A plea for the establishment of psychiatric forensic units in Israel. The growing interaction between psychiatric and legal systems justifies the establishment of specialized services. From a theoretical viewpoint, the obligation of judges to apply a dichotomic categorization between 'mentally ill' offenders and the rest--encompassing a wide spectrum of normal people as well as those suffering from severe personality disorders--contradicts the psychiatrist's conception of continuum in pathology and liability. In practice, the criterion of accountability determines whether an offender will be punished or treated in a mental institution. Mentally disturbed but non-psychotic offenders cannot benefit from advances in psychiatric techniques. This article details suggestions for change: The decision about mentally disturbed offenders should be based on two criteria--liability and chance of improvement through treatment. The judicial decision may then integrate punishment and treatment. The establishment of psychiatric forensic units would significantly add to the present range of services handling mentally disturbed offenders, would end the dispersion of the professionals (psychiatrists, psychologists, criminologists, social workers, probation officers) involved in the management of such offenders, and could provide an academic base and a framework for training residents.


Judicial murder.

Judicial murder. It is catastrophic when a judicial error results in the implementation of the death penalty. The western system of courts of appeal diminishes the risk of the condemnation of innocent persons but does not rule it out. Intrinsic influences of psychological effects are just as detrimental as preconceived notions as was the case, for instance, when Socrates' life ended unnaturally. This happened despite the fact that he was able to establish persuasively that the court had considered false evidence and had therefrom made unfair and untruthful deductions. This article uses the example in psychosomatic medicine of a member of a family who becomes aggressive because of envy and jealousy and this results in often tragic consequences for the 'victim' of his offensive behaviour. The principle is the same. The only solution is the intercession of an unbiased influence to work out the problem from a point of view that is unaffected by such turmoils which are often inherent in the system. If this is not done any organization or society can make deadly mistakes.


Legal and therapeutic interventions with incestuous families. Explanations for the occurrence of incest can be grouped into four general categories. Although some authors and clinicians have stated that one category of explanations best explains incest, the literature contains empirical and case report support for each category. In this article, it is argued that each category of explanations is useful for understanding incest, and that a single category can explain only a small minority of incest cases. Most cases are more effectively characterized by a combination of explanations. Assessing which of the explanations describes a particular incestuous family will provide valuable guidelines for determining the most appropriate legal and therapeutic interventions for that family.


On mitigating professional arrogance in the treatment of sex offenders. This article suggests that the adversarial approach of the criminal justice system towards handling of the paraphilias ultimately does more harm than good. The acceptance by helping professionals of the criminal justice model into their diagnostic consideration and treatment procedures is discussed, along with a discussion of some of the debilitating ethical and scientific implications of such an alignment. Historical, political and professional factors which have contributed to these disturbing trends are discussed and proposals are made as to how helping professionals might reclaim and reassert their traditional roles in service of their clientele.


Treatment of chronic nonvalvular atrial fibrillation in the elderly: a decision analysis. The objective of the study was to determine the preferred treatment strategy for elderly patients with chronic nonvalvular atrial fibrillation (CNVAF). A Markov decision-analytic model was used to compare three treatment strategies for CNVAF: 1) warfarin; 2) aspirin; and 3) no treatment. Five-year quality-adjusted life years (QALYs) were calculated for male and female cohorts aged 70 and 75 years. In the baseline analysis (effectiveness of warfarin = 0.70, effectiveness of aspirin = 0.45, utility of warfarin = 0.99, and utility of aspirin = 0.999) the quality-adjusted survival rates for 70-year-old males were 4.03 QALYs on warfarin, 4.02 QALYs on aspirin, and 3.95 QALYs on no treatment. Results were similar for all age and sex cohorts. Sensitivity analyses revealed that the results were very sensitive to the effectiveness of aspirin and the disutility of warfarin. The authors conclude that the optimal strategy for the treatment of CNVAF in elderly patients varies with the disutility assigned to warfarin therapy and the effectiveness value for aspirin therapy.


Data-source effects on the sensitivities and specificities of clinical features in the diagnosis of rheumatoid arthritis: the relevance of multiple sources of knowledge for a decision-support system. An experimental computer system was developed to support diagnosis of rheumatic disorders by computing diagnostic probabilities using modified likelihood ratios. The authors examined whether the performance of the model was affected by the settings in which the data used to derive the likelihood ratios were collected. The sensitivities and specificities of various clinical features for diagnosing rheumatoid arthritis (RA) were obtained from: 1) a study of 1,570 consecutive outpatients at a rheumatology clinic; 2) a review of the literature; 3) estimates by rheumatologists; and 4) a population study. Considerable variations in sensitivity and specificity but satisfactory agreement in likelihood ratios were found across the four data sets. The likelihood ratios were then used to compute the probabilities of RA in a test series of 570 of the rheumatology clinic outpatients. The model's diagnoses with likelihood ratios from the other sources were adequate. When the likelihood ratios from these sources were combined, discrimination came close to what could be achieved by using the likelihood ratios based on the data from the clinic. The method applied in the study, which makes use of variation of input data instead of variation of test series, and the results are relevant to assessing the external validity and transferability of Bayesian decision-support systems.


Hormonal replacement therapy: analysis of clinical strategies used by residents. The authors investigated strategies employed by resident physicians to decide whether to prescribe hormonal replacement therapy (HRT) for menopausal women, a matter of continuing clinical controversy. Verbal protocols were obtained from 21 residents in three specialties as they responded to 12 brief case descriptions. The cases incorporated three levels of cancer risk and two levels of osteoporosis risk in a 3 x 2 factorial design with two replications in each cell. Substantial variation in willingness to prescribe HRT was observed. By clustering subjects with relatively similar approaches to the problem, three treatment strategies were formulated that accounted for the decisions of 20 subjects. Each strategy is a simplified representation of the conflicting considerations in this clinical dilemma that facilitates rapid decision making. The differences between these representations and formal decision-analytic models help to explain why observed clinical decisions were inconsistent with expected utility maximization.


Birthweight-adjusted mortality rates for assessing the effectiveness of neonatal intensive care. Mortality rates for very-low-birthweight infants vary significantly among different neonatal intensive care units (NICUs). Computational models and computer simulation are used to predict the performance of an algorithm for identifying individual NICUs within a network that have greater than 110% of the expected birthweight-adjusted mortality risk. The algorithm maintains high sensitivity and specificity with as few as three moderately heterogeneous risk categories when applied to large health care networks; the model parameters were based on preliminary data from a real NICU network. The performance of the algorithm depends on the number of admissions at the individual NICU. A NICU with a center-specific risk 130% of the network average would be correctly identified as an outlier 50% of the time if it had 35 admissions, 59% of the time if it had 70 admissions, and 77% of the time if it had 280 admissions. A NICU with average risk would be incorrectly identified as an outlier 16%, 12%, or 2% of the time if it had 35, 70, or 280 admissions, respectively. Severity-of-illness casemix adjustment did not improve these results. It is concluded that the sensitivity and specificity of the algorithm in determining which facilities have higher-than-expected mortality will be less in typical NICU networks than in large health care networks that treat adult patients. It is unlikely that severity-of-illness adjustments will overcome the problem of the small numbers of admissions at individual NICUs.


The Fis protein: it's not just for DNA inversion anymore. Higher-order nucleoprotein complexes are associated with many biological processes. In bacteria the formation of these macromolecular structures for DNA recombination, replication, and transcription often requires not only the participation of specific enzymes and co-factors, but also a class of DNA-binding proteins collectively known as 'nucleoid-associated' or 'histone-like' proteins. Examples of this class of proteins are HU, Integration Host Factor, H-NS, and Fis. Fis was originally identified as the factor for inversion stimulation of the homologous Hin and Gin site-specific DNA recombinases of Salmonella and phage Mu, respectively. This small, basic, DNA-bending protein has recently been shown to function in many other reactions including phage lambda site-specific recombination, transcriptional activation of rRNA and tRNA operons, repression of its own synthesis, and oriC-directed DNA replication. Cellular concentrations of Fis vary tremendously under different growth conditions which may have important regulatory implications for the physiological role of Fis in these different reactions. The X-ray crystal structure of Fis has been determined and insights into its mode of DNA binding and mechanisms of action in these disparate systems are being made.


Assessing utilities by means of conjoint measurement: an application in medical decision analysis. A method is presented for helping patients who have laryngeal cancer to decide between laryngectomy and radiotherapy in cases where these treatments are deemed medically equivalent. The method is based on the model of additive conjoint measurement. The treatment with the higher utility is determined from pair comparisons among outcomes that vary in quality and quantity of life. Pair comparisons enable a (partial) test of the axioms of additive conjoint measurement. This is in contradistinction to earlier work on decision making for patients with laryngeal cancer, and most of the work in medical decision making in general, in which underlying axioms have almost never been tested. Besides testing the axioms, another important advantage of pair comparisons is that they avoid difficulties with other, risk-based, assessment procedures by presenting only riskless alternatives. Encouraging results have been found in a study among patients.


Use of formal methods in medical decision making: a survey and analysis. Apparent low usage of formal decision techniques by general clinicians has raised questions about dissemination methods and about the techniques' perceived usefulness. Two literature searches examined whether use of formal decision techniques among clinicians had indeed failed to increase from the 1970s to the 1980s. A general MEDLINE search for the period 1983-87 relative to 1973-77 indicated that usage of formal decision techniques had more than doubled. This increase, however, was due to increased coverage of formal decision techniques in specialist methods journals. A manual search of seven major clinical journals and a MEDLINE search restricted to the clinical journals of the manual search disclosed no increase in overall usage for the same time periods. MEDLINE detected only a small subset of the actual instances of formal method usage found by the manual search. Individual medical subspecialties were found to utilize different formal decision techniques to different degrees. The authors suggest interventions that may increase the usage of formal decision techniques among general clinicians.


