Scleral erosion after surgery of retinal detachment disclosed by isolated corticodependent hyalitis. Apropos of 3 cases].

A chronic steroid-dependent hyalitis was the first sign of a transscleral erosion in three patients with severe myopia. This erosion was seen for more than 5 years after the procedure which consisted of a very tight scleral buckling with a 5 mm wide Lincoff sponge. Hyalitis disappeared in all three cases after removal of the material. In one case, the transscleral erosion was the cause of a recurrent retinal detachment. The sensitivity of hyalitis to oral steroid therapy suggests an immune process. Hyalitis in patients with a tight buckle must be cured by removal of the material.


[Spontaneous reattachment of retinal detachment caused by small atrophic holes].

Spontaneous retinal reattachment developed in 8 eyes with retinal detachments due to atrophic holes in lattice. The scar was characterized by massive proliferation of the pigment epithelial cells. The fundus changes were associated with an absolute scotoma of the corresponding visual field.


[Results of early treatment of congenital strabismus].

The authors analyse the results obtained after very early treatment of Esotropia in 38 children. These children were divided into 4 groups according to their age at the time of treatment. At the age of 30 months, they studied binocular vision, manifest latent nystagmus (NML) and dissociated vertical deviation (DVD). In groups 1 and 2, treatment was instituted before the age of 6 weeks (13 children) no DVD was noted, only one NML and 11 children have binocular vision. In groups 3 and 4, treatment was instituted after the age of 3 months (25 children) 4 cases of DVD and 10 of NML are noted, and only 9 children have binocular vision. In case of congenital esotropia, the authors recommend treatment before 2 months old to obtain a possibility of binocular vision and to decrease the risk of NML and DVD.


[Serous retinal detachment. Value of acetazolamide].

The effect of acetazolamide in the treatment of chronic macular edema has been well established. The pharmacologic action of this product suggested possible efficacy in the treatment of serous retinal detachment. We studied 38 patients presenting with serous retinal detachments of various etiologies divided into four groups: age related macular degeneration, central serous chorioretinopathy or diffuse epithelial retinopathy, epiretinal membranes, and other causes. Treatment with acetazolamide, at a dosage of 0.375 g/day, in three divided doses was proposed for five weeks. We observed a reduction of metamorphopsia in all cases, a stability or even an improvement of visual acuity, and a resorption of serous retinal detachment confirmed by decreased pooling of fluorescein on the angiographic examination. Considering each etiology, clinical and angiographic findings demonstrated the value of this treatment, although this study was not prospective. The encouraging results observed in many cases, raise hopes concerning the treatment for these diseases, usually not amenable to treatment.


[Stilling Duane syndrome and MRI: 2 preliminary results].

Dynamic mode magnetic resonance imaging (DMMRI) allows good visualization of the oculomotor muscles and allows their dimensions to be measured both when they contract and when they relax. The accuracy of this method has been checked and the measurements of the cross section of medial and inferior recti and of superior obliques can be considered to be valid. Measurements of length are inaccurate and the other muscles are not perpendicular to the sectional planes generally used in MRI of the head. By means of a fixation scale situated in the tunnel of the machine, the maximum diameter of medial recti in their thickest part was evaluated in two girls affected by a Stilling Duane retraction syndrome of the left eye. Two direction of the gaze were explored: 25 degrees at the right, then 25 degrees at the left, these angles being obtained by the fixation of particular points of the tunnel scale. The measurements have been made on axial sections, then on coronal sections, both medio-orbital and apical. The first finding is that the diseased medial rectus is much bigger than the healthy one. When relaxed, its thickness is about the same as that of the contracted normal muscle. Coronal orbital cross sections clearly show recession of the belly of the diseased muscle towards the back of the orbit. When contracted it stays in the apical plane and when relaxed in the medio-orbital plane. Lastly the relaxation is much weaker for the pathological muscle than for the healthy one.(ABSTRACT TRUNCATED AT 250 WORDS)


[Comparative results of flowmeter studies before and after urodynamic exploration].

Results of flowmeter studies in 145 patients before and then immediately after urodynamic exploration were unchanged in 80% of women and 72% of men. Abnormal results on flowmetric examination, detected in 18% of cases prior to urodynamic studies, were assessed as normal during follow-up urodynamic tests. These findings raise the question of the validity of flowmeter parameters determined during urethrocystometric exploration.


[Neuropathy due to stretching of the internal pudendal nerve and female urinary incontinence].

For many years, perineal neurogenic abnormalities associated with stress urinary incontinence have been described using electromyography examination, evoked potentials or neuromuscular biopsy. It has been suggested that the progressive denervation of the striated pelvic sphincter musculature that occurs in genuine stress incontinence is due to repeated stretch injury of the innervation of these muscles when the pelvic floor diaphragm is weak. New investigations such as perineal nerve motor latency confirmed this hypothesis. A real "perineal stretch neuropathy" may be described. It is very important to know about this neurogenic factor before considering rehabilitation therapy.


[Treatment of strictures of the male urethra by internal urethrotomy].

Seventy patients with urethral strictures underwent endoscopic urethrotomy in the Department of Urology of the Ionnina University Hospital since 1983. The mean age of the patients was 58 years and they were treated for single (53 cases) or multiple (17 cases) urethral strictures. The cause of stricture was traumatic, post-infections, iatrogenic (post-TURP or open adenomectomy) or unknown in 6, 21, 28 and 15 patients respectively. Good results were obtained after the first endoscopic urethrotomy in 36% of cases (25 patients), at 5 year follow-up. The success rate of repeated internal urethrotomies was satisfactory in 54% of cases (38 patients). Finally, 4 patients (6%) had 5 or 6 internal urethrotomies and many urethral dilatations and were then treated by urethrectomy followed by termino-terminal urethrraphy.


Proper use of gastrointestinal tract to achieve continent urinary diversion in 73 patients.

Different segments of the gastrointestinal tract have been used to reconstruct the bladder and all have been reviewed in regard to achieving urinary continence. In 53 patients with detubularized ileocecal cystoplasty, the continence rate, both during the day and night, was 88%, while 95% of the patients were continent during the daytime. In nine patients in whom an ileocecal continent reservoir was made, 100% had dry stoma on intermittent catheterization, both during the day and night. We conclude that detubularization of the right colon has a significant effect in achieving urinary control and making a good low pressure pouch. This has helped us to avoid conduits with their inherent problems. Also, the right colon by virtue of the ileocecal valve has good versatility for use in both anti-incontinence or anti-reflux procedures as needed.


Urethral instability after radical hysterectomy.

The incidence of urethral instability after total hysterectomy for cervical cancer was analyzed in 154 patients allocated to one of two groups according to the extent of vaginal resection. Evaluations were conducted during urodynamic exploration prior to and 1 year after surgery. Persistent instability of urethra at 1 year follow-up was noted only in the group in which the resection had involved 2/3rds of the vagina, 18% of these patients being assessed as possessing urethral instability. Variations in maximum pressure greater than 30 cm H2O resulted in major clinical and urinary disorders.


[Ureterovaginal fistulas: diagnosis and surgical tactic. Apropos of 19 personal cases].