Three-stranded DNA structure; is this the secret of DNA homologous recognition? A novel type of triple-stranded DNA structure was proposed by several groups to play a crucial role in homologous recognition between single- and double-stranded DNA molecules. In this still putative structure a duplex DNA was proposed to co-ordinate a homologous single strand in its major groove side. In contrast to the well-characterized pyrimidine-purine-pyrimidine triplexes in which the two like strands are antiparallel and which are restricted to poly-pyrimidine-containing stretches, the homology-specific triplexes would have like strands in parallel orientation and would not be restricted to any particular sequence provided that there is a homology between interacting DNA molecules. For many years the stereo-chemical possibility of forming homology-dependent three- or four-stranded DNA structures during the pairing stage of recombination reactions was seriously considered in published papers. However, only recently has there been a marked increase in the number of papers that have directly tested the formation of triple-stranded DNA structures during the actual pairing stage of the recombination reaction. Unfortunately the results of these tests are not totally clear cut; while some laboratories presented experimental evidence consistent with the formation of triplexes, others studying the same or very similar systems offered alternative explanations. The aim of this review is to present the current state of the central question in the mechanism of homologous recombination, namely, what kind of DNA structure is responsible for DNA homologous recognition. Is it a novel triplex structure or just a classical duplex?


How bacterial protein toxins enter cells; the role of partial unfolding in membrane translocation. Bacterial protein toxins translocate across membranes by processes that are still mysterious. Studies on diphtheria toxin have shown that partial unfolding processes play a major role in toxin membrane insertion and translocation. Similar unfolding behaviour is seen with other bacterial toxins. The lessons gained from this behaviour allow us to propose novel mechanisms for toxin translocation.


Combining and comparing area estimates across studies or strata. A method for combining and comparing medical tests across studies or strata is presented. The area under the receiver operating characteristic (ROC) curve is the parameter of interest to be used for comparison. The combined area is a weighted average of the areas under the curve in each study or stratum. A chi-square test for equality of areas across strata can be used to compare the areas. The power of the test is also explored. The methods presented are simple and require only knowledge of estimates of area and their standard errors. Either parametric or nonparametric estimates of the area can be used.


Role of the RNA polymerase alpha subunit in transcription activation. The N-terminal two-thirds of the alpha subunit of Escherichia coli RNA polymerase plays an essential role in the initiation of subunit assembly, by gathering two large subunits, beta and beta', together into a core-enzyme complex. One group of RNA polymerase mutants deficient in response to transcription activation carries mutations in the C-terminal region of the alpha subunit, indicating that the C-terminal region of the alpha subunit is involved in protein-protein contact in positive control of transcription. A set of activators (class I transcription factors) which make contact with this contact site I region on RNA polymerase alpha subunit bind in most cases to DNA upstream of the promoter -35 signal. Genetic fine mapping indicates that a cluster of subsites exists in the contact site I region, each interacting with a set of the class I factors and each consisting of a structure formed by only 5-10 amino acid residues.


Reproducibility of predictor variables from a validated clinical rule. It has been suggested that clinical prediction rules are not reproducible, and that the most important variables frequently do not appear in replicate models. The authors studied the reproducibility of a validated rule for predicting radiographic evidence of pneumonia (ROC areas for the training and validation cohorts, 0.816 and 0.821, respectively). Two hundred replicate samples of size 250 and size 500 were generated by sampling without replacement from the original training cohort of 905 patients with a 14.6% prevalence of pneumonia. Forward selection was performed among 31 candidate variables by stepwise logistic regression. Using as reproducibility criteria: 1) inclusion of all five variables from the original model in the original order; 2) inclusion of all five variables in any order; 3) inclusion of the first three variables; 4) inclusion of the first two variables; 5) inclusion of the first variable; and 6) inclusion of any of the five variables: 2.5%, 13.5%, 48.5%, 85.5%, 98.0%, and 100% of replicate models of sample size 500, respectively, met the criteria, whereas 0%, 0%, 16.5%, 49.0%, 71.5%, and 97.5% of models of sample size 250 met the criteria (all comparisons by sample size p < .0001 except for criteria 1 and 6, p = 0.07). Mean ROC areas in the training and validation samples were 0.829 and 0.791 for replicate models of sample size 500, and 0.831 and 0.779 for models of sample size 250. There was no significant difference in ROC areas between training and validation cohorts for 80.5% of models of sample size 500, and for 75.3% of models of sample size 250.(ABSTRACT TRUNCATED AT 250 WORDS)


Subtelomeric expression regions of Borrelia hermsii linear plasmids are highly polymorphic. Borrelia hermsii, a relapsing fever agent, undergoes multiphasic antigenic variation to evade its host's immune response. Serotype specificity is determined by variable membrane lipoproteins, Vmps, which are expressed from genes located near the end of a linear plasmid. Using the polymerase chain reaction and primers representing the promoter of the active vmp and a conserved telomeric sequence, we characterized the subtelomeric expression regions of the 25 known serotypes of strain HS1. The distance from the promoter to the telomere fell into three size classes of approximately 1.0, 1.5, and 2.5 kilobases. In the sequenced serotypes the size differences were accounted for by variable lengths of the vmp genes and intervening sequences between 3' end of the vmp gene and the start of a downstream homology block. The degree of nucleotide identity between different vmp genes, or between the different 3' flanking DNA varied from 39-78%. Thus, there is length and sequence variability not only between vmp genes themselves but also between the 3' flanking regions of vmp genes.


Characterization of the micro-environment of Salmonella typhimurium-containing vacuoles within MDCK epithelial cells. Salmonella typhimurium has the capacity to enter into and multiply within epithelial cells. During the entire intracellular stage, bacteria are enclosed within a vacuole. To characterize the micro-environment of the bacteria-containing vacuoles, we have used a new method to measure the expression levels of several S. typhimurium genes in intracellular bacteria within Madin-Darby canine kidney (MDCK) epithelial cells. Our study was based on the determination of beta-galactosidase activity derived from lacZ transcriptional fusions using the highly sensitive substrate fluorescein-di-beta-D-galactoside (FDG). Expression of the iroA and mgtB genes (induced by Fe2+ and Mg2+ limitation respectively), and cadA (induced by pH 6.0 in the presence of lysine, with enhanced expression under anaerobiosis) were characterized at different post-infection times. High intracellular expression levels were detected for the iroA and mgtB genes, suggesting that the concentrations of free Fe2+ and Mg2+ in the vacuole may be low. cadA activity was detected only at early post-infection times (4 h), suggesting that the vacuole may have a mild-acidic pH, and oxygen and lysine present at this time. Globally, the results reported indicate that the use of a highly sensitive beta-galactosidase substrate can provide information about the micro-environment within which an intracellular pathogen, such as S. typhimurium, resides.


Site-directed mutagenesis of an amino acid residue in the bacteriophage P2 ogr protein implicated in interaction with Escherichia coli RNA polymerase. The P2 ogr gene encodes a 72-amino-acid protein required for P2 late gene expression. This gene was defined originally by a class of compensatory mutations which overcome the block to P2 late transcription imposed by a host mutation, rpoA109, in the gene encoding the alpha subunit of Escherichia coli RNA polymerase. Spontaneous compensatory ogr mutations substitute a Cys for a Tyr residue at amino acid 42 in the Ogr polypeptide. Using suppression of an ogr amber mutation and site-directed oligonucleotide mutagenesis, we have studied the effect of amino acid substitutions at this position in Ogr. Substitution of charged residues at this site renders Ogr protein inactive, in rpoA+ and rpoA109 strains. While 11 different amino acids are capable of replacing the wild-type Tyr-42 to allow P2 growth to varying degrees in a wild-type E. coli strain, only three of these allow phage growth in strains carrying the rpoA109 mutation. Phages carrying Cys or Ala in place of Tyr-42 gave burst sizes at least as high as P2 ogr+ in a rpoA+ strain; a Gly substitution also allowed P2 to grow in either a rpoA+ or rpoA109 background, but markedly reduced the burst size. These results are consistent with a direct interaction between Ogr and the alpha subunit of E. coli RNA polymerase in positive control of P2 late transcription, and indicate that the block imposed by the rpoA109 mutation is due to steric hindrance.


Differential expression of nodS accounts for the varied abilities of Rhizobium fredii USDA257 and Rhizobium sp. strain NGR234 to nodulate Leucaena spp. Transfer of a cosmid containing nodSU from Rhizobium sp. NGR234 to Rhizobium fredii USDA257 expands the host range for nodulation to include the perennial tropical legumes, Leucaena leucocephala and Leucaena diversifolia. Complementation experiments with a series of subclones established that nodS and its associated nod-box promoter from NGR234 are sufficient to confer this extended host-range phenotype to L. leucocephala. Strain USDA257 contains its own copy of nodSU, including upstream nod-box sequences. Although both nucleotide and deduced amino acid sequences of the reading frames are homologous between the two strains, there are gaps within the promoter region and the 5'-end of nodS of USDA257. Consequently, the deduced NodS protein of USDA257 is shorter than its counterpart from NGR234, and the distance between the nod-box and the initiation codon is greater. A 36 bp deletion encompasses the extreme right border of the USDA257 nod-box and extends into the upstream leader sequence. Transcriptional fusions with both nod-boxes confirmed that the promoter from NGR234 is flavonoid-inducible, and that the nod-box from USDA257 is not. These observations were corroborated by Northern analysis with a nodS-containing Xhol fragment as hybridization probe. Flavonoid-induced cells of NGR234 gave an intense signal, but those of USDA257 yielded only a weak trace of hybridization. EcoRI fragments with homology to nodSU of USDA257 are present in 17 of 35 tested strains, including several representatives of Bradyrhizobium japonicum, Rhizobium sp., R. loti, and R. fredii. Two wild-type, leucaena-nodulating strains of Rhizobium sp. lack this homology. We conclude that a genetic defect in expression of nodS accounts for the inability of USDA257 to nodulate leucaena and that diverse rhizobia may have evolved alternative mechanisms to nodulate this legume species.


Quelling: transient inactivation of gene expression in Neurospora crassa by transformation with homologous sequences. Up to 36% of Neurospora crassa transformants showing an albino phenotype were recovered by transforming a wild-type strain with different portions of the carotenogenic albino-3 (al-3) and albino-1 (al-1) genes. The presence of the exogenous sequences (which were randomly integrated in ectopic locations) provoked a severe impairment in the expression of the endogenous al-1 or al-3 genes. This phenomenon, which we have termed 'quelling', was found to be spontaneously and progressively reversible, leading to wild-type or intermediate phenotypes. The phenotypic reversion is characterized by a progressive release of the transcriptional inhibition and seems to correlate with a reduction of the number of the ectopic integrated sequences. Moreover, quelling appears to be monodirectional, as, once relieved, it cannot take place again, despite the continuing presence of some of the ectopic sequences in the genome.