Personal experience of the treatment of 19 ureterovaginal fistulae, observed from september 1987 to june 1991 on 17 patients in Africa is described and analysed. Occurring after gynecological or obstetrical surgery, the main cause is hysterectomy (82.3%). Elements for diagnosis were: the appearance of a urine leak, which in most cases came rapidly, echography, and most important, intravenous urography (IVU). Surgical management in all of the cases was mainly aimed at conservation. One end-to-end anastomosis and 18 cuff reimplantations were performed, combined in 2 cases with a sub-mucus tunnel (Politano), in 14 cases combined with a tubular Boari bladder flap (wherein 1 case was bilateral), 3 combined with a bladder psoas hitch and 2 with an isolated ileal graft (ileo-ureterocystoplasty). One case of vesicouterine fistula and 4 associated vesicovaginal fistulae benefited from a simultaneous surgical operation. In this study of 17 patients treated, except for one patient deceased 14 months following a neoplastic recurrence, the results were excellent. 16 patients were cured. Follow-up extended to more than a year and have shown the perfect conservation of the excretory ducts in all of the cases studied. The cuffed ureterovesical reimplantation combined with a tubular bladder plasty definitively seem to be a most reliable management technique for all ureter injury encountered. While allowing the preservation of the kidney located just below, it has, in particular, prevented ureter stenosis. If the use of simpler methods (psoas bladder hitch) may be sufficient for some cases, the use of more complex method (ileoureterocystoplasty) for other cases, may be indispensable.


[Gunshot wounds of the ureter].

Lesions of the ureter caused by penetrating wounds of the abdomen rare a are complication of abdominal gunshot wounds, of which the reported incidence is 2 to 17%. The preoperative diagnosis is difficult and unrecognized initially in every third case. There are no early clinical signs of ureteral lesions. There is often no hematuria. Only IVP can male the preoperative diagnosis possible. As a matter of fact, the diagnosis will often be established by the surgical exploration made during the laparotomy required by the extent of the associated lesions. The ureteral blast contusion is an important cause of secondary necrosis with fistula. The treatment is mainly based on ureteroureterostomy after debridement. The transanasmotic drainage of urine is controversial. Mortality results from associated abdominal lesions and morbidity consists in a risk of secondary nephrectomy.


[Tumor of the urinary tract and renal lithiasis. Apropos of 4 cases].

The authors present four observation of renal lithiasis associated with a tumor of the upper urinary tract. The rarity of this association and the facility to only consider lithiasis often conceal the tumor. They define the "high risk lithiasis" for which CT-scan is mandatory. Tumor of the urinary tract has to be treated and the prognosis becomes less favorable.


[Kidney carbuncle: diagnostic, bacteriological and therapeutic considerations. Apropos of 11 cases].

Renal carbuncle is a cortical lesion following bacteremia, occurring in patient without any urologic known problems. The analysis of 11 consecutive renal carbuncles showed that one should consider the diagnosis of renal carbuncle in young patients with flank pain, fever, and absence of significant leucocyturia. Our study confirms that renal carbuncle is always caused by staphylococcus aureus and that treatment is based on appropriate antibiotherapy. Isolation of the bacteria was difficult unless ponction of carbuncle under ultrasound control was performed. The usefulness of ultrasonography for the diagnosis of renal carbuncle and for its distinction from other suppurative renal lesions is emphasized.


Myocardial salvage after reperfusion. Observations from analysis of serial electrocardiographic and biochemical indices.

Careful assessment of the ECG and the release patterns of biochemical markers after established reperfusion has made it possible to relate the observed changes to the degree of myocardial salvage, left ventricular function, and clinical outcomes. These observations will become increasingly important in assisting the clinician to stratify patients into different prognostic categories during acute MI treated with thrombolytic therapy. In the future, risk stratification based on noninvasive indices provided by ECG and biochemical markers will aid physicians in optimally using thrombolytic therapy.


A statistical analysis of the ECG measurements used in computerized interpretation of acute anterior myocardial infarction with applications to interpretive criteria development.

Computerized interpretation of the electrocardiogram (ECG) for detection of acute myocardial infarction (AMI) has been an area of active investigation for the past few years. Advances in the development of criteria for increased accuracy have resulted through the use of clinically correlated databases. Previously, using such databases, the sensitivity for interpretation of AMI in the Marquette 12SL ECG analysis program has increased from 21% to 65% with specificity remaining unchanged (99%). This study attempted to find measurements of the QRS and ST-segment from 7 of the 12 standard ECG leads to increase the sensitivity of detection of anterior AMI to the level of a trained physician while maintaining the current level of specificity. Regression analyses were performed on the measurements to see which ones could improve sensitivity and what effect they had on specificity. There was no clear separation of the individual measurements between the normal database or the true positive and true negative anterior AMI databases for maintaining high specificity. In a parallel study of the same data, deterministic criteria combining both ST and T wave information increased the sensitivity of the 12SL analysis program for detection of anterior AMI to 71% on a clinically correlated anterior AMI database and 75% on a physician interpreted anterior AMI database while maintaining the specificity at 99%.


Assessment of diagnostic ECG results using information and decision theory. Results from the CSE diagnostic study.

Information and decision theory were applied to assess the interpretation results of 15 computer programs (9 electrocardiogram and 6 vectorcardiogram) and 9 cardiologists; 8 of whom analyzed the electrocardiogram and 5 the vectorcardiogram, using a database of 1,220 clinically validated cases. The study demonstrates that information content and utility indices, by providing a comprehensive view of diagnostic performance, can enhance the insight given by the more classic statistical performance measures.


Combination of diagnostic classifications from ECG and VCG computer interpretations.

The Common Standards for Quantitative Electrocardiography (CSE) study showed that the weighted combined diagnostic classification of a group of experts or a set of electrocardiographic (ECG) programs is superior to the average expert or program, and sometimes even better than the best expert. For that reason the authors investigated whether the combination of classifications from the authors' programs for ECG and vectorcardiographic (VCG) interpretation would deliver better results than either one separately. The CSE diagnostic database (n = 1,220) was used for testing purposes. Since the combination of computer interpretations from the ECG and VCG requires a separate and preferably simultaneous recording of the VCG, the authors also examined the combined interpretation of the ECG with a simulated VCG reconstructed from the eight independent leads of the 12-lead ECG (the rVCG). Besides that, the authors investigated the combined interpretation from all single beats of the dominant waveform from the same ECG recording (sECG). The performance of all combinations, that is, the ECG + VCG, ECG + rVCG, and sECG proved to be significantly better (74.2%, 73.6%, and 71.2%, respectively) than that of the ECG or VCG separately (69.8% and 70.2%, respectively; p < 0.001 for all cases). However, the difference in performance between the sECG and the VCG was not significant.


Should the JT rather than the QT interval be used to detect prolongation of ventricular repolarization? An assessment in normal conduction and in ventricular conduction defects.

It has been suggested that the JT rather than QT interval properly reflects repolarization duration in ventricular conduction defects (VCD). The authors examined the influence of QRS duration on the JT and QT intervals in 20,687 normal adult subjects and 2,865 subjects with various categories of VCD. Estimates for coefficients for multiple regression of QRS duration on QT and JT intervals combined with a correction term for heart rate (HR) were determined for each VCD category. QRS duration accounted for about 16% of total QT variation, but had a practically negligible effect on JT interval in complete bundle branch blocks. A single-parameter formula was derived for the JT prolongation index of the form JTI = JT(HR + 100)/518, with a JTI > or = 112 identifying repolarization prolongation in all VCD categories. It is concluded that it is preferable to predict JT rather than QT as a more appropriate index of duration of repolarization in VCD.


Quantitative assessment of 12-lead ECG synthesis using CAVIAR.

The objective of this study is to assess the performance of patient-specific segment-specific (PSSS) synthesis in QRST complexes using CAVIAR, a new method of the serial comparison for electrocardiograms and vectorcardiograms. A collection of 250 multi-lead recordings from the Common Standards for Quantitative Electrocardiography (CSE) diagnostic pilot study is employed. QRS and ST-T segments are independently synthesized using the PSSS algorithm so that the mean-squared error between the original and estimated waveforms is minimized. CAVIAR compares the recorded and synthesized QRS and ST-T segments and calculates the mean-quadratic deviation as a measure of error. The results of this study indicate that estimated QRS complexes are good representatives of their recorded counterparts, and the integrity of the spatial information is maintained by the PSSS synthesis process. Analysis of the ST-T segments suggests that the deviations between recorded and synthesized waveforms are considerably greater than those associated with the QRS complexes. The poorer performance of the ST-T segments is attributed to magnitude normalization of the spatial loops, low-voltage passages, and noise interference. Using the mean-quadratic deviation and CAVIAR as methods of performance assessment, this study indicates that the PSSS-synthesis algorithm accurately maintains the signal information within the 12-lead electrocardiogram.


Ventricular fibrillation detection using the evoked electrogram from the braided endocardial defibrillation lead.

Life-threatening consequences can be the result of inappropriate classification of ventricular fibrillation for patients with implantable cardioverter defibrillators. The objective of this study was to determine if analysis of the asynchronously paced evoked electrogram using the braided endocardial defibrillation lead could improve the detection of ventricular fibrillation. The depolarization portion of the evoked electrogram was integrated to obtain the paced depolarization integral. The results demonstrated that the mean of the paced depolarization integral, its SD, and the mean +/- SD were significantly different between sinus rhythm and ventricular fibrillation (p < 0.005, p < 0.05, p < 0.01, respectively). These results suggest that the paced depolarization integral obtained with the braided endocardial defibrillation lead could improve the specificity and sensitivity of ventricular fibrillation detection.


Detection of late potentials. Comparison of two commercial high-resolution ECG systems.

Signal-averaged electrocardiogram (SAECG) is used for detection of ventricular late potentials (LPs) in cardiac patients. As many commercial SAECG systems become available, it is essential to determine if they provide equivalent diagnostic information. Two high-resolution (Hi-Res) ECG systems (MAC-12, Marquette Electronics, Inc (MEI), Milwaukee, WI and LVP101, Arrhythmia Research Technology (ART), Austin, TX) were tested on 143 subjects (13 controls and 130 cardiac patients, 21 of whom were tested for inducible ventricular tachycardia [VT]). Late potential measurements (total QRS duration, high-frequency low-amplitude signal duration, and root-mean-square voltage) obtained from the two systems were in good agreement in most of the controls and patients. Application of Multicenter criteria for the MEI system and Gomes criteria for the ART system yielded very good agreement in LP diagnosis (at least 2 parameters abnormal). The two Hi-Res systems predicted inducible VT with good accuracy. The MEI system gave slightly higher sensitivity (90% vs 70%) and specificity (91% vs 82%) than the ART system in patients tested for inducible VT. In controls, both systems gave the same specificity (92%) and the LP diagnosis agreed in all controls (100%). Although the number of patients was small, neither sensitivity nor specificity were significantly different between the two systems at p < 0.05. To conclude, MEI and ART Hi-Res systems gave very similar LP diagnoses when appropriate criteria were applied.


Validation of an adaptive software trigger and arrhythmia diagnostic algorithm.

The authors have developed an algorithm for the identification of arrhythmias using intracardiac atrial and ventricular leads. The algorithm is based on the rate of the depolarizations and a measure of the organization of electrical activity in each of the cardiac chambers. The most important requirement of the algorithm is to identify the occurrence of each cardiac event correctly. A robust amplitude-adaptive software trigger is developed, which accurately detects depolarizations in both chambers. With this reliable trigger the authors demonstrate the veracity of the arrhythmia identification algorithm.


Evolution of an automated ST-segment analysis program for dynamic real-time, noninvasive detection of coronary occlusion and reperfusion.

Patients in whom early and stable reperfusion through the infarct artery fails after thrombolytic treatment might benefit from further revascularization therapy. A reliable noninvasive technique able to detect both reperfusion and reocclusion would be useful to test this hypothesis. However, no such technique presently exists. ST-segment recovery analysis using continuous digital 12-lead ST monitoring has been shown to be an accurate predictor of infarct artery patency in real time. This method was dependent on a trained clinician's analysis of the recordings on a personal computer. For optimal bedside application, salient principles of this ST-segment recovery analysis were converted into algorithms and built into the ST monitor software. The essentials of these algorithms are described in this report.


Advanced time-frequency methods for signal-averaged ECG analysis.

Frequency-domain techniques have been extensively investigated for the analysis of high-resolution electrocardiograms (ECGs), although the merit of frequency-domain analysis is still subject to controversy. Time-frequency analysis methods, which estimate the frequency content of a signal as a function of time, potentially provide even more information for improved ECG analysis. Some researchers report impressive results in predicting the outcome of electrophysiologic studies using the short-time Fourier transform (spectrogram). Other time-frequency representations, such as the Wigner distribution, short-time spectral estimators, and the wavelet transform, have also been investigated. The authors present a unified overview of time-frequency representations, showing that only four classes characterize most time-frequency representations. The authors describe the advantages and drawbacks of the various approaches and speculate on their promise for ECG analysis. Very preliminary experiments in applying some of these techniques to the prediction of the outcome of electrophysiologic studies have suggested some possible new research directions.


Karhunen-Loeve representation of ECG data.

Quantitative representation of mathematical functions or random data provides a useful and often necessary step for analyzing complex physical or physiological phenomena. In general, the representation process converts complex functions or observations into weighted combinations of simple, elementary components. Rationale for use of representation lies in the simplification of restructuring the original functions or data in terms of these basic elements, which can facilitate understanding or analysis of the phenomena under study. Representation provides a basis for feature extraction in classification problems, filtering for noise reduction, and information assessment. In this paper the author describes some of the classical representation methods and demonstrates specific implementation of the statistical representation of electrocardiographic data using the Karhunen-Loeve method.


Risk assessment of future myocardial infarction from automated serial ECG analysis.