The beta-tubulin gene from rat and human isolates of Pneumocystis carinii. The development of new drugs for treating Pneumocystis carinii infections in AIDS patients is hampered by the lack of long-term culture systems, and by our generally limited knowledge of this organism. Recently, however, we observed significant activity of various benzimidazoles against growth of this organism in short-term cultures. Benzimidazoles inhibit microtubule polymerization; there is strong evidence that the primary target is the beta-tubulin subunit. To understand the basis for benzimidazole activity against P. carinii, and to examine the apparent relatedness of this organism to fungi, we have cloned and sequenced the single beta-tubulin gene from a rat P. carinii isolate. There was 89-91% identity at the amino acid level to beta-tubulins from filamentous fungi, but only 79-82% identity to yeast and protozoal beta-tubulins. Also, eight introns were distributed throughout the P. carinii beta-tubulin gene in a pattern characteristic of filamentous fungi. Specific residues previously implicated in benzimidazole sensitivity were conserved in P. carinii beta-tubulin. The polymerase chain reaction was used to amplify a segment of P. carinii beta-tubulin DNA from bronchoalveolar lavages obtained from two patients with AIDS. There was considerable divergence at the DNA level between the human and rat sequences, but 100% identity at the amino-acid level.


The Rhizobium leguminosarum FnrN protein is functionally similar to Escherichia coli Fnr and promotes heterologous oxygen-dependent activation of transcription. An open reading frame from Rhizobium leguminosarum bv. viciae strain VF39, previously identified and found to be similar to Escherichia coli fnr and Rhizobium meliloti fixK (orf240, thereafter called fnrN), was further analysed. Analysis of the expression of an fnrN-lacZ transcriptional fusion revealed that fnrN is preferentially expressed under oxygen limitation. Using R. meliloti fixN-lacZ fusions it was shown that the fnrN gene product only mediates transcriptional activation under microaerobiosis, indicating that the FnrN protein responds, directly or indirectly, to oxygen. Plasmids which expressed fnrN under the control of an E. coli promoter were able to complement an E. coli fnr mutant with respect to anaerobic growth on nitrate but not fumarate, and to promote anaerobic but not aerobic activation of the Fnr-dependent E. coli genes narGHJI, nirB and fdnGHI coding for nitrate reductase, NADH-dependent nitrite reductase and formate dehydrogenase-N, respectively. Fumarate and DMSO reductase activities were not induced by FnrN. The E. coli fnr gene substituted for fnrN in oxygen-regulated transcription of nirB- and fixN-lacZ fusions in R. leguminosarum. The results indicate that Fnr and FnrN are functionally very similar and share a common mode of oxygen-dependent transcriptional activation. From hybridization studies, it appeared that fnrN-like genes are present in a number of different R. leguminosarum strains.


Genetic analysis of the immunity region of phage-plasmid P4. In the prophage P4, expression of the early genes is prevented by premature termination of transcription from the constitutive promoter PLE. In order to identify the region coding for the immunity determinant, we cloned several fragments of P4 DNA and tested their ability to confer immunity to P4 superinfection. A 357 bp long fragment (P4 8418-8774) is sufficient to confer immunity to an infecting P4 phage and to complement the immunity-defective P4 cl405 mutant, both in the presence and in the absence of the helper phage P2. The immunity region covers PLE and the cl locus. We were unable to obtain evidence of translation of the region, thus we suggest that P4 immunity is not elicited by a protein but by a transcript (or transcripts) encoded by the region downstream of the promoter PLE. The promoter PLE appears to be necessary for the expression of P4 immunity: fragments in which the PLE region is deleted did not complement P4 cl405 for lysogenization, although they still interfered with P4 growth. Two complementary sequences downstream of PLE (seqA and seqB) at the 5' and 3' ends of the immunity region play an essential role in the control of P4 immunity.


Bacteriophage P4 immunity controlled by small RNAs via transcription termination. Satellite bacteriophage P4 immunity is encoded within a short DNA region 357 bp long containing the promoter PLE and 275 bp downstream. PLE is active both in the early post-infection phase, when genes necessary for P4 lytic cycle are transcribed from this promoter, and in the lysogenic condition, when expression of the above genes is prevented by prophage immunity. In order to understand how P4 immunity is elicited, we have characterized the transcription pattern during the establishment and the maintenance of the satellite phage P4 lysogenic condition. We found that prophage transcription starting at PLE ends prematurely and the transcripts do not extend beyond 300-400 nucleotides downstream of PLE. Thus P4 immunity acts by causing premature transcription termination rather than by repressing transcription initiation. The P4 immunity region is transcribed in the prophage, but it does not seem to be translated; this region contains two elements (seqA and seqB) of a palindromic sequence. In addition to transcripts about 300 nucleotides long, P4 prophage produces a family of shorter transcripts, about 80 nucleotides long, containing seqA or seqB. Evidence is presented suggesting that SeqB RNA is the trans-acting immunity factor, and that interaction of SeqB RNA with the complementary nascent RNA containing seqA may be involved in bringing about premature transcription termination.


Neuronal metabolism and sympathetic pupillary activity in infants. A delayed or immature transmission dynamics of an otherwise diffuse mesolimbic catecholamine circuit is suggested to be the reason behind lack of pupillary activity and reflex often observed in infants less than one year of age. This deficiency is known to be fully compensated in later years following a growing curve of neuronal metabolic change and as well as a curve for synaptoogenesis.


Ophthalmologic manifestations of type B Niemann-Pick diseases. Type B Niemann-Pick Disease (NPB) is a rare lysosomal storage disease resulting from diminished activity or deficiency of sphingomyelinase and is characterized by multi-system involvement with visceromegaly. Rare ocular involvement (the Macula Halo Syndrome) has been reported. Eight patients (ages 4-36) with NPB underwent complete ophthalmologic evaluations. All patients had periorbital fullness, a hitherto unreported clinical feature. Two patients had a classic Macula Halo Syndrome. One patient developed peri-macular granular deposits forming an incomplete Macula Halo over 5 years. Another patient had macular granular deposits and developed deterioration of central vision and abnormal visual evoked potentials. Ophthalmologic involvement in NPB is more common than previously described. Complete ophthalmologic evaluation is recommended in all patients suspected to have NPB.


Blood viscosity and retinopathy of prematurity: a preliminary report. Whole blood viscosity (WBV) and haematocrit (Hct) were measured in 8 very low birth weight premature neonates developing acute severe retinopathy of prematurity (ROP) and 7 control neonates without retinopathy or mild ROP. Single samples were collected at 32-34 weeks conceptual age. There was no statistically significant difference in WBV or Hct between the two groups. The results of this preliminary report suggest that WBV does not appear to play a major role in the development of advanced ROP, though larger studies are required to investigate this further.


Platelet function in diabetic retinopathy: levels of beta-thromboglobulin and platelet factor 4. Altered platelet function has been reported in diabetic patients. This article reports plasma levels of beta-thromboglobulin and platelet factor 4 as measures of in vivo platelet activity in diabetic and control groups. Both beta-thromboglobulin and platelet factor 4 were significantly higher in diabetics than in controls (p < 0.01). The levels observed were not significantly affected by age, sex, diabetes type or whether the diabetic had nonproliferative or proliferative retinopathy, but beta-thromboglobulin levels were significantly higher in diabetics of less than 10 years standing than in those who had suffered diabetes for over 20 years (p < 0.05).


Retinitis pigmentosa and discoid lupus erythematosus. A 41 year old male is presented who suffers from both advanced retinitis pigmentosa and active discoid lupus erthematosus. A possible association between the two pigmenting disorders is discussed as well as the treatment of the discoid lupus with potentially retinotoxic hydroxychloroquine.


Isolation, characterization and immunolocalization of a 53-kDal dentin sialoprotein (DSP). We isolated a sialic-rich protein from rat dentin extracts and have named it dentin sialoprotein, DSP (formerly called 95K glycoprotein). DSP is rich in aspartic acid, glutamic acid, glycine and serine, but contains no cysteine or phosphate. The 30% carbohydrate content includes about 9% sialic acid and indicates that several N-glycosides and O-glycosides are present. Sedimentation equilibrium analysis gave a M(r) of 52,570. Based on this molecular weight we calculated that DSP contains about 350-amino acids and 75 monosaccharides. With automated Edman degradation the sequence of the first 8-amino acids was shown to be: Ile-Pro-Val-Pro-Gln-Leu-Val-Pro. The initial 3 residues of this sequence are identical to the first 3 in human osteopontin (OPN) and are closely similar to the Leu-Pro-Val sequences of OPN from other species, as well as at the beginning of bone acidic glycoprotein-75 (BAG-75). On Western immunoblots, purified polyclonal antibodies reacted only with DSP in dentin extracts and with none of the proteins from bone. Similarly, immunolocalization experiments showed the presence of DSP in dentin but not in enamel or alveolar bone. Along with immunohistochemical localization data reported elsewhere, these observations suggest that DSP may be an important marker for cells in the odontoblast lineage.


Type IV collagen synthesis and accumulation in neonatal rat aortic smooth muscle cell cultures. The production of type IV collagen by cultured neonatal rat aortic smooth muscle cells was monitored over a three-week period to further characterize the extracellular matrix of this unique culture system. Type IV collagen was quantified using a dot immunobinding assay and was found to represent 1% or less of the total collagen produced by these cells in culture. Total collagen represented up to 33% of the total protein. The pattern of type IV collagen production in the media and the cell layer suggests that although these cells synthesize and secrete type IV collagen from the onset of culture, type IV collagen deposition only occurs after the cells have reached confluence. In the presence of ascorbate the amount of type IV collagen peaked in the media in preconfluent cultures. In the absence of ascorbate, little type IV collagen was detected in the media. On the other hand, the presence or absence of ascorbate made little difference in the amount of the total collagen detected in the media, although hydroxylation was affected. Remarkably, in the absence of ascorbate type IV collagen accumulation in the cell layer was similar by the end of the culture period to that in cultures treated with ascorbate. Laminin was not affected by the presence or absence of ascorbate. When these cells were exposed to ascorbate for 24 hours, a peak of soluble elastin was detected in the media. However, soluble elastin was not detected in the media in the absence of ascorbate or in cultures which were maintained in the presence of ascorbate. Modulation of the extracellular matrix with ascorbic acid indicated that type IV collagen deposition did not depend on the presence of ascorbic acid and that there was no discernable interaction between type IV collagen, laminin, and elastin.