From 1980 to 1990 a cohort of 7,542 employees took part in the MARISK study. This study was designed in order to explore the utility of computerized electrocardiographic (ECG) measurements for predicting future myocardial infarction. After an initial period of annual examinations, follow-up information was collected by mailed questionnaires and obtained from 89.3% of all study participants with a median follow-up time of more than 7 years. Eighty-three participants suffered from myocardial infarction during the course of the study. Multivariate logistic regression analysis revealed that automated ECG measurements contribute significant additional information to risk estimates obtained from classical risk factors. Serial ECG analysis yields stronger risk indicators than single measurements. Results are represented via receiver operating characteristic (ROC) curves and regression coefficients, which can be used in independent applications. The results of this study indicate that it is useful to include automated serial ECG analysis in cardiovascular screening programs. It still has to be evaluated whether successful preventive measures may be based on such screening programs.


Robust adaptive parameter estimators in arrhythmia detection.

The authors consider the statistical analysis of threshold crossing intervals, as applied to estimation of tachycardia rates from intracavitary electrograms. The authors developed a class of robust algorithms designed to produce minimum variance estimates for tachycardia rates. The authors formulated the algorithms using order statistic filters, and obtained the minimum variance unbiased order statistic estimator. The potential gain in efficiency achieved by this approach is demonstrated via a representative example. The results indicated that the order statistics operator can produce dramatic reductions for typical errors in error variance as compared to linear estimators.


Problems in measuring heart rate variability of patients with congestive heart failure.

Heart rate variability (HRV) has become an important noninvasive measure of the integrity of the autonomic nervous system in various disease states. The power spectrum of HRV is a means to separate the instability oscillations of the various feedback mechanisms that contribute to cardiovascular homeostasis. The reliability of HRV data is largely unexplored. The day-to-day correlations in the low and mid-frequency components of HRV spectra average 91%, and that of the high-frequency component averages 81%. The correlations among spectral and nonspectral measures of HRV (SD) for the same data segment average 50-60%, suggesting that they encode similar information. Heart rate variability spectra exhibit diurnal variation consistent with physiologic expectation: respiratory sinus arrhythmia (thought to be mediated by parasympathetic tone) and to a lesser extent, the low-frequency spectral component (thought to be of mixed sympathetic-parasympathetic origin) are higher at night than in the daytime; the mid-frequency component (associated with the baroreflex, which is more excited when the patient is upright) is slightly higher during the daytime. Increased frequency of ectopic beats, such as occurs in congestive heart failure, reduces the reliability of the power spectrum since the number of usable data segments falls off rapidly with even small increases in rate of ectopy, and the variance of the estimate (in the method of averaged periodograms) is inversely proportional to the square root of the number of data segments. Using shorter data segments increases the number of segments available, but reduces resolution. Interpolation over ectopic beats (by either linear or cubic splint interpolation) increases the apparent power in low frequencies.(ABSTRACT TRUNCATED AT 250 WORDS)


Details of a real world implementation of Fourier techniques for power spectral analysis of heart rate variability.

A software package designed to perform a power spectral analysis of heart rate variability for Holter data is presented. The implementation is for the SpaceLabs Medical FT series 386/486-based Holter analysis workstation (Redmond, WA). The package is designed to allow rapid assessment of both short-term and long-term fluctuations in the heart rate spectrum. The package can be used to make a variety of spectral measurements of heart rate variability.


Autoregressive spectral models of heart rate variability. Practical issues.

Autoregressive time series model-based spectral estimates of heart period sequences can provide a parsimonious and visually attractive representation of the dynamics of interbeat intervals. While a corollary to Wold's decomposition theorem implies that the discrete Fourier periodogram spectral estimate and the autoregressive spectral estimate converge asymptotically, there are practical differences between the two approaches when applied to short blocks of data. Autoregressive spectra can achieve good frequency resolution and excellent statistical stability on short segments of heart period data of sinus origin. However, the order of the autoregressive model (number of free parameters to be estimated) must be explicitly chosen, a decision that influences the trade-off of frequency resolution with statistical stability. Akaike's Information Criterion (AIC), an information-theoretic rule for picking the optimum order, is sensitive to the aggregate amount of data in the analysis. Thus, the best model order for estimating the spectrum of a 4-minute segment of data will generally be lower than the best order for estimating an hourly spectrum based on averaging 15 4-minute spectra. A major advantage of the autoregressive model approach to spectral analysis is the ease with which it can be extended to handle messy data frequently seen in heart rate variability studies. A number of autoregressive-based robust-resistant techniques are available for the analysis of heart period sequences that contain a high volume of nonsinus and other unusual beats intervals. A theoretically satisfying framework is also available for spectral analysis of unevenly sampled data and missing data.


Comparison of autoregression and fast Fourier transform techniques for power spectral analysis of heart period variability of persons with sudden cardiac arrest before and after therapy to increase heart period variability.

Clinical studies have used two types of analysis of the power spectral estimates of heart period variability: autoregressive and fast Fourier transform techniques. Controversy exists regarding which method is the most valid. The specific aims of this study are: (1) to describe the power spectra of heart period variability before and after an intervention designed to increase heart period variability in persons after sudden cardiac arrest; (2) to compare the integral of power spectral density between autoregressive and fast Fourier transform techniques within low and high-frequency bands; (3) to compare the magnitude of the spectral peak values determined by autoregressive and fast Fourier transform techniques approaches within low and high-frequency bands; and (4) to compare the aforementioned parameters using 4-minute, 1-hour, and 24-hour blocks of heart period data. Results indicated high correlations between spectral estimations by autoregressive and fast Fourier transform techniques using integrals or peak values within either the low or high-frequency ranges. The autoregressive technique demonstrated better resolution of sharp peaks than the fast Fourier transform technique, and makes a smoother, more interpretable curve. Lastly, people can cognitively change their heart rate variability.


The significance of lead strength on ST changes during treadmill stress tests.

The contribution of relative lead strengths to ST depression during exercise was evaluated in 334 patients who had both a treadmill stress test and an angiogram. Patients were referred for exercise testing for the evaluation of suspected or known coronary artery disease. This was accomplished by comparing the magnitude of ST-segment depression to a constructed ST/R ratio. Using a cutoff of 0.1 for the ST/R ratio, the data were compared to the sensitivity and specificity of the 1 mm criteria for ST depression. There was only a slight increase in sensitivity (59% vs 63%) and specificity (60% vs 78%) for the ST/R ratio in comparison to the standard ST depression. However, when these two criteria were reevaluated for patients with less than or equal to 10.0 mm of R wave amplitude, the 0.1 ST/R ratio had a small decrease in specificity (94% vs 80%) when compared to 1 mm of ST depression and a marked increase in sensitivity with 31% for the standard ST depression and 82% using the ST/R ratio. In those with an R wave greater than 20 mm, 1 mm of ST depression was much more sensitive than the ST/HR ratio (95% vs 59%), but the ratio was more specific than the conventional ST depression (78% vs 59%). It is concluded that ST depression should be corrected for R wave amplitude in patients with R waves less than 10 mm and over 20 mm.


Effect of measurement interval on performance of the ST integral for the identification of three-vessel coronary disease.

Measurement of the ST integral has usually incorporated ST-segment depression integrated between the J point and 80 ms after the J point (J + 80). To assess the effect of varied onset and offset of ST measurement on performance of the ST integral for the identification of three-vessel coronary disease, the exercise electrocardiograms (ECGs) of 60 patients with angiographically proven coronary disease were analyzed using J point or J + 20 onsets and J + 60 or J + 80 offsets of ST integral calculation. Simple ST-segment depression of greater than 200 microV, measured at 60 ms after the J point, identified three-vessel disease with a specificity of 68% (17 out of 25 patients) and sensitivity of 69% (22 out of 35 patients). At a matched specificity of 68% (17 out of 25 patients), there was identical sensitivity (54%, 19 out of 35 patients) of ST integrals measured either from the J point to J + 80, from the J point to J + 60, or from J + 20 to J + 60. A trend toward increased sensitivity (60%, 21 out of 35 patients) when the ST integral was measured from J + 20 to J + 80 did not reach statistical significance, and comparison of receive operating characteristics (ROC) curves demonstrated that varying the onset and offset of ST-segment measurement had no significant effect on the overall performance of ST integral criteria for the detection of three-vessel disease.(ABSTRACT TRUNCATED AT 250 WORDS)


Filters for the reduction of baseline wander and muscle artifact in the ECG.

Contamination of the electrocardiographic (ECG) signal by extraneous electrical potentials is a significant problem in exercise electrocardiography. Baseline wander and muscle artifact are particularly troublesome sources of interference. This paper describes two digital filters that were constructed and found effective in reducing these two types of signal contamination. The baseline wander filter presented here is a linear phase high-pass filter having a cutoff frequency lower than the heart rate. The low computational overhead makes this filter practical for multiple channel implementation on a low-cost digital signal processor. Because the muscle artifact signal, generated by skeletal muscle activity, occupies the same spectrum space as the heart-generated signal, spectral filtering is not very effective in eliminating it. Described here is a time-varying filter that employs a combination of linear and nonlinear filtering techniques.


Prediction of severe coronary artery disease using computerized ECG measurements and discriminant function analysis.

This study tested the hypothesis that discriminant function analysis of clinical and exercise-test variables including computerized ST measurements could improve the prediction of severe coronary artery disease. Secondary objectives were to demonstrate the effect of digoxin and/or resting electrocardiographic (ECG) abnormalities, and to evaluate the relative importance of ST measurements made during the recovery phase and in the three lead group areas. The design was a retrospective analysis of data collected during exercise testing and coronary angiography. The ECG data were gathered and stored in digital format on optical discs and all ST measurements were made off-line using the authors' own software. Univariate and multivariate analytic methods were used to analyze all pretest characteristics as well as hemodynamic and computerized ECG responses to exercise. A 1,000-bed Veterans Affairs Medical Center served as the setting. The study included 446 male veterans who underwent a sign or symptom limited treadmill exercise test and coronary angiography. Analysis was also performed on a subset of this population formed by excluding patients receiving digoxin or with resting ECGs exhibiting left ventricular hypertrophy or ST depression (n = 328). In the total study population, the authors derived a treadmill score using discriminant function analysis. This score included: (1) the time-slope area in lead V5 during recovery; (2) delta heart rate; (3) angina pectoris during the exercise test; and (4) presence of diagnostic Q waves on the resting ECG. This score was effective in predicting triple vessel/left main disease and outperformed exercise-induced ST depression for predicting severe coronary artery disease. After exclusion of patients with ECGs exhibiting left ventricular hypertrophy or resting ST depression and patients receiving digoxin, discriminant function analysis chose: (1) the time-slope area in lead V5 during recovery and (2) delta heart rate. Exclusion of these patients resulted in a nonsignificant decrease in specificity of all ST criteria. ST-segment amplitude or slope in lead V5 at 3.5 minutes in recovery clearly outperformed the maximal exercise measurements in both groups. Summing the depressions or selecting the most depression in the three areas (ie, lateral-V5, inferior-II, anterior-V2) did not improve test performance. Leads other than V5 did not contain significant diagnostic information. A quantitative approach to exercise testing using discriminant function analysis enhanced the tests' performance for predicting severe coronary disease. The inclusion of patients taking digoxin or with resting ECG abnormalities nonsignificantly decreases the specificity of all ST criteria.(ABSTRACT TRUNCATED AT 400 WORDS)


Description of cardiac sources in anisotropic cardiac muscle. Application of bidomain model.

If the anisotropy ratios of the inner and outer domains of the myocardium are equal, then the volume distribution of cardiac sources can be replaced by an appropriate double layer on the heart surface. For an intramyocardial electrode there is an additional term proportional to the transmembrane potential.


Propagation of activation in cardiac muscle.

The hypothesis of local circuit current flow underlying propagation of activation in cardiac muscle has been extensively documented by one-dimensional and two-dimensional simulation studies. The assumptions of spatially uniform membrane capacitance and membrane ionic properties yield simulation results that are in good agreement with experimental observations in healthy cardiac muscle, thereby indicating that differences in propagation velocity and action potential upstroke between longitudinal and transverse directions can be explained solely on the basis of anisotropic intercellular coupling. Two-dimensional model studies of anisotropic propagation have also stressed the more efficient charging of the membrane capacitance and higher safety factor of propagation in the transverse direction. These conditions favor the occurrence of longitudinal unidirectional block and the initiation of reentry via transverse propagation. The authors simulated rotating waves initiated by properly phased transverse and longitudinal plane waves in a two-dimensional sheet model. Sustained propagation requires a minimum anisotropy ratio, corresponding to a velocity ratio of about 4:1. It was found, for uniform anisotropy, that the central focus wandered slightly. A higher anisotropy ratio favors a more stable rotating pattern and a more restricted movement of the central focus.


Implicit and explicit constraints in inverse electrocardiography.

This paper reviews the major distributed source models that have been postulated over the years to support the interpretation of observed body surface potentials: double-layer models, the source description in terms of epicardial (ie, pericardial) potentials, and its equivalent: the distributed monolayer. This includes a presentation and discussion of a source model that has been developed over the past decade: the uniform double-layer model. The properties of this model are contrasted to those of other distributed source models from the perspective of their inherent capacity for imposing the constraints that are essential for regularizing the involved inverse problem.


Parallel computation of ECG fields.

A parallel implementation of a finite difference model for computing the electric field of cardiac sources is presented. On a relatively inexpensive SIMD parallel computer, a full-forward solution is obtained in minutes, using accurate thoracic detail including anisotropy if required. Because the computation is based on a volume grid with constant size voxels, it readily accepts anatomical data from classified magnetic resonance imaging scans. By using a variation of the colored successive over-relaxation iteration, our finite difference model takes full advantage of the performance of massively parallel computers. Evaluations of the accuracy and performance of the model show the practicality of using specific anatomical models to recover the electrocardiographic field distributions for individual subjects. A relatively modest parallel machine is capable of assembling and computing a specific direct inverse solution from body surface potentials within an hour of measurement, assuming the magnetic resonance imaging classification has been previously completed.


n-3 fatty acids: biochemical actions in cancer.