Initiation of bone regeneration in adult baboons by osteogenin, a bone morphogenetic protein. Osteogenin, and related bone morphogenetic proteins, induce endochondral bone differentiation through a cascade of events which include formation of cartilage, hypertrophy and calcification of the cartilage, vascular invasion, differentiation of osteoblasts, and formation of bone. These events have been studied in a postnatal model of bone development in rodents. Information concerning the morphogenetic potential of osteogenin in primates is a prerequisite for potential clinical application in man. The efficacy of allogeneic osteogenin in primates was investigated in both extraskeletal and skeletal sites in 19-Chacma baboons (Papio ursinus). Osteogenin was isolated from demineralized baboon bone matrix and purified by chromatography on heparin-Sepharose, hydroxyapatite, and Sephacryl S-200. Protein fractions with a molecular mass range of 26-42 kDa induced cartilage and bone differentiation in the subcutaneous space of rats. Final purification to homogeneity was obtained by electroendosmotic elution from a preparative sodium dodecyl sulphate (SDS) polyacrylamide gel, resulting in a single band on a SDS-polyacrylamide gel with an apparent molecular mass of 30-34 kDa, with biological activity in rats. The osteoinductive potential of osteogenin in primates was tested first in intramuscular sites in baboons and found to be active. The bone regeneration potential was investigated in nonhealing calvarial defects surgically prepared in adult male baboons. Baboon osteogenin induced complete regeneration of the cranial wound. These findings in adult primates establish a primary role for osteogenin in initiation and promotion of osteogenesis, and imply a potential therapeutic application based on cell biology of extracellular matrix-cell interactions.


Isolation of hydroxylysyl pyridinoline, a mature collagen crosslink from neonatal rat aorta smooth muscle cell cultures. Hydroxylysyl pyridinoline (HP) is a nonreducible collagen crosslink derived from three posttranslationally modified lysyl residues. Neonatal rat aorta smooth muscle cell cultures (NNRSMC) produce mg amounts of insoluble collagen. The purpose of the present study was to evaluate the capability of NNRSMC to produce collagen containing HP crosslinks. Cultures were pulsed with [14C]-lysine and then chased for five weeks. Insoluble collagen was prepared by digestion of the cell layer material with porcine pancreatic elastase and trypsin. After acid hydrolysis and cation-exchange chromatography, purified HP was isolated by reversed phase ion-paired chromatography. The material eluting from the HPLC was monitored continuously at 295 nm and the ultraviolet absorption spectrum was recorded every 21 msec. The ultraviolet spectrum of the HP peak was virtually identical to that of standard HP run on the HPLC. The HP exhibited a homogeneity of 97.3% when the ultraviolet spectrum of the apex of the peak was compared with the spectra of the shoulders of the peak. The radioactive HP also exhibited the expected fluorescence emission spectrum. We calculate a mean of 0.40 +/- 0.03 nmol HP/nmol collagen in the three experiments as compared with reported values of 0.57 +/- 0.1 for rabbit aorta. This is the first report of cell culture biosynthesis of chemically measurable amounts of HP. Using such pulse-chase techniques one can study the maturation of intermediate collagen crosslinks into HP. HP can also be used as a marker to study the metabolism of mature collagen molecules during normal and pathologic states.


A substrate-gel assay for hyaluronidase activity. Hyaluronic acid (HA) is a key structural element of the extracellular matrix. Turnover rates of HA are determined in part by hyaluronidases, that are themselves modulated by hyaluronidase inhibitors. A substrate polyacrylamide gel electrophoresis procedure is described here that separates enzyme from inhibitors. The HA is embedded in the gel, and following electrophoretic separation, enzymatic digestion of the HA is allowed to occur. The gel is stained with Alcian blue and can be secondarily stained with Coomassie blue. Enzymatic activities appear as cleared bands on a light blue background, while major proteins appear as dark blue bands. The procedure can be performed in the presence or absence of sodium dodecylsulfate, though levels of hyaluronidase activity decrease when the detergent is used. Hyaluronidases active in the neutral or acid pH range can be detected. This technique will facilitate characterization of hyaluronidases and inhibitors from a wide variety of sources.


Type X collagen is transcriptionally activated and specifically localized during sternal cartilage maturation. Type X collagen is an extracellular matrix protein which is synthesized by chondrocytes when they undergo hypertrophy. We present evidence here that the expression of type X collagen in the developing chick sternum is controlled primarily by transcriptional mechanisms. Using chondrocyte nuclei isolated from 15-, 16-, 17- and 18-day chick embryonic sterna, nuclear run-off assays demonstrate that type X collagen gene transcription begins at day 16 in chondrocytes isolated from the cephalic portion. This occurs two days prior to mineralization of this tissue as observed by alizarin red staining. The rate of type X transcription increases dramatically through days 17 and 18. Western blot analyses of extracts of freshly isolated sternal chondrocytes from the same stages show that intracellular levels of the type X protein follow the same time course. Immunostaining with a monoclonal antibody specific for type X collagen demonstrates that the initial appearances of hypertrophic cells and pericellular type X collagen occur at embryonic day 16 in the cephalic portion of sterna. Observation of immunostained cephalic sternal sections from day 18 embryos by confocal microscopy reveals that type X collagen is localized in a capsule-like configuration around each hypertrophic chondrocyte.


Telehealth: the delayed revolution in health care. It is recognized that health care in rural communities could be improved significantly with the assistance of telehealth, the term by which the combined application of computer and telecommunications technologies to health care has come to be known. Yet in spite of its obvious potential, the telehealth literature has shown a surprising lack of growth. This paper reports an analysis which revealed that, between 1975 and 1990, few telehealth articles were catalogued by the National Library of Medicine, and suggests why this might have been the case. Following a brief discussion of the origins of telehealth, terminology, and the rural health care crisis, this overview examines the status of telehealth in terms of its main applications: telemedicine and tele-education. An analysis of the pattern of publications between 1975 and 1990 is then used to suggest why telehealth has not fulfilled its potential. Corrective measures are proposed and the paper concludes with a summary of recent telehealth initiatives.


An image management and communications (IMAC) system for radiology. Managing x-ray films is a difficult problem in a hospital. Advances in digital imaging, high speed networks and high fidelity displays make it possible to develop an image management and communication system for a hospital. As many of the technical problems are solved, many operational problems remain. Experience with a prototype installation became the basis for a much more comprehensive implementation of a fully digital filmless imaging support system in a number of hospitals. The use of IMAC technology will bring about profound changes in the radiology community; physicians, administrators, manufactures of imaging systems and the users of radiology service, the patients.


Public medicine and global security: the challenge and the opportunities. The new discipline of Global Security Studies is defined as the consideration of transnational issues with global implications that can only be solved by collaborative endeavour. There is a need for new thinking leading to actions for a sustainable future. An analogy is drawn with the preventive activities of public health medicine, and the opportunities presented to Medical Action for Global Security are examined.


Spectroscopic quantitative analysis of blood glucose by Fourier transform infrared spectroscopy with an attenuated total reflection prism. As an alternative way of long-term glycemic monitoring, the glucose measurement by analyzing Fourier transform infrared absorbance spectra with an attenuated total reflection prism has been developed. In glucose aqueous solution, glucose has characteristic absorptions at the wave numbers of 1033 and 1080 cm-1 and the absorption intensities are proportional to glucose concentrations. In serum and whole blood samples, however, red blood cell corpuscles, serum albumin and serum gamma-globulin interfere with the absorbance spectra of glucose and shift the base line upward significantly. Therefore, to eliminate these interferences in serum and whole blood samples, the feasibility of the calibration curves obtained by using difference absorbance spectra with those of fasting samples was studied. As a result, highly significant correlations between glucose concentrations estimated by Fourier transform infrared spectroscopic method and those measured by glucose oxidase method were obtained (r = 0.981 and 0.989 for serum and whole blood samples, respectively). From these experiments, it was concluded that by infrared spectroscopy glucose concentrations in the serum and whole blood samples could be measured quantitatively or monitored if the base line drifts and interferences were subtracted.


Biomedical engineering basis of traditional Chinese medicine. Traditional Chinese medicine is an ancient medical science that can be traced back for three to four thousand years of written history. Using the transient response characteristic method, we studied the frequency property of some simulated organs. We tried to explain the concept that the energy in the blood pressure wave is distributed to different organs in the body according to the frequency. This will elucidate the ancient teaching of Chinese medicine in terms of current engineering terminology.


[EEG in HIV infection].

[EEG in HIV infection]. Since 1985, early changes in the EES have been demonstrated in the course of HIV infection. This method can be considered one of the accurate tests for the assessment of evolution of the disease. Abnormal anterior changes are present in about 30% of HIV+subjects with at least stage II disease. EEG abnormalities during the disease form a spectrum ranging from minor changes to slow diffuse activity, usually found in cortical lesions. These are associated in some cases with a periodic or pseudo-periodic activity as often found in white matter lesions.


[Evoked potentials in HIV infection].

[Evoked potentials in HIV infection]. The study of the literature data on the multimodal evoked potentials in HIV infected patients shows many abnormalities as well in asymptomatic subjects without AIDS as in AIDS subjects with or without neurological signs. Visual evoked potentials (VEPs) reveal prolonged P100 wave latency in 22% of HIV asymptomatic subjects and in 26% of HIV symptomatic subjects; brainstem auditory evoked potentials (BAEPs) reveal an increase of the interpeak latency I-V in 16% of asymptomatic subjects and in 32% of symptomatic subjects; somatosensory evoked potentials (SEPs) by median nerve stimulation reveal prolonged central conduction time in 6% of asymptomatic subjects and in 11% of symptomatic subjects; somatosensory evoked potentials (SEPs) by tibial nerve stimulation reveal prolonged central conduction time in 4% of asymptomatic subjects and in 45% of symptomatic subjects; motor evoked potentials (MEPs) by magnetic stimulation reveal prolonged central motor conduction time in 46% of asymptomatic subjects.


[Cognitive evoked potentials and HIV infection]. Endogenous event-related potentials (and especially the P300 component) have delayed latencies relative to normal controls in patients with dementias of diverse aetiologies. Moreover, the subcortical varieties of dementia tend to affect also the early-stage N1 and P2 components whereas both types of dementias affect the later-stage N2 and P3 components. However it has become obvious that patients with HIV infection are susceptible to develop progressive, AIDS-related dementia, renamed 'HIV encephalopathy' by the Center for Disease Control. Several studies have shown that endogenous, but also early, components of long latency auditory evoked potentials are prolonged in latency in HIV-demented patients. However, these changes may also be present in class II and III patients and may permit the early recognition of HIV encephalopathy.