A number of reports indicate that fish n-3 PUFA inhibit the development, growth and progression of several experimental tumors. There emerges a pattern of complex and diverse biochemical actions of n-3 PUFA in different animal tumor models, from the studies undertaken to date to evaluate the underlying mechanisms. These findings, along with the recent epidemiological evidence of an inverse correlation between fish intake and incidence of some human cancers, makes it worthwhile to determine the role of n-3 PUFA in cancer.


Bioavailability and biological activity of L-ascorbic acid 2-O-alpha-glucoside.

AA-2G is a new stable derivative of AsA which is efficiently synthesized by regioselective transglucosylation with alpha-glucosidase and CGTase. AA-2G serves as a vitamin C supplement in experimental animals. AA-2G is easily hydrolyzed in vivo by alpha-glucosidase and also synthesized as a metabolite under some specified conditions. AA-2G stimulates collagen synthesis in cultured fibroblasts and enhances antibody production in cultured splenocytes. AA-2G which has no cytotoxicity is a promising AsA derivative for medical and nutritional uses.


Recommended dietary allowance: support from recent research.

Increasing evidence is accumulating that a synergistic role of the so-called antioxidant vitamins (C, E, beta-carotene) may have a dominant role in the prevention of cancer, cardiovascular diseases and cataract formation. Controversy still exists regarding the optimum intake of vitamin C. This is partly due to lack of accurate and easily accessible health-relevant end-points, and lack of knowledge of the role of vitamin C in biochemical functions. Today, it is clearly recognized and broadly accepted that optimal health is a consequence of dietary optimization. Attainment of optimal health rather than prevention of deficiency symptoms is the goal. There can be little doubt that in this respect the requirements for vitamin C are greater than the amount required for the mere prevention of overt or classical scurvy. The recommendation of varying levels of requirement could overcome the controversy. The following is therefore proposed: The lowest level is that value which prevents deficiency symptoms. The second level is valid for healthy populations (< 200 mg/d). This level would take into account needs which differ according to age, sex, physical activity, physiological status (e.g. pregnancy or lactation) and environmental factors such as smoking, pollution and alcohol intake. Finally, a third level should be determined for the prevention of the above-mentioned non-communicable diseases. These diseases are an important cause of disability, resulting in costs of billions of dollars annually in medical costs. Many of the above-mentioned diseases can be prevented by supplementation with vitamin C. Medical costs could thereby also be dramatically reduced.


Prevention of aortic calcification in patients on hemodialysis by long-term administration of vitamin E.

The effects of vitamin E on the progress of atherosclerosis in patients on hemodialysis was investigated clinically using ACI. There was a significant suppression of the increase in ACI in group A, compared to group B, at the time of observation in each year. On the other hand, no significant changes were noted in BWD, CTR, BP and blood chemical examination, except that the level of MDA was significantly decreased in group A as compared with that in group B 4 years later. Since ACI is an index representing atherosclerosis, the results of this study seemed to suggest that the progress of atherosclerosis was suppressed by long-term administration of vitamin E in patients on hemodialysis.


Alpha-tocopherol: a potent inhibitor of platelet adhesion.

Administration of vitamin E in doses of 400 IU/day exerts a potent inhibition of platelet adhesion as measured in a laminar flow chamber. Adhesion to all surfaces tested was reduced and appeared to be related to a limited pseudopodia formation in alpha-tocopherol-enriched platelets.


Atherosclerosis from a viewpoint of arterial wall cell function: relation to vitamin E.

Vitamin E affects many key events in atheromatous lesions. Inhibition of EC injury and platelet aggregation was already reported. Foam cell formation must be inhibited according to the data presented by us and other speakers. However, effects on cell proliferation of SMC are paradoxical. The in vivo effects will be dependent on the effective concentration of vitamin E in the loci.


Aspartate aminotransferase of E. coli: effects of site-directed mutagenesis on substrate recognition.

R292 is crucial for both the binding and the catalysis of the transamination reaction of dicarboxylic acid substrates. Substitution of R292 to uncharged residues greatly enhanced the catalytic efficiency of transamination of neutral amino acids without any effect on the binding. Residues at position 292 may not be involved in recognition of the neutral side chain. The indole ring of W140 not only regulates the rotational movement of the coenzyme ring during catalysis, but it also may be involved in binding the carboxyl side chain of dicarboxylic substrates. The phenol group of Y70 is essential for the stabilization of the transition states with all substrates. Benzene ring at position 70 is necessary to recognize the glutamate-2-oxoglutarate substrate pair.


Aging of the brain and vitamin E.

Using a recently-developed membrane lipid peroxidation (MLP) system, we demonstrated the important role of vitamin E in the prevention of MLP and the possible relationship between MLP and pathogenesis of Parkinson's disease.


Endogenous arginine-specific ADP-ribosyltransferases and target proteins.

We investigated vertebrate arginine-specific ADP-ribosyltransferases and target proteins for the enzyme. ADP-ribosyltransferase found in each organelle ADP-ribosylated preferentially an endogenous acceptor protein co-localized with the enzyme. We propose that the ADP-ribosylation of tissue-specific target protein by the endogenous ADP-ribosyltransferase may participate in the regulation of cellular processes, including signal transduction.


Biomodulators of glucocorticoid: amplifiers and suppressors of glucocorticoid action.

We have found several compounds that specifically modulate the action of glucocorticoid in vivo and in vitro without themselves having any glucocorticoid-like action and have proposed the concept of "Glucocorticoid Action Biomodulators". These biomodulators consist of "Glucocorticoid Sensitivity Amplifier" (GSA), "Glucocorticoid Potency Amplifiers" (GPAs), and suppressors of glucocorticoid action. GSA increased the incorporation of glucocorticoid into the liver and its binding to cytosol receptor without changing the total receptor concentration in liver cytosol and the equilibrium constant of the glucocorticoid binding reaction. GPAs, potent activators of protein kinase C, markedly enhanced the glucocorticoid action and the glucocorticoid action was inhibited by the inhibitors of protein kinase C. H-7, an inhibitor of protein kinase C, inhibited the translocation of glucocorticoid-receptor complex into nuclei without affecting the extent of phosphorylation of glucocorticoid receptor. These findings suggest that GPA(s) and the suppressors modulate some protein(s) which regulates the translocation of glucocorticoid receptor into nuclei.


Vitamins and carcinogenesis: an overview.

The pathophysiology of carcinogenesis as a multistage process has been reviewed and the rationale for the action of vitamins and biofactors has been presented. This overview will now be followed by presentations of the actions of retinoids, carotenoids, vitamin D and marine natural products by other members of this Symposium.


Carotenoids in cancer chemoprevention and therapeutic interventions.

Carotenoid (CARs: beta-carotene BC and/or canthaxanthin CX) supplementation have been shown to be chemopreventive in animals, since 1980, against direct or indirect chemical carcinogenesis/photo-carcinogenesis of the skin, breast, stomach, salivary glands, colon-rectum, urinary bladder, and against transplanted tumors. This action could be either independent of or dependent on pro-vitamin A activity of BC. In vitro, both BC and CX proved to be antimutagenic and to have anti-malignant transformation properties in cell cultures. Preliminary interventions in humans with BC +/- CX prevented the onset of second primary tumors in lung, colon, urinary bladder, and head and neck. The powerful antioxidant properties of CARs, possibly associated with their retinoid potential, played a role in all the above observations, producing free-radical quenching and immunostimulation.(ABSTRACT TRUNCATED AT 250 WORDS)


Marine natural products against tumor development.

This review article deals with significant effects of marine natural products in carcinogenesis, namely as chemical probes to understand the process of carcinogenesis and as possible cancer preventive agents in humans.


Thiamin triphosphate synthesis in animals.

All the evidence obtained indicates that the synthesis of TTP in vitro and in vivo is catalyzed by cytosolic adenylate kinase. Further studies should explore whether adenylate kinase is the only enzyme involved in TTP synthesis, together with physiological roles of TTP in living organisms.


Thiamin pyrophosphate binding mechanism and the function of the aminopyrimidine part.

Besides the pyrophosphate group, acting as the essential and primary binding function of TPP the N1-atom of the aminopyrimidine component functions as a second and also essential anchor to the protein component. Only if both of the contacts are formed the productive conformation of TPP within the active site of TPP enzymes is realized. A mechanism is proposed, which explains the results of our experiments with TPP-analogs.


Molecular genetic aspects of human pyruvate dehydrogenase and its defect.

Genomic clones encompassing the entire genes for the human pyruvate dehydrogenase alpha and beta subunits (PDH alpha or beta) have been isolated by screening the leukocyte genomic libraries with a nick-translated human foreskin fibroblast PDH alpha or beta cDNA probe. These genomic clones were characterized by restriction enzyme analysis. extensive DNA sequencing and primer extension analysis. The PDH alpha gene spans 17.08 kilobases and is composed of 11 exons and 10 introns within its coding region. The 18-kilobase clone of PDH beta gene is composed of 10 exons and 9 introns. All intron-exon splice junctions of two genes follow the GT/AG rule. A total of seven Alu repeats in the PDH alpha gene were found in five introns and two Alu family in the PDH beta gene were found in intron 2 and 8. The 5'-flanking region of the PDH alpha gene contains typical CCAAT and TATA-like consensus promoter sequence and two Sp1 binding sequences. That of the PDH beta gene contains a TCAAT sequence but no TATA sequence. Primer extension analyses indicated that the PDH alpha and beta genes transcription start sites are thymine and adenine residues located 124 and 132 bases upstream from initiation codon in exon 1, respectively. Genomic DNA of patient, died 93 hours after birth with acidemia and defect of PDH activity, was isolated and all of the exons of PDH alpha and beta genes were amplified by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)


How and why are some riboflavin coenzymes covalently attached to proteins?

Covalent flavinylation as elucidated by the formation of the histidyl(N3)-8 alpha-flavin bond in 6-hydroxy-D-nicotine oxidase of A. oxidans proceeds by an non-enzymatic mechanism. Incubation of the apoenzyme, FAD and a three-carbon phosphate ester at neutral pH leads to the formation of an enzymatically fully active holoenzyme. The role of His71 in this process was illustrated by site-directed mutagenesis. Nevertheless, the question whether covalent attachment of the cofactor in a holoenzyme has prevailed throughout the evolutionary screening process because of biological significance or whether it is a chance event of neutral selective value is still open.


Thiamin and Alzheimer's disease.

Because of clinical and neuropathological overlap between the characteristics of dementia of the Alzheimer type (DAT) and of a human thiamin deficiency syndrome (Wernicke-Korsakoff syndrome), thiamin pyrophosphate (TPP) dependent processes have been studied in DAT brain and other tissues. The activities of 3 TPP-dependent enzymes are reduced in DAT brain: transketolase (TK), the pyruvate dehydrogenase complex (PDHC), and the alpha-ketoglutarate dehydrogenase complex (KGDHC). Quantitatively, the most marked reductions are in KGDHC (to less than 20% of normal). In cultured skin fibroblasts, KGDHC activity is reduced to 50-60% of normal, TK activity to 80-90% of normal, and PDHC is normal. Structural and molecular studies of the DAT and non-DAT enzymes are in process. A lesion of KGDHC may be related to the pathogenesis of DAT. Treatment with large doses of thiamin has not been beneficial, but the data are not totally negative. Further studies of thiamin-dependent mechanisms in DAT seem justified.


Blood levels and urinary excretion of thiamin and riboflavin during oral administration of multivitamin tablets to healthy adults.

1. The baseline blood thiamin concentration increased gradually during the long-term administration of TTFD, and the blood concentration was dose-dependent. The cumulative urinary thiamin excretion showed the same dose-dependence as the blood concentration. 2. The baseline blood riboflavin concentration also increased steadily during the administration period, but the increase was less than that of thiamin. Dose-dependence of the cumulative urinary excretion of riboflavin was noted. 3. No side effect were observed.


Vitamin C bioavailability.

The above brief review indicates that the bioavailability of vitamin C in humans is complex and that our current understanding of that process and factors that influence it are incomplete. It is important that an overall pharmacokinetic scheme be developed and tested to completely describe the complex dispositional and absorption processes of the vitamin. Such information will provide a better understanding of the absorption and disposition of the vitamin per se. Furthermore, that information will permit us to better understand how those factors influence the participation of the vitamin in events associated with maintenance of health.


Biochemical and molecular genetic aspects of eukaryotic pyruvate dehydrogenase multienzyme complexes.

The alpha-keto acid dehydrogenase multienzyme complexes play central roles in metabolism, are major sites of regulation, and are clinically important. Genes and cDNAs encoding the components of these complexes have been cloned and sequenced. Protein engineering and molecular cloning experiments are providing new insight into organization, structure-function relationships, and the molecular basis of genetic defects in these multienzyme complexes.


Role of enzymes in tetrahydrobiopterin biosynthesis: computer analysis of the sequential reaction of the last step.

Computer simulation analysis of the experimental data showed that Cl'-keto PH4 and C2'-keto PH4 were sequential intermediates of the reduction of PPH4 to BH4 by SPR and that the reaction in the last step of the BH4 biosynthesis proceeds as follows: PPH4-->Cl'-keto PH4-->C2'-keto PH4-->BH4 Cl'-keto PH4 is not detectable in the reduction of PPH4 by the purified SPR at neutral pH since isomerization (-->) [8] may occur far more rapidly than the first reduction (-->).


Zinc status in proliferative response of T lymphocytes.

The in vitro proliferation of T lymphocytes are highly susceptible to Zn deprivation and Cd addition. In order to define Zn status in T cell proliferation, toxicological and biochemical situation of Zn in proliferative response of T cells was investigated by use of mouse spleen cell cultures stimulated by T cell-mitogen, Con A. The inhibitory effect of Cd on T cell proliferation was protected specifically by Zn. The protection by Zn was effective when Zn was added within 16 h after Con A stimulation. Zn addition affected neither Cd content in cells nor induction of Cd-thionein. These findings indicate that Zn-dependent processes expressed before the S phase of cell cycle are critical for T cell proliferation and are targets susceptible to Cd. Moreover, electrophoretical analysis showed two unknown Zn-binding proteins (49 and 100 KD) induced in spleen cells incubated with Con A and radioactive Zn. These Zn-binding proteins may be associated with the Zn-dependent processes critical for T cell proliferation.