Peripheral and central nervous system anomalies in HIV-1 infection: an electrophysiological study. This study explored the neurophysiological changes in 87 HIV1+ (20 AIDS, 24 ARC, 24 LAS and 19 AC) patients showing no clinical evidence of neurological impairment. Tracing somatosensory responses by recording SEPs from upper and lower limbs, we found a slowing of both peripheral and central nerve conduction. Peripheral alterations occurred in virtually all patients of the AIDS group. Central anomalies, confined largely to the lower spinal cord, manifested themselves only during the later stages of the disease (ARC and AIDS) and then only in about half of our sample. More marked neurotropic varieties of HIV1 may account for these differences. We feel that SEP studies can serve to reveal pre-clinical NS involvement in HIV1+ subjects and should be included among research strategies aimed at tracing the evolution of AIDS.


[Study of sensory involvement and dysautonomia in HIV infected patients. A prospective study of 55 cases]. Subclinical impairment of the peripheral nervous system (PNS) is frequent during HIV infection. Nevertheless, little attention has been given to the autonomic nervous system (ANS). We undertook a prospective study of the ANS, exploring 55 HIV+ subjects with non-invasive functional tests for the cardiac ANS. We also made a quantitative study of thermic (small fibers) and vibratory (large fibers) sensibilities. The results do not show any statistically significant difference between HIV+ subjects and control subjects or between HIV+ subjects of groups I, II and III and those of group IV of the CDC classification. However, an individual analysis comparing the results of the infected subjects with those of the control group indicated the presence of functional abnormalities of the ANS (small fibers) in 34.5% of HIV+ patients with an equally frequent impairment of the thermic perception (small fibers) and of the vibratory perception (large fibers). Moreover, the signs of subclinical dysautonomia were more frequent in group IV (48.3%) than in groups I, II and III (19%) showing a progressive accentuation of the troubles during the course of the infection.


Pediatric nutrition surveillance system--United States, 1980-1991. The CDC Pediatric Nutrition Surveillance System (PedNSS) monitors the general health and nutritional characteristics of low-income U.S. children who participate in multiple public health programs. This system is intended to characterize trends and patterns in key indicators of nutritional status so that the information can be used for program planning and targeting. The indicators monitored by PedNSS are birth weight, childhood growth status, anemia, and breast-feeding patterns. From 1980 through 1991, the trends for low birth weight, low height-for-age (shortness), low weight-for-height (thinness), and high weight-for-height (overweight) were stable for all children monitored by the PedNSS, with the exception of Asian children, who were predominantly of Southeast Asian refugee background. In the early 1980s, the prevalence of low birth weight and shortness was higher among Asian children than among children of other racial or ethnic groups who were monitored by the PedNSS. However, these prevalences declined steadily from 1980 through 1991. By 1991, the prevalences of low birth weight and shortness for Asian children were similar to those observed for children of other races/ethnic groups. Overall, low-income U.S. children had a slightly lower height-for-age than expected, indicating that some of these children were at a health and nutritional disadvantage. The prevalence of overweight varied among different racial/ethnic groups; Hispanic and Native American children had the highest prevalences of overweight. The 20%-30% prevalence of anemia among low-income children monitored by the PedNSS was higher than among the general population, reflecting in part the preferential enrollment and retention of anemic children by public health nutrition programs and also indicating that many children had inadequate iron nutrition. From 1980 through 1991, the prevalence of anemia declined > 5% for most of the age- and race/ethnicity-specific groups monitored by PedNSS. That decline represents an improvement in iron nutritional status. PedNSS is a useful system for the monitoring and characterization of the nutrition status of low-income children at both state and national levels.


Pregnancy nutrition surveillance system--United States, 1979-1990. Since 1979, the CDC Pregnancy Nutrition Surveillance System (PNSS) has monitored behavior and nutritional risk factors among low-income pregnant women participating in public health programs. Although the states contributing to the system have varied over the period, the PNSS is able to characterize the behavior and health outcomes of pregnant women from diverse low-income populations. In 1990, 66.2% of the women in the system initiated prenatal care during the first trimester of pregnancy; 26.4% smoked during pregnancy. Since 1979, the prevalence of smoking remained relatively stable for white women, but declined for blacks and Hispanics. Prepregnancy body mass index (BMI, defined as kg/m2) showed marked changes from 1979 through 1990; the prevalence of underweight (BMI < 19.8) declined steadily and the prevalence of overweight (BMI > 26) increased steadily. In 1990, 39.3% of the women had gestational weight gains below levels recommended by the National Academy of Sciences. Both prepregnancy underweight and inadequate gestational weight gain were associated with greater risk for low birth weight in the PNSS. The prevalence of anemia at each trimester has remained stable since 1979. In 1990, 9.8%, 13.8%, and 33% of the women reported by the PNSS were anemic in the first, second, and third trimesters, respectively. Anemia in the first trimester appeared to be strongly associated with a high risk of low birth weight; this association was attenuated in later trimesters. These findings indicate the need to improve iron nutrition among low-income women.


Golfers' cramp: clinical characteristics and evidence against it being an anxiety disorder. The clinical characteristics of 20 golfers suffering from golfers' cramp or the "yips" are described. The typical description is that of a middle-aged golfer who has played competitive golf since his teens and develops the problem during a tournament in the form of a jerk, spasm, or freezing of movement while putting or chipping, with the rest of the game being relatively unaffected. The problem generally takes a chronic fluctuating course, and a number of 'trick' strategies are partially or fully successful. In this study, the subjects were compared with a matched group of 20 unaffected golfers on a number of indices of psychopathology; no significant differences emerged. The more severely affected golfers also did not differ significantly from the mildly affected ones, except on the subjective report of anxiety. These data support the argument that golfers' cramp is not an anxiety disorder or a neurosis. The important role of anxiety and arousal in its manifestation is, nevertheless, recognized and its pathophysiology speculated upon.


Noise-induced psychogenic tremor associated with post-traumatic stress disorder. Tremors in post-traumatic stress disorders have not been previously well characterized. A 67-year-old man has a 46-year history of a noise-induced exaggerated startle reflex followed by a large amplitude rest, postural and kinetic tremor that may persist for up to 3 days. This tremor is superimposed on a continuous mild organic postural/kinetic tremor whose electrophysiological characteristics are different from those of the overlying tremor. We attribute the exaggerated startle reflex and the noise-induced tremor to Post-Traumatic Stress Disorder (PTSD) and postulate a psychogenic origin for the noise-induced tremor. The patient also believes the noise-induced tremor to be psychologically based and to be produced by the fear and anxiety he experiences when he hears loud, unexpected noises. The sudden onset of the noise-induced tremor, its intermittent character, its temporary disappearance on distraction despite the patient's inability to suppress it, inconsistencies in handwriting and figure drawing, and the fact that the noise-induced tremor is stimulus specific and persists long after the offending stimulus (noise) is no longer present all suggest a tremor of psychogenic origin.


Premorbid smoking, alcohol consumption, and coffee drinking habits in Parkinson's disease: a case-control study. A number of studies have reported lower cigarette consumption in patients with Parkinson's disease (PD) previous to onset of the disease. In an attempt to determine whether there existed a "premorbid attitude" by patients against the use of socially accepted "drugs," the premorbid tobacco, alcohol, and coffee consumption habits were compared in 128 PD patients and 256 controls. Patients and controls were selected by case control method and were recruited from the same health area and socioeconomic stratum. In males, the habits of smoking more than 10 cigarettes/day (p < 0.001) and drinking more than 50 g/day of alcohol (p < 0.001) were significantly less frequent in the PD patients than in the controls, but the differences in coffee consumption were nonsignificant. In females behavior did not differ significantly between the PD group and the controls for any of the three habits. There was no correlation between the amount of smoking and alcohol drinking and age at onset of PD or current Hoehn and Yahr's staging. Our results suggest the existence of a premorbid personality in males with PD, possibly conditioning a restrictive attitude toward the consumption of such toxic substances as tobacco and alcohol, yet a more tolerant attitude toward habits more widely accepted socially, like coffee consumption.


The undulating toe flexion sign in brain death. Brain-dead patients may exhibit gross spontaneous and reflex movements (e.g., Babinski sign, stereotypic flexion of one or more limbs, and Lazarus sign). We report three brain-dead patients who had unusual complex sequential movements of the toes. Undulating toe flexion was elicited by noxious stimuli to the lower extremities, and consisted of initial plantar flexion of the great toe, followed by sequential brief plantar flexion of the second, third, fourth, and fifth toes. The undulating toe flexion sign differs from previously described responses characterized by plantar flexion of the toes (e.g., Rosselimo's sign and the Mendel-Bechterew sign) in that it consists of complex patterned sequential movements of the digits rather than brief simultaneous flexion and/or fanning of the toes. Neurologists should be aware of this unusual finding, which should not preclude the diagnosis of brain death.


Corticobasal degeneration: decreased and asymmetrical glucose consumption as studied with PET. Cerebral energy metabolism was studied by positron emission tomography and [18F]fluorodeoxyglucose in five patients with clinical diagnoses of probable corticobasal degeneration. A reduction in glucose consumption was observed in most cortical and subcortical structures compared to age-matched controls. The reduction was greatest on the side of the brain contralateral to the most affected limbs, as shown by the significantly lower ratios of contralateral to homolateral metabolic rates, in the temporal and sensorimotor cortex of patients compared to controls. A distinct asymmetry between the two hemispheres could be observed in a patient who was examined twice in the course of his illness. Detection of this asymmetrical decrease in brain cortical and subcortical glucose metabolism may prove useful as additional evidence supporting clinical diagnoses of the disease.


Diffuse Lewy body disease presenting with supranuclear gaze palsy, parkinsonism, and dementia: a case report. A 67-year-old man with a family history of parkinsonism had visual complaints due to difficulty in convergence, which was followed 2 years later by development of bradykinesia and rigidity. The diagnosis of Steele-Richardson-Olszewski syndrome was made on the basis of a supranuclear gaze palsy, bradykinesia, rigidity, and poor response to levodopa. However, subsequent neuropathological examination revealed diffuse Lewy body disease with no evidence of neurofibrillary tangles involving either subcortical or brain stem structures.


Recumbent tic.