Membrane transport of folate compounds.

All eukaryotic cells and some prokaryotes that are unable to synthesize folic acid utilize membrane-associated transport systems for acquisition of the pre-formed vitamin or its coenzyme forms from external sources. These transport systems, in addition to providing folates essential for cell replication, are also important because of their role in the internalization of antifolates such as Methotrexate (MTX) that are used extensively in cancer chemotherapy. Information about the components and mechanism of folate transport systems has been derived, in large part, from studies with Lactobacillus casei and L1210 mouse leukemia cells, which serve as convenient models for prokaryotes and eukaryotes, respectively. L. casei contain a single folate transport system whose Kt value (i.e., concentration for half-maximum rate of uptake) for the preferred substrate folate is in the nanomolar range. The hydrophobic membrane-associated folate transport protein (18 kDa) has been purified to homogeneity and characterized. Expression of this transporter is repressed in cells grown on high concentrations (microM) of folate. L1210 cells contain two separate transport systems for folate compounds: (1) the low affinity system (Kt values for the preferred substrates 5-methyl- and 5-formyltetrahydrofolate and MTX in the microM range); and (2) the high affinity system (Kt for folate in the nM range). Fluorescein and biotin derivatives of MTX and folate, after conversion to N-hydroxysuccinimide esters, can be attached covalently to the transporters. These probes have been used for visualizing the transporters by fluorescence and electron microscopy and for their purification to homogeneity.(ABSTRACT TRUNCATED AT 250 WORDS)


Role of zinc in surgical nutrition.

Redistribution of zinc in tissues was induced during zinc-free TPN in PEM, and a marked decrease in skin zinc level may contribute to skin lesions and to impaired wound healing in skin. And clinical studies suggest that plasma zinc level is one of the sensitive markers for stress following surgery.


The mode of action of lipid-soluble antioxidants in biological membranes. Relationship between the effects of ubiquinol and vitamin E as inhibitors of lipid peroxidation in submitochondrial particles.

The effects of ubiquinol and vitamin E on ascorbate- and ADP-Fe(3+)-induced lipid peroxidation were investigated in beef heart submitochondrial particles before and after extraction of ubiquinone and vitamin E, and after reincorporation of either or both of these components. It is concluded that ubiquinol is capable of inhibiting lipid peroxidation without the mediation of vitamin E, but may also amplify the antioxidant effect of the latter. It is pointed out that ubiquinol is the only known lipid-soluble antioxidant that can be synthesized de novo in animal cells, and for which there exists an enzymic mechanism--the mitochondrial electron-transport system--that can regenerate the antioxidant from its oxidized form resulting from its inhibitory effect on lipid peroxidation. These features, together with its high degree of hydrophobicity and its general occurrence in biological membrane and in low-density lipoprotein, suggest a highly important role of ubiquinol in cellular defense against oxidative damage.


Antioxidant function of coenzyme Q.

Evidence for in vivo antioxidative activity of reduced CoQ homologs has been presented. This came from studies with experimental endotoxemia in mice, reoxygenation of rat liver following ischemia, and reoxygenation of canine heart following 24-hour cold preservation. In radical-induced injury of hepatocytes, it has been first shown that reduced CoQ9 acts as a potential antioxidant regardless of its cellular concentration, whereas reduced CoQ10 acts in cells containing CoQ10 as the predominant homolog. The antioxidant activity of reduced CoQ homologs appears to be independent of that of alpha-tocopherol under the conditions employed.


beta-Carotene and disease prevention.

Cancer and cardiovascular disease are still the number one and two killer diseases in most developed countries. There is justified hope that beta-carotene will be proven efficacious in the prevention and/or delaying of the onset of these chronic diseases. Chronic disease prevention through better nutrition, judicious use of supplements and better lifestyles will assume added importance in the coming years as the proportion of the population over 65 years increases.


Brain histamine: psychoneuroimmune regulator in physiological and pathological conditions.

HA is a biogenic amine widely distributed in the CNS, with neurons located in the posterior hypothalamus. HA acts as a neurotransmitter and/or neuromodulator regulating neuroendocrine and neuroimmune functions, circadian rhythms, sleep-wakefulness cycle, body temperature, centrally-mediated neurovegetative functions, cerebrovascular control, and behavior and learning. Changes in brain HA are observed in aging. High levels of HA in CSF and CNS of AD patients might reflect a reactive response to neuroimmune activation and tissue damage.


Diurnal monoamine variation in young and old rats: a microdialysis study.

The levels of striatal extracellular DA, DOPAC, HVA and 5-HIAA significantly decreased in aged rats compared to young adults. The magnitude of age-related reduction was greater in dopaminergic than serotonergic substances. The levels of striatal extracellular monoamines in young adult rats showed significant diurnal variations. On the other hand, these substances of aged rats, except for HVA, did not exhibit significant diurnal variations. Enriched environment housing increased levels of striatal extracellular DOPAC in aged rats, but did not influence on the age-related changes of diurnal variations in the striatal extracellular monoamines.


Thiamine responsive pyruvate dehydrogenase deficiency.

We studied a PDH deficient patient who is clinically responsive to thiamine. High Km and low Vmax values for the TPP were identified in the patient's cultured cells. Immunoblot analysis detected trace amount of mutant E1 alpha polypeptide which was 3.5 KD larger than normal in size. Four-nucleotide deletion in the E1 alpha gene causes a reading frame shift, producing an abnormal polypeptide with additional 31 amino acids at C-terminus of the E1 alpha subunit. The tryptophan (codon 383) and lysine (385) residues near the C-terminus might play a crucial role in the binding of TPP to the E1.


The family of protein kinase C in transmembrane signalling for cellular regulation.

Signal-induced hydrolysis of inositol phospholipid produces two second messengers, diacylglycerol and inositol trisphosphate. Diacylglycerol activates protein kinase C, whereas inositol trisphosphate mobilizes Ca2+ from its internal store. Analogously, signal-induced hydrolysis of choline phospholipid generates two second messengers, unsaturated free fatty acid and lysophosphatidylcholine. The free fatty acid synergizes with diacylglycerol to activate protein kinase C and causes full activation of the enzyme even at the basal level of Ca2+. On the other hand, lysophosphatidylcholine dramatically enhances cellular responses such as cell proliferation and differentiation under the conditions where diacylglycerol and Ca2+ are available. It is likely that all of the immediate products of signal-induced degradation of inositol and choline phospholipids are involved directly in concert in the transmembrane control of cellular functions.


Further metabolism of 1 alpha,25-dihydroxyvitamin D3 in target cells.

Calcitriol-inducible C-24 oxidation in target cells gives rise to calcitroic acid in a variety of cells. The pathway probably involves a transient C23-aldehyde intermediate. The pathway appears to play a crucial role in the duration of the 1,25-(OH)2D3 signal in target cells. New analogs can be designed to render the molecule more susceptible or more resistant to target cell catabolism. However, these changes do not guarantee survival of the drug due to alternative degradatory pathways.