Recumbent tic. A 59-year-old man with a 30-year history of an unusual movement disorder characterised by involuntary axial spasms that occur only in recumbency is described. Clinical and electrophysiological evidence suggest that this disorder is best characterised as a simple tic of unusual form. We have coined the term "recumbent tic" to describe this disorder.


Isolated continuous rhythmic lingual myoclonus. Isolated continuous lingual myoclonus is an exceptional entity, poorly documented and understood. A patient with a nonepileptic continuous rhythmical myoclonus, affecting the anterior portion of the tongue, as an independent involuntary disorder, is reported. Electromyography showed low frequency (2-4 Hz) bursts of genioglossus muscles activity. The EEG, visual, auditory and somatosensory evoked responses were normal. Imaging techniques like CT and MRI failed to reveal any brainstem or cerebellar lesion. Lingual myoclonus showed a very good response to sodium valproate.


Hemiballism and tremor due to ependymal cyst. A 21-year-old woman was admitted with right hemiballism and tremor. She had tremor since the age of 6 years. At age 12, an intracerebral, left paraventricular space-occupying lesion was found and treated with 4,500 rads. Increasing tremor was associated with mass enlargement. By age 20, there was insidious presentation of right hemiballism. At age 21, she had craniotomy and a large septate cyst was opened and drained. Biopsy of the cyst wall revealed that it was consistent with ependymal cyst. Postoperatively the hemiballism resolved and the tremor improved. This case is unusual due to the presentation of hemiballism caused by ependymal cyst.


Cloning and characterization of a Loa loa-specific repetitive DNA. A Loa loa EcoRI genomic library in lambda gt11 was screened with 32P-labeled L. loa DNA and 1 repetitive clone, LL20, was isolated. An 800-bp Rsa I fragment of LL20, which is L. loa specific, was subcloned into pUC19 and the recombinant plasmid was designated pRsa4. While the 3.8-kb Eco RI fragment of LL20 cross-hybridized to other filarial DNA under low stringency conditions, the 800-bp fragment of pRsa4 was L. loa specific under the same conditions. Further characterization of the insert of pRsa4 was therefore carried out. Its lower limit of detection is 800 pg of L. loa genomic DNA, it has a low copy number (50-100) and an interspersed distribution in the genome. As a probe it does not distinguish between simian and human L. loa DNA. The nucleotide sequence contains 69% A + T and 31% G + C and shows no notable internal repeats.


The expression of small heat shock proteins in the microfilaria of Brugia pahangi and their possible role in development. Development of the microfilariae of Brugia pahangi in the mammalian host is blocked until uptake by a mosquito vector when the developmental cycle is re-initiated. Comparison of the profile of polypeptides labelled in microfilariae cultured at mammalian temperature (37 degrees C) or mosquito temperature (28 degrees C) revealed a complex of low-molecular-weight proteins (18 kDa and 22-24 kDa) synthesized only in microfilariae at 37 degrees C. The synthesis of these proteins was also induced by transfer of microfilariae to 41 degrees C (i.e., heat shock conditions), suggesting that these are heat shock proteins. The expression of the small heat shock proteins in the Brugia life cycle is developmentally regulated, as they are not observed in the mature adult female. Their synthesis is strictly temperature dependent and is repressed upon transfer of the microfilariae to 28 degrees C.


Expression of small heat shock proteins by the third-stage larva of Brugia pahangi. Changes in proteins synthesised by the infective third-stage larvae (L3) of the filarial nematode Brugia pahangi were examined with respect to the temperature shift encountered by the parasite as it migrates from insect to mammal, and the presence of serum in the culture medium. While the synthesis of a number of polypeptides is regulated by the temperature shift of the L3 from 28 degrees C to 37 degrees C in vitro, there is no evidence that serum has any significant effect on protein synthesis. Two complexes of small acidic polypeptides (22-24 kDa and 18 kDa) are synthesised for a limited period only by L3 transferred to 37 degrees C. One component of each complex appears to be constitutively expressed at 28 degrees C, but its synthesis is up-regulated at 37 degrees C, while the remaining members of each complex are synthesised only at 37 degrees C. Subjection of L3 and post-infective (p.i.) L3 to heat shock (41 degrees C) also induces synthesis of both complexes, indicating that these heat-inducible polypeptides are related to the family of small heat shock proteins. The possible role of the heat shock-related proteins in this important environmental transition is considered.


Alpha-tubulin II is a male-specific protein in Plasmodium falciparum. The tubulin gene family in Plasmodium falciparum consists of one beta-tubulin and two alpha-tubulin genes (alpha-tubulin I and II). We present here data indicating that alpha-tubulin II is expressed only in male sexual stage parasites. An IgM mAb, 5E7, specifically reacted with stage III (day 4-5) through mature (day 10-11) male gametocytes and with emerging, exflagellating, or freely moving male gametes. No reactivity was detected in female gametocytes, female gametes, sporozoites, or asexual parasites. mAb 5E7 also specifically recognized male gametes of the avian parasite, Plasmodium gallinaceum, and immunoblotted a 50 kDa protein in extracts of male gametes from both species. This 50 kDa antigen was localized by immunoelectron microscopy to axonemes of male gametes in a pattern similar to that obtained with anti-alpha- and anti-beta-tubulin antibodies. Furthermore, mAb 5E7 specifically reacted with recombinant alpha-tubulin II protein obtained using the PCR-amplified alpha-tubulin II gene from a gametocyte-specific cDNA library. The sex-specific expression of alpha-tubulin II and its localization to axoneme of the male parasite suggest a role for this molecule in the morphologic changes that occur during exflagellation and in the motility of the parasite. alpha-Tubulin II and mAb 5E7 may prove useful tools in studies of the biology of sexual stage differentiation and development in P. falciparum in addition to the general understanding of post-translational modifications of tubulin isoforms.


Energization-dependent Ca2+ accumulation in Trypanosoma brucei bloodstream and procyclic trypomastigotes mitochondria. The permeabilization of Trypanosoma brucei procyclic and bloodstream trypomastigotes with digitonin permitted the quantitative estimation of a mitochondrial membrane potential of the order of 130-140 mV, in both forms, using safranine O. Dependence on substrate oxidation and response of the procyclic mitochondrial membrane potential to phosphate, FCCP, valinomycin, and Ca2+ indicate that these mitochondria behave similarly to vertebrate mitochondria regarding the properties of their electrochemical proton gradient. In contrast, in bloodstream mitochondria, development of a membrane potential was independent of substrate oxidation and dependent on hydrolysis of ATP by the mitochondrial oligomycin-sensitive ATPase, as demonstrated by collapse of the membrane potential by oligomycin and its insensitivity to the respiratory chain-inhibitor antimycin A. Mitochondria of T. brucei bloodstream forms were also able to take up Ca2+ by an electrophoretic mechanism. This is the first report of the presence of a Ca2+ transport mechanism in an eukaryotic cell devoid of complete tricarboxylic acid cycle and respiratory chain, the activities of which are known to be regulated by changes in intramitochondrial calcium concentration in other cells.


Filarial parasites contain a ras homolog of the TC4/ran/Spil family. We have isolated and characterized a gene encoding a novel GTP-binding protein of the GTPase superfamily in the filarial parasites Brugia malayi and Onchocerca volvulus. The deduced amino acid sequence of the cloned molecule has approximately 30% overall homology to ras proteins and approximately 90% homology to the 'ras-like' nuclear proteins TC4, ran and Spil. Rabbit antisera to bacterially expressed filarial protein detect a 24-22 kDa doublet in extracts of adult B. malayi and mature microfilariae, which is absent from immature microfilariae. Increased expression of the native parasite protein occurs when worms are cultured in the presence of epidermal growth factor.


A cloned antigen for serological diagnosis of Wuchereria bancrofti microfilaremia with daytime blood samples. By differentially screening an adult Brugia malayi cDNA library with sera from microfilaremic and amicrofilaremic donors infected with Wuchereria bancrofti, we have identified a novel parasite antigen denoted SXP-1. Recombinant SXP-1 filarial antigen is preferentially recognized by sera from microfilaremic persons with bancroftian filariasis and from skin snip-positive patients with onchocerciasis. Antibodies to SXP-1 are restricted to the IgG4 subclass and gradually decline after treatment with diethylcarbamazine. These findings indicate that it may be possible to replace microscopic examination of night blood films with a serological test designed to detect antibodies to a mix of SXP-1 and other suitable antigens for the diagnosis of microfilaremia due to bancroftian filariasis.


Galactosamine-synthesizing enzymes are induced when Giardia encyst. Galactosamine, a Giardia filamentous cyst wall specific-sugar, is below the limits of detection in non-encysting trophozoites. Radiolabeling studies suggest that Giardia synthesize galactosamine primarily from endogenous glucose rather than salvage it from the environment. Enzymes responsible for galactosamine synthesis from glucose are induced during encystment and have been characterized in crude homogenates and in supernatant (soluble) fractions. These enzymes (specific activity; time after encystment is induced for maximal activity; x-fold increase) include glucosamine 6-phosphate isomerase (in the deaminating direction, 167 mU mg protein-1; 20 h; x 182-fold; in the aminating direction, 258 mU mg protein-1; 20 h; x 13-fold), glucosamine 6-phosphate N-acetylase (11 mU mg protein-1; 20 h; x 20-fold), phosphoacetylglucosamine mutase (160 mU mg protein-1; 20 h; x 12-fold), UDP-N-acetylglucosamine pyrophosphorylase (22 mU mg protein-1; 48 h; x 8-fold), and UDP-N-acetylglucosamine 4'-epimerase (13 mU mg protein-1; 48 h; x 4000-fold). This represents the first report of these enzymes and of an inducible carbohydrate-synthesizing pathway in any protozoan.


Cloning and sequencing of an hsp70 gene of Schistosoma mansoni. Schistosomes have a complex life cycle (vertebrate and molluscan hosts as well as larvae living freely in water) in which they are exposed to different environments and temperatures (20 degrees C - 37 degrees C). Since heat shock genes are activated in response to stress and during development [1], it is of interest to study the hsp70 gene family in schistosome. To approach this issue we have isolated from Schistosoma mansoni a genomic clone containing the complete coding region of hsp70 and the 5' flanking DNA with transcription regulatory elements including HSE (heat shock element) sequences.


Phospholipase D in heart: basal activity and stimulation by phorbol esters and aluminum fluoride. Evidence for a general role of phospholipase D in signal transduction is accumulating. In the present study, the activity of the enzyme was investigated in heart tissue under basal conditions and after addition of phorbol esters or aluminum fluoride (AlF-4; 10 mM NaF plus 10 microM AlCl3). Atria of rats and chickens were incubated with [3H]-myristic acid in order to label preferentially phosphatidylcholine. Under basal conditions, the tissues generated choline and phosphatidic acid (PtdOH), the primary catalytic products of phospholipase D. When 0.5 or 2.0% ethanol was present, [3H]-phosphatidylethanol (PETH) was rapidly formed at the expense of [3H]-PtdOH. This transphosphatidylation reaction is specific for phospholipase D activity. The basal formation of PETH was not inhibited by a Ca(2+)-free, EGTA-containing medium. The phorbol ester 4 beta-phorbol-12 beta, 13 alpha-dibutyrate (PDB), which is known to activate protein kinase C, enhanced the net formation of choline, whereas the inactive 4 beta-phorbol-13 alpha-acetate (PAc) was ineffective. PDB (0.2 microM), in contrast to PAc, also increased the formation of [3H]-PtdOH and, in the presence of ethanol, of [3H]-PETH. The PDB-evoked formation of PETH occurred again at the expense of PtdOH. Treshold and maximum effective concentrations of PDB were 10 nM and 0.2-0.6 microM, respectively. The effects of PDB on either choline efflux and generation of PETH showed the same Ca(2+)-dependency, i.e., both effects were blocked by a Ca(2+)-free, EGTA-containing medium, but not by a Ca(2+)-free medium without EGTA.(ABSTRACT TRUNCATED AT 250 WORDS)


Reactivity of human iris-sphincter to muscarinic drugs in vitro. From tissue to tissue the contractile response of human irides to carbachol varied by 40 fold. The mean EC50 value of carbachol in tissues remaining in an in vitro environment for 24-37 h was equal, however, to that obtained from tissues examined during 79-161 h. The maximum response of the tissue to the highest concentration of carbachol increased up to 24 h, then a gradual decline in the maximum occurred. In 38 observations, the average decline after 72 h was approximately 30%. A plot of negative log EC50 values (n = 38) of carbachol exhibited normal Gaussian curve. The geometric mean EC50 value of carbachol was 0.38 mumol/l (0.28-0.51 mumol/l, 95% C.L.). Based on EC50 values, the rank order of potency of cholinergic agonists is as follows: Muscarine = carbachol, 1 > pilocarpine, 1/5 > methacholine, 1/23 > bethanechol, 1/29 > acetylcholine, 1/1310. The percent maximum contraction of irides to muscarine, carbachol, pilocarpine, methacholine and bethanechol were 100, 100, 80, 76 and 95, respectively. Acetylcholine at the highest concentration tested produced 71% of the maximum produced by carbachol. Within a concentration range of 1 to 100 mumol/l, physostigmine consistently contracted isolated irides. The mean EC50 value was 6.73 mumol/l. The effect was sensitive to blockade by atropine. When the temperature of the bathing medium was lowered from 37.5 degrees C to 27.5 degrees C or 17.5 degrees C the magnitude and the duration of the response of the iris to carbachol was increased, the EC50 value, however, was not changed significantly. The response to pilocarpine was similarly altered by the lower temperature.(ABSTRACT TRUNCATED AT 250 WORDS)


Cholinergic sensitivity of irides from donors with various pathological conditions and lens implants. In vitro, iris contractions after muscarinic agonists were measured in mg of tension change and the concentration producing 50% of the response was expressed as EC50 mumol/l. Although the average EC50 value of carbachol in the iris sphincter of the donors with diabetes or Parkinson's disease did not change significantly when compared with the control, the maximum contraction of the tissue from the diseased state was increased significantly. Thus, in addition to the well known denervation supersensitivity of the iris-dilator, the iris-sphincter also develops adaptive sensitivity changes. Antimuscarinic drug treatment in some Parkinson's patients interfered with the estimation of supersensitivity in vitro studies. The enhanced response of carbachol at the low temperatures or the relative potency of carbachol and pilocarpine in the tissue obtained from the diseased donors was not significantly different from that of controls. Based on EC50 values, the potency of arecoline on the iris was 1/3 that of carbachol. Significantly lower EC50 values of carbachol were found in irides which were in contact with open loop type anterior chamber lens implants compared with those in contact with the closed loop anterior chamber lens implants. Maximum responses of irides to carbachol were less when the tissue was in contact with open loop lens compared with those in contact with closed loop anterior chamber implants. Irides from many donors having unilateral or bilateral replacement of the artificial lenses responded with EC50 of carbachol which was approximately equal to that of the contralateral eye. The maximum difference between EC50 values of the left and right iris was less than 5 fold.(ABSTRACT TRUNCATED AT 250 WORDS)


5-Hydroxytryptamine-induced increase in left ventricular dP/dtmax does not suggest the presence of ventricular 5-HT4 receptors in the pig. Although 5-hydroxytryptamine (5-HT) increases porcine atrial force and rate via 5-HT4 receptors, its effect on left ventricular contractility is not known. Therefore, using the maximum rate of rise of left ventricular pressure (LVdP/dtmax) as an index of cardiac contractility, we have attempted to analyze the possible role of ventricular 5-HT4 receptors in the anaesthetized pig. The full agonists at 5-HT4 receptors, 5-HT and 5-methoxytryptamine (each 3, 10 and 30 micrograms.kg-1), and the beta-adrenoceptor agonist, isoprenaline (0.01, 0.03 and 0.1 micrograms.kg-1), increased heart rate, LVdP/dtmax and cardiac output. For a given degree of tachycardia, the increase in LVdP/dtmax by isoprenaline was substantially more than that observed with either 5-HT or 5-methoxytryptamine. The 5-HT4 receptor partial agonist, renzapride (3, 10, 30, 100 and 300 micrograms.kg-1), also increased heart rate and LVdP/dtmax dose-dependently. When the heart was paced at 150 beats.min-1, increases in LVdP/dtmax as well as cardiac output (except with the highest doses) by 5-HT, 5-methoxytryptamine and isoprenaline were clearly attenuated. However, the magnitude of attenuation of LVdP/dtmax responses by cardiac pacing was more marked in the case of 5-HT and 5-methoxytryptamine than with isoprenaline. The effects of renzapride (300 micrograms.kg-1) and tropisetron (0.3 and 3 mg.kg-1) on increases in heart rate and LVdP/dtmax by 5-HT, 5-methoxytryptamine and isoprenaline were also studied.(ABSTRACT TRUNCATED AT 250 WORDS)


Effects of adenosine derivatives on human and rabbit platelet aggregation. Correlation of adenosine receptor affinities and antiaggregatory activity. The inhibitory effects of several adenosine analogues, including the new A2-selective agonists 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido-adenosi ne (CGS 21680) and 2-hexynyl-5'-N-ethylcarbox-amidoadenosine (2-hexynyl-NECA), were investigated in vitro on human and rabbit platelet aggregation. The compounds examined inhibited ADP-induced platelet aggregation over a wide range of potency. The rank order of activity was similar between the two species thus showing that the rabbit is a useful animal model for studying the effects of adenosine derivatives on platelet aggregation. 2-Hexynyl-NECA was found to be the most potent adenosine compound of those currently available, having IC50 values of 0.10 and 0.07 microM in human and rabbit platelets, respectively. Conversely, the A1 agonists R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA), S(+)-N6-(2-phenylisopropyl) adenosine (S-PIA) and 2-chloro-N6-cyclopentyladenosine (CCPA) were the least potent compounds with IC50 values in the micromolar range. The potency of the compounds in inhibiting platelet aggregation was found to be highly correlated with their affinity for A2 receptors as measured using 3H-CGS 21680 binding in rat brain striatum.


Differential effects of locally-applied capsaicin on distension-stimulated gastric acid secretion in the anesthetized rat. The effects induced by the local administration of capsaicin on acid production have been investigated in the continuously perfused stomach of the anesthetized rat. Basal acid secretion was not influenced by 10 min intragastric perfusion with capsaicin (300 micrograms min-1). Acid responses elicited by distension of the stomach with increases in intragastric pressure of 5 and 10 cm H2O were not modified after a 10 min intraluminal infusion with 80 or 300 micrograms min-1 of capsaicin. H+ output stimulated by higher intraluminal pressure (20 cm H2O) were significantly decreased by intraluminal infusion of capsaicin (20, 80, 300 and 600 micrograms min-1). Acid responses to carbachol (4 micrograms kg-1, i.p.) were not influenced by intragastric (300 micrograms min-1), or systemic neonatal, treatment with capsaicin. Intraluminal infusion of the neurotoxin tetrodotoxin (0.12 micrograms min-1, 10 min) decreased acid responses to an increase in intragastric pressure of 20 cm H2O but not those elicited by distention with a pressure of 10 cm H2O. Neonatal systemic treatment (s.c.) with capsaicin or local gastric serosal application of either capsaicin or tetrodotoxin abolished acid responses to gastric distension (+20 cm H2O). Capsaicin (80 micrograms min-1) and tetrodotoxin (0.12 micrograms min-1) infused concurrently into the lumen did not inhibit gastric acid secretion stimulated by an increase of 20 cm H2O in intragastric pressure to any greater extent than did either drug given alone.(ABSTRACT TRUNCATED AT 250 WORDS)


K+ channel openers, cromakalim and Ki4032, inhibit agonist-induced Ca2+ release in canine coronary artery. The effects of K+ channel openers, cromakalim and an acetoxyl derivative of KRN2391 (Ki4032), were studied on force of contraction, increases in intracellular calcium concentration ([Ca2+]i) measured by fura-2 and inositol 1,4,5-trisphosphate (IP3) production induced by the thromboxane A2 analogue, U46619, in canine coronary arteries. Upon single dose applications of U46619 at 300 nmol/l, phasic and tonic increases in [Ca2+]i and force were seen, which were almost abolished by cromakalim (10 mumol/l) and Ki4032 (100 mumol/l). In the absence of extracellular Ca2+, U46619 induced a transient increase in [Ca2+]i with a contraction. Cromakalim (0.01-10 mumol/l) and Ki4032 (0.1-100 mumol/l) concentration-dependently inhibited the increases in [Ca2+]i and contraction. The inhibitory effects of cromakalim and Ki4032 were blocked by the K+ channel blocker tetrabutylammonium (TBA) and counteracted by 20 mmol/l KCl-induced depolarization. Cromakalim and Ki4032 did not affect caffeine-induced Ca2+ release. Cromakalim reduced U46619-induced IP3 production significantly and TBA blocked this inhibitory effect. These results suggest that the hyperpolarization of the plasma membrane by K+ channel openers inhibits the production of IP3 and Ca2+ release from intracellular stores related to stimulation of the thromboxane A2 receptor.


Erythromycin and motilin stimulate sphincter of Oddi motility and inhibit trans-sphincteric flow in the Australian possum. The actions of erythromycin lactobionate and porcine motilin on trans-sphincteric flow and simultaneous sphincter of Oddi motility were studied in 15 anaesthetized Australian Brush-tailed possums (Trichosurus vulpecula). Erythromycin (25-200 micrograms/kg) and motilin (25-200 ng/kg) were administered as graded doses by close intraarterial injection. Trans-sphincteric flow was measured as inflow and outflow. Both motilin and erythromycin decreased trans-sphincteric inflow (both P < 0.0001) and outflow (P < 0.0001 and P = 0.0017 respectively) in a dose-dependent manner. The highest dose of each agent abolished trans-sphincteric flow. These agents increased sphincter of Oddi phasic contraction frequency and basal pressure up to 2 and 3 fold respectively (P < 0.05). The amplitude of the sphincter of Oddi phasic contractions were not influenced in any consistent fashion by either agent. The durations of the responses (trans-sphincteric inflow) elicited by erythromycin and motilin were dose dependent (P = 0.0225 and P = 0.0001 respectively). The actions of erythromycin (200 micrograms/kg) or motilin (100 ng/kg) on trans-sphincteric flow and sphincter of Oddi motility were not influenced by neural blockade with tetrodotoxin. These findings support the hypothesis that erythromycin acts as a motilin agonist and both substances increase the resistance to flow through the sphincter of Oddi by raising the basal pressure and frequency of contractions.


[Use of 24-hour casette monitoring of the EEG recording in the differential diagnosis of attacks of unconsciousness in adults]. 24-hour cassette recording of EEG using the Medilog 9000 system was done in 36 patients referred for observations because of diagnostic difficulties in cases of refractors unconsciousness attacks. The method made possible isolation of 3 groups: 1. 6 patients with attacks not suggestive of epilepsy 2. 12 patients with false unconsciousness attacks which were in fact short partial complex seizures (temporal lobe absence) 3. 17 patients with actual unconsciousness attacks. The study demonstrated a high usefulness of 24-hour EEG monitoring in the differential diagnosis of unconsciousness attacks increasing the likelihood of attack recording and making possible their precise clinical and EEG characteristics which is often impossible with routine EEG and history taking.


[Effects of age and body height on somatosensory evoked potentials]. The influence of age and height on somatosensory evoked potentials (SEP) following median and tibial nerve stimulation was studied. Age correlated with increase of latencies and decrease of amplitudes; exceptionally the amplitude of cortical N20 component increased with age. The central conduction time P31-P40 (tibial nerve stimulation) was longer in elderly subjects, whereas the time N13-N20 (median nerve stimulation) was independent of age. Height showed a positive correlation with latencies and peripheral conduction times; central conduction times (N13-N20 and P31-P40) were independent on height. The correlations of SEP parameters with age and height were expressed quantitatively by regression equations. The presented equations should be treated as a valuable complement to normative data in interpretation of SEP testing results.


[Paroxysmal EEG changes in patients with multiple sclerosis]. The electroencephalograms (EEG) and visual evoked potentials (VEP) were recorded in 100 multiple sclerosis patients treated from 1981 to 1989. In 35 cases the EEG records were pathological and in 12 of them they showed paroxysmal changes. Pathological EEG were mostly seen in young patients, during the first relapse, with high degree of Kurtzke's disability score. Patients with paroxysmal changes showed on physical examination brain stem lesions that could be responsible for paroxysmal activity in EEG. The latencies of P100 wave and amplitudes of P100/N120 complex were analysed in two groups of patients (with and without paroxysmal activity in EEG). There was no statistically important difference between two groups, although in the group with paroxysmal changes in EEG some prolongation of the latency of P100 wave and a little higher amplitude of P100/N120 complex were recorded.


[Diagnostic value of 24-hour simultaneous EEG and ECG monitoring of patients with heart diseases and atypical consciousness disorders]. In 24 patients with diagnostically not clear, short, recurrent episodes of consciousness disturbances and heart diseases and/or a history of arrhythmia simultaneous 24-hour recording was done of eeg and ecg. In the differential diagnosis epilepsy was considered, especially since in most cases routine eeg records demonstrated slight episodic changes. During 24-hour recording in 8 cases typical episodes of consciousness disturbances developed but in none of them these episodes were associated with arrhythmia which ruled out their cardiogenic origin. In 2 cases EEG recording served for establishing the diagnosis of partial complex seizures, 2 patients had hyperventilation syncope, one had TIA, in the remaining 3 cases absence of eeg and ecg changes during these episodes and coexistence of anxiety neurosis suggested functional origin. So the combined 24-hour eeg+ecg recording made possible establishing of diagnosis in 1/3 of these patients, enabling adequate treatment to be instituted.


[Atrophy of the granular layer of the cerebellar cortex in patients with nonlymphoblastic leukemia treated with cytosine arabinoside]. The reported analysis comprised 81 patients dying of acute non-lymphoblastic leukaemia type M1, M2, M4 and blastic crises in chronic myelocytic leukaemia. It was observed that the number of cases of cerebellar granular layer atrophy rose markedly in the years 1984-1990 as compared with 1976-1983 (45.4% vs 16.2%). It is suggested that this was due to the introduction of cytostatic treatment schedules with higher doses of cytosine arabinoside (ARAC), especially TAD (6-thioguanine, ARAC, daunorubicin). Cerebellar granular layer atrophy seems to be dependent rather on the cumulative dose of ARAC and not on a single high dose of that drug.


[Non-traumatic cerebral hematoma and the mechanisms of intracranial volume compensation]. The results are presented of measurements of the intracranial pressure, pressure instability index and shifting of ventricular structures in 42 patients with non-traumatic intracerebral haematoma. Only the value of the instability index showed a correlation with the state of consciousness. For a more complete assessment of the state of sufficiency of the intracranial pressure compensation mechanism all these parameters should be analysed jointly.


[Intracranial pressure in cases of non-traumatic cerebral hematoma-- personal observations and review of the literature]. The analysis of intracranial pressure records in 95 cases of non-traumatic intracerebral haematoma is presented. In 74 cases continuous recording was done. No correlation was found between the values of this pressure and consciousness disturbances. Three types of pressure change patterns were demonstrated: type A - low or normal values unchanging in 43 cases, type B - high initial values with normalization during conservative treatment, type C - very high initial values which decreased after operation in only some patients.


[Significance of oligoclonal proteins and magnetic resonance imaging in the diagnosis of multiple sclerosis]. The new techniques identifying inactive clinical injury, as well as revealing immunological disturbances connected with the CNS, are very helpful for arriving at the correct diagnosis of multiple sclerosis. In their analysis the authors of the work include six cases and emphasize the great practical significance of magnetic resonance imaging and oligoclonal bands in the cerebrospinal fluid in making the diagnosis of multiple sclerosis.


[History of discoveries and advances in the studies of parkinsonism]. A review is presented of the more important discoveries and advances in the 175-year history of the studies and therapeutic trials on parkinsonism. The personality and achievements of James Parkinson are described, with a brief discussion on his most important paper "An Essay on Shaking Palsy". The important works of clinicians, neuropathologists and pharmacologists in the 19th and 20th centuries, especially in the "era of L-DOPA", are reviewed. The development of neurosurgical methods of parkinsonism treatment, including intracerebral grafting of dopamine-producing cells, is outlined.


[Antifibrinolytic treatment after subarachnoid hemorrhage]. The value of the antifibrinolytic treatment was assessed in two groups od patients treated after subarachnoid haemorrhage from ruptured aneurysm. One group of 449 patients received EACA before the operation, and 308 were not given EACA. The effectiveness of this treatment was analysed considering the frequency of recurrent haemorrhages, site of aneurysm and sequelae of recurrent haemorrhage as well as ischaemic complications of subarachnoid haemorrhage. The frequency of recurrent haemorrhages was significantly lower in the group not treated with EACA, and the frequency of ischaemic complications of subarachnoid haemorrhage was significantly higher in those treated with EACA.


[Diplomyelia and diastematomyelia. Case reports]. Diplomyelia and diastematomyelia. Case report. Three cases of diplomyelia [1] and diastematomyelia [2] were studied and treated between 1980 and 1990 years. All patients had symptomatic onset in adulthood. Pathological features were caused by localization on the lesion in cervical, thoracic and lumbar segment of the spinal cord. Plain X-rays showed a variety of osseous malformations associated with spinal dysraphism. The most usefull radiographic examination was computerized tomography (CT). Indications to surgical treatment are discussed.


[A case of progressive multisystem damage of the central nervous system with suspected olivopontocerebellar atrophy type I]. A case of progressive multisystem damage to the central nervous system was observed in a patient aged 36 years. On the ground of family history, disease course, clinical findings and results of laboratory investigations type I of olivo-ponto-cerebellar atrophy according to McKusick's classification was suspected.


[Clinico-electrophysiological image and the results of the treatment of Isaacs-Mertens syndrome]. A case of Isaacs-Mertens syndrome is reported in which the predominating clinical symptom was muscular rigidity. Characteristic bioelectric activity was recorded in resting muscles. Good response was observed after diphenylhydantoin.


[Problems in general management during barbiturate therapy]. Sixty-three patients (aged from 4 to 75 years) who had suffered severe head injury or cerebrovascular disease were placed on barbiturate regimens in which intravenous administration was given in amounts of 1-4 mg/kg/hr. Dobutamine and dopamine were also administered to prevent cardiac failure and renal failure. Immediate and delayed complications caused by barbiturate therapy were investigated and analyzed. Immediate complications included tachycardia which was seen in 16 cases (25%), and hypotension in 14 cases (22%), respectively. Higher incidence of those complications was noted among the patients who underwent surgery. Delayed complications included hypokalemia (41 cases, 65%), liver dysfunction hypernatremia (24 cases, 38%), infection (21 cases, 33%), cardiac failure (8 cases, 13%) and renal failure (1 case, 2%), respectively. Therefore, in patients treated under barbiturate regimens great care should be taken in order to avoid above mentioned complications